bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential expression of the angiogenic Tie receptor family in arthritic and normal synovial tissue
Authors: Shahrara Shiva , Volin Michael V , Connors Matthew A , Haines G Kenneth , Koch Alisa E 
Published: September 2002

AbstractAngiopoietins (Ang) are vascular endothelial cell-specific growth factors that play important roles principally during the later stages of angiogenesis. We have compared the distribution of the receptor tyrosine kinase (Tie) and the Ang ligands in synovial tissues from normal subjects and those with rheumatoid arthritis (RA) and osteoarthritis (OA).Immunohistochemical analysis was used to determine the expression of Ang-1, Ang-2, Tie1 and Tie2 in synovial tissue of normal subjects and those with RA and OA. Ang-1, Ang-2, Tie1 and Tie2 mRNA and protein expression were quantified in synovial tissues and RA synovial tissue fibroblasts with real-time reverse transcription polymerase chain reaction and western blot analysis.In RA, Ang-1 positive immunostaining on lining cells, macrophages and endothelial cells was significantly higher than in OA and normal synovial tissue. The expression pattern of Ang-2 in synovial tissue was similar in RA and OA, whereas the Ang-2 expression was low in normal tissue. Synovial tissue from subjects with RA and OA showed a significant upregulation of Tie1 on lining cells, macrophages and endothelial cells compared to that from normal subjects. Tie2 was significantly upregulated in the RA and OA synovial tissue lining cells, macrophages and smooth muscle cells compared to normal synovial tissue. Generally Ang-1, Ang-2, Tie1 and Tie2 mRNA levels were higher in RA synovial tissue compared to normal and OA synovial tissues, and RA synovial tissue fibroblasts. Western blot analysis also demonstrated greater Tie1 and Tie2 protein expression in RA and OA synovial tissue compared to RA synovial tissue fibroblasts. In conclusion, the dominance of Ang-1 mRNA and protein expression over Ang-2 is in agreement with an active neovascularization in RA synovial tissue.
Differential binding of chemokines to macrophages and neutrophils in the human inflamed synovium
Authors: Patterson Angela M , Schmutz Caroline , Davis Scott , Gardner Lucy , Ashton Brian A , Middleton Jim 
Published: September 2002

AbstractIn chronic inflammatory foci, such as the rheumatoid joint, there is enhanced recruitment of phagocytes from the blood into the tissues. Chemokines are strongly implicated in directing the migration of these cells, although little is known regarding the chemokine receptors that could mediate their chemotaxis into the joint tissue. Therefore the objective of the study was to identify chemokine binding sites on macrophages and neutrophils within the rheumatoid synovium using radiolabeled ligand binding andin situautoradiography. Specific binding sites for CCL3 (macrophage inflammatory protein-1α), CCL5 (RANTES), CCL2 (monocyte chemoattractant protein-1) and CXCL8 (IL-8) were demonstrated on CD68+macrophages in the subintimal and intimal layers. The number and percentage of intimal cells that bound chemokines were greater in inflamed regions compared to noninflamed regions. The intensity of intimal binding varied between chemokines with the rank order, CCL3 > CCL5 > CCL2 > CXCL8. Neutrophils throughout the synovium bound CXCL8 but did not show any signal for binding CCL2, CCL3 or CCL5.Immunohistochemistry showed that both CXCR1 and CXCR2 are expressed by macrophages and neutrophils in the rheumatoid and nonrheumatoid synovia, suggesting that both of these receptors are responsible for the CXCL8 binding. The chemokine binding sites described on phagocytes may be involved in the migration of these cells into the inflamed joint.
Highly efficient genetic transduction of primary human synoviocytes with concentrated retroviral supernatant
Authors: Yang Jianmin , Friedman Michael S , Bian Huimin , Crofford Leslie J , Roessler Blake , McDonagh Kevin T 
Published: September 2002

AbstractWe are developing retroviral-mediated gene transfer to human fibroblast-like synovial cells (FLS) as one approach to characterizing genetic pathways involved in synoviocyte pathophysiology. Prior work has suggested that FLS are relatively refractory to infection by Moloney murine leukemia virus based vectors. To determine if viral titer influenced the transduction efficiency of FLS, we optimized a rapid, efficient, and inexpensive centrifugation method to concentrate recombinant retroviral supernatant. The technique was evaluated by measurement of the expression of a viral enhanced green fluorescent protein transgene in transduced cells, and by analysis of viral RNA in retroviral supernatant. Concentration (100-fold) was achieved by centrifugation of viral supernatant for four hours, with 100% recovery of viral particles. The transduction of FLS increased from approximately 15% with unconcentrated supernatant, to nearly 50% using concentrated supernatant. This protocol will be useful for investigators with applications that require efficient, stable, high level transgene expression in primary FLS.
Proteinase-3 as the major autoantigen of c-ANCA is strongly expressed in lung tissue of patients with Wegener's granulomatosis
Authors: Brockmann Holger , Schwarting Andreas , Kriegsmann Jörg , Petrow Peter , Gaumann Andreas , Müller Klaus-Michael , Galle Peter Robert , Mayet Werner 
Published: September 2002

AbstractProteinase-3 (PR-3) is a neutral serine proteinase present in azurophil granules of human polymorphonuclear leukocytes and serves as the major target antigen of antineutrophil cytoplasmic antibodies with a cytoplasmic staining pattern (c-ANCA) in Wegener's granulomatosis (WG). The WG disease appears as severe vasculitis in different organs (e.g. kidney, nose and lung). Little is known about the expression and distribution of PR-3 in the lung. We found that PR-3 is expressed in normal lung tissue and is upregulated in lung tissue of patients with WG. Interestingly, the parenchymal cells (pneumocytes type I and II) and macrophages, and not the neutrophils, express PR-3 most strongly and may contribute to lung damage in patients with WG via direct interaction with antineutrophil cytoplasmic antobodies (ANCA). These findings suggest that the PR-3 expression in parenchymal cells of lung tissue could be at least one missing link in the etiopathogenesis of pulmonary pathology in ANCA-associated disease.
Production of interleukin-1 receptor antagonist by human articular chondrocytes
Authors: Palmer Gaby , Guerne Pierre-Andre , Mezin Francoise , Maret Michel , Guicheux Jerome , Goldring Mary B , Gabay Cem 
Published: September 2002

AbstractInterleukin-1 receptor antagonist (IL-1Ra) is a natural IL-1 inhibitor possessing anti-inflammatory properties. IL-1Ra is produced as different isoforms, one secreted (sIL-1Ra) and three intracellular (icIL-1Ra1, icIL-1Ra2 and icIL-1Ra3), derived from the same gene. We examined the production of IL-1Ra species by cultured human articular chondrocytes in response to various cytokines. The levels of IL-1Ra were undetectable in culture supernatants of untreated cells, but were significantly increased by IL-1β. Cell lysates contained very low levels of IL-1Ra, even in response to IL-1β, suggesting that chondrocytes produce predominantly sIL-1Ra. IL-6, which had no effect on its own, enhanced the effect of IL-1β, while dexamethasone prevented the response. We observed by RT-PCR that IL-1β and IL-6 induced primarily the production ofsIL-1RamRNA. Furthermore, IL-1β alone or combined with IL-6 increased the levels of nascent unsplicedsIL-1RamRNA, suggesting that sIL-1Ra expression is regulated at the transcriptional level. Reporter gene assays in immortalized chondrocytes, C-20/A4, consistently showed increasedsIL-1Rapromoter activity in response to IL-1β and IL-6. In conclusion, human articular chondrocytes produce sIL-1Ra in response to IL-1β and IL-6. The production of sIL-1Ra by chondrocytes may have a protective effect against articular inflammatory and catabolic responses.
Systematic review: The relation between nutrition and nosocomial pneumonia: randomized trials in critically ill patients
Authors: Cook Deborah , Jonghe Bernard De , Heyland Daren 
Published: September 2002

Abstract
Objective
To review the effect of enteral nutrition on nosocomial pneumonia in critically ill patients as summarized in randomized clinical trials.

Study identification and selection
Studies were identified through MEDLINE, SCISEARCH, EMBASE, the Cochrane Library, bibliographies of primary and review articles, and personal files. Through duplicate independent review, we selected randomized trials evaluating approaches to nutrition and their relation to nosocomial pneumonia.

Data abstraction
In duplicate, independently, we abstracted key data on the design features, population, intervention and outcomes of the studies.

Results
We identified four trials of enteral vs total parenteral nutrition, one trial of early enteral nutrition vs delayed enteral nutrition, one trial of gastric vs jejunal tube feeding, one trial of intermittent vs continuous enteral feeding, and three trials evaluating different enteral feeding formulae. Sample sizes were small, pneumonia definitions were variable and blinded outcome assessment was infrequent. Randomized trial evidence is insufficient to draw conclusions about the relation between enteral nutrition and nosocomial pneumonia.

Conclusions
Nutritional interventions in critically ill patients appear to have a modest and inconsistent effect on nosocomial pneumonia. This body of evidence neither supports nor refutes the gastropulmonary route of infection.
Phase I Trial Evaluating the Concurrent Combination of Radiotherapy and Capecitabine in Rectal Cancer
Authors: Dunst Jürgen , Reese Thomas , Sutter Thomas , Zühlke Helmut , Hinke Axel , Kölling-Schlebusch Katrin , Frings Stefan 
Published: September 2002

PURPOSE: To establish the feasibility of concurrent radiotherapy and capecitabine and define the maximum-tolerated dose (MTD) in patients with rectal cancer. PATIENTS AND METHODS: Thirty-six patients with rectal cancer received treatment in the adjuvant, neoadjuvant, or palliative setting with a total irradiation dose of 50.4 Gy with 1.8 Gy/d in approximately 6 weeks. Capecitabine was administered at escalating doses from 250 to 1,250 mg/m2 bid (including weekends) for the duration of radiotherapy. The MTD was defined when two or more patients in a cohort of three or six patients experienced dose-limiting toxicities. RESULTS: Dose-limiting grade 3 hand-foot syndrome was observed in two of six patients treated at a capecitabine dose of 1,000 mg/m2 bid. Other toxicities were generally rare and/or mild, with only one case of non–dose-limiting grade 3 diarrhea and a single patient with grade 3 skin toxicity. Myelosuppression consisted mainly of leukocytopenia, with a maximum severity of grade 2. Thus, a dosage of 825 mg/m2 bid is the recommended dose level for further evaluation. One pathologic complete remission of a T3N1 tumor and nine partial remissions were observed in 10 patients treated in the neoadjuvant setting. CONCLUSION: The recommended dose for phase II evaluation is capecitabine 825 mg/m2 bid, administered without break during a conventional radiotherapy period of about 6 weeks. This combined-modality approach proved to be a feasible and well-tolerated treatment option with promising preliminary efficacy results in rectal cancer.
Quality of Life of Women With Recurrent Breast Cancer and Their Family Members
Authors: Northouse Laurel L. , Mood Darlene , Kershaw Trace , Schafenacker Ann , Mellon Suzanne , Walker Julie , Galvin Elizabeth , Decker Veronica 
Published: September 2002

PURPOSE: Little information is available about the effects of recurrent breast cancer on the quality of life of women and their family members. The present study assessed patients’ and family members’ quality of life within 1 month after recurrence, and effects of multiple factors on quality-of-life scores. PATIENTS AND METHODS: Patient/family member dyads (N = 189) participated in this study. A stress-appraisal model guided selection of person factors, social/family factors, illness-related factors, appraisal factors, and quality of life, measured with psychometrically sound instruments. Quality of life was measured with both generic (Medical Outcomes Study SF-36) and cancer-specific (Functional Assessment of Cancer Therapy) scales. RESULTS: Patients reported significant impairments in physical, functional, and emotional well-being. Family members reported significant impairments in their own emotional well-being. Structural equation modeling revealed that self-efficacy, social support, and family hardiness had positive effects on quality of life, whereas symptom distress, concerns, hopelessness, and negative appraisal of illness or caregiving had detrimental effects. Study variables accounted for a sizable amount of variance in patients’ and family members’ physical and mental dimensions of quality of life (72% to 81%). Contrary to findings observed in studies of newly diagnosed breast cancer patients and spouses, little relationship was found between recurrent patients’ and family members’ quality of life. CONCLUSION: Women with recurrent breast cancer are in need of programs to assist them with the severe effects of the disease on their quality of life. Programs need to include family members to help counteract the negative effects of the recurrent disease on their mental health, and to enable them to continue as effective caregivers.
Standard Versus Intensified Chemotherapy With Granulocyte Colony-Stimulating Factor Support in Small-Cell Lung Cancer: A Prospective European Organization for Research and Treatment of Cancer–Lung Cancer Group Phase III Trial—08923
Authors: Ardizzoni Andrea , Tjan-Heijnen Vivianne C.G. , Postmus Pieter E. , Buchholz Erica , Biesma Bonne , Karnicka-Mlodkowska Hanna , Dziadziuszko Rafal , Burghouts Jos , van Meerbeeck Jan P. , Gans Steven , Legrand Catherine , Debruyne Channa , Giaccone Giuseppe , Manegold for the Christian ,   European Organization for Research and Treatment of Cancer–Lung Cancer Group
Published: September 2002

PURPOSE: To assess the impact on survival of increasing dose-intensity (DI) of cyclophosphamide, doxorubicin, and etoposide (CDE) in small-cell lung cancer (SCLC). PATIENTS AND METHODS: Previously untreated SCLC patients were randomized to standard CDE (cyclophosphamide 1,000 mg/m2 and doxorubicin 45 mg/m2 on day 1, and etoposide 100 mg/m2 on days 1 to 3 every 3 weeks, for five cycles) or intensified CDE (cyclophosphamide 1,250 mg/m2 and doxorubicin 55 mg/m2 on day 1, and etoposide 125 mg/m2 on days 1 to 3 with granulocyte colony-stimulating factor [G-CSF] 5 μg/kg/d on days 4 to 13 every 2 weeks, for four cycles). Projected cumulative dose was almost identical on the two arms, whereas projected DI was nearly 90% higher on the intensified arm. Two hundred forty-four patients were enrolled. The first 163 patients were also randomized (2 × 2 factorial design) to prophylactic antibiotics or placebo to assess their impact on preventing febrile leukopenia (FL). This report focuses on chemotherapy DI results. RESULTS: With a median follow-up of 54 months, 216 deaths have occurred. Actually delivered DI on the intensified arm was 70% higher than on the standard arm. Intensified CDE was associated with more grade 4 leukopenia (79% v 50%), grade 4 thrombocytopenia (44% v 11%), anorexia, nausea, and mucositis. FL and number of toxic deaths were similar on the two arms. The objective response rate was 79% for the standard arm and 84% for the intensified arm (P = .315). Median survival was 54 weeks and 52 weeks, and the 2-year survival rates were 15% and 18%, respectively (P = .885). CONCLUSION: A 70% increase of CDE actual DI does not translate into an improved outcome in SCLC patients.
Randomized Clinical Trial of an Implantable Drug Delivery System Compared With Comprehensive Medical Management for Refractory Cancer Pain: Impact on Pain, Drug-Related Toxicity, and Survival
Authors: Smith Thomas J. , Staats Peter S. , Deer Timothy , Stearns Lisa J. , Rauck Richard L. , Boortz-Marx Richard L. , Buchser Eric , Català Elena , Bryce David A. , Coyne Patrick J. , Pool George E. 
Published: September 2002

PURPOSE: Implantable intrathecal drug delivery systems (IDDSs) have been used to manage refractory cancer pain, but there are no randomized clinical trial (RCT) data comparing them with comprehensive medical management (CMM). PATIENTS AND METHODS: We enrolled 202 patients on an RCT of CMM versus IDDS plus CMM. Entry criteria included unrelieved pain (visual analog scale [VAS] pain scores ≥ 5 on a 0 to 10 scale). Clinical success was defined as ≥ 20% reduction in VAS scores, or equal scores with ≥ 20% reduction in toxicity. The main outcome measure was pain control combined with change of toxicity, as measured by the National Cancer Institute Common Toxicity Criteria, 4 weeks after randomization. RESULTS: Sixty of 71 IDDS patients (84.5%) achieved clinical success compared with 51 of 72 CMM patients (70.8%, P = .05). IDDS patients more often achieved ≥ 20% reduction in both pain VAS and toxicity (57.7% [41 of 71] v 37.5% [27 of 72], P = .02). The mean CMM VAS score fell from 7.81 to 4.76 (39% reduction); for the IDDS group, the scores fell from 7.57 to 3.67 (52% reduction, P = .055). The mean CMM toxicity scores fell from 6.36 to 5.27 (17% reduction); for the IDDS group, the toxicity scores fell from 7.22 to 3.59 (50% reduction, P = .004). The IDDS group had significant reductions in fatigue and depressed level of consciousness (P < .05). IDDS patients had improved survival, with 53.9% alive at 6 months compared with 37.2% of the CMM group (P = .06). CONCLUSION: IDDSs improved clinical success in pain control, reduced pain, significantly relieved common drug toxicities, and improved survival in patients with refractory cancer pain.
Effectiveness of Adjuvant Fluorouracil in Clinical Practice: A Population-Based Cohort Study of Elderly Patients With Stage III Colon Cancer
Authors: Iwashyna Theodore J. , Lamont Elizabeth B. 
Published: September 2002

PURPOSE: Although randomized controlled trials (RCTs) consistently show that adjuvant fluorouracil (5-FU) extends the survival of patients with stage III colon cancer, it is not yet known whether this benefit exists in populations underrepresented on clinical trials, particularly the elderly with medical comorbidity treated in the community. In this study, we ask the following: (1) What is the hazard of death associated with adjuvant 5-FU in the general population of elderly stage III colon cancer patients? (2) Does the hazard vary with patient age? PATIENTS AND METHODS: In this prospective, nonrandomized, population-based cohort study of 3,357 elderly Medicare beneficiaries who had undergone resection of stage III colon cancer according to the Surveillance, Epidemiology, and End-Results registries, we use propensity score matching to compare the all-cause mortality of patients who received 5-FU to matched untreated patients. RESULTS: 5-FU reduces the hazard of death by 27% (hazard ratio, 0.73; 95% confidence interval [CI], 0.65 to 0.82) across the 6 years of our data in a Cox model. At 5 years, 52.7% (95% CI, 49.6% to 55.6%) of the treated and 40.7% (95% CI, 38.1% to 43.4%) of the matched untreated are still alive. We find that these effects do not diminish with advancing patient age. CONCLUSION: The survival benefit of adjuvant 5-FU that has been demonstrated in participants of RCTs is also evident in a population sample of elderly Medicare beneficiaries with stage III colon cancer treated in the community. Furthermore, this survival benefit does not appear to diminish with patient age. These findings support the continued use of adjuvant 5-FU in the general population of elderly patients with stage III colon cancer and suggest that oncologists in the community are practicing at a high level of effectiveness.
Recursive Partitioning Identifies Patients at High and Low Risk for Ipsilateral Tumor Recurrence After Breast-Conserving Surgery and Radiation
Authors: Freedman G. M. , Hanlon A. L. , Fowble B. L. , Anderson P. R. , Nicoloau N. 
Published: September 2002

PURPOSE: Recursive partitioning analysis (RPA), a method of building decision trees of significant prognostic factors for outcome, was used to determine subgroups at significantly different risk for ipsilateral breast tumor recurrence (IBTR) in early-stage breast cancer. PATIENTS AND METHODS: Nine hundred twelve women underwent breast-conserving surgery, axillary dissection, and radiation. Systemic therapy was chemotherapy with or without tamoxifen in 32%, tamoxifen in 27%, or none in 41%. RPA was used to create a decision tree according to predictive variables that classify patients by IBTR risk, and the Kaplan-Meier method was used to calculate 10-year risks. Median follow-up was 5.9 years. RESULTS: Age was the first split in the partition tree. Patients more than 55 years old had a 4% 10-year IBTR, the only further division being use of tamoxifen or not (2% v 5%, P = .03). For patients ≤ 55 years old, extensive intraductal component (EIC) was the next significant split. For EIC-negative tumors, age ≤ 35 years and negative margins were associated with a 10-year IBTR of 3%; with close (≤ 2 mm) or positive margins, 34%. Patients 36 to 55 years old with estrogen receptor–positive tumors receiving tamoxifen had a risk of IBTR of 5%, but had a 20% risk without tamoxifen. CONCLUSION: This RPA showed that age ≤ 55 versus more than 55 years was the most significant factor for IBTR. Patients ≤ 35 years old had a low risk of IBTR when tumors were EIC-negative with negative margins. EIC was an independent factor for IBTR for ages ≤ 55 years. Use of tamoxifen was the most significant factor for patients older than 55 years, but it resulted in a greater absolute decrease in risk of IBTR for patients 36 to 55 years old.