bluuebunny/crossref_metadata_2025 huggingface dataset:
Governmentality and Lifestyle Studies
Authors: Binkley Sam
Published: July 2007

In recent years, a research focus on lifestyles has drawn considerable attention from many quarters. Within this area, the influence of several European and continental intellectual currents not widely embraced in American sociology can be detected, some traceable to the work of Michel Foucault. This article will provide a summary and overview of one area of lifestyle sociology that is touched by Foucault's broad influence on the social sciences, particularly his theories on governmentality. Governmentality studies consider the manner in which personal autonomy and self‐responsibility is conveyed to individuals as an ongoing life‐project. Through the lens of governmentality studies, everyday lifestyle choices of individuals are viewed as elements of larger projects of self‐development, implemented by therapeutic discourses of risk management, self‐realization, and enhanced personal well‐being. After a summary of debates within the sociology of lifestyle informed by governmentality theories, commentary and recommendations will be offered on new directions in governmentality research focusing on subjective well‐being or ‘happiness’ as a feature of contemporary lifestyles and as an object of sociological research. A brief survey of new research comprising the interdisciplinary field of ‘happiness studies’ suggests a new direction not only for lifestyle research, but for governmentality studies as well.
Utility of hypertonic histamine challenge in distinguishing difficult‐to‐diagnose asthma
Authors: Purokivi Minna , Koskela Heikki O. , Koistinen Tiina , Magga Jarkko , Peuhkurinen Keijo , Kiviniemi Vesa , Kontra Kirsi M.
Published: July 2007

Introduction:  Although classical asthma is associated with airway hyperresponsiveness (AHR), this condition is also present in many cardiopulmonary disorders undermining the rational basis of its measurement in the differential diagnosis of asthma. We have recently introduced a new method to investigate AHR, the hypertonic histamine challenge (HHC).

Objective:  The aim of this study was to evaluate the differential diagnostic power of HHC in a clinically representative sample of 138 patients.

Methods:  Fifty‐seven patients from the outpatient clinic of the authors' hospital with symptoms indicative of asthma were consecutively recruited. Asthma was confirmed in 31 subjects. The remaining 26 subjects formed the control group, in conjunction with seven patients with COPD, 15 patients with interstitial lung disease, 21 patients with rhinitis, 13 patients with heart failure and 25 healthy controls. Hypertonic histamine solution was administered with an ultrasonic nebuliser.

Results:  Only the PC20 values of asthmatic subjects differed statistically significantly from those of the healthy group (P < 0.0001). The receiver operator characteristic curve indicated that a PC20 value of 0.83 mg/mL would be the optimal cut‐off point of HHC to separate the asthmatics from the symptomatic controls with a sensitivity of 81% and specificity of 70%. With the PC20 values of 0.1 and 4.0 mg/mL, the sensitivities were 42% and 100%, and the specificities were 96% and 40%, respectively. In these limits, HHC either confirmed or excluded asthma in 64 out of 138 patients (46%).

Conclusion:  The authors' attempt to improve the accuracy of the airway challenge test by combining direct and indirect challenges did not overcome the diagnostic limitations of previously utilised airway challenges.

Please cite this paper as: Purokivi M, Koskela HO, Koistinen T, Magga J, Peuhkurinen K, Kiviniemi V and Kontra KM. Utility of hypertonic histamine challenge in distinguishing difficult‐to‐diagnose asthma. The Clinical Respiratory Journal 2007; 1:91–98.
Hormonal responses to a 160-km race across frozen Alaska
Authors: Kraemer W J , Fragala M S , Watson G , Volek J S , Rubin M R , French D N , Maresh C M , Vingren J L , Hatfield D L , Spiering B A , Yu-Ho J , Hughes S L , Case H S , Stuempfle K J , Lehmann D R , Bailey S , Evans D S
Published: July 2007

Background:

Severe physical and environmental stress seems to have a suppressive effect on the hypothalamic–pituitary–gonadal (HPG) axis in men. Examining hormonal responses to an extreme 160-km competition across frozen Alaska provides a unique opportunity to study this intense stress.

Objective:

To examine hormonal responses to an ultra-endurance race.

Methods:

Blood samples were obtained from 16 men before and after racing and analyzed for testosterone, interleukin-6 (IL-6), growth hormone (GH) and cortisol. Six subjects (mean (SD) age 42 (7) years; body mass 78.9 (7.1) kg; height 1.78 (0.05) m raced by bicycle (cyclists) and 10 subjects (age 35 (9) years; body mass 77.9 (10.6) kg; height, 1.82 (0.05) m) raced by foot (runners). Mean (SD) finish times were 21.83 (6.27) and 33.98 (6.12) h, respectively.

Results:

In cyclists there were significant (p⩽0.05) mean (SD) pre-race to post-race increases in cortisol (254.83 (135.26) to 535.99 (232.22) nmol/l), GH (0.12 (0.23) to 3.21 (3.33) µg/ml) and IL-6 (2.36 (0.42) to 10.15 (3.28) pg/ml), and a significant decrease in testosterone (13.81 (3.19) to 5.59 (3.74) nmol/l). Similarly, in runners there were significant pre-race to post-race increases in cortisol (142.09 (50.74) to 452.21 (163.40) ng/ml), GH (0.12 (0.23) to 3.21 (3.33) µg/ml) and IL-6 (2.42 (0.68) to 12.25 (1.78) pg/ml), and a significant decrease in testosterone (12.32 (4.47) to 6.96 (3.19) nmol/l). There were no significant differences in the hormonal levels between cyclists and runners (p>0.05).

Conclusions:

These data suggest a suppression of the hypopituitary–gonadal axis potentially mediated by amplification of adrenal stress responses to such an ultra-endurance race in environmentally stressful conditions.
QUANTUM MECHANICAL TREATMENT OF THE PROBLEM OF CONSTRAINTS IN NON-EXTENSIVE FORMALISM REVISITED
Authors: BAĞCI G. B. , ARDA ALTUĞ , SEVER RAMAZAN
Published: July 2007

The purity of Werner state in non-extensive formalism associated with two different constraints has been calculated in a previous paper by Bağci et al.17 Two different results have been obtained corresponding to ordinary probability and escort probability. The former has been shown to result in negative values thereby leading authors to deduce the advantage of escort probabilities over ordinary probabilities. However, these results have only been for a limited interval of q values which lie between 0 and 1. In this paper, we solve the same problem for all values of non-extensive index q by using a perturbative approach and show that the simultaneous use of both types of constraint is necessary in order to obtain the solution for a whole spectrum of non-extensive index. In this sense, the existence of these different constraints in non-extensive formalism must not be seen as a deficiency in the formalism but rather must be welcomed as a means of providing solution for all values of parameter q.
A TECHNIQUE FOR PORCINE FLEXOR TENDON HARVEST
Authors: Hirpara Kieran M. , Abouazza Omar , O'Neill Barry , O'Sullivan Michael
Published: July 2007

There is a growing body of work on the ex vivo tensile testing of tendon repairs, an appreciable amount of which are performed on cadaveric porcine flexor tendons. However, there is little information in the literature on exactly how to perform the dissections necessary to obtain flexor tendons from porcine trotters. We present a simple method to rapidly harvest tendons from the porcine foot, allowing large amounts of material to be harvested in little time for the purpose of tensile testing of tendon repairs.
RELIABILITY OF SURFACE EMG MEASUREMENTS OF THE QUADRICEPS DURING MAXIMAL ISOMETRIC CONTRACTIONS FOLLOWING WATER IMMERSION
Authors: Abbiss Chris R. , Peiffer Jeremiah J. , Netto Kevin J. , Laursen Paul B.
Published: July 2007

Background: The influence of water immersion on neuromuscular function is of importance to a number of disciplines; however, the reliability of surface electromyography (SEMG) following water immersion is not known. This study examined the reliability of SEMG amplitude during maximal voluntary isometric contractions (MVICs) of the vastus lateralis following water immersion. Methods: Using a Biodex isokinetic dynamometer and in a randomized order, 12 healthy male subjects performed four MVICs at 60° knee flexion on both the dominant and nondominant kicking legs, and the SEMG was recorded. Each subject's dominant and nondominant kicking leg was then randomly assigned to have SEMG electrodes removed or covered during 15 min of water immersion (20°C–25°C). Following water immersion, subjects performed a further four MVICs. Results: Intraclass correlation coefficient (ICC) and the relative standard error of measurement (%SEM) of SEMG amplitude showed moderate to high trial-to-trial reliability when electrodes were covered (0.93% and 2.79%) and removed (0.95% and 2.10%, respectively). Conclusions: The results of the this study indicate that SEMG amplitude of the vastus lateralis may be accurately determined during maximal voluntary contractions following water immersion if electrodes are either removed or covered with water-resistive tape during the immersion.
Opportunities for Plasma-Assisted Atomic Layer Deposition
Authors: Kessels Erwin , Heil Stephan , Langereis Erik , van Hemmen Hans , Knoops Harm , Keuning Wytze , van de Sanden Richard
Published: July 2007

Within the method of atomic layer deposition (ALD), additional reactivity can be delivered to the surface in the form of plasma-produced species. The application of such a low- temperature plasma in the ALD cycle can therefore open up a processing parameter space that is unattainable by the strictly thermally driven process. In this contribution several possible benefits of plasma-assisted ALD will be reviewed showing bright prospect for plasma-assisted ALD for a large variety of applications, also far beyond the typical use in semiconductor devices.
Atomic Layer Deposition on Biological Macromolecules
Authors: Knez Mato , Nielsch Kornelius , Patil Avinash J. , Mann Stephen , Gösele Ulrich
Published: July 2007

Biomolecules play an increasingly important role in nanoscale science in recent years. Particularly, biomolecules with nanoscale dimensions are of special interest as templates for the fabrication of semiconducting or metallic nanostructures. In this work, we show the application of atomic layer deposition (ALD), a gas phase thin film deposition process, to biological macromolecules which are frequently used as templates in nanoscale science, and the possibility to fabricate thin films with embedded biomolecules.
Both orexin receptors are expressed in rat ovaries and fluctuate with the estrous cycle: effects of orexin receptor antagonists on gonadotropins and ovulation
Authors: Silveyra Patricia , Lux-Lantos Victoria , Libertun Carlos
Published: July 2007

Orexins are peptides controlling feeding, sleep, and neuroendocrine functions. They are synthesized by the hypothalamus with projections throughout the brain. Orexins and their orexin 1 (OX1) and orexin 2 receptors (OX2) are present outside the central nervous system. Here the expression of preproorexin (PPO), OX1, and OX2was studied in rat ovaries. PPO, OX1, and OX2were determined by quantitative real-time RT-PCR in ovaries of cycling Sprague-Dawley rats on all days of the cycle. Serum hormones and food consumption were determined. Ovarian OX1and OX2expression was then studied after ovulation blockade with Cetrorelix or Nembutal. Finally, proestrous rats were treated at 1400 and 1900 with a selective OX1antagonist (SB-334867-A) and/or a selective OX2antagonist (JNJ-10397049), and hormone levels, ovulation, and ovarian histology were studied. Both receptors' expression increased in the ovary between 1700 and 2300 of proestrus exclusively, in coincidence with hormone peaks, but not with the dark-light cycle or food intake. PPO was not detected. Cetrorelix or Nembutal prevented the increases of OX1and OX2while blunting gonadotropin peaks. SB-334867-A and JNJ-10397049, alone or combined, decreased serum gonadotropins and reduced ova number the following morning; ovaries showed a bloody (hyperemic and/or hemorrhagic) reaction with more preovulatory follicles and less corpora lutea. Here we demonstrate for the first time an increased ovarian expression of both OX1and OX2, only during proestrous afternoon, and its hormone dependence but not dependence on the dark-light cycle. Two new receptor antagonists reduced proestrous gonadotropins and/or ova number while producing ovarian structural changes.
Peroxisomal-mitochondrial oxidation in a rodent model of obesity-associated insulin resistance
Authors: Noland Robert C. , Woodlief Tracey L. , Whitfield Brian R. , Manning Steven M. , Evans Jasper R. , Dudek Ronald W. , Lust Robert M. , Cortright Ronald N.
Published: July 2007

Peroxisomal oxidation yields metabolites that are more efficiently utilized by mitochondria. This is of potential clinical importance because reduced fatty acid oxidation is suspected to promote excess lipid accumulation in obesity-associated insulin resistance. Our purpose was to assess peroxisomal contributions to mitochondrial oxidation in mixed gastrocnemius (MG), liver, and left ventricle (LV) homogenates from lean and fatty ( fa/fa) Zucker rats. Results indicate that complete mitochondrial oxidation (CO2production) using various lipid substrates was increased approximately twofold in MG, unaltered in LV, and diminished ∼50% in liver of fa/fa rats. In isolated mitochondria, malonyl-CoA inhibited CO2production from palmitate 78%, whereas adding isolated peroxisomes reduced inhibition to 21%. These data demonstrate that peroxisomal products may enter mitochondria independently of CPT I, thus providing a route to maintain lipid disposal under conditions where malonyl-CoA levels are elevated, such as in insulin-resistant tissues. Peroxisomal metabolism of lignoceric acid in fa/fa rats was elevated in both liver and MG (LV unaltered), but peroxisomal product distribution varied. A threefold elevation in incomplete oxidation was solely responsible for increased hepatic peroxisomal oxidation (CO2unaltered). Alternatively, only CO2was detected in MG, indicating that peroxisomal products were exclusively partitioned to mitochondria for complete lipid disposal. These data suggest tissue-specific destinations for peroxisome-derived products and emphasize a potential role for peroxisomes in skeletal muscle lipid metabolism in the obese, insulin-resistant state.
Fiberoptic System for Recording Dendritic Calcium Signals in Layer 5 Neocortical Pyramidal Cells in Freely Moving Rats
Authors: Murayama Masanori , Pérez-Garci Enrique , Lüscher Hans-Rudolf , Larkum Matthew E.
Published: July 2007

Calcium influx into the dendritic tufts of layer 5 neocortical pyramidal neurons modifies a number of important cellular mechanisms. It can trigger local synaptic plasticity and switch the firing properties from regular to burst firing. Due to methodological limitations, our knowledge about Ca2+ spikes in the dendritic tuft stems mostly from in vitro experiments. However, it has been speculated that regenerative Ca2+ events in the distal dendrites correlate with distinct behavioral states. Therefore it would be most desirable to be able to record these Ca2+ events in vivo, preferably in the behaving animal. Here, we present a novel approach for recording Ca2+ signals in the dendrites of populations of layer 5 pyramidal neurons in vivo, which ensures that all recorded fluorescence changes are due to intracellular Ca2+ signals in the apical dendrites. The method has two main features: 1) bolus loading of layer 5 with a membrane-permeant Ca2+ dye resulting in specific loading of pyramidal cell dendrites in the upper layers and 2) a fiberoptic cable attached to a gradient index lens and a prism reflecting light horizontally at 90° to the angle of the apical dendrites. We demonstrate that the in vivo signal-to-noise ratio recorded with this relatively inexpensive and easy-to-implement fiberoptic-based device is comparable to conventional camera-based imaging systems used in vitro. In addition, the device is flexible and lightweight and can be used for recording Ca2+ signals in the distal dendritic tuft of freely behaving animals.
Bone Microenvironment and Androgen Status Modulate Subcellular Localization of ErbB3 in Prostate Cancer Cells
Authors: Cheng Chien-Jui , Ye Xiang-cang , Vakar-Lopez Funda , Kim Jeri , Tu Shi-Ming , Chen Dung-Tsa , Navone Nora M. , Yu-Lee Li-Yuan , Lin Sue-Hwa , Hu Mickey C-T.
Published: July 2007

ErbB-3, an ErbB receptor tyrosine kinase, has been implicated in the pathogenesis of several malignancies, including prostate cancer. We found that ErbB-3 expression was up-regulated in prostate cancer cells within lymph node and bone metastases. Despite being a plasma membrane protein, ErbB-3 was also detected in the nuclei of the prostate cancer cells in the metastatic specimens. Because most metastatic specimens were from men who had undergone androgen ablation, we examined the primary tumors from patients who have undergone hormone deprivation therapy and found that a significant fraction of these specimens showed nuclear localization of ErbB3. We thus assessed the effect of androgens and the bone microenvironment on the nuclear translocation of ErbB-3 by using xenograft tumor models generated from bone-derived prostate cancer cell lines, MDA PCa 2b, and PC-3. In subcutaneous tumors, ErbB-3 was predominantly in the membrane/cytoplasm; however, it was present in the nuclei of the tumor cells in the femur. Castration of mice bearing subcutaneous MDA PCa 2b tumors induced a transient nuclear translocation of ErbB-3, with relocalization to the membrane/cytoplasm upon tumor recurrence. These findings suggest that the bone microenvironment and androgen status influence the subcellular localization of ErbB-3 in prostate cancer cells. We speculate that nuclear localization of ErbB-3 may aid prostate cancer cell survival during androgen ablation and progression of prostate cancer in bone. (Mol Cancer Res 2007;5(7):675–84)
Endogenous γ-H2AX-ATM-Chk2 Checkpoint Activation in Bloom's Syndrome Helicase–Deficient Cells Is Related to DNA Replication Arrested Forks
Authors: Rao V. Ashutosh , Conti Chiara , Guirouilh-Barbat Josee , Nakamura Asako , Miao Ze-Hong , Davies Sally L. , Saccá Barbara , Hickson Ian D. , Bensimon Aaron , Pommier Yves
Published: July 2007

The Bloom syndrome helicase (BLM) is critical for genomic stability. A defect in BLM activity results in the cancer-predisposing Bloom syndrome (BS). Here, we report that BLM-deficient cell lines and primary fibroblasts display an endogenously activated DNA double-strand break checkpoint response with prominent levels of phosphorylated histone H2AX (γ-H2AX), Chk2 (pT68Chk2), and ATM (pS1981ATM) colocalizing in nuclear foci. Interestingly, the mitotic fraction of γ-H2AX foci did not seem to be higher in BLM-deficient cells, indicating that these lesions form transiently during interphase. Pulse labeling with iododeoxyuridine and immunofluorescence microscopy showed the colocalization of γ-H2AX, ATM, and Chk2 together with replication foci. Those foci costained for Rad51, indicating homologous recombination at these replication sites. We therefore analyzed replication in BS cells using a single molecule approach on combed DNA fibers. In addition to a higher frequency of replication fork barriers, BS cells displayed a reduced average fork velocity and global reduction of interorigin distances indicative of an elevated frequency of origin firing. Because BS is one of the most penetrant cancer-predisposing hereditary diseases, it is likely that the lack of BLM engages the cells in a situation similar to precancerous tissues with replication stress. To our knowledge, this is the first report of high ATM-Chk2 kinase activation and its linkage to replication defects in a BS model. (Mol Cancer Res 2007;5(7):713–24)
Solitary Papillary Muscle Hypertrophy: A New Echo-Electrocardiographic Syndrome? A Case Report
Authors: Ker J.
Published: July 2007

Hypertrophic cardiomyopathy is the term for a heterogeneous group of disorders for which various mutations of genes involving proteins of the cardiac sarcomere lead to hypertrophy of various segments of the left ventricle. The hypertrophy can involve the left and/or right ventricle, be symmetric or asymmetric, involving the septum, free wall, mid-ventricle, or apex. The phenomenon of solitary papillary muscle hypertrophy is rare with only 2 references in the literature. Furthermore, giant negative T and U waves are 2 common electrocardiographic phenomena in hypertrophic cardiomyopathy and have been attributed to hypertrophy of the posterior papillary muscle. Solitary hypertrophy of the anterior papillary muscle might be a new echo-electrocardiographic syndrome.
Intergroup Threat and Experienced Affect: The Distinct Roles of Causal Attributions, Ingroup Identification, and Perceived Legitimacy of Intergroup Status
Authors: Costarelli Sandro
Published: July 2007

Across three studies, it was predicted and found that in the case of intergroup threat, low ingroup identifiers experience greater negative affect when they make an ingroup-internal rather than an outgroup-internal attribution, and high ingroup identifiers experience greater negative affect when they make an outgroup-internal rather than an ingroup-internal attribution. These effects were mediated by the perceived legitimacy of ingroup— outgroup status differences that results from their reflecting social reality (i.e., actual differences in the groups' standing on a relevant comparison dimension). Combining the findings of two distinct literatures, the current work provides new insights into the yet-unexplored distinct roles played by intergroup attributions as a predictor and ingroup identification as a moderator of the affective responses produced by social identity threat.
Preferences for Health Inquiry among Adults Aged 50 and Over
Authors: Kruger Judy , Prohaska Thomas R. , Furner Sylvia E.
Published: July 2007

The study has two main objectives: (1) to determine the proportion of adults ≥ 50 years of age who prefer to have their physician inquire about their functional and emotional health status, and (2) what physician, patient, and medical care system factors are associated with these preferences. The findings suggest that 76% of patients want their physician to inquire about their functional health and 72% want their physician to inquire about their emotional health during the medical encounter. Further analyses show that type of inquiry is strongly associated with patient's preference. Multiple regression models showed congruence regarding physician inquiry about functional and emotional health and patients' preferences for this type of inquiry. The current study is valuable because it highlights the importance of communication exchange during the medical encounter. Physicians are encouraged to inquire into older patients' functional and emotional health status.
Productive Engagement and Late Life Physical and Mental Health
Authors: Hinterlong James E. , Morrow-Howell Nancy , Rozario Philip A.
Published: July 2007

This study examines the association between engagement in productive roles and the physical and mental health of adults aged 60 and over. We present secondary analyses of data from three waves of the Americans' Changing Lives Study ( n = 1,644). Self-rated health, functional impairment, and depressive mood were regressed on measures of engagement during the previous 12 months using generalized estimating equations, while controlling for sociodemographic characteristics and health measures at the previous wave. Five productive roles were included: paid worker, irregular paid worker, unpaid volunteer, caregiver, and provider of informal social assistance. The findings reveal that being engaged in at least one productive role and the total role number are associated with better self-rated health and less functional impairment but not depressive mood. There is no effect of hours of engagement. The findings illuminate productive engagement as an important, but not necessarily causal, pathway to health in late life.
Parenting During Toddlerhood
Authors: Verhoeven Marjolein , Junger Marianne , Van Aken Chantal , Deković Maja , Van Aken Marcel A. G.
Published: July 2007

The present study examines the contribution of parental, contextual, and child characteristics to parenting behavior during toddlerhood in 111 two-parent families with a 17-month-old son ( M = 16.9 months, SD = 0.57). Parenting was conceptualized in terms of five dimensions: support, structure, positive discipline, psychological control, and physical punishment. In general, results indicate that the effects of parental, contextual, and child characteristics on parenting dimensions do not differ for mothers and fathers. The only uncovered difference concerns the effect of children's inhibitory control, which was significant for maternal but not for paternal support. For both mothers and fathers, support, structure, and the use of psychological control are mainly influenced by parental characteristics, whereas the use of positive discipline and physical punishment are best predicted by contextual characteristics. Overall, the contribution of child characteristics to parenting dimensions was moderate.
Persons With Intellectual Disabilities in the Criminal Justice System
Authors: Jones Jessica
Published: July 2007

Although the vast majority of individuals with intellectual disabilities (ID) are law-abiding citizens, there is a small percentage with offending behaviour that is considered antisocial, socially inappropriate, or defined as illegal. It has long been recognised that individuals with ID or mental-health needs who break the law should be dealt with differently from the general population. There have been an increasing number of empirical studies in this area; however, these have been plagued by various definitional and methodological issues. Prevalence estimates of offenders with ID are complicated by diagnostic variations and inconsistencies in the criminal justice process. International studies have shown a large range, from 2% to 40%, depending on methodological approaches. The following review will highlight the salient issues including prevalence of offending, characteristics of offenders, vulnerabilities within the legal system, assessment, and a brief overview of intervention and treatment approaches.
Contradictory Consequences of Mandatory Conscription
Authors: Sasson-Levy Orna
Published: July 2007

This article examines the implications of mandatory conscription for women by studying the experience of women soldiers who serve as secretaries in the Israeli military. The author argues that the military service of the secretaries is shaped by three organizing principles: an employment principle of cheap labor, a matrimonial principle of the office wife, and a hierarchy principle that shapes the secretaries as status symbols. Employing the theory of gendered organizations, the author maintains that each one of these organizing principles operates as a gendering and a power mechanism. The convergence of these three gender/power principles results in overgendering of these women and their military experience. This overgendering reflects gender discrimination and creates feelings of alienation and frustration. For them, military service is not an experience that articulates their citizenship or enhances feelings of national belonging but rather stands in opposition to the values and goals of the mandatory people's army by estranging them from the state and its major institution.
Prolonged Ventilator Dependence
Authors: O'Shea Forbes Maryann
Published: July 2007

The purpose of this qualitative inquiry was to examine the meaning of prolonged mechanical ventilation from the perspective of the patient with a diagnosis of chronic obstructive pulmonary disease (COPD). Interviews were conducted with four individuals with a diagnosis of COPD who had experienced long-term ventilator dependence. Participants were asked to reflect on their experiences while they were ventilator dependent, and their narratives were utilized as text for hermeneutical analysis. The study's findings describe three distinct phases experienced by the participants, beginning with intubation and lasting until well after discharge from the hospital. The support of nurses was an important aspect of maintaining hope for the participants. The study revealed that prolonged mechanical ventilation had a profound impact on COPD patients and their sense of self. Postdischarge psychological support and follow-up with survivors of this experience is warranted.
Lentiviral-mediated RNAi inhibition of Sbds in murine hematopoietic progenitors impairs their hematopoietic potential
Authors: Rawls Amy S. , Gregory Alyssa D. , Woloszynek Jill R. , Liu Fulu , Link Daniel C.
Published: July 2007

Shwachman-Diamond syndrome (SDS) is a rare multisystem disorder characterized by exocrine pancreatic insufficiency, multilineage hematopoietic dysfunction, and metaphyseal chondrodysplasia. Bone marrow dysfunction is present in nearly all patients with SDS, with neutropenia being the most common abnormality. The majority of patients with SDS have mutations in the Shwachman Bodian Diamond syndrome (SBDS) gene. We have developed a strategy to examine the consequences of lentiviral-mediated RNA interference (RNAi) of Sbds on hematopoiesis. Here, we report that both Sbds RNA and protein expression can be efficiently inhibited in primary murine hematopoietic cells using lentiviral-mediated RNAi. Inhibition of Sbds results in a defect in granulocytic differentiation in vitro and impairs myeloid progenitor generation in vivo. In addition, short-term hematopoietic engraftment was impaired, which is due in part to reduced homing of hematopoietic progenitors to the bone marrow. Finally, we show that inhibition of Sbds is associated with a decrease in circulating B lymphocytes, despite evidence of normal B lymphopoiesis. These data provide the first evidence that loss of Sbds is sufficient to induce abnormalities in hematopoiesis.
Expression of CYP3A4 as a predictor of response to chemotherapy in peripheral T-cell lymphomas
Authors: Rodríguez-Antona Cristina , Leskelä Susanna , Zajac Magdalena , Cuadros Marta , Alvés Javier , Moneo Maria Victoria , Martín Carmen , Cigudosa Juan Cruz , Carnero Amancio , Robledo Mercedes , Benitez Javier , Martínez-Delgado Beatriz
Published: July 2007

Peripheral T-cell lymphomas (PTCLs) are aggressive tumors in which the current therapy based on multiagent chemotherapy is not successful. Since cytochrome P450 3A subfamily (CYP3A) enzymes are involved in the inactivation of chemotherapy drugs, we hypothesized that CYP3A and P-glycoprotein (MDR1) expression in these lymphomas could result in a poor clinical response. We measured tumoral CYP3A and MDR1 mRNA content in 44 T-cell lymphomas, finding a large variation in CYP3A expression. Multiplex polymerase chain reaction (PCR) analysis and fluorescence in situ hybridization (FISH) analysis showed genomic gains affecting CYP3A and MDR1 genes in T-cell lines and primary tumors, suggesting that this could be the mechanism underlying the tumoral expression variation. To test whether the tumoral expression of CYP3A and/or MDR1 could influence PTCL treatment outcome, their expression levels were compared with the clinical response and survival of the patients, finding that a high tumoral expression of CYP3A4 was significantly associated with a lower complete remission rate. This was further investigated with cell lines stably expressing CYP3A4 that exhibited an increased resistance to doxorubicin and etoposide. In conclusion, a high CYP3A4 tumoral expression could be useful to predict poor response to the standard PTCL chemotherapy; in these cases alternative chemotherapy combinations or doses should be explored.
Role of epigenetic modifications in normal globin gene regulation and butyrate-mediated induction of fetal hemoglobin
Authors: Fathallah Hassana , Weinberg Rona S. , Galperin Yelena , Sutton Millicent , Atweh George F.
Published: July 2007

Butyrate is a prototype of histone deacetylase inhibitors that is believed to reactivate silent genes by inducing epigenetic modifications. Although butyrate was shown to induce fetal hemoglobin (HbF) production in patients with hemoglobin disorders, the mechanism of this induction has not been fully elucidated. Our studies of the epigenetic configuration of the β-globin cluster suggest that DNA methylation and histone H3 acetylation are important for the regulation of developmental stage-specific expression of the β-like globin genes, whereas acetylation of both histones H3 and H4 seem to be important for the regulation of tissue-specific expression. These studies suggest that DNA methylation may be important for the silencing of the β-like globin genes in nonerythroid hematopoietic cells but may not be necessary for their silencing in nonhematopoietic cells. Furthermore, our studies demonstrate that butyrate exposure results in a true reversal of the normal developmental switch from γ- to β-globin expression. This is associated with increased histone acetylation and decreased DNA methylation of the γ-globin genes, with opposite changes in the β-globin gene. These studies provide strong support for the role of epigenetic modifications in the normal developmental and tissue-specific regulation of globin gene expression and in the butyrate-mediated pharmacologic induction of HbF production.
Absence of gemin5 from SMN complexes in nuclear Cajal bodies
Authors: Hao Le thi , Fuller Heidi R , Lam Le Thanh , Le Thanh T , Burghes Arthur HM , Morris Glenn E
Published: July 2007

Background

Spinal muscular atrophy is caused by reduced levels of the survival of motor neurons (SMN) protein. SMN is found in large complexes with Sm proteins and at least eight other proteins, including seven "gemins". These complexes are involved in the assembly of snRNPs in the cytoplasm and their transport into the nucleus, but the precise roles of the individual protein components are largely unknown.

Results

We have investigated the subcellular distribution of gemins using novel antibodies against gemins 3–7, and existing mAbs against SMN, gemin2, unrip, fibrillarin and profilin II. Most gemins were equally distributed between nuclear and cytoplasmic fractions of HeLa cells, but gemin5 and unrip were more abundant in the cytoplasm. In a cytoplasmic extract obtained by mild disruption of HeLa cells, nearly all the SMN and gemins 2–4 were in large complexes, but most of the gemin5 sedimented separately with a lower S value. Most of the unrip sedimented with gemins 6 and 7 near the top of the sucrose density gradients, separate from both SMN and gemin5. Anti-SMN mAbs pulled down gemin5 from cytoplasmic extracts, but not from nuclear extracts, and gemin5 did not co-sediment with large SMN complexes in nuclear extracts. These data suggest that gemin5 is easily detached from SMN-gemin complexes in the nucleus. By immuno-histochemistry, gemin5 was rarely detectable in nuclear gems/Cajal bodies, although it was accessible to antibody and easily detectable when present. This suggests that gemin5 is normally absent from SMN complexes in these nuclear storage sites.

Conclusion

We conclude that SMN complexes usually exist without gemin5 in nuclear gems/Cajal bodies. Gemin5 is believed to be involved in capturing snRNA into SMN complexes in the cytoplasm for transport into the nucleus. We hypothesize that gemin5, though present in the nucleus, is no longer needed for SMN complex function during the time these complexes are stored in gems/Cajal bodies.
TSLP is involved in expansion of early thymocyte progenitors
Authors: Jiang Qi , Coffield V McNeil , Kondo Motonari , Su Lishan
Published: July 2007

Background

Thymic stromal derived lymphopoietin (TSLP) is preferentially and highly expressed in the thymus, but its function in T cell development is not clear.

Results

We report here that TSLP, independently or in combination with IL-7, enhances thymopoiesis in the murine fetal thymic organ culture (FTOC) model. Furthermore, TSLP preferentially increases the number and proliferation of the (DN1 and DN2) pro-T progenitor cells, and FTOC lobes from TSLP receptor-null mice show a decreased number of these cells. Finally, DN1-DN2 cells expanded with TSLP in vitro are functional T progenitors that are able to differentiate into mature T cells in fetal or adult thymus organs.

Conclusion

Together, these data suggest that TSLP plays an important role in expansion of thymocyte progenitors and may be of value for expanding T progenitor cells in vitro.
Combination therapy targeting the tumor microenvironment is effective in a model of human ocular melanoma
Authors: Mangiameli David P , Blansfield Joseph A , Kachala Stephan , Lorang Dominique , Schafer Peter H , Muller George W , Stirling David I , Libutti Steven K
Published: July 2007

Background

Ocular melanoma is the leading intraocular malignancy. There is no effective treatment for metastatic ocular melanoma. We sought a treatment targeting the tumor microenvironment as well as the tumor cells.

Methods

Migration of HUVEC cells, the ability of HUVEC cells to form tubes, and proliferative capacity of a human ocular melanoma cell line were tested in the presence of lenalidomide and sorafenib alone and in combination. The compounds were also tested in a rat aortic ring assay and were tested in a highly aggressive human ocular melanoma xenograft model.

Results

Lenalidomide and Sorafenib inhibit HUVEC ability to migrate and form tubes and when used in combination the inhibition is increased. The agents alone and in combination inhibit outgrowth in the rat aortic ring model. The combination of the agents improved the inhibition over either single agent. In a xenograft model, combination therapy inhibited tumor growth over inhibition by single agent alone in a significant fashion (p < 0.004: lenalidomide and p < 0.0035: sorafenib). Furthermore, spontaneous lung metastasis development was completely inhibited in the combination treated animals. Sixty percent of vehicle treated animals developed lung metastases compared to 50% of lenalidomide treated animals, and 33% of sorafenib treated animals.

Conclusion

Lenalidomide and sorafenib are effective at targeting endothelial cells, inhibiting growth of ocular melanoma cells and can inhibit growth of tumors in a xenograft model as well as inhibit development of metastases. Combining these agents works in an additive to synergistic way to inhibit the growth of tumors and development of metastases.
The Francisella Pathogenicity Island
Authors: NANO FRANCIS E. , SCHMERK CRYSTAL
Published: July 2007

Abstract:  The Francisella pathogenicity island (FPI) is a cluster of 16–19 genes, which is found duplicated in most of the Francisella genomes that have been sequenced. Although 16 FPI genes are highly conserved there are 2–3 putative genes that are absent or interrupted by stop codons in some strains. Francisella strains with experimentally induced mutations in FPI genes are highly attenuated in virulence and show defects in intramacrophage growth. There is experimental evidence indicating that the regulation of most FPI genes is affected by the presence of the virulence regulator MglA and by the concentration of iron in the growth medium. Although studies of mRNA expression show that essentially all FPI genes are transcribed, only a handful of FPI‐encoded proteins have been detected by biochemical methods. The cumulative biochemical and genetic data to date have not yet been able to ascribe a biochemical function to any of the FPI‐encoded proteins. However, bioinformatics analysis suggests that some of the FPI‐encoded proteins are part of a type VI secretion system.
Animal Models of Francisella tularensis Infection
Authors: RICK LYONS C. , WU TERRY H.
Published: July 2007

Abstract:  The increased incidence of emerging infections has caused a resurgence in the development of animal models in order to study their pathophysiology and develop therapeutics against them. Optimizing these models and improving our ability to extrapolate information from animals to humans is critical because in many cases the animal model will represent the only modality for efficacy testing. Francisella tularensis (F. tularensis) is an emerging pathogen that fits this category. While there is a significant body of literature that has examined infections with F. tularensis in a variety of species, the optimal small animal model has yet to be defined. A vast majority of studies have used two strains of F. tularensis, the more virulent type A strain commonly found in North America and the less virulent type B strain common to Europe. None of the small animal models described in the literature thus far behave in a fashion identical to humans with respect to their sensitivity to SCHU S4 (type A) or live vaccine strains (LVS) (attenuated type B) and an ability of LVS vaccination to consistently protect against a SCHU S4 aerosol challenge, suggesting that significant work on animal model development still remains. This report briefly describes the parameters important for animal model development and reviews the literature related to animal models of F. tularensis, including the human model, and the characterization performed for those models.
Francisella Tularensis: Activation of the Inflammasome
Authors: WEISS DAVID S. , HENRY THOMAS , MONACK DENISE M.
Published: July 2007

Abstract: 
Francisella tularensis (F. tularensis) is a facultative intracellular pathogen that causes the systemic disease tularemia. This pathogen can replicate in the cytosol of macrophages, an ability that is linked with its virulence. We discuss recent data demonstrating that in macrophages, cytosolic Francisella induce the activation of the cysteine protease caspase‐1 within a multiprotein complex called the inflammasome. NOD‐like receptors (NLRs), which may have important roles in innate immunity as intracellular sensors of microbial components and cell injury, and the adaptor molecule ASC are thought to regulate caspase‐1 within the inflammasome. Both ASC and caspase‐1 play a critical role in host defense against Francisella infection in vivo. Activation of caspase‐1 leads to the cleavage and activation of proinflammatory cytokines, such as interleukin‐1β (IL‐1β) and IL‐18, as well as the induction of host cell death, which are required for innate immune defense against Francisella and other intracellular pathogens. The cytokine IFN‐β is secreted from infected cells in response to cytosolic Francisella and its signaling through the type I interferon receptor is required for activation of the inflammasome. Despite the effort of the host to induce inflammasome activation, Francisella modulates this host defense pathway, limiting its efficacy. These results highlight the role that the inflammasome plays in the tug‐of‐war between Francisella and the immune system.
Pneumonic Tularemia on Martha's Vineyard
Authors: MATYAS BELA T. , NIEDER HENRY S. , TELFORD SAM R.
Published: July 2007

Abstract:  Martha's Vineyard, Massachusetts, is the site of the only two recognized outbreaks of primary pneumonic tularemia in the United States. Beginning in 2000 and continuing through 2006, 59 presumed or confirmed tularemia cases have been reported from Martha's Vineyard, with more than 60% of these presumed to be due to inhalation of the agent. A joint CDC/Massachusetts Department of Public Health case–control study identified landscaping activities such as lawnmowing or brush cutting to be important risk factors. The fomites that serve as the basis for risk for landscapers, however, remain unidentified. Clinically, cases generally have a pneumonic component, but the development of pulmonary signs can be greatly delayed. The spectrum of illness ranges from relatively mild disease, in which cases may be treated on an outpatient basis, to severe illness requiring hospitalization. In each scenario, gentamicin therapy tends to rapidly induce defervescence, although exceptions have been noted. Even with heightened awareness during the current outbreak, physicians may easily miss a diagnosis of tularemia, usually by attributing illness to the more common Febrile illnesses. Dog ticks appear to maintain the agent on this island, with as many as 5% infected by the agent of tularemia. The main hosts for dog ticks, skunks and raccoons, are very frequently seroreactive, suggesting the possibility for their involvement in environmental contamination due to their peridomestic habits. Why tularemia is prevalent on Martha's Vineyard and why it commonly presents as a pneumonic disease there remain undescribed.
Innate and Adaptive Immunity to Francisella
Authors: ELKINS KAREN L. , COWLEY SIOBHÁN C. , BOSIO CATHARINE M.
Published: July 2007

Abstract:  Studies of immune responses to Francisella have been conducted for well over 50 years. Here, the basic parameters of innate and adaptive immune responses to Francisella are reviewed, with an emphasis on those that may contribute directly to protection against infection. Although older literature provides a wealth of information on human immune responses to infection and vaccination, most recent information has been derived largely from studies in animals and using animal cells, particularly mice. In experimental animals, activation of macrophages, a major and probably preferred host cell for Francisella, appears central to control of infection. Thus, in animal models and in vitro studies using mouse macrophages, cytokines such as IFN‐γ and TNF‐α, derived first from both nonspecific cells such as natural killer cells and later from Francisella‐specific T cells, collaborate to effect intracellular killing. In mice, these intracellular killing mechanisms include reactive nitrogen and oxygen species, but killing mechanisms remain to be identified in humans. Ultimately both CD4+ and CD8+ T cells develop into Francisella‐specific memory cells and are important for control of primary Francisella infection or vaccination‐induced protection. The effector mechanisms invoked by either CD4+ or CD8+ T cells, beyond production of IFN‐γ and TNF‐α, are the subject of ongoing studies. Both specific antibodies and B cells may contribute to control of primary infection or vaccination‐induced protection in some circumstances, particularly against lower virulence Francisella strains. Thus a number of known proinflammatory and Th‐1 T cell related components of the immune system combat this virulent bacterium; no doubt others remain to be discovered.