bluuebunny/crossref_metadata_2025_split huggingface dataset:
Distinct functions for signal transducer and activator of transcription 1 and PU.1 in transcriptional activation of Fc γ receptor I promoter
Authors: Aittomäki Saara , Yang Jie , Scott Edward W. , Simon M. Celeste , Silvennoinen Olli 
Published: October 2002

Abstract
The myeloid cell–specific expression and interferon-γ (IFN-γ) induction of Fc γ receptor I (FcγRI) requires cooperation between PU.1 and signal transducer and activator of transcription 1 (Stat1) by means of mechanisms that are unknown. We found that PU.1 and Stat1 mediated distinct functions in the activation of FcγRI promoter. The basal activity of the natural FcγRI promoter was strictly dependent on PU.1, and IFN-γ induction required both PU.1 and Stat1. Recruitment of TATA-binding protein (TBP) to the FcγRI promoter did not replace PU.1 in promoter activation, suggesting that TBP is not sufficient for FcγRI activation and that PU.1 mediates additional contacts with basal transcription machinery. In contrast, Stat1 did not interact with basal transcription machinery, but the Stat1-mediated activation of FcγRI promoter critically required CREB-binding protein (CBP)/p300. These results define functional cooperativity between PU.1 and Stat1 in FcγRI promoter activation, in which PU.1 appears to serve as a bridging factor with the basal transcription machinery and IFN-γ–mediated induction of transcription occurs through recruitment of CBP/p300 by Stat1.
Analysis of Vλ-Jλ expression in plasma cells from primary (AL) amyloidosis and normal bone marrow identifies 3r(λIII) as a new amyloid-associated germline gene segment
Authors: Perfetti Vittorio , Casarini Simona , Palladini Giovanni , Vignarelli Maurizio Colli , Klersy Catherine , Diegoli Marta , Ascari Edoardo , Merlini Giampaolo 
Published: October 2002

AbstractPrimary (AL) amyloidosis is a plasma cell dyscrasia characterized by extracellular deposition of monoclonal light-chain variable region (V) fragments in the form of amyloid fibrils. Light-chain amyloid is rare, and it is not fully understood why it occurs in only a fraction of patients with a circulating monoclonal component and why it typically associates with λ isotype and λVI family light-chain proteins. To provide insights into these issues, we obtained complete nucleotide sequences of monoclonal Vλ regions from 55 consecutive unselected cases of primary amyloidosis and the results were compared with the light-chain expression profile of polyclonal marrow plasma cells from 3 healthy donors (a total of 264 sequences). We demonstrated that: (1) the λIII family is the most frequently used both in amyloidosis (47%) and in polyclonality (43%); (2) both conditions are characterized by gene restriction; (3) a very skewed repertoire is a feature of amyloidosis, because just 2 germline genes belonging to the λIII and λVI families, namely 3r (22% of cases, λIII) and 6a (20%, λVI), contributed equally to encode 42% of amyloid Vλ regions; (4) these same 2 gene segments have a strong association with amyloidosis if their prevalences are compared with those in polyclonal conditions (3r, 8.3%,P = .024; 6a, 2.3%, P = .0008, χ2 test); (5) the Jλ2/3 segment, encoding the fourth framework region, appears to be slightly overrepresented in AL (83% versus 67%, P = .03), and this might be related to preferential Jλ2/3 rearrangement in amyloid (11 of 12 cases) versus polyclonal 3r light chains (13 of 22 cases). These findings demonstrate that Vλ-Jλ expression is more restricted in plasma cells from amyloidosis than from polyclonal bone marrow and identify 3r as a new disease-associated gene segment. Overusage of just 2 gene segments,3r and 6a, can thus account for the λ light-chain overrepresentation typical of this disorder.
Evidence for the involvement of a hematopoietic progenitor cell in systemic mastocytosis from single-cell analysis of mutations in the c-kit gene
Authors: Yavuz A. Selim , Lipsky Peter E. , Yavuz Sule , Metcalfe Dean D. , Akin Cem 
Published: October 2002

AbstractMast cells are derived from multipotential hematopoietic progenitors and are clonally increased in systemic mastocytosis, a disease associated with point mutations of codon 816 (most commonly Asp816Val) of c-kit. To study the lineage relationship and the extent of expansion of cells derived from the mutated clone, we examined the occurrence of the Asp816Val c-kit mutation in genomic DNA of individual sorted peripheral blood T cells, B cells, and monocytes in patients with indolent systemic mastocytosis. The mutation was detected in varying frequencies in the genomic DNA of individual B cells and monocytes and bone marrow mast cells in patients with extensive disease. In B cells, the immunoglobulin repertoire was polyclonal, indicating that the mutation occurred before VH/(D)/JH recombination. These results show that mastocytosis is a disorder of a pluripotential hematopoietic progenitor cell that gives rise to B cells and monocytes in addition to mast cells and that the affected clone shows variable expansion in these lineages in the peripheral blood of patients with systemic mastocytosis.
c-myc proto-oncogene expression in hemophilic synovitis: in vitro studies of the effects of iron and ceramide
Authors: Wen Fei-Qiu , Jabbar Adnan A. , Chen Yi-Xin , Kazarian Tamara , Patel Dharmesh A. , Valentino Leonard A. 
Published: October 2002

AbstractHemophilia is a rare congenital bleeding disorder that is due to the deficiency of blood coagulation factor VIII or IX. Recurrent musculoskeletal bleeding is common and bleeding into joints results in a chronic inflammatory condition termed hemophilic synovitis. This destructive process is characterized by hemosiderin deposition in the superficial and deeper layers of the synovial membrane as well as a proliferation of synovial fibroblasts and vascular cells. The hyperplastic synovium and neovascular changes are reminiscent of the histopathologic appearance observed in malignant tissues. Indeed, the benign hyperplastic synovium in patients with hemophilia displays similar invasive and destructive behaviors suggesting the possibility of analogous disturbances in growth control and locally invasive mechanisms. Iron plays a role in malignant cell growth, local invasion, and tumor progression, possibly due to changes in the expression of the proto-oncogene, c-myc. We hypothesized that iron plays a similar role in hemophilic synovitis. To explore this hypothesis, we investigated the in vitro effects of iron on the proliferation of a primary, human synovial fibroblast cell (HSFC) line and the involvement of c-myc in this process. We also examined the role of ceramide, a sphingolipid capable of inducing apoptosis in this model system. HSFC proliferation was increased in a dose-dependent fashion and c-myc expression was enhanced by ferric citrate compared to sodium citrate control. Ceramide prevented both the iron-induced increases in HSFC proliferation andc-myc expression. These results indicate that iron probably plays a role in the proliferative changes observed in hemophilic joint disease and that aberrant expression of c-myc may underlie the iron effects. Furthermore, these results suggest that there may be a therapeutic role for ceramide in reversing these changes.
Maintenance therapy with alternate-day prednisone improves survival in multiple myeloma patients
Authors: Berenson James R. , Crowley John J. , Grogan Thomas M. , Zangmeister Jeffrey , Briggs Adrienne D. , Mills Glenn M. , Barlogie Bart , Salmon Sydney E. 
Published: October 2002

AbstractThe role of maintenance therapy in multiple myeloma is controversial. Recent studies have shown an improvement in both progression-free and overall survival for patients receiving maintenance treatment with a combination of interferon and glucocorticoids, compared with interferon alone. The role of glucocorticoids alone as maintenance therapy has not been previously addressed. We compared alternate-day, oral prednisone at 2 different dose levels (10 mg versus 50 mg) for remission maintenance among previously untreated myeloma patients following a response to induction with standard-dose vincristine, doxorubicin, and dexamethasone with prednisone (VAD-P) or VAD-P plus quinine (VAD-P/Q). There were 250 eligible patients registered on Southwest Oncology Group study 9210 and randomized to receive VAD-P or VAD-P/Q. There were 125 patients achieving at least a 25% tumor reduction following induction therapy who were randomized to either physiologic (10 mg) or pharmacologic (50 mg) doses of alternate-day, oral prednisone until disease progression. At the time of study entry, patient characteristics were similar in VAD-P and VAD-P/Q patients and in the 2 arms randomized to maintenance therapy. After a median follow-up of 53 months, there was no difference in either progression-free or overall survival between the 2 induction regimens. However, from the time of maintenance randomization, both progression-free (14 versus 5 months; P = .003) and overall survival (37 versus 26 months; P = .05) were significantly improved in patients receiving 50 mg as compared with 10 mg alternate-day prednisone. There was no difference in treatment-related adverse events between the groups. Thus, 50 mg, oral, alternate-day prednisone is effective maintenance treatment for multiple myeloma patients who achieve a response to induction chemotherapy.
Antithrombotic effects of controlled inhibition of factor VIII with a partially inhibitory human monoclonal antibody in a murine vena cava thrombosis model
Authors: Singh Inderjit , Smith Alberto , Vanzieleghem Beatrijs , Collen Désiré , Burnand Kevin , Saint-Remy Jean-Marie , Jacquemin Marc 
Published: October 2002

AbstractThe human monoclonal antibody mAb-LE2E9 partially inactivates human factor VIII (FVIII), leaving approximately 10% residual activity. The antithrombotic efficacy of the antibody was evaluated in mouse models of inferior vena cava thrombosis. Thrombi were induced in wild-type mice given either the antibody or saline. No thrombi occurred in any of 8 mice treated with mAb-LE2E9, whereas 6 of 8 control mice developed thrombi (P = .007). Treatment with mAb-LE2E9 did not result in a severe bleeding phenotype: a tail-cutting experiment that resulted in death of C57BL/6 FVIII-deficient (FVIII−/−) mice did not cause hemorrhagic death in mice treated with mAb-LE2E9. To evaluate the antithrombotic effect of mAb-LE2E9 in presence of human FVIII, thrombus formation was induced in FVIII−/− mice reconstituted intravenously with recombinant human FVIII (rhFVIII) or rhFVIII preincubated with mAb-LE2E9. Only 1 of 9 mice produced a thrombus in the rhFVIII/antibody complex–treated group, compared with 7 of 9 in the control group (P = .015). FVIII−/− mice were also reconstituted with rhFVIII and then injected with either mAb-LE2E9 or saline. One of 14 mice in the group treated with the antibody developed a thrombus, compared with 10 of 14 in the control group (P = .001). The thrombi occurring in antibody-treated animals were smaller than in controls (P &lt; .01). All animals survived, and there were no bleeding complications. Thus, the mAb-LE2E9 antibody inhibits thrombosis without causing an overt bleeding tendency.
Significance of the detection of antineutrophil antibodies in children with chronic neutropenia
Authors: Kobayashi Masao , Nakamura Kazuhiro , Kawaguchi Hiroshi , Sato Takashi , Kihara Hirotaka , Hiraoka Asako , Tanihiro Misae , Taniguchi Kikuyo , Takata Noboru , Ueda Kazuhiro 
Published: October 2002

AbstractWe evaluated the clinical characteristics of 41 children with chronic neutropenia based on the quantitative analysis of antineutrophil antibodies in serum by flow cytometry. According to the strength of antineutrophil antibodies, the patients were divided into 3 groups: 12 patients presented negative antibodies, 13 patients showed weak positive antibodies, and 16 patients showed strong positive antibodies. No significant differences were seen in age of diagnosis, severity of neutropenia, and infectious complications associated with neutropenia among the 3 groups. The spontaneous resolution of neutropenia was observed in all patients with negative antibodies and in 22 of 29 patients with positive antibodies. The age of the recovery of neutropenia and the duration until spontaneous resolution of neutropenia were significantly dependent on the antibody strength at the time of diagnosis. These results demonstrate that the quantification of antineutrophil antibodies at the time of diagnosis may be useful in considering the clinical course of chronic neutropenia in childhood.
Arbitrary source and receiver positioning in finite‐difference schemes using Kaiser windowed sinc functions
Authors: Hicks Graham. J. 
Published: October 2002

In finite‐difference methods a seismic source can be implemented using either initial wavefield values or body forces. However, body forces can only be specified at finite‐difference nodes, and, if using initial values, a source cannot be located close to a reflecting boundary or interface in the model. Hence, difficulties can exist with these schemes when the region surrounding a source is heterogeneous or when a source either is positioned between nodes or is arbitrarily close to a free surface. A completely general solution to these problems can be obtained by using Kaiser windowed sinc functions to define a small region around the true source location that contains several nodal body forces. Both monopole and dipole point sources can be defined, enabling many source types to be implemented in either acoustic or elastic media. Such a function can also be used to arbitrarily locate receivers. If the number of finite‐difference nodes per wavelength is four or more (and with a source region half‐width of only four nodes) this scheme results in insignificant phase errors and in amplitude errors of no more than 0.1%. Numerical examples for sources located less than one node from either a free surface or an image source demonstrate that the scheme can be used successfully for any surface‐source or multisource configuration.
Local‐trace zeroing and spike zeroing: Two short automated noise‐rejection routines to remove noise and spikes on seismic traces
Authors: Stanghellini Giuseppe , Bonazzi Claudia 
Published: October 2002

The acquisition of marine seismic data is often affected by noise that introduces spurious signals. Due to the length of the receiver streamer, bad weather conditions can produce low‐frequency, high‐intensity incoherent noise and/or spikes that can be difficult to remove by means of conventional mathematical filters. In this paper we present two Fortran routines suitable to locate and remove the noise in the low and very low frequency ranges and to locate and suppress spikes. These two routines are designed to run without user interaction once the processing parameters are selected. Both routines are simple and compact, and can be included in any processing software.
P‐wave velocity and permeability distribution of sandstones from a fractured tight gas reservoir
Authors: Dürrast Helmut , Rasolofosaon P. N. J. , Siegesmund Siegfried 
Published: October 2002

Fractures are an important fabric element in many tight gas reservoirs because they provide the necessary channels for fluid flow in rocks which usually have low matrix permeabilities. Several sandstone samples of such a reservoir type were chosen for a combined study of rock fabric elements and petrophysical properties. Geological investigations of the distribution and orientation of the fractures and sedimentary layering were performed. In addition, laboratory measurements were carried out to determine the directional dependence of the permeability and P‐wave velocities. Higher permeability values are generally in the plane of the nearly horizontal sedimentary layering with regard to the core axis. With the occurrence of subvertical fractures, however, the highest permeabilities were determined to be parallel to the core axis.Compressional wave velocities were measured on spherical samples in more than 100 directions to get the VPsymmetry without prior assumptions. Below 50 MPa confining pressure, all samples show a monoclinic symmetry of the P wave velocity distribution, caused by sedimentary layering, fractures, and crossbedding. At higher confining pressure, sedimentary layering is approximately the only effective fabric element, resulting in a more transverse isotropic VPsymmetry. Using the geological‐petrophysical model introduced here, the complex symmetry of the VPdistributions can only be explained by the rock fabric elements. Furthermore, water saturation increases the velocities and decreases the anisotropy but does not change VPsymmetry. This indicates that at this state, all fabric elements, including the fractures, have an influence on P‐wave velocity distribution.
Effect of fluid viscosity on elastic wave attenuation in porous rocks
Authors: Gurevich Boris 
Published: October 2002

Attenuation and dispersion of elastic waves in fluid‐saturated rocks due to pore fluid viscosity is investigated using an idealized exactly solvable example of a system of alternating solid and viscous fluid layers. Waves in periodic layered systems at low frequencies can be studied using an asymptotic analysis of Rytov's exact dispersion equations. Since the wavelength of the shear wave in the fluid (viscous skin depth) is much smaller than the wavelength of the shear or compressional waves in the solid, the presence of viscous fluid layers requires a consideration of higher‐order terms in the low‐frequency asymptotic expansions. This expansion leads to asymptotic low‐frequency dispersion equations. For a shear wave with the directions of propagation and of particle motion in the bedding plane, the dispersion equation yields the low‐frequency attenuation (inverse quality factor) as a sum of two terms which are both proportional to frequency ω but have different dependencies on viscosity η: one term is proportional to ω/η, the other to ωη. The low‐frequency dispersion equation for compressional waves allows for the propagation of two waves corresponding to Biot's fast and slow waves. Attenuation of the fast wave has the same two‐term structure as that of the shear wave. The slow wave is a rapidly attenuating diffusion‐type wave, whose squared complex velocity again consists of two terms which scale with iω/η and iωη. For all three waves, the terms proportional to η are responsible for the viscoelastc phenomena (viscous shear relaxation), whereas the terms proportional to η−1 account for the visco‐inertial (poroelastic) mechanism of Biot's type. Furthermore, the characteristic frequencies of visco‐elastic ωV and poroelastic ωB attenuation mechanisms obey the relation ωVωB = AωR2, where ωR is the resonant frequency of the layered system, and A is a dimensionless constant of order 1. This result explains why the visco‐elastic and poroelastic mechanisms are usually treated separately in the context of macroscopic theories that imply ω << ωR. The poroelastic mechanism dominates over the visco‐elastic one when the frequency‐indepenent parameter B = ωB/ωV = 12η2/μsρfhf2 << 1, and vice versa, where hf is the fluid layer thickness, ρf the fluid density, and μs represents the shear modulus of the solid.
Randomized Phase II Study of Cisplatin With Gemcitabine or Paclitaxel or Vinorelbine as Induction Chemotherapy Followed by Concomitant Chemoradiotherapy for Stage IIIB Non–Small-Cell Lung Cancer: Cancer and Leukemia Group B Study 9431
Authors: Vokes Everett E. , Herndon James E. , Crawford Jeffrey , Leopold Kenneth A. , Perry Michael C. , Miller Antonius A. , Green Mark R. 
Published: October 2002

PURPOSE: To evaluate new drugs in combination with cisplatin in unresectable stage III non–small-cell lung cancer, Cancer and Leukemia Group B (CALGB) conducted a randomized phase II study of two cycles of induction chemotherapy followed by two additional cycles of the same drugs with concomitant radiotherapy. PATIENTS AND METHODS: Eligible patients received four cycles of cisplatin at 80 mg/m2 on days 1, 22, 43, and 64 with arm 1: gemcitabine 1,250 mg/m2 on days 1, 8, 22, and 29 and 600 mg/m2 on days 43, 50, 64, and 71; arm 2: paclitaxel 225 mg/m2 for 3 hours on days 1 and 22 and 135 mg/m2 on days 43 and 64; and arm 3: vinorelbine 25 mg/m2 on days 1, 8, 15, 22, and 29 and 15 mg/m2 on days 43, 50, 64, and 71. Radiotherapy was initiated on day 43 at 2 Gy/d (total dose, 66 Gy). RESULTS: One hundred seventy-five eligible patients were analyzed. Toxicities during induction chemotherapy consisted primarily of grade 3 or 4 granulocytopenia. Grade 3 or 4 toxicities during concomitant chemoradiotherapy consisted of thrombocytopenia, granulo-cytopenia, and esophagitis. Response rates after completion of radiotherapy were 74%, 67%, and 73% for arms 1, 2, and 3, respectively. Median survival for all patients was 17 months. One-, 2-, and 3-year survival rates for the patients on the three arms were 68%/37%/28%, 62%/29%/19%, and 65%/40%/23%. CONCLUSION: Four cycles of gemcitabine, vinorelbine, or paclitaxel in combination with cisplatin can be administered at these doses and schedules. The observed survival rates exceed those of previous CALGB trials and may be attributable to the use of concomitant chemoradiotherapy. Induction chemotherapy added to concomitant chemoradiotherapy is being evaluated in a phase III randomized trial.
Family History and Prostate Cancer Screening With Prostate-Specific Antigen
Authors: Mäkinen Tuukka , Tammela Teuvo L.J. , Stenman Ulf-Håkan , Määttänen Liisa , Rannikko Sakari , Aro Jussi , Juusela Harri , Hakama Matti , Auvinen Anssi 
Published: October 2002

PURPOSE: Early detection of prostate cancer has been recommended for men with affected first-degree relatives despite the lack of evidence for mortality reduction. We therefore evaluated the impact of family history in the Finnish prostate cancer screening trial. PATIENTS AND METHODS: Approximately 80,000 men were identified from the population register for the first screening round. Of the 32,000 men randomized to the screening arm, 30,403 were eligible at the time of invitation. A blood sample was drawn from the participants (n = 20,716), and serum prostate-specific antigen (PSA) was determined. Men with a PSA level ≥ 4.0 ng/mL were referred for prostate biopsy. Information on family history was obtained through a self-administered questionnaire at baseline. RESULTS: A total of 964 (5%) of the 20,716 screening participants had a positive family history, and 105 (11%) were screening-positive. Twenty-nine tumors were diagnosed, corresponding to a detection rate of 3.0% (29 of 964) and a positive predictive value of 28% (29 of 105). Of the 19,347 men without a family history, 1,487 (8%) had a PSA level ≥ 4.0 ng/mL. The detection rate was 2.4% (462 of 19,347) and the positive predictive value was 31% (462 of 1,487). The risk associated with a positive family history was not substantially increased (rate ratio, 1.3; 95% confidence interval, 0.9 to 1.8). The results were not affected by the age of the screenee or age at diagnosis of the affected relative. The program sensitivity was 6% (29 of 491) (ie, selective screening policy would have missed 94% of cancers in the population). No differences were seen in the characteristics of screen-detected cancers by family history. CONCLUSION: Our findings provide no support for selective screening among men with affected relatives.