bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bone marrow mesenchymal stem cells induce division arrest anergy of activated T cells
Authors: Glennie Sarah , Soeiro Inês , Dyson Peter J. , Lam Eric W.-F. , Dazzi Francesco 
Published: March 2005

AbstractIt has been shown that mesenchymal stem cells (MSCs) induce T cells to become unresponsive. We characterized the phenotype of these T cells by dissecting the effect of MSCs on T-cell activation, proliferation, and effector function. For this purpose, an in vitro murine model was used in which T-cell responses were generated against the male HY minor histocompatibility antigen. In the presence of MSCs, the expression of early activation markers CD25 and CD69 was unaffected but interferon-γ (IFN-γ) production was reduced. The inhibitory effect of MSCs was directed mainly at the level of cell proliferation. Analysis of the cell cycle showed that T cells, stimulated in the presence of MSCs, were arrested at the G1 phase. At the molecular level, cyclin D2 expression was profoundly inhibited, whereas p27kip1 was up-regulated. When MSCs were removed from the cultures and restimulated with the cognate peptide, T cells produced IFN-γ but failed to proliferate. The addition of exogenous interleukin-2 (IL-2) did not restore proliferation. MSCs did not preferentially target any T-cell subset, and the inhibition was also extended to B cells. MSC-mediated inhibition induces an unresponsive T-cell profile that is fully consistent with that observed in division arrest anergy.
MBEToolbox: a Matlab toolbox for sequence data analysis in molecular biology and evolution
Authors: Cai James J , Smith David K , Xia Xuhua , Yuen Kwok-yung 
Published: March 2005

Abstract
Background
MATLAB is a high-performance language for technical computing, integrating computation, visualization, and programming in an easy-to-use environment. It has been widely used in many areas, such as mathematics and computation, algorithm development, data acquisition, modeling, simulation, and scientific and engineering graphics. However, few functions are freely available in MATLAB to perform the sequence data analyses specifically required for molecular biology and evolution.

Results
We have developed a MATLAB toolbox, called MBEToolbox, aimed at filling this gap by offering efficient implementations of the most needed functions in molecular biology and evolution. It can be used to manipulate aligned sequences, calculate evolutionary distances, estimate synonymous and nonsynonymous substitution rates, and infer phylogenetic trees. Moreover, it provides an extensible, functional framework for users with more specialized requirements to explore and analyze aligned nucleotide or protein sequences from an evolutionary perspective. The full functions in the toolbox are accessible through the command-line for seasoned MATLAB users. A graphical user interface, that may be especially useful for non-specialist end users, is also provided.

Conclusion
MBEToolbox is a useful tool that can aid in the exploration, interpretation and visualization of data in molecular biology and evolution. The software is publicly available at http://web.hku.hk/~jamescai/mbetoolbox/ and http://bioinformatics.org/project/?group_id=454.
Human immunodeficiency virus type 1 (HIV-1) proviral DNA load in purified CD4+ cells by LightCycler® Real-time PCR
Authors: Kabamba-Mukadi Benoît , Henrivaux Philippe , Ruelle Jean , Delferrière Nicole , Bodéus Monique , Goubau Patrick 
Published: March 2005

Abstract
Background
The human immunodeficiency virus type 1 (HIV-1) proviral DNA persists in infected cells, even after prolonged successful HAART. In the present study, a relative quantification assay of HIV-1 proviral DNA by LightCycler® real-time PCR based on SYBR Green I detection was developed in comparison to the number of purified CD4+ cells as estimated by the quantification of the β-globin gene.

Methods
The ability of the designed gag primers to quantify HIV-1 Group M and the PCR efficiency were assessed on HIV-1 reference isolate subtypes A, B, C and D. The 8E5 cell line containing a single defective copy of HIV-1 proviral DNA was used as a standard for both the HIV-1 target gene and the β-globin reference gene. The assay was applied on thirty consecutive patient samples received for RNA viral load determinations and on retrospective samples from fifteen patients undergoing 2 years of structured treatment interruption (STI).

Results
The lower limit of quantification was 50 HIV-1 DNA proviral copies per CD4+ cell sample. The dynamic range was from 50 to 106 HIV-1 DNA copies per CD4+ cell sample with intra- and inter-assay coefficients of variability ranging from 3.1% to 37.1%. The β-globin reference gene was quantified down to a limit of 1.5 pg of DNA/μl (approximately 5 cells) with intra- and interassay coefficients of variability ranging from 1.8% to 21%. DNA proviral load varies widely among HIV-1 infected patients. Proviral load and plasma viral load rebound were high in STI patients who took longer to achieve an undetectable plasma viral load under therapy. A statistically significant correlation was observed between DNA proviral load and RNA steady state viral load in STI patients (p-value = 0,012).

Conclusion
We have developed a fast, sensitive and specific relative quantification assay of HIV-1 proviral DNA in purified CD4+ cells. The assay enables the monitoring of HIV-1 proviral load, which may be useful to monitor therapy efficacy especially in patients with undetectable plasma RNA viral load, and allows the exploration of viral reservoirs.
Surgical revascularization versus amputation for peripheral vascular disease in dialysis patients: a cohort study
Authors: Logar Christine M , Pappas Lisa M , Ramkumar Nirupama , Beddhu Srinivasan 
Published: March 2005

Abstract
Background
Surgical treatment of peripheral vascular disease (PVD) in dialysis patients is controversial.

Methods
We examined the post-operative morbidity and mortality of surgical revascularization or amputation for PVD in a retrospective analysis of United States Renal Data System. Propensity scores for undergoing amputation were derived from a multivariable logistic regression model of amputation.

Results
Of the Medicare patients initiated on dialysis from Jan 1, 1995 to Dec 31, 1999, patients underwent surgical revascularization (n = 1,896) or amputation (n = 2,046) in the first 6 months following initiation of dialysis were studied. In the logistic regression model, compared to claudication, presence of gangrene had a strong association with amputation [odds ratio (OR) 19.0, 95% CI (confidence interval) 13.86–25.95]. The odds of dying within 30 days and within1 year were higher (30 day OR: 1.85, 95% CI: 1.45–2.36; 1 yr OR: 1.46, 95% CI: 1.25–1.71) in the amputation group in logistic regression model adjusted for propensity scores and other baseline factors. Amputation was associated with increased odds of death in patients with low likelihood of amputation (< 33rd percentile of propensity score) and moderate likelihood of amputation (33rd to 66th percentile) but not in high likelihood group (>66th percentile). The number of hospital days in the amputation and revascularization groups was not different.

Conclusion
Amputation might be associated with higher mortality in dialysis patients. Where feasible, revascularization might be preferable over amputation in dialysis patients.
Crystal structure of THEP1 from the hyperthermophile Aquifex aeolicus: a variation of the RecA fold
Authors: Roßbach Michael , Daumke Oliver , Klinger Claudia , Wittinghofer Alfred , Kaufmann Michael 
Published: March 2005

Abstract
Background
aaTHEP1, the gene product of aq_1292 from Aquifex aeolicus, shows sequence homology to proteins from most thermophiles, hyperthermophiles, and higher organisms such as man, mouse, and fly. In contrast, there are almost no homologous proteins in mesophilic unicellular microorganisms. aaTHEP1 is a thermophilic enzyme exhibiting both ATPase and GTPase activity in vitro. Although annotated as a nucleotide kinase, such an activity could not be confirmed for aaTHEP1 experimentally and the in vivo function of aaTHEP1 is still unknown.

Results
Here we report the crystal structure of selenomethionine substituted nucleotide-free aaTHEP1 at 1.4 Å resolution using a multiple anomalous dispersion phasing protocol. The protein is composed of a single domain that belongs to the family of 3-layer (α/β/α)-structures consisting of nine central strands flanked by six helices. The closest structural homologue as determined by DALI is the RecA family. In contrast to the latter proteins, aaTHEP1 possesses an extension of the β-sheet consisting of four additional β-strands.

Conclusion
We conclude that the structure of aaTHEP1 represents a variation of the RecA fold. Although the catalytic function of aaTHEP1 remains unclear, structural details indicate that it does not belong to the group of GTPases, kinases or adenosyltransferases. A mainly positive electrostatic surface indicates that aaTHEP1 might be a DNA/RNA modifying enzyme. The resolved structure of aaTHEP1 can serve as paradigm for the complete THEP1 family.
An assessment of food supplementation to chronically sick patients receiving home based care in Bangwe, Malawi : a descriptive study
Authors: Bowie Cameron , Kalilani Linda , Marsh Reg , Misiri Humphrey , Cleary Paul , Bowie Claire 
Published: March 2005

Abstract
Background
The effect of food supplementation provided by the World Food Programme to patients and their families enrolled in a predominantly HIV/AIDS home based care programme in Bangwe Malawi is assessed.

Methods
The survival and nutritional status of patients and the nutritional status of their families recruited up to six months before a food supplementation programme started are compared to subsequent patients and their families over a further 12 months.

Results
360 patients, of whom 199 died, were studied. Food supplementation did not improve survival but had an effect (not statistically significant) on nutritional status. Additional oil was given to some families; it may have improved survival but not nutritional status.

Conclusion
Food supplementation to HIV/AIDS home based care patients and their families does not work well. This may be because the intervention is too late to affect the course of disease or insufficiently targeted perhaps due to problems of distribution in an urban setting. The World Food Programme's emphasis on supplementary feeding for these families needs to be reviewed.
Therapeutic targets for HIV-1 infection in the host proteome
Authors: Liang Winnie S , Maddukuri Anil , Teslovich Tanya M , de la Fuente Cynthia , Agbottah Emmanuel , Dadgar Shabnam , Kehn Kylene , Hautaniemi Sampsa , Pumfery Anne , Stephan Dietrich A , Kashanchi Fatah 
Published: March 2005

AbstractBackgroundDespite the success of HAART, patients often stop treatment due to the inception of side effects. Furthermore, viral resistance often develops, making one or more of the drugs ineffective. Identification of novel targets for therapy that may not develop resistance is sorely needed. Therefore, to identify cellular proteins that may be up-regulated in HIV infection and play a role in infection, we analyzed the effects of Tat on cellular gene expression during various phases of the cell cycle.ResultsSOM and k-means clustering analyses revealed a dramatic alteration in transcriptional activity at the G1/S checkpoint. Tat regulates the expression of a variety of gene ontologies, including DNA-binding proteins, receptors, and membrane proteins. Using siRNA to knock down expression of several gene targets, we show that an Oct1/2 binding protein, an HIV Rev binding protein, cyclin A, and PPGB, a cathepsin that binds NA, are important for viral replication following induction from latency andde novoinfection of PBMCs.ConclusionBased on exhaustive and stringent data analysis, we have compiled a list of gene products that may serve as potential therapeutic targets for the inhibition of HIV-1 replication. Several genes have been established as important for HIV-1 infection and replication, including Pou2AF1 (OBF-1), complement factor H related 3, CD4 receptor, ICAM-1, NA, and cyclin A1. There were also several genes whose role in relation to HIV-1 infection have not been established and may also be novel and efficacious therapeutic targets and thus necessitate further study. Importantly, targeting certain cellular protein kinases, receptors, membrane proteins, and/or cytokines/chemokines may result in adverse effects. If there is the presence of two or more proteins with similar functions, where only one protein is critical for HIV-1 transcription, and thus, targeted, we may decrease the chance of developing treatments with negative side effects.
Increased serum HO-1 in hemophagocytic syndrome and adult-onset Still's disease: use in the differential diagnosis of hyperferritinemia
Authors: Kirino Yohei , Takeno Mitsuhiro , Iwasaki Mika , Ueda Atsuhisa , Ohno Shigeru , Shirai Akira , Kanamori Heiwa , Tanaka Katsuaki , Ishigatsubo Yoshiaki 
Published: March 2005

AbstractHeme oxygenase-1 (HO-1), an inducible heme-degrading enzyme, is expressed by macrophages and endothelial cells in response to various stresses. Because ferritin synthesis is stimulated by Fe2+, which is a product of heme degradation, we examined the relation between HO-1 and ferritin levels in the serum of patients with hemophagocytic syndrome (HPS), adult-onset Still's disease (ASD), and other diseases that may cause hyperferritinemia. Seven patients with HPS, 10 with ASD, 73 with other rheumatic diseases, 20 with liver diseases, 10 recipients of repeated blood transfusion because of hematological disorders, and 22 healthy volunteers were enrolled. Serum HO-1 and ferritin levels were determined by ELISA. Expression of HO-1 mRNA and protein by peripheral blood mononuclear cells (PBMCs) was determined by real-time PCR and immunocytochemical techniques, respectively. Serum levels of HO-1 were significantly higher in patients with active HPS and ASD than in the other groups (P < 0.01). HO-1 levels were not elevated in patients with other causes of hyperferritinemia but were moderately elevated in patients with dermatomyositis/polymyositis. Among patients with HPS and ASD, serum HO-1 levels correlated closely with serum ferritin levels, and the levels of both returned to normal after therapy had induced remission. Increased expression of HO-1 mRNA was confirmed in PBMCs from some patients with HPS and ASD. Hyperferritinemia correlated closely with increased serum HO-1 in patients with HPS and ASD but not other conditions, indicating that measurement of serum HO-1 and ferritin levels would be useful in the differential diagnosis of hyperferritinemia and perhaps also in monitoring disease activity in HPS and ASD.
CD134 as target for specific drug delivery to auto-aggressive CD4+T cells in adjuvant arthritis
Authors: Boot Elmieke PJ , Koning Gerben A , Storm Gert , Wagenaar-Hilbers Josée PA , van Eden Willem , Everse Linda A , Wauben Marca HM 
Published: March 2005

AbstractT cells have an important role during the development of autoimmune diseases. In adjuvant arthritis, a model for rheumatoid arthritis, we found that the percentage of CD4+ T cells expressing the activation marker CD134 (OX40 antigen) was elevated before disease onset. Moreover, these CD134+ T cells showed a specific proliferative response to the disease-associated epitope of mycobacterial heat shock protein 60, indicating that this subset contains auto-aggressive T cells. We studied the usefulness of CD134 as a molecular target for immune intervention in arthritis by using liposomes coated with a CD134-directed monoclonal antibody as a drug targeting system. Injection of anti-CD134 liposomes subcutaneously in the hind paws of pre-arthritic rats resulted in targeting of the majority of CD4+CD134+ T cells in the popliteal lymph nodes. Furthermore, we showed that anti-CD134 liposomes bound to activated T cells were not internalized. However, drug delivery by these liposomes could be established by loading anti-CD134 liposomes with the dipalmitate-derivatized cytostatic agent 5'-fluorodeoxyuridine. These liposomes specifically inhibited the proliferation of activated CD134+ T cells in vitro, and treatment with anti-CD134 liposomes containing 5'-fluorodeoxyuridine resulted in the amelioration of adjuvant arthritis. Thus, CD134 can be used as a marker for auto-aggressive CD4+ T cells early in arthritis, and specific liposomal targeting of drugs to these cells via CD134 can be employed to downregulate disease development.
Complete Response to Neoadjuvant Chemoradiotherapy in Esophageal Carcinoma Is Associated With Significantly Improved Survival
Authors: Berger Adam C. , Farma Jeffrey , Scott Walter J. , Freedman Gary , Weiner Louis , Cheng Jonathan D. , Wang Hao , Goldberg Melvyn 
Published: March 2005

PurposeAttempts to improve survival of patients with esophageal cancer have been made using induction chemoradiotherapy (CRT) followed by surgery. A large single-center experience was reviewed to determine which treatment-related variables could predict survival and recurrence.Patients and MethodsAll patients undergoing esophagectomy between January 1994 and December 2002 were reviewed. Univariate and multivariate analyses were performed using log-rank and Cox proportional hazards models, and survival curves were estimated using the Kaplan-Meier method.ResultsOf 171 patients with invasive cancer, 131 (77%) underwent preoperative CRT. The average age was 60 years, and most patients were male (85%). Operations performed included Ivor-Lewis (60%), transhiatal (8%), three-hole (23%), or left thoracoabdominal (8%) esophagectomy. Perioperative mortality rate was 5%. Median overall survival (OS) of the entire group was 33 months, and the 5-year OS rate was 26%. Induction CRT was associated with a 33% 5-year survival rate compared with 11% for surgery alone (P = .43). Patients downstaged to pathologic stage 0 or I had an improved OS and disease-free survival (DFS) compared with those patients who were not downstaged (P = .022). Additionally, the ability to perform an R0 resection was a significant factor for OS and DFS (n = 130; P < .0001 and P <.0002, respectively).ConclusionResponse to CRT and the ability to perform an R0 resection are associated with significantly improved survival in patients with esophageal carcinoma.
Survival After Recurrence of Ewing’s Sarcoma Family of Tumors
Authors: Barker Lisa M. , Pendergrass Thomas W. , Sanders Jean E. , Hawkins Douglas S. 
Published: March 2005

Purpose The overall survival (OS) of patients with relapsed Ewing’s sarcoma family of tumors (ESFT) is poor, and the relative benefit of high-dose therapy (HDT) is controversial. Patients and Methods We retrospectively identified 55 consecutive ESFT patients with adequate medical records for review, who were treated at Children’s Hospital and Regional Medical Center and who developed disease recurrence between January 1, 1985 and December 31, 2002. Results The median relapse-free interval (RFI) from diagnosis to first recurrence was 17 months (range, 5 to 90 months). Most recurrences were metastatic only (39 patients) or local and metastatic (10 patients). Twenty-seven patients (49%) achieved a partial or complete response to second-line treatment, with a median duration of response of 27 months (range, 5 to 119+ months). The 5-year OS rate for all relapsed patients was 23% (95% CI, 11% to 35%). By univariate analysis, improved OS was associated with response to second-line treatment versus no response (46% v 0%, respectively; P < .0001), RFI ≥ 24 months versus less than 24 months (48% v 12%, respectively; P = .0001), and no metastases at initial diagnosis versus presence of metastases (31% v 12%, respectively; P = .05). Because all 13 patients who received HDT also had responsive relapse, we performed a multivariate analysis. Reduced risk of death was associated with response to second-line therapy (relative risk, 0.14; 95% CI, 0.05 to 0.40), RFI ≥ 24 months (relative risk, 0.29; 95% CI, 0.13 to 0.66), and receiving HDT (relative risk, 0.26; 95% CI, 0.08 to 0.85). Conclusion HDT as consolidation therapy for relapsed ESFT seems to be associated with improved OS, even after adjusting for RFI and response to second-line treatment.
Improved Detection of Prostate Cancer Using Classification and Regression Tree Analysis
Authors: Garzotto Mark , Beer Tomasz M. , Hudson R. Guy , Peters Laura , Hsieh Yi-Ching , Barrera Eduardo , Klein Thomas , Mori Motomi 
Published: March 2005

Purpose To build a decision tree for patients suspected of having prostate cancer using classification and regression tree (CART) analysis. Patients and Methods Data were uniformly collected on 1,433 referred men with a serum prostate-specific antigen (PSA) levels of ≤ 10 ng/mL who underwent a prostate biopsy. Factors analyzed included demographic, laboratory, and ultrasound data (ie, hypoechoic lesions and PSA density [PSAD]). Twenty percent of the data was randomly selected and reserved for study validation. CART analysis was performed in two steps, initially using PSA and digital rectal examination (DRE) alone and subsequently using the remaining variables. Results CART analysis selected a PSA cutoff of more than 1.55 ng/mL for further work-up, regardless of DRE findings. CART then selected the following subgroups at risk for a positive biopsy: (1) PSAD more than 0.165 ng/mL/cc; (2) PSAD ≤ 0.165 ng/mL/cc and a hypoechoic lesion; (3) PSAD ≤ 0.165 ng/mL/cc, no hypoechoic lesions, age older than 55.5 years, and prostate volume ≤ 44.0 cc; and (4) PSAD ≤ 0.165 ng/mL/cc, no hypoechoic lesions, age older than 55.5 years, and 50.25 cc less than prostate volume ≤ 80.8 cc. In the validation data set, specificity and sensitivity were 31.3% and 96.6%, respectively. Cancers that were missed by the CART were Gleason score 6 or less in 93.4% of cases. Receiver operator characteristic curve analysis showed that CART and logistic regression models had similar accuracy (area under the curve = 0.74 v 0.72, respectively). Conclusion Application of CART analysis to the prostate biopsy decision results in a significant reduction in unnecessary biopsies while retaining a high degree of sensitivity when compared with the standard of performing a biopsy of all patients with an abnormal PSA or DRE.
Measurement of Gmax and Estimation of K of Saturated Clay Using Bender Elements in an Oedometer
Authors: Zeng X , Grolewski B 
Published: March 2005

Abstract
Recent developments in bender element technique have made it possible to determine Gmax and estimate K0 of soils under complex loading conditions. By measuring the shear wave velocities in different shear planes, the cross anisotropy in Gmax of soil induced by axial-symmetric loading can also be determined. The shear wave velocities can also be used to estimate the horizontal earth pressure coefficient at rest K0. This paper reports on an experimental setup that uses bender elements installed in an oedometer to measure shear wave velocities in four shear planes of a saturated clay specimen under different consolidation pressures. The data is used to investigate the cross anisotropy of stiffness in clay due to a K0 stress condition. The measured Gmax is compared with the results from a commonly used empirical formula. The measured shear wave velocities on different shear planes are also used to calculate K0 of clay under different consolidation pressures and compared with results from empirical formulae. The applied stress condition includes loading, unloading, and reloading of up to 22 cycles, thus providing information to study the influence of repeated loading on Gmax and K0 of a saturated clay.