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We present a case of cutaneous and systemic infection with Scedosporium apiospermum occurring in a patient with systemic lupus erythematosus. Scedosporium apiospermum is a rare cause of systemic mycosis but is associated with a high rate of mortality in immunocompromised hosts. Because the patient presented in an advanced state of infection, supportive measures were unsuccessful and definitive diagnosis could not be made until postmortem examination. We discuss the presentation, pathology, diagnosis, and treatment strategies for Scedosporium infection.

Amyotrophic lateral sclerosis (ALS) is a fatal neurological disorder characterized by motor neuron degeneration. Mutations in Cu,Zn-superoxide dismutase (SOD1) are responsible for 20% of familial ALS cases via a toxic gain of function. In mutant SOD1 transgenic mice, mitochondria of spinal motor neurons develop abnormal morphology, bioenergetic defects and degeneration, which are presumably implicated in disease pathogenesis. SOD1 is mostly a cytosolic protein, but a substantial portion is associated with organelles, including mitochondria, where it localizes predominantly in the intermembrane space (IMS). However, whether mitochondrial mutant SOD1 contributes to disease pathogenesis remains to be elucidated. We have generated NSC34 motor neuronal cell lines expressing wild-type or mutant SOD1 containing a cleavable IMS targeting signal to directly investigate the pathogenic role of mutant SOD1 in mitochondria. We show that mitochondrially-targeted SOD1 localizes to the IMS, where it is enzymatically active. We prove that mutant IMS-targeted SOD1 causes neuronal toxicity under metabolic and oxidative stress conditions. Furthermore, we demonstrate for the first time neurite mitochondrial fragmentation and impaired mitochondrial dynamics in motor neurons expressing IMS mutant SOD1. These defects are associated with impaired maintenance of neuritic processes. Our findings demonstrate that mutant SOD1 localized in the IMS is sufficient to determine mitochondrial abnormalities and neuronal toxicity, and contributes to ALS pathogenesis.

The magnetic ground state phase diagram of the ferromagnetic Kondo-lattice model is constructed by calculating internal energies of all possible bipartite magnetic configurations of the simple cubic lattice explicitly. This is done in one dimension (1D), 2D and 3D for a local moment of S = 3/2. By assuming saturation in the local moment system we are able to treat all appearing higher local correlation functions within an equation of motion approach exactly. A simple explanation for the obtained phase diagram in terms of bandwidth reduction is given. Regions of phase separation are determined from the internal energy curves by an explicit Maxwell construction., Comment: 8 pages, 6 figures, accepted for publication in PRB (2009)

In this work we compare numerically exact Quantum Monte Carlo (QMC) calculations and Green function theory (GFT) calculations of thin ferromagnetic films including second order anisotropies. Thereby we concentrate on easy plane systems, i.e. systems for which the anisotropy favors a magnetization parallel to the film plane. We discuss these systems in perpendicular external field, i.e. B parallel to the film normal. GFT results are in good agreement with QMC for high enough fields and temperatures. Below a critical field or a critical temperature no collinear stable magnetization exists in GFT. On the other hand QMC gives finite magnetization even below those critical values. This indicates that there occurs a transition from non-collinear to collinear configurations with increasing field or temperature. For slightly tilted external fields a rotation of magnetization from out-of-plane to in-plane orientation is found with decreasing temperature., 7 pages, 9 figures, accepted for publication in PRB

Neurological manifestations in Whipple's disease are highly variable and tend to occur at later stages of the disease. However, isolated, focal neurological symptoms are reported to be rare. Here we describe the successful treatment of a case of cerebral Whipple's disease initially presenting solely with isolated myoclonic jerks of the left hand and forearm evolving to a segmental myoclonus at a later stage. Additionally, we present - to our knowledge - a novel treatment by administration of immunomodulatory therapy (IVIg) in addition to established antibiotics.

A 19-year-old woman presented with a five-year history of guttate macules and yellow to skin-colored papules with collarette of fine scale on the trunk and the upper and lower extremities. Guttate pityriasis lichenoides chronica is an uncommon presentation of this T-cell-mediated disease. It is of unknown etiology; however, an infectious agent has been suspected. It is considered in a spectrum with pityriasis lichenoides et varioloformis acuta and rarely mycosis fungoides and CD30 lymphomas. Improvement has been shown after treatment with oral tetracyclines, ultraviolet B and UVA1 phototherapy, and PUVA photochemotherapy.

A 19-year-old woman presented with a five-year history of guttate macules and yellow to skin-colored papules with collarette of fine scale on the trunk and the upper and lower extremities. Guttate pityriasis lichenoides chronica is an uncommon presentation of this T-cell-mediated disease. It is of unknown etiology; however, an infectious agent has been suspected. It is considered in a spectrum with pityriasis lichenoides et varioloformis acuta and rarely mycosis fungoides and CD30 lymphomas. Improvement has been shown after treatment with oral tetracyclines, ultraviolet B and UVA1 phototherapy, and PUVA photochemotherapy.

Monocyte chemoattractant protein-1 (MCP-1) is an essential chemokine involved in monocyte traffic across endo- and epithelial barriers both in vitro and in vivo. However, the contribution of endothelial MCP-1 signaling via its CCR2 receptor in monocyte adhesion to inflamed endothelium under flow is incompletely understood. A sensitive flow chamber assay was used to assess monocyte adhesion to TNF-α-activated primary human pulmonary artery endothelial cells (HPAEC) during physiological shear stress. Monocyte adhesion was markedly reduced (∼45%) when HPAEC-derived MCP-1 was either neutralized with anti-MCP-1 mAb or inhibited by translational arrest of MCP-1 mRNA transcripts with MCP-1 antisense oligomers. Corresponding efficacy was observed for blockade of monocyte CCR2 receptor function by anti-CCR2 mAb or MCP-1 antagonists (9–76 analog). The impact of endothelial MCP-1 on monocyte-HPAEC adhesion occurred via β2-integrin but not via β1-integrin adhesion pathways. In this line, pretreatment of monocytes with MCP-1 but not RANTES provoked a rapid and transient neoepitope 24 expression on β2-integrin α-chains, as analyzed by increased reporter mAb24 binding. Collectively, our data show an important cross talk of endothelial MCP-1 with monocyte CCR2 effecting monocyte firm adhesion to inflamed HPAEC under physiological flow conditions.

Aim: To describe the clinical practice of the use of voriconazole and posaconazole in lung transplant recipients, since the introduction of posaconazole in 2006. .Method: Data was obtained from medical charts of all lung transplant recipients treated with voriconazole or posaconazole between 2006 and 2011.Results: Eighty-eight patients and 44 patients who received voriconazole and posaconazole contributed data to the study, respectively. The main indications for voriconazole treatment were prophylaxis and pre-emptive invasive fungal infection, and for posaconazole treatment were pre-emptive and probable invasive fungal infection.The treatments were mainly used for aspergillosis. Voriconazole was administered as intravenous and oral formulation (twice daily) at doses of 4.0 ± 0.5mg/kg and 217.0 ± 48.9mg, respectively. Posaconazole was administered orally at total daily doses of 834.7± 130.2mg. Seventy percent and 90% of patients had been received different antifungal agents prior to the voriconazole and posaconazole treatment, respectively. 53% of patients reported adverse effects in the voriconazole group and 12% of patients in the posaconazole group, with hepatotoxicity being the most common adverse effect in the voriconazole (37.4%) and the posaconazole (48.7%) group. Therapeutic drug monitoring was performed in 54% and 53% of patients in the voriconazole and the posaconazole group, respectively. Complete resolved fungal infections were seen at the end of 47.3% of treatment courses in the voriconazole group and 31.3% in the posaconazole group. Introduction of the triazole treatment increased the concentrations of calcineurin inhibitors, which led to dose reduction of tacrolimus in both groups by59.5%, and dose reduction of cyclosporin by 40.8% and 29.4% in the voriconazole and posaconazole group, respectively. Conclusion: Voriconazole has been used commonly for the treatment of invasive fungal infections, but was generally less tolerated. Posaconazole was used less commonly and led to fewer adverse effects. Therapeutic drug monitoring of the triazoles was inconsistent and no conclusion can be drawn about a link between concentrations and adverse effects or treatment response from the current data.

The host protein CPSF6 possesses a domain that can interact with the HIV-1 capsid (CA) protein. CPSF6 has been implicated in regulating HIV-1 nuclear entry. However, its functional significance for HIV-1 replication has yet to be firmly established. Here we provide evidence for two divergent functions of CPSF6 for HIV-1 replication in vivo. We demonstrate that endogenous CPSF6 exerts an inhibitory effect on naturally occurring HIV-1 variants in individuals carrying the HLA-B27 allele. Conversely, we find a strong selective pressure in these individuals to preserve CPSF6 binding, while escaping from the restrictive activity by CPSF6. This active maintenance of CPSF6 binding during HIV-1 CA evolution in vivo contrasts with the in vitro viral evolution, which can reduce CPSF6 binding to evade from CPSF6-mediated restriction. Thus, these observations argue for a beneficial role of CPSF6 for HIV-1 in vivo. CPSF6-mediated restriction renders HIV-1 less dependent or independent from TNPO3, RanBP2 and Nup153, host factors implicated in HIV-1 nuclear entry. However, viral evolution that maintains CPSF6 binding in HLA-B27+ subjects invariably restores the ability to utilize these host factors, which may be the major selective pressure for CPSF6 binding in vivo. Our study uncovers two opposing CA-dependent functions of CPSF6 in HIV-1 replication in vivo; however, the benefit for binding CPSF6 appears to outweigh the cost, providing support for a vital function of CPSF6 during HIV-1 replication in vivo., Author Summary The viral capsid (CA) protein of HIV-1 determines both the ability to infect non-dividing cells and the utilization of host factors implicated in nuclear entry. Understanding how CA controls these two properties is critical. CPSF6, a CA-interacting host protein, may be important for these properties but its precise role remains unclear. Here we provide direct evidence for the involvement of endogenous CPSF6 during HIV-1 infection. We found that CPSF6 blocks CA mutants that are impaired for infection of non-dividing cells. This CPSF6-mediated inhibition also targets early escape variants that arise in HIV-1 infected HLA-B27+ patients. Moreover, this CPSF6-mediated inhibition, together with robust CTL response, appears to be critical for viral suppression, because viruses derived after late viral breakthrough in these individuals were no longer sensitive to the antiviral activity of CPSF6. However, we also report indirect evidence for a potentially beneficial role for CPSF6 in HIV-1 replication, because escape from this inhibition in vivo was paradoxically accompanied by a strict preservation of the CPSF6 binding pocket. These results highlight the unique characteristics of the HIV-CPSF6 interactions in which CPSF6 can be either beneficial or detrimental for viral replication in a CA-specific manner.

The use of serum lactate level to risk-stratify emergency department (ED) patients with sepsis is widely used. Studies in nonsepsis populations also suggest its utility in predicting adverse outcomes. Whether lactate prognosticates equally across disease states is not clearly defined. This study compares the ability of lactate to identify patients at risk for deterioration (intubation, acute renal dysfunction, vasopressor use, or death) and mortality during hospitalization in infected and non-infected populations.

We investigated the micromechanical properties using doses from 1 up to 7 Gray and could observe a roughening on the surface of the bone material in the microscopic range by scanning acoustic microscopic measurements. In addition, a preceding irradiation promoted an extension of microcracks during the polishing process indicating an embrittlement. After irradiation and removal of the surface layer, the SAM measurements indicate a preferential increasing of hardness of softer regions. These results are consistent with our measurements by environmental scanning electron microscopy.

The ring-opening polymerization of epsilon-caprolactone, delta-valerolactone (VL) and D,L-lactide, respectively, in the presence of different proportions of hydroxyapatite (HA) was catalyzed by stannous (II)octoate (SnOct2) at 130 degrees C and resulted in composites. The lactones were almost completely converted to the polymers within a reaction time of 70 up to 240 min. The number-average molecular weights Mn as determined by size exclusion chromatography decreased with increasing content of HA. The initiating efficiency of HA as calculated from the difference of the polymerization degrees P. obtained with and without HA turned out to be relatively low with ca. 11 to 0.5% for 1 to 80 wt% HA, respectively. For the polymerization of VL, the initiating efficiency of HA was on the average threefold higher. The quantitative proof of non-extractable polymer on HA by means of thermogravimetric analysis, fourier transform infrared spectroscopy with photoacoustic detection and differential scanning calorimetry confirmed the initiating efficiency of HA as mentioned above. This poly(lactone) can be debound from HA by treatment with aqueous HCl. Hence it is assumed to be ionically bound.

The internal structure and failure of crazes in linear and long-chain branched poly(styrene) (PS) were investigated by means of in situ transmission electron microscopy (TEM). It was found that long-chain branched PS presents more finely fibrillated up to homogeneous crazes at room temperature instead of the typical fibrillated ones for linear PS. The failure of homogeneous crazes in long-chain branched PS indicates a more ductile behavior than the fibrillated ones. The microhardness of these materials was measured, and it was seen that the hardness value increased with increasing amount of long branches in the PS. In addition, the rate of creep under the indenter (creep constant) for these materials was investigated. The lowest value for the creep constant corresponded to the PS sample with the largest amount of long branches.

Myeloperoxidase (MPO), an enzyme that is highly expressed in neutrophil leukocytes, transforms precarcinogens such as benzo(a)pyrene and aromatic amines to highly reactive intermediates. A G/A polymorphism located 463 bp upstream of exon 1 in the promoter region strongly reduces MPO mRNA expression. In a matched case-control study, 196 lung cancer, 245 laryngeal cancer, and 255 pharyngeal cancer patients from the Berlin area were investigated for frequency of the G-463A polymorphism by PCR/RFLP, using AciI. They were matched by age and gender to hospital patients without known malignancies. Moreover, 270 healthy volunteers were genotyped, obtaining 61.1% of individuals with MPO genotype -463G/G, 34.8% of individuals with genotype G/A, and 4.1% of individuals with genotype A/A. In lung and laryngeal cancer patients, but not in pharyngeal cancer patients, mutant genotypes were significantly less frequent. Crude odds ratios for carriers of one or two A alleles, compared to wild-type G/G, were 0.58 [95% confidence interval (CI), 0.38-0.88; P = 0.011] for lung cancer patients, 0.63 (95% CI, 0.43-0.92; P = 0.017) for laryngeal cancer patients, and 0.82 (95% CI, 0.57-1.17; P = 0.27) for pharyngeal cancer patients. The relative risks, adjusted for age, gender, and extent of cigarette smoking were 0.47 (95% CI, 0.28-0.79; P = 0.004), 0.66 (95% CI, 0.44-1.01; P = 0.054), and 0.75 (95% CI, 0.51-1.12; P = 0.16) for lung, larynx, and pharyngeal cancer, respectively. Strikingly, relative risk for carriers of -463A among adenocarcinoma of the lung was 0.24 (95% CI, 0.10-0.58; P = 0.002). Two cases with larynx cancer, one case with lung cancer, and one reference subject displayed novel G/A mutations at -297 nucleotide and -296 nucleotide, destroying a constitutive AciI cleavage site. Our data finally suggest that the MPO -463A variant is a protective factor in the etiology of lung and larynx cancer, but possibly not of pharyngeal cancer.

Acute dissecting thoracic aortic aneurysm is a rare cause of chest pain in young adults. Patients require prompt surgical treatment to reduce the high risk of early mortality. This report describes the case of a young Army officer who developed a dissecting aortic aneurysm in Mogadishu, Somalia, during Operation Continue Hope. Moving the patient from an isolated hostile country to a location where definitive surgical treatment could be quickly performed presented a significant challenge. Military physicians who may be deployed to isolated locations should be familiar with this unusual cause of chest pain and be prepared to rapidly evacuate patients to facilities that can treat them.

The transcription factor, Nuclear Factor of Activated T cells (NFAT) is a major target for p21ras and calcium signalling pathways in the IL-2 gene and is induced by p21ras signals acting in synergy with calcium/calcineurin signals. One p21ras effector pathway involves the MAP kinase ERK-2, and we have examined its role in NFAT regulation. Expression of dominant negative MAPKK-1 prevents NFAT induction. Constitutively active MAPKK-1 fully activates ERK-2 and the transcription factor Elk-1, but does not substitute for activated p21ras and synergize with calcium/calcineurin signals to induce NFAT. Expression of dominant negative N17Rac also prevents TCR and p21ras activation of NFAT, but without interfering with the ERK-2 pathway. The transcriptional activity of the NFAT binding site is mediated by a complex comprising a member of the NFAT group and AP-1 family proteins. The induction of AP-1 by p21ras also requires Rac-1 function. Activated Rac-1 could mimic activated p21ras to induce AP-1 but not to induce NFAT. Moreover, the combination of activated MAPKK-1 and Rac-1 could not substitute for activated p21ras and synergize with calcium signals to induce NFAT. Thus, p21ras regulation of NFAT in T cells requires the activity of multiple effector pathways including those regulated by MAPKK-1/ERK-2 and Rac-1.

Twenty acutely traumatised patients with a rupture of the anterior talofibular ligament were studied by MRI. The results of 3D-studies were correlated with conventional stress x-ray studies. The ruptured ligament was directly visualised in all cases as a thickened structure of high signal intensity. In case of complete ruptured ligaments free flowing ligamentous structures were seen in the signal intense exudation in the ankle joint. MRI can help to decide between surgery or conservative therapy.

Eight of 13 children pre- or perinatally infected with the HIV virus subsequently developed neurological symptoms. Three children also had other nonspecific symptoms (fever, lymphadenopathy, diarrhoea, hepatosplenomegaly, failure to thrive and mucocutaneous thrush). Five children developed illnesses associated with AIDS (opportunistic infections, cachexia and lymphocytic interstitial pneumonia). The neurological abnormalities predominantly affected motor functions, only later also involving sensory ones. Motor, cognitive and language development was impaired in all eight children. A loss of developmental milestones occurred in three children with HIV encephalopathy: they have since died. In all the children the HIV infection caused symptoms within the first year, progressing more quickly in the three with encephalopathy. There were no discernible risk factors to account for the difference in the course of the disease.

Before I address nuclear cooperation in Latin America, it is important to understand the Brazilian government’s policy on nuclear energy. It is based on the following principles, derived from Brazil’s constitution: To ensure the country’s sovereignty. To further the fundamental aims of national development, eradication of poverty and reduction of social and regional discrepancies. To support the principles underlying Brazil’s international relations — national independence, self-determination of nations, nonintervention, equality among nations, defence of the peace, peaceful resolution of conflict and cooperation among nations for the progress of mankind.

We have used polyclonal and monoclonal antibodies raised against calf thymus profilin to localize the corresponding protein in translocating, spreading, and stationary rat fibroblasts. Immunofluorescence of whole cells and immunogold labeling on ventral membranes of lysis-squirted cells showed that profilin was markedly enriched in the highly dynamic lamellipodia or pseudopodial lobes. Within these regions, a significant fraction was colocalized with dynamic actin filaments organized in actin ribs, cortical filaments, or stress fiber-like bundles, and little profilin was found in membrane areas appearing free of actin. In contrast, stress fibers of stationary cells as well as actin arcs and ring-like bundles of spreading and migrating cells showed very little label. These results are discussed in context with the proposed role of profilin in regional membrane dynamics typical for fibroblasts and are compared to previous data (Hartwig et al.: J. Cell Biol. 109:1571-1579, 1989) on profilin distribution in platelets and granulocytes.

16099 Background: Constitutive NF-κB activation is observed in prostate cancer and represents a predictor for biochemical recurrence after radical prostatectomy. Heightened activation of NF-κB is o...

Acute dissecting thoracic aortic aneurysm is a rare cause of chest pain in young adults. Patients require prompt surgical treatment to reduce the high risk of early mortality. This report describes the case of a young Army officer who developed a dissecting aortic aneurysm in Mogadishu, Somalia, during Operation Continue Hope. Moving the patient from an isolated hostile country to a location where definitive surgical treatment could be quickly performed presented a significant challenge. Military physicians who may be deployed to isolated locations should be familiar with this unusual cause of chest pain and be prepared to rapidly evacuate patients to facilities that can treat them.

Raman spectra have been obtained from silica aerogel, a porous low‐density material having grain sizes near 70 A. The Raman spectra are qualitatively similar to those from fused silica, thus indicating that the aerogel is amorphous. However, a greatly intensified peak (relative to ordinary fused silica) occurs near 478 cm−1 and is assigned to small rings, e.g., six (3‐SiO) or eight (4‐SiO) membered. Such rings may be more important in the aerogel than in fused silica, but the observed absence of the 600 cm−1 ring peak indicates that only one ring type, e.g., eight membered, is predominant. Other marked frequency and intensity changes in the Si–O–Si bending and Si–O stretching region, compared to fused silica, were also observed.

Production of rho ^{0}, K*^{0}, and phi have been measured in proton-proton collisions at the CERN Intersecting Storage Rings (ISR) at low p/sub T/ in the central region. The transverse mass spectra are well described by exp (-a mu /sub T/), with a=-6.4+or-0.2 GeV/sup -1/. The cross sections for d sigma /dy mod /sub y=0/ are 6.5+or-0.8+or-1.2 mb for rho ^{0}, 1.9+or-0.3+or-0.3 mb for K*^{0}, 1.9+or-0.3+or-0.3 mb for K*^{0}, and 0.60+or-0.12+or-0.13 mb for phi , where the first error is statistical and the second is systematic.

The associated charged particle multiplicities of high-p/sub T/ pi /sup 0/ and single-photon events were measured at the CERN intersecting storage rings using lead/liquid-argon calorimeters and a scintillation counter array placed around the intersection region. The average multiplicity on the trigger side for the single-photon events was found to be significantly lower than that for the pi /sup 0/ events. The away-side multiplicity for both pi /sup 0/ and single- photon events increases with the trigger particle p/sub T/, but, at a fixed p/sub T/, the direct photon sample was found to have a slightly lower average multiplicity. The differences in the event structure can be explained if a large fraction of the single photons are produced via qg to gamma q constituent scattering. (16 refs).

The central detector of the Axial Field Spectrometer (AFS) is a cylindrical drift chamber using a "bicycle-wheel" geometry. Its design has been optimized for jet-like events with high track densities. This is accomplished through a high degree of azimuthal segmentation (4° sectors) with up to 42 space points per track, using measurements of drift time and charge division. Particle identification in the non-relativistic region is obtained by (dE/dx) sampling. The detector is operated in an inhomogeneous magnetic field at event rates of typically > 5 × 105 collisions per second. Preliminary results will be presented on the detector performance achieved after the first months of operation at the ISR.

We study the production of identified charged particles in pp collisions at a c.m. energy of 63 GeV in events with an identified high-pT trigger particle. The measurements were performed at the CERN Intersecting Storage Rings using the Axial Field Spectrometer. Production ratios are presented as a function of pT in the range 2.5 to 8 GeV/c.

The central detector of the Axial Field Spectrometer (AFS) is a cylindrical drift chamber using a bicycle-wheel geometry. Its design has been optimized for jet-like events with high track densities. This is accomplished through a high degree of azimuthal segmentation (4/sup 0/ sectors) with up to 42 space points per track, using measurements of drift time and charge division. Particle identification in the non-relativistic region is obtained by (dE/dx) sampling. The detector is operated in an inhomogeneous magnetic field at event rates of typically 5 x 10/sup 5/ collisions per second. Preliminary results will be presented on the detector performance achieved after one year of operation at the ISR.

Divorce is a definite crisis period during which the nuclear family disintegrates. The dissolution and reorganizing process of divorce extends to children as well as to parents (Despert, 1953). Children of spouses obtaining a divorce can be seriously affected by the divorce process. The parents are in conflict and their ability to support and nurture their children is substantially decreased. Divorce may kindle in the children conflicts of loyalty to the respective parents (Schoen & Nelson, 1974). The children may become pawns in the parents’ displacement of anger, jealousy, raw hurt or embarrassed guilt. The children may also be required to accommodate two different patterns of living and two sets of values. Divorce is typically characterized as an abbreviated legal procedure with court proceedings as the final episode. The reality is that the separation and divorce process is a long one which can involve arguments, physical abuse, threats, and violent disagreements long before and after the adu...

Physical properties have been measured dynamically at relevant high pressures and temperatures for three materials thought to constitute the outer planets.