julilili42/papers huggingface dataset:
The adhesion molecule L1 (CD171) promotes melanoma progression
2006-02-27

Abstract The adhesion molecule L1 is expressed in primary melanomas and cutaneous metastases in contrast to melanocytic nevi and melanocytes, and is significantly associated with metastatic spread. Recent studies have demonstrated that in carcinomas L1 expression is associated with sustained activation of the extracellular signal‐regulated kinase (ERK) pathway and upregulation of ERK‐dependent, motility‐ and invasion‐associated gene products including αvβ3 integrin. The objective of this study was to further investigate the role of the adhesion molecule L1 in melanoma progression, and to evaluate whether targeting the L1 adhesion molecule would have therapeutic effects against invasive melanoma growth. Using human melanoma cells from different stages of progression in monolayer and organotypic human skin culture mimicking the pathophysiological environment of cutaneous melanoma, we found that (1) L1 expression mostly correlates with melanoma progression and αvβ3 integrin expression, (2) overexpression of L1 in early radial growth phase melanoma cells promotes conversion from radial to vertical growth phase melanoma without upregulation of αvβ3 integrin expression, and (3) suppression of L1 function significantly reduces migration and invasion of melanoma cells, but does not completely block invasive melanoma growth. Altogether, L1 plays a critical role in melanoma invasion and progression and offers therapeutic potential in combination with conventional anticancer agents. © 2006 Wiley‐Liss, Inc.
Pretreatment social functioning predicts 1‐year outcome in early onset psychosis
2006-02-27

Objective: The aim was to investigate the association of pretreatment social functioning (12 months before initial presentation) with symptom dimensions and social functioning at 1‐year follow‐up. Method: Fifty‐six adolescents, age 14–18, first admitted for early onset psychosis, were evaluated at baseline and 1‐year follow‐up assessing psychopathology (PANSS), social functioning (Strauss and Carpenter Prognostic Scale), and duration of untreated psychosis (DUP). Results: Adolescents with low pretreatment social functioning were at risk of more severe negative symptoms and lower social functioning at follow‐up. Negative symptoms at baseline were less predictive and DUP was not predictive in this sample. Conclusion: Results of this study suggest a strong longitudinal inter‐relatedness between social functioning and negative symptoms in this age group. An integrative treatment approach including family interventions, social skills training, long‐term specialized work/school rehabilitation, and adequate antipsychotic treatment is warranted to improve both, social functioning and negative symptoms.
The tryptase positive compact round cell infiltrate of the bone marrow (TROCI-BM): a novel histopathological finding requiring the application of lineage specific markers
2006-02-27

Aims: Compact tryptase-positive round cell infiltrates of the bone marrow (TROCI-BM) are very rare histopathological findings and may pose challenging problems with regard to the cell type involved (either mast cells or basophilic granulocytes) and the exact diagnosis. Methods: A selected panel of immunohistochemical markers against mast cell and basophil related antigens, including CD25, CD34, CD117/Kit, and the 2D7 antigen (which is found only in basophilic granulocytes) on a total of 410 routinely processed bone marrow biopsy specimens (including 88 cases of systemic mastocytosis (SM), 20 cases of chronic myeloid leukaemia (CML), 92 cases of myeloid neoplasms other than CML, and 210 controls with normal/reactive bone marrows). Results: In total, 17 cases with TROCI-BM could be identified: 11 SM (including two cases of well-differentiated SM and two mast cell leukaemias; MCL), 2 myelomastocytic leukaemia (MML), 2 CML with excess of basophils (secondary basophilic leukaemia (CMLba)), and 2 tryptase positive acute myeloid leukaemia (AML). Regarding the cell types involved, TROCI-BM cells were found to express CD117/Kit in all cases of SM and MCL. In MML and tryptase postitive AML, TROCI-BM cells were found to coexpress CD34 and Kit. The basophil specific antigen 2D7 was only detected in CD34/Kit negative TROCI-BM cells in two patients with CMLba. The activating point mutation D816V was detected in 8/11 patients with SM but not in any of the other haematological malignancies. Conclusions: In summary, a total of six rare myeloid neoplasms may present with a novel immunohistochemical phenomenon tentatively termed TROCI-BM.
An unusual case of systemic mastocytosis associated with chronic lymphocytic leukaemia (SM-CLL)
2006-02-27

Aims: Whereas focal accumulations of reactive lymphocytes around mast cell (MC) infiltrates are often seen in indolent systemic mastocytosis (ISM) involving the bone marrow, an association of systemic mastocytosis (SM) with malignant lymphoma/lymphatic leukaemia is very rare. This report contributes to the differential diagnosis of ISM by demonstrating that such lymphocytic aggregates may be neoplastic. Methods: Biopsy specimens (bone marrow and gastrointestinal mucosa) of a 69 year old woman with mild blood lymphocytosis and a history of urticaria pigmentosa-like skin lesions that had disappeared a few years earlier, were investigated immunohistochemically using antibodies against CD3, CD5, CD20, CD23, CD25, CD34, CD117, chymase, and tryptase. Rearrangements of the IgH and TCRy genes were studied by seminested PCR. Mutation analysis of c- kit was performed by melting point analysis of nested PCR using amplified DNA from pooled microdissected single cells (MC and B cells) of both sites. Results: The histomorphological features of the bone marrow corresponded to that of ISM with multifocal accumulations of MC surrounded by clusters of lymphocytes of mature appearance. However, these lymphocytes revealed an aberrant immunophenotype with coexpression of CD5, CD20, and CD23, thus enabling the final diagnosis of SM with an associated clonal haematological non-MC lineage disease, in particular SM with associated B cell chronic lymphocytic leukaemia (SM-CLL). Monoclonality for both ISM and B-CLL could be confirmed by demonstrating the typical activating c-kit point mutation D816V in bone marrow MC, and a monoclonal IgH rearrangement in bone marrow B cells. Conclusions: Usually, focal accumulations of lymphocytes around MC infiltrates in the bone marrow of patients with SM are reactive in nature (lymphocytosis). However, a low grade malignant lymphoma should also be included in the differential diagnosis. We describe here the first case, to our knowledge, with synchronous diagnosis of SM and associated B-CLL. This diagnosis could only be established by application of appropriate immunohistochemical and molecular techniques, as the bone marrow histology on first investigation resembled that of typical ISM.
Multiple reflections and diffuse scattering in Bragg scattering at optical lattices
2006-02-27

We study Bragg scattering at 1D atomic lattices. Cold atoms are confined by\\noptical dipole forces at the antinodes of a standing wave generated inside a\\nlaser-driven cavity. The atoms arrange themselves into an array of lens-shaped\\nlayers located at the antinodes of the standing wave. Light incident on this\\narray at a well-defined angle is partially Bragg-reflected. We measure\\nreflectivities as high as 30%. In contrast to a previous experiment devoted to\\nthe thin grating limit [S. Slama, et al., Phys. Rev. Lett. 94, 193901 (2005)]\\nwe now investigate the thick grating limit characterized by multiple\\nreflections of the light beam between the atomic layers. In principle multiple\\nreflections give rise to a photonic stop band, which manifests itself in the\\nBragg diffraction spectra as asymmetries and minima due to destructive\\ninterference between different reflection paths. We show that close to\\nresonance however disorder favors diffuse scattering, hinders coherent multiple\\nscattering and impedes the characteristic suppression of spontaneous emission\\ninside a photonic band gap.\\n
Modulation of Visual Stimulus Discrimination by Sustained Focal Attention: An MEG Study
2006-02-27

Sustained attention facilitates target detection. The component that is localized in the parieto-occipital cortex in the noncued condition is thought to reflect a transient shift of attention toward the target location.
Randomized Dose-Escalation Study Evaluating Peginterferon Alfa-2a in Patients With Metastatic Malignant Melanoma
2006-02-28

Purpose A pegylated interferon, peginterferon alfa-2a (PEG-IFNα-2a; 40 kd), has the potential for improved tumor response and survival with lower toxicity than IFNα. This open-label, randomized study evaluated the safety, tolerability, and efficacy of subcutaneous PEG-IFNα-2a in patients with metastatic malignant melanoma (stage IV American Joint Committee on Cancer staging system). Patients and Methods PEG-IFNα-2a was administered subcutaneously at 180 (n = 48), 360 (n = 53), or 450 μg (n = 49) once weekly for 24 weeks, with maintenance therapy for responders. Efficacy was assessed by the proportion of patients with complete response (CR) or partial response (PR). Results The major response rate (CR or PR) was 6% in the 180-μg group (CR, 2%; PR, 4%), 8% in the 360-μg group (CR, 2%; PR, 6%), and 12% in the 450-μg group (CR, 6%; PR, 6%). The times to achieve a major response, duration of major response, rate of disease progression, and 12-month survival were similar between groups, although overall median survival was significantly different among the three groups (P = .0136). More patients required dose adjustment for safety reasons in the higher dose groups, but PEG-IFNα-2a was generally well tolerated, with few withdrawals because of adverse events (6%, 19%, and 16% in the 180-, 360-, and 450-μg groups, respectively). The most common adverse events were fatigue, pyrexia, and nausea. Conclusion PEG-IFNα-2a at doses up to 450 μg once weekly has shown good tolerability and similar efficacy to conventional IFNα and monochemotherapy in stage IV metastatic melanoma.
Malarial Parasites vs. Antimalarials: Never-Ending Rumble in the Jungle
2006-02-28

Development of resistance is an increasing problem for antimalarial chemotherapy because resistance against most available drugs has developed in the majority of world-wide parasite populations. Therefore, several strategies to counteract resistance-development are in place. From the pharmaceutical side, identification of new targets and compounds, development of structural relatives of known antimalarials, and fixed combination therapy are pursued. On the other hand, clinical studies focus on novel regimens, distribution schemes and drug combinations. A third possibility to diminish progression of resistance is the application of evolutionary concepts to design new strategies for validation, monitoring and interference with the selection-process that leads to the spread of multidrug-resistance. Since the pharmacologic and clinical side of antimalarial chemotherapy is covered by recent reviews we refer to the newest developments only and lay our focus on determinants of selection for drug resistance in human malaria.
Outcome and prognostic factors in adrenocortical cancer after complete tumor resection
2006-02-28

Objective: Adrenocortical cancer (ACC) is a rare and highly malignant neoplasm. Reliable data on outcome and prognosis are still limited. Due to improved imaging modalities a majority of patients is currently diagnosed with a localised tumor amenable to complete surgical removal. Optimum treatment and follow up of these patients is a matter of debate, and predictors of outcome in patients with seemingly complete tumor resection remain to be established.
Proteolytic Release of Soluble UL16-Binding Protein 2 from Tumor Cells
2006-03-01

Abstract The MHC class I–related ligands of the immunoreceptor NKG2D are frequently expressed by tumor cells and stimulate tumor immunity mediated by CD8 T cells and natural killer (NK) cells. In humans, NKG2D ligands (NKG2DL) are encoded by the MHC-encoded MIC and non–MHC-encoded UL16-binding protein (ULBP) families of proteins. Recently, we and others showed that tumor cells release soluble MICA (sMICA), thereby counteracting NKG2D-mediated tumor immunosurveillance. Here, we now report that ULBP2 molecules are likewise released from tumor cells in a processed soluble form, and that soluble ULBP2 (sULBP2) can be detected in sera of some patients with hematopoietic malignancies. Tumor cell–derived sULBP2 as opposed to cell-bound ULBP2 does not down-regulate NKG2D on NK cells. Unexpectedly, the glycosylphosphatidylinositol-anchored ULBP2 molecules are not released by phospholipases but by the action of metalloproteases. Proteolytic shedding of both NKG2D ligands MICA and ULBP2 by tumor cells was strongly enhanced after phorbol 12-myristate 13-acetate treatment and paralleled by a markedly reduced susceptibility to NKG2D-mediated cytotoxicity. Shedding of MICA and ULBP2 can be blocked by the same inhibitors, suggesting the involvement of related metalloproteases. Thus, our data suggest that reducing NKG2DL surface densities is due to a common cleavage process executed by metalloproteases that promotes escape of tumors from NKG2D-mediated immunosurveillance. (Cancer Res 2006; 66(5): 2520-6)
Perfusion MR Imaging with FAIR True FISP Spin Labeling in Patients with and without Renal Artery Stenosis: Initial Experience
2006-03-01

The purpose of this study was to prospectively evaluate an arterial spin-labeling technique, flow-sensitive alternating inversion-recovery (FAIR) true fast imaging with steady-state precession (FISP), for noninvasive quantification of renal perfusion in patients without a history of renal artery stenosis (RAS) and in patients with proved RAS. The study was approved by the local ethics committee, and all participants provided written informed consent. Six patients with hypertension but no history of renal artery disease and 12 patients with RAS underwent FAIR true FISP magnetic resonance (MR) imaging in a whole-body 1.5-T unit. RAS grade and scintigraphic perfusion data served as the reference standards. On the FAIR true FISP perfusion images, severe RAS (>70% luminal narrowing) could be clearly distinguished from no or mild RAS and moderate RAS (< or =70% luminal narrowing) (P < .005). Significant correlations between FAIR perfusion data and stenosis grade (r = -0.76) and between FAIR and single photon emission computed tomographic perfusion values (r = 0.83) were observed. FAIR true FISP was found to be suitable for quantitative perfusion imaging of the kidneys in patients with RAS.
Multipolar Radiofrequency Ablation with Internally Cooled Electrodes: Experimental Study in ex Vivo Bovine Liver with Mathematic Modeling
2006-03-01

Multipolar RF ablation with three bipolar applicators may produce large volumes of confluent coagulation ex vivo. A compromise is necessary between prolonged RF ablations at lower power outputs, which produce larger volumes of coagulation, and faster RF ablations at higher power outputs, which produce smaller volumes of coagulation.
Histone deacetylase inhibitors induce cell death and enhance the susceptibility to ionizing radiation, etoposide, and TRAIL in medulloblastoma cells
2006-03-01

Histone deacetylase inhibitors (HDIs) are a promising new class of antineoplastic agents with the ability to induce apoptosis and growth arrest of cancer cells. In addition, HDIs have been suggested to enhance the anticancer efficacy of other therapeutic regimens, such as ionizing radiation (IR) or chemotherapy. The objective of this study was to evaluate the activity of HDIs against medulloblastoma cells when applied either as single agents or in combination with IR, cytostatics, or TRAIL. The HDIs, suberoyl anilide hydroxamic acid (SAHA), sodium butyrate, and trichostatin A, were examined for their effects on the medulloblastoma cell lines, DAOY and UW228-2. We found that treatment with HDIs induced the dissipation of mitochondrial membrane potential, activation of caspase-9 and -3 and, consequently, apoptotic cell death. Moreover, all three HDIs significantly enhanced the cytotoxic effects of IR in DAOY cells. Likewise, treatment with SAHA markedly augmented the cytotoxicity of etoposide, while it had no effect on vincristine-mediated cell death. HDIs also potently increased the killing efficiency of TRAIL. TRAIL-induced, but not SAHA-induced, cell killing could be prevented by the caspase-8 inhibitor, z-IEDT-fmk. We conclude that HDIs may be useful for the treatment of medulloblastoma as monotherapy and particularly when given in combination with IR, appropriate cytostatics, or TRAIL.
Atrial Linear Lesions: Feasibility Using Cryoablation
2006-03-01

Background: Long linear lesions are created in the left atrium to modify the atrial substrate, thereby curing atrial fibrillation. The creation of long linear left atrial lesions using radiofrequency (RF) ablation is time consuming and difficult. Furthermore, it might result in significant complications. Cryoablation might overcome some of the disadvantages of RF ablation. Therefore, the aim of our study was to assess whether the creation of a long linear lesion is possible using cryotherapy. Methods: A right atrial septal linear lesion was created in six pigs (median weight: 50 kg; range: 40–60 kg). The ablation procedure was performed with a 7‐F Freezor cryocatheter. The nonfluoroscopic mapping system LocaLisa was used as a navigation tool. At each point, freezing was maintained at the lowest attainable temperature (−75°C) for 4 minutes. The CARTO system was used for the evaluation of the linear lesions. Furthermore, all animals were sacrificed immediately after the ablation procedure and a postmortem examination of the lesions was performed. Additionally, an analysis of the amplitudes of the intracardiac electrograms registered via the ablation catheter was performed before and after the ablation procedure. Results: A right atrial septal linear lesion could be created successfully in all six pigs. For the performance of this ablation line, a median number of 16 cryoapplications (range, 11–26) was necessary. The amplitudes of the intracardiac electrograms registered via the ablation catheter decreased significantly after ablation. The CARTO bipolar voltage map revealed very low potentials along the ablation line and showed a sharply demarcated ablation area at the septum in all pigs. Further analysis of the CARTO map revealed an incomplete conduction block in all cases. Most of the pigs had a small gap close to the fossa ovalis. The postmortem examination of 2,3,5‐triphenyl‐tetrazolium chloride‐stained specimens showed sharply demarcated lesions without any ulcerations. There were no major complications during the procedure. Conclusions: The creation of long linear lesions using cryoablation is feasible and safe. Lesion characteristics are different and more favorable than those created by RF. However, the aim of creating a transmural lesion and a complete conduction block remains an unsolved problem even with current cryoablation techniques. Nevertheless, growing experience and technical improvements might overcome some of the current limitations of this new technique.
Optimized contrast-enhanced CT protocols for diagnostic whole-body 18F-FDG PET/CT: technical aspects of single-phase versus multiphase CT imaging.
2006-03-01

Multiphase CT protocols presented a technical disadvantage represented by suboptimal image coregistration compared with single-phase protocols. Nevertheless, multiphase protocols are technically feasible and should be considered for patients who will benefit from a contrast-enhanced multiphase CT examination for diagnosis.
Spinal cord injury–induced expression of the immune-regulatory chemokine interleukin-16 caused by activated microglia/macrophages and CD8+ cells
2006-03-01

Object Spinal cord injury (SCI) elicits a strong inflammatory response that readily participates in lipid oxygenation, edema formation, apoptotic cell death, and tissue remodeling. Because cytokines determine the postinjury inflammatory milieu, the authors analyzed the expression of the immunomodulatory chemokine interleukin-16 (IL-16) after SCI. Methods The authors detected a highly significant, persistent, lesional accumulation of parenchymal IL-16 + microglia/macrophages, which reached a maximal level 3 days postinjury compared with control rats. The majority of cells that demonstrated positive labeling for IL-16 also had positive labeling for ED1 (&gt; 70%) and OX-8/CD8; these cells exhibited the morphological hallmarks of activated microglia/macrophages and pronounced MHC Class II expression. In contrast to IL-16 + ED1 + cells, IL-16 + microglia/macrophages that coexpressed OX-8 were exclusively seen in the pannecrotic lesion core. In addition, clustering of IL-16 + cells was observed in perivascular Virchow–Robin-like spaces in areas of the primary injury (lesion core) and in immediately adjacent areas of secondary injury. Furthermore, on Day 3 postinjury, IL-16 + microglia/macrophages were frequently observed in a perineuronal position. Conclusions The early lesional accumulation of IL-16 + microglia/macrophages suggests a role for IL-16 in the early postinjury immune response such as recruitment and activation of immune cells, leading to microvessel clustering and secondary damage progression.
Programmed cell death in African trypanosomes
2006-03-01

Until recently it had generally been assumed that apoptosis and other forms of programmed cell death evolved during evolution of the metazoans to regulate growth and development in these multicellular organisms. However, recent research is adding strength to the original phenotypic observations described almost a decade ago which indicated that some parasitic protozoa may have evolved a cell death pathway analogous to the process described as apoptosis in metazoa. Here we explore the implications of a programmed cell death pathway in the African tsetse-transmitted trypanosomes.
Immunorejuvenation in the Elderly
2006-03-01

Dysregulated T-cell-mediated immunity contributes materially to the increased susceptibility to infectious disease, and possibly cancer, in the elderly. One hallmark of this state of "immunosenescence" in humans is the predominance of large clones of peripheral T cells with limited antigen receptor heterogeneity and a corresponding contraction of diversity in the T-cell antigen recognition repertoire. Surprisingly, a major driving force for these clonal expansions in humans is cytomegalovirus. The lifelong chronic antigenic stress caused by infection with this persistent activating virus results in clonal exhaustion of specific CD8 T cells, and their acquisition of a state of anergy and apoptosis resistance similar in many respects, and, the authors believe for similar reasons, to that commonly seen in the tumor-specific T cells of cancer patients. This excess of dysfunctional cells is indirectly immunosuppressive by filling the "immunologic space" and shrinking the T-cell repertoire for new antigens, as well as directly suppressive via cytokine secretion. It is associated with the "immunologic risk profile" predicting 2- and 4-year mortality in longitudinal studies of very old people. Therefore, it is hypothesized that deletion of such accumulations of dysfunctional cells would be beneficial to the individual. It may be possible to distinguish functional CMV-specific cells (which are essential to maintain immunosurveillance) from dysfunctional ones by their expression of certain surface molecules. This, coupled with methods directed at reinvigorating the thymus (e.g., use of interleukin 7), and targeting CMV by pharmacologic and immunotherapeutic interventions might result in a degree of "immunorejuvenation" sufficient to take elderly individuals out of the risk category and thereby extend healthy longevity.