bluuebunny/crossref_metadata_2025_split huggingface dataset:
The cardiac calsequestrin gene (CASQ2) is up‐regulated in the thyroid in patients with Graves’ ophthalmopathy – support for a role of autoimmunity against calsequestrin as the triggering event
Authors: Wescombe Leon , Lahooti Hooshang , Gopinath Bamini , Wall Jack R. 
Published: December 2009

SummaryBackground  Graves’ Ophthalmopathy (GO) is a complex eye and orbital disorder that is uniquely linked to Graves’ Hyperthyroidism (GH) and has traditionally been considered a cross‐reactive immune response against the thyroid stimulating hormone receptor (TSHR) in orbital tissue. However, because there is no direct evidence, such as specific TSHR antibodies or T lymphocytes targeting the orbital tissues in patients with GO compared to those without eye disease, it is important to consider alternative hypotheses for the pathogenesis of GO. The aim of this study was to identify differentially expressed genes within the thyroid of patients with GO and GH as a possible explanation for a thyroid initiated orbital autoimmunity.Methods  RNA was extracted from thyroid glands of patients with GO (n = 10) and GH (n = 8) post‐total thyroidectomy. RNA samples were arrayed on Illumina® Human Ref‐8 Expression BeadChips™ representing 20 589 genes. Microarray results of selected genes were validated by quantitative PCR (qPCR) and levels of protein translation measured by Western blot analysis.Findings  Two hundred and nighty‐five genes were differentially expressed between patients with GO and GH. Of these, the cardiac calsequestrin gene (CASQ2) was the most highly expressed gene in GO (2·2‐fold increase, P < 0·05). The succinate dehydrogenase flavoprotein subunit gene (SDHA) was also significantly up‐regulated in GO (P < 0·05), 1·4‐fold, while genes encoding the thyroid antigens thyroglobulin, thyroid peroxidase and TSHR were not differentially expressed. qPCR verified up‐regulation of CASQ2 and down‐regulation BMP7, CD80, IGFBP5, and MYD88 genes in GO. Western blot analysis showed that the average CASQ/GAPDH protein expression ratios for GH and GO were 1·04 and 1·03, respectively. t‐Test analysis of data generated a P‐value of 0·26, therefore no significant difference was found for CASQ protein expression in thyroid tissue between GH and GO.Interpretation  The skeletal and cardiac calsequestrin proteins share 68·4% amino acid homology. Previous work has shown that RNA levels of skeletal muscle calsequestrin are 4·7 times higher in extraocular muscle (EOM) than in masticatory skeletal muscle (jaw), and cardiac calsequestrin is expressed 2·7 times more in EOM. We postulate that up‐regulation of casq2 gene in the thyroid of patients with GH may lead to the production of autoantibodies and sensitized T‐lymphocytes, which cross‐react with calsequestrin in the EOM of patients who develop ophthalmopathy.
The 4‐mg intravenous dexamethasone suppression test in the diagnosis of Cushing’s syndrome
Authors: Jung Caroline , Alford Frank P. , Topliss Duncan J. , Burgess John R. , Long Fiona , Gome James J. , Stockigt Jim R. , Inder Warrick J. 
Published: December 2009

SummaryObjective  Optimal diagnostic criteria for the 4‐mg intravenous dexamethasone suppression test (IVDST) in patients with Cushing’s syndrome (CS), compared with normal subjects, have not been established. We evaluated the performance of the 4‐mg IVDST for differentiating CS from normal subjects and to define the responses in CS of various aetiologies.Design, subjects, measurements  Thirty‐two control subjects [normal and overweight/obese participants with or without type 2 diabetes) were prospectively studied, and data from 66 patients with Cushing’s disease (CD), three with ectopic ACTH syndrome (EAS), 14 with adrenal Cushing’s (AC)] and 15 with low probability of CS (LPC) from three tertiary hospitals were retrospectively evaluated. Dexamethasone was infused at 1 mg/h for 4 h. Plasma cortisol and ACTH were measured at −60 min (baseline), −5 min, +3 h, +4 h, +5 h and at +23 and +23·5 h on Day 2.Results  Control subjects (including those with type 2 diabetes) exhibited a marked suppression of cortisol which was maintained until Day 2. Two of 15 patients with LPC had Day 2 cortisol results that overlapped with CS. Patients with CD demonstrated partial suppression, with rebound hypercortisolism on Day 2. Patients with AC and EAS did not suppress cortisol levels. Day 2 cortisol level of >130 nmol/l (or >20% of the baseline) diagnosed CS with 100% sensitivity and 96% specificity.Conclusion  While the IVDST allowed complete discrimination between control subjects and CS, 13% of LPC overlapped with CS. Given the small number of EAS, no conclusion can be drawn regarding the utility of this test in the differential diagnosis of CS.
Predictive value of pentagastrin test for preoperative differential diagnosis between C‐cell hyperplasia and medullary thyroid carcinoma in patients with moderately elevated basal calcitonin levels
Authors: Milone F. , Ramundo V. , Chiofalo M. G. , Severino R. , Paciolla I. , Pezzullo L. , Lombardi G. , Colao A. , Faggiano A. 
Published: December 2009

SummaryBackground and Objectives  Medullary thyroid carcinoma (MTC) is a calcitonin (CT)‐secreting neuroendocrine tumour originating from thyroid C cells. Serum CT concentrations are helpful in the early detection of MTC, while it is still unclear whether they can be used also for the differential diagnosis between MTC and C‐cell hyperplasia (CCH), a precancerous condition in familial MTCs but with unclear clinical significance in sporadic MTCs. Nowadays, surgery is recommended in all patients with basal or pentagastrin (PG)‐stimulated CT value of 100 pg/ml or more, without discriminating if they are affected with MTC or CCH only. The objective of this study was to investigate the utility of the PG test for CT in distinguishing CCH from MTC before surgery.Patients and Methods  Sixteen of 20 patients with thyroid nodules and basal CT levels between 15 and 100 ng/l had a positive PG test (>100 ng/l PG CT peak) and form the basis of the data analysis. A diagnosis of MTC was histologically proved on surgical samples in seven patients and of CCH in nine other patients. Four patients with neither FNAB nor PG test consistent with a diagnosis of MTC did not undergo thyroidectomy.Results  A peak of CT of 275 ng/l after PG was able to significantly distinguish patients with MTC from patients with CCH, with 100% sensitivity and 89% specificity (P = 0·002). PG‐stimulated calcitonin levels >275 ng/l had a positive predictive value (PPV) value for diagnosis of MTC of 100%, and PG‐stimulated calcitonin levels <275 had a PPV for the diagnosis of CCH of 89%.Conclusions  A CT cut‐off after PG of 275 ng/l is suggested to be highly predictive in distinguishing CCH from MTC before surgery, and this may be helpful in selecting patients for thyroid surgery.
A catalogue of reporting guidelines for health research
Authors: Simera I. , Moher D. , Hoey J. , Schulz K. F. , Altman D. G. 
Published: December 2009

Eur J Clin Invest 2010; 40 (1): 35–53AbstractGrowing evidence demonstrates widespread deficiencies in the reporting of health research studies. The EQUATOR Network is an international initiative that aims to enhance the reliability and value of the published health research literature. EQUATOR provides resources, education and training to facilitate good research reporting and assists in the development, dissemination and implementation of robust reporting guidelines. This paper presents a collection of tools and guidelines available on the EQUATOR website (http://www.equator‐network.org) that have been developed to increase the accuracy and transparency of health research reporting.
Surface morphology of unalloyed steels remelted with intense plasma pulses
Authors: SARTOWSKA B. , PIEKOSZEWSKI J. , WALIŚ L. , BARLAK M. 
Published: December 2009

SummaryThe set of unalloyed steels with various carbon concentrations were irradiated with intense plasma pulses with following process parameters: energy density 5 J cm−2, pulse duration 2 μs, argon or nitrogen atmosphere. The energy density of each pulse was high enough to melt the surface layer of material. The cooling rate was estimated for 108 K s−1 using the modelling method which takes into account heat evolution in the iron sample. Samples were characterized using the scanning electron microscopy technique for remelted surface morphology investigations. The tests with profilometer allowed us to investigate the changes of roughness of the surface layers.
Microstructure and mechanical properties of AA7039+20%SiCw composite
Authors: BLAZ L. , KULA A. , KANEKO J. , SUGAMATA M. , WLOCH G. , SOBOTA K. 
Published: December 2009

SummaryHot deformation tests were performed on an AA7039‐matrix composite reinforced with a 20% addition of SiC whiskers. The flow stress maximum was reduced with deformation temperature from 640 MPa to ∼8 MPa at 293 K and 823 K, respectively. TEM observations, performed on as deformed samples, revealed a highly recovered substructure of the matrix and a striated structure of the whiskers. The fringes, which are perpendicular to the whiskers’ longitudinal axis, were ascribed to nano‐sized twins and stacking faults formed during the crystal growth rather than to some effects of the deformation process.
Tyrosinase gene (TYR) mutations in Chinese patients with oculocutaneous albinism type 1
Authors: Liu Jing , Choy Kwong‐Wai , Chan Leo WL , Leung Tak‐Yeung , Tam Pancy OS , Chiang Sylvia WY , Lam Dennis SC , Pang Chi‐Pui , Lai Timothy YY 
Published: December 2009

AbstractBackground:  To identify the sequence variants of the tyrosinase (TYR) gene in Chinese families with oculocutaneous albinism.Methods:  Three families with oculocutaneous albinism type 1 and 95 unrelated healthy Chinese individuals with normal pigmentation were screened for mutations in the TYR gene by direct sequencing. Computational algorithms were used to characterize the biological significance of the mutants.Results:  Four previously reported mutations (R299C, R299H, W400L and frame‐shift c.930insC) and one novel mutation (F214del) were identified, and probands had homozygous or compound heterozygous TYR mutant alleles. None of the mutants were identified among the 95 normal control subjects. Computational analysis predicted that the R299C mutant inactivates the tyrosinase enzyme by misfolding of protein tertiary structure and/or retention of the misfolded tyrosinase within the endoplasmic reticulum, and F214del causes dysfunction of tyrosine enzyme by affecting the copper binding sites and altering substrate orientation and electronic transfers during catalytic reactions for melanosynthesis.Conclusion:  We have identified five different TYR mutations, including one novel mutation, which caused oculocutaneous albinism type 1 in Chinese. Further analysis of the patients will be useful to determine the effects of these mutations on the tyrosinase activities.
From ‘cryptic species’ to integrative taxonomy: an iterative process involving DNA sequences, morphology, and behaviour leads to the resurrection of Sepsis pyrrhosoma (Sepsidae: Diptera)
Authors: Tan Denise S. H. , Ang Yuchen , Lim Gwynne S. , Ismail Mirza Rifqi Bin , Meier Rudolf 
Published: December 2009

Tan, D. S. H., Ang, Y., Lim, G. S., Ismail, M. R. B. & Meier, R. (2010). From ‘cryptic species’ to integrative taxonomy: an iterative process involving DNA sequences, morphology, and behaviour leads to the resurrection of Sepsis pyrrhosoma (Sepsidae: Diptera). —Zoologica Scripta, 39, 51–61.The increased availability of DNA sequences has led to a surge of ‘cryptic species’ in the literature. These units are usually proposed based on finding genetically distinct lineages within species that were initially defined based on morphological characters. However, few authors attempt to confirm whether these ‘cryptic’ units are species and even fewer authors are explicit about which species concept is applied. Here, we use an example from Sepsidae (Diptera) to demonstrate how cryptic species can be validated by an iterative process involving several data sources and an evaluation of the data under different species concepts. A phylogeographic analysis based on 50 specimens for five species of the flavimana group revealed deep mitochondrial splits within Sepsis flavimana which was suggestive of a cryptic species. We resolve the initial conflict between DNA sequences and morphology by adding new morphological data as well as behavioural evidence and tests for reproductive isolation. One cryptic species is confirmed and Sepsis pyrrhosoma, a former synonym of S. flavimana, is here shown to be a valid species under most species concepts. We can thus document that the same data can lead to similar conclusions under conflicting concepts once different kinds of data are integrated.
Interactions between inducible nitric oxide synthase and cyclooxygenase‐2 in response to ischaemia‐reperfusion of rabbit bladder
Authors: Masuda Hitoshi , Kawano Keizo , Matsuoka Yoh , Yokoyama Minato , Koga Fumitaka , Saito Kazutaka , Kihara Kazunori , Azuma Hiroshi 
Published: December 2009

OBJECTIVETo investigate the interactions between inducible nitric oxide synthase (iNOS) and cyclooxygenase‐2 (COX‐2) in response to ischaemia‐reperfusion (I/R) of rabbit bladder.MATERIALS AND METHODSRabbit bladders were exposed to 2 h of ischaemia by bilaterally clamping the major arteries entering the bladder and then a subsequent 36 h of reperfusion (I/R) with or without intraperitoneal administration of a selective iNOS inhibitor n‐(3‐(amynomethyl)benzyl)acetamidine (1400W) or a selective COX‐2 inhibitor NS‐398 given 1 h before killing. The bladder tissues were processed for isometric tension experiments, enzymatic NOS activitiy, tissue contents of nitrite/nitrate (NOX), cyclic guanosine monophosphate (cGMP) and COX activity determined by prostaglandin E2 (PGE2) production.RESULTSiNOS and constitutive NOS (cNOS) activities, NOX and PGE2 contents in the bladder tissues at 36 h after reperfusion were significantly higher than those in the sham group with no significant increase in cGMP. Treatment with 1400W abrogated the increases in iNOS activity and NOX as well as PGE2 without changing cNOS activity. In the tension experiments, a NOS substrate, l‐arginine, induced detrusor contraction only in the I/R group, which was inhibited by 1400W or NS‐398 but not by a selective soluble guanylate cyclase inhibitor 1H‐[1,2,4] oxadiazole[4,3‐a]quinoxalin‐1‐one (ODQ). 8‐Br‐cGMP induced detrusor relaxation in the sham and I/R groups. Also, l‐arginine increased NOX and PGE2 in the bladder tissues only in the I/R group, which were inhibited by pretreatment with 1400W. While, l‐arginine increased cGMP contents in the I/R group and this increase was suppressed by ODQ but not by 1400W.CONCLUSIONThese results show that NO derived from an up‐regulation of iNOS after I/R increases COX‐2‐derived PG via a cGMP‐independent mechanism. NO‐mediated activation of COX‐2 may be an important mechanism for the modulation of bladder function after I/R injury.
Glucose‐regulated protein 78 expression in urothelial carcinoma of the upper urinary tract
Authors: Uematsu Kenji , Ogata Sho , Nakanishi Kuniaki , Hiroi Sadayuki , Tominaga Susumu , Aida Shinsuke , Kawai Toshiaki 
Published: December 2009

OBJECTIVETo examine glucose‐regulated protein 78 (GRP78; a major molecular chaperone at the endoplasmic reticulum, strongly expressed in several tumours) expression in urothelial carcinoma (UC) of the upper urinary tract (UUT) and to evaluate the diagnostic and progressive importance of GRP78 expression in UC‐UUT.PATIENTS AND METHODSWe investigated GRP78 expression (using immunohistochemistry) in 126 UC‐UUTs to assess its relevance to progression. GRP78 overexpression was recognised in 23 (18.3%) of tumour samples.RESULTSThere was no association between GRP78 overexpression and clinicopathological findings, except for an association with low grade in invasive tumours. GRP78 overexpression significantly improved the disease‐free survival rate in all patients (according to univariate and multivariate analyses), but did not alter the overall survival rate.CONCLUSIONThe detection of GRP78 overexpression would appear to provide valuable information for the prognosis of UC‐UUT.
Predicting renal functional outcomes after surgery for renal cortical tumours: a multifactorial analysis
Authors: Barlow LaMont J. , Korets Ruslan , Laudano Melissa , Benson Mitchell , McKiernan James 
Published: December 2009

Study Type – Therapy (case series) Level of Evidence 4OBJECTIVETo examine the functional outcomes after radical (RN) and partial nephrectomy (PN) stratified by variables before and after surgery, using estimated glomerular filtration rate (eGFR), as nephrectomy is the standard treatment for localized renal tumours, but the risk of developing chronic kidney disease (CKD) increases after surgery.PATIENTS AND METHODSWe retrospectively analysed patients treated with PN or RN for renal cancer at one institution from 1988 to 2008. Chronic renal function before and after surgery was measured using the eGFR computed using the Modification of Diet in Renal Disease equation. Four outcomes were measured: (i) presence of new‐onset renal insufficiency (eGFR <60 mL/min/1.73m2); (ii) the percentage change in eGFR; (iii) the change in CKD stage; and (iv) the presence of CKD upstaging. Regression models were used to determine the effect of surgical procedure (RN vs PN), access technique (open vs laparoscopic) and several preoperative characteristics on functional outcomes.RESULTSIn all, 276 patients met the inclusion criteria (174 RN and 102 PN) of whom 209 had a preoperative eGFR of >60 mL/min/1.73m2. After ≥3 months from surgery, 108/209 (52%) patients developed new‐onset eGFR of <60 mL/min/1.73m2. On multivariate analysis, preoperative CKD stage (P < 0.001) and procedure (P= 0.001) were both independent predictors of all four functional outcomes measured. Also, hypertension was an independent predictor of CKD upstaging (P= 0.02). Surgical access technique was not an independent predictor of any of the renal functional outcomes measured.CONCLUSIONPatients undergoing renal surgery have a high rate of new‐onset CKD afterward. After controlling for preoperative risk factors, patients undergoing RN are at greater risk of a decline in renal function. However, surgical access technique was not a significant predictor for renal impairment.
Pecking Order Behavior in Emerging Markets*
Authors: Seifert Bruce , Gonenc Halit 
Published: December 2009

AbstractThis paper examines the validity of the pecking order hypothesis in 23 emerging market countries. Emerging market countries would appear to be an ideal setting for the pecking order hypothesis to hold because of the presence of strong asymmetric information issues and agency costs. We observe, however, little support for the pecking order hypothesis as the primary financing theory for all emerging market firms. Firms in these countries finance their deficit mainly with equity, the opposite of what would be expected under this hypothesis. However, we do find support for the pecking order for firms in emerging market countries that suffer the most from either asymmetric information issues and/or agency costs. Our findings are consistent with the idea that the environment the firm operates in influences the financial decisions the firm makes.
The Impact of the Asian Financial Crisis on Conservatism and Timeliness of Earnings: Evidence from Hong Kong, Malaysia, Singapore, and Thailand
Authors: Vichitsarawong Thanyaluk , Eng Li Li , Meek Gary K. 
Published: December 2009

AbstractThis paper examines conservatism and timeliness of earnings in the period surrounding the 1997 Asian financial crisis in Hong Kong, Malaysia, Singapore, and Thailand. Prior research suggests that managers tended to be more aggressive in reporting good news and delayed recognition of bad news during the financial crisis (less conservative and less timely in financial reporting). After the crisis, these four countries implemented corporate governance measures to stabilize their financial systems and improve regulation and supervision (that should improve conservatism and timeliness). We examine and find that conservatism and timeliness of earnings during the crisis period are low, but improved in the post‐crisis period. More importantly, conservatism and timeliness in the post‐crisis period is even greater than in the pre‐crisis period. We measure conservatism using Basu's model and the accumulation of non‐operating accruals suggested by Givoly and Hayn. The findings from both measures are consistent with an increase in conservatism after the crisis period. Overall, the results indicate that corporate governance reforms in these four countries had a positive impact on conservatism and timeliness of earnings.
Large differences in levodopa dose requirement in Parkinson’s disease: men use higher doses than women
Authors: Nyholm D. , Karlsson E. , Lundberg M. , Askmark H. 
Published: December 2009

Background and purpose:  The characteristics of levodopa dosing are not well described in the literature. The aims were to investigate the use of levodopa in a nationwide Swedish survey and to study the characteristics of low‐dose and high‐dose patients with Parkinson’s disease (PD) in a university hospital.Methods:  Patients with ≥ 1 and ≥ 2 purchases of levodopa during 2007 were selected from the prescribed drug register. Daily levodopa doses were estimated. Records of 504 patients with PD who visited the neurology clinic at Uppsala University Hospital during 2006–2007 were examined to select a low‐dose group (≤ 400 mg levodopa daily, n = 21) and a high‐dose group (≥ 1200 mg daily, n = 26) with at least 5 years of PD duration.Results:  In total, 33 534 levodopa users with ≥ 1 levodopa purchase were found. Daily levodopa dose range was large; median daily dose was 465 mg for men and 395 mg for women (P < 0.0001). Almost half (46%) of the patients used < 400 mg levodopa daily. Significantly, more men were treated with doses ≥ 1200 mg daily. Dose and age correlated negatively (P < 0.0001). Patients with high dose at 5 years PD duration continuously increased their dosage the following years, whereas low‐dose patients did not. The occurrence of dyskinesias was about the same in both groups despite the large difference in levodopa dose.Conclusions:  We conclude that the levodopa requirement in PD ranges considerably, and that men use higher levodopa dose than women. Levodopa requirement is constant during the progression of the disease in low‐dose patients but increases in high‐dose patients.
A Fuller Account: The Role of ‘Fittingness’ in Thomas Aquinas' Development of the Doctrine of the Atonement
Authors: JOHNSON ADAM 
Published: December 2009

AbstractThis article draws attention to Thomas Aquinas' under‐appreciated development of the doctrine of the atonement. I argue that Thomas' pursuit of the ‘fittingness’ of the passion yields an exceptional grasp of the multiplicity of effects accomplished by Christ's death. To defend this thesis, I explore the methodology underlying Thomas' approach to the atonement, contrasting it with that of Anselm. I then follow the implications of Thomas' methodology in his stance toward the diverse atonement theories of his day. In conclusion, I briefly note the significance of Thomas' method and conclusions for contemporary debates concerning the efficacy of Christ's passion.