bluuebunny/crossref_metadata_2025_split huggingface dataset:
CTLA-4+49A/G and CT60 gene polymorphisms in primary Sjögren syndrome
Authors: Gottenberg Jacques-Eric , Loiseau Pascale , Azarian Mariam , Chen Chun , Cagnard Nicolas , Hachulla Eric , Puechal Xavier , Sibilia Jean , Charron Dominique , Mariette Xavier , Miceli-Richard Corinne 
Published: March 2007

Abstract
CTLA-4 encodes cytotoxic T lymphocyte-associated antigen-4, a cell-surface molecule providing a negative signal for T-cell activation. CTLA-4 gene polymorphisms have been widely studied in connection with genetic susceptibility to various autoimmune diseases, but studies have led to contradictory results in different populations. This case-control study sought to investigate whether CTLA-4 CT60 and/or +49A/G polymorphisms were involved in the genetic predisposition to primary Sjögren syndrome (pSS). We analysed CTLA-4 CT60 and +49A/G polymorphisms in a first cohort of 142 patients with pSS (cohort 1) and 241 controls, all of Caucasian origin. A replication study was performed on a second cohort of 139 patients with pSS (cohort 2). In cohort 1, the CTLA-4 +49A/G*A allele was found on 73% of chromosomes in patients with pSS, compared with 66% in controls (p = 0.036; odds ratio (OR) 1.41, 95% confidence interval (CI) 1.02 to 1.95). No difference in CTLA-4 CT60 allelic or genotypic distribution was observed between patients (n = 142) and controls (n = 241). In the replication cohort, the CTLA-4 +49A/G*A allele was found on 62% of chromosomes in patients with pSS, compared with 66% in controls (p = 0.30; OR 0.85, 95% CI 0.63 to 1.16). Thus, the CTLA-4 +49A/G*A allele excess among patients from cohort 1 was counterbalanced by its under-representation in cohort 2. When the results from the patients in both cohorts were pooled (n = 281), there was no difference in CTLA-4 +49A/G allelic or genotypic distribution in comparison with controls. Our results demonstrate a lack of association between CTLA-4 CT60 or +49A/G polymorphisms and pSS. Premature conclusions might have been made if a replication study had not been performed. These results illustrate the importance of case-control studies performed on a large number of patients. In fact, sampling bias may account for some contradictory results previously reported for CTLA-4 association studies in autoimmune diseases.
Differential expression of RANK, RANK-L, and osteoprotegerin by synovial fluid neutrophils from patients with rheumatoid arthritis and by healthy human blood neutrophils
Authors: Poubelle Patrice E , Chakravarti Arpita , Fernandes Maria J , Doiron Karine , Marceau Andrée-Anne 
Published: March 2007

Abstract
Functional links between bone remodeling and the immune system in chronic inflammatory arthritis are mediated, in part, by the ligand of receptor activator of nuclear factor-kappa-B (RANK-L). Because neutrophils play a crucial role in chronic inflammation, the goal of this study was to determine whether proteins of the RANK/RANK-L pathway are expressed by synovial fluid (SF) neutrophils from patients with rheumatoid arthritis (RA) and to characterize this pathway in normal human blood neutrophils. The expression of RANK-L, osteoprotegerin (OPG), RANK, and tumor necrosis factor receptor-associated factor 6 (TRAF6) was determined by polymerase chain reaction, enzyme-linked immunosorbent assay, Western blotting, and cytofluorometry. RANK signaling was analyzed by the degradation of inhibitor of kappaB-alpha (I-κB-α). SF neutrophils from patients with RA express and release OPG and express the membrane-associated forms of RANK-L and RANK. In contrast, normal blood neutrophils express only the membrane-associated form of RANK-L. They do not express the mRNAs encoding OPG and RANK. SF neutrophils from RA patients and normal blood neutrophils release no soluble RANK-L. They express the mRNA for TRAF6. The expression of OPG and RANK by normal human blood neutrophils, however, can be induced by interleukin-4 + tumor necrosis factor-alpha and by SFs from patients with RA. In contrast, SFs from patients with osteoarthritis do not induce the expression of OPG and RANK. Moreover, the addition of RANK-L to normal blood neutrophils pretreated by SF from patients with RA decreased I-κB-α, indicating that RANK signaling by neutrophils stimulated with SF is associated with nuclear factor-kappa-B activation. In summary, RANK-L is expressed by inflammatory and normal neutrophils, unlike OPG and RANK, which are expressed only by neutrophils exposed to an inflammatory environment. Taken together, these results suggest that neutrophils may contribute to bone remodeling at inflammatory sites where they are present in significantly large numbers.
The association between patellar alignment on magnetic resonance imaging and radiographic manifestations of knee osteoarthritis
Authors: Kalichman Leonid , Zhang Yuqing , Niu Jingbo , Goggins Joyce , Gale Daniel , Zhu Yanyan , Felson David T , Hunter David J 
Published: March 2007

Abstract
The aim of our study was to evaluate the association between patellar alignment by using magnetic resonance imaging images and radiographic manifestations of patello-femoral osteoarthritis (OA). Subjects were recruited to participate in a natural history study of symptomatic knee OA. We examined the relation of patellar alignment in the sagittal plane (patellar length ratio (PLR)) and the transverse plane (sulcus angle (SA), lateral patellar tilt angle (LPTA), and bisect offset (BO)) to radiographic features of patello-femoral OA, namely joint space narrowing and patellar osteophytes, using a proportional odds logistic regression model while adjusting for age, sex, and bone mass index (BMI). The study sample consisted of 126 males (average age 68.0 years, BMI 31.2) and 87 females (average age 64.7 years, BMI 31.6), 75% of whom had tibiofemoral OA (a Kellgren-Lawrence score of 2 or more). PLR showed a statistically significant association with joint space narrowing and osteophytosis in the lateral compartment. SA showed significant association with medial joint space narrowing and with lateral and medial patellar osteophytosis. LPTA and BO showed significant association with both radiographic indices of the lateral compartment. Clear linear trends were found in association between PLR, LPTA and BO, and with outcomes associated with lateral patello-femoral OA. SA, LPTA, and BO showed linear trends of association with medial joint space narrowing. Results of our study clearly suggest the association between indices of patellar alignment and such features of patello-femoral OA as osteophytosis and joint space narrowing. Additional studies will be required to establish the normal and abnormal ranges of patellar alignment indices and their longitudinal relation to patello-femoral OA.
Association of estrogen receptor-α and progesterone receptor A expression with hormonal mammary carcinogenesis: role of the host microenvironment
Authors: Montero Girard Guadalupe , Vanzulli Silvia I , Cerliani Juan Pablo , Bottino María Cecilia , Bolado Julieta , Vela Jorge , Becu-Villalobos Damasia , Benavides Fernando , Gutkind Silvio , Patel Vyomesh , Molinolo Alfredo , Lanari Claudia 
Published: March 2007

Abstract
Introduction
Medroxyprogesterone acetate (MPA) induces estrogen receptor (ER)-positive and progesterone receptor (PR)-positive ductal invasive mammary carcinomas in BALB/c mice. We sought to reproduce this MPA cancer model in C57BL/6 mice because of their widespread use in genetic engineering. Within this experimental setting, we studied the carcinogenic effects of MPA, the morphologic changes in mammary glands that are induced by MPA and progesterone, and the levels of ER and PR expression in MPA-treated and progesterone-treated mammary glands. Finally, we evaluated whether the differences found between BALB/c and C57BL/6 mouse strains were due to intrinsic differences in epithelial cells.

Methods
The carcinogenic effect of MPA was evaluated in C57BL/6 mice using protocols proven to be carcinogenic in BALB/c mice. In addition, BALB/c and C57BL/6 females were treated with progesterone or MPA for 1 or 2 months, and mammary glands were excised for histologic studies and for immunohistochemical and Western blot evaluation of ER and PR. Hormone levels were determined by radioimmunoassay. Isolated mammary epithelial cells were transplanted into cleared fat pads of 21-day-old female Swiss nu/nu mice or control congenic animals.

Results
MPA failed to induce mammary carcinomas or significant morphologic changes in the mammary glands of C57BL/6 mice. The expression of ER-α and PR isoform A in virgin mice was surprisingly much higher in BALB/c than in C57BL/6 mammary glands, and both receptors were downregulated in progestin-treated BALB/c mice (P < 0.05). PR isoform B levels were low in virgin control mice and increased after progestin treatment in both strains. ER-β expression followed a similar trend. No differences in hormone levels were found between strains. Surprisingly, the transplantation of the epithelial mammary gland cells of both strains into the cleared fat pads of Swiss (nu/nu) mice abolished the mammary gland morphologic differences and the ER and PR differences between strains.

Conclusion
C57BL/6 mammary glands are resistant to MPA-induced carcinogenesis and to hormone action. MPA and progesterone have different effects on mammary glands. Low ER-α and PR-A levels in untreated mammary glands may be associated with a low-risk breast cancer profile. Although we cannot at this time rule out the participation of other, untested factors, our findings implicate the stroma as playing a crucial role in the strain-specific differential hormone receptor expression and hormone responsiveness.
Case mix, outcome, and activity for admissions to UK critical care units with severe acute pancreatitis: a secondary analysis of the ICNARC Case Mix Programme Database
Authors: Harrison David A , D'Amico Giovanna , Singer Mervyn 
Published: March 2007

Abstract
Introduction
Severe acute pancreatitis (SAP) requiring admission to a critical care unit is associated with high mortality and long lengths of stay. We describe the case mix, outcome, and activity of admissions with SAP who were identified from a high-quality clinical database.

Methods
We conducted a secondary analysis of the ICNARC (Intensive Care National Audit & Research Centre) Case Mix Programme Database of 219,468 admissions to 159 adult, general critical care units in England, Wales, and Northern Ireland for the period of 1995 to 2003 to identify admissions with SAP. The ability of the modified Glasgow criteria to discriminate hospital survivors from non-survivors was compared to that of the Acute Physiology and Chronic Health Evaluation (APACHE) II score and a number of individual physiological parameters.

Results
A total of 2,677 admissions with SAP were identified (1.2% of all admissions). Mortality for these admissions was 31% in the critical care unit and 42% in hospital. The median length of stay in the critical care unit was 3.8 days and was similar for survivors and non-survivors. Increasing numbers of modified Glasgow criteria were associated with increasing hospital mortality, but better discrimination was provided by the APACHE II score and by several physiological parameters.

Conclusion
SAP requiring critical care is associated with high mortality and long length of stay. The modified Glasgow criteria represent a simple measure of severity but were not designed to predict hospital mortality. It may be possible to develop a specific model for risk prediction in patients with SAP requiring critical care.
Alternative ion channel splicing in mesial temporal lobe epilepsy and Alzheimer's disease
Authors: Heinzen Erin L , Yoon Woohyun , Weale Michael E , Sen Arjune , Wood Nicholas W , Burke James R , Welsh-Bohmer Kathleen A , Hulette Christine M , Sisodiya Sanjay M , Goldstein David B 
Published: March 2007

Abstract
Background
Alternative gene transcript splicing permits a single gene to produce multiple proteins with varied functions. Bioinformatic investigations have identified numerous splice variants, but whether these transcripts are translated to functional proteins and the physiological significance of these alternative proteins are largely unknown. Through direct identification of splice variants associated with disease states, we can begin to address these questions and to elucidate their roles in disease predisposition and pathophysiology. This work specifically sought to identify disease-associated alternative splicing patterns in ion channel genes by comprehensively screening affected brain tissue collected from patients with mesial temporal lobe epilepsy and Alzheimer's disease. New technology permitting the screening of alternative splice variants in microarray format was employed. Real time quantitative PCR was used to verify observed splice variant patterns.

Results
This work shows for the first time that two common neurological conditions are associated with extensive changes in gene splicing, with 25% and 12% of the genes considered having significant changes in splicing patterns associated with mesial temporal lobe epilepsy and Alzheimer's disease, respectively. Furthermore, these changes were found to exhibit unique and consistent patterns within the disease groups.

Conclusion
This work has identified a set of disease-associated, alternatively spliced gene products that represent high priorities for detailed functional investigations into how these changes impact the pathophysiology of mesial temporal lobe epilepsy and Alzheimer's disease.
Measurement of Serum Free Cortisol Shows Discordant Responsivity to Stress and Dynamic Evaluation
Authors: Christ-Crain Mirjam , Jutla Sukhdeep , Widmer Isabelle , Couppis Orestes , König Caroline , Pargger Hans , Puder Jardena , Edwards Ray , Müller Beat , Grossman Ashley B. 
Published: March 2007

Abstract
Context: Routinely available assays of adrenal function measure serum total cortisol (TC) and not the biologically active free cortisol (FC). However, there are few data on FC levels during surgical stress and in response to standard pharmacological tests.
Objective: Our objective was to evaluate TC and FC levels in different states of physical stress.
Design and Setting: We conducted a prospective observational study in a university hospital.
Participants and Main Outcome Measures: We measured TC and FC levels in 64 patients: group A, 17 healthy controls without stress; group B, 23 medical patients with moderate stress; and group C, 24 surgical patients undergoing coronary bypass grafting. Cortisol levels in group C were measured basally and at several time points thereafter and were compared with responsivity to a pharmacological dose of ACTH. FC was measured using equilibrium dialysis.
Results: In group C patients after extubation, the relative increase above basal FC was higher than the increase in TC levels (399 ± 266 vs. 247 ± 132% of initial values, respectively; mean ± sd; P = 0.02) and then fell more markedly, FC levels falling to 67 ± 49% and TC levels to 79 ± 36% (P = 0.04). After ACTH stimulation, TC levels increased to 680 ± 168 nmol/liter, which was similar to the increase with major stress (811 ± 268 nmol/liter). In contrast, FC levels increased to 55 ± 16 nmol/liter after ACTH stimulation but significantly greater with surgical stress to 108 ± 56 nmol/liter (P &lt; 0.001).
Conclusion: The more pronounced increase in FC seen during stress as compared with the ACTH test suggests that this test does not adequately anticipate the FC levels needed during severe stress.
Stress Responsiveness in Adult Life: Influence of Mother’s Diet in Late Pregnancy
Authors: Reynolds Rebecca M. , Godfrey Keith M. , Barker Mary , Osmond Clive , Phillips David I. W. 
Published: March 2007

Abstract
Context: Men and women whose mothers ate an unbalanced high-protein, low-carbohydrate diet in late pregnancy have raised blood pressure. We recently showed that they also have raised fasting plasma cortisol concentrations. Because raised fasting cortisol concentrations probably reflect a greater response to the stress of fasting and venesection, we suspected that this diet may have led to increased stress responsiveness in the adult offspring.
Objective: The aim was to determine whether an unbalanced high-protein diet during pregnancy is associated with increased cortisol secretion in response to psychological stress in the offspring.
Design and Participants: Salivary cortisol concentrations were measured during a modified Trier Social Stress Test in 70 men and women aged 36.3 yr whose mothers had taken part in a dietary intervention in which they were advised to eat 1 pound (0.45 kg) of red meat daily during pregnancy and to avoid carbohydrate-rich foods.
Results: The offspring of women who reported greater consumption of meat and fish in the second half of pregnancy had higher cortisol concentrations during the Trier Test. Compared with the offspring of mothers who had reported eating no more than 13 meat/fish portions per week, the average cortisol concentrations were raised by 22% (95% confidence interval, 13 to 71%) and 46% (5 to 103%) in the offspring of those eating 14–16 and at least 17 portions per week, respectively.
Conclusions: These findings provide the first human evidence that an unbalanced high protein maternal diet during late pregnancy leads to increased cortisol secretion in response to psychological stress in the offspring.
Ikaros Is Regulated through Multiple Histone Modifications and Deoxyribonucleic Acid Methylation in the Pituitary
Authors: Zhu Xuegong , Asa Sylvia L. , Ezzat Shereen 
Published: March 2007

Abstract
The transcription factor Ikaros (Ik) is at the center of a functionally diverse chromatin-remodeling network that is critical for the development and regulation of both the immune and endocrine systems. Dominant negative forms of Ik result in neoplastic growth in mouse genetic studies and have been identified in human tumors. Ik modulates chromatin accessibility through associations with members of the NURD complex including histone deacetylase complexes. We show here that Ik expression in mouse pituitary corticotroph cells is itself regulated through histone modifications as well as DNA methylation. Examination of primary human pituitary specimens also identified a correlation of loss of Ik expression with the presence of DNA methylation in the untranslated exon 1 CpG island. These findings have important implications for the understanding of Ikaros’ role in epigenetic functions and suggest a potential role for demethylating agents in the treatment of related disorders.
Field linguistics: a minor manual
Authors: Dixon R.M.W. 
Published: March 2007

Abstract
This manual provides basic information concerning linguistic fieldwork. What is it? Why do it? The ethics involved. How to choose a field language and a field location. How to go about it. What to get – a comprehensive reference grammar (written in terms of basic linguistic theory), a volume of texts, and a dictionary/thesaurus. What to do: insofar as possible, become a member of the community (for ‘immersion fieldwork’); analyse texts; only use elicitation at a late stage, within the language of study (not from a lingua franca). How to work with consultants (and some things which should be avoided). Writing up the grammar. There is a short final section concerning field methods courses in a university.
A separate and peculiar people – fieldwork and the Pennsylvania Germans
Authors: Burridge Kate 
Published: March 2007

AbstractThe following is an account of fieldwork experience in the Old Order Mennonite community of Waterloo County, Ontario. The language spoken here is Pennsylvania German and this paper focuses on methodological and ethical challenges that arise for any linguist wanting to study this language in its natural setting. This is a close-knit, ultra-conservative and deeply religious speech community, specifically one that wants to remain apart from the outside world. Even the issue of language survival does not give the linguist a natural role to play. Formal maintenance efforts are not in demand. Pennsylvania German is a language that has been holding its own for nearly 400 years and it is the humble, separate and ‘peculiar’ existence of these speakers that holds the key to the continued existence of this language.
Fieldwork among the Goemai in Nigeria: discovering the grammar of property expressions
Authors: Hellwig Birgit 
Published: March 2007

Abstract
This paper describes fieldwork experiences among the Goemai of Central Nigeria. It first introduces the fieldwork setting, and then focuses on one illustrative example: the investigation of property-denoting (‘adjectival’) expressions. The paper describes the different methods employed, compares them, and evaluates their results. It shows some advantages and disadvantages, and – on this basis – advocates using a combination of methods in order to benefit from each method's advantages while counterbalancing its disadvantages. In particular, the paper argues in favour of a semantics-based approach to fieldwork, illustrating the invaluable insights to be gained from it.
Effects of Population Increase on Cui‐ui Growth and Maturation
Authors: Scoppettone G. Gary , Rissler Peter H. 
Published: March 2007

AbstractCui‐ui Chasmistes cujus is endemic to Pyramid Lake, Nevada. The cui‐ui population declined during much of the 20th century as a result of water diversion and the formation of a shallow and virtually impassable delta at the mouth of the Truckee River, its spawning habitat. The population increased more than 10‐fold to more than 1 million adults after access to the river was restored, creating a period of relatively higher density. This change presented the opportunity to test intraspecific density effects on cui‐ui age and length at maturity and on growth. We also compared the year‐class structure of the adult population before and after improved access. At low density, cui‐ui mean age at maturation was 9.2 years for males and 9.6 for females; at high density, it was significantly higher: 11.8 years for males and 12.0 for females. There was no significant change in mean fork length at maturity related to population increase. Growth patterns differed between high and low density, the low‐density fish growing faster than high‐density fish before their respective mean age of maturity; past their mean age at maturity, high‐density fish grew significantly faster than low‐density fish. Fish in both density periods reached similar lengths by about 19–20 years of age. Year‐class structure for both density periods consisted of strong year‐classes, which predominated the adult population for several years.
Field‐Based Estimates of Thermal Tolerance Limits for Trout: Incorporating Exposure Time and Temperature Fluctuation
Authors: Wehrly Kevin E. , Wang Lizhu , Mitro Matthew 
Published: March 2007

AbstractWe used temperature and fish data from streams across Michigan and Wisconsin to estimate upper thermal tolerance limits for brook trout Salvelinus fontinalis and brown trout Salmo trutta. Tolerance limits were estimated for the maximum daily mean temperature (MEANT), maximum daily maximum temperature (MAXT), and maximum daily temperature range (RNGT) at exposure lengths of 1, 3, 7, 14, 21, 28, 35, 42, 49, 56, and 63 d. We found no difference in the upper thermal tolerance limit for brook and brown trout. For time periods of 1–14 d, the upper temperatures tolerated by trout decreased rapidly from 25.3°C to 22.5°C for MEANT and from 27.6°C to 24.6°C for MAXT. For time periods from 21 to 63 d, the upper temperatures tolerated by trout declined more gradually from 22.1°C to 21.0°C for MEANT and from 24.2°C to 22.9°C for MAXT. The 7‐d upper tolerance limit was 23.3°C for MEANT and 25.4°C for MAXT. The maximum RNGT tolerated by trout varied as a function of mean temperature and length of exposure. Our findings suggest that chronic temperature effects as well as temperature fluctuation play an important role in limiting salmonid distributions and therefore should be considered when developing management objectives and water quality standards.