bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differentiation of the Local Structure Around Tryptophan 51 and 64 in Recombinant Human Erythropoietin by Tryptophan Phosphorescence
Authors: Kerwin Bruce A. , Aoki Kenneth H. , Gonelli Margherita , Strambini Giovanni B. 
Published: March 2008

AbstractRecombinant human erythropoietin is a 4‐helix bundle, glycosylated cytokine containing three tryptophan residues at positions 51, 64 and 88 whose phosphorescence emission may represent a sensitive probe of the structure at multiple sites near or at the protein surface. This report characterizes the phosphorescence properties (spectral energy, thermal spectral relaxation and phosphorescence lifetime), from low temperature glasses to ambient temperature, of the native protein plus that of three single point mutation analogs where each Trp was replaced by Phe. The structural information inferred from the phosphorescence parameters was essentially in good agreement with the structure of the Escherichia coli‐produced nonglycosylated protein determined by nuclear magnetic resonance (Cheetham et al., Nat Struct Biol [1998] 5:861). The results showed that the fluorescence and phosphorescence spectra of the native protein were entirely due to independent contributions of Trp51 and Trp64 and that Trp88 was quenched under all conditions. The phosphorescence emissions of Trp51 and Trp64 were differentiated by their unique spectra at 77 K with Trp64 exhibiting an unusually blueshifted spectrum likely due to the attractive interaction of Arg110 and Lys116 with the ground state dipole of Trp64. In the native protein the room temperature phosphorescence lifetime of Trp64 was relatively short with a time of 1.62 ms whereas the lifetime of Trp51 was five‐fold longer. Characterization of the single point mutation analogs showed that each lifetime was composed of multiple components revealing the presence of multiple stable conformations of the protein at these surface sites.
Probability Integrals of the MultivariatetDistribution
Authors: Nadarajah Saralees , Kotz Samuel 
Published: March 2008

SummaryResults on probability integrals of multivariatetdistributions are reviewed. The results discussed include: Dunnett and Sobel's probability integrals, Gupta and Sobel's probability integrals, John's probability integrals, Amos and Bulgren's probability integrals, Steffens' non‐central probabilities, Dutt's probability integrals, Amos' probability integral, Fujikoshi's probability integrals, probabilities of cone, probabilities of convex polyhedra, probabilities of linear inequalities, maximum probability content, and Monte Carlo evaluation.
Econometric Causality
Authors: Heckman James J. 
Published: March 2008

Summary This paper presents the econometric approach to causal modelling. It is motivated by policy problems. New causal parameters are defined and identified to address specific policy problems. Economists embrace a scientific approach to causality and model the preferences and choices of agents to infer subjective (agent) evaluations as well as objective outcomes. Anticipated and realized subjective and objective outcomes are distinguished. Models for simultaneous causality are developed. The paper contrasts the Neyman–Rubin model of causality with the econometric approach.
Anomalies in the Foundations of Ridge Regression
Authors: Jensen Donald R. , Ramirez Donald E. 
Published: March 2008

SummaryErrors persist in ridge regression, its foundations, and its usage, as set forth inHoerl & Kennard (1970)and elsewhere. Ridge estimators need not be minimizing, nor a prospective ridge parameter be admissible. Conventional estimators are not LaGrange's solutions constrained to fixed lengths, as claimed, since such solutions are singular. Of a massive literature on estimation, prediction, cross–validation, choice of ridge parameter, and related issues, little emanates from constrained optimization to include inequality constraints. The problem traces to a misapplication of LaGrange's Principle, unrecognized singularities, and misplaced links between constraints and ridge parameters. Alternative principles, based on condition numbers, are seen to validate both conventional ridge andsurrogate ridgeregression to be defined. Numerical studies illustrate that ridge regression as practiced often exhibits pathologies it is intended to redress.
Mutual regulation of EBV LMP1 and CD99 in the pathogenesis of EBV‐associated Hodgkin lymphomas
Authors: Min Hye Sook , Lee Im‐Soon , Park Seong Hoe 
Published: March 2008

ABSTRACTDespite considerable progress over the last decade, Hodgkin lymphoma (HL) remains a malignant tumor of unknown pathogenesis. The role of Epstein‐Barr virus (EBV) and the activation of transcription factor NF‐κB have been noted in the tumorigenesis of classic HL. Recently, a distinctive interaction between CD99 and the EBV viral latent membrane protein 1 (LMP1) was observed in the process of the malignant transformation of EBV‐infected B cells. It was previously reported that CD99 expression is negatively regulated by LMP1, subsequently generating cells with Hodgkin and Reed‐Sternberg (HRS) cell phenotype. Interestingly, several pieces of evidence have been recently revealed the presence of mutual regulation between CD99 and LMP1, which may assist in determining HL pathogenesis. In this review, the roles of CD99 and LMP1 in the generation of the HRS cell, a tumor cell of HL, will be discussed. We also suggest that CD99 and LMP1 interaction in an in vivo system may provide new insight into the understanding of the molecular mechanism of HL.
Carbonic anhydrase II gene upregulation and tumorigenesis in Lewis lung carcinoma‐bearing mice
Authors: Seok Seung‐Hyeok , Baek Min‐Won , Lee Hui‐Young , Kim Dong‐Jae , Cho Kiho , Park Jae‐Hak 
Published: March 2008

ABSTRACT Background and aims: The carbonic anhydrases (CA), a family of metalloenzymes, play an important role in catalyzing the equilibration of carbon dioxide (CO2) and carbonic acid (H2CO3). CAs are involved in many physiological process connected with respiration and transport of CO2/bicarbonate (HCO3‐). CA inhibitors have been investigated in a variety of tumors. The role of CAs in tumorigenesis is controversial, especially in relation to the expression of CA isoenzymes between normal and malignant cells. This study was performed to elucidate the correlation of CA in the regulation of the transplant acceptance in the mice model. Methods: A rejection rate of 16.7% for transplantation, 1 × 106 cells by subcutaneous injection in the axillary region, of wild‐type Lewis lung carcinoma (LLC) cells was observed in syngeneic C57BL/6 mice. We hypothesize that the rejection is caused by the regulation of multiple genes. Differential display was performed to identify the response of genes to the rejection. Results: Initial characterization of differentially amplified products demonstrated that carbonic anhydrase II (CAII) mRNA was differently regulated in the spleens of mice bearing LLC and the spleens of non‐LLC bearing mice. RT‐PCR analysis of the mouse spleens suggested that expression of CAII was significantly increased in mice bearing LLC, when compared to non‐LLC bearing mice. Conclusions: The results indicated that CAII expression may be involved in the transplant acceptance and growth of LLC cells in the mouse model. To our knowledge, this is the first demonstration of the different of mRNA expression levels of CAII in LLC‐transplanted mice.
Pathology of lupus nephritis is better classified by the International Society of Nephrology‐Renal Pathology Society system
Authors: Seo Jinwon , Do In‐Gu , Park Eun Su , Kwon Ghee Young , Ko Young Hyeh 
Published: March 2008

ABSTRACT Background and aims: The goal of this study was to assess the diagnostic value of the new International Society of Nephrology‐Renal Pathology Society (ISN‐RPS) classification system for lupus nephritis (LN). Methods: We reviewed 170 biopsy specimens according to the WHO and the ISN‐RPS systems. Results: The frequencies of class I, class II, class III, class IV, class V, and class VI LN for the WHO/ISN‐RPS systems were 0.6%/1.8%, 2.4%/2.4%, 28.2%/24.7%, 52.4%/60%, 14.7%/9.4%, and 1.8%/1.8%, respectively. Class‐switch events occurred in 22 cases, with 12 cases switched from class III under the WHO system to class IV under the ISN‐RPS system. Class IV‐S LN showed a higher frequency of fibrinoid necrosis than IV‐G LN (P = 0.003), but endocapillary proliferation was more pronounced in class IV‐G than class IV‐S (P = 0.003). The frequency of coexistent class V LN was higher in class III LN than class IV LN (P = 0.008). The interobserver reproducibility of the ISN/RPS system was better (κ = 0.76) than that of the WHO system (κ = 0.33). Conclusions: Interobserver reproducibility for the ISN‐RPS system for lupus nephritis is greater than for the WHO system. The prognostic value of class IV‐S, IV‐G, and coexistent class V should be verified by future study.
Cutaneous hemangiosarcoma in a German Shepherd dog
Authors: Park Jin‐Kyu , Goo Moon‐Jung , Hong Il‐Hwa , Yang Hai‐Jie , Yuan Dong‐Wei , Lee Hye‐Rim , Han Jung‐Youn , Jeong Kyu‐Shik 
Published: March 2008

ABSTRACTA mass taken from the right mandibular region of a 9‐year‐old female German Shepherd dog was presented for histopathological examination. Grossly, the surgically resected 7 × 5 cm mass was dark reddish, poorly circumscribed and had infiltrated the mandibular bone. The cut surface of the mass was characterized by dark reddish parts and multi focal whitish components. Microscopically, the mass revealed locally extensive necrotic lesions with infiltration of inflammatory cells, multifocal hemorrhagic lesions and numerous hemosiderin laden macrophages. Numerous neovascular structures had been formed by atypical neoplastic tumor cells – themselves composed of undifferentiated round, ovoid, and spindle shaped neoplastic cells with pleomorphic, hyperchromatic, large nucleus and scant cytoplasm. The mass also showed abundant mitotic figures, invasions of the neovascular structures by neoplastic epitheloid tumor cells and adjacent tissue, characteristic of malignancy. The neoplastic tumor cells forming neovascular structures originated from vascular endothelial cells, therefore, the tumor was diagnosed as canine cutaneous hemangiosarcoma.
Liquid‐based cytology provides higher diagnostic accuracy than conventional Papanicolaou smears in uterine cervical cytology
Authors: Joo Hee Jae , Lee Jeongmin , Song Sang Yong , Hong Sung Ran , Jin So‐Young , Gong Gyungyub , Park Rae‐Woong , Lee Kwang Gil 
Published: March 2008

ABSTRACT Background and aims: The objective of this study was to evaluate diagnostic accuracy and cytomorphological quality of MonoPrep2 (MP) (a manual liquid‐based cytology preparation system) in comparison with the conventional Papanicolaou smear (CP) in cervical cancer screening. Methods: Six departments of pathology in university hospitals, and one pathology laboratory center, in Korea were included in the study. Retrospective analysis of 795 patients in whom CP, MP or both CP and MP with cervical biopsy had been performed was undertaken. A total of 33 cases were unsatisfactory for evaluation. A total of 933 cervical specimens (290 CP, 301 MP, and 171 CP & MP) were enrolled. Among of them, 461 cases of CP and 472 cases of MP were correlated with histopathological diagnoses. Results: Diagnostic accuracy by MP was greater than CP in all parameters including sensitivity (92.7% versus 90.2%), specificity (87.2% versus 66.2%), positive likelihood ratio (7.23 versus 2.67) and negative likelihood ratio (0.08 versus 0.15). There was marked decrease in the ratio of atypical squamous cells of undetermined significance to low‐grade squamous intraepithelial lesions. Conclusions: MP provides higher diagnostic accuracy when compared with CP. MP is an easy and economic preparation with high‐quality results, making the technique useful in primary screening for cervical cytology.
Spontaneous coronary artery dissection as a cause of sudden, unexpected death
Authors: Han Man‐Hoon , Nam Sang‐Chul , Kim Young‐Su , Lee Sang‐Han 
Published: March 2008

ABSTRACTTwo cases of sudden unexpected death due to spontaneous coronary artery dissection are reported, retrieved from a series of forensic autopsies of 3300 cases since 1997. The first case was a 52‐year‐old man who had no previous health problem but cardiomegaly and atherosclerosis in coronary arteries. The dissection was found between the intima and the media at the proximal and mid‐portion of the left anterior descending coronary artery, 6.6cm in segment. The second case was a 39‐year‐old woman who had a history of hypertension and an intrauterine device. The dissection was also found between the intima and the media of the mid‐portion of the left anterior descending coronary artery, 8.7cm in segment. There was no myocardial infarct probably due to the hyperacute nature of this coronary obstruction. No significant predispositions were noted although hypertension and the intrauterine device may have causal association. Both reported cases present previously healthy adults who experienced sudden, unexpected death.
Antimicrobial Resistance of Salmonella enterica Isolates from Apparently Healthy and Clinically Ill Finishing Pigs in Spain
Authors: García‐Feliz C. , Collazos J. A. , Carvajal A. , Herrera S. , Echeita M. A. , Rubio P. 
Published: March 2008

SummaryThis study was the first conducted in Spain to evaluate the occurrence of antimicrobial resistance and multi‐resistance in Salmonella isolates recovered from finishing pigs from Spanish swine farms distributed over the whole country. For this purpose, 290 Salmonella isolates recovered from apparently healthy finishing pigs in a farm‐based cross‐sectional study and 192 Salmonella isolates recovered from faecal samples of finishing pigs suffering from diarrhoea were investigated. Resistance to a panel of 17 antimicrobials was determined using a broth microdilution technique. Resistance was a common finding and was detected in 90.3% of the Salmonella isolates from apparently healthy finishing pigs and 95.3% of the Salmonella isolates from clinically diseased finishing pigs. Resistance was particularly high among isolates of serogroup B and serovars Typhimurium and its monophasic variant S. 4,5,12:i:‐. Higher frequencies of resistance were found to tetracycline, sulphamethoxazole, streptomycin, spectinomycin, ampicillin, chloramphenicol and trimethoprim‐sulphamethoxazole. Less than 10% of the isolates were resistant to amoxicillin/clavulanic acid, neomycin, cephalotin, apramycin and gentamicin. Resistance to ciprofloxacin, colistin and ceftiofur was rare (under 1%). Multi‐resistance, defined as resistance to four or more drugs, was detected in more than 50% of the isolates. Although multi‐resistance was particularly frequent among isolates of S. Typhimurium, it was also high among other serovars as Bredeney and the S. Typhimurium monophasic variant. 4,5,12:i:‐.
Clinical importance of the presence of giant cells in temporal arteritis
Authors: Armstrong A T , Tyler W B , Wood G C , Harrington T M 
Published: March 2008

Background:The clinical significance of giant cells seen on temporal artery biopsy in temporal arteritis is unknown.Aim:To help define the prognostic value of the presence of giant cells in temporal arteritis.Methods:The clinical course of all patients with biopsy proven temporal arteritis from 1994 to 2004 was reviewed. The 92 patients were divided into those with giant cells (GC) (n = 76) seen on biopsy and those with no giant cells (NGC) (n = 16). Clinical findings were compared between groups. An additional analysis combined results with a previous study at the same institution to compare occurrence of blindness.Results:The GC group had a higher proportion of polymyalgia rheumatica (PMR) (36.8%) compared to the NGC group (12.5%) (p = 0.059). There was no significant difference in patient age, sex, sedimentation rate, or presenting symptoms. The length of time treated with corticosteroids and relapse rate was nearly identical for both groups. When combining data with the previous study, in the GC group 21/109 (19%) developed blindness, while only 2/34 (6%) became blind in the NGC group (p = 0.11).Conclusion:The presence of giant cells is not a significant factor in determining treatment or clinical progression of temporal arteritis. However, results showed the GC group to have three times the occurrence of blindness and PMR compared to the NGC group. Although the differences were not significant, this analysis suggests an association with giant cells and more aggressive disease.
The histological diagnosis of leprosy type 1 reactions: identification of key variables and an analysis of the process of histological diagnosis
Authors: Lockwood D N J , Lucas S B , Desikan K V , Ebenezer G , Suneetha S , Nicholls P 
Published: March 2008

Background:Type 1 leprosy reactions (T1R) are a major inflammatory complication of leprosy affecting 30% of patients with borderline leprosy, but there has been no diagnostic evaluation of the histological diagnosis of this entity.Methods:In a prospective study based in India, skin biopsies were taken from 99 patients with clinically diagnosed T1R and 52 non-reactional controls. These were assessed histologically by four histopathologists whose assessments were then compared.Results:Reactions were under-diagnosed, with 32–62% of clinically diagnosed reactions being given a histological diagnosis. The pathologists showed good specificities (range 72% to 93%) but much poorer sensitivities (range 42% to 78%). The most commonly reported histological features of TIR were cell maturity, oedema and giant cells. Five key variables were identified that the pathologists used in diagnosing a reaction: intra-granuloma oedema, giant cell size, giant cell numbers, dermal oedema and HLA-DR expression. A predictive model for the diagnosis of T1R was developed using stepwise logistic regression analysis, with clinical diagnosis of reaction as an outcome, and then identification of the key variables that each pathologist used in making the diagnosis of T1R. 34–53% of the variation between pathologists could be accounted for. The four pathologists used a similar diagnostic model and for all of them their estimations of epithelioid cell granuloma oedema, dermal oedema, plasma cells and granuloma fraction were significant variables in the diagnosis of T1R. Each pathologist then added in variables that were specific to themselves.Conclusions:This study has identified T1R as being under-diagnosed in comparison with clinical assessments. Key variables for diagnosing T1R were established. This comparative masked study highlights the need for such studies in other inflammatory conditions.
A quality assurance exercise to evaluate the accuracy and reproducibility of chromogenic in situ hybridisation for HER2 analysis in breast cancer
Authors: Di Palma S , Collins N , Bilous M , Sapino A , Mottolese M , Kapranos N , Schmitt F , Isola J 
Published: March 2008

Background:Chromogenic in situ hybridisation (CISH) is an alternative to immunohistochemistry or FISH for the assessment of HER2 oncogene status in breast cancer. Although CISH is being used increasingly in routine diagnostics, there are no established inter-laboratory quality assurance programmes for this test.Methods:The reproducibility of HER2 CISH analysis was assessed when performed by seven different centres that use the test routinely in diagnostic service.Results:The results from 28 cases showed overall concordance of 98.5% (192/195 tests; κ coefficient 0.91). One of the discrepancies was due to the invasive carcinoma having been cut out in the sections received by two of the centres, and the other two were in the non-amplified/equivocal/low-amplified category.Conclusion:This is believed to be the first report of a quality assurance study assessing laboratories that use HER2 CISH routinely in clinical diagnostics. The results show that CISH is a robust technique providing a suitable assay for the frontline testing of HER2 status in breast cancer.
Vacuum assisted stereotactic guided mammotome biopsies in the management of screen detected microcalcifications: experience of a large breast screening centre
Authors: Kumaroswamy V , Liston J , Shaaban A M 
Published: March 2008

Aim:To evaluate the usefulness of vacuum assisted stereotactic guided mammotome biopsy in the diagnostic management of screen detected calcifications and to rationalise its use versus diagnostic excision.Methods:The first 100 mammotome biopsies preceded by a conventional needle core biopsy (NCB) were identified from the database of Leeds/Wakefield Breast Screening Service. The histological diagnosis on NCB and mammotome were reviewed and compared with the surgical histological diagnosis if excision had been performed.Results:Using mammotome, diagnoses were changed in 74 of the 100 cases. In 66 cases a definitive diagnosis (B2 or B5) was obtained. The incidence of inadequate/unsatisfactory (B1) biopsies was reduced from 36% to 9%. In 34 cases mammotome was not helpful in arriving at a definite diagnosis (B1/B3/B4). All cases diagnosed as malignant with mammotome were proven to have in situ or invasive malignancy on excision except for one case of ductal carcinoma in situ fully excised by mammotome. There was one false negative case of in-situ carcinoma with a prior benign (B2) mammotome diagnosis. Almost half the NCB uncertain (B3) cases required excision as the mammotome biopsies were also uncertain (B3). The majority were flat epithelial atypia and atypical intraductal proliferation.Conclusions:Mammotome biopsy is particularly useful for further assessment of an inadequate (B1) or suspicious (B4) NCB diagnosis. Diagnostic surgical excision remains the method of choice for managing atypical/uncertain lesions (B3).
High expression of Polycomb group protein EZH2 predicts poor survival in salivary gland adenoid cystic carcinoma
Authors: Vékony H , Raaphorst F M , Otte A P , van Lohuizen M , Leemans C R , van der Waal I , Bloemena E 
Published: March 2008

Background:The prognosis of adenoid cystic carcinoma (ACC), a malignant salivary gland tumour, depends on clinicopathological parameters. To decipher the biological behaviour of ACC, and to identify patients at risk of developing metastases, additional markers are needed.Methods:Expression of the cell cycle proteins p53, cyclin D1, p16INK4a, E2F1 and Ki-67, together with the Polycomb group (PcG) proteins BMI-1, MEL-18, EZH2 and EED was investigated immunohistochemically 21 formalin-fixed, paraffin-embedded primary ACCs in relation to tumour characteristics.Results:ACC revealed significantly increased expression of the cell cycle proteins compared to normal salivary tissue (n = 17). Members of the two PcG complexes displayed mutually exclusive expression in normal salivary gland tissue, with BMI-1 and MEL-18 being abundantly present. In ACC, this expression pattern was disturbed, with EZH2 and EED showing significantly increased expression levels. In univariate analysis, presence of recurrence, poor differentiation and high EZH2 levels (>25% immunopositivity) significantly correlated with unfavourable outcome. ACCs with high proliferative rate (>25% Ki-67 immunopositivity) significantly correlated with high levels of EZH2 and p16. Only the development of recurrence was an independent prognostic factor of survival in multivariate analysis.Conclusions:Expression of PcG complexes and of essential cell cycle proteins is highly deregulated in ACC. Also, EZH2 expression has prognostic relevance in this malignancy.