bluuebunny/crossref_metadata_2025 huggingface dataset:
Expression of XBP1s in bone marrow stromal cells is critical for myeloma cell growth and osteoclast formation
Authors: Xu Guoshuang , Liu Kai , Anderson Judy , Patrene Kenneth , Lentzsch Suzanne , Roodman G. David , Ouyang Hongjiao
Published: March 2012

BM stromal cells (BMSCs) are key players in the microenvironmental support of multiple myeloma (MM) cell growth and bone destruction. A spliced form of the X-box–binding protein-1 (XBP1s), a major proximal effector of unfolded protein response signaling, is highly expressed in MM cells and plays an indispensable role in MM pathogenesis. In the present study, we found that XBP1s is induced in the BMSCs of the MM microenvironment. XBP1s overexpression in healthy human BMSCs enhanced gene and/or protein expression of VCAM-1, IL-6, and receptor activator of NF-κB ligand (RANKL), enhancing BMSC support of MM cell growth and osteoclast formation in vitro and in vivo. Conversely, deficiency of XBP1 in healthy donor BMSCs displayed a range of effects on BMSCs that were opposite to those cells with overexpression of XBP1s. Knock-down of XBP1 in MM patient BMSCs greatly compromised their increased VCAM-1 protein expression and IL-6 and RANKL secretion in response to TNFα and reversed their enhanced support of MM-cell growth and osteoclast formation. Our results demonstrate that XBP1s is a pathogenic factor underlying BMSC support of MM cell growth and osteoclast formation and therefore represents a therapeutic target for MM bone disease.
Mitochondrial myopathy caused by arsenic trioxide therapy
Authors: Echaniz-Laguna Andoni , Benoilid Aurélien , Vinzio Stéphane , Fornecker Luc-Matthieu , Lannes Béatrice , Goullé Jean-Pierre , Broly Frank , Mousson de Camaret Bénédicte
Published: March 2012

Arsenic trioxide (ATO) has been successfully used as a treatment for acute promyelocytic leukemia (APL) for more than a decade. Here we report a patient with APL who developed a mitochondrial myopathy after treatment with ATO. Three months after ATO therapy withdrawal, the patient was unable to walk without assistance and skeletal muscle studies showed a myopathy with abundant cytoplasmic lipid droplets, decreased activities of the mitochondrial respiratory chain complexes, multiple mitochondrial DNA (mtDNA) deletions, and increased muscle arsenic content. Six months after ATO treatment was interrupted, the patient recovered normal strength, lipid droplets had decreased in size and number, respiratory chain complex activities were partially restored, but multiple mtDNA deletions and increased muscle arsenic content persisted. ATO therapy may provoke a delayed, severe, and partially reversible mitochondrial myopathy, and a long-term careful surveillance for muscle disease should be instituted when ATO is used in patients with APL.
CD47 functions as a molecular switch for erythrocyte phagocytosis
Authors: Burger Patrick , Hilarius-Stokman Petra , de Korte Dirk , van den Berg Timo K. , van Bruggen Robin
Published: March 2012

CD47 on erythrocytes inhibits phagocytosis through interaction with the inhibitory immunoreceptor SIRPα expressed by macrophages. Thus, the CD47-SIRPα interaction constitutes a negative signal for erythrocyte phagocytosis. However, we report here that CD47 does not only function as a “do not eat me” signal for uptake but can also act as an “eat me” signal. In particular, a subset of old erythrocytes present in whole blood was shown to bind and to be phagocytosed via CD47-SIRPα interactions. Furthermore, we provide evidence that experimental aging of erythrocytes induces a conformational change in CD47 that switches the molecule from an inhibitory signal into an activating one. Preincubation of experimentally aged erythrocytes with human serum before the binding assay was required for this activation. We also demonstrate that aged erythrocytes have the capacity to bind the CD47-binding partner thrombospondin-1 (TSP-1) and that treatment of aged erythrocytes with a TSP-1–derived peptide enabled their phagocytosis by human red pulp macrophages. Finally, CD47 on erythrocytes that had been stored for prolonged time was shown to undergo a conformational change and bind TSP-1. These findings reveal a more complex role for CD47-SIRPα interactions in erythrocyte phagocytosis, with CD47 acting as a molecular switch for controlling erythrocyte phagocytosis.
Integrated protein quality-control pathways regulate free α-globin in murine β-thalassemia
Authors: Khandros Eugene , Thom Christopher S. , D'Souza Janine , Weiss Mitchell J.
Published: March 2012

Cells remove unstable polypeptides through protein quality-control (PQC) pathways such as ubiquitin-mediated proteolysis and autophagy. In the present study, we investigated how these pathways are used in β-thalassemia, a common hemoglobinopathy in which β-globin gene mutations cause the accumulation and precipitation of cytotoxic α-globin subunits. In β-thalassemic erythrocyte precursors, free α-globin was polyubiquitinated and degraded by the proteasome. These cells exhibited enhanced proteasome activity, and transcriptional profiling revealed coordinated induction of most proteasome subunits that was mediated by the stress-response transcription factor Nrf1. In isolated thalassemic cells, short-term proteasome inhibition blocked the degradation of free α-globin. In contrast, prolonged in vivo treatment of β-thalassemic mice with the proteasome inhibitor bortezomib did not enhance the accumulation of free α-globin. Rather, systemic proteasome inhibition activated compensatory proteotoxic stress-response mechanisms, including autophagy, which cooperated with ubiquitin-mediated proteolysis to degrade free α-globin in erythroid cells. Our findings show that multiple interregulated PQC responses degrade excess α-globin. Therefore, β-thalassemia fits into the broader framework of protein-aggregation disorders that use PQC pathways as cell-protective mechanisms.
Necrotizing fasciitis involving the chest and abdominal wall caused by Raoultella planticola
Authors: Kim Si-Hyun , Roh Kyoung Ho , Yoon Young Kyung , Kang Dong Oh , Lee Dong Woo , Kim Min Ja , Sohn Jang Wook
Published: March 2012

Background

Raoultella planticola was originally considered to be a member of environmental Klebsiella. The clinical significance of R. planticola is still not well known.

Case presentation

We describe the first case of necrotizing fasciitis involving the chest and abdominal wall caused by R. planticola. The identity of the organism was confirmed using 16S rRNA sequencing. The patient was successfully treated with the appropriate antibiotics combined with operative drainage and debridement.

Conclusions

R. planticola had been described as environmental species, but should be suspected in extensive necrotizing fasciitis after minor trauma in mild to moderate immunocompromised patients.
Single channel speech separation in modulation frequency domain based on a novel pitch range estimation method
Authors: Mahmoodzadeh Azar , Abutalebi Hamid Reza , Soltanian-Zadeh Hamid , Sheikhzadeh Hamid
Published: March 2012

Computational Auditory Scene Analysis (CASA) has been the focus in recent literature for speech separation from monaural mixtures. The performance of current CASA systems on voiced speech separation strictly depends on the robustness of the algorithm used for pitch frequency estimation. We propose a new system that estimates pitch (frequency) range of a target utterance and separates voiced portions of target speech. The algorithm, first, estimates the pitch range of target speech in each frame of data in the modulation frequency domain, and then, uses the estimated pitch range for segregating the target speech. The method of pitch range estimation is based on an onset and offset algorithm. Speech separation is performed by filtering the mixture signal with a mask extracted from the modulation spectrogram. A systematic evaluation shows that the proposed system extracts the majority of target speech signal with minimal interference and outperforms previous systems in both pitch extraction and voiced speech separation.
Intraneuronal Aβ detection in 5xFAD mice by a new Aβ-specific antibody
Authors: Youmans Katherine L , Tai Leon M , Kanekiyo Takahisa , Stine Jr W Blaine , Michon Sara-Claude , Nwabuisi-Heath Evelyn , Manelli Arlene M , Fu Yifan , Riordan Sean , Eimer William A , Binder Lester , Bu Guojun , Yu Chunjiang , Hartley Dean M , LaDu Mary Jo
Published: March 2012

Background

The form(s) of amyloid-β peptide (Aβ) associated with the pathology characteristic of Alzheimer's disease (AD) remains unclear. In particular, the neurotoxicity of intraneuronal Aβ accumulation is an issue of considerable controversy; even the existence of Aβ deposits within neurons has recently been challenged by Winton and co-workers. These authors purport that it is actually intraneuronal APP that is being detected by antibodies thought to be specific for Aβ. To further address this issue, an anti-Aβ antibody was developed (MOAB-2) that specifically detects Aβ, but not APP. This antibody allows for the further evaluation of the early accumulation of intraneuronal Aβ in transgenic mice with increased levels of human Aβ in 5xFAD and 3xTg mice.

Results

MOAB-2 (mouse IgG2b) is a pan-specific, high-titer antibody to Aβ residues 1-4 as demonstrated by biochemical and immunohistochemical analyses (IHC), particularly compared to 6E10 (a commonly used commercial antibody to Aβ residues 3-8). MOAB-2 did not detect APP or APP-CTFs in cell culture media/lysates (HEK-APPSwe or HEK-APPSwe/BACE1) or in brain homogenates from transgenic mice expressing 5 familial AD (FAD) mutation (5xFAD mice). Using IHC on 5xFAD brain tissue, MOAB-2 immunoreactivity co-localized with C-terminal antibodies specific for Aβ40 and Aβ42. MOAB-2 did not co-localize with either N- or C-terminal antibodies to APP. In addition, no MOAB-2-immunreactivity was observed in the brains of 5xFAD/BACE-/- mice, although significant amounts of APP were detected by N- and C-terminal antibodies to APP, as well as by 6E10. In both 5xFAD and 3xTg mouse brain tissue, MOAB-2 co-localized with cathepsin-D, a marker for acidic organelles, further evidence for intraneuronal Aβ, distinct from Aβ associated with the cell membrane. MOAB-2 demonstrated strong intraneuronal and extra-cellular immunoreactivity in 5xFAD and 3xTg mouse brain tissues.

Conclusions

Both intraneuronal Aβ accumulation and extracellular Aβ deposition was demonstrated in 5xFAD mice and 3xTg mice with MOAB-2, an antibody that will help differentiate intracellular Aβ from APP. However, further investigation is required to determine whether a molecular mechanism links the presence of intraneuronal Aβ with neurotoxicity. As well, understanding the relevance of these observations to human AD patients is critical.
Bacterial reprogramming of PBMCs impairs monocyte phagocytosis and modulates adaptive T cell responses
Authors: André Maya C , Gille Christian , Glemser Philip , Woiterski Jeanette , Hsu Hsin-Yun , Spring Baerbel , Keppeler Hildegard , Kramer Boris W , Handgretinger Rupert , Poets Christian F , Lauber Kirsten , Orlikowsky Thorsten W
Published: March 2012

Septic diseases are characterized by an initial systemic, proinflammatory phase, followed by a period of anti-inflammation. In the context of the latter, monocytes have been described to display altered functions, including reduced TNF secretion and T cell-stimulating capacities in response to recall antigens. This hyporesponsiveness is supposed to be detrimental for coping with secondary infections. We here characterize bacterially reprogrammed PBMC-derived monocytes with special focus on their phagocytic activity. Hence, we have implemented a surrogate model of the early, postinflammatory period by exposing PBMCs to Escherichia coli on d0 and rechallenging them with bacteria on d2. This induced the emergence of a distinct monocytic phenotype with profound phagocytic impairments but a preserved ability for naïve T cell stimulation. The compromising effects on phagocytosis required the presence of bacteria and were not mimicked by TLR4 ligation or exposure to isolated cytokines alone. Moreover, the impairments were specific for the engulfment of bacteria and were coupled to a selective down-regulation of FcγR and SR expression. Intriguingly, this monocytic phenotype contributed to the stimulation of a TH17-polarized adaptive immune response in the context of secondary infection. Our findings extend the current knowledge of monocytic reprogramming and identify the phagocytic capacity of monocytes as a putative sepsis biomarker.
Role of IL-6 in the resolution of pancreatitis in obese mice
Authors: Pini Maria , Rhodes Davina H , Castellanos Karla J , Hall Andrew R , Cabay Robert J , Chennuri Rohini , Grady Eileen F , Fantuzzi Giamila
Published: March 2012

Obesity increases severity of acute pancreatitis and risk of pancreatic cancer. Pancreatitis and obesity are associated with elevated IL-6, a cytokine involved in inflammation and tumorigenesis. We studied the role of IL-6 in the response of lean and obese mice to pancreatitis induced by IL-12 + IL-18. Lean and diet-induced obese (DIO) WT and IL-6 KO mice and ob/ob mice pretreated with anti-IL-6 antibodies were evaluated at Days 1, 7, and 15 after induction of pancreatitis. Prolonged elevation of IL-6 in serum and visceral adipose tissue was observed in DIO versus lean WT mice, whereas circulating sIL-6R declined in DIO but not lean mice with pancreatitis. The severe inflammation and lethality of DIO mice were also observed in IL-6 KO mice. However, the delayed resolution of neutrophil infiltration; sustained production of CXCL1, CXCL2, and CCL2; prolonged activation of STAT-3; and induction of MMP-7 in the pancreas, as well as heightened induction of serum amylase A of DIO mice, were blunted significantly in DIO IL-6 KO mice. In DIO mice, production of OPN and TIMP-1 was increased for a prolonged period, and this was mediated by IL-6 in the liver but not the pancreas. Results obtained in IL-6 KO mice were confirmed in ob/ob mice pretreated with anti-IL-6 antibodies. In conclusion, IL-6 does not contribute to the increased severity of pancreatitis of obese mice but participates in delayed recovery from acute inflammation and may favor development of a protumorigenic environment through prolonged activation of STAT-3, induction of MMP-7, and sustained production of chemokines.
TIG3 Interaction at the Centrosome Alters Microtubule Distribution and Centrosome Function
Authors: Scharadin Tiffany M. , Jiang Haibing , Martin Stuart , Eckert Richard L.
Published: March 2012

TIG3 is an importantpro-differentiation regulator that is expressed in the suprabasal epidermis. We have shown that TIG3 activates select keratinocyte differentiation-associated processesleading to cornified envelop formation. However, TIG3 also suppresses cell proliferation by an unknown mechanism. Our present studies suggest that growth cessation may be mediated via the impact of TIG3 on the centrosome and on microtubules. The centrosome regulates microtubule function in interphase cells and microtubule spindle formation in mitotic cells. We show that TIG3 co-localizes with γ-tubulin and pericentrin at the centrosome. TIG3 localization at the centrosome alters microtubule nucleation and reduces anterograde microtubule growth, increases acetylation and detyrosination of α-tubulin, increases insoluble tubulin and drives formation of a peripheral microtubule ring adjacent the plasma membrane. In addition, TIG3 suppresses centrosome separation, but not duplication, and reduces cell proliferation. We propose that TIG3 may regulate formation of the peripheral microtubule ring observed in keratinocytes in differentiated epidermis and also play a role in proliferation cessation in these cells.
The SEC6 protein is required for function of the contractile vacuole inChlamydomonas reinhardtii
Authors: Komsic-Buchmann Karin , Stephan Lisa Marie , Becker Burkhard
Published: March 2012

Contractile vacuoles (CVs) are key players of osmoregulation in many protists. To investigate the mechanism of CV function in Chlamydomonas, we isolated novel osmoregulatory mutants. 4 isolated mutant cell lines carried the same 33,641 b deletion rendering the cell lines unable to grow under strong hypotonic conditions. One mutant cell line (Osmo75) was analyzed in detail. Mutant cells contained a variable CV morphology with most cells displaying multiple small CVs. In addition enlarged 1 or 2 CVs or no light microscopically visible CVs at all were observed. These findings suggest that the mutant is impaired in homotypic vacuolar and exocytotic membrane fusion. Furthermore the mutants displayed a long flagella phenotype. One of the affected genes is the only SEC6 homologue in Chlamydomonas (CreSEC6). The SEC6 protein is a component of the exocyst complex required for efficient exocytosis. Transformation of the Osmo75 mutant with CreSEC6GFP construct rescued the mutant completely (osmoregulation and flagellar length). Rescued strains overexpressed CreSEC6 (as GFP-tagged protein) and displayed a modified CV activity. CVs were significantly larger, whereas the CV contraction interval remained unchanged leading to increased water efflux rates. Electron microspical analysis of Osmo75 showed that the mutant is able to form the close contact zones between the PM (plasma membrane) and the CV membrane observed during late diastole and systole. These results indicate that the CreSEC6 is essential for CV function and required for homotypic vesicle fusion during diastole and water expulsion during systole. In addition CreSEC6 is not only necessary for CV function, but possibly influencing the CV cycle in an indirect way and flagellar length control in Chlamydomonas.
Characterization of Mid1 domains for targeting and scaffolding in fission yeast cytokinesis
Authors: Lee I-Ju , Wu Jian-Qiu
Published: March 2012

Division-site selection and contractile-ring assembly are two crucial steps in cytokinesis. In fission yeast, the anillin-like Mid1 specifies the division site at the cell equator by assembling cortical nodes, the precursors of the contractile ring. Thus, Mid1 is essential for linking the positional cues for the cleavage site to contractile-ring formation. However, how Mid1 domains cooperate to regulate cytokinesis is poorly understood. Here we unravel the functions of different Mid1 domains/motifs by a series of truncations. The conserved PH domain stabilizes Mid1 in nodes by binding to lipids and is required for Mid1 cortical localization during interphase in the absence of Cdr2 kinase. Mid1 lacking an internal region that is ∼1/3 of the full-length protein has higher nuclear and cortical concentration and suppresses the division-site positioning defects in cells with a deletion of the DYRK kinase Pom1. The N-terminus of Mid1 physically interacts with cytokinesis node proteins. When fused to cortical node protein Cdr2, Mid1(1-100) is sufficient to assemble cytokinesis nodes and the contractile ring. Collectively, our study recognizes domains regulating Mid1 cortical localization and reveals domains sufficient for contractile-ring assembly.
Metabolic Heterogeneity in Polycystic Ovary Syndrome Is Determined by Obesity: Plasma Metabolomic Approach Using GC-MS
Authors: Escobar-Morreale Héctor F , Samino Sara , Insenser María , Vinaixa María , Luque-Ramírez Manuel , Lasunción Miguel A , Correig Xavier
Published: March 2012

BACKGROUND

Abdominal adiposity and obesity influence the association of polycystic ovary syndrome (PCOS) with insulin resistance and diabetes. We aimed to characterize the intermediate metabolism phenotypes associated with PCOS and obesity.

METHODS

We applied a nontargeted GC-MS metabolomic approach to plasma samples from 36 patients with PCOS and 39 control women without androgen excess, matched for age, body mass index, and frequency of obesity.

RESULTS

Patients with PCOS were hyperinsulinemic and insulin resistant compared with the controls. The increase in plasma long-chain fatty acids, such as linoleic and oleic acid, and glycerol in the obese patients with PCOS suggests increased lipolysis, possibly secondary to impaired insulin action at adipose tissue. Conversely, nonobese patients with PCOS showed a metabolic profile consisting of suppression of lipolysis and increased glucose utilization (increased lactic acid concentrations) in peripheral tissues, and PCOS patients as a whole showed decreased 2-ketoisocaproic and alanine concentrations, suggesting utilization of branched-chain amino acids for protein synthesis and not for gluconeogenesis. These metabolic processes required effective insulin signaling; therefore, insulin resistance was not universal in all tissues of these women, and different mechanisms possibly contributed to their hyperinsulinemia. PCOS was also associated with decreased α-tocopherol and cholesterol concentrations irrespective of obesity.

CONCLUSIONS

Substantial metabolic heterogeneity, strongly influenced by obesity, underlies PCOS. The possibility that hyperinsulinemia may occur in the absence of universal insulin resistance in nonobese women with PCOS should be considered when designing diagnostic and therapeutic strategies for the management of this prevalent disorder.
Population Growth Enhances the Mean Fixation Time of Neutral Mutations and the Persistence of Neutral Variation
Authors: Waxman D
Published: March 2012

A fundamental result of population genetics states that a new mutation, at an unlinked neutral locus in a randomly mating diploid population, has a mean time of fixation of ∼4Ne generations, where Ne is the effective population size. This result is based on an assumption of fixed population size, which does not universally hold in natural populations. Here, we analyze such neutral fixations in populations of changing size within the framework of the diffusion approximation. General expressions are derived for the mean and variance of the fixation time in changing populations. Some explicit results are given for two cases: (i) the effective population size undergoes a sudden change, representing a sudden population expansion or a sudden bottleneck; (ii) the effective population changes linearly for a limited period of time and then remains constant. Additionally, a lower bound for the mean time of fixation is obtained for an effective population size that increases with time, and this is applied to exponentially growing populations. The results obtained in this work show, among other things, that for populations that increase in size, the mean time of fixation can be enhanced, sometimes substantially so, over 4Ne,0 generations, where Ne,0 is the effective population size at the time the mutation arises. Such an enhancement is associated with (i) an increased probability of neutral polymorphism in a population and (ii) an enhanced persistence of high-frequency neutral variation, which is the variation most likely to be observed.
Allopolyploidization Lays the Foundation for Evolution of Distinct Populations: Evidence From Analysis of SyntheticArabidopsisAllohexaploids
Authors: Matsushita Starr C , Tyagi Anand P , Thornton Gerad M , Pires J Chris , Madlung Andreas
Published: March 2012

Polyploidization is an important mechanism for introducing diversity into a population and promoting evolutionary change. It is believed that most, if not all, angiosperms have undergone whole genome duplication events in their evolutionary history, which has led to changes in genome structure, gene regulation, and chromosome maintenance. Previous studies have shown that polyploidy can coincide with meiotic abnormalities and somatic cytogenetic mosaics in Arabidopsis allotetraploids, but it is unclear whether this phenomenon can contribute to novel diversity or act as a mechanism for speciation. In this study we tested the hypothesis that mosaic aneuploidy contributes to the formation of incipient diversity in neoallopolyploids. We generated a population of synthesized Arabidopsis allohexaploids and monitored karyotypic and phenotypic variation in this population over the first seven generations. We found evidence of sibling line-specific chromosome number variations and rapidly diverging phenotypes between lines, including flowering time, leaf shape, and pollen viability. Karyotypes varied between sibling lines and between cells within the same tissues. Cytotypic variation correlates with phenotypic novelty, and, unlike in allotetraploids, remains a major genomic destabilizing factor for at least the first seven generations. While it is still unclear whether new stable aneuploid lines will arise from these populations, our data are consistent with the notion that somatic aneuploidy, especially in higher level allopolyploids, can act as an evolutionary relevant mechanism to induce rapid variation not only during the initial allopolyploidization process but also for several subsequent generations. This process may lay the genetic foundation for multiple, rather than just a single, new species.
A Non-Mendelian MAPK-Generated Hereditary Unit Controlled by a Second MAPK Pathway inPodospora anserina
Authors: Lalucque Hervé , Malagnac Fabienne , Brun Sylvain , Kicka Sébastien , Silar Philippe
Published: March 2012

The Podospora anserina PaMpk1 MAP kinase (MAPK) signaling pathway can generate a cytoplasmic and infectious element resembling prions. When present in the cells, this C element causes the crippled growth (CG) cell degeneration. CG results from the inappropriate autocatalytic activation of the PaMpk1 MAPK pathway during growth, whereas this cascade normally signals stationary phase. Little is known about the control of such prion-like hereditary units involved in regulatory inheritance. Here, we show that another MAPK pathway, PaMpk2, is crucial at every stage of the fungus life cycle, in particular those controlled by PaMpk1 during stationary phase, which includes the generation of C. Inactivation of the third P. anserina MAPK pathway, PaMpk3, has no effect on the development of the fungus. Mutants of MAPK, MAPK kinase, and MAPK kinase kinase of the PaMpk2 pathway are unable to present CG. This inability likely relies upon an incorrect activation of PaMpk1, although this MAPK is normally phosphorylated in the mutants. In PaMpk2 null mutants, hyphae are abnormal and PaMpk1 is mislocalized. Correspondingly, stationary phase differentiations controlled by PaMpk1 are defective in the mutants of the PaMpk2 cascade. Constitutive activation of the PaMpk2 pathway mimics in many ways its inactivation, including an effect on PaMpk1 localization. Analysis of double and triple mutants inactivated for two or all three MAPK genes undercover new growth and differentiation phenotypes, suggesting overlapping roles. Our data underscore the complex regulation of a prion-like element in a model organism.
V-ATPase V1 Sector Is Required for Corpse Clearance and Neurotransmission in Caenorhabditis elegans
Authors: Ernstrom Glen G , Weimer Robby , Pawar Divya R L , Watanabe Shigeki , Hobson Robert J , Greenstein David , Jorgensen Erik M
Published: March 2012

The vacuolar-type ATPase (V-ATPase) is a proton pump composed of two sectors, the cytoplasmic V1 sector that catalyzes ATP hydrolysis and the transmembrane Vo sector responsible for proton translocation. The transmembrane Vo complex directs the complex to different membranes, but also has been proposed to have roles independent of the V1 sector. However, the roles of the V1 sector have not been well characterized. In the nematode Caenorhabditis elegans there are two V1 B-subunit genes; one of them, vha-12, is on the X chromosome, whereas spe-5 is on an autosome. vha-12 is broadly expressed in adults, and homozygotes for a weak allele in vha-12 are viable but are uncoordinated due to decreased neurotransmission. Analysis of a null mutation demonstrates that vha-12 is not required for oogenesis or spermatogenesis in the adult germ line, but it is required maternally for early embryonic development. Zygotic expression begins during embryonic morphogenesis, and homozygous null mutants arrest at the twofold stage. These mutant embryos exhibit a defect in the clearance of apoptotic cell corpses in vha-12 null mutants. These observations indicate that the V1 sector, in addition to the Vo sector, is required in exocytic and endocytic pathways.
Environmental lead poisoning among children in Porto Alegre state, Southern Brazil
Authors: Ferron Mariana Maleronka , Lima André Klafke de , Saldiva Paulo Hilário Nascimento , Gouveia Nelson
Published: March 2012

OBJECTIVE: To estimate the prevalence of lead poisoning in children and to identify associated factors, as well as possible local sources of contamination. METHODS: A cross-sectional prevalence study conducted in 2006 with a random sample of 97 children age zero to five years from a neighborhood in Porto Alegre, Southern Brazil. Blood lead levels were measured and a questionnaire administered to collect information on sociodemographics, recycling and dwelling. A preliminary environmental evaluation was carried out with direct analysis of soil and indirect analysis of air pollution with bioindicators to identify possible sources of contamination. To analyze lead concentrations from the different collection sites, for each type of material studied, ANOVA was performed with a Brown-Forsythe adjustment for heteroscedasticity and with Dunnett's T3 procedure for multiple comparisons of unequal variances. RESULTS: Blood lead levels > 10.0 µg/dL was found in 16.5% of children. Recycling of waste at home, low father's education level, and increased age of children were associated with increase blood lead levels. High lead levels were found in soil, and there was little indication of lead air pollution. CONCLUSIONS: A high prevalence of lead poisoning was identified, and the potential sources of contamination in this community appear related to waste recylcing activities. Studies should be conducted with other populations of Brazilian children and evaluate potential sources of local and general contamination, to accurately characterize this issue in Brazil.
Perspectives on access to in vitro fertilization in Portugal
Authors: Silva S. , Barros H.
Published: March 2012

OBJECTIVE: To analyze users' reasons for choosing in vitro fertilization treatment in public or private services and to identify their suggestions for improving fertility treatment. METHODS: A qualitative study using an interpretative approach was conducted. Fifteen semi-structured interviews were conducted with patients undergoing in vitro fertilization treatment (nine women, one man and five couples) at home or at their workplace in the districts of Viana do Castelo, Braga, Porto and Lisbon, Portugal, between July 2005 and February 2006. RESULTS: Users evaluated access to in vitro fertilization treatment in public and private services based mainly on their individual experiences and called for more access to less costly, faster and friendlier care with suitable facilities, appropriate time management and caring medical providers. These perceptions were also associated with views on the need for fighting stigmatization of infertility, protecting children's rights and guaranteeing sustainability of health care system. Interviewees sought to balance reduced waiting time and more attentive care with costs involved. The choice of services depended on the users' purchase power and place of residence and availability of attentive care. CONCLUSIONS: Current national policies on in vitro fertilization treatment meet user's demands of promoting access to, and quality, availability and affordability of in vitro fertilization treatment. However, their focus on legal regulation and technical-scientific aspects contrasts with the users' emphasis on reimbursement, insurance coverage and focus on emotional aspects of the treatment. The study showed these policies should ensure insurance coverage, participation of user representatives in the National Council for Assisted Reproductive Technology, promotion of infertility research and certification of fertility laboratories.
Uso de agrotóxicos e impactos econômicos sobre a saúde
Authors: Soares Wagner Lopes , Porto Marcelo Firpo de Souza
Published: March 2012

OBJETIVO: Estimar externalidades associadas às intoxicações agudas por agrotóxicos. MÉTODOS: Foram estimadas as probabilidades de intoxicação aguda segundo as características dos estabelecimentos rurais e de municípios no Paraná. Foram utilizadas informações sobre intoxicações agudas obtidas da Pesquisa de Previsão de Safras de 1998 a 1999. Os custos esperados com a intoxicação nessas propriedades foram calculados a partir da soma das despesas médicas-hospitalares e dos dias de convalescência necessários para restabelecer a saúde dos intoxicados. Foi construído um modelo multinível para análise. RESULTADOS: O custo associado à intoxicação aguda pode representar até US$ 149 milhões para o Paraná, i.e., para cada dólar gasto com a compra dos agrotóxicos no estado, cerca de US$ 1,28 poderiam ser gerados em custos externos com a intoxicação. Essa situação poderia ser revertida com a implementação de políticas públicas, como adoção de programa de incentivo à agricultura orgânica nos municípios, cujo custo social com a intoxicação aguda poderia ser reduzido em torno de US$ 25 milhões. CONCLUSÕES: A sociedade, em especial as populações mais atingidas pelos agrotóxicos, seriam beneficiadas se riscos de intoxicação aguda associados ao atual modelo de produção agrícola fossem reconhecidos e eliminados. É necessária a implementação de políticas públicas e ações integradas envolvendo os campos da economia, da saúde pública, da agronomia, do meio ambiente, da educação e da ciência e tecnologia, dentre outros.
Correção endovascular do aneurisma da aorta abdominal: análise dos resultados de único centro
Authors: Novero Eduardo Rafael , Metzger Patrick Bastos , Angelieri Fernanda Maria Resegue , Colli Marcelo Bueno de Oliveira , Moreira Samuel Martins , Izukawa Nilo Mitsuru , Rossi Fabio Henrique , Kambara Antonio Massamitsu
Published: March 2012

OBJETIVO: Avaliar os resultados clínicos imediatos e em médio prazo do tratamento endovascular em pacientes portadores de aneurisma da aorta abdominal em um centro de referência para doenças cardiovasculares. MATERIAIS E MÉTODOS: Estudo retrospectivo de uma série de pacientes submetidos a tratamento endovascular de aneurisma da aorta abdominal, no período de janeiro de 2009 a julho de 2010. Foram avaliados as características demográficas, o sucesso técnico, o sucesso terapêutico, a morbimortalidade, as complicações e a taxa de reintervenções perioperatórias imediatos, e após um ano de acompanhamento. RESULTADOS: Foram analisados 102 pacientes consecutivos com idade média de 72 ± 9 anos, sendo 79% deles do sexo masculino. Houve sucesso técnico em 97,1% e êxito terapêutico em 81% dos casos. A mortalidade perioperatória foi de 0,9% e a anual, de 7,8%. Foram necessárias reintervenções em 18,8% dos pacientes durante o seguimento. CONCLUSÃO: Em nosso estudo, os resultados obtidos justificam a realização desse procedimento nos pacientes com anatomia adequada.
Incidência e aspectos de imagem do linfoma pós-transplante hepático em crianças
Authors: Bitencourt Almir Galvão Vieira , Pinto Paula Nicole Vieira , Almeida Maria Fernanda Arruda , Cerqueira Wagner Santana , Assis André Moreira de , Rodrigues Adriana Michiko da Silva Tanaka , Chojniak Rubens
Published: March 2012

OBJETIVO: Avaliar a incidência e os aspectos de imagem do linfoma pós-transplante hepático em crianças. MATERIAIS E MÉTODOS: Foram revisados os prontuários e exames de imagem de crianças submetidas a transplante hepático entre 2000 e 2008 em uma única instituição. RESULTADOS: De 241 crianças submetidas a transplante hepático, com seguimento médio de 41,4 ± 26,4 meses, 16 (6,6%) tiveram linfoma. A média de idade no transplante hepático das crianças que desenvolveram linfoma foi inferior à das crianças que não desenvolveram (23,9 ± 18,9 vs. 38,0 ± 48,9 meses; p = 0,02). O tempo entre o transplante e o desenvolvimento do linfoma variou de 6 a 103 meses. A apresentação clínica e radiológica foi variável e a localização mais comum do tumor foi no abdome (n = 13; 81,3%), seguida de tórax e cabeça e pescoço (n = 4; 25,0% cada). Os achados de imagem incluíram: linfonodomegalias, massas mediastinais, pulmonares e mesentéricas, espessamento parietal de alças intestinais e nódulos hepáticos e renais. Quatro crianças (25,0%) faleceram devido a complicações do linfoma. CONCLUSÃO: Linfomas são complicações relativamente incomuns e potencialmente fatais que podem acontecer a qualquer momento após o transplante hepático em crianças, e que têm diversas apresentações clínicas e de imagem.
Dificuldades diagnósticas no osteoma osteoide do cotovelo: estudo clínico, radiológico e histopatológico
Authors: Cotta Ana Cristina , Melo Rogério Teles de , Castro Renato César Rezende de , Souza Francineide Sadala de , Najjar Yana Senna Jeronymo , Paim Júlia Filardi de Oliveira , Kalil Ricardo Karam
Published: March 2012

OBJETIVO: Descrever os aspectos clínicos e de imagem que podem auxiliar no diagnóstico correto do osteoma osteoide no cotovelo. MATERIAIS E MÉTODOS: Realizado estudo retrospectivo de sete pacientes com diagnóstico de osteoma osteoide no cotovelo confirmado histologicamente por biópsia óssea. Eles tiveram seus prontuários médicos e exames de imagem revisados. RESULTADOS: Do total de 142 pacientes identificados em nossos arquivos, 4,9% apresentavam a lesão no cotovelo, com predomínio no sexo masculino (2,5:1) e idade média de 25 anos. Dor e limitação de movimento foram os sintomas mais comuns. Cinco pacientes (71,4%) receberam outro diagnóstico clínico prévio. A duração média dos sintomas foi de 21 meses. As radiografias não demonstraram o nidus em 42,8% dos casos. A tomografia computadorizada e a ressonância magnética mostraram claramente o nidus. Derrame articular foi um achado constante. O aspecto histológico observado foi o usual. A ressecção cirúrgica promoveu alívio dos sintomas e/ou melhora funcional em todos os casos. CONCLUSÃO: É importante considerar a possibilidade de osteoma osteoide em paciente adulto jovem com dor, limitação do movimento e sinais de sinovite no cotovelo, refratária ao tratamento conservador. Esclerose óssea, espessamento cortical e/ou reação periosteal detectados na radiografia permitem direcionar a tomografia computadorizada para a visualização precisa do nidus.
Preferência do paciente no rastreamento do câncer colorretal: uma comparação entre colonografia por tomografia computadorizada e colonoscopia
Authors: Maia Marcos Vinicius Alvim Soares , Atzingen Augusto Castelli von , Tiferes Dario Ariel , Saad Sarhan Sydney , Deak Elisabeth , Matos Delcio , D'Ippolito Giuseppe
Published: March 2012

OBJETIVO: Avaliar o grau de aceitação do paciente submetido a colonografia por tomografia computadorizada (CTC) em comparação com a colonoscopia, quando realizadas para rastreamento de doença colorretal. MATERIAIS E MÉTODOS: Cinquenta pacientes com suspeita de doença colorretal foram submetidos a CTC e colonoscopia. Questionários foram aplicados antes e após a realização da CTC e após a colonoscopia. Graduou-se o desconforto esperado e experimentado antes e após a realização da CTC e da colonoscopia, bem como a preferência do paciente por exame. RESULTADOS: Em relação à CTC, antes de iniciar o exame 18% dos pacientes afirmaram esperar pouco desconforto, 78%, desconforto moderado e 4%, muito desconforto. Após a realização do exame, 72% dos pacientes relataram pouco desconforto, 26%, desconforto moderado e apenas um (2%) dos pacientes referiu muito desconforto. Após a realização da colonoscopia, 86% dos pacientes relataram preferência pela CTC. O grau de distensão colônica e a quantidade de fluido residual não influenciaram na preferência dos pacientes. CONCLUSÃO: Os pacientes preferiram a CTC à colonoscopia, não havendo relação estatística com o grau de distensão colônica na CTC e a eficiência do preparo intestinal.
CAD e mamografia: por que usar esta ferramenta?
Authors: Calas Maria Julia Gregorio , Gutfilen Bianca , Pereira Wagner Coelho de Albuquerque
Published: March 2012

A mamografia representa o melhor método de detecção precoce do câncer de mama, porém cerca de 10% a 30% das lesões mamárias são perdidas no rastreamento, devido a limitações próprias dos observadores humanos. A detecção auxiliada por computador (computer-aided detection - CAD) é uma tecnologia relativamente nova que tem sido implementada em alguns serviços de mamografia, com o intuito de prover uma dupla leitura. Estudos clínicos têm demonstrado que o CAD aumenta a sensibilidade de detecção do câncer da mama, por radiologistas, em até 21%. Um sistema CAD é útil em situações em que exista alta variabilidade interobservador, falta de observadores treinados, ou na impossibilidade de se realizar a dupla leitura com dois ou mais radiologistas. O objetivo desta revisão está baseado na necessidade de atualizar a comunidade médica acerca desta ferramenta, como um método auxiliar, quantitativo, não operador-dependente, e que visa a melhorar a qualidade do diagnóstico do câncer de mama.
Avaliação por imagem dos gossipibomas abdominais
Authors: Chagas Neto Francisco Abaeté das , Agnollitto Paulo Moraes , Mauad Fernando Marum , Barreto André Rodrigues Façanha , Muglia Valdair Francisco , Elias Junior Jorge
Published: March 2012

O termo gossipiboma é usado para descrever uma massa formada a partir de uma matriz de algodão cercada por uma reação inflamatória/granulomatosa. Sua incidência é estimada em 0,15% a 0,2%. O corpo estranho na cavidade abdominal pode servir de nicho para a proliferação de microrganismos e agir como foco primário para formação de abscessos e de peritonite. Vários estudos têm demonstrado a importância da correlação clínica com os diversos métodos de imagem (radiografia convencional, ultrassonografia, tomografia computadorizada e ressonância magnética) no diagnóstico dos gossipibomas. Este ensaio tem por objetivo demonstrar uma série de casos típicos de gossipibomas abdominais e ilustrar suas diversas formas de apresentação, com ênfase nos achados dos diferentes métodos de imagem, visando a familiarizar os radiologistas com esta enfermidade e seus principais diagnósticos diferenciais.
Bilioma espontâneo: relato de caso e revisão da literatura
Authors: Gössling Pedro Augusto Mânica , Alves Giordano Rafael Tronco , Silva Régis Vinícius de Andrade , Corrêa José Roberto Missel , Marques Henrique Ferreira , Haygert Carlos Jesus Pereira
Published: March 2012

Bilioma é qualquer coleção de bile fora das vias biliares. Geralmente, resulta de complicações cirúrgicas e trauma abdominal. A ocorrência espontânea é rara, ocasionalmente associada a coledocolitíase. Relata-se um caso de bilioma espontâneo, cujo diagnóstico foi confirmado radiologicamente. À laparotomia, observou-se bilioma retroperitoneal. A colangiografia transoperatória não evidenciou fístula. Após drenagem, o paciente teve boa evolução e alta hospitalar.
Embolização arterial no tratamento de hemobilia pós-trauma hepático: relato de caso
Authors: Queiroz Hercilia Maria Carvalho , Costa Francisco de Assis , Campos Junior Manoel Messias de , Aquino Ricardo Leite de , Linhares Filho Frederico Augusto de Carvalho , Otoch Marcelo
Published: March 2012

Hemobilia é causa rara de hemorragia digestiva e complicação incomum no trauma hepático. Ocorre devido à comunicação entre ductos biliares e vasos intra-hepáticos. Os autores relatam um caso de paciente vítima de ferimento penetrante abdominal que evoluiu, após três meses da hepatorrafia, com dor, icterícia e hemorragia digestiva. Foi realizada angiografia, que demonstrou pseudoaneurisma de artéria hepática direita, e efetuada embolização com sucesso.
Pode a gestação influenciar a evolução de nódulo tireoidiano maligno?
Authors: Kerr Lucy , Vidigal Maria Edith Lutz , Rozenkwit Deborah
Published: March 2012

Os autores descrevem um nódulo tireoidiano com padrões ultrassonográfico e citopatológico benignos que diminuiu mais de 50% em três anos e se modificou durante a gestação, constatando-se que era carcinoma papilífero. Conclui-se que a gestação pode aumentar o risco de malignização ou acelerar o crescimento de nódulo tireoidiano maligno preexistente, corroborando dados da literatura.
Density and rheological parameters of goat milk
Authors: Gabas Ana Lúcia , Cabral Renato Alexandre Ferreira , Oliveira Carlos Augusto Fernandes de , Telis-Romero Javier
Published: March 2012

The rheological behavior and density of goat milk was studied as a function of solids concentration (10.5 to 50.0%) and temperature (273 to 331 k). Newtonian behavior was observed for values of total solids (TS) between 10.5 and 22.0% and temperatures from 276 to 331 k changing to pseudoplastic behavior without yield stress for TS from 25.0 to 39.4% at the same range of temperature. Goat milk with TS between 44.3 to 50.0% and temperatures of 273 to 296 k showed yield stress in addition to pseudoplastic behavior. At 303 to 331 k the power law model was observed again, without yield stress. The density of goat milk ranged from 991.7 to 1232.4 kg.m-3.
Estudo sobre a aplicação do método de avaliação do modelo de processos de negócio do EKD
Authors: Pádua Silvia Inês Dallavalle de
Published: March 2012

A modelagem de processos de negócio e a simulação têm sido amplamente utilizadas para realizar melhoria contínua, gestão por processos e mudanças na estrutura organizacional. Assim, este trabalho tem o objetivo principal de apresentar e discutir a aplicação do método de avaliação do modelo de processos de negócios do EKD. O método inclui a simulação do modelo de processos de negócio para verificar se o modelo está livre de travamentos e erros. Essa pesquisa é uma revisão da literatura, com uma aplicação pautada em dados secundários. A aplicação do método mostrou que o desenvolvimento do modelo de processos de negócio com base nos objetivos organizacionais facilita o entendimento por todas as pessoas envolvidas no processo de modelagem e a simulação identificou se o modelo estava correto e livre de travamentos.
Contornos negociados del "buen morir": la toma de decisiones médicas en el final de la vida
Authors: Alonso Juan Pedro
Published: March 2012

El artículo analiza la toma de decisiones médicas en el final de la vida, explorando las nociones legas y profesionales respecto al "buen morir" que estas decisiones ponen de relieve. A partir de un planteamiento etnográfico en un servicio de cuidados paliativos de la ciudad de Buenos Aires, Argentina, el artículo encara empíricamente la forma en que los significados en torno a estas nociones se negocian en contextos prácticos y situacionales. El análisis de casos concretos de toma de decisiones en el final de la vida evidencia el carácter problemático de definir estas nociones en ámbitos médicos, y que el significado y la definición de una muerte como "buena" o "digna" se sujeta a un proceso de construcción interpretativa por parte de los actores. Asimismo, se señalan las tensiones entre los proyectos de "humanización" de los cuidados en el final de la vida y la medicación de la muerte y el morir.
O conceito de racismo institucional: aplicações no campo da saúde
Authors: López Laura Cecilia
Published: March 2012

O artigo propõe-se a refletir sobre o conceito de racismo institucional, em relação a sua pertinência para pensar a realidade social brasileira, assim como ao seu vínculo com ações, demandas e disputas do movimento negro contemporâneo frente ao poder público. O racismo institucional atua de forma difusa no funcionamento cotidiano de instituições e organizações, provocando uma desigualdade na distribuição de serviços, benefícios e oportunidades aos diferentes segmentos da população do ponto de vista racial. Aponta-se que, para sua desconstrução, é preciso a implementação de políticas públicas que provoquem um processo de desrracialização, assim como gerar reflexões acadêmicas de como operam esses mecanismos. Na área da saúde, eles podem ser analisados como dispositivos de biopoder, na medida em que gerenciam a vida da população sob um olhar racial. Demanda-se a necessidade de realização de pesquisas qualitativas de abordagem etnográfica que reflitam sobre como operam esses dispositivos no cotidiano das instituições.