bluuebunny/crossref_metadata_2025 huggingface dataset:
A Case of 11β-Hydroxylase Deficiency Detected in a Newborn Screening Program by Second-Tier LC-MS/MS
Authors: Peter M. , Janzen N. , Sander S. , Korsch E. , Riepe F.G. , Sander J.
Published: January 2008

Background/Aim: 21-Hydroxylase deficiency congenital adrenal hyperplasia (CAH) is one of the target diseases in many newborn screening programs. 11β-Hydroxylase defiency is less frequent and does not cause salt-losing crisis. Thus, it is not a target disease for newborn screening. However, affected newborns might show slightly elevated levels of 17-OH-progesterone (17-OHP) in the standard immunoassay screening test. The objective is to show that the diagnosis of 11β-hydroxylase deficiency can be done using a dried blood spot from newborn screening. Case Report: A male newborn was born at term. Blood sample for newborn screening was taken 36 h after birth. 17-OHP was slightly elevated using time-resolved fluorescence immunoassay (72.8 nmol/l; cut-off <60 nmol/l). Results: We performed second-tier LC-MS/MS from the same blood sample and found elevated levels of 11-deoxycortisol and androstenedione and low cortisol. The family history was positive with an affected older sister born with ambiguous genitalia. Confirmation of diagnosis was done by hormonal analysis and molecular genetic testing of the CYP11B1 gene. A known CYP11B1 gene mutation W116C was identified in this family. Conclusions: The diagnosis of 11β-hydroxylase deficiency can be made by second-tier LC-MS/MS from dried blood spots. This method is very helpful in the work-up of elevated immunoassay 17-OHP.
Beta-Interferon Protects Multiple Sclerosis Patients against Enhanced Susceptibility to Infections Caused by Poor Air Quality
Authors: Oikonen Mervi K. , Erälinna Juha-Pekka
Published: January 2008

Background: The monthly multiple sclerosis relapse rate was studied from January 1995 to March 2001 from hospital records in Southwestern Finland as a retrospective open-label study. Methods: The relapse rates of β-interferon users and nonusers were compared to ambient air inhalable particle levels and viral infections in the population with logistic regression. Results: In the non-user group, relapses were more frequent 1 month following the episodes when PM10 was in the highest quartile [logistic regression odds ratio = 1.196 (95% CI = 1.019–1.404), p = 0.028] and following adenovirus epidemics in the general population [logistic regression odds ratio = 2.234 (95% CI = 1.013–4.926), p = 0.046]. PM10 and virus infections had no significant effects in interferon users. Conclusion: In addition to being antiviral, interferon also protected multiple sclerosis patients against an enhanced susceptibility to infections caused by PM10.
The Incidence of Childhood Traumatic Brain Injury in Tartu and Tartu County in Estonia
Authors: Ventsel Gerli , Kolk Anneli , Talvik Inga , Väli Marika , Vaikmaa Maarja , Talvik Tiina
Published: January 2008

Background: Traumatic brain injury (TBI) is a major health problem in childhood. Estonia and other Baltic states have the highest trauma-related mortality in the European Union. There are no data on the incidence and causes of TBI for children in Estonia. The aim of this study was to estimate the incidence, structure and main causes of TBI in Tartu and Tartu County. Methods: The study was carried out at Tartu University Hospital, between January 1, 2001, and December 31, 2005. For inclusion in the study the following criteria had to be fulfilled: age 0–14 years, documented brain trauma and neurological symptoms and residency in Tartu or Tartu County. Over the study period the inclusion criteria were fulfilled in 478 cases [272 boys (57%) and 206 girls (43%)]. Results: The incidence of TBI in childhood in Tartu and Tartu County was 369:100,000 (405:100,000 for boys, 330:100,000 for girls). The incidence was highest among children from 0 to 4 years of age – 566:100,000. The main cause of TBI in all age groups was falling – 63.6%. According to severity, 82% of the cases were mild and 18% were moderate and severe. Conclusions: There is an urgent need for governmental prevention programs for TBI in children in Estonia.
Management of Jaundice and Prevention of Severe Neonatal Hyperbilirubinemia in Infants ≥35 Weeks Gestation
Authors: Bhutani Vinod K. , Maisels M. Jeffrey , Stark Ann R. , Buonocore Giuseppe
Published: January 2008

Kernicterus is still occurring but should be largely preventable if health care personnel follow the recommendations listed in this guideline. These recommendations emphasize the importance of universal, systematic assessment of the risk of severe hyperbilirubinemia, lactation support, close follow-up, and prompt intervention when necessary. A systems-based approach to prevent severe neonatal hyperbilirubinemia should be implemented at all birthing facilities and coordinated with continuing ambulatory care. Translational research is needed to better understand the mechanisms of bilirubin neurotoxicity and potential therapeutic interventions.
Cytopathic Effect of Classical Swine Fever Virus NS3 Protein on PK-15 Cells
Authors: Xu Hao , Hong Hai-Xia , Zhang Yan-Ming , Guo Kang-Kang , Deng Xiao-Ming , Ye Gui-Sheng , Yang Xiao-Yun
Published: January 2008

In order to further research the relationship between classical swine fever virus’ (CSFV) NS3 protein and the cytopathic effect (CPE) in cells infected with the CSFV, and to reveal the effect of protein NS3 on the host cells, the NS3 of CSFV Shimen strain amplified by RT-PCR was subcloned into the pEGFP-C1, named pEGFP-C1-NS3. The insert position, the size and the reading frame were correct for restriction enzyme digestion and sequence analysis. The pEGFP-C1-NS3 and pEGFP-C1 were transfected into PK-15 cells by liposome, and positive cell clones were gained by G418. The NS3-EGFP fusion protein expressed in pEGFP-C1-NS3 cells was observed by inverted fluorescence microscopy and identified by Western blot. The CPE appeared in positive pEGFP-C1-NS3 cells 72 h after passaging, apoptosis detection was also performed on positive pEGFP-C1-NS3 cells and pEGFP-C1 cells 72 h after passaging by TUNEL assay. The apoptosis rates in the positive pEGFP-C1-NS3 and pEGFP-C1 cells were 43.4 and 13.1%, respectively (p < 0.05). The results suggest that the CPE in positive pEGFP-C1-NS3 cells was induced by apoptosis and there is a relationship between the expression of NS3 and apoptosis.
Cellular in vitro Assays in the Diagnosis of Hymenoptera Venom Allergy
Authors: Scherer K. , Weber J.M. , Jermann T.M. , Krautheim A. , Tas E. , Ueberschlag E.V. , Cammarata M. , Bircher A.J.
Published: January 2008

Background: The current diagnostic procedures of anaphylactic reactions to hymenoptera stings include intradermal tests, venom-specific IgE (sIgE) and possibly sting challenge tests. Sometimes, the culprit insect remains unidentified. The usefulness of the cellular assays CAST®-ELISA and Flow-CAST® in the management of hymenoptera venom allergy was investigated. Methods: 134 patients with systemic reactions after a yellow jacket wasp and/or honey bee sting and 44 healthy controls underwent skin tests, as well as determination of sIgE (CAP-FEIA), leukocyte sulfidoleukotriene release (CAST-ELISA) and basophil CD63 expression (Flow-CAST) upon insect venom stimulation. The clinical diagnosis based on the history alone served as reference. Sensitivity, specificity, and positive and negative predictive value of all methods were compared. Concordance and correlations among methods were calculated. Results: Sensitivity and specificity of all in vitro tests were consistently high. The combination of all tests (skin tests, sIgE, combined cellular assays) yielded a positive predictive value of 100% for both venoms, if all 3 were positive, and a negative predictive value of 100%, if at least 1 test was positive. Relative specificities were considerably higher for the cellular assays (honey bee: CAST 91.1%, Flow-CAST 85.7%; yellow jacket wasp: CAST 98.4%, Flow-CAST 92.1%) and allow the detection of the culprit insect in patients with reactivity to both insects. The concordance between methods was good. There is no correlation between severity of clinical reaction and cellular assays. Conclusion: CAST-ELISA and Flow-CAST are valuable additional diagnostic tools for establishing the true culprit insect in patients with unclear clinical history or sensitization to both insects.
Angiotensin II Infusion Induces Nephrin Expression Changes and Podocyte Apoptosis
Authors: Jia Junya , Ding Guohua , Zhu Jili , Chen Cheng , Liang Wei , Franki Nicholas , Singhal Pravin C.
Published: January 2008

Background/Aim: In in vitro studies, angiotensin (Ang) II has been demonstrated to promote podocyte apoptosis. The present study evaluates the effects of Ang II infusion in rats on podocyte nephrin expression and apoptosis and the molecular mechanisms involved in Ang II-induced proteinuria and mesangial expansion. Methods: Sprague-Dawley rats were randomly assigned to receive either normal saline or Ang II (400 ng·kg–1·min–1) by means of a mini-osmotic pump for variable time periods. Systolic blood pressure and urinary protein and albumin excretion rate measurements were carried out on days 7, 14, 21, and 28. The animals were sacrificed on days 14 and 28 and evaluated for serum creatinine, renal pathological changes, podocyte apoptosis, renal nephrin mRNA, and protein expression. Results: The Ang II-infused rats developed hypertension and proteinuria. On day 14, the Ang II-infused rats showed narrowing of the slit diaphragm, an increase in podocyte nephrin mRNA and protein expression, and alterations in its distribution along the foot processes. On day 28, the Ang II-infused rats demonstrated the presence of apoptotic podocytes and decreased nephrin mRNA and protein expression. There was a negative correlation between nephrin expression and the numbers of apoptotic podocytes (r = –0.63, p < 0.05). Conclusion: These results suggest that changes in nephrin expression may play a role in the pathogenesis of Ang II-induced podocyte apoptosis.
Individual Heterogeneity in Platelet Response to Lysophosphatidic Acid
Authors: Pamuklar Zehra , Lee Jin Sun , Cheng Hsin-Yuan , Panchatcharam Manikandan , Steinhubl Steve , Morris Andrew J. , Charnigo Richard , Smyth Susan S.
Published: January 2008

Objective—

The bioactive lipid lysophosphatidic acid (LPA) stimulates platelet actin reorganization, adhesion, shape change, and aggregation. LPA is present in blood and exposure or release of LPA after atherosclerotic plaque rupture has been proposed to trigger platelet thrombus formation.

Methods and Results—

In this report, we characterize heterogeneity in LPA responses among individuals. Platelets isolated from approximately 20% of healthy donors consistently failed to aggregate in response to LPA. Our studies indicate that, rather than lacking stimulatory pathways, platelets from “nonresponsive” donors respond to LPA by triggering inhibitory pathway(s) to block platelet aggregation. Consistent with this observation, LPA-induced aggregation could be partially restored to “nonresponsive” platelets by pharmacological inhibition of cAMP generation. LPA “nonresponsiveness” may be related to heightened platelet expression of LPA receptor 4 and PPARγ. Among 70 patients with stable coronary artery disease (CAD), only 1 (1.4%) was identified as an LPA nonresponder. Moreover, in 33 patients presenting for diagnostic catheterization, CAD was identified as having a bivariate association with platelet LPA responder/nonresponder status.

Conclusions—

Platelet LPA signaling may involve stimulatory and inhibitory pathways, with the inhibitory pathway predominating in ≈20% of individuals. Diseases such as CAD that affect platelet reactivity may attenuate this inhibitory pathway in platelets.
Fibrinogen Genes and Myocardial Infarction
Authors: Koch Werner , Hoppmann Petra , Biele Janita , Mueller Jakob C. , Schömig Albert , Kastrati Adnan
Published: January 2008

Objective—

Fibrinogen has a role in inflammatory processes and participates in atherosclerotic plaque formation. Despite intensive investigation, there is no clear evidence for a role of variations in the genes coding for the fibrinogen-α, fibrinogen-β, and fibrinogen-γ polypeptide chains in myocardial infarction. We examined the association of haplotypes in the 50-kb fibrinogen gene region with myocardial infarction in 2 large case-control samples.

Methods and Results—

Study sample 1 consisted of 3657 patients with myocardial infarction and 1211 control individuals and sample 2 comprised 1392 patients and 1392 controls. Haplotypes were inferred from genotype analyses of tagging single nucleotide polymorphisms dispersed among the fibrinogen genes. The frequencies of these haplotypes were not significantly different between the case and control groups in either sample (
P
≥0.07). In addition, haplotypes specific for individual fibrinogen genes were analyzed. No substantial differences in the frequencies of these haplotypes were observed between the groups (
P
≥0.13). Finally, haplotypes composed of SNPs that exhibited relatively low pairwise allelic associations among each other were examined. The proportions of the haplotypes were not significantly different between cases and controls (
P
≥0.12).

Conclusion—

A haplotype analysis did not reveal a link between genetic variations in the fibrinogen gene region and myocardial infarction.
Elevated Gamma-Glutamyltransferase Activity and Perturbed Thiol Profile Are Associated With Features of Metabolic Syndrome
Authors: Giral Philippe , Jacob Nelly , Dourmap Caroline , Hansel Boris , Carrié Alain , Bruckert Eric , Girerd Xavier , Chapman M. John
Published: January 2008

Background—

Prospective cohort studies have revealed that plasma γ-glutamyltransferase (GGT) activity exhibits a positive association with coronary artery disease. GGT which is equally elevated in metabolic syndrome (MS), is the major regulator of circulating concentrations of thiol compounds derived from glutathione (GSH) cleavage, ie, cysteine and cysteinyl glycine. We compared the circulating thiol profile in a cohort of patients displaying atherogenic dyslipidemia with and without MS.

Methods and Results—

This cross-sectional study involved 1131 dyslipidemic patients in primary prevention of whom 26% presented with MS. GGT activity and plasma cysteinyl-glycine and cysteine concentrations were higher in MS patients; by contrast, levels of GSH were significantly lower (
P
<10 to 4 for all comparisons versus patients without MS). We compared patient groups on the basis of the number of MS criteria which were concomitantly present. A progressive decrease in glutathione levels in contrast to a progressive increase in both cysteinyl–glycine and cysteine levels, and GGT activity, was observed as a function of the number of MS components in the overall population (
P
for trend <10
−6
).

Conclusion—

Dyslipidemic patients exhibiting MS are characterized by elevated GGT activity which is associated with perturbed metabolism of thiol compounds.
Far Infrared Therapy Inhibits Vascular Endothelial Inflammation via the Induction of Heme Oxygenase-1
Authors: Lin Chih-Ching , Liu Xiao-Ming , Peyton Kelly , Wang Hong , Yang Wu-Chang , Lin Shing-Jong , Durante William
Published: January 2008

Objective—

Survival of arteriovenous fistulas (AVFs) in hemodialysis patients is associated with both far infrared (FIR) therapy and length polymorphisms of the heme oxygenase-1 (HO-1) promoter. In this study, we evaluated whether there is an interaction between FIR radiation and HO-1 in regulating vascular inflammation.

Methods and Results—

Treatment of cultured human umbilical vein endothelial cells (ECs) with FIR radiation stimulated HO-1 protein, mRNA, and promoter activity. HO-1 induction was dependent on the activation of the antioxidant responsive element/NF-E2-related factor-2 complex, and was likely a consequence of heat stress. FIR radiation also inhibited tumor necrosis factor (TNF)-α–mediated expression of E-selectin, vascular cell adhesion molecule-1, intercellular cell adhesion molecule-1, monocyte chemoattractant protein-1, interleukin-8, and the cytokine-mediated adhesion of monocytes to ECs. The antiinflammatory action of FIR was mimicked by bilirubin, and was reversed by the HO inhibitor, tin protoporphyrin-IX, or by the selective knockdown of HO-1. Finally, the antiinflammatory effect of FIR was also observed in patients undergoing hemodialysis.

Conclusions—

These results demonstrate that FIR therapy exerts a potent antiinflammatory effect via the induction of HO-1. The ability of FIR therapy to inhibit inflammation may play a critical role in preserving blood flow and patency of AVFs in hemodialysis patients.
Transglutaminase 2 Is Central to Induction of the Arterial Calcification Program by Smooth Muscle Cells
Authors: Johnson Kristen A. , Polewski Monika , Terkeltaub Robert A.
Published: January 2008

Arterial calcification is a phenotype of vascular repair in atherosclerosis, diabetes, hyperphosphatemic renal failure, and aging. Arterial calcification is modulated by transition of arterial smooth muscle cells (SMCs) from contractile to chondro–osseous differentiation programmed in response to increases in P
i
, bone morphogenetic protein-2, and certain other stimuli. Transglutaminase (TG)2 release modulates tissue repair, partly by transamidation-catalyzed covalent crosslinking of extracellular matrix substrates. TG2 regulates cultured SMC differentiation, resistance artery remodeling to vasoconstriction, and atherosclerotic lesion size. Here, TG2 expression was required for the majority of TG activity in mouse and human aortic SMCs. TG2
−/−
SMCs lost the capacity for P
i
donor–induced formation of multicellular bone-like nodules and for increased expression of the type III sodium–dependent P
i
cotransporter Pit-1 and certain osteoblast and chondrocyte genes (tissue-nonspecific alkaline phosphatase, the osteoblast master transcription factor runx2, and chondrocyte-restricted aggrecan), and for P
i
donor– and bone morphogenetic protein-2–induced calcification. Uniquely in TG2
−/−
SMCs, P
i
donor treatment increased expression of the physiological SMC chondro–osseous differentiation and calcification inhibitors osteoprotegerin, matrix Gla protein, and osteopontin. Conversely, TG2
−/−
SMCs, unlike wild-type SMCs, failed to maintain contractile differentiation on laminin. Exogenous catalytically active TG2 augmented calcification by TG2
−/−
SMC in response to P
i
donor treatment. TG2 expression also drove P
i
-stimulated calcification of mouse aortic ring organ cultures, which was suppressed by the TG2 catalytic site-specific inhibitor Boc-DON-Gln-Ile-Val-OMe (10 μmol/L). Our results suggest that TG2 release in injured arteries is critical for programming chondro–osseous SMC differentiation and calcification in response to increased P
i
and bone morphogenetic protein-2.
Identification of Cardiac-Specific Myosin Light Chain Kinase
Authors: Chan Jason Y. , Takeda Morihiko , Briggs Laura E. , Graham Megan L. , Lu Jonathan T. , Horikoshi Nobuo , Weinberg Ellen O. , Aoki Hiroki , Sato Naruki , Chien Kenneth R. , Kasahara Hideko
Published: January 2008

Two myosin light chain (MLC) kinase (MLCK) proteins, smooth muscle (encoded by
mylk1
gene) and skeletal (encoded by
mylk2
gene) MLCK, have been shown to be expressed in mammals. Even though phosphorylation of its putative substrate, MLC2, is recognized as a key regulator of cardiac contraction, a MLCK that is preferentially expressed in cardiac muscle has not yet been identified. In this study, we characterized a new kinase encoded by a gene homologous to
mylk1
and -
2
, named cardiac MLCK, which is specifically expressed in the heart in both atrium and ventricle. In fact, expression of cardiac MLCK is highly regulated by the cardiac homeobox protein Nkx2-5 in neonatal cardiomyocytes. The overall structure of cardiac MLCK protein is conserved with skeletal and smooth muscle MLCK; however, the amino terminus is quite unique, without significant homology to other known proteins, and its catalytic activity does not appear to be regulated by Ca
2+
/calmodulin in vitro. Cardiac MLCK is phosphorylated and the level of phosphorylation is increased by phenylephrine stimulation accompanied by increased level of MLC2v phosphorylation. Both overexpression and knockdown of cardiac MLCK in cultured cardiomyocytes revealed that cardiac MLCK is likely a new regulator of MLC2 phosphorylation, sarcomere organization, and cardiomyocyte contraction.
Asymmetric Involution of the Myocardial Field Drives Heart Tube Formation in Zebrafish
Authors: Rohr Stefan , Otten Cécile , Abdelilah-Seyfried Salim
Published: January 2008

Many vertebrate organs are derived from monolayered epithelia that undergo morphogenesis to acquire their shape. Whereas asymmetric left/right gene expression within the zebrafish heart field has been well documented, little is known about the tissue movements and cellular changes underlying early cardiac morphogenesis. Here, we demonstrate that asymmetric involution of the myocardium of the right-posterior heart field generates the ventral floor, whereas the noninvoluting left heart field gives rise to the dorsal roof of the primary heart tube. During heart tube formation, asymmetric left/right gene expression within the myocardium correlates with asymmetric tissue morphogenesis. Disruption of left/right gene expression causes randomized myocardial tissue involution. Time-lapse analysis combined with genetic analyses reveals that motility of the myocardial epithelium is a tissue migration process. Our results demonstrate that asymmetric morphogenetic movements of the 2 bilateral myocardial cell populations generate different dorsoventral regions of the zebrafish heart tube. Failure to generate a heart tube does not affect the acquisition of atrial versus ventricular cardiac cell shapes. Therefore, establishment of basic cardiac cell shapes precedes cardiac function. Together, these results provide the framework for the integration of single cell behaviors during the formation of the vertebrate primary heart tube.
Activation of Cardiac Progenitor Cells Reverses the Failing Heart Senescent Phenotype and Prolongs Lifespan
Authors: Gonzalez Arantxa , Rota Marcello , Nurzynska Daria , Misao Yu , Tillmanns Jochen , Ojaimi Caroline , Padin-Iruegas M. Elena , Müller Patrick , Esposito Grazia , Bearzi Claudia , Vitale Serena , Dawn Buddhadeb , Sanganalmath Santosh K. , Baker Mathue , Hintze Thomas H. , Bolli Roberto , Urbanek Konrad , Hosoda Toru , Anversa Piero , Kajstura Jan , Leri Annarosa
Published: January 2008

RETRACTION

This article has been retracted:

Circ Res
. 2018;123:e00. DOI: 10.1161/RES.0000000000000244
Integrin β1 Subunit Controls Mural Cell Adhesion, Spreading, and Blood Vessel Wall Stability
Authors: Abraham Sabu , Kogata Naoko , Fässler Reinhard , Adams Ralf H.
Published: January 2008

Growth, maturation, and integrity of the blood vessel network require extensive communication between the endothelial cells, which line the vascular lumen, and associated mural cells, namely vascular smooth muscle cells and pericytes. Pericytes extend long processes, make direct contact with the capillary endothelium, and promote vascular quiescence by suppressing angiogenic sprouting. Vascular smooth muscle cells are highly contractile, extracellular matrix–secreting cells that cover arteries and veins and provide them with mechanical stability and elasticity. In the damaged blood vessel wall, for example in atherosclerotic lesions, vascular smooth muscle cells lose their differentiated state and acquire a highly mitotic, so-called “synthetic” phenotype, which is thought to promote pathogenesis. Among other factors, extracellular matrix molecules and integrin family cell–matrix receptors may regulate this phenotypic transition. Here we show that the inactivation of the gene encoding the integrin β1 subunit (
Itgb1
) with a Cre-loxP approach in mice leads to mural cell defects and postnatal lethality. Integrin β1–deficient vascular smooth muscle cells display several hallmarks of the synthetic phenotype: Cell proliferation is enhanced, whereas differentiation and their ability to support blood vessels are compromised. Similarly, mutant pericytes are poorly spread but present in larger numbers. Our analysis of this mutant model shows that integrin β1–mediated cell–matrix adhesion is a major determinant of the mural cell phenotype.
E-Mail Marketing by International Hotel Chains
Authors: O'Connor Peter
Published: January 2008

E-mail's utility as a marketing medium is being limited by unprecedented growth in spam—unsolicited commercial bulk e-mail messages. Given the access that hotels have to their customers' personal data and the potential for using this resource for marketing and promotional purposes, this study sets out to establish whether international hotel chains conform to the legislative guidelines found in the U.S. Controlling the Assault of Non-Solicited Pornography and Marketing (CAN-SPAM) Act of 2003 with regard to use of personal data for e-mail marketing purposes. By monitoring multiple e-mail accounts over a one-year period, the study found that not only is hotel companies' behavior highly ethical with regard to their use of customers' personal data, but in fact it may serve as an example of best practice for other businesses.
Contextual Factors and Cost Profiles Associated with Employee Turnover
Authors: Tracey J. Bruce , Hinkin Timothy R.
Published: January 2008

To gain insights about the nature and expenses of specific aspects of employee turnover, the authors gathered data from thirty-three U.S. hotels and found that the costs of turnover were generally higher for (1) high-complexity jobs; (2) independent properties; (3) high—average daily rate (ADR) properties; (4) large properties; and (5) high-occupancy properties. The authors also identified several activities associated with recruitment, selection, and training that were linked to lower overall costs of turnover. The results shed new light on the nature and consequences of turnover and provide some prescriptive guidance for managing this serious operational and strategic challenge.
Reconciling the Architectural Preferences of Architects and the Public
Authors: Fawcett William , Ellingham Ian , Platt Stephen
Published: January 2008

The article reports on a survey of visual preferences for suburban office buildings. The participants comprised members of the professions involved in the speculative development of these buildings and building users. The survey method used paired comparisons of photographs representing eight different design types for suburban office buildings. The data were processed using a form of conjoint analysis. Differences in the preferences of architects and users were revealed, confirming previous surveys. Analysis of the preferences showed a different weighting of design attributes. Despite these differences, a design type could be identified that would combine the preferences of both architects and users. This finding is generalized in the proposal for an “ordered preference model” to generate designs which reconcile the preferences of both architects and laypersons.
Use of a Mouth-Wiping Response to Reduce Drooling by Two Persons With Profound Developmental Disabilities
Authors: Lancioni Giulio E. , Singh Nirbhay N. , O'Reilly Mark F. , Sigafoos Jeff , Pichierri Sabrina , Iaffaldano Daniela , Latrofa Alessandra , Oliva Doretta
Published: January 2008

Two men with profound developmental disabilities used a mouth-wiping response instrumental to reduce drooling via a micro-switch-based program (i.e., a program in which the response was automatically monitored and followed by positive stimulation). The wiping response was performed via a napkin or a handkerchief placed inside a belt pocket. The micro-switch technology consisted of two mini-tilt sensors and a radio transmitter hidden inside the napkin, or an optic sensor and a radio transmitter fixed inside the belt pocket. The study was carried out according to a multiple baseline across participants and included a 3-month postintervention check. During the baseline, the participants' mean frequencies of mouth wiping were near zero, and mean percentages of wet chin intervals were about 45 and 50. During the intervention, the mean wiping frequencies increased to 1.6 and 1.9 per min, whereas the mean percentages of wet-chin intervals were mostly below 10. These values were maintained at the postintervention check. Implications of the findings and limitations of the study are discussed.
Barriers to College Opportunity
Authors: Perna Laura W. , Thomas Scott L.
Published: January 2008

This study explores the ways that state high school testing policies shape college opportunity among students attending 15 high schools in five states. The authors use multiple descriptive case studies to explore how testing policies influence key predictors of college enrollment (e.g., high school graduation, academic preparation, knowledge, and information) and a high school's capacity to promote college enrollment. The study identifies several unintended consequences of state-mandated high school tests for factors related to college enrollment and shows that the unintended negative consequences are greater at schools with the lowest average socioeconomic status and academic achievement than at other schools.
Plexiform Neurofibroma of the Cauda Equina: A Case Report and Review of the Literature
Authors: Simou Nafsika , Zioga Aikaterini , Zygouris Andreas , Pahatouridis Dimitrios , Charalabopoulos Konstatinos , Batistatou Anna
Published: January 2008

Plexiform neurofibroma of the cauda equina is extremely rare. Herein, a case is reported in a 56-year-old man who also had muscle atrophy, severe motor disturbance, and mild sensory disturbance of the left leg due to childhood poliomyelitis. The clinical symptoms manifested insidiously until the patient developed cauda equina syndrome. At operation, the tumor mass was observed to engulf the nerve roots of the cauda equina. After pathological examination, the diagnosis of plexiform neurofibroma was made. Neither the patient described herein nor any previously reported patients had neurofibromatosis.
Pediatric Renal Cell Carcinoma Associated With Xp11.2 Translocation/TFE3 Gene Fusion
Authors: Ni Wayan Winarti  , Argani Pedram , De Marzo Angelo M. , Hicks Jessica , Mulyadi Ketut
Published: January 2008

Renal cell carcinoma (RCC) in children and young adults is rare and pathologically problematic. RCC can be either hereditary or sporadic and has a guarded prognosis because appropriate management has not been established. A case of RCC in an 11-year-old is reported. The clinical presentation was a right abdominal mass, hematuria, urinary tract infection, and wasting. Radio-logically, the mass was found within the right kidney with calcification and paraaortic lymphadenopathy. The postsurgical diagnosis was Wilms' tumor stage T4N2M0. On gross inspection, the tumor was ill defined, extending across Gerota's fascia and into the ureter lumina. Microscopically, the tumor consisted of malignant epithelial cells with clear and eosinophilic cytoplasm in nested, papillary, and alveolar configuration. Hyaline nodules, psammoma bodies, vascular invasion, capsular invasion, and extension into the ureter were also found. Immunohistochemically, the cells showed strong nuclear immunoreactivity for TFE3. We concluded that this case was an RCC associated with Xp11.2 translocation/ TFE3 fusion, Fuhrman grade 3, stage IV.
Correlation of p63 Immunoreactivity With Tumor Grade in Meningiomas
Authors: Rushing Elisabeth J. , Olsen Cara , Man Yan-Gao
Published: January 2008

Predicting tumor behavior in meningiomas based on morphologic features alone remains difficult. The present study was undertaken to assess the correlation between p63 expression and histological grade of meningiomas. A total of 37 archival intracranial meningiomas were classified into 20 grade I, 13 grade II, and 4 grade III meningiomas. Using immunohistochemical methods, staining was scored based on nuclear and/or cytoplasmic distribution as follows: 0, no staining; 1, 50% or less of the cells; 2, more than 50% of the cells. Of grade I meningiomas, 95% (19/20) lacked nuclear p63 expression and none exhibited cytoplasmic staining. Overall, 92% of grade II tumors showed nuclear expression and 31% (4/13) showed cytoplasmic expression. Grade III tumors showed an overall nuclear expression of 75% (3/4) with all exhibiting cytoplasmic staining. Our results indicate a good correlation exists between histological grade and p63 protein expression, suggesting that p63 expression might be correlated with the clinical outcome.
Hybrid Verrucous—Squamous Cell Carcinoma of the Ovary With Synchronous Squamous Cell Carcinoma of the Endometrium
Authors: Fancher Tiffany T. , Hamzi Munir H. , Macaron Shady H. , Magno Winston B. , Dudrick Stanley J. , Palesty J. Alexander
Published: January 2008

Verrucous carcinoma, a variant of well-differentiated squamous cell carcinoma, is usually described in the literature as arising in the oral cavity, skin, and larynx. The reports on verrucous carcinoma arising in the genital tract, usually originating in the vagina, vulva, or uterine cervix, are few. Verrucous carcinoma arising in the ovary has not been previously reported. In this article, a unique hybrid carcinoma, a large aggressive verrucous carcinoma in combination with squamous carcinoma of the left ovary and synchronously occurring with a squamous cell carcinoma in the endometrium, is presented. This unique case of a hybrid carcinoma includes the first-known case of this type of carcinoma involving the ovary. The negative cervical evaluation findings, together with the histologic patterns of the tumors in the uterus and the ovary, support the conclusion that these 2 carcinomas are synchronous, one arising in the left ovary and the other arising in the uterus.
Frequency of Clinically Occult Intraepithelial and Invasive Neoplasia in Reduction Mammoplasty Specimens: A Study of 516 Cases
Authors: Dotto Jorge , Kluk Michael , Geramizadeh Bita , Tavassoli Fattaneh A.
Published: January 2008

Reduction mammoplasty is a frequently performed procedure for the treatment of macromastia and for the achievement of symmetry in breast cancer patients following lumpectomy. Slides from 516 consecutive bilateral reduction mammoplasties performed for macromastia over 15 years were reviewed. Among these, 92 (18%) low-risk ductal intraepithelial neoplasia/intraductal hyperplasia, 28 (5%) ductal intraepithelial neoplasia 1 (1 low-grade ductal carcinoma in situ, 11 atypical intraductal hyperplasia, and 16 flat type), 17 (3%) lobular intraepithelial neoplasia, and 1 (0.2%) tubular carcinoma were identified. The patients were categorized into 3 age groups: <40 (n = 352), 40 to 50 (n = 107), and over 50 years (n = 57); the frequency of the lesions increased with age. These data confirm the low frequency of clinically occult malignancies identified in reduction mammoplasty specimens and provide substantial information about the frequency of a variety of intraepithelial proliferations. Preoperative mammography, specimen orientation, and inking of margins with 1 color are advised when reduction mammoplasty is scheduled for women ≥ 40 years of age.
Expression of p21Cip1/Waf1 and p27Kip1 in Small Cell Neuroendocrine Carcinoma of the Uterine Cervix
Authors: Kataoka Tatsuki R. , Tsukamoto Yoshitane , Matsumura Makiko , Miyake Asako , Kamiura Shoji , Ishiguro Shingo , Nishizawa Yasuko
Published: January 2008

Small-cell neuroendocrine carcinoma of the uterine cervix (SCCC), a rare but malignant cervical neoplasm, has a highly aggressive phenotype that requires more intensive treatment than other cervical tumors. Immunohistochemical methods were used to compare the expression of p21Cip1/Waf1 and p27Kip1 in SCCC and squamous cell carcinoma, the most common type of cervical cancer. In SCCC, p21 expression was significantly reduced compared with squamous cell carcinoma, whereas expression of p27 was similar in both carcinomas. Reduced expression of p21 could be a helpful diagnostic marker and may contribute to the invasive phenotype of SCCC.
Are There Any Differences in the Expression of Hormonal Receptors and Proliferation Markers Between Uterine and Extrauterine Leiomyomas?
Authors: Şen Nilay , Demirkan Nese C. , Colakoglu Nagihan , Duzcan Suleyman E.
Published: January 2008

The aim of this study is to determine the immunohistochemical expressions of estrogen receptor, progesterone receptor, and Ki-67 proliferation marker in 8 extrauterine leiomyomas and to compare these values with their uterine counterparts. In all, 8 patients with extrauterine leiomyomas and 20 patients with uterine leiomyomas as a control group were studied. Sections were immunohistochemically stained with estrogen receptor, progesterone receptor, and Ki-67 antibodies. Labeling indices for estrogen receptor, progesterone receptor, and Ki-67 were found to be 33.05 % ± 31.70%, 14.18 % ± 18.80%, and 0.52 % ± 1.32% for extrauterine leiomyomas and 65.09% ± 26.65%, 32.53% ± 32.80%, and 0.37% ± 0.71% for uterine leiomyomas, respectively. The difference of labeling indices for progesterone receptor between uterine leiomyomas and extrauterine leiomyomas was statistically significant ( P = .002). This study shows that increased expression of progesterone receptor is observed only in uterine leiomyomas during the reproductive period. However, it seems that additional factors to hormone receptors contribute to the development of extrauterine leiomyomas.
PEComa: Another Member of the MiT Tumor Family?
Authors: Righi Alberto , Dimosthenous Kypros , Rosai Juan
Published: January 2008

We report 2 cases of PEComa, one occurring in the colon of an 11-year-old boy and the other in the bone (fibula) of a 92-year-old woman. Both tumors consisted of nests of large epithelioid cells surrounded by a fibrovascular stroma. The nuclei were large and vesicular, with prominent centrally located nucleoli. The cytoplasm was eosinophilic, with a fine to coarse granularity. Mitoses and individual cell necrosis were infrequent. Immunohistochemically, both tumors showed strong cytoplasmic expression of HMB-45 and intense nuclear positivity for TFE3. To our knowledge, nuclear positivity for TFE3 has been previously reported in only 5 cases of PEComa. Reactivity to this marker suggests that PEComa should be added to the growing list of human tumors of the so-called MiT family gene.
Roundtable Retrospective 2007
Authors: Sherwyn David
Published: January 2008

A review of sexual harassment case law was presented at the 2007 Labor and Employment Roundtable at the Cornell University School of Hotel Administration. The foremost lesson is that employers should take steps to prevent harassment, but failing that, an employer should maintain and follow a strong policy on sexual harassment and immediately make an effective response to a complaint.
Outback Steakhouse in Korea
Authors: Verma Rohit
Published: January 2008

Economics is only the beginning of the puzzle for successful international expansion by food-service firms. As depicted in the accompanying case study, Outback Korea seems to have considered such other factors as local culture and proper entry strategy.
HO-1 underlies resistance of AML cells to TNF-induced apoptosis
Authors: Rushworth Stuart A. , MacEwan David J.
Published: January 2008

In human monocytes, tumor necrosis factor (TNF) induces a proinflammatory response. In NF-κB–inhibited monocytes, TNF stimulates cell death/apoptosis. In the present study, we analyzed the response of acute myeloid leukemia (AML) cells to TNF stimulation in conjunction with NF-κB inhibition. In all AML-derived cells tested, NF-κB–inhibited cells were resistant to TNF-induced apoptosis. Further investigation revealed that the cytoprotective gene heme oxygenase-1 (HO-1) was induced in NF-κB–inhibited AML cells in response to TNF stimulation, and HO-1 was responsible for the resistance of AML cells to the cytotoxic actions of TNF. Moreover, after transfection with HO-1 siRNA, the resistance to TNF-induced cell death signals of AML cells was removed. The HO-1 promoter region contains antioxidant-response elements that can bind the transcription factor NF-E2–related factor 2 (Nrf2). We further demonstrated that Nrf2 was activated by TNF under NF-κB–inhibited conditions, to play the major role in up-regulating HO-1 expression and ultimately the fate of AML cells. These results demonstrate a novel mechanism by which TNF-induced cell death is inhibited in AML cells through the induction of HO-1, via Nrf2 activation.
Enhanced efficacy and reduced toxicity of multifactorial adjuvants compared with unitary adjuvants as cancer vaccines
Authors: Ahonen Cory L. , Wasiuk Anna , Fuse Shinichiro , Turk Mary Jo , Ernstoff Marc S. , Suriawinata Arief A. , Gorham James D. , Kedl Ross M. , Usherwood Edward J. , Noelle Randolph J.
Published: January 2008

Identification of Toll-like receptors (TLRs) and their ligands, and tumor necrosis factor–tumor necrosis factor receptor (TNF-TNFR) pairs have provided the first logical, hypothesis-based strategies to molecularly concoct adjuvants to elicit potent cell-mediated immunity via activation of innate and adaptive immunity. However, isolated activation of one immune pathway in the absence of others can be toxic, ineffective, and detrimental to long-term, protective immunity. Effective engineered vaccines must include agents that trigger multiple immunologic pathways. Here, we report that combinatorial use of CD40 and TLR agonists as a cancer vaccine, compared with monotherapy, elicits high frequencies of self-reactive CD8+ T cells, potent tumor-specific CD8+ memory, CD8+ T cells that efficiently infiltrate the tumor-burdened target organ; therapeutic efficacy; heightened ratios of CD8+ T cells to FoxP3+ cells at the tumor site; and reduced hepatotoxicity. These findings provide intelligent strategies for the formulation of multifactorial vaccines to achieve maximal efficacy in cancer vaccine trials in humans.
Repression via the GATA box is essential for tissue-specific erythropoietin gene expression
Authors: Obara Naoshi , Suzuki Norio , Kim Kibom , Nagasawa Toshiro , Imagawa Shigehiko , Yamamoto Masayuki
Published: January 2008

In response to anemia, erythropoietin (Epo) gene transcription is markedly induced in the kidney and liver. To elucidate how Epo gene expression is regulated in vivo, we established transgenic mouse lines expressing green fluorescent protein (GFP) under the control of a 180-kb mouse Epo gene locus. GFP expression was induced by anemia or hypoxia specifically in peritubular interstitial cells of the kidney and hepatocytes surrounding the central vein. Surprisingly, renal Epo-producing cells had a neuronlike morphology and expressed neuronal marker genes. Furthermore, the regulatory mechanisms of Epo gene expression were explored using transgenes containing mutations in the GATA motif of the promoter region. A single nucleotide mutation in this motif resulted in constitutive ectopic expression of transgenic GFP in renal distal tubules, collecting ducts, and certain populations of epithelial cells in other tissues. Since both GATA-2 and GATA-3 bind to the GATA box in distal tubular cells, both factors are likely to repress constitutively ectopic Epo gene expression in these cells. Thus, GATA-based repression is essential for the inducible and cell type–specific expression of the Epo gene.
Angiopoietin-like 5 and IGFBP2 stimulate ex vivo expansion of human cord blood hematopoietic stem cells as assayed by NOD/SCID transplantation
Authors: Zhang Cheng Cheng , Kaba Megan , Iizuka Satoru , Huynh HoangDinh , Lodish Harvey F.
Published: January 2008

Hematopoietic stem cells (HSCs) are the basis of bone marrow transplantation and are attractive target cells for hematopoietic gene therapy, but these important clinical applications have been severely hampered by difficulties in ex vivo expansion of HSCs. In particular, the use of cord blood for adult transplantation is greatly limited by the number of HSCs. Previously we identified angiopoietin-like proteins and IGF-binding protein 2 (IGFBP2) as new hormones that, together with other factors, can expand mouse bone marrow HSCs in culture. Here, we measure the activity of multipotent human severe combined immunodeficient (SCID)–repopulating cells (SRCs) by transplantation into the nonobese diabetic SCID (NOD/SCID) mice; secondary transplantation was performed to evaluate the self-renewal potential of SRCs. A serum-free medium containing SCF, TPO, and FGF-1 or Flt3-L cannot significantly support expansion of the SRCs present in human cord blood CD133+ cells. Addition of either angiopoietin-like 5 or IGF-binding protein 2 to the cultures led to a sizable expansion of HSC numbers, as assayed by NOD/SCID transplantation. A serum-free culture containing SCF, TPO, FGF-1, angiopoietin-like 5, and IGFBP2 supports an approximately 20-fold net expansion of repopulating human cord blood HSCs, a number potentially applicable to several clinical processes including HSC transplantation.
Broadly sampled multigene trees of eukaryotes
Authors: Yoon Hwan Su , Grant Jessica , Tekle Yonas I , Wu Min , Chaon Benjamin C , Cole Jeffrey C , Logsdon John M , Patterson David J , Bhattacharya Debashish , Katz Laura A
Published: January 2008

Background

Our understanding of the eukaryotic tree of life and the tremendous diversity of microbial eukaryotes is in flux as additional genes and diverse taxa are sampled for molecular analyses. Despite instability in many analyses, there is an increasing trend to classify eukaryotic diversity into six major supergroups: the 'Amoebozoa', 'Chromalveolata', 'Excavata', 'Opisthokonta', 'Plantae', and 'Rhizaria'. Previous molecular analyses have often suffered from either a broad taxon sampling using only single-gene data or have used multigene data with a limited sample of taxa. This study has two major aims: (1) to place taxa represented by 72 sequences, 61 of which have not been characterized previously, onto a well-sampled multigene genealogy, and (2) to evaluate the support for the six putative supergroups using two taxon-rich data sets and a variety of phylogenetic approaches.

Results

The inferred trees reveal strong support for many clades that also have defining ultrastructural or molecular characters. In contrast, we find limited to no support for most of the putative supergroups as only the 'Opisthokonta' receive strong support in our analyses. The supergroup 'Amoebozoa' has only moderate support, whereas the 'Chromalveolata', 'Excavata', 'Plantae', and 'Rhizaria' receive very limited or no support.

Conclusion

Our analytical approach substantiates the power of increased taxon sampling in placing diverse eukaryotic lineages within well-supported clades. At the same time, this study indicates that the six supergroup hypothesis of higher-level eukaryotic classification is likely premature. The use of a taxon-rich data set with 105 lineages, which still includes only a small fraction of the diversity of microbial eukaryotes, fails to resolve deeper phylogenetic relationships and reveals no support for four of the six proposed supergroups. Our analyses provide a point of departure for future taxon- and gene-rich analyses of the eukaryotic tree of life, which will be critical for resolving their phylogenetic interrelationships.