bluuebunny/crossref_metadata_2025 huggingface dataset:
Infective Endocarditis
Authors: Peters Priscilla J.
Published: June 2005

Infective endocarditis is a life-threatening illness associated with significant morbidity and mortality. Previously a uniformly fatal disease, antibiotic therapy has reduced the mortality of native valve endocarditis to less than 20%. The incidence of infective endocarditis has not decreased, however, and 20,000 new cases are reported each year. Continued improvement in the prognosis of endocarditis is largely dependent on early and accurate diagnosis of the disease and its complications. Echocardiography has assumed an important role in the evaluation of infective endocarditis, both for the detection of vegetations and in the assessment of complications of the infectious process.
Spermatic Cord Torsion in the Neonate: A False Negative by Sonography
Authors: Reidman Daniel A. , Peterson Andrew C. , Allen Robert C.
Published: June 2005

Multiple challenges are encountered in the evaluation and treatment of spermatic cord torsion in the neonate, including confident evaluation and treatment. The authors report a full-term male presenting with multiple birth-related injuries, including suspected torsion of the spermatic cord, at 22 hours of life. Diagnostic Doppler sonography study was normal. This case is an example in which a high clinical index of suspicion, despite a reassuring sonographic examination, guided the appropriate therapy for salvaging a viable testicle with torsion of the spermatic cord.
Sonographic Evaluation of Chronic Venous Insufficiency in Right Heart Failure
Authors: Abbas Manzoor , Yahya Mohd Mazri , Hamilton Mark , Mwipatayi B. Patrice , Sieunarine Kishore
Published: June 2005

Clinical and sonographic findings of three octogenarian patients with recent-onset venous insufficiency with venous ulcer were evaluated with clinical examination and venous duplex scanning. The venous duplex findings in the affected lower limb of patients with right heart failure showed phasic flow in the long saphenous vein. The phasic flow was traced back up to the inferior vena cava and the hepatic veins. Echocardiogram confirmed marked tricuspid regurgitation. Clinically, a simple compression of the sapheno-femoral junction showed an absence of pulsation in the long saphenous veins, giving clinical confirmation that venous backflow caused the pulsation in the limb veins. Right heart failure in patients with late-onset venous insufficiency and venous ulcer should be suspected. Sonography complemented with clinical examination is the key to the proper evaluation and management of chronic venous insufficiency with right heart failure.
Papillary Thyroid Cancer: A Classic Example
Authors: Kuntz Kathryn M. , Youngs Diane J.
Published: June 2005

Palpable thyroid nodules can be seen on sonograms with a high degree of accuracy. Although most thyroid nodules are benign, it is important to recognize the sonographic features that make a nodule worrisome for malignancy. Thyroid cancer often appears sonographically as solid and hypoechoic. Fine punctate internal calcifications within a hypoechoic solid mass are features commonly seen with papillary thyroid cancer, which is the most common form of thyroid malignancy.
Pediatric Echocardiography
Authors: Witt Sandra A.
Published: June 2005

When evaluating congenital heart disease, echocardiography is a powerful diagnostic tool. The availability, mobility, diagnostic accuracy, and noninvasive nature of echocardiography provide distinct advantages over other diagnostic modalities such as cardiac catheterization. Pediatric echocardiography has distinct differences from echocardiography performed on adults. First, the scanning techniques employed are tailored to the smaller size and younger age of the pediatric age group. Second, the types of diseases for which echocardiography is employed are necessarily different and usually consist of complex congenital lesions.
Relation between oxidation/crystallization and degassing upon reheating of basalt glass from Kilauea, Hawaii
Authors: Burkhard D. J. M.
Published: June 2005

Basalt glass from Kilauea, Hawaii (SBG) starts to crystallize upon heat treatment in air at ∽840°C. In addition, oxidation takes place. The kinetics of both processes may be readily quantified though the mechanism is difficult to access. This work investigates the relationship between these processes, crystallization and oxidation, and the escape of volatiles from the glass/liquid upon reheating. Evolved gas analyses and differential scanning calorimetry are the techniques used. In addition, isothermal heat treatment in argon is carried out in order to eliminate the external reason for oxidation, the oxygen gradient, and to focus on intrinsic oxidation. Products are examined with 57Fe Mössbauer spectroscopy. As expected, degassing temperatures of SBG, and of two MORB samples, considered for comparison, are above the glass transition temperature. We find no convincing evidence of intrinsic oxidation. Degassing is likely to induce interface-controlled crystallization.
Ilmenite exsolution in olivine from the serpentinite body at Zöblitz, Saxonian Erzgebirge – microstructural evidence using EBSD
Authors: Massonne H.-J. , Neuser R. D.
Published: June 2005

In the large serpentinite body at Zöblitz, which is part of the Gneiss-Eclogite Unit of the Saxonian Erzgebirge, ilmenite rods have been detected in olivine. Although these rods are ≤1 μm wide, they can be unequivocally identified as ilmenite using electron backscatter diffraction. We also applied this method to prove that ilmenite is topotactically intergrown with the olivine host ([100]ol ‖ [001]ilm). This relation was found previously, e.g. for ilmenite exsolved from olivine of garnet peridotite from Alpe Arami, Swiss Alps. The degree of this exsolution phenomenon in the Alpe Arami rocks was taken as an indication of the original formation of a Ti-bearing mineral at depths of ∽300 km. As in the olivines of the serpentinite from Zöblitz, the density of the ilmenite rods is significantly less than in the rock from Alpe Arami. We think that our observation is compatible with previous P-T estimates of close to 4 GPa and 1000–1100°C for the ultramafic bodies in the central Saxonian Erzgebirge.
A silica-deficient, shallow-marine zeolite assemblage in the Foveaux Formation, Bluff Peninsula, New Zealand
Authors: Coombs D. S. , Bosel C. A. , Kawachi Y. , Paterson L. A.
Published: June 2005

A gonnardite-thomsonite-chabazite-calcite assemblage forms a cement in the Foveaux Formation, a fossiliferous gabbroic boulder bed that accumulated at the base of a sea cliff cut in a Permian igneous complex during late Oligocene±early Miocene time. Gonnardite was the earliest zeolite to form, locally following minor calcite. It was followed epitaxially by thomsonite, co-precipitating with chabazite. Crystal habits indicate a low-temperature origin. The maximum temperature to which the deposit may have been subjected is estimated as not more than ∽30°C. The chabazites are Ca-poor chabazite-K and chabazite-Na. Representative electron microprobe analyses are as follows, all + nH2O:

thomsonite: Na3.77Ca7.73(Al19.39Si20.65)O80 and Na3.78K0.04Ca7.25Mg0.05(Al19.13Si21.05)O80;

gonnardite: Na6.95K0.03Ca4.73(Al16.99Si23.15)O80 and Na8.56K0.03Ca4.05(Al17.32Si22.84)O80;

chabazite-K: Na1.18K1.72Ca0.08Mg0.23(Al3.51Si8.49)O24 and Na1.67K1.92Ca0.18Mg0.17(Al4.11Si7.85)O24;

chabazite-Na: Na2.51K1.13Ca0.17Mg0.02(Al4.08Si7.93)O24.

Such a Si-poor zeolite assemblage is unusual for marine sediments and is attributed to precipitation from marine water impoverished in silica in the gabbroic boulder bed and interacting with shell material and calcic plagioclase. In contrast, a dioritic clast in the boulder bed provides an example of less silica-poor zeolites originally formed in the parent igneous complex. Veinlets in the clast contain scolecite averaging Na1.19Ca7.36(Al15.84Si24.14)O80.nH2O, and mesolite averaging Na5.13K0.03Ca5.24 (Al15.93Si24.13)O80.nH2O, in part as sub-microscopic intergrowths. The composition of scolecite closely corresponds to the most Na-rich scolecite reported hitherto.
Identification of mixite minerals – an SEM and Raman spectroscopic analysis
Authors: Frost R. L. , Weier M. , Martens W. , Duong L.
Published: June 2005

Two mixites from Boss Tweed Mine, Tintic District, Juab County, Utah and Tin Stope, Majuba Hill, Pershing County, Nevada, USA, were analysed by scanning electron microscopy (SEM) with energy dispersive X-ray (EDX) analysis and by Raman spectroscopy. The SEM images show the mixite crystals to be elongated fibres up to 200 μm long and 2 μm wide. Detailed images of the mixite crystals show the mineral to be composed of bundles of fibres. The EDX analyses depend on the crystal studied, though the Majuba mixite gave analyses which matched the formula BiCu6(AsO4)3(OH)6.3H2O. Raman bands observed in the 880–910 cm−1 and 867–870 cm−1 regions are assigned to the AsO-stretching vibrations of (HAsO4)2− and (H2AsO4)− units, whilst bands at 803 and 833 cm−1 are assigned to the stretching vibrations of uncomplexed (AsO4)3- units. Intense bands observed at 473.7 and 475.4 cm−1 are assigned to the v4 bending mode of AsO4 units. Bands observed at 386.5, 395.3 and 423.1 cm−1 are assigned to the v2 bending modes of the HAsO4 (434 and 400 cm−1) and the AsO4 groups (324 cm−1). Raman spectroscopy lends itself to the identification of minerals on host matrices and is especially useful for the identification of mixites.
Determination of the Eu(II)/Eu(III) ratios in minerals by X-ray absorption near-edge structure (XANES) and its application to hydrothermal deposits
Authors: Takahashi Y. , Kolonin G. R. , Shironosova G. P. , Kupriyanova I. I. , Uruga T. , Shimizu H.
Published: June 2005

Europium LIII-edge X-ray absorption near-edge structure (XANES) was employed to determine the Eu(II)/Eu(III) ratios in minerals. This ratio can be determined based on the peak-area ratio of white lines, the resonance peak, in normalized XANES spectra for Eu(II) and Eu(III) species. For precise determination of the Eu(II)/Eu(III) ratios, however, it was revealed that the transition probabilities for each individual Eu(II) and Eu(III) species in the system must be quantified, because we found that the peak area in normalized XANES spectra is different in each Eu(II) and Eu(III) species. Despite this ambiguity, the method was applied to Eu in natural hydrothermal apatites (Eu = 39 and 64 ppm) and fluocerite (Eu = 282 ppm). The relationship between the Eu(II)/Eu(III) ratio in these hydrothermal minerals, and the distribution coefficients of Eu(II) and Eu(III) were discussed, taking into account Eu anomalies in their REE patterns. It is considered that by combining the Eu(II)/Eu(III) ratios determined by XANES and the degree of Eu anomaly in REE patterns, we can provide new information on the distribution of Eu(II) and Eu(III) in various geochemical studies.
Myeloma cells block RUNX2/CBFA1 activity in human bone marrow osteoblast progenitors and inhibit osteoblast formation and differentiation
Authors: Giuliani Nicola , Colla Simona , Morandi Francesca , Lazzaretti Mirca , Sala Roberto , Bonomini Sabrina , Grano Maria , Colucci Silvia , Svaldi Mirija , Rizzoli Vittorio
Published: June 2005

Decreased bone formation contributes to the development of bone lesions in multiple myeloma (MM) patients. In this study, we have investigated the effects of myeloma cells on osteoblast formation and differentiation and the potential role of the critical osteoblast transcription factor RUNX2/CBFA1 (Runt-related transcription factor 2/core-binding factor Runt domain α subunit 1) in the inhibition of osteoblastogenesis in MM. We found that human myeloma cells suppress the formation of human osteoblast progenitors in bone marrow (BM) cultures. Moreover, an inhibitory effect on osteocalcin, alkaline phosphatase, collagen I mRNA, protein expression, and RUNX2/CBFA1 activity by human preosteoblastic cells was observed in cocultures with myeloma cells. The inhibitory effect was more pronounced in the cell-to-cell contact conditions compared with those without the contact and involved the very late antigen 4 (VLA-4) integrin system. Among the soluble osteoblast inhibitors screened, we show the potential contribution of interleukin-7 (IL-7) in the inhibitory effect on osteoblast formation and RUNX2/CBFA1 activity by human myeloma cells in coculture. Finally, our in vitro results were supported in vivo by the finding of a significant reduction in the number of Runx2/Cbfa1-positive cells in the BM biopsies of patients with MM who had osteolytic lesions compared with those who did not have bone lesions, suggesting the critical involvement of RUNX2/CBFA1 in the decreased bone formation in MM. (Blood. 2005;106:2472-2483)
Induction of autotaxin by the Epstein-Barr virus promotes the growth and survival of Hodgkin lymphoma cells
Authors: Baumforth Karl R. N. , Flavell Joanne R. , Reynolds Gary M. , Davies Gillian , Pettit Trevor R. , Wei Wenbin , Morgan Susan , Stankovic Tanya , Kishi Yasuhiro , Arai Hiroyuki , Nowakova Marketa , Pratt Guy , Aoki Junken , Wakelam Michael J. O. , Young Lawrence S. , Murray Paul G.
Published: June 2005

A proportion of patients with Hodgkin lymphoma carry Epstein-Barr virus (EBV), an oncogenic herpesvirus, in their tumor cells. Although it is generally assumed that EBV contributes to the malignant phenotype of Hodgkin lymphoma cells, direct evidence in support of this is lacking. Here we show that EBV infection of Hodgkin lymphoma cells results in the induction of autotaxin, a secreted tumor-associated factor with lysophospholipase-D activity. Up-regulation of autotaxin increased the generation of lysophosphatidic acid (LPA) and led to the enhanced growth and survival of Hodgkin lymphoma cells, whereas specific down-regulation of autotaxin decreased LPA levels and reduced cell growth and viability. In lymphoma tissues, autotaxin expression was mainly restricted to CD30+ anaplastic large-cell lymphomas and Hodgkin lymphoma; in the latter, high levels of autotaxin were strongly associated with EBV positivity (P = .006). Our results identify the induction of autotaxin and the subsequent generation of LPA as key molecular events that mediate the EBV-induced growth and survival of Hodgkin lymphoma cells and suggest that this pathway may provide opportunities for novel therapeutic intervention. (Blood. 2005;106:2138-2146)
Antineutrophil cytoplasm antibodies directed against myeloperoxidase augment leukocyte-microvascular interactions in vivo
Authors: Little Mark A. , Smyth C. Lucy , Yadav Rashmi , Ambrose Lyn , Cook H. Terence , Nourshargh Sussan , Pusey Charles D.
Published: June 2005

Systemic small vessel vasculitis is associated with antineutrophil cytoplasm antibodies (ANCAs). While there is mounting in vitro evidence to suggest that ANCAs are capable of enhancing leukocyte-endothelial interactions, no in vivo evidence for this has been provided. In this study a novel rat model of ANCA-associated experimental autoimmune vasculitis (EAV), induced by immunization with human myeloperoxidase (MPO), was used to analyze directly the potential effect of ANCAs on leukocyte-venular wall interactions in vivo as observed by intravital microscopy. These rats developed anti-MPO antibodies directed against rat leukocytes, showed pathologic evidence of small vessel vasculitis, and had enhanced leukocyte adhesion and transmigration in response to the chemokine Groα (CXCL1 [CXC ligand 1]). Passive transfer of immunoglobulin from rats with EAV to naive rats conferred enhanced adhesion and transmigration responses in the recipients. Furthermore, rats with EAV and recipients of ANCA-positive immunoglobulin developed extensive microvascular injury, as manifested by mesenteric hemorrhage, in response to CXCL1. This study provides the first direct in vivo evidence for the ability of ANCAs to enhance leukocyteendothelial interactions and cause microvascular hemorrhage, thereby providing a mechanism by which ANCAs could exert pathogenic effects in systemic vasculitis. (Blood. 2005;106:2050-2058)
Recurrent retroviral vector integration at the Mds1/Evi1 locus in nonhuman primate hematopoietic cells
Authors: Calmels Boris , Ferguson Cole , Laukkanen Mikko O. , Adler Rima , Faulhaber Marion , Kim Hyeoung-Joon , Sellers Stephanie , Hematti Peiman , Schmidt Manfred , von Kalle Christof , Akagi Keiko , Donahue Robert E. , Dunbar Cynthia E.
Published: June 2005

Recent reports linking insertional activation of LMO2 following gene therapy for X-linked severe combined immunodeficiency (X-SCID) have led to a re-evaluation of risks following gene therapy with retroviral vectors. In our analysis of 702 integration sites in rhesus macaques that underwent transplantation up to 7 years earlier with autologous CD34+ cells transduced with amphotropic murine leukemia virus (MLV)-derived retroviral vectors containing marker genes, we detected insertion into one locus, the Mds1/Evi1 region, a total of 14 times in 9 animals. Mds1/Evi1 integrations were observed stably long term, primarily in myeloid cells. We hypothesize that this over-representation likely results from an impact on the self-renewal and engraftment potential of CD34+ progenitor cells via insertional mutagenesis at this specific locus. There is no evidence of ongoing in vivo clonal expansion of the Mds1/Evi1 populations, and all animals are hematologically normal without evidence for leukemia. Characterization of integration sites in this relevant preclinical model provides critical information for gene therapy risk assessment as well as identification of genes controlling hematopoiesis. (Blood. 2005;106:2530-2533)
Natural-killer cells and dendritic cells: “l'union fait la force”
Authors: Walzer Thierry , Dalod Marc , Robbins Scott H. , Zitvogel Laurence , Vivier Eric
Published: June 2005

Several recent publications have focused on the newly described interactions between natural-killer (NK) cells and dendritic cells (DCs). Activated NK cells induce DC maturation either directly or in synergy with suboptimal levels of microbial signals. Immature DCs appear susceptible to autologous NK-cell-mediated cytolysis while mature DCs are protected. NK-cell-induced DC activation is dependent on both tumor necrosis factor-α (TNF-α)/interferon-γ (IFN-γ) secretion and a cell-cell contact involving NKp30. In vitro, interleukin-12 (IL-12)/IL-18, IL-15, and IFN-α/β production by activated DCs enhance, in turn, NK-cell IFN-γ production, proliferation, and cytotoxic potential, respectively. In vivo, NK-cell/DC interactions may occur in lymphoid organs as well as in nonlymphoid tissues, and their consequences are multiple. By inducing DC activation, NK-cell activation induced by tumor cells can indirectly promote antitumoral T-cell responses. Reciprocally, DCs activated through Toll-like receptors (TLRs) induce potent NK-cell activation in antiviral responses. Thus, DCs and NK cells are equipped with complementary sets of receptors that allow the recognition of various pathogenic agents, emphasizing the role of NK-cell/DC crosstalk in the coordination of innate and adaptive immune responses.
Nuclear substructure reorganization during late-stage erythropoiesis is selective and does not involve caspase cleavage of major nuclear substructural proteins
Authors: Krauss Sharon Wald , Lo Annie J. , Short Sarah A. , Koury Mark J. , Mohandas Narla , Chasis Joel Anne
Published: June 2005

Enucleation, a rare feature of mammalian differentiation, occurs in 3 cell types: erythroblasts, lens epithelium, and keratinocytes. Previous investigations suggest that caspase activation functions in lens epithelial and keratinocyte enucleation, as well as in early erythropoiesis encompassing erythroid burst-forming unit (BFU-E) differentiation to proerythroblast. To determine whether caspase activation contributes to later erythropoiesis and whether nuclear substructures other than chromatin reorganize, we analyzed distributions of nuclear subcompartment proteins and assayed for caspase-induced cleavage of subcompartmental target proteins in mouse erythroblasts. We found that patterns of lamin B in the filamentous network interacting with both the nuclear envelope and DNA, nuclear matrix protein NuMA (Nuclear mitotic apparatus), and splicing factors Sm and SC35 persisted during nuclear condensation, consistent with effective transcription of genes expressed late in differentiation. Thus, nuclear reorganization prior to enucleation is selective, allowing maintenance of critical transcriptional processes independent of extensive chromosomal reorganization. Consistent with these data, we found no evidence for caspase-induced cleavage of major nuclear subcompartment proteins during late erythropoiesis, in contrast to what has been observed in early erythropoiesis and in lens epithelial and keratinocyte differentiation. These findings imply that nuclear condensation and extrusion during terminal erythroid differentiation involve novel mechanisms that do not entail major activation of apoptotic machinery. (Blood. 2005;106:2200-2205)
Analysis of multiple biomarkers shows that lymphoma-associated macrophage (LAM) content is an independent predictor of survival in follicular lymphoma (FL)
Authors: Farinha Pedro , Masoudi Hamid , Skinnider Brian F. , Shumansky Karey , Spinelli John J. , Gill Karamjit , Klasa Richard , Voss Nicolas , Connors Joseph M. , Gascoyne Randy D.
Published: June 2005

We studied the role of multiple biomarkers in determining outcome in follicular lymphoma (FL), concentrating in particular on the role of benign macrophages. The study group consisted of uniformly staged and treated patients with FL enrolled in a phase 2 trial between 1987 and 1993. All patients were younger than 61 years of age, had advanced-stage FL, and were treated with a multiagent chemotherapy regimen, BP-VACOP (bleomycin, cisplatin, etoposide, doxorubicin, cyclophosphamide, vincristine, and prednisone), followed by involved region radiation. The median follow-up of living patients was 12.5 years, and the median survival was 16.3 years. The International Prognostic Index (IPI) was predictive of overall survival (OS) (P = .003). Biopsy specimens from all cases were stained with an anti-CD68 antibody. Of the 99 evaluable patients with FL, 87 had less than 15 CD68+ macrophages/high-power field (hpf) (median, 7; range, 1-14) and 12 had more than 15 CD68+ macrophages/hpf (median, 20; range, 16-25) with a median OS of 16.3 vs 5.0 years, respectively (P < .001). A multivariate Cox model that included the IPI score, the histologic grade, and the lymphoma-associated macrophage (LAM) score, showed IPI and LAM to be independent predictors of OS (P = .009 and P = .004, respectively). The LAM content of FL predicts survival, and these data support a prominent role for nonneoplastic immune cells in the biology of FL. (Blood. 2005;106:2169-2174)
Synthetic hepcidin causes rapid dose-dependent hypoferremia and is concentrated in ferroportin-containing organs
Authors: Rivera Seth , Nemeth Elizabeta , Gabayan Victoria , Lopez Miguel A. , Farshidi Dina , Ganz Tomas
Published: June 2005

Hepcidin is the principal iron regulatory hormone and its overproduction contributes to anemia of inflammation (AI). In vitro, hepcidin binds to and induces the degradation of the exclusive iron exporter ferroportin. We explored the effects and distribution of synthetic hepcidin in the mouse. A single intraperitoneal injection of hepcidin caused a rapid fall of serum iron in a dose-dependent manner, with a 50-μg dose resulting in iron levels 80% lower than in control mice. The full effect was seen within only 1 hour, consistent with a blockade of iron export from tissue stores and from macrophages involved in iron recycling. Serum iron remained suppressed for more than 48 hours after injection. Using radiolabeled hepcidin, we demonstrated that the serum concentration of hepcidin at the 50-μg dose was 1.4 μM, consistent with the inhibitory concentration of 50% (IC50) of hepcidin measured in vitro. Radiolabeled hepcidin accumulated in the ferroportin-rich organs, liver, spleen, and proximal duodenum. Our study highlights the central role of the hepcidin-ferroportin interaction in iron homeostasis. The rapid and sustained action of a single dose of hepcidin makes it an appealing agent for the prevention of iron accumulation in hereditary hemochromatosis. (Blood. 2005;106:2196-2199)
Chlamydophila pneumoniae induces expression of Toll-like Receptor 4 and release of TNF-α and MIP-2 via an NF-κB pathway in rat type II pneumocytes
Authors: Wissel Heide , Schulz Christian , Koehne Petra , Richter Ekkehard , Maass Matthias , Rüdiger Mario
Published: June 2005

Background

The role of alveolar type II cells in the regulation of innate and adaptive immunity is unclear. Toll-like receptors (TLRs) have been implicated in host defense. The purpose of the present study was to investigate whether Chlamydophila pneumoniae (I) alters the expression of TLR2 and/orTLR4 in type II cells in a (II) Rho-GTPase- and (III) NF-κB-dependent pathway, subsequently (IV) leading to the production of (IV) pro-inflammatory TNF-α and MIP-2.

Methods

Isolated rat type II pneumocytes were incubated with C. pneumoniae after pre-treatment with calcium chelator BAPTA-AM, inhibitors of NF-κB (parthenolide, SN50) or with a specific inhibitor of the Rho-GTPase (mevastatin). TLR2 and TLR4 mRNA expressions were analyzed by PCR. Activation of TLR4, Rac1, RhoA protein and NF-κB was determined by Western blotting and confocal laser scan microscopy (CLSM) and TNF-α and MIP-2 release by ELISA.

Results

Type II cells constitutively expressed TLR4 and TLR2 mRNA. A prominent induction of TLR4 but not TLR2 mRNA was detected after 2 hours of incubation with C. pneumoniae. The TLR4 protein expression reached a peak at 30 min, began to decrease within 1–2 hours and peaked again at 3 hours. Incubation of cells with heat-inactivated bacteria (56°C for 30 min) significantly reduced the TLR4 expression. Treated bacteria with polymyxin B (2 μg/ml) did not alter TLR4 expression. C. pneumoniae-induced NF-κB activity was blocked by TLR4 blocking antibodies. TLR4 mRNA and protein expression were inhibited in the presence of BAPTA-AM, SN50 or parthenolide. TNF-α and MIP-2 release was increased in type II cells in response to C. pneumoniae, whereas BAPTA-AM, SN50 or parthenolide decreased the C. pneumoniae-induced TNF-α and MIP-2 release. Mevastatin inhibited C. pneumoniae-mediated Rac1, RhoA and TLR4 expression.

Conclusion

The TLR4 protein expression in rat type II cells is likely to be mediated by a heat-sensitive C. pneumoniae protein that induces a fast Ca2+-mediated NF-κB activity, necessary for maintenance of TLR4 expression and TNF-α and MIP-2 release through possibly Rac and Rho protein-dependent mechanism. These results indicate that type II pneumocytes play an important role in the innate pulmonary immune system and in inflammatory response mechanism of the alveolus.
Genome-wide localization of mobile elements: experimental, statistical and biological considerations
Authors: Martinez-Vaz Betsy M , Xie Yang , Pan Wei , Khodursky Arkady B
Published: June 2005

Background

The distribution and location of insertion elements in a genome is an excellent tool to track the evolution of bacterial strains and a useful molecular marker to distinguish between closely related bacterial isolates. The information about the genomic locations ofISelements is available in public sequence databases. However, the locations of mobile elements may vary from strain to strain and within the population of an individual strain. Tools that allowde novolocalization ofISelements and are independent of existing sequence information are essential to map insertion elements and advance our knowledge of the role that such elements play in gene regulation and genome plasticity in bacteria.

Results

In this study, we present an efficient and reliable method for linear mapping of mobile elements using whole-genome DNA microarrays. In addition, we describe an algorithm for analysis of microarray data that can be applied to find DNA sequences physically juxtaposed with a target sequence of interest. This approach was used to map the locations of theIS5elements in the genome ofEscherichia coliK12. AllIS5elements present in theE. coligenome known from GenBank sequence data were identified. Furthermore, previously unknown insertion sites were predicted with high sensitivity and specificity. Two variants ofE. coliK-12 MG1655 within a population of this strain were predicted by our analysis. The only significant difference between these two isolates was the presence of anIS5element upstream of the main flagella regulator,flhDC. Additional experiments confirmed this prediction and showed that these isolates were phenotypically distinct. The effect ofIS5on the transcriptional activity of motility and chemotaxis genes in the genome ofE. colistrain MG1655 was examined. Comparative analysis of expression profiles revealed that the presence ofIS5results in a mild enhancement of transcription of the flagellar genes that translates into a slight increase in motility.

Conclusion

In summary, this work presents a case study of an experimental and analytical application of DNA microarrays to map insertion elements in bacteria and gains an insight into biological processes that might otherwise be overlooked by relying solely on the available genome sequence data.
(TG/CA)n repeats in human gene families: abundance and selective patterns of distribution according to function and gene length
Authors: Sharma Vineet K , Brahmachari Samir K , Ramachandran Srinivasan
Published: June 2005

Background

Creation of human gene families was facilitated significantly by gene duplication and diversification. The (TG/CA)n repeats exhibit length variability, display genome-wide distribution, and are abundant in the human genome. Accumulation of evidences for their multiple functional roles including regulation of transcription and stimulation of recombination and splicing elect them as functional elements. Here, we report analysis of the distribution of (TG/CA)n repeats in human gene families.

Results

The 1,317 human gene families were classified into six functional classes. Distribution of (TG/CA)n repeats were analyzed both from a global perspective and from a stratified perspective based on their biological properties. The number of genes with repeats decreased with increasing repeat length and several genes (53%) had repeats of multiple types in various combinations. Repeats were positively associated with the class of Signaling and communication whereas, they were negatively associated with the classes of Immune and related functions and of Information. The proportion of genes with (TG/CA)n repeats in each class was proportional to the corresponding average gene length. The repeat distribution pattern in large gene families generally mirrored the global distribution pattern but differed particularly for Collagen gene family, which was rich in repeats. The position and flanking sequences of the repeats of Collagen genes showed high conservation in the Chimpanzee genome. However the majority of these repeats displayed length polymorphism.

Conclusion

Positive association of repeats with genes of Signaling and communication points to their role in modulation of transcription. Negative association of repeats in genes of Information relates to the smaller gene length, higher expression and fundamental role in cellular physiology. In genes of Immune and related functions negative association of repeats perhaps relates to the smaller gene length and the directional nature of the recombinogenic processes to generate immune diversity. Thus, multiple factors including gene length, function and directionality of recombinogenic processes steered the observed distribution of (TG/CA)n repeats. Furthermore, the distribution of repeat patterns is consistent with the current model that long repeats tend to contract more than expand whereas, the reverse dynamics operates in short repeats.
Synaptic and genomic responses to JNK and AP-1 signaling in Drosophila neurons
Authors: Etter Paul D , Narayanan Radhakrishnan , Navratilova Zaneta , Patel Chirag , Bohmann Dirk , Jasper Heinrich , Ramaswami Mani
Published: June 2005

Background

The transcription factor AP-1 positively controls synaptic plasticity at the Drosophila neuromuscular junction. Although in motor neurons, JNK has been shown to activate AP-1, a positive regulator of growth and strength at the larval NMJ, the consequences of JNK activation are poorly studied. In addition, the downstream transcriptional targets of JNK and AP-1 signaling in the Drosophila nervous system have yet to be identified. Here, we further investigated the role of JNK signaling at this model synapse employing an activated form of JNK-kinase; and using Serial Analysis of Gene Expression and oligonucleotide microarrays, searched for candidate early targets of JNK or AP-1 dependent transcription in neurons.

Results

Temporally-controlled JNK induction in postembryonic motor neurons triggers synaptic growth at the NMJ indicating a role in developmental plasticity rather than synaptogenesis. An unexpected observation that JNK activation also causes a reduction in transmitter release is inconsistent with JNK functioning solely through AP-1 and suggests an additional, yet-unidentified pathway for JNK signaling in motor neurons. SAGE profiling of mRNA expression helps define the neural transcriptome in Drosophila. Though many putative AP-1 and JNK target genes arose from the genomic screens, few were confirmed in subsequent validation experiments. One potentially important neuronal AP-1 target discovered, CG6044, was previously implicated in olfactory associative memory. In addition, 5 mRNAs regulated by RU486, a steroid used to trigger conditional gene expression were identified.

Conclusion

This study demonstrates a novel role for JNK signaling at the larval neuromuscular junction and provides a quantitative profile of gene transcription in Drosophila neurons. While identifying potential JNK/AP-1 targets it reveals the limitations of genome-wide analyses using complex tissues like the whole brain.
Gender and age differences among current smokers in a general population survey
Authors: John Ulrich , Hanke Monika , Meyer Christian , Schumann Anja
Published: June 2005

Background

Evidence suggests a higher proportion of current smokers among female than among male ever smokers at the age above 50. However, little is known about the proportion of current smokers among ever smokers in old age groups with consideration of women in comparison to men from general population samples. The goal was to analyze the proportions of current smokers among female and among male ever smokers including those older than 80.

Methods

Cross-sectional survey study with a national probability household sample in Germany. Data of 179,472 participants aged 10 or older were used based on face-to-face in-home interviews or questionnaires. The proportions of current smokers among ever smokers were analyzed dependent on age, age of onset of smoking and cigarettes per day including effect modification by gender.

Results

Proportions of current smokers tended to be larger among female than among male ever smokers aged 40 or above. Women compared to men showed adjusted odds ratios of 1.7 to 6.9 at ages 40 to 90 or older in contrast to men. No such interaction existed for age of onset of smoking or cigarettes per day.

Conclusion

Special emphasis should be given to current smokers among the female general population at the age of 40 or above in public health intervention.
The use of simplified verbal autopsy in identifying causes of adult death in a predominantly rural population in Ethiopia
Authors: Lulu Kidest , Berhane Yemane
Published: June 2005

Background

Information on adult mortality is essentially non-existent in Ethiopia particularly from rural areas where access to health services is limited and most deaths occur at home. This study was conducted with the aim of identifying causes of adult death in a rural population of Ethiopia using a simplified verbal autopsy instrument.

Methods

All deaths in the age-group 15–49 years during the period of 1995–99 were taken from computerized demographic surveillance database maintained by the Butajira Rural Health Program. Data on the causes of death were collected from close relatives of the deceased persons by lay interviewers. Causes of death were diagnosed using "expert algorithm" programmed onto a computer.

Results

The major causes of death were acute febrile illnesses (25.2%), liver diseases (11.3%), diarrheal diseases (11.1%), tuberculosis (9.7%) and HIV/AIDS (7.4%). Overall communicable diseases accounted for 60.8% of the deaths. The high levels of mortality from communicable diseases reflect the poor socioeconomic development of the country, and the general poor coverage of health and education services in rural Ethiopia. The tools used in this study can easily be added-on to the numerous health surveys conducted in the country.

Conclusion

The simplified approach to verbal autopsy diagnosis can produce useful data that can effectively guide priority health interventions in rural areas where routine information system is either very weak or non-existent.
Is complementary and alternative medicine (CAM) cost-effective? a systematic review
Authors: Herman Patricia M , Craig Benjamin M , Caspi Opher
Published: June 2005

Background

Out-of-pocket expenditures of over $34 billion per year in the US are an apparent testament to a widely held belief that complementary and alternative medicine (CAM) therapies have benefits that outweigh their costs. However, regardless of public opinion, there is often little more than anecdotal evidence on the health and economic implications of CAM therapies. The objectives of this study are to present an overview of economic evaluation and to expand upon a previous review to examine the current scope and quality of CAM economic evaluations.

Methods

The data sources used were Medline, AMED, Alt-HealthWatch, and the Complementary and Alternative Medicine Citation Index; January 1999 to October 2004. Papers that reported original data on specific CAM therapies from any form of standard economic analysis were included. Full economic evaluations were subjected to two types of quality review. The first was a 35-item checklist for reporting quality, and the second was a set of four criteria for study quality (randomization, prospective collection of economic data, comparison to usual care, and no blinding).

Results

A total of 56 economic evaluations (39 full evaluations) of CAM were found covering a range of therapies applied to a variety of conditions. The reporting quality of the full evaluations was poor for certain items, but was comparable to the quality found by systematic reviews of economic evaluations in conventional medicine. Regarding study quality, 14 (36%) studies were found to meet all four criteria. These exemplary studies indicate CAM therapies that may be considered cost-effective compared to usual care for various conditions: acupuncture for migraine, manual therapy for neck pain, spa therapy for Parkinson's, self-administered stress management for cancer patients undergoing chemotherapy, pre- and post-operative oral nutritional supplementation for lower gastrointestinal tract surgery, biofeedback for patients with "functional" disorders (eg, irritable bowel syndrome), and guided imagery, relaxation therapy, and potassium-rich diet for cardiac patients.

Conclusion

Whereas the number and quality of economic evaluations of CAM have increased in recent years and more CAM therapies have been shown to be of good value, the majority of CAM therapies still remain to be evaluated.
Use of pIVEX plasmids for protein overproduction in Escherichia coli
Authors: Rogé Julie , Betton Jean-Michel
Published: June 2005

Background

The pIVEX plasmids are vectors optimized for expression in the Rapid Translation System (RTS) cell-free system under control of bacteriophage T7 transcription elements. Even if these plasmids are intended for use in vitro, it is usually worthwhile to compare both cell-free and bacterial expression from the same genetic construct. However, some RTS users encountered problems when they introcuded these plasmids into Escherichia coli host strains producing the T7 RNA polymerase.

Results

We verified that difficulties in transforming the commonly used BL21(λDE3) strain with pIVEX arose from the presence of a strong T7 promoter combined with a high-copy number plasmid, independent of gene expression. When these vectors were introduced into this strain harboring a compatible plasmid carrying the lactose repressor (lacI), we improved the transformation efficiency by 4 orders of magnitude. Moreover, we designed a transformation protocol that allows, after induction, the overproduction of pIVEX-encoded proteins in the BL21(λDE3) strain.

Conclusion

Using the correct plasmid/host combination and transformation-expression protocol, we could directly compare overproduction of the same pIVEX-encoded proteins from both in vivo and in vitro expression systems.
Diethylcarbamazine activity against Brugia malayimicrofilariae is dependent on inducible nitric-oxide synthase and the cyclooxygenase pathway
Authors: McGarry Helen F , Plant Leigh D , Taylor Mark J
Published: June 2005

Background

Diethylcarbamazine (DEC) has been used for many years in the treatment of human lymphatic filariasis. Its mode of action is not well understood, but it is known to interact with the arachidonic acid pathway. Here we have investigated the contribution of the nitric oxide and cyclooxygenase (COX) pathways to the activity of DEC against B. malayi microfilariae in mice.

Methods

B. malayi microfilariae were injected intravenously into mice and parasitaemia was measured 24 hours later. DEC was then administered to BALB/c mice with and without pre-treatment with indomethacin or dexamethasone and the parasitaemia monitored. To investigate a role for inducible nitric oxide in DEC's activity, DEC and ivermectin were administered to microfilaraemic iNOS-/- mice and their background strain (129/SV). Western blot analysis was used to determine any effect of DEC on the production of COX and inducible nitric-oxide synthase (iNOS) proteins.

Results

DEC administered alone to BALB/c mice resulted in a rapid and profound reduction in circulating microfilariae within five minutes of treatment. Microfilarial levels began to recover after 24 hours and returned to near pre-treatment levels two weeks later, suggesting that the sequestration of microfilariae occurs independently of parasite killing. Pre-treatment of animals with dexamethasone or indomethacin reduced DEC's efficacy by almost 90% or 56%, respectively, supporting a role for the arachidonic acid and cyclooxygenase pathways in vivo. Furthermore, experiments showed that treatment with DEC results in a reduction in the amount of COX-1 protein in peritoneal exudate cells. Additionally, in iNOS-/- mice infected with B. malayi microfilariae, DEC showed no activity, whereas the efficacy of another antifilarial drug, ivermectin, was unaffected.

Conclusion

These results confirm the important role of the arachidonic acid metabolic pathway in DEC's mechanism of action in vivo and show that in addition to its effects on the 5-lipoxygenase pathway, it targets the cyclooxygenase pathway and COX-1. Moreover, we show for the first time that inducible nitric oxide is essential for the rapid sequestration of microfilariae by DEC.
Long-term survival after an aggressive surgical resection and chemotherapy for stage IV pulmonary giant cell carcinoma
Authors: Shoji Fumihiro , Maruyama Riichiroh , Okamoto Tatsuro , Ikeda Jiro , Nakamura Tomomi , Wataya Hiroshi , Ichinose Yukito
Published: June 2005

Background

Pulmonary giant cell carcinoma is one of the rare histological subtypes with pleomorphic, sarcomatoid or sarcomatous elements. The prognosis of patients with this tumor tends to be poor, because surgery, irradiation and chemotherapy are not usually effective.

Case presentation

We herein report a patient with pulmonary giant cell carcinoma with stage IV disease in whom aggressive multi-modality therapy resulted in a long-term survival. A 51-year-old male underwent an emergent operation with a partial resection of small intestinal metastases due to bleeding from the tumor. The patient also underwent a left pneumonectomy due to hemothorax as a result of the rapid growth of the primary tumor. Thereafter, two different regimens of chemotherapy and a partial resection for other site of small intestinal metastases and a splenectomy for splenic metastases were performed. The patient is presently doing well without any evidence of recurrence for 3 years after the initial operation.

Conclusion

This is a first report of a rare case with stage IV pulmonary giant cell carcinoma who has survived long-term after undergoing aggressive surgical treatment and chemotherapy.
The impact of glucose-insulin-potassium infusion in acute myocardial infarction on infarct size and left ventricular ejection fraction [ISRCTN56720616]
Authors: van der Horst Iwan CC , Ottervanger Jan Paul , van 't Hof Arnoud WJ , Reiffers Stoffer , Miedema Kor , Hoorntje Jan CA , Dambrink Jan-Henk E , Gosselink AT Marcel , Nijsten Maarten WN , Suryapranata Harry , de Boer Menko-Jan , Zijlstra Felix
Published: June 2005

Background

Favorable clinical outcomes have been observed with glucose-insulin-potassium infusion (GIK) in acute myocardial infarction (MI). The mechanisms of this beneficial effect have not been delineated clearly. GIK has metabolic, anti-inflammatory and profibrinolytic effects and it may preserve the ischemic myocardium. We sought to assess the effect of GIK infusion on infarct size and left ventricular function, as part of a randomized controlled trial.

Methods

Patients (n = 940) treated for acute MI by primary percutaneous coronary intervention (PCI) were randomized to GIK infusion or no infusion. Endpoints were the creatinine kinase MB-fraction (CK-MB) and left ventricular ejection fraction (LVEF). CK-MB levels were determined 0, 2, 4, 6, 24, 48, 72 and 96 hours after admission and the LVEF was measured before discharge.

Results

There were no differences between the two groups in the time course or magnitude of CK-MB release: the peak CK-MB level was 249 ± 228 U/L in the GIK group and 240 ± 200 U/L in the control group (NS). The mean LVEF was 43.7 ± 11.0 % in the GIK group and 42.4 ± 11.7% in the control group (P = 0.12). A LVEF ≤ 30% was observed in 18% in the controls and in 12% of the GIK group (P = 0.01).

Conclusion

Treatment with GIK has no effect on myocardial function as determined by LVEF and by the pattern or magnitude of enzyme release. However, left ventricular function was preserved in GIK treated patients.