bluuebunny/crossref_metadata_2025_split huggingface dataset:
Detection of JC virus DNA sequences and expression of viral T antigen and agnoprotein in esophageal carcinoma
Authors: Del Valle Luis , White Martyn K. , Enam Sahnila , Oviedo Sergio Piña , Bromer Matthew Q. , Thomas Rebecca M. , Parkman Henry P. , Khalili Kamel 
Published: January 2005

AbstractBACKGROUNDThe human polyomavirus JC virus (JCV) causes progressive multifocal leukoencephalopathy. Subclinical infection with JCV occurs in 85–90% of the population worldwide. The virus usually remains latent but can reactivate under immunosuppressive conditions, resulting in progressive multifocal leukoencephalopathy. JCV is oncogenic in experimental animals and is associated with human brain tumors. JCV is found in normal mucosa of the gastrointestinal tract, and some colon carcinomas express the oncogenic JCV T‐antigen protein. The objective of this study was to examine the presence of JCV DNA sequences and JCV protein expression in normal and malignant human esophageal tissues.METHODSThe authors examined the presence of JCV DNA sequences and protein expression in normal and malignant human esophageal tissues. Seventy well characterized biopsy specimens from patients with a spectrum of esophageal disorders were studied by immunohistochemistry, and 18 specimens were analyzed further by polymerase chain reaction amplification.RESULTSJC viral DNA was isolated from 11 of 13 normal esophageal biopsy specimens (85%) and from 5 of 5 esophageal carcinomas (100%). Using immunohistochemistry, JCV T antigen was detected in 10 of 19 carcinomas (53%), agnoprotein was detected in 8 carcinomas (42%), p53 tumor suppressor was detected in 11 carcinomas (58%), and β‐catenin was detected in 4 carcinomas (21%). Zero of 51 normal, benign, and premalignant esophageal samples expressed viral proteins. Laser‐capture microdissection verified the presence and specificity of JCV DNA sequences. β‐Catenin and p53 were colocalized with JCV T‐antigen in the nuclei of neoplastic cells.CONCLUSIONSThe results provide evidence for infection of gastrointestinal tract cells by JCV and suggest a potential role of JCV in the development of upper digestive tract carcinomas. Cancer 2005. © 2005 American Cancer Society.
Repeat needle biopsies combined with clinical observation are safe and accurate in the management of a solitary pulmonary nodule
Authors: Welker James A. , Alattar Mohammed , Gautam Sandeep 
Published: January 2005

AbstractBACKGROUNDSixty percent of removed solitary pulmonary nodules (SPNs) are benign. An approach that reduces the unnecessary excision of benign nodules is consistent with the oncologic objective of organ preservation.METHODSA prospective observational study was performed at a lung cancer referral center in which consecutive patients were evaluated who presented with SPNs measuring < 4 cm on computed tomography (CT) scans. Patients underwent transbronchial biopsy (TBB), percutaneous needle aspiration (PCNA), clinical observation, repeat CT scans, and repeat biopsies. Patients were observed clinically and underwent repeat biopsies in an effort to reduce unnecessary surgical intervention.RESULTSOne hundred eighteen patients underwent 194 biopsy sessions, including 137 TBB sessions and 57 PCNA sessions. The mean follow‐up was 4 years. The shortest follow‐up of a benign lesion was 3 years. The incidence of malignancy was 61%. The positive predictive value, negative predictive value, sensitivity, specificity, and accuracy all were 100%. Five patients had a delayed change in diagnosis from benign to malignant. This delay in diagnosis neither resulted in a change in tumor stage nor had an impact on patient management or survival.CONCLUSIONSRepeat needle biopsies combined with clinical observation and repeat CT scans can classify an SPN as benign versus malignant with 100% accuracy (95% confidence interval, 96.1–100.0%). An SPN diagnostic approach that includes a TBB, then PCNA, clinical observation, repeat CT scans, and repeat biopsies for continued suspicion of malignancy appears to reduce the unnecessary surgical excision of benign nodules from the current rate of 60% to 5% of SPN resections without affecting the survival of patients who have malignant SPNs. Cancer 2005. © 2005 American Cancer Society.
Development of prognostic factors and survival in cutaneous melanoma over 25 years
Authors: Buettner Petra G. , Leiter Ulrike , Eigentler Thomas K. , Garbe Claus 
Published: January 2005

AbstractBACKGROUNDRecent studies revealed that incidence rates of cutaneous melanoma (CM) were leveling off predominantly among younger people and patterns suggested birth‐cohort effects. The current study analyzed the development of prognostic factors and survival in incident CM over 25 years.METHODSAll 45,483 patients with incident CM diagnosed between 1976 and 2000 recorded by the German Central Malignant Melanoma Registry were considered. Linear and logistic regression analyses were used to judge time trends. Trends of survival rates were tested with the multivariate Cox model.RESULTSMedian tumor thickness decreased from 1.81 mm in 1976 to 0.53 mm in 2000 (P < 0.0001). The percentages of in situ and level II CM increased, respectively (P < 0.0001). The percentage of ulcerated CM decreased (P < 0.0001). The percentage of superficial spreading melanoma increased, whereas the percentage of nodular melanoma decreased (P < 0.0001). These time trends were all significant in the strata of gender, however, male patients presented in general with more advanced disease. Between 1976 and 2000, the average patient got older (P < 0.0001). The percentage of patients diagnosed with the primary tumor alone increased (P < 0.0001). Across the 25 years of observation, adjusted survival rates did not increase for females (P = 0.1561) but they increased for males (P < 0.0001).CONCLUSIONSThe data demonstrated a strong trend towards prognostically more favorable CM most likely due to earlier diagnosis. Men and older people should be the focus of health promotion activities as they presented with more advanced disease. Cancer 2005. © 2005 American Cancer Society.
The MHC class II transactivator (CIITA) mRNA stability is critical for the HLA class II gene expression in myelomonocytic cells
Authors: De Lerma Barbaro Andrea , Procopio Francesco A. , Mortara Lorenzo , Tosi Giovanna , Accolla Roberto S. 
Published: January 2005

AbstractThe human promyelocytic U937 cells express detectable levels of MHC class II (MHC‐II) molecules. Treatment with 12‐o‐‐tetradecanoyl phorbol 13‐acetate (TPA), inducing macrophage‐like differentiation, produces a dramatic decrease of MHC‐II expression as result of down‐modulation of the activation of immune response gene 1 (AIR‐1)‐encoded MHC‐II transactivator (CIITA). This event is specific, as MHC class I remains unaffected. Similar results are observed with U937 cells expressing an exogenous full‐length CIITA. Molecular studies demonstrate that TPA treatment affects the stability of CIITA mRNA rather than CIITA transcription. Importantly, cis‐acting elements within the distal 650 bp of the 1035‐bp 3′ untranslated region (3′UTR, nucleotides 3509–4543) are associated to transcript instability. Transcription inhibitors actinomycin D and 5,6‐dichlororibofuranosyl benzimidazole, and the translation inhibitor cycloheximide significantly rescue the accumulation of CIITA mRNA in TPA‐treated cells. A similar effect is also observed after treatment with staurosporine and the PKC‐specific inhibitor GF109203X. The instability of CIITA mRNA produced by TPA in U937 cells is not seen in B cells. These results demonstrate the presence of an additional level of control of MHC‐II expression in the macrophage cell lineage depending upon the control of CIITA mRNA stability, most likely mediated by differentiation‐induced, 3′UTR‐interacting factors which require kinase activity for their destabilizing function.
Single nucleotide polymorphisms as a prerequisite for autoantigens
Authors: Stadler Michael B. , Arnold Diana , Frieden Sara , Luginbühl Sarah , Stadler Beda M. 
Published: January 2005

AbstractIt is still elusive why certain self proteins induce an autoimmune response. One immunological hypothesis is that only modified or altered self‐proteins may become a target. Thus, we asked whether such alterations may actually be genetic polymorphisms that can be revealed by analyzing sequence variability in the known human autoantigens. Indeed, we found autoantigens to contain significantly more single nucleotide polymorphisms (SNP) than other human genes do. Our finding may offer an explanation for autoimmune responses through allogeneic exposure. Besides other contributing factors in autoimmunity, SNP may represent an essential prerequisite for the primary induction of an autoimmune response.See accompanying Commentary: http://dx.doi.org/10.1002/eji.200425888
Critical role of the liver CD8+ CD122+ T cells in the generalized Shwartzman reaction of mice
Authors: Sato Kengo , Kinoshita Manabu , Motegi Akira , Habu Yoshiko , Takayama Eiji , Nonoyama Shigeaki , Hiraide Hoshio , Seki Shuhji 
Published: January 2005

AbstractWe examined the role of mouse CD8+ CD122+ T cells, which increase in number with age, in the generalized Shwartzman reaction. This reaction was induced by IL‐12 priming and subsequent LPS challenge (after 24 h) in mice of various ages (4–50 weeks of age). Although most young mice (4 or 6 weeks of age) survived, mortality essentially increased with increasing age of the mice, and all mice of 20 weeks of age or older died within 48 h. Serum TNF‐α levels after LPS challenge also increased age dependently. The neutralization of either IL‐12‐induced IFN‐γ or LPS‐induced TNF‐α improved the survival of middle‐aged (25‐week‐old) mice. Both IFN‐γ production after IL‐12 priming and TNF‐α production from the liver mononuclear cells after LPS challenge were also prominent in the middle‐aged mice. CD8+CD122+ T cells cultured with IL‐12 produced a much larger amount of IFN‐γ than CD8+CD122– T cells. Although the depletion of NK/NK T cells did not decrease the IFN‐γ or TNF‐α production in the Shwartzman reaction of the middle‐aged mice, an additional depletion of CD8+CD122+ T cells did decrease such production and also improved mouse survival. Furthermore, young mice transferred with CD8+CD122+ T cells from aged B6 nude mice showed an enhanced Shwartzman reaction.
Isolation of potent human Fab fragments against a novel highly immunogenic region on human muscle acetylcholine receptor which protect the receptor from myasthenic autoantibodies
Authors: Fostieri Efrosini , Tzartos Socrates J. , Berrih‐Aknin Sonia , Beeson David , Mamalaki Avgi 
Published: January 2005

AbstractIn the autoimmune disease myasthenia gravis (MG), antibodies against the muscle nicotinic acetylcholine receptor (AChR) cause loss of functional AChR in the neuromuscular junction. To isolate AChR‐specific human antibody fragments (Fab), a phage‐display library was constructed from an MG patient's thymic B lymphocytes. The first Fab isolated had a low affinity for human AChR, but two sequential antibody chain shufflings using the MG donor heavy and light chain gene repertoires resulted in isolating two new Fab with an approximately 30‐fold higher binding ability. The selected Fab contained extensively mutated heavy and light chains and probably represent intraclonal variants of a common progenitor having diverged in vivo by somatic hypermutation. Interestingly, the isolated Fab bound to an extracellular highly immunogenic region located either on an α‐subunit site affected by the γ/ϵ‐subunits or on the interface between α‐ and γ/ϵ‐subunits. This region is not the previously described "main immunogenic region" (MIR), although it seems to be close to it, as one improved Fab and an anti‐MIR mAb competed for AChR binding with distinctly different subpopulations of MG sera. Furthermore, this Fab protected surface AChR in cell cultures against MG autoantibody‐induced antigenic modulation, suggesting a potential therapeutic use in MG, especially in combination with a human anti‐MIR Fab.
High epitope density in a single protein molecule significantly enhances antigenicity as well as immunogenicity: a novel strategy for modern vaccine development and a preliminary investigation about B cell discrimination of monomeric proteins
Authors: Liu Wanli , Chen Ying‐Hua 
Published: January 2005

AbstractAlthough early studies have shown a close correlation between epitope density and epitope‐specific humoral immune responses, few attempts have been made to quantitatively compare the antigenic and immunogenic differences between protein molecules bearing low or high degrees of epitope density, nor have studies quantitatively investigated the mechanism of B cell discrimination of monomeric antigens. In this study, we prepared glutathione S‐transferase (GST) fusion proteins bearing various copies of the M2e epitope from the influenza virus M2 protein [GST‐(M2e)8, GST‐(M2e)4 and GST‐(M2e)1], which were used to detect and compare the real‐time kinetic binding with M2e‐specific mAb by surface plasma resonance. Our data show clearly that fusion proteins bearing higher M2e epitope density resulted in higher average avidity for M2e‐specific mAb. Furthermore, it was observed that fusion proteins bearing high M2e epitope density could induce polyclonal antibodies (pAb) with enhanced an average affinity constant (KA) for M2e epitope peptide compared to fusion proteins bearing low epitope density. The average KA of pAb induced by GST‐(M2e)8 (3.08 × 108 M–1 or 9.96 × 108 M–1) was up to two orders of magnitude greater than the average KA of pAb induced by GST‐(M2e)1 (2.00 × 106 M–1 or 3.43 × 106 M–1). Thus, the data presented here demonstrate that high epitope density in a single protein molecule significantly enhances antigenicity and immunogenicity. These findings enrich our knowledge of how epitope density might relate to the recognition, activation and antibody production processes of epitope‐specific immature B cells.
Do autoantigens define autoimmunity or vice versa?
Authors: Eisenberg Robert 
Published: January 2005

AbstractThe basic function of the adaptive immune system is to distinguish self from foreign. The failure of self tolerance can result in autoimmunity, which comes in many forms but still targets a limited selection of the total available autologous determinants. This selectivity must reflect the underlying mechanisms of the autoimmune reaction, as well as the particular features of the autoantigens that are targeted. Here I discuss the overall paradigm of autoimmunity, and what kinds of mechanisms might play a role. It is likely that multiple different pathways are critical in various diseases, and even in a single condition.See accompanying article: http://dx.doi.org/10.1002/eji.200425481
Syntheses, Structures and Magnetic Properties of Layered Metal(II) Mandelates
Authors: Beghidja Adel , Hallynck Sylvain , Welter Richard , Rabu Pierre 
Published: January 2005

AbstractA series of MnII, FeII, CoII, NiII and CuII layered mandelates has been synthesised in the form of crystalline powders by a hydrothermal route. The five compounds are isostructural with the copper analogue, also obtained in a single crystal form, except that the latter shows a strong Jahn−Teller distortion of the coordination spheres around the CuII centres. The complexes crystallise in the monoclinic centrosymmetric space group P21/a and their structures consist of layers of six‐coordinate metal(II) ions interconnected through carboxylato bridges in a diamond‐like network. The magnetic data indicate very small antiferromagnetic in‐plane couplings for 1, 2, 3 and 5, with J/kB = −0.122 K for 1. The NiII compound 4 exhibits ferromagnetic coupling within the layers (J/kB = +1.213 K) and ferromagnetic 3D ordering can be observed at TC = 2.7 K. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
Polarized fluorescence correlation spectroscopy of DNA‐DAPI complexes
Authors: Barcellona Maria Luisa , Gammon Seth , Hazlett Theodore , Digman Michelle A. , Gratton Enrico 
Published: January 2005

AbstractWe discuss the use of fluorescence correlation spectroscopy for the measurement of relatively slow rotations of large macromolecules in solution or attached to other macromolecular structures. We present simulations and experimental results to illustrate the range of rotational correlation times and diffusion times that the technique can analyze. In particular, we examine various methods to analyze the polarization fluctuation data. We have found that by first constructing the polarization function and then calculating the autocorrelation function, we can obtain the rotational motion of the molecule with very little interference from the lateral diffusion of the macromolecule, as long as the rotational diffusion is significantly faster than the lateral diffusion. Surprisingly, for common fluorophores the autocorrelation of the polarization function is relatively unaffected by the photon statistics. In our instrument, two‐photon excitation is used to define a small volume of illumination where a few molecules are present at any instant of time. The measurements of long DNA molecules labeled with the fluorescent probe DAPI show local rotational motions of the polymers in addition to translation motions of the entire polymer. For smaller molecules such as EGFP, the viscosity of the solution must be increased to bring the relaxation due to rotational motion into the measurable range. Overall, our results show that polarized fluorescence correlation spectroscopy can be used to detect fast and slow rotational motion in the time scale from microsecond to second, a range that cannot be easily reached by conventional fluorescence anisotropy decay methods. Microsc. Res. Tech. 65:205–217, 2004. © 2005 Wiley‐Liss, Inc.
Microscopy of biological sample through advanced diffractive optics from visible to x‐ray wavelength regime
Authors: Di Fabrizio Enzo , Cojoc Dan , Emiliani Valentina , Cabrini Stefano , Coppey‐Moisan Maite , Ferrari Enrico , Garbin Valeria , Altissimo Matteo 
Published: January 2005

AbstractThe aim of this report is to demonstrate a unified version of microscopy through the use of advanced diffractive optics. The unified scheme derives from the technical possibility of realizing front wave engineering in a wide range of electromagnetic spectrum. The unified treatment is realized through the design and nanofabrication of phase diffractive elements (PDE) through which wave front beam shaping is obtained. In particular, we will show applications, by using biological samples, ranging from micromanipulation using optical tweezers to X‐ray differential interference contrast (DIC) microscopy combined with X‐ray fluorescence. We report some details on the design and physical implementation of diffractive elements that besides focusing also perform other optical functions: beam splitting, beam intensity, and phase redistribution or mode conversion. Laser beam splitting is used for multiple trapping and independent manipulation of micro‐beads surrounding a cell as an array of tweezers and for arraying and sorting microscopic size biological samples. Another application is the Gauss to Laguerre‐Gauss mode conversion, which allows for trapping and transfering orbital angular momentum of light to micro‐particles immersed in a fluid. These experiments are performed in an inverted optical microscope coupled with an infrared laser beam and a spatial light modulator for diffractive optics implementation. High‐resolution optics, fabricated by means of e‐beam lithography, are demonstrated to control the intensity and the phase of the sheared beams in x‐ray DIC microscopy. DIC experiments with phase objects reveal a dramatic increase in image contrast compared to bright‐field x‐ray microscopy. Besides the topographic information, fluorescence allows detection of certain chemical elements (Cl, P, Sc, K) in the same setup, by changing the photon energy of the x‐ray beam. Microsc. Res. Tech. 65:252–262, 2004. © 2005 Wiley‐Liss, Inc.
Monitoring of glass derivatization with pulsed force mode atomic force microscopy
Authors: Ebner Andreas , Kienberger Ferry , Stroh Cordula M. , Gruber Hermann J. , Hinterdorfer Peter 
Published: January 2005

AbstractNon‐specific adsorption of proteins at solid/liquid interfaces is a major problem in the use of synthetic biomaterials and in ultrasensitive detection methods. Grafting surfaces with a dense layer of poly(ethylene glycol) (PEG) or other polymers is a most widely used strategy to solve this task. While such modified surfaces have been characterized by their ability to resist protein adsorption, the polymer layers themselves have rarely been studied in fine detail. Atomic force microscopy (AFM) using the pulsed force mode (PFM), is an ideal technique to investigate structural features and physiochemical properties of surfaces because topology and adhesion are simultaneously detected with high lateral resolution. In the present study, PFM‐AFM was applied to thoroughly characterize different stages of glass derivatization, up to the formation of a dense PEG layer. Lateral inhomogeneities in topology and/or adhesion were observed at all stages before PEG attachment. The covalently bound PEG, however, was seen to form a densely packed monolayer with maximal thickness, smooth surface, and weak adhesion. Thus, PFM‐AFM appears to be a valuable tool for the characterization of protein‐repelling surfaces in solution. Microsc. Res. Tech. 65:246–251, 2004. © 2005 Wiley‐Liss, Inc.
Single molecule spectroscopic characterization of GFP‐mut2 mutant for two‐photon microscopy applications
Authors: Cannone Fabio , Caccia Michele , Bologna Sara , Diaspro Alberto , Chirico Giuseppe 
Published: January 2005

AbstractGreen Fluorescent Protein (GFP) mutants are extensively used in optical microscopy studies of in vivo biological processes in cells. Nonetheless, blinking and bleaching of the GFP chromophore at the single molecule level greatly limits its usefulness. We have worked out what we think are the best experimental conditions for the use of the GFP mutant, GFP‐mut2, as a single molecule marker in two‐photon excitation measurements. We have measured molecular brightness, excited state lifetime, blinking and photo‐bleaching times versus the two‐photon excitation intensity on proteins embedded in silica gel matrices versus the excitation wavelength in the range 700–1,000 nm. Our results indicate that GFPmut2 can be employed as a long‐lived reporter of biological processes. Microsc. Res. Tech. 65:186–193, 2004. © 2005 Wiley‐Liss, Inc.