bluuebunny/crossref_metadata_2025 huggingface dataset:
Branchial expression patterns of claudin isoforms in Atlantic salmon during seawater acclimation and smoltification
Authors: Tipsmark C. K. , Kiilerich P. , Nilsen T. O. , Ebbesson L. O. E. , Stefansson S. O. , Madsen S. S.
Published: March 2008

In euryhaline teleosts, permeability changes in gill epithelia are essential during acclimation to changed salinity. This study examined expression patterns of branchial tight junction proteins called claudins, which are important determinants of ion selectivity and general permeability in epithelia. We identified Atlantic salmon genes belonging to the claudin family by screening expressed sequence tag libraries available at NCBI, and classification was performed with the aid of maximum likelihood analysis. In gill libraries, five isoforms (10e, 27a, 28a, 28b, and 30) were present, and quantitative PCR analysis confirmed tissue-specific expression in gill when compared with kidney, intestine, heart, muscle, brain, and liver. Expression patterns during acclimation of freshwater salmon to seawater (SW) and during the smoltification process were examined. Acclimation to SW reduced the expression of claudin 27a and claudin 30 but had no overall effect on claudin 28a and claudin 28b. In contrast, SW induced a fourfold increase in expression of claudin 10e. In accord, a peak in branchial claudin 10e was observed during smoltification in May, coinciding with optimal SW tolerance. Smoltification induced no significant changes in expression of the other isoforms. This study demonstrates the expression of an array of salmon claudin isoforms and shows that SW acclimation involves inverse regulation, in the gill, of claudin 10e vs. claudin 27a and 30. It is possible that claudin 10e is an important component of cation selective channels, whereas reduction in claudin 27a and 30 may change permeability conditions in favor of the ion secretory mode of the SW gill.
Nedd4-2 isoforms ubiquitinate individual epithelial sodium channel subunits and reduce surface expression and function of the epithelial sodium channel
Authors: Raikwar Nandita S. , Thomas Christie P.
Published: March 2008

We previously reported the existence of multiple isoforms of human Nedd4-2 ( Am J Physiol Renal Physiol 285: F916–F929, 2003). When overexpressed in M-1 collecting duct epithelia, full-length Nedd4-2 (Nedd4-2), Nedd4-2 lacking the NH2-terminal C2 domain (Nedd4-2ΔC2), and Nedd4-2 lacking WW domains 2 and 3 (Nedd4-2ΔWW2,3) variably reduce benzamil-sensitive Na+ transport. We investigated the effect of each of the Nedd4-2 isoforms on cell surface expression and ubiquitination of ENaC subunits. We find that αENaC when transfected alone or with β and γENaC is expressed at the cell surface and this membrane expression is variably reduced by coexpression with each of the Nedd4-2 isoforms. Nedd4-2 reduces the half-life of ENaC subunits and enhances the ubiquitination of α, β, and γENaC subunits when expressed alone or together suggesting that each subunit is a target for Nedd4-2-mediated ubiquitination. As has been reported recently, we confirm that the surface-expressed pool of ENaC is multi-ubiquitinated. Inhibitors of the proteasome increase ubiquitination of ENaC subunits and stimulate Na+ transport in M-1 cells consistent with a role for the ubiquitin-proteasome pathway in regulating Na+ transport in the collecting duct.
LOX-1 and inflammation: a new mechanism for renal injury in obesity and diabetes
Authors: Kelly Katherine J. , Wu Pengfei , Patterson Carolyn E. , Temm Constance , Dominguez Jesus H.
Published: March 2008

The early nephropathy in obese, diabetic, dyslipidemic (ZS) rats is characterized by tubular lipid accumulation and pervasive inflammation, two critically interrelated events. We now tested the hypothesis that proximal tubules from ZS obese diabetic rats in vivo, and proximal tubule cells (NRK52E) exposed to oxidized LDL (oxLDL) in vitro, change their normally quiescent epithelial phenotype into a proinflammatory phenotype. Urine of obese diabetic rats contained more lipid peroxides, and LOX-1, a membrane receptor that internalizes oxidized lipids, was mobilized to luminal sites. Levels of ICAM-1 and focal adhesion kinase, which participate in leukocyte migration and epithelial dedifferentiation, respectively, were also upregulated in tubules. NRK52E cells exposed to oxLDL showed similar modifications, plus suppression of anti-inflammatory transcription factor peroxisome proliferator-activated receptor-δ. In addition, oxLDL impaired epithelial barrier function. These alterations were prevented by an anti-LOX-1 antibody. The data support the concept that tubular LOX-1 activation driven by lipid oxidants in the preurine fluid is critical in the inflammatory changes. We suggest that luminal lipid oxidants and abnormal tubular permeability may be partly responsible for the renal tubulointerstitial injury of obesity, diabetes, and dyslipidemia.
Loss of prostaglandin E2 release from immortalized urothelial cells obtained from interstitial cystitis patient bladders
Authors: Rastogi Prerna , Rickard Alice , Dorokhov Nikolay , Klumpp David J. , McHowat Jane
Published: March 2008

Interstitial cystitis (IC) is associated with increased activated mast cell numbers in the bladder and impairment of the barrier function of the urothelium. We stimulated immortalized urothelial cells derived from the inflamed region of IC bladders (SR22A or SM28 abn) or from healthy bladders (PD07i or PD08i) with tryptase and measured phospholipase A2 (PLA2) activity and the resultant release of arachidonic acid and prostaglandin E2 (PGE2). Tryptase stimulation of either PD07i or SR22A resulted in similar increases in PLA2 activity and arachidonic acid release. However, tryptase stimulation of SR22A and SM28 abn did not result in a significant increase in PGE2 release compared with the increase in PGE2 release from tryptase-stimulated PD07i and PD08i cells. Expression of mRNA for cyclooxygenase-2 and PGE synthase was lower and mRNA for 15-hydroxyprostaglandin dehydrogenase was higher in SR22A compared with PD07i, suggesting that both decreased synthesis and increased metabolism are responsible for the lack of a PGE2 response in tryptase-stimulated SR22A cells. Since PGE2 is a cytoprotective eicosanoid, the failure to produce this metabolite in cells isolated from the IC bladder may represent an increased susceptibility to damage by proinfammatory stimuli.
Mouse model of type II Bartter's syndrome. II. Altered expression of renal sodium- and water-transporting proteins
Authors: Wagner Carsten A. , Loffing-Cueni Dominique , Yan Qingshang , Schulz Nicole , Fakitsas Panagiotis , Carrel Monique , Wang Tong , Verrey Francois , Geibel John P. , Giebisch Gerhard , Hebert Steven C. , Loffing Johannes
Published: March 2008

Bartter's syndrome represents a group of hereditary salt- and water-losing renal tubulopathies caused by loss-of-function mutations in proteins mediating or regulating salt transport in the thick ascending limb (TAL) of Henle's loop. Mutations in the ROMK channel cause type II antenatal Bartter's syndrome that presents with maternal polyhydramnios and postnatal life-threatening volume depletion. We have developed a colony of Romk null mice showing a Bartter-like phenotype and with increased survival to adulthood, suggesting the activation of compensatory mechanisms. To test the hypothesis that upregulation of Na+-transporting proteins in segments distal to the TAL contributes to compensation, we studied expression of salt-transporting proteins in ROMK-deficient ( Romk−/−) mice. Plasma aldosterone was 40% higher and urinary PGE2 excretion was 1.5-fold higher in Romk−/− compared with wild-type littermates. Semiquantitative immunoblotting of kidney homogenates revealed decreased abundances of proximal tubule Na+/H+ exchanger (NHE3) and Na+-Pi cotransporter (NaPi-IIa) and TAL-specific Na+-K+-2Cl−-cotransporter (NKCC2/BSC1) in Romk−/− mice, while the distal convoluted tubule (DCT)-specific Na+-Cl− cotransporter (NCC/TSC) was markedly increased. The abundance of the α-,β-, and γ-subunits of the epithelial Na+ channel (ENaC) was slightly increased, although only differences for γ-ENaC reached statistical significance. Morphometry revealed a fourfold increase in the fractional volume of DCT but not of connecting tubule (CNT) and collecting duct (CCD). Consistently, CNT and CD of Romk−/− mice revealed no apparent increase in the luminal abundance of the ENaC compared with those of wild-type mice. These data suggest that the loss of ROMK-dependent Na+ absorption in the TAL is compensated predominately by upregulation of Na+ transport in downstream DCT cells. These adaptive changes in Romk−/− mice may help to limit renal Na+ loss, and thereby, contribute to survival of these mice.
Impact of acute ascites on the action of the canine abdominal muscles
Authors: Leduc Dimitri , De Troyer André
Published: March 2008

Although ascites causes abdominal expansion, its effects on abdominal muscle function are uncertain. In the present study, progressively increasing ascites was induced in supine anesthetized dogs, and the changes in abdominal (ΔPab) and airway opening (ΔPao) pressure obtained during stimulation of the internal oblique and transversus abdominis muscles were measured; the changes in internal oblique muscle length were also measured. As ascites increased from 0 to 100 ml/kg body wt, Pab and muscle length during relaxation increased. ΔPab also showed a threefold increase ( P < 0.001). However, ΔPao decreased ( P < 0.001). When ascites increased further to 200 ml/kg, resting muscle length continued to increase and muscle shortening during stimulation became very small so that active muscle length was 155% of the resting muscle length in the control condition. Concomitantly, ΔPab returned to the control value, and ΔPao continued to decrease. Similar results were obtained with the animals in the head-up posture, although the decrease in ΔPao appeared only when ascites was greater than 125 ml/kg. It is concluded that 1) ascites adversely affects the expiratory action of the abdominal muscles on the lung; 2) this effect results primarily from the increase in diaphragm elastance; and 3) when ascites is severe, the abdomen cross-sectional area is also increased and the abdominal muscles are excessively lengthened so that their active pressure-generating ability itself is reduced.
Progression of White Matter Hyperintensities and Incidence of New Lacunes Over a 3-Year Period
Authors: Gouw Alida A. , van der Flier Wiesje M. , Fazekas Franz , van Straaten Elisabeth C.W. , Pantoni Leonardo , Poggesi Anna , Inzitari Domenico , Erkinjuntti Timo , Wahlund Lars O. , Waldemar Gunhild , Schmidt Reinhold , Scheltens Philip , Barkhof Frederik
Published: March 2008

Background and Purpose—

We studied the natural course of white matter hyperintensities (WMH) and lacunes, the main MRI representatives of small vessel disease, over time and evaluated possible predictors for their development.

Methods—

Baseline and repeat MRI (3-year follow-up) were collected within the multicenter, multinational Leukoaraiosis and Disability study (n=396). Baseline WMH were scored on MRI by the Fazekas scale and the Scheltens scale. WMH progression was assessed using the modified Rotterdam Progression scale (absence/presence of progression in 9 brain regions). Baseline and new lacunes were counted per region. WMH and lacunes at baseline and vascular risk factors were evaluated as predictors of WMH progression and new lacunes.

Results—

WMH progressed (mean±SD=1.9±1.8) mostly in the subcortical white matter, where WMH was also most prevalent at baseline. The majority of new lacunes, which were found in 19% of the subjects (maximum=9), also appeared in the subcortical white matter, mainly of the frontal lobes, whereas most baseline lacunes were located in the basal ganglia. Baseline WMH and lacunes predicted both WMH progression and new lacunes. Furthermore, previous stroke, diabetes, and blood glucose were risk factors for WMH progression. Male sex, hypertension, systolic blood pressure, previous stroke, body mass index, high-density lipoprotein, and triglyceride levels were risk factors for new lacunes.

Conclusion—

WMH and lacunes progressed over time, predominantly in the subcortical white matter. Progression was observed especially in subjects with considerable WMH and lacunes at baseline. Moreover, the presence of vascular risk factors at baseline predicted WMH progression and new lacunes over a 3-year period.
Unrecognized Myocardial Infarction in Relation to Risk of Dementia and Cerebral Small Vessel Disease
Authors: Ikram M. Arfan , van Oijen Marieke , de Jong Frank Jan , Kors Jan A. , Koudstaal Peter J. , Hofman Albert , Witteman Jacqueline C.M. , Breteler Monique M.B.
Published: March 2008

Background and Purpose—

Men, but not women, with unrecognized myocardial infarction (MI) have an increased risk of cardiac events and stroke compared with those without MI or with recognized MI. We investigated whether unrecognized MI is also a risk factor for dementia and cerebral small vessel disease (white matter lesions and brain infarction) in 2 population-based cohort studies.

Methods—

In the Rotterdam Study, 6347 participants were classified at baseline (1990 to 1993) into those with recognized MI (subdivided into Q-wave and non-Q-wave MI), with unrecognized MI, and without MI based on electrocardiography and interview and were followed for incident dementia (n=613) until January 1, 2005. In the Rotterdam Scan Study, 436 nondemented persons were similarly classified based on electrocardiography and interview and underwent brain MRI for the assessment of white matter lesions and brain infarction.

Results—

In men, unrecognized MI was associated with an increased risk of dementia (compared with men without MI hazard ratio, 2.14; 95% CI, 1.37 to 3.35) and with more white matter lesions and more often brain infarction on MRI. In women, no associations were found with unrecognized MI. Recognized MI was not associated with the risk of dementia in either sex. Men, but not women, with recognized MI had more often any brain infarction or asymptomatic brain infarction, especially if they had Q-wave MI. No consistent associations were found between recognized Q-wave or non-Q-wave MI and severity of white matter lesions. Additional adjustment for cardiovascular risk factors did not change the results.

Conclusions—

Men with unrecognized MI have an increased risk of dementia and more cerebral small vessel disease.
A Generalized Subsurface Flow Parameterization Considering Subgrid Spatial Variability of Recharge and Topography
Authors: Huang Maoyi , Liang Xu , Leung L. Ruby
Published: March 2008

Subsurface flow is an important hydrologic process and a key component of the water budget. Through its direct impacts on soil moisture, it can affect water and energy fluxes at the land surface and influence the regional climate and water cycle. In this study, a new subsurface flow formulation is developed that incorporates the spatial variability of both topography and recharge. It is shown through theoretical derivation and case studies that the power-law and exponential subsurface flow parameterizations and the parameterization proposed by Woods et al. are all special cases of the new formulation. The subsurface flows calculated using the new formulation compare well with values derived from observations at Tulpehocken Creek, Pennsylvania, and Walnut Creek, Iowa. Sensitivity studies show that when the spatial variability of topography or recharge, or both is increased, the subsurface flows increase at the two aforementioned sites and at the Maimai hillslope, New Zealand. This is likely due to enhancement of interactions between the groundwater table and the land surface that reduce the flow path. An important conclusion of this study is that the spatial variability of recharge alone, and/or in combination with the spatial variability of topography can substantially alter the behaviors of subsurface flows. This suggests that in macroscale hydrologic models or land surface models, subgrid variations of recharge and topography can make significant contributions to the grid mean subsurface flow and must be accounted for in regions with large surface heterogeneity. This is particularly true for regions with humid climate and a relatively shallow groundwater table where the combined impacts of spatial variability of recharge and topography are shown to be more important. For regions with an arid climate and a relatively deep groundwater table, simpler formulations, for example, the power law, for subsurface flow can work well, and the impacts of subgrid variations of recharge and topography may be ignored.
The Leopard Cannot Change His Spots, or Can He? Culture and the Development of Lay Theories of Change
Authors: Ji Li-Jun
Published: March 2008

Chinese and Canadian children were compared to examine cultural and developmental differences in lay theories of change: implicit beliefs about how the world develops and changes over time. Chinese and Canadian children (ages 7, 9, and 11 years) made predictions about future performance, relationships, happiness, and parental incomes based on a series of scenarios. Overall, the Chinese children predicted greater change than did the Canadian children, indicating that they believed more in change than did the Canadians. Moreover, cultural differences increased significantly with age: In comparison with their Canadian counterparts, Chinese children made no more change predictions at age 7, made slightly more change predictions at age 9, and made significantly more change predictions at age 11. This was true for questions starting with an extremely positive or negative state and those starting with a neutral state. Reasons for cultural and developmental differences were discussed.
A Meta-Analysis of Parent-Involved Treatment for Child Sexual Abuse
Authors: Corcoran Jacqueline , Pillai Vijayan
Published: March 2008

Sexual abuse in children not only occurs with alarming frequency, it also potentially leads to deleterious consequences for victims. Previous narrative reviews have touted the benefits of including the nonoffending caregiver in child sexual treatment. Objective: A meta-analysis is conducted to determine the effects of parent-involved treatment in four major child symptom areas: internalizing, externalizing, sexualized behaviors, and posttraumatic stress. Method: Only comparison/control group studies are included. Participant, treatment, and methodological characteristics of studies are coded, as well as information to calculate effect sizes. An overall effect size is calculated, though the small number of studies precluded moderator analysis. Results: Seven studies are located that met the inclusion criteria. At posttest, treatment had small effects in the four outcome domains over alternative interventions and was reduced still further at follow-up. Conclusion: Parent-involved treatment confers some advantage over comparison conditions (typically child-only treatment).
Seeking What's Best During the Transition to Adult Day Health Services
Authors: Bull Margaret J. , McShane Ruth E.
Published: March 2008

Family caregivers provide more than 80% of the long-term care for elders in the United States and experience a variety of transitions that are intertwined with those of their elders. Previous research on health care transitions documents problems elders and family caregivers encountered following hospitalization, following nursing home admission, and in adjusting to home health care. Little is known about the transition to adult day health services (ADHS). The purpose of this study was (a) to examine family caregivers' perspectives on the transition to ADHS and (b) to develop a situation-specific theory to guide interventions for elders and their family caregivers during the transition. Semistructured interviews were conducted with 16 family caregivers 1 month and 3 months following the elder's enrollment in ADHS. The constant comparative method was used in analyzing the data. The findings indicate that family caregivers consistently sought what was best for elders throughout the transition.
Security, Dignity, Caring Relationships, and Meaningful Work
Authors: Ayers David F. , Miller-Dyce Cherrel , Carlone David
Published: March 2008

Researchers asked 17 participants in a job-training program to describe their personal struggles following an economic restructuring. Examined through a critical theoretical lens, findings indicate that the learners enrolled in the program to reclaim security, dignity, meaningful work, and caring relationships. Program planners at community colleges are therefore urged to employ democratic program planning models, ask learners about their educational needs as they see them, and listen compassionately to their responses.
The Impact of Strategic Orientation on Intellectual Capital Investments in Customer Service Firms
Authors: Walsh Kate , Enz Cathy A. , Canina Linda
Published: March 2008

This study examines the influence of intellectual capital on performance in customer service firms pursuing different strategic orientations (e.g., low-cost leader, differentiation). Grounding these arguments in the resource-based view and using 538 hotels in the lodging industry, this article employs an economic-based production model to empirically explore the performance effects of investing in three different types of intellectual capital: systems capital (operational knowledge), customer capital (brand and marketing knowledge), and human capital (knowledge from both service and professional employees). In addition, the authors account for key controls, including the physical asset, cost of living, customer demand, market segment, and company affiliation. Results reveal that for firms pursuing a differentiation strategy only, investments in both service employees and professional employees enhance performance. However, investments in systems capital and customer capital enhance performance for all the firms studied. The authors discuss the implications of this study for research in the services arena.
Performance of ventilators for noninvasive positive-pressure ventilation in children
Authors: Fauroux B. , Leroux K. , Desmarais G. , Isabey D. , Clément A. , Lofaso F. , Louis B.
Published: March 2008

The aim of the present study was to evaluate the performance characteristics of all the ventilators proposed for home noninvasive positive-pressure ventilation in children in France.

The ventilators (one volume-targeted, 12 pressure-targeted and four dual) were evaluated on a bench which simulated six different paediatric ventilatory patterns. For each ventilator, the quality of the inspiratory and expiratory trigger and the ability to reach and maintain the preset pressures and volumes were evaluated with the six patient profiles.

The performance of the ventilators showed great variability, and depended upon the type of trigger (flow or pressure), type of circuit and patient profile. Differences were observed between the preset and measured airway pressure and between the tidal volume measured by the ventilator and on the bench. Leaks were associated with an inability to detect the patient’s inspiratory effort or autotriggering. No single ventilator was able to adequately ventilate the six paediatric profiles. Only a few ventilators were able to ventilate the profiles simulating the youngest patients.

A systematic paediatric bench evaluation is recommended for every ventilator proposed for home ventilation, in order to detect any dysfunction and guide the choice of the appropriate ventilator for a specific patient.
Extracellular matrix components and regulators in the airway smooth muscle in asthma
Authors: Araujo B. B. , Dolhnikoff M. , Silva L. F. F. , Elliot J. , Lindeman J. H. N. , Ferreira D. S. , Mulder A. , Gomes H. A. P. , Fernezlian S. M. , James A. , Mauad T.
Published: March 2008

There is an intimate relationship between the extracellular matrix (ECM) and smooth muscle cells within the airways. Few studies have comprehensively assessed the composition of different ECM components and its regulators within the airway smooth muscle (ASM) in asthma.

With the aid of image analysis, the fractional areas of total collagen and elastic fibres were quantified within the ASM of 35 subjects with fatal asthma (FA) and compared with 10 nonfatal asthma (NFA) patients and 22 nonasthmatic control cases. Expression of collagen I and III, fibronectin, versican, matrix metalloproteinase (MMP)-1, -2, -9 and -12 and tissue inhibitor of metalloproteinase-1 and -2 was quantified within the ASM in 22 FA and 10 control cases.

In the large airways of FA cases, the fractional area of elastic fibres within the ASM was increased compared with NFA and controls. Similarly, fibronectin, MMP-9 and MMP-12 were increased within the ASM in large airways of FA cases compared with controls. Elastic fibres were increased in small airways in FA only in comparison with NFA cases.

There is altered extracellular matrix composition and a degradative environment within the airway smooth muscle in fatal asthma patients, which may have important consequences for the mechanical and synthetic functions of airway smooth muscle.
Ranking analysis of F-statistics for microarray data
Authors: Tan Yuan-De , Fornage Myriam , Xu Hongyan
Published: March 2008

Background

Microarray technology provides an efficient means for globally exploring physiological processes governed by the coordinated expression of multiple genes. However, identification of genes differentially expressed in microarray experiments is challenging because of their potentially high type I error rate. Methods for large-scale statistical analyses have been developed but most of them are applicable to two-sample or two-condition data.

Results

We developed a large-scale multiple-groupF-test based method, named ranking analysis ofF-statistics (RAF), which is an extension of ranking analysis of microarray data (RAM) for two-sample t-test. In this method, we proposed a novel random splitting approach to generate the null distribution instead of using permutation, which may not be appropriate for microarray data. We also implemented a two-simulation strategy to estimate the false discovery rate. Simulation results suggested that it has higher efficiency in finding differentially expressed genes among multiple classes at a lower false discovery rate than some commonly used methods. By applying our method to the experimental data, we found 107 genes having significantly differential expressions among 4 treatments at <0.7% FDR, of which 31 belong to the expressed sequence tags (ESTs), 76 are unique genes who have known functions in the brain or central nervous system and belong to six major functional groups.

Conclusion

Our method is suitable to identify differentially expressed genes among multiple groups, in particular, when sample size is small.
Detecting the molecular scars of evolution in the Mycobacterium tuberculosis complex by analyzing interrupted coding sequences
Authors: Deshayes Caroline , Perrodou Emmanuel , Euphrasie Daniel , Frapy Eric , Poch Olivier , Bifani Pablo , Lecompte Odile , Reyrat Jean-Marc
Published: March 2008

Background

Computer-assisted analyses have shown that all bacterial genomes contain a small percentage of open reading frames with a frameshift or in-frame stop codon We report here a comparative analysis of these interrupted coding sequences (ICDSs) in six isolates ofM. tuberculosis, two ofM. bovisand one ofM. africanumand question their phenotypic impact and evolutionary significance.

Results

ICDSs were classified as "common to all strains" or "strain-specific". Common ICDSs are believed to result from mutations acquired before the divergence of the species, whereas strain-specific ICDSs were acquired after this divergence. Comparative analyses of these ICDSs therefore define the molecular signature of a particular strain, phylogenetic lineage or species, which may be useful for inferring phenotypic traits such as virulence and molecular relationships. For instance,in silicoanalysis of the W-Beijing lineage ofM. tuberculosis, an emergent family involved in several outbreaks, is readily distinguishable from other phyla by its smaller number of common ICDSs, including at least one known to be associated with virulence. Our observation was confirmed through the sequencing analysis of ICDSs in a panel of 21 clinicalM. tuberculosisstrains. This analysis further illustrates the divergence of the W-Beijing lineage from other phyla in terms of the number of full-length ORFs not containing a frameshift. We further show that ICDS formation is not associated with the presence of a mutated promoter, and suggest that promoter extinction is not the main cause of pseudogene formation.

Conclusion

The correlation between ICDSs, function and phenotypes could have important evolutionary implications. This study provides population geneticists with a list of targets, which could undergo selective pressure and thus alters relationships between the various lineages ofM. tuberculosisstrains and their host. This approach could be applied to any closely related bacterial strains or species for which several genome sequences are available.
Basis for treatment of tuberculosis among HIV-infected patients in Tanzania: the role of chest x-ray and sputum culture
Authors: Bakari Muhammad , Arbeit Robert D , Mtei Lillian , Lyimo Johnson , Waddell Richard , Matee Mecky , Cole Bernard F , Tvaroha Susan , Horsburgh C Robert , Soini Hanna , Pallangyo Kisali , von Reyn C Fordham
Published: March 2008

Background

Active tuberculosis (TB) is common among HIV-infected persons living in tuberculosis endemic countries, and screening for tuberculosis (TB) is recommended routinely. We sought to determine the role of chest x-ray and sputum culture in the decision to treat for presumptive TB using active case finding in a large cohort of HIV-infected patients.

Methods

Ambulatory HIV-positive subjects with CD4 counts ≥ 200/mm3 entering a Phase III TB vaccine study in Tanzania were screened for TB with a physical examination, standard interview, CD4 count, chest x-ray (CXR), blood culture for TB, and three sputum samples for acid fast bacillus (AFB) smear and culture.

Results

Among 1176 subjects 136 (12%) were treated for presumptive TB. These patients were more frequently male than those without treatment (34% vs. 25%, respectively; p = 0.049) and had lower median CD4 counts (319/μL vs. 425/μL, respectively; p < .0001). Among the 136 patients treated for TB, 38 (28%) had microbiologic confirmation, including 13 (10%) who had a normal CXR and no symptoms. There were 58 (43%) treated patients in whom the only positive finding was an abnormal CXR. Blood cultures were negative in all patients.

Conclusion

Many ambulatory HIV-infected patients with CD4 counts ≥ 200/mm3 are treated for presumptive TB. Our data suggest that optimal detection requires comprehensive evaluation, including CXR and sputum culture on both symptomatic and asymptomatic subjects.
CDKN1C/p57kip2is a candidate tumor suppressor gene in human breast cancer
Authors: Larson Pamela S , Schlechter Benjamin L , King Chia-Lin , Yang Qiong , Glass Chelsea N , Mack Charline , Pistey Robert , de las Morenas Antonio , Rosenberg Carol L
Published: March 2008

Background

CDKN1C (also known as p57KIP2) is a cyclin-dependent kinase inhibitor previously implicated in several types of human cancer. Its family members (CDKN1A/p21CIP1 and B/p27KIP1) have been implicated in breast cancer, but information about CDKN1C's role is limited. We hypothesized that decreased CDKN1C may be involved in human breast carcinogenesis in vivo.

Methods

We determined rates of allele imbalance or loss of heterozygosity (AI/LOH) in CDKN1C, using an intronic polymorphism, and in the surrounding 11p15.5 region in 82 breast cancers. We examined the CDKN1C mRNA level in 10 cancers using quantitative real-time PCR (qPCR), and the CDKN1C protein level in 20 cancers using immunohistochemistry (IHC). All samples were obtained using laser microdissection. Data were analyzed using standard statistical tests.

Results

AI/LOH at 11p15.5 occurred in 28/73 (38%) informative cancers, but CDKN1C itself underwent AI/LOH in only 3/16 (19%) cancers (p = ns). In contrast, CDKN1C mRNA levels were reduced in 9/10 (90%) cancers (p < 0.0001), ranging from 2–60% of paired normal epithelium. Similarly, CDKN1C protein staining was seen in 19/20 (95%) cases' normal epithelium but in only 7/14 (50%) cases' CIS (p < 0.004) and 5/18 (28%) cases' IC (p < 0.00003). The reduction appears primarily due to loss of CDKN1C expression from myoepithelial layer cells, which stained intensely in 17/20 (85%) normal lobules, but in 0/14 (0%) CIS (p < 0.00001). In contrast, luminal cells displayed less intense, focal staining fairly consistently across histologies. Decreased CDKN1C was not clearly associated with tumor grade, histology, ER, PR or HER2 status.

Conclusion

CDKN1C is expressed in normal epithelium of most breast cancer cases, mainly in the myothepithelial layer. This expression decreases, at both the mRNA and protein level, in the large majority of breast cancers, and does not appear to be mediated by AI/LOH at the gene. Thus, CDKN1C may be a breast cancer tumor suppressor.
Cracked mercury dental amalgam as a possible cause of fever of unknown origin: a case report
Authors: Bamonti Fabrizia , Guzzi Gianpaolo , Ferrero Maria Elena
Published: March 2008

Introduction

Sudden fever of unknown origin is quite a common emergency and may lead to hospitalization. A rise in body temperature can be caused by infectious diseases and by other types of medical condition. This case report is of a woman who had fever at night for several days and other clinical signs which were likely related to cracked dental mercury amalgam.

Case presentation

A healthy women developed fever many days after had cracked a mercury dental amalgam filling. Blood tests evidenced increased erythrocyte sedimentation rate, anemia and elevated white cell count; symptoms were headache and palpitations. Blood tests and symptoms normalized within three weeks of removal of the dental amalgam.

Conclusion

This case highlights the possible link between mercury vapor exposure from cracked dental amalgam and early activation of the immune system leading to fever of unknown origin.
Dysfunctional interferon-α production by peripheral plasmacytoid dendritic cells upon Toll-like receptor-9 stimulation in patients with systemic lupus erythematosus
Authors: Kwok Seung-Ki , Lee June-Yong , Park Se-Ho , Cho Mi-La , Min So-Youn , Park Sung-Hwan , Kim Ho-Youn , Cho Young-Gyu
Published: March 2008

Background

It is well known that interferon (IFN)-α is important to the pathogenesis of systemic lupus erythematosus (SLE). However, several reports have indicated that the number of IFN-α producing cells are decreased or that their function is defective in patients with SLE. We studied the function of plasmacytoid dendritic cells (pDCs) under persistent stimulation of Toll-like receptor (TLR)9 via a TLR9 ligand (CpG ODN2216) or SLE serum.

Methods

The concentrations of IFN-α were determined in serum and culture supernatant of peripheral blood mononuclear cells (PBMCs) from SLE patients and healthy controls after stimulation with CpG ODN2216 or SLE serum. The numbers of circulating pDCs were analyzed by fluoresence-activated cell sorting analysis. pDCs were treated with CpG ODN2216 and SLE serum repeatedly, and levels of produced IFN-α were measured. The expression of IFN-α signature genes and inhibitory molecules of TLR signaling were examined in PBMCs from SLE patients and healthy control individuals.

Results

Although there was no significant difference in serum concentration of IFN-α and number of circulating pDCs between SLE patients and healthy control individuals, the IFN-α producing capacity of PBMCs was significantly reduced in SLE patients. Interestingly, the degree which TLR9 ligand-induced IFN-α production in SLE PBMCs was inversely correlated with the SLE serum-induced production of IFN-α in healthy PMBCs. Because repeated stimulation pDCs with TLR9 ligands showed decreased level of IFN-α production, continuous TLR9 stimulation may lead to decreased production of IFN-α in SLE PBMCs. In addition, PBMCs isolated from SLE patients exhibited higher expression of IFN-α signature genes and inhibitory molecules of TLR signaling, indicating that these cells had already undergone IFN-α stimulation and had become desensitized to TLR signaling.

Conclusion

We suggest that the persistent presence of endogenous IFN-α inducing factors induces TLR tolerance in pDCs of SLE patients, leading to impaired production of IFN-α.
The histopathology of septic acute kidney injury: a systematic review
Authors: Langenberg Christoph , Bagshaw Sean M , May Clive N , Bellomo Rinaldo
Published: March 2008

Introduction

Sepsis is the most common trigger of acute kidney injury (AKI) in critically ill patients; understanding the structural changes associated with its occurrence is therefore important. Accordingly, we systematically reviewed the literature to assess current knowledge on the histopathology of septic AKI.

Methods

A systematic review of the MEDLINE, EMBASE and CINHAL databases and bibliographies of the retrieved articles was performed for all studies describing kidney histopathology in septic AKI.

Results

We found six studies reporting the histopathology of septic AKI for a total of only 184 patients. Among these patients, only 26 (22%) had features suggestive of acute tubular necrosis (ATN). We found four primate studies. In these, seven out of 19 (37%) cases showed features of ATN. We also found 13 rodent studies of septic AKI. In total, 23% showed evidence of ATN. In two additional studies performed in a dog model and a sheep model there was no evidence of ATN on histopathologic examination. Overall, when ATN was absent, studies reported a wide variety of kidney morphologic changes in septic AKI – ranging from normal (in most cases) to marked cortical tubular necrosis.

Conclusion

There are no consistent renal histopathological changes in human or experimental septic AKI. The majority of studies reported normal histology or only mild, nonspecific changes. ATN was relatively uncommon.
How Should We Design Supportive Cancer Care? The Patient's Perspective
Authors: Casarett David , Fishman Jessica , O'Dwyer Peter J. , Barg Frances K. , Naylor Mary , Asch David A.
Published: March 2008

Purpose

Hospice services are designed to meet the needs of patients near the end of life. Although so-called open-access hospice programs and bridge programs are beginning to offer these services to patients who are still receiving treatment, it is not known whether they best meet patients’ needs.

Patients and Methods

Three hundred adult patients receiving treatment for cancer completed interviews in which each patient's value or ability for supportive care services were calculated from the choices that they made among combinations of those services. Preferences for five traditional hospice services and six alternative supportive care services were measured, and patients were followed up for 6 months or until death.

Results

Patients’ utilities for alternative services were higher than those for traditional hospice services (0.53 v 0.39; sign-rank test P < .001). Alternative services were also preferred among patients with poor functional status (Eastern Cooperative Oncology Group performance score > 2; n = 54; 0.65 v 0.48; P < .001) and among those who were in the last 6 months of life (0.68 v 0.56; sign-rank test P = .003). Even patients who were willing to forgo cancer treatment (n = 38; 13%) preferred alternative services (3.1 v 1.8; P < .001).

Conclusion

Patients who are receiving active treatment for cancer, and even those who are willing to stop treatment, express a clear preference for alternative supportive care services over traditional hospice services. Supportive care programs for patients with advanced cancer should reconsider the services that they offer and might seek to include novel services in addition to, or perhaps instead of, traditional hospice services.
Use of Different Postmenopausal Hormone Therapies and Risk of Histology- and Hormone Receptor–Defined Invasive Breast Cancer
Authors: Fournier Agnès , Fabre Alban , Mesrine Sylvie , Boutron-Ruault Marie-Christine , Berrino Franco , Clavel-Chapelon Françoise
Published: March 2008

Purpose

We previously found that the risk of invasive breast cancer varied according to the progestagen component of combined postmenopausal hormone therapy (CHT): progesterone, dydrogesterone, or other progestagens. We conducted the present study to assess how these CHTs were associated with histology- and hormone receptor-defined breast cancer.

Patients and Methods

We used data from the French E3N cohort study, with 80,391 postmenopausal women followed for a mean duration of 8.1 years; 2,265 histologically confirmed invasive breast cancers were identified through biennial self-administered questionnaires completed from 1990 to 2002. The relative risks (RRs) were estimated using Cox proportional hazards models.

Results

Compared with postmenopausal hormone therapy (HT) never-use, ever-use of estrogen+progesterone was not significantly associated with the risk of any breast cancer subtype, but increasing duration of estrogen+progesterone was associated with increasing risks of lobular (P = .06) and estrogen receptor–positive/progesterone receptor–negative (ER+/PR−; P = .02). Estrogen+dydrogesterone was associated with a significant increase in risk of lobular carcinoma (RR, 1.7; 95% CI, 1.1 to 2.6). Estrogen+other progestagens was associated with significant increases in risk of ductal and lobular carcinomas (RR, 1.6; 95% CI, 1.3 to 1.8; and 2.0; 95% CI, 1.5 to 2.7, respectively), of ER+/PR+ and ER+/PR− carcinomas (RR, 1.8; 95% CI, 1.5 to 2.1; and 2.6; 95% CI, 1.9 to 3.5, respectively), but not of ER−/PR+ or ER−/PR− carcinomas (RR, 1.0; 95% CI, 0.5 to 2.1; and 1.4; 95% CI, 0.9 to 2.0, respectively).

Conclusion

The increase in risk of breast cancer observed with the use of CHTs other than estrogen+progesterone and estrogen+dydrogesterone seems to apply preferentially to ER+ carcinomas, especially those ER+/PR−, and to affect both ductal and lobular carcinomas.
Targeting Vascular Endothelial Growth Factor in Advanced Carcinoid Tumor: A Random Assignment Phase II Study of Depot Octreotide With Bevacizumab and Pegylated Interferon Alfa-2b
Authors: Yao James C. , Phan Alexandria , Hoff Paulo M. , Chen Helen X. , Charnsangavej Chusilp , Yeung Sai-Ching J. , Hess Kenneth , Ng Chaan , Abbruzzese James L. , Ajani Jaffer A.
Published: March 2008

Purpose

Effective systemic therapy for advanced carcinoid is lacking. The combination of bevacizumab (BEV) and pegylated (PEG) interferon alfa-2b was evaluated among patients with metastatic or unresectable carcinoid tumors.

Patients and Methods

Forty-four patients on stable doses of octreotide were randomly assigned to 18 weeks of treatment with bevacizumab or PEG interferon alfa-2b. At disease progression (PD) or at the end of 18 weeks (whichever occurred earlier), patients received bevacizumab plus PEG interferon until progression. Functional computer tomography (CT) scans were performed to measure effect on tumor blood flow.

Results

In the bevacizumab arm, four patients (18%) achieved confirmed partial response (PR), 17 patients (77%) had stable disease (SD), and one patient (5%) had PD. In the PEG interferon arm, 15 patients (68%) had SD and six patients (27%) had PD. Progression-free survival (PFS) rates after 18 weeks of monotherapy were 95% in bevacizumab versus 68% on the PEG interferon arm. The overall median PFS for all 44 patients is 63 weeks. Compared with paired baseline measurements on functional CT scans, we observed a 49% (P < .01) and 28% (P < .01) decrease in tumor blood flow at day 2 and week 18 among patients treated with bevacizumab. No significant changes in tumor blood flow were observed following PEG interferon. PEG interferon alfa-2b treatment was associated with decrease in plasma basic fibroblast growth factor (bFGF; P = .04) and increase in plasma interleukin-18 (IL-18; P < .01). No significant changes in bFGF or IL-18 following treatment with bevacizumab were observed.

Conclusion

Bevacizumab therapy resulted in objective responses, reduction of tumor blood flow, and longer PFS in patients with carcinoid than PEG interferon treatment.
Hypermetabolic Syndrome as a Consequence of Repeated Psychological Stress in Mice
Authors: Depke Maren , Fusch Gerhard , Domanska Grazyna , Geffers Robert , Völker Uwe , Schuett Christine , Kiank Cornelia
Published: March 2008

Stress is a powerful modulator of neuroendocrine, behavioral, and immunological functions. After 4.5-d repeated combined acoustic and restraint stress as a murine model of chronic psychological stress, severe metabolic dysregulations became detectable in female BALB/c mice. Stress-induced alterations of metabolic processes that were found in a hepatic mRNA expression profiling were verified by in vivo analyses. Repeatedly stressed mice developed a hypermetabolic syndrome with the severe loss of lean body mass, hyperglycemia, dyslipidemia, increased amino acid turnover, and acidosis. This was associated with hypercortisolism, hyperleptinemia, insulin resistance, and hypothyroidism. In contrast, after a single acute stress exposure, changes in expression of metabolic genes were much less pronounced and predominantly confined to gluconeogenesis, probably indicating that metabolic disturbances might be initiated already early but will only manifest in repeatedly stressed mice. Thus, in our murine model, repeated stress caused severe metabolic dysregulations, leading to a drastic reduction of the individual’s energy reserves. Under such circumstances stress may further reduce the ability to cope with new stressors such as infection or cancer.
Jump City: Parkour and the Traces
Authors: Thomson David
Published: March 2008

Parkour, the art of moving quickly in urban areas using only the body and staying true to the principle of “displacement,” a call to ceaseless forward movement combined with a kind of Zen-like self-presence, is dangerous to the practitioner (traceur) but also, in a sense, to the logic of the city. As documented on YouTube, Jump London, and Casino Royale or seen in the flesh, parkour is the most spectacular of a set of unruly practices in the specular city, from skateboarding to flash mobbing. The traceur can be situated in the history of urban wanderers in the midst of capital, from the nineteenth-century Parisian flaneur to the strange urban hieroglyphics of the Situationist drifters and the new psychogeographers. The city is an accretion of forms characterized by a nostalgia for self-presence (roughly, democracy) and by economy (transnational capital flow), the first a desire to be here, the second a reckoning with the impossibility of being simply here. In the most literal, architectural sense, these might be civic buildings on the one hand and commercial on the other, and as it turns out, these are the best buildings to jump off, over, and around. Late capital's urban matrix hardly has time to be itself in the haste with which it hums a threnody of global evocations, and the traceur moving soundlessly in such a sensorium, or glimpsed briefly against a cityscape of allusive forms, will tell us everything we need to know about presence if he or she will but tarry for a moment.
“It Couldn't Happen Here”: A Cross-Cultural Rhetoric
Authors: Mandrell James
Published: March 2008

Although separated by thirty months, the al-Qaeda attacks in Madrid and in New York offer a unique opportunity to compare the rhetorical and practical reactions to the bombings on March 11, 2004, and destruction of the World Trade Center on September 11, 2001, revealing their countries' strikingly different assumptions about and approaches to terrorism. Ultimately, the rhetorical dimensions of domestic security come to involve a threat to civic discourse that can be cured only by a civilian-imposed silence on the government.