bluuebunny/crossref_metadata_2025_split huggingface dataset:
Onset of autoimmune glomerulonephritis derived from the telomeric region of MRL-chromosome 1 is associated with the male sex hormone in mice
Authors: Ichii O , Konno A , Sasaki N , Endoh D , Hashimoto Y , Kon Y 
Published: April 2009

Female B6.MRLc1(82–100) congenic mice develop more severe autoimmune glomerulonephritis (AGN) than males. We assessed the effects of gonadectomy on the pathogenesis of AGN in these mice. One-month-old male and female mice were divided into sham-operated group (SG) and gonadectomized group (GG), and the pathological changes were investigated at 8 months. SG females showed higher spleen and thymus weights, serum total IgG and autoantibody levels, glomerular damage scores and percent IgG- and CD3-positive glomeruli as compared with SG males. Gonadectomy showed more remarkable effects in males than in females. Spleen and thymus weights, urinary albumin excretion, glomerular damage scores, percent IgG- and CD3-positive glomeruli, and CD3-positive areas in the spleen were significantly higher in GG males than in SG males. CD3-positive cells were observed in both the thymic cortex and medulla in all animals except SG males. The expression ratio of active Fc gamma receptor ( Fcgr) 3 to inhibitory Fcgr2b in the kidneys, which we have previously demonstrated to have a great impact on pathogenesis in B6.MRLc1(82–100), was significantly higher in GG males than in SG males. These results suggested that the differences in the pathogenesis of AGN are primarily because of the inhibitory roles of the male sex hormones.
Increased expression of soluble inducible costimulator ligand (ICOSL) in patients with systemic lupus erythematosus
Authors: Her M , Kim D , Oh M , Jeong H , Choi I 
Published: April 2009

To investigate the level of costimulating molecules in systemic lupus erythematosus (SLE), we assessed the plasma concentrations of soluble forms of costimulatory molecules such as programmed death-1 (PD-1), B7-H1 (also called PD-L1 or CD274) and inducible costimulator ligand (ICOSL) in patients with SLE. Plasma concentrations of soluble PD-1, B7-H1 and ICOSL were measured by ELISA using plasma samples from 57 SLE patients with or without the active disease, 21 rheumatoid arthritis (RA) patients and 35 healthy subjects. We also evaluated surface ICOSL expression on B cells using flow cytometry to gain a better understanding of ICOSL expression. To compare the level of ICOSL mRNA expression, reverse transcriptase-polymerase chain reaction (RT-PCR) was performed using total RNA from peripheral blood mononuclear cells (PBMCs) isolated from eight healthy subjects and 11 patients with SLE. The concentration of plasma ICOSL was significantly higher in patients with SLE compared with healthy subjects ( P = 0.005). Plasma ICOSL concentrations in patients with active SLE were also significantly higher than those of either patients with inactive SLE or patients with RA ( P = 0.001, P = 0.015, respectively). Plasma ICOSL concentrations in patients with SLE correlated modestly with the SLE disease activity index score ( r = 0.298, P = 0.024). We also found a significant inverse correlation between the soluble ICOSL expression and the surface ICOSL expression on B cells ( r = −0.690, P = 0.001). However, ICOSL mRNA levels of patients with SLE were comparable with those of the control subjects. There was also no significant difference in plasma B7-H1 concentrations between groups, and plasma PD-1 was not detectable in any of the groups. The plasma concentration of soluble ICOSL might be correlated to the disease severity of lupus. The increased levels of ICOSL in active lupus suggest that this pathway is involved in the pathogenesis of SLE. The mechanism and physiological role of soluble ICOSL in the pathogenesis of SLE, however, remains to be investigated.
Prevalence, predictors and outcome of vascular damage in systemic lupus erythematosus
Authors: Becker-Merok A , Nossent JC 
Published: April 2009

Despite improved prognosis, patients with systemic lupus erythematosus (SLE) remain at increased risk for early death. Vascular events (VE) occur with increased frequency and contribute to premature death in SLE patients. As conventional cardiovascular risk factors do not fully explain this hazard, this study investigated the contribution of disease-specific features to VE development. Documented VE were classified as atherothrombotic, venous thrombotic, arterial thrombotic or tissue loss inducing vasculitis during a mean follow-up of nearly 12 years in the Tromsø Lupus cohort ( n = 158). The impact of disease-specific factors (organ manifestations, laboratory findings, drug treatment, weighted average SLE Disease Activity Index (WAS) and cumulative Damage Index) was assessed by odds ratios for VE in multivariate analysis. A total of 41 patients (26%) developed VE, and atherothrombotic events were most common (73%). Overall, VE prevalence was 3.5/100 patient years, and VE risk increased linearly over time, reaching 35% after 20 years. WAS scores >3 increased, and use of hydroxychloroquine and antihypertensive medication reduced overall VE risk. Age >40 years was the main risk factor for atherothrombotic events. VE nearly quadrupled the risk of death. VE occurred in 26% of SLE patients, predominantly as atherothrombotic disease. VE prevalence increased linearly over time leading to a four-fold risk of mortality. Strategies for reducing disease activity, including treatment with antimalarials and antihypertensive drugs, are most likely to reduce the risk associated with VE in SLE.
Does mycophenolate mofetil prevent extra-renal flares in systemic lupus erythematosus? Results from an observational study of patients in a single practice treated for up to 5 years
Authors: Posalski JD , Ishimori ML , Wallace DJ , Weisman MH 
Published: April 2009

In this study, the clinical course and change in extra-renal manifestations of patients with SLE taking mycophenolate mofetil (MMF) were evaluated. The charts of 75 consecutively identified patients on MMF from a single practice were reviewed for demographics, dates of SLE diagnosis, initiation, indication or discontinuation of MMF and other medications. British Isles Lupus Assessment Group (BILAG) organ system data were identified for 3 months prior to MMF and then for the subsequent 5 years. BILAG scores for each organ system and an overall score were calculated for intervals of 6 months. The mean age of 75 subjects was 35.8 years with SLE mean disease duration of 99.2 months. Indications for starting MMF were renal (70.7%), musculoskeletal (10.6%), mucocutaneous (9.3%), cardiorespiratory (5.3%), haematologic (4%), vasculitic (2.7%), neurologic (1.3%) and other (18.7%). The mean duration of treatment was 3.3 years; 22 discontinuations occurred. Overall, there was a >50% improvement in composite BILAG scores for 49.3% (37/75) of patients in the first year of treatment and in 20% (15/75) of patients who were still on MMF at ≥5 years. Most flares occurred at second and third year of treatment. The general and renal systems have the most improvement and clinical remissions; the musculoskeletal, mucocutaneous and haematological systems have the most recurrences. Approximately, 50% and 20% of patients taking MMF showed improvement in overall lupus disease activity at both 1 and 5 years, respectively. When evaluating organ system subsets separately, MMF improved disease activity in the first year, but had little effect in preventing new organ-specific flares, with most flares taking place in second and third year of treatment.
Arterial wall dysfunction in systemic lupus erythematosus
Authors: Cypiene A , Kovaite M , Venalis A , Dadoniene J , Rugiene R , Petrulioniene Z , Ryliskyte L , Laucevicius A 
Published: April 2009

Carotid-radial pulse wave velocity (PWV), aortic augmentation index (AIx) and endothelium-dependent flow-mediated dilatation (FMD) have been repeatedly showed to be related to premature atherosclerosis and cardiovascular diseases in different settings of population. The increased arterial stiffness and endothelium dysfunction may add to premature aging of the arteries in systemic lupus erythematosus (SLE) patients. Still data about arterial stiffness and endothelium function in inflammatory rheumatic diseases are not well described. The aim of this study was to determine the PWV, its derivate marker AIx and FMD and factors possibly influencing them in young SLE women without significant organ damage. Thirty women between 23 and 55 years with an established SLE diagnosis and 66 healthy women were consequently included in the study and both groups were comparable according to age, body mass index (BMI), serum lipid profile and creatinine. PWV was determined by measuring carotid-radial pulse wave transit time with the help of applanation tonometry and AIx, its derivate marker, was calculated as a difference between two waveform peaks expressed as a percentage of the pulse pressure. The FMD was performed by obtaining the repeated scans of the brachial artery at rest and during reactive hyperemia. In SLE women, PWV and AIx were significantly higher and FMD was not different from controls. In linear multiple stepwise regression analysis if patients and controls were both considered, PWV was weakly related to mean blood pressure (MBP), AIx was mostly predicted by age and MBP and FMD was predicted by the diameter of blood vessel, BMI, high density lipoproteins. If the sole SLE setting was analyzed, PWV was not related to any of the pending parameters, AIx turned out to be related to organ damage measured by Systemic Lupus International collaborative Clinics (SLICC) index and age, and FMD obtained strong and significant relation with vessel diameter, and BMI, and disease duration. Regardless of the small number of study group patients, we can state that controlling for MBP and taking measures towards organ damage prevention can partially slow down the process of early atherosclerosis in SLE patients.
Serum complement activation on heterologous platelets is associated with arterial thrombosis in patients with systemic lupus erythematosus and antiphospholipid antibodies
Authors: Peerschke EIB , Yin W , Alpert DR , Roubey RAS , Salmon JE , Ghebrehiwet B 
Published: April 2009

Complement plays a major role in inflammation and thrombosis associated with systemic lupus erythematosus (SLE) and the antiphospholipid syndrome (APS). A cross-sectional retrospective analysis was performed to evaluate serum complement fixation on platelets and thrombotic incidence using banked sera and clinical data from patients with SLE ( n = 91), SLE with antiphospholipid antibodies (aPL) or APS ( n = 78) and primary aPL ( n = 57) or APS ( n = 96). In-situ complement fixation was measured as C1q and C4d deposition on heterologous platelets using an enzyme-linked immunosorbent assay approach. Platelet activation by patient serum in the fluid phase was assessed via serotonin release assay. Enhanced in-situ complement fixation was associated with the presence of IgG aPL and IgG anti-β2 glycoprotein 1 antibodies ( P < 0.05) and increased platelet activation ( P < 0.005). Moreover, enhanced complement fixation, especially C4d deposition on heterologous platelets, was positively associated with arterial thrombotic events in patients with SLE and aPL ( P = 0.039). Sera from patients with aPL possess an enhanced capacity for in-situ complement fixation on platelets. This capacity may influence arterial thrombosis risk in patients with SLE.
Fulminant leucocytoclastic brainstem vasculitis in a patient with otherwise indolent systemic lupus erythematosus
Authors: Kleinig TJ , Koszyca B , Blumbergs PC , Thompson P 
Published: April 2009

The spectrum of central nervous system (CNS) vascular pathology in systemic lupus erythematosus (SLE) includes small vessel vasculopathy, thromboembolism, perivascular lymphocytic infiltration and, rarely, overt transmural vasculitis. We present the case of a patient, who experienced three CNS relapses over total disease duration of 26 years, with otherwise indolent disease. The first two relapses were suspicious of vasculitis and the last was proven at autopsy. The short duration between final relapse onset and death in this SLE CNS vasculitis case was, to our knowledge, unique. Histopathological investigation demonstrated multiple confluent areas of haemorrhage in the medulla due to an acute small vessel leucocytoclastic vasculitis.
Ultraviolet light output of compact fluorescent lamps: comparison to conventional incandescent and halogen residential lighting sources
Authors: Nuzum-Keim AD , Sontheimer RD 
Published: April 2009

Patients with photosensitive dermatologic and systemic diseases often question the ultraviolet light (UVL) output of household lighting sources. Such individuals have increasing concern about potential UVL exposure from energy-efficient compact fluorescent lamps (CFL), as little data have been presented concerning their UVL output. The objective was to compare, via pilot study, the levels of ultraviolet A (UVA) and ultraviolet B (UVB) leak between residential lighting sources. Equivalent wattage CFL, incandescent and halogen bulbs were purchased from local retailers in Oklahoma City, Oklahoma, USA. The UVA and UVB outputs of these sources were measured under controlled conditions at 10, 25, 50, 100 and 150 cm away from the light source using an IL-1700 research radiometer equipped with UVA and UVB detectors. Negligible UVB and UVA was detected at 100 and 150 cm. Therefore, data were analysed from measurements at 10, 25 and 50 cm only. The results demonstrated UVA leak highest from incandescent and halogen bulbs, and UVB leak highest from CFL. The overall UVA/UVB leak was lowest from CFL shielded during the manufacturing process. In conclusion, patients with photosensitivity have choices depending on their relative risk from different UVL wavelength spectra. UVB exposure risk may be reduced the greatest by utilising CFL with manufacturer-provided shields.
Gene synteny comparisons between different vertebrates provide new insights into breakage and fusion events during mammalian karyotype evolution
Authors: Kemkemer Claus , Kohn Matthias , Cooper David N , Froenicke Lutz , Högel Josef , Hameister Horst , Kehrer-Sawatzki Hildegard 
Published: April 2009

Abstract

Background
Genome comparisons have made possible the reconstruction of the eutherian ancestral karyotype but also have the potential to provide new insights into the evolutionary inter-relationship of the different eutherian orders within the mammalian phylogenetic tree. Such comparisons can additionally reveal (i) the nature of the DNA sequences present within the evolutionary breakpoint regions and (ii) whether or not the evolutionary breakpoints occur randomly across the genome. Gene synteny analysis (E-painting) not only greatly reduces the complexity of comparative genome sequence analysis but also extends its evolutionary reach.

Results
E-painting was used to compare the genome sequences of six different mammalian species and chicken. A total of 526 evolutionary breakpoint intervals were identified and these were mapped to a median resolution of 120 kb, the highest level of resolution so far obtained. A marked correlation was noted between evolutionary breakpoint frequency and gene density. This correlation was significant not only at the chromosomal level but also sub-chromosomally when comparing genome intervals of lengths as short as 40 kb. Contrary to previous findings, a comparison of evolutionary breakpoint locations with the chromosomal positions of well mapped common fragile sites and cancer-associated breakpoints failed to reveal any evidence for significant co-location. Primate-specific chromosomal rearrangements were however found to occur preferentially in regions containing segmental duplications and copy number variants.

Conclusion
Specific chromosomal regions appear to be prone to recurring rearrangement in different mammalian lineages ('breakpoint reuse') even if the breakpoints themselves are likely to be non-identical. The putative ancestral eutherian genome, reconstructed on the basis of the synteny analysis of 7 vertebrate genome sequences, not only confirmed the results of previous molecular cytogenetic studies but also increased the definition of the inferred structure of ancestral eutherian chromosomes. For the first time in such an analysis, the opossum was included as an outgroup species. This served to confirm our previous model of the ancestral eutherian genome since all ancestral syntenic segment associations were also noted in this marsupial.
Two-stage genome-wide association study identifies integrin beta 5 as having potential role in bull fertility
Authors: Feugang Jean M , Kaya Abdullah , Page Grier P , Chen Lang , Mehta Tapan , Hirani Kashif , Nazareth Lynne , Topper Einko , Gibbs Richard , Memili Erdogan 
Published: April 2009

Abstract

Background
Fertility is one of the most critical factors controlling biological and financial performance of animal production systems and genetic improvement of lines. The objective of this study was to identify molecular defects in the sperm that are responsible for uncompensable fertility in Holstein bulls. We performed a comprehensive genome wide analysis of single nucleotide polymorphisms (SNP) for bull fertility followed by a second-stage replication in additional bulls for a restricted set of markers.

Results
In the Phase I association study, we genotyped the genomic sperm DNA of 10 low-fertility and 10 high-fertility bulls using Bovine SNP Gene Chips containing approximately 10,000 random SNP markers. In these animals, 8,207 markers were found to be polymorphic, 97 of which were significantly associated with fertility (p < 0.01). In the Phase II study, we tested the four most significant SNP from the Phase I study in 101 low-fertility and 100 high-fertility bulls, with two SNPs (rs29024867 and rs41257187) significantly replicated. Rs29024867 corresponds to a nucleotide change of C → G 2,190 bp 3' of the collagen type I alpha 2 gene on chromosome 4, while the rs41257187 (C → T) is in the coding region of integrin beta 5 gene on chromosome 1. The SNP rs41257187 induces a synonymous (Proline → Proline), suggesting disequilibrium with the true causative locus (i), but we found that the incubation of bull spermatozoa with integrin beta 5 antibodies significantly decreased the ability to fertilize oocytes. Our findings suggest that the bovine sperm integrin beta 5 protein plays a role during fertilization and could serve as a positional or functional marker of bull fertility.

Conclusion
We have identified molecular markers associated with bull fertility and established that at least one of the genes harboring such variation has a role in fertility. The findings are important in understanding mechanisms of uncompensatory infertility in bulls, and in other male mammals. The findings set the stage for more hypothesis-driven research aimed at discovering the role of variation in the genome that affect fertility and that can be used to identify molecular mechanisms of development.
A high resolution RH map of the bovine major histocompatibility complex
Authors: Brinkmeyer-Langford Candice L , Childers Christopher P , Fritz Krista L , Gustafson-Seabury Ashley L , Cothran Marian , Raudsepp Terje , Womack James E , Skow Loren C 
Published: April 2009

Abstract

Background
The cattle MHC is termed the bovine leukocyte antigen (BoLA) and, along with the MHCs of other ruminants, is unique in its genomic organization. Consequently, correct and reliable gene maps and sequence information are critical to the study of the BoLA region. The bovine genome sequencing project has produced two assemblies (Btau_3.1 and 4.0) that differ substantially from each other and from conventional gene maps in the BoLA region. To independently compare the accuracies of the different sequence assemblies, we have generated a high resolution map of BoLA using a 12,000rad radiation hybrid panel. Seventy-seven unique sequence tagged site (STS) markers chosen at approximately 50 kb intervals from the Btau 2.0 assembly and spanning the IIa-III-I and IIb regions of the bovine MHC were mapped on a 12,000rad bovine radiation hybrid (RH) panel to evaluate the different assemblies of the bovine genome sequence.

Results
Analysis of the data generated a high resolution RH map of BoLA that was significantly different from the Btau_3.1 assembly of the bovine genome but in good agreement with the Btau_4.0 assembly. Of the few discordancies between the RH map and Btau_4.0, most could be attributed to closely spaced markers that could not be precisely ordered in the RH panel. One probable incorrectly-assembled sequence and three missing sequences were noted in the Btau_4.0 assembly. The RH map of BoLA is also highly concordant with the sequence-based map of HLA (NCBI build 36) when reordered to account for the ancestral inversion in the ruminant MHC.

Conclusion
These results strongly suggest that studies using Btau_3.1 for analyses of the BoLA region should be reevaluated in light of the Btau_4.0 assembly and indicate that additional research is needed to produce a complete assembly of the BoLA genomic sequences.
Characterization of the bovine pregnancy-associated glycoprotein gene family – analysis of gene sequences, regulatory regions within the promoter and expression of selected genes
Authors: Telugu Bhanu Prakash VL , Walker Angela M , Green Jonathan A 
Published: April 2009

Abstract

Background
The Pregnancy-associated glycoproteins (PAGs) belong to a large family of aspartic peptidases expressed exclusively in the placenta of species in the Artiodactyla order. In cattle, the PAG gene family is comprised of at least 22 transcribed genes, as well as some variants. Phylogenetic analyses have shown that the PAG family segregates into 'ancient' and 'modern' groupings. Along with sequence differences between family members, there are clear distinctions in their spatio-temporal distribution and in their relative level of expression. In this report, 1) we performed an in silico analysis of the bovine genome to further characterize the PAG gene family, 2) we scrutinized proximal promoter sequences of the PAG genes to evaluate the evolution pressures operating on them and to identify putative regulatory regions, 3) we determined relative transcript abundance of selected PAGs during pregnancy and, 4) we performed preliminary characterization of the putative regulatory elements for one of the candidate PAGs, bovine (bo) PAG-2.

Results
From our analysis of the bovine genome, we identified 18 distinct PAG genes and 14 pseudogenes. We observed that the first 500 base pairs upstream of the translational start site contained multiple regions that are conserved among all boPAGs. However, a preponderance of conserved regions, that harbor recognition sites for putative transcriptional factors (TFs), were found to be unique to the modern boPAG grouping, but not the ancient boPAGs. We gathered evidence by means of Q-PCR and screening of EST databases to show that boPAG-2 is the most abundant of all boPAG transcripts. Finally, we provided preliminary evidence for the role of ETS- and DDVL-related TFs in the regulation of the boPAG-2 gene.

Conclusion

PAGs represent a relatively large gene family in the bovine genome. The proximal promoter regions of these genes display differences in putative TF binding sites, likely contributing to observed differences in spatial and temporal expression. We also discovered that boPAG-2 is the most abundant of all boPAG transcripts and provided evidence for the role of ETS and DDVL TFs in its regulation. These experiments mark the crucial first step in discerning the complex transcriptional regulation operating within the boPAG gene family.