bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification and characterization of the heme-binding proteins SeShp and SeHtsA of Streptococcus equi subspecies equi
Authors: Nygaard Tyler K , Liu Mengyao , McClure Michael J , Lei Benfang 
Published: September 2006

AbstractBackgroundHeme is a preferred iron source of bacterial pathogens.Streptococcus equisubspeciesequiis a bacterial pathogen that causes strangles in horses. WhetherS. equihas a heme acquisition transporter is unknown.ResultsAnS. equigenome database was blasted with the heme binding proteins Shp and HtsA ofStreptococcus pyogenes, and found thatS. equihas the homologue of Shp (designated SeShp) and HtsA (designated SeHtsA). Tag-free recombinant SeShp and SeHtsA and 6xHis-tagged SeHtsA (SeHtsAHis) were prepared and characterized. Purified holoSeShp and holoSeHtsA bind Fe(II)-protoporphyrin IX (heme) and Fe(III)-protoporphyrin IX (hemin) in a 1:1 stoichiometry, respectively, and are designated hemoSeShp and hemiSeHtsA. HemiSeShp and hemiSeHtsAHiscan be reconstituted from apoSeShp and apoSeHtsAHisand hemin. HemoSeShp is stable in air and can be oxidized to hemiSeShp by ferricyanide. HemiSeHtsA can be reduced into hemoSeHtsA, which autoxidizes readily. HemoSeShp rapidly transfers its heme to apoSeHtsAHis. In addition, hemoSeShp can also transfer its heme to apoHtsA, and hemoShp is able to donate heme to apoSeHtsAHis.ConclusionThe primary structures, optical properties, oxidative stability, and in vitro heme transfer reaction of SeShp and SeHtsA are very similar to those ofS. pyogenesShp and HtsA. The data suggest that the putative cell surface protein SeShp and lipoprotein SeHtsA are part of the machinery to acquire heme inS. equi. The results also imply that the structure, function, and functional mechanism of the heme acquisition machinery are conserved inS. equiandS. pyogenes.
Endovascular control of haemorrhagic urological emergencies: an observational study
Authors: Somani Bhaskar K , Nabi Ghulam , Thorpe Peter , McClinton Sam 
Published: September 2006

Abstract

Background
Transarterial embolisation (TAE) is an effective method in control of haemorrhage irrespective of the nature of urological emergency. As the technique and technology have evolved, it is now possible to perform highly selective embolisation. The aim of this study was to critically appraise feasibility and efficacy of therapeutic TAE in control of haemorrhagic urological emergencies using selective and non-selective embolisation. Specifically, we aimed to assess the impact of timing of embolisation on the requirement of blood transfusion and long-term morphological and functional follow-up of embolised organs.

Methods
This is a single institutional observational study carried out between March 1992 and March 2006. Records of all patients who underwent selective and non-selective angioembolisation to control bleeding in urological emergencies were reviewed. Data on success rate, periprocedural complications, timing of embolisation, requirement of blood transfusion and the long-term morphological and functional outcomes of embolised organs was recorded.

Results
Fourteen patients underwent endovascular control of bleeding as a result of trauma, iatrogenic injury and spontaneous perinephric haemorrhage during a period of 14 years. All these patients would have required emergency open surgery without the option of embolisation procedure. The mean time between the first presentation and embolisation was 22 hours (range 30 minutes to 60 hours). Mean pre-embolisation transfusion requirement was 6.8 units (range 0–22 units). None of the patients with successful embolisation required post-procedural blood transfusion. Permanent haemostasis was achieved in all but one patient, who required emergency nephrectomy. There were no serious procedure related post-embolisation complications.

Conclusion
Endovascular control using transarterial angioembolisation is an effective method for managing haematuria or haemorrhage in urological emergencies. Wherever and whenever indicated, this option should be considered early in the management of these cases.
The impact of a decision aid about heart disease prevention on patients' discussions with their doctor and their plans for prevention: a pilot randomized trial
Authors: Sheridan Stacey L , Shadle John , Simpson Ross J , Pignone Michael P 
Published: September 2006

Abstract
Background
Low utilization of effective coronary heart disease (CHD) prevention strategies may be due to many factors, but chief among them is the lack of patient involvement in prevention decisions. We undertook this study to test the effectiveness of an individually-tailored, computerized decision aid about CHD on patients' discussions with their doctor and their plans for CHD prevention.

Methods
We conducted a pilot randomized trial in a convenience sample of adults with no previous history of cardiovascular disease to test the effectiveness of an individually-tailored, computerized decision aid about CHD prevention against a risk factor list that patients could present to their doctor.

Results
We enrolled 75 adults. Mean age was 53. 59% were female, 73% white, and 23% African-American. 66% had some college education. 43% had a 10-year CHD risk of 0–5%, 25% a risk of 6–10%, 24% a risk of 11–20%, and 5% a risk of > 20%. 78% had at least one option to reduce their CHD risk, but only 45% accurately identified the strategies best supported by evidence. 41 patients received the decision aid, 34 received usual care. In unadjusted analysis, the decision aid increased the proportion of patients who discussed CHD risk reduction with their doctor from 24% to 40% (absolute difference 16%; 95% CI -4% to +37%) and increased the proportion who had a specific plan to reduce their risk from 24% to 37% (absolute difference 13%; 95% CI -7% to +34%). In pre-post testing, the decision aid also appeared to increase the proportion of patients with plans to intervene on their CHD risk (absolute increase ranging from 21% to 47% for planned medication use and 5% to 16% for planned behavioral interventions).

Conclusion
Our study confirms patients' limited knowledge about their CHD risk and effective risk reduction options and provides preliminary evidence that an individually-tailored decision aid about CHD prevention might be expected to increase patients' discussions about CHD prevention with their doctor and their plans for CHD risk reduction. These findings should be replicated in studies with a larger sample size and patients at overall higher risk of CHD.
Trial Registration: ClinicalTrials.gov NCT00315978
Preparation of platelet-rich plasma as a tissue adhesive for experimental transplantation in rabbits
Authors: Luengo Gimeno Federico , Gatto Silvia , Ferro José , Croxatto Juan Oscar , Gallo Juan Eduardo 
Published: September 2006

Abstract

Purpose
Platelet-rich plasma (PRP) is an autologous substance with adhesive properties. We aimed at developing and testing the efficacy of a method for PRP preparation in rabbits.

Materials and methods
An in vitro study was carried out to obtain PRP from forty rabbits and to analyze the number of platelets and type of substance needed to trigger platelet activation. To induce platelet activation, 5%, 10%, 25% and 50% CaCl solutions were used. Then, an in vivo study was performed in twelve rabbits to test PRP adhesiveness in lamellar corneal graft. A control group made up of six rabbits underwent corneal transplantation without using PRP.

Results
5% CaCl was the most effective concentration in activating PRP, with a mean time of 19 minutes. An attached corneal flap was seen 3 months after surgery. A detached corneal button was seen in all controls.

Conclusion
Our method was able to produce rabbit-derived PRP with suitable properties for soft tissue adhesion. These results could be useful for researchers of the growing fields of tissue repair and experimental transplantation.
CD97 neutralisation increases resistance to collagen-induced arthritis in mice
Authors: Kop Else N , Adriaansen Janik , Smeets Tom JM , Vervoordeldonk Margriet J , van Lier René AW , Hamann Jörg , Tak Paul P 
Published: September 2006

AbstractSynovial tissue of rheumatoid arthritis (RA) patients is characterised by an influx and retention of CD97-positive inflammatory cells. The ligands of CD97, CD55, chondroitin sulfate B, and α5β1 (very late antigen [VLA]-5) are expressed abundantly in the synovial tissue predominantly on fibroblast-like synoviocytes, endothelium, and extracellular matrix. Based upon this expression pattern, we hypothesise CD97 expression to result in accumulation of inflammatory cells in the synovial tissue of RA patients. To determine the therapeutic effect of blocking CD97 in an animal model of RA, collagen-induced arthritis was induced in a total of 124 DBA/J1 mice. Treatment was started on day 21 (early disease) or on day 35 (longstanding disease) with the blocking hamster anti-mouse CD97 monoclonal antibody (mAb) 1B2, control hamster immunoglobulin, or NaCl, applied intraperitoneally three times a week. The paws were evaluated for clinical signs of arthritis and, in addition, examined by radiological and histological analysis. Mice receiving 0.5 mg CD97 mAb starting from day 21 had significantly less arthritis activity and hind paw swelling. Furthermore, joint damage and inflammation were reduced and granulocyte infiltration was decreased. When treatment was started on day 35, CD97 mAb treatment had similar effects, albeit less pronounced. The results support the notion that CD97 contributes to synovial inflammation and joint destruction in arthritis.
Mycobacteria directly induce cytoskeletal rearrangements for macrophage spreading and polarization through TLR2-dependent PI3K signaling
Authors: Lasunskaia Elena B , Campos Mariana N N , de Andrade Marcelle R M , DaMatta Renato A , Kipnis Thereza L , Einicker-Lamas Marcelo , Da Silva Wilmar D 
Published: September 2006

Abstract
Macrophage migration and adhesion are important for the control of mycobacterial infection and are critically dependent on the reorganization of the cytoskeleton. Mycobacteria elicit rapid morphological changes, such as cell spreading, a process relevant to in vivo changes of macrophage shape during extravasation and migration. In this study, we investigated the BCG mycobacteria-induced signaling events leading to macrophage cytoskeletal rearrangements employing specific pharmacological inhibitors to suppress distinct kinase pathways known to be elicited by infection. Viable or lysed mycobacteria, as well as purified cell wall lipoprotein p19, TLR2 agonist, induced RAW264.7 cells to extend actin-rich pseudopods, which impart radial spreading within 3 h, leading later to persistent cell polarization. BCG induced rapid activation of phosphatidylinositol 3-kinase, PI3K, activation that was recruited to the activated TLR2 receptor. TLR2- neutralizing antibody inhibited macrophage spreading and PI3K activation induced by p19. Additionally, BCG induced spreading and polarization of bone marrow-derived macrophages from TLR2- expressing mice in contrast to their TLR2-knockout counterparts. Neither MEK1/ERK, p38 MAPK, nor NF-κB activation were important for the early cytoskeletal rearrangements observed, although suppression of these pathways is known to inhibit chemokine secretion by activated macrophages. Β2-integrins blockade with a corresponding antibody inhibited macrophage spreading and polarization but had no effect on pseudopodia protrusions demonstrating the downstream position of integrin-mediated adhesion in PI3K- dependent signaling pathway leading to the motility phenotype. The obtained data demonstrate that the direct effect of mycobacteria on macrophage shape might be mediated through TLR2-dependent PI3K activation.
Genomic Prediction of Locoregional Recurrence After Mastectomy in Breast Cancer
Authors: Cheng Skye H. , Horng Cheng-Fang , West Mike , Huang Erich , Pittman Jennifer , Tsou Mei-Hua , Dressman Holly , Chen Chii-Ming , Tsai Stella Y. , Jian James J. , Liu Mei-Chin , Nevins Joseph R. , Huang Andrew T. 
Published: September 2006

Purpose This study aims to explore gene expression profiles that are associated with locoregional (LR) recurrence in breast cancer after mastectomy. Patients and Methods A total of 94 breast cancer patients who underwent mastectomy between 1990 and 2001 and had DNA microarray study on the primary tumor tissues were chosen for this study. Eligible patient should have no evidence of LR recurrence without postmastectomy radiotherapy (PMRT) after a minimum of 3-year follow-up (n = 67) and any LR recurrence (n = 27). They were randomly split into training and validation sets. Statistical classification tree analysis and proportional hazards models were developed to identify and validate gene expression profiles that relate to LR recurrence. Results Our study demonstrates two sets of gene expression profiles (one with 258 genes and the other 34 genes) to be of predictive value with respect to LR recurrence. The overall accuracy of the prediction tree model in validation sets is estimated 75% to 78%. Of patients in validation data set, the 3-year LR control rate with predictive index more than 0.8 derived from 34-gene prediction models is 91%, and predictive index 0.8 or less is 40% (P = .008). Multivariate analysis of all patients reveals that estrogen receptor and genomic predictive index are independent prognostic factors that affect LR control. Conclusion Using gene expression profiles to develop prediction tree models effectively identifies breast cancer patients who are at higher risk for LR recurrence. This gene expression–based predictive index can be used to select patients for PMRT.
Changing Epidemiology of Small-Cell Lung Cancer in the United States Over the Last 30 Years: Analysis of the Surveillance, Epidemiologic, and End Results Database
Authors: Govindan Ramaswamy , Page Nathan , Morgensztern Daniel , Read William , Tierney Ryan , Vlahiotis Anna , Spitznagel Edward L. , Piccirillo Jay 
Published: September 2006

Purpose Small-cell lung cancer (SCLC) is a histologic subtype of lung cancer with a distinct biology and clinical course. It has been observed that the incidence of SCLC has been decreasing over the last several years. Methods We used the Surveillance, Epidemiologic, and End Results (SEER) database to determine the incidence of SCLC over the last 30 years. In addition, we sought to determine sex- and stage-based differences in the incidence and survival of SCLC among a proportion of reported cases of lung cancer over the last 30 years (1973 to 2002). Joinpoint analyses were applied to test the trends in annual percentage change for statistical significance. Results The proportion of SCLC (among all lung cancer histologic types) decreased from 17.26% in 1986 to 12.95% in 2002. Of all patients with SCLC, the proportion of women with SCLC increased from 28% in 1973% to 50% in 2002. A modest but statistically significant improvement in 2- and 5-year survival was noted among both limited-stage SCLC and extensive-stage SCLC cohorts during the study period. Conclusion Our analysis indicates that the incidence of SCLC is decreasing in the United States, and only modest improvements have been seen in survival over the last 30 years. Possible explanations for the decreasing incidence include the decrease in the percentage of smokers and the change to low-tar filter cigarettes. Despite trends toward modest improvement in survival, the outcome remains very poor.
Clinical and Pharmacologic Study of the Farnesyltransferase Inhibitor Tipifarnib in Cancer Patients With Normal or Mildly or Moderately Impaired Hepatic Function
Authors: Siegel-Lakhai Wandena S. , Crul Mirjam , De Porre Peter , Zhang Steven , Chang Ilsung , Boot Henk , Beijnen Jos H. , Schellens Jan H.M. 
Published: September 2006

Purpose This study explored the feasibility of treating patients with impaired hepatic function with tipifarnib. The safety profile, pharmacokinetics, and relationship between the pharmacokinetics and toxicities were evaluated. Patients and Methods Patients with mildly or moderately impaired hepatic function (Child-Pugh classification) were treated with tipifarnib bid on days 1 to 5 of cycle 1. Further dosing was based on the individual day 5 pharmacokinetic data and absolute neutrophil count. For patients with normal hepatic function, tipifarnib was dosed on days 1 to 14, followed by 1 week of rest. For all patients, in subsequent cycles, tipifarnib was administered for 21 consecutive days out of every 28 days. Results Twenty-eight patients were included in the normal (n = 16), mild (n = 9), and moderate (n = 3) impairment groups. The most important grade 3 to 4 hematologic toxicity was leukocytopenia/neutropenia, which was mostly observed in patients with moderate impairment. Common nonhematologic toxicities were fatigue, nausea, and vomiting. The pharmacokinetic data showed higher plasma concentrations of tipifarnib in patients with liver impairment compared with patients with normal hepatic function. Conclusion In patients with mildly impaired hepatic function, tipifarnib can be administered safely at a starting dose of 200 mg bid, but it is not safe to treat patients with moderate hepatic impairment.
Long-Term Follow-Up of High-Dose Methotrexate-Based Therapy With and Without Whole Brain Irradiation for Newly Diagnosed Primary CNS Lymphoma
Authors: Gavrilovic Igor T. , Hormigo Adília , Yahalom Joachim , DeAngelis Lisa M. , Abrey Lauren E. 
Published: September 2006

Purpose We previously reported a series of patients treated with high-dose methotrexate (MTX) -based chemotherapy, with or without whole brain radiotherapy. The purpose of this report is to update the initial results and provide long-term data regarding overall survival, patterns of relapse, and the risk of treatment-related neurotoxicity. Patients and Methods Fifty-seven patients with an average age of 65 and median Karnofsky performance score of 70 were treated; all patients have been observed longitudinally with serial magnetic resonance imaging scans and neurologic examinations. Results The overall median survival was 51 months with a median follow-up of 115 months for surviving patients. Twenty-five patients relapsed or developed progressive disease; median progression-free survival was 129 months. Seventeen patients developed treatment-related neurotoxicity; all but one had received whole brain radiotherapy as a component of treatment. Seventy-four percent of patients younger than 60 years who received both MTX-based chemotherapy and whole brain radiotherapy were alive at last follow-up. Median survival for patients older than 60 years was 29 months regardless of whether or not they received whole brain radiotherapy. Conclusion Long-term follow-up of our initial cohort confirms the observation of excellent overall survival, particularly for those patients younger than age 60 at diagnosis. For older patients, it appears to be reasonable to defer whole brain radiotherapy in an effort to minimize treatment-related neurotoxicity.
Preoperative Radiotherapy With or Without Concurrent Fluorouracil and Leucovorin in T3-4 Rectal Cancers: Results of FFCD 9203
Authors: Gérard Jean-Pierre , Conroy Thierry , Bonnetain Franck , Bouché Olivier , Chapet Olivier , Closon-Dejardin Marie-Thérèse , Untereiner Michel , Leduc Bernard , Francois Éric , Maurel Jean , Seitz Jean-François , Buecher Bruno , Mackiewicz Rémy , Ducreux Michel , Bedenne Laurent 
Published: September 2006

Purpose In 1992, preoperative radiotherapy was considered in France as the standard treatment for T3-4 rectal cancers. The present randomized trial compares preoperative radiotherapy with chemoradiotherapy. Patients and Methods Patients were eligible if they presented a resectable T3-4, Nx, M0 rectal adenocarcinoma accessible to digital rectal examination. Preoperative radiotherapy with 45 Gy in 25 fractions during 5 weeks was delivered. Concurrent chemotherapy with fluorouracil 350 mg/m2/d during 5 days, together with leucovorin, was administered during the first and fifth week in the experimental arm. Surgery was planned 3 to 10 weeks after the end of radiotherapy. All patients should receive adjuvant chemotherapy with the same fluorouracil/leucovorin regimen. The primary end point of the trial was overall survival. Results A total of 733 patients were eligible. Grade 3 or 4 acute toxicity was more frequent with chemoradiotherapy (14.6% v 2.7%; P < .05). There was no difference in sphincter preservation. Complete sterilization of the operative specimen was more frequent with chemoradiotherapy (11.4% v 3.6%; P < .05). The 5-year incidence of local recurrence was lower with chemoradiotherapy (8.1% v 16.5%; P < .05). Overall 5-year survival in the two groups did not differ. Conclusion Preoperative chemoradiotherapy despite a moderate increase in acute toxicity and no impact on overall survival significantly improves local control and is recommended for T3-4, N0-2, M0 adenocarcinoma of the middle and distal rectum.
Early Response Evaluation in Malignant Pleural Mesothelioma by Positron Emission Tomography With [18F]Fluorodeoxyglucose
Authors: Ceresoli Giovanni L. , Chiti Arturo , Zucali Paolo A. , Rodari Marcello , Lutman Romano F. , Salamina Silvia , Incarbone Matteo , Alloisio Marco , Santoro Armando 
Published: September 2006

PurposeResponse evaluation with conventional criteria based on computed tomography (CT) is particularly challenging in malignant pleural mesothelioma (MPM) due to its diffuse pattern of growth. There is growing evidence that therapy-induced changes in tumor [18F]fluorodeoxyglucose (FDG) uptake as measured by positron emission tomography (PET) may predict response and patient outcome early in the course of treatment.Patients and MethodsPatients with histologically proven MPM, not candidates to curative surgery, scheduled to undergo palliative chemotherapy with a pemetrexed-based regimen were eligible for this study. Patients were evaluated by FDG-PET and CT at baseline and after two cycles of therapy. A decrease of 25% or more in tumor FDG uptake as measured by standardized uptake value was defined as a metabolic response (MR). Best overall response from CT scans was determined according to previously published criteria.ResultsTwenty-two patients were included in the study, and 20 were assessable for early metabolic response with FDG-PET. Of these, eight were classified as responders (40%) and 12 as nonresponders (60%). Early MR was significantly correlated to median time-to-tumor progression (TTP) with a median TTP for metabolic responders of 14 months versus 7 months for nonresponders (P = .02). No correlation was found between TTP and radiologic response evaluated by CT. Patients with a MR had a trend toward longer overall survival.ConclusionThe use of MR evaluated by FDG-PET in the assessment of treatment efficacy in MPM appears promising. Our observations need to be validated in a larger prospective series.