bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased GILZ expression in transgenic mice up-regulates Th-2 lymphokines
Authors: Cannarile Lorenza , Fallarino Francesca , Agostini Massimiliano , Cuzzocrea Salvatore , Mazzon Emanuela , Vacca Carmine , Genovese Tiziana , Migliorati Graziella , Ayroldi Emira , Riccardi Carlo 
Published: October 2005

AbstractGILZ (glucocorticoid-induced leucine zipper), a gene induced by dexamethasone, is involved in control of T lymphocyte activation and apoptosis. In the present study, using Gilz transgenic mice (TG), which overexpress GILZ in the T-cell lineage, we demonstrate that Gilz is implicated in T helper-2 (Th-2) response development. After in vitro stimulation by CD3/CD28 antibodies, peripheral naive CD4+ T cells from TG mice secrete more Th-2 cytokines such as interleukin-4 (IL-4), IL-5, IL-13, and IL-10, and produce less Th-1 cytokines such as interferon-γ (IFN-γ) than wild-type mice (WT). CD4+ TG lymphocytes up-regulated Th-2 cytokine expression in the specific response to ovalbumin chicken egg (OVA) antigen immunization. Up-regulation correlated with increased expression of GATA-3 and signal transducer and activator of transcription 6 (Stat6), Th-2–specific transcription factors and decreased expression of T-bet, a transcription factor involved in Th-1 differentiation. Finally, in TG mice delayed-type hypersensitivity, a Th-1 response, was inhibited and bleomycin-induced pulmonary fibrosis, a Th-2 mediated disease, was more severe. These results indicate that Gilz contributes to CD4+ commitment toward a Th-2 phenotype and suggest this contribution may be another mechanism accounting for glucocorticoid immunomodulation.
Phospholipase C-γ2 is essential for NK cell cytotoxicity and innate immunity to malignant and virally infected cells
Authors: Caraux Anouk , Kim Nayoung , Bell Sarah E. , Zompi Simona , Ranson Thomas , Lesjean-Pottier Sarah , Garcia-Ojeda Marcos E. , Turner Martin , Colucci Francesco 
Published: October 2005

AbstractPhospholipase C-γ2 (PLC-γ2) is a key component of signal transduction in leukocytes. In natural killer (NK) cells, PLC-γ2 is pivotal for cellular cytotoxicity; however, it is not known which steps of the cytolytic machinery it regulates. We found that PLC-γ2-deficient NK cells formed conjugates with target cells and polarized the microtubule-organizing center, but failed to secrete cytotoxic granules, due to defective calcium mobilization. Consequently, cytotoxicity was completely abrogated in PLC-γ2-deficient cells, regardless of whether targets expressed NKG2D ligands, missed self major histocompatibility complex (MHC) class I, or whether NK cells were stimulated with IL-2 and antibodies specific for NKR-P1C, CD16, CD244, Ly49D, and Ly49H. Defective secretion was specific to cytotoxic granules because release of IFN-γ on stimulation with IL-12 was normal. Plcg2-/- mice could not reject MHC class I-deficient lymphoma cells nor could they control CMV infection, but they effectively contained Listeria monocytogenes infection. Our results suggest that exocytosis of cytotoxic granules, but not cellular polarization toward targets, depends on intracellular calcium rise during NK cell cytotoxicity. In vivo, PLC-γ2 regulates selective facets of innate immunity because it is essential for NK cell responses to malignant and virally infected cells but not to bacterial infections.
The future prospects of Lithuanian family physicians: a 10-year forecasting study
Authors: Starkiene Liudvika , Smigelskas Kastytis , Padaiga Zilvinas , Reamy Jack 
Published: October 2005

Abstract

Background
When health care reform was started in 1991, the physician workforce in Lithuania was dominated by specialists, and the specialty of family physician (FP) did not exist at all. During fifteen years of Lithuania's independence this specialty evolved rapidly and over 1,900 FPs were trained or retrained. Since 2003, the Lithuanian health care sector has undergone restructuring to optimize the network of health care institutions as well as the delivery of services; specific attention has been paid to the development of services provided by FPs, with more health care services shifted from the hospital level to the primary health care level. In this paper we analyze if an adequate workforce of FPs will be available in the future to take over new emerging tasks.

Methods
A computer spreadsheet simulation model was used to project the supply of FPs in 2006–2015. The supply was projected according to three scenarios, which took into account different rates of retirement, migration and drop out from training. In addition different population projections and enrolment numbers in residency programs were also considered. Three requirement scenarios were made using different approaches. In the first scenario we used the requirement estimated by a panel of experts using the Delphi technique. The second scenario was based on the number of visits to FPs in 2003 and took into account the goal to increase the number of visits. The third scenario was based on the determination that one FP should serve no more than 2,000 inhabitants. The three scenarios for the projection of supply were compared with the three requirement scenarios.

Results
The supply of family physicians will be higher in 2015 compared to 2005 according to all projection scenarios. The largest differences in the supply scenarios were caused by different migration rates, enrolment numbers to training programs and the retirement age. The second supply scenario, which took into account 1.1% annual migration rate, stable enrolment to residency programs and later retirement, appears to be the most probable. The first requirement scenario, which was based on the opinion of well-informed key experts in the field, appears to be the best reflection of FP requirements; however none of the supply scenarios considered would satisfy these requirements.

Conclusion
Despite the rapid expansion of the FP workforce during the last fifteen years, ten-year forecasts of supply and requirement indicate that the number of FPs in 2015 will not be sufficient. The annual enrolment in residency training programs should be increased by at least 20% for the next three years. Accurate year-by-year monitoring of the workforce is crucial in order to prevent future shortages and to maintain the desired family physician workforce.
Identification of moaA3 gene in patient isolates of Mycobacterium tuberculosis in Kerala, which is absent in M. tuberculosisH37Rv and H37Ra
Authors: Sarojini Suma , Soman Smitha , Radhakrishnan Indulakshmi , Mundayoor Sathish 
Published: October 2005

Abstract

Background
Tuberculosis is endemic to developing countries like India. Though the whole genome sequences of the type strain M. tuberculosis H37Rv and the clinical strain M. tuberculosis CDC1551 are available, the clinical isolates from India have not been studied extensively at the genome level. This study was carried out in order to have a better understanding of isolates from Kerala, a state in southern India.

Results
A PCR based strategy was followed making use of the deletion region primers to understand the genome level differences between the type strain H37Rv and the clinical isolates of M. tuberculosis from Kerala. PCR analysis of patient isolates using RD1 region primers revealed the amplification of a 386 bp region, in addition to the expected 652 bp amplicon. Southern hybridization of genomic DNA with the 386 bp amplicon confirmed the presence of this new region in a majority of the patient isolates from Kerala. Sequence comparison of this amplicon showed close homology with the moaA3 gene of M. bovis. In M. bovis this gene is present in the RvD5 region, an IS6110 mediated deletion that is absent in M. tuberculosis H37Rv.

Conclusion
This study demonstrates the presence of moaA3 gene, that is absent in M. tuberculosis H37Rv and H37Ra, in a large number of local isolates. Whether the moaA3 gene provides any specific advantage to the field isolates of the pathogen is unclear. Field strains from Kerala have fewer IS6110 sequences and therefore are likely to have fewer IS6110 dependent rearrangements. But as deletions and insertions account for much of the genomic diversity of M. tuberculosis, the mechanisms of formation of sequence polymorphisms in the local isolates should be further examined. These results suggest that studies should focus on strains from endemic areas to understand the complexities of this pathogen.
Birth outcomes in Colorado's undocumented immigrant population
Authors: Reed Mary M , Westfall John M , Bublitz Caroline , Battaglia Catherine , Fickenscher Alexandra 
Published: October 2005

Abstract

Background
The birth outcomes of undocumented women have not been systematically studied on a large scale. The growing number of undocumented women giving birth in the United States has important implications for clinical care and public health policy. The objective of this study was to describe birth outcomes of undocumented immigrants in Colorado.

Methods
Retrospective descriptive study of singleton births to 5961 undocumented women using birth certificate data for 1998–1999.

Results
Undocumented mothers were younger, less educated, and more likely to be single. They had higher rates of anemia, were less likely to gain enough weight, and less likely to receive early prenatal care. They were much less likely to use alcohol or tobacco. Undocumented women had a lower rate of low birth weight (5.3% v 6.5%, P < .001) or preterm infants (12.9% v 14.5%; p = .001). Undocumented women experienced higher rates of labor complications including excessive bleeding (2.3% v 0.8%, p < .001) and fetal distress (8.7% v 3.6%, p < .001).

Conclusion
Undocumented women have lower rates of preterm delivery and low birth weight infants, but higher rates of pregnancy related risk factors. Higher prevalence of some risk factors which are amenable to medical intervention reveals the need for improved prenatal care in this group.
The antihyperlipidemic activities of 4(3H) quinazolinone and two halogenated derivatives in rats
Authors: Refaie Fawzia M , Esmat Amr Y , Gawad Soad M Abdel , Ibrahim Aida M , Mohamed Mona A 
Published: October 2005

Abstract
In the present study, the effects of subchronic treatments (4 weeks) of hypercholesterolemic (single) and diabetic-hypercholesterolemic (combined) rats with 4 (3H) quinazolinone and 2 halogenated derivatives (6, 8-dibromo-2-methy-4 (3H) quinazolinone and 6-iodo-2-methyl-4(3H) quinazolinone) at a sublethal dose level (2 mg/Kg) on cholesterol metabolism were investigated. Bezafibrate, a hypolipidemic drug was used as a reference compound for data comparison. Treatment of rats with single and combined hypercholesterolemia with quinazolinone compounds gave rise to highly significant reductions in serum total cholesterol and cholesterol ester levels, whereas serum triacylglycerol level was significantly reduced only after treatment with halogen-substituted quinazolinones in single hyper-cholesterolemia, compared to the control group. The effects of different quinazolinones and bezafibrate on reduction of serum LDL-C level were comparable in single hypercholesterolemia but significantly different in combined hypercholesterolemia. Results obtained from this study suggest that the antihyperlipidemic effect of quinazolinone compounds was brought about by inhibition of dietary cholesterol absorption and / or intestinal ACAT activity.
12thinternational conference on human retrovirology: HTLV and related retroviruses
Authors: Lairmore Michael D , Fujii Masahiro 
Published: October 2005

Abstract
The 12th International Conference on Human Retrovirology: HTLV and Related Retroviruses, was held at the Half Moon Hotel in Montego Bay, Jamaica, from June 22nd to June 25th 2005. The scientific conference, sponsored by the International Retrovirology Association, is held biennially at rotating international venues around the world. The meeting brings together basic scientists, epidemiologists and clinical researchers to discuss findings to prevent HTLV infection or develop new therapies against HTLV-mediated diseases. The Association fosters the education and training of young scientists to bring new approaches to the complex problems of HTLV research, such as translational research to bring findings from the laboratory into clinical trials that benefit HTLV-infected patients. The breadth and quality of research presentations and workshops at the 12th International Conference indicate that these goals are being accomplished. As HTLV research enters its third decade a new generation of scientists face many challenges. However, HTLV scientists and clinicians displayed exciting new approaches and discoveries during plenary talks and poster sessions. The conference encouraged research in HTLV infections and disease, fostered collaborations, and stimulated new partnerships between clinicians and scientists to encourage clinical trials and novel therapeutic interventions.
Combustion of dried animal dung as biofuel results in the generation of highly redox active fine particulates
Authors: Mudway Ian S , Duggan Sean T , Venkataraman Chandra , Habib Gazala , Kelly Frank J , Grigg Jonathan 
Published: October 2005

Abstract

Background
The burning of biomass in the developing world for heating and cooking results in high indoor particle concentrations. Long-term exposure to airborne particulate matter (PM) has been associated with increased rates of acute respiratory infections, chronic obstructive lung disease and cancer. In this study we determined the oxidative activity of combustion particles derived from the biomass fuel dung cake by examining their capacity to deplete antioxidants from a model human respiratory tract lining fluid (RTLF). For comparison, the observed oxidative activity was compared with that of particles derived from industrial and vehicular sources.

Results
Incubation of the dung cake particle suspensions in the RTLF for 4 h resulted in a mean loss of ascorbate of 72.1 ± 0.7 and 89.7 ± 2.5% at 50 and 100 μg/ml, respectively. Reduced glutathione was depleted by 49.6 ± 4.3 and 63.5 ± 22.4% under the same conditions. The capacity of these samples to deplete ascorbate was in excess of that observed with diesel or gasoline particles, but comparable to that seen with residual oil fly ash and considerably in excess of all three control particles in terms of glutathione depletion. Co-incubation with the metal chelator diethylenetriaminepentaacetate inhibited these losses, whilst minimal inhibition was seen with superoxide dismutase and catalase treatment. The majority of the activity observed appeared to be contained within aqueous particle extracts.

Conclusion
These data demonstrate that biomass derived particles have considerable oxidative activity, largely attributable to their transition metal content.
MHC II molecules and invariant chain reside in membranes distinct from conventional lipid rafts
Authors: Karacsonyi Claudia , Bedke Tanja , Hinrichsen Nils , Schwinzer Reinhard , Lindner Robert 
Published: October 2005

AbstractMajor histocompatibility complex class II (MHC II) peptide complexes can associate with lipid rafts, and this is a prerequisite for their recruitment to the immunological synapse and for efficient T cell stimulation. One of the most often used criterion for raft association is the resistance to extraction by the detergent Triton X-100 (TX-100) at low temperature. For MHC II, a variety of detergents have been used under different conditions, leading to variable and often conflicting conclusions about the association of MHC II with detergent-resistant membranes (DRMs). To clarify whether these inconsistencies were caused by variations in the isolation protocols or reflect different biochemical properties of MHC II lipid complexes, we used two standardized procedures for the isolation of membranes resistant to TX-100, 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS), or Brij 98. Our results suggest that some of the reported variations in the association of MHC II with DRMs are caused by differences in the methods. We also show that in our hands, specific and efficient flotation of MHC II and the MHC II-associated invariant chain from mouse B-lymphoma cells was only achieved with Brij 98, but not with TX-100 and CHAPS. We furthermore used DRMs prepared from hen egg lysozyme-fed B-lymphoma cells to activate the T cell hybridoma 3A9. In agreement with our biochemical data, T cell activation could only be achieved with Brij 98- but not with TX-100-resistant membranes. Thus, MHC II and also the invariant chain belong to a set of proteins comprising the T cell receptor, prominin, and the prion protein, which reside in membrane environments distinct from conventional lipid rafts.
Leukocyte-versus microparticle-mediated tissue factor transfer during arteriolar thrombus development
Authors: Gross Peter L , Furie Barbara C , Merrill-Skoloff Glenn , Chou Janet , Furie Bruce 
Published: October 2005

AbstractCirculating tissue factor accumulates in the developing thrombus and contributes to fibrin clot formation. To determine whether tissue factor derived from hematopoietic cells is delivered to the thrombus via tissue factor-bearing microparticles or circulating leukocytes expressing tissue factor on the plasma membrane, we compared the kinetics of tissue factor accumulation in the developing arteriolar thrombus with the time course of leukocyte-thrombus interaction and microparticle-thrombus interaction in the microcirculation of a living mouse using intravital high-speed widefield and confocal microscopy. Tissue factor rapidly accumulated in the developing thrombus, appearing immediately following vessel wall injury, reaching a first peak in ∼100 s. In contrast, leukocyte-thrombus interaction was not observed until after 2–3 min following vessel wall injury. Maximal leukocyte rolling and firm leukocyte adherence on thrombi in wild-type mice were observed after ∼8 min and were dependent on P-selectin and P-selectin glycoprotein ligand-1. This delay in P-selectin-dependent leukocyte rolling is a result of time-dependent platelet activation and P-selectin expression on the luminal surface of the thrombus. In contrast, microparticle accumulation in the developing arteriolar thrombus was rapid, and peak accumulation was within 60 s. The accumulation of hematopoietic cell-derived tissue factor in the developing thrombus correlates to the kinetics of microparticle accumulation and does not correlate temporally with leukocyte-thrombus interaction. These results indicate that tissue factor derived from hematopoietic cells is delivered by microparticles during the initial phase of thrombus development in vivo.
Identification of novel mediators of NF-κB through genome-wide survey of monocyte adherence-induced genes
Authors: Diatchenko Luda , Romanov Sergei , Malinina Inga , Clarke Julie , Tchivilev Igor , Li Xiangli , Makarov Sergei S 
Published: October 2005

AbstractThe transcription factor nuclear factor (NF)-κB controls the expression of genes involved in inflammation, cell proliferation, apoptosis, and differentiation. Impaired regulation of NF-κB has been associated with many diseases; thus, there is significant interest in therapeutic approaches based on modulation of this transcription factor. NF-κB activity is controlled by numerous signaling molecules, many of which are potentially to be identified. Monocytes are principal effectors of the immune system, and monocyte adherence is the first step leading to their activation and differentiation. Adherence induces activation of NF-κB, resulting in the induction of proinflammatory genes as well as anti-inflammatory genes, which counterbalance and limit the intensity and duration of NF-κB activation. Here, to identify novel mediators of NF-κB signaling, we used the model of monocyte adherence to perform a systematic, genome-wide survey of adherence-induced genes. Having isolated mRNAs from nonadherent and adherent primary human monocytes, we constructed suppressive subtraction hybridization libraries containing cDNAs, which were differentially regulated by adherence. Of 366 identified differentially expressed genes, most were found to be up-regulated by adherence. Having analyzed a subset of these genes, we found that the library was enriched with inhibitors of NF-κB. Three of those (an orphan nuclear receptor NUR77, a guanosine 5′-diphosphate/guanosine 5′-triphosphate exchange factor RABEX5, and a PRK1-associated protein AWP1) were particularly potent inhibitors of NF-κB activation. Thus, the collection of monocyte adherence-regulated genes represents a rich source for the identification of novel components of the machinery that controls NF-κB activation.
Cocaine and σ-1 receptors modulate HIV infection, chemokine receptors, and the HPA axis in the huPBL-SCID model
Authors: Roth Michael D , Whittaker Katherine M , Choi Ruth , Tashkin Donald P , Baldwin Gayle Cocita 
Published: October 2005

AbstractCocaine is associated with an increased risk for, and progression of, clinical disease associated with human immunodeficiency virus (HIV) infection. A human xenograft model, in which human peripheral blood mononuclear cells were implanted into severe combined immunodeficiency mice (huPBL-SCID) and infected with a HIV reporter virus, was used to investigate the biological interactions between cocaine and HIV infection. Systemic administration of cocaine (5 mg/kg/d) significantly increased the percentage of HIV-infected PBL (two- to threefold) and viral load (100- to 300-fold) in huPBL-SCID mice. Despite the capacity for cocaine to increase corticosterone and adrenocorticotropic hormone levels in control mice, the hypothalamic-pituitary-adrenal axis was suppressed in HIV-infected animals, and corticosterone levels were further decreased when animals were exposed to HIV and cocaine. Activating huPBL in vitro in the presence of 10−8 M cocaine increased expression of CC chemokine receptor 5 (CCR5) and CXC chemokine receptor 4 (CXCR4) coreceptors. Expression of CCR5 was also increased at early time-points in the huPBL-SCID model following systemic exposure to cocaine (54.1±9.4% increase over control, P&lt;0.01). This effect preceded the boost in viral infection and waned as HIV infection progressed. Cocaine has been shown to mediate immunosuppressive effects by activating σ-1 receptors in immune cells in vitro and in vivo. Consistent with these reports, a selective σ-1 antagonist, BD1047, blocked the effects of cocaine on HIV replication in the huPBL-SCID mouse. Our results suggest that systemic exposure to cocaine can enhance HIV infection in vivo by activating σ-1 receptors and by modulating the expression of HIV coreceptors.