bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cytokine storm in a mouse model of IgG-mediated hemolytic transfusion reactions
Authors: Hod Eldad A. , Cadwell Chantel M. , Liepkalns Justine S. , Zimring James C. , Sokol Set A. , Schirmer David A. , Jhang Jeffrey , Spitalnik Steven L. 
Published: May 2008

AbstractCytokines are hypothesized to play a central role in the pathophysiology of IgG-mediated hemolytic transfusion reactions (HTRs), and deeper understanding is required for improving therapy for these events. After establishing well-defined mouse models of HTRs, we tested whether cytokines were involved. Red blood cells (RBCs) from human glycophorin A transgenic (hGPA-Tg) or wild-type (WT) mice were transfused into non-Tg recipients passively immunized with monoclonal antibodies (Mabs). Only transfusions of incompatible RBCs induced IgG-mediated HTRs, exemplified by rapid clearance and hemoglobinuria. Very high plasma levels of monocyte chemoattractant protein-1 (MCP-1) and interleukin-6 (IL-6), and lower levels of tumor necrosis factor-α (TNF-α), were induced after incompatible transfusion. No significant changes in IL-10, IL-12, or interferon-γ (IFN-γ) levels were observed. The proinflammatory cytokines elaborated in this in vivo mouse model are also implicated in the systemic inflammatory response syndrome (SIRS) and confirm the hypothesis that cytokine storm occurs as a result of HTRs.
The Xenopus FcR family demonstrates continually high diversification of paired receptors in vertebrate evolution
Authors: Guselnikov Sergey V , Ramanayake Thaminda , Erilova Aleksandra Y , Mechetina Ludmila V , Najakshin Alexander M , Robert Jacques , Taranin Alexander V 
Published: May 2008

AbstractBackgroundRecent studies have revealed an unexpected diversity of domain architecture among FcR-like receptors that presumably fulfill regulatory functions in the immune system. Different species of mammals, as well as chicken and catfish have been found to possess strikingly different sets of these receptors. To better understand the evolutionary history of paired receptors, we extended the study of FcR-like genes in amphibian representativesXenopus tropicalisandXenopus laevis.ResultsThe diploid genome ofX. tropicaliscontains at least 75 genes encoding paired FcR-related receptors designated XFLs. The allotetraploidX. laevisdisplays many similar genes primarily expressed in lymphoid tissues. Up to 35 domain architectures generated by combinatorial joining of six Ig-domain subtypes and two subtypes of the transmembrane regions were found in XFLs. None of these variants are shared by FcR-related proteins from other studied species. Putative activating XFLs associate with the FcRγ subunit, and their transmembrane domains are highly similar to those of activating mammalian KIR-related receptors. This argues in favor of a common origin for the FcR and the KIR families. Phylogenetic analysis shows that the entire repertoires of theXenopusand mammalian FcR-related proteins have emerged after the amphibian-amniotes split.ConclusionFcR- and KIR-related receptors evolved through continual species-specific diversification, most likely by extensive domain shuffling and birth-and-death processes. This mode of evolution raises the possibility that the ancestral function of these paired receptors was a direct interaction with pathogens and that many physiological functions found in the mammalian receptors were secondary acquisitions or specializations.
Insight into the early steps of root hair formation revealed by the procuste1 cellulose synthase mutant of Arabidopsis thaliana
Authors: Singh Sunil K , Fischer Urs , Singh Manoj , Grebe Markus , Marchant Alan 
Published: May 2008

Abstract

Background
Formation of plant root hairs originating from epidermal cells involves selection of a polar initiation site and production of an initial hair bulge which requires local cell wall loosening. In Arabidopsis the polar initiation site is located towards the basal end of epidermal cells. However little is currently understood about the mechanism for the selection of the hair initiation site or the mechanism by which localised hair outgrowth is achieved. The Arabidopsis procuste1 (prc1-1) cellulose synthase mutant was studied in order to investigate the role of the cell wall loosening during the early stages of hair formation.

Results
The prc1-1 mutant exhibits uncontrolled, preferential bulging of trichoblast cells coupled with mislocalised hair positioning. Combining the prc1-1 mutant with root hair defective6-1 (rhd6-1), which on its own is almost completely devoid of root hairs results in a significant restoration of root hair formation. The pEXPANSIN7::GFP (pEXP7::GFP) marker which is specifically expressed in trichoblast cell files of wild-type roots, is absent in the rhd6-1 mutant. However, pEXP7::GFP expression in the rhd6-1/prc1-1 double mutant is restored in a subset of epidermal cells which have either formed a root hair or exhibit a bulged phenotype consistent with a function for EXP7 during the early stages of hair formation.

Conclusion
These results show that RHD6 acts upstream of the normal cell wall loosening event which involves EXP7 expression and that in the absence of a functional RHD6 the loosening and accompanying EXP7 expression is blocked. In the prc1-1 mutant background, the requirement for RHD6 during hair initiation is reduced which may result from a weaker cell wall structure mimicking the cell wall loosening events during hair formation.
Evaluation of left ventricular outflow tract gradient during treadmill exercise and in recovery period in orthostatic position, in patients with hypertrophic cardiomyopathy
Authors: Miranda Rita , Cotrim Carlos , Cardim Nuno , Almeida Sofia , Lopes Luís , Loureiro Maria José , Simões Otília , Cordeiro Pedro , Fazendas Paula , João Isabel , Carrageta Manuel 
Published: May 2008

Abstract

Background-
Left ventricular outflow tract obstruction is an independent predictor of adverse outcome in hypertrophic cardiomyopathy (HCM). The classical quantification of intraventricular obstruction is performed in resting conditions in supine position, but this assessment does not reflect what happens in HCM patients (pts) in their daily activities, neither during effort nor during orthostatic recovery.

Aim-
To assess intraventricular gradients with echocardiography during treadmill exercise and in the recovery period in upright position, in HCM pts.

Methods-
We studied 17 HCM pts (9 males, mean age 53 ± 16 years, 11 with obstructive HCM). Each pt had 2 echocardiographic evaluations at rest (left lateral decubitus (LLD) and orthostatic position). The pts then underwent a treadmill exercise test and intraventricular gradients were measured at peak exercise and during recovery in orthostatic position.

Results-
3 pts with non-obstructive HCM at rest developed intraventricular gradients during exercise. 1 pt developed this gradient only during orthostatic recovery. The mean intraventricular gradient in LLD was 49 ± 24 mmHg; in orthostatic position was 62 ± 29 mmHg (p < 0.001 versus in LLD); at peak exercise was 83 ± 35 mmHg (p < 0.001 versus supine rest); during recovery it was 96 ± 35 mmHg (p < 0.001 versus peak exercise)

Conclusion-
In HCM pts the intraventricular gradient increases in orthostatic position, increases significantly during treadmill exercise and continues increasing in the recovery period in orthostatic position. This type of evaluation can help us to better understand the physiopathology, the symptoms and the efficacy of different therapeutic modalities in this disease and should be routinely used in the assessment of HCM pts.
Individual mRNA expression profiles reveal the effects of specific microRNAs
Authors: Arora Amit , Simpson David AC 
Published: May 2008

Abstract
Background
MicroRNAs (miRNAs) are oligoribonucleotides with an important role in regulation of gene expression at the level of translation. Despite imperfect target complementarity, they can also significantly reduce mRNA levels. The validity of miRNA target gene predictions is difficult to assess at the protein level. We sought, therefore, to determine whether a general lowering of predicted target gene mRNA expression by endogenous miRNAs was detectable within microarray gene expression profiles.

Results
The target gene sets predicted for each miRNA were mapped onto known gene expression data from a range of tissues. Whether considering mean absolute target gene expression, rank sum tests or 'ranked ratios', many miRNAs with significantly reduced target gene expression corresponded to those known to be expressed in the cognate tissue. Expression levels of miRNAs with reduced target mRNA levels were higher than those of miRNAs with no detectable effect on mRNA expression. Analysis of microarray data gathered after artificial perturbation of expression of a specific miRNA confirmed the predicted increase or decrease in influence of the altered miRNA upon mRNA levels. Strongest associations were observed with targets predicted by TargetScan.

Conclusion
We have demonstrated that the effect of a miRNA on its target mRNAs' levels can be measured within a single gene expression profile. This emphasizes the extent of this mode of regulation in vivo and confirms that many of the predicted miRNA-mRNA interactions are correct. The success of this approach has revealed the vast potential for extracting information about miRNA function from gene expression profiles.
Cell cycle regulation by FasL and Apo2L/TRAIL in human T-cell blasts. Implications for autoimmune lymphoproliferative syndromes
Authors: Bosque Alberto , Aguiló Juan I , del Rey Manuel , Paz-Artal Estela , Allende Luis M , Naval Javier , Anel Alberto 
Published: May 2008

AbstractThe Fas-FasL pathway plays an important role in the homeostasis of mature lymphocytes, with defects causing autoimmune lymphoproliferative syndromes (ALPS). Human T-cell blasts are not sensitive to FasL or Apo2L/TRAIL-induced apoptosis unless they get reactivated, but either of those ligands inhibits their growth in the absence of cell death induction due to a cell cycle arrest in S-G2/M. In the present work, we have studied the mechanism(s) by which FasL or Apo2L/TRAIL regulate T-cell blast cell cycle in healthy donors and in two types of ALPS patients. Our data indicate that in human CD8+ T-cell blasts, Fas ligation, and especially Apo2L/TRAIL induce the p53-dependent decrease in cyclin-B1 levels. However, the induction of the negative cell cycle regulator p21WAF1 by FasL or Apo2L/TRAIL in either CD4+ or CD8+ T-cell blasts seems to be the main regulatory mechanism. This mechanism is dependent on caspase activation and on H2O2 generation. The increase in p21 levels by FasL or Apo2L/TRAIL is concomitant with p53 increases only in CD8+ T-cell blasts, with p21 levels maintained high for longer times than p53 levels. In CD4+ T-cell blasts p21 levels are controlled through a transient and p53-independent mechanism. The present results suggest that the etiology of ALP syndromes could be related not only to defects in apoptosis induction, but also in cell cycle regulation.
No end in site: TWEAK/Fn14 activation and autoimmunity associated- end-organ pathologies
Authors: Zheng Timothy S , Burkly Linda C 
Published: May 2008

AbstractGrowing evidence suggests that the tumor necrosis factor superfamily (TNFSF) member TWEAK and its cognate receptor Fn14 play an important role in both physiological and pathological tissue remodeling. Herein, we review the various lines of experimental evidence that support the involvement of this ligand/receptor pair in triggering a wide range of cellular responses crucial to tissue remodeling, including angiogenic, proliferative, and inflammatory responses, and discuss the molecular mechanisms by which TWEAK/Fn14-induced tissue responses can lead to desired vs. undesired consequences in a context-dependent manner. We explore the key features of TWEAK-induced end-organ pathologies in various autoimmune disorders and the potential therapeutic benefits of TWEAK inhibition therein. We submit the viewpoint that TWEAK/Fn14-mediated pathogenic tissue remodeling represents an important, universal mechanism leading to various end-organ pathologies associated with autoimmune and inflammatory disorders. The highly specific and localized nature of its pathogenic contribution, therefore, makes the TWEAK/Fn14 pathway a unique and promising therapeutic target.
Sleep/Wake Patterns of Individuals With Advanced Cancer Measured by Ambulatory Polysomnography
Authors: Parker Kathy P. , Bliwise Donald L. , Ribeiro Maria , Jain Sanjay R. , Vena Catherine I. , Kohles-Baker Mary Kay , Rogatko Andre , Xu Zhiheng , Harris Wayne B. 
Published: May 2008

Purpose Sleep/wake disturbances are prevalent in patients with advanced cancer, but 24-hour polysomnography (PSG) examinations of these patterns have not been undertaken. The purpose of this study was to describe these sleep/wake patterns using continuous PSG and to explore relationships with selected demographic and clinical variables. Patients and Methods The sample included patients with advanced cancer (solid tumors); those with neurologic disorders or psychosis, substance abuse, or brain metastasis were excluded. The final sample included 114 participants with a mean age of 51.1 years (± 9.1 years). Participants underwent continuous, ambulatory PSG for 42 hours in their home environments. Standard PSG measures were calculated. Analysis included data from 2 nights and the intervening day. Descriptive statistics were used to summarize sleep/wake parameters of the average of the 2 nights and the intervening day. Nonparametric analyses were used to detect differences and relationships among the variables. Results Compared with normative data, participants had reduced quantity and quality of nocturnal sleep and episodes of sleep scattered throughout the day. Increased daytime sleep was negatively associated with several key parameters of nocturnal sleep quantity and quality. Women, whites, and those who were married/partnered and had more education had better nocturnal sleep. Cancer type and selected medications may be risk factors for disturbed sleep and waking. Conclusion Participants experienced severe difficulty with “state maintenance”, or the ability to maintain both the sleep and waking states. Research designed to identify the etiology of these problems is needed to develop effective interventions.
Estrogen- and Progesterone-Receptor Status in ECOG 2197: Comparison of Immunohistochemistry by Local and Central Laboratories and Quantitative Reverse Transcription Polymerase Chain Reaction by Central Laboratory
Authors: Badve Sunil S. , Baehner Frederick L. , Gray Robert P. , Childs Barrett H. , Maddala Tara , Liu Mei-Lan , Rowley Steve C. , Shak Steven , Perez Edith D. , Shulman Lawrence J. , Martino Silvana , Davidson Nancy E. , Sledge George W. , Goldstein Lori J. , Sparano Joseph A. 
Published: May 2008

Purpose Central and local laboratory concordance for hormone receptor measurement is therapeutically important. This study compares estrogen receptor (ER) and progesterone receptor (PR) measured by local laboratory immunohistochemistry (IHC), central IHC, and central reverse-transcriptase polymerase chain reaction (RT-PCR) using a proprietary 21-gene assay. Patients and Methods A case-control sample of 776 breast cancer patients from Eastern Cooperative Oncology Group (ECOG) study E2197 was evaluated. Central IHC Allred score for ER and PR was obtained using tissue microarrays and 1D5 ER antibody and 636 PR antibody. Quantitative RT-PCR for ER and PR in whole sections was performed using the 21-gene assay. Results For ER, the concordance between local and central IHC was 90% (95% CI, 88% to 92%), between local IHC and central RT-PCR was 91% (95% CI, 89% to 93%), and between central IHC and central RT-PCR was 93% (95% CI, 91% to 95%). For PR, the concordance between local IHC and central IHC was 84% (95% CI, 82% to 87%), between local IHC and central RT-PCR was 88% (95% CI, 85% to 90%), and between central IHC and central RT-PCR was 90% (95% CI, 88% to 92%). Although concordance was high, IHC ER-negative cases that were RT-PCR positive were more common than IHC ER-positive cases that were RT-PCR negative. In ER-positive patients, ER expression by central IHC Allred score was marginally associated with recurrence (P = .091), and ER expression by central RT-PCR was significantly associated with recurrence (P = .014). However, recurrence score, which incorporates additional genes/pathways, was a highly significant predictor of recurrence (P < .0001). Conclusion There is a high degree of concordance among local IHC, central IHC, and central RT-PCR by the proprietary gene assay for ER and PR status. Although ER expression is marginally associated with relapse in ER-positive patients treated with chemohormonal therapy, recurrence score is a highly significant predictor of recurrence.
Randomized Phase II Trial of Induction Chemotherapy Followed by Concurrent Chemotherapy and Dose-Escalated Thoracic Conformal Radiotherapy (74 Gy) in Stage III Non–Small-Cell Lung Cancer: CALGB 30105
Authors: Socinski Mark A. , Blackstock A. William , Bogart Jeffrey A. , Wang Xiaofei , Munley Michael , Rosenman Julian , Gu Lin , Masters Gregory A. , Ungaro Peter , Sleeper Arthur , Green Mark , Miller Antonius A. , Vokes Everett E. 
Published: May 2008

Purpose To evaluate 74 Gy thoracic radiation therapy (TRT) with induction and concurrent chemotherapy in stage IIIA/B non–small-cell lung cancer (NSCLC). Patients and Methods Patients with stage IIIA/B NSCLC were randomly assigned to induction chemotherapy with either carboplatin (area under the curve [AUC], 6; days 1 and 22) with paclitaxel (225 mg/m2; days 1 and 22; arm A) or carboplatin (AUC, 5; days 1 and 22) with gemcitabine (1,000 mg/m2; days 1, 8, 22, and 29; arm B). On day 43, arm A received weekly carboplatin (AUC, 2) and paclitaxel (45 mg/m2) while arm B received biweekly gemcitabine (35 mg/m2) both delivered concurrently with 74 Gy of TRT utilizing three-dimensional treatment planning. The primary end point was survival at 18 months. Results Forty-three and 26 patients were accrued to arms A and B, respectively. Arm B was closed prematurely due to a high rate of grade 4 to 5 pulmonary toxicity. The overall response rate was 66.6% (95% CI, 50.5% to 80.4%) and 69.2% (95% CI, 48.2% to 85.7%) on arm A and B, respectively. The median survival time (MST) and 1-year survival rate was 24.3 months (95% CI, 12.3 to 36.4) and 66.7% (95% CI, 50.3 to 78.7) and 12.5 months (95% CI, 9.4 to 27.6) and 50.0% (95% CI, 29.9 to 67.2) for arms A and B, respectively. The primary toxicities included esophagitis, pulmonary, and fatigue. Conclusion Arm A reached the primary end point with an estimated MST longer than 18 months and will be compared with a standard dose of TRT in a planned randomized phase III trial in the United States cooperative groups.
Prospective Phase II Trial of Neoadjuvant Chemotherapy With Gemcitabine and Cisplatin for Resectable Adenocarcinoma of the Pancreatic Head
Authors: Heinrich Stefan , Pestalozzi Bernhard C. , Schäfer Markus , Weber Achim , Bauerfeind Peter , Knuth Alexander , Clavien Pierre-Alain 
Published: May 2008

Purpose To test the safety of neoadjuvant chemotherapy for resectable pancreatic cancer. Patients and Methods Patients with cytologically proven resectable adenocarcinoma of the pancreatic head were eligible for this prospective phase II trial. After confirmation of resectability by contrast-enhanced computed tomography (ceCT), positron emission tomography/CT, laparoscopy, and endoscopic ultrasound, patients received four biweekly cycles of gemcitabine 1,000 mg/m2 and cisplatin 50 mg/m2. Thereafter, staging was repeated and patients underwent surgery. Quality of life (QoL) and prealbumin serum levels were determined pre- and postchemotherapy. Follow-up included 3-month CA 19-9 measurements and ceCT after 6, 12, 18, and 24 months. Histologic tumor response was assessed by two scoring systems. Results Twenty-eight patients entered this study. Adverse effects were mainly gastrointestinal and hematologic, most often mild, and never of grade 4. Twenty-six patients (93%) had resectable cancer on restaging examinations, and the R0 resection rate was 80%. Histologic tumor response and cytopathic effects were documented in 54% and 83% of patients, respectively. On intention-to-treat analysis, disease-free and overall survival were 9.2 months (95% CI, 5.6 to 12.9 months) and 26.5 months (95% CI, 11.4 to 41.5 months) and 9 months (95% CI, 6.99 to 10.1 months) and 19.1 months (95% CI, 15 to 23.1 months) for ductal adenocarcinoma, respectively. QoL improved in two items and was unchanged in all other items. Moreover, prealbumin serum levels significantly improved during chemotherapy (P = .008). Conclusion Neoadjuvant chemotherapy with gemcitabine and cisplatin is well tolerated and does not impair resectability of pancreatic cancer. Furthermore, it improves the QoL and the nutritional status of affected patients with favorable overall and disease-free survival.
Adjuvant Chemotherapy for Stage III Colon Cancer: Do Physicians Agree About the Importance of Patient Age and Comorbidity?
Authors: Keating Nancy L. , Landrum Mary Beth , Klabunde Carrie N. , Fletcher Robert H. , Rogers Selwyn O. , Doucette William R. , Tisnado Diana , Clauser Steven , Kahn Katherine L. 
Published: May 2008

Purpose We surveyed cancer physicians to understand how patients' age and comorbidity influence adjuvant chemotherapy recommendations and whether physician or practice characteristics also affect these recommendations. Methods National survey of surgeons and medical oncologists caring for patients with colorectal cancer regarding whether they would recommend adjuvant chemotherapy for hypothetical patients with stage III colon cancer who varied by age (55 v 80 years) and comorbid illness (none, moderate, severe congestive heart failure [CHF]). Repeated measures logistic regression was used to assess the influence of patient, physician, and practice characteristics on chemotherapy recommendations. Results Of 1,096 physicians, nearly all recommended chemotherapy for patients who were 55 years old with no comorbidity (99.0%), 55-years old with moderate CHF (88.6%), or 80 years old with no comorbidity (92.6%); many fewer recommended chemotherapy for 55-year-old patients with severe CHF (24.9%) or 80-year-old patients with moderate (47.2%) or severe (9.0%) CHF (P < .001). Younger physicians (P < .001) were more likely than others to recommend adjuvant chemotherapy overall, although physician factors explained little of the variability in recommendations. Conclusion Physicians agree with guidelines recommending adjuvant chemotherapy for young, healthy patients with stage III colon cancer but differ widely on recommendations for patients who are older and sicker. Few physician or practice characteristics were associated with recommendations. For older and sicker patients, the individual physicians seen may have a substantial impact on the likelihood of receiving chemotherapy. Understanding better the sources of variation not explained by patients' clinical characteristics may allow improved tailoring of therapy to patients most likely to benefit.