bluuebunny/crossref_metadata_2025_split huggingface dataset:
Saturated free fatty acids and apoptosis in microvascular mesangial cells: palmitate activates pro-apoptotic signaling involving caspase 9 and mitochondrial release of endonuclease G
Authors: Mishra Rangnath , Simonson Michael S 
Published: January 2005

Abstract
Background
In type 2 diabetes, free fatty acids (FFA) accumulate in microvascular cells, but the phenotypic consequences of FFA accumulation in the microvasculature are incompletely understood. Here we investigated whether saturated FFA induce apoptosis in human microvascular mesangial cells and analyzed the signaling pathways involved.

Methods
Saturated and unsaturated FFA-albumin complexes were added to cultured human mesangial cells, after which the number of apoptotic cells were quantified and the signal transduction pathways involved were delineated.

Results
The saturated FFA palmitate and stearate were apoptotic unlike equivalent concentrations of the unsaturated FFA oleate and linoleate. Palmitate-induced apoptosis was potentiated by etomoxir, an inhibitor of mitochondrial β-oxidation, but was prevented by an activator of AMP-kinase, which increases fatty acid β-oxidation. Palmitate stimulated an intrinsic pathway of pro-apoptotic signaling as evidenced by increased mitochondrial release of cytochrome-c and activation of caspase 9. A caspase 9-selective inhibitor blocked caspase 3 activation but incompletely blocked apoptosis in response to palmitate, suggesting an additional caspase 9-independent pathway. Palmitate stimulated mitochondrial release of endonuclease G by a caspase 9-independent mechanism, thereby implicating endonuclease G in caspase 9-indpendent regulation of apoptosis by saturated FFA. We also observed that the unsaturated FFA oleate and linoleate prevented palmitate-induced mitochondrial release of both cytochrome-c and endonuclease G, which resulted in complete protection from palmitate-induced apoptosis.

Conclusions
Taken together, these results demonstrate that palmitate stimulates apoptosis by evoking an intrinsic pathway of proapoptotic signaling and identify mitochondrial release of endonuclease G as a key step in proapoptotic signaling by saturated FFA and in the anti-apoptotic actions of unsaturated FFA.
Protein secretion in Lactococcus lactis: an efficient way to increase the overall heterologous protein production
Authors: Le Loir Yves , Azevedo Vasco , Oliveira Sergio C , Freitas Daniela A , Miyoshi Anderson , Bermúdez-Humarán Luis G , Nouaille Sébastien , Ribeiro Luciana A , Leclercq Sophie , Gabriel Jane E , Guimaraes Valeria D , Oliveira Maricê N , Charlier Cathy , Gautier Michel , Langella Philippe 
Published: January 2005

AbstractLactococcus lactis, the model lactic acid bacterium (LAB), is a food grade and well-characterized Gram positive bacterium. It is a good candidate for heterologous protein delivery in foodstuff or in the digestive tract. L. lactis can also be used as a protein producer in fermentor. Many heterologous proteins have already been produced in L. lactis but only few reports allow comparing production yields for a given protein either produced intracellularly or secreted in the medium. Here, we review several works evaluating the influence of the localization on the production yields of several heterologous proteins produced in L. lactis. The questions of size limits, conformation, and proteolysis are addressed and discussed with regard to protein yields. These data show that i) secretion is preferable to cytoplasmic production; ii) secretion enhancement (by signal peptide and propeptide optimization) results in increased production yield; iii) protein conformation rather than protein size can impair secretion and thus alter production yields; and iv) fusion of a stable protein can stabilize labile proteins. The role of intracellular proteolysis on heterologous cytoplasmic proteins and precursors is discussed. The new challenges now are the development of food grade systems and the identification and optimization of host factors affecting heterologous protein production not only in L. lactis, but also in other LAB species.
Evolutionary autonomous agents and the nature of apraxia
Authors: Borrett Donald S , Jin Frank , Kwan Hon C 
Published: January 2005

Abstract
Background
Evolutionary autonomous agents are robots or robot simulations whose controller is a dynamical neural network and whose evolution occurs autonomously under the guidance of a fitness function without the detailed or explicit direction of an external programmer. They are embodied agents with a simple neural network controller and as such they provide the optimal forum by which sensorimotor interactions in a specified environment can be studied without the computational assumptions inherent in standard neuroscience.

Methods
Evolutionary autonomous agents were evolved that were able to perform identical movements under two different contexts, one which represented an automatic movement and one which had a symbolic context. In an attempt to model the automatic-voluntary dissociation frequently seen in ideomotor apraxia, lesions were introduced into the neural network controllers resulting in a behavioral dissociation with loss of the ability to perform the movement which had a symbolic context and preservation of the simpler, automatic movement.

Results
Analysis of the changes in the hierarchical organization of the networks in the apractic EAAs demonstrated consistent changes in the network dynamics across all agents with loss of longer duration time scales in the network dynamics.

Conclusion
The concepts of determinate motor programs and perceptual representations that are implicit in the present day understanding of ideomotor apraxia are assumptions inherent in the computational understanding of brain function. The strength of the present study using EAAs to model one aspect of ideomotor apraxia is the absence of these assumptions and a grounding of all sensorimotor interactions in an embodied, autonomous agent. The consistency of the hierarchical changes in the network dynamics across all apractic agents demonstrates that this technique is tenable and will be a valuable adjunct to a computational formalism in the understanding of the physical basis of neurological disorders.
The biological effects of diagnostic cardiac imaging on chronically exposed physicians: the importance of being non-ionizing
Authors: Andreassi Maria Grazia 
Published: January 2005

AbstractUltrasounds and ionizing radiation are extensively used for diagnostic applications in the cardiology clinical practice. This paper reviewed the available information on occupational risk of the cardiologists who perform, every day, cardiac imaging procedures. At the moment, there are no consistent evidence that exposure to medical ultrasound is capable of inducing genetic effects, and representing a serious health hazard for clinical staff. In contrast, exposure to ionizing radiation may result in adverse health effect on clinical cardiologists. Although the current risk estimates are clouded by approximations and extrapolations, most data from cytogenetic studies have reported a detrimental effect on somatic DNA of professionally exposed personnel to chronic low doses of ionizing radiation. Since interventional cardiologists and electro-physiologists have the highest radiation exposure among health professionals, a major awareness is crucial for improving occupational protection. Furthermore, the use of a biological dosimeter could be a reliable tool for the risk quantification on an individual basis.
Ultrasound imaging versus morphopathology in cardiovascular diseases. Coronary atherosclerotic plaque
Authors: Baroldi Giorgio , Bigi Riccardo , Cortigiani Lauro 
Published: January 2005

AbstractThis review article is aimed at comparing the results of histopathological and clinical imaging studies to assess coronary atherosclerotic plaques in humans. In particular, the gap between the two techniques and its effect on the understanding of the pathophysiological basis of coronary artery disease is critically discussed.
Atrial fibrillation and survival in colorectal cancer
Authors: Walsh Stewart R , Gladwish Kelly M , Ward Nicholas J , Justin Timothy A , Keeling Neil J 
Published: January 2005

Abstract
Background
Survival in colorectal cancer may correlate with the degree of systemic inflammatory response to the tumour. Atrial fibrillation may be regarded as an inflammatory complication. We aimed to determine if atrial fibrillation is a prognostic factor in colorectal cancer.

Patients and methods
A prospective colorectal cancer patient database was cross-referenced with the hospital clinical-coding database to identify patients who had underwent colorectal cancer surgery and were in atrial fibrillation pre- or postoperatively.

Results
A total of 175 patients underwent surgery for colorectal cancer over a two-year period. Of these, 13 patients had atrial fibrillation pre- or postoperatively. Atrial fibrillation correlated with worse two-year survival (p = 0.04; log-rank test). However, in a Cox regression analysis, atrial fibrillation was not significantly associated with survival.

Conclusion
The presence or development of atrial fibrillation in patients undergoing surgery for colorectal cancer is associated with worse overall survival, however it was not found to be an independent factor in multivariate analysis.
Pancreatic metastasis from gastric carcinoma: a case report
Authors: Wente Moritz N , Bergmann Frank , Fröhlich Boris E , Schirmacher Peter , Büchler Markus W , Friess Helmut 
Published: January 2005

Abstract
Background
The pancreas is a rare but occasionally favored target for metastasis. Metastatic lesions in the pancreas have been described for various primary cancers, such as carcinomas of the lung, the breast, renal cell carcinoma and sarcomas.

Case presentation
We report the case of a 60-year old female with a mass in the pancreatic head four years after partial gastrectomy for gastric adenocarcinoma. The patient underwent a pancreatoduodenectomy. Pathological examination revealed metastases of the primary gastric carcinoma within the pancreatic head and in regional lymph nodes.

Conclusions
Pancreatic tumors in patients with a history of non-pancreatic malignancy should always be considered to be a putative metastatic lesion at an unusual site. If the pancreas can be identified as the only site of spread, radical resection may prolong survival.
Seroma formation after surgery for breast cancer
Authors: Hashemi Esmat , Kaviani Ahmad , Najafi Masoume , Ebrahimi Mandana , Hooshmand Homeira , Montazeri Ali 
Published: January 2005

Abstract
Background
Seroma formation is the most frequent postoperative complication after breast cancer surgery. We carried out a study to investigate the effect of various demographic, clinical and therapeutic variables on seroma formation.

Patients and methods
A retrospective cross sectional study of patients who underwent surgical therapy for breast cancer with either modified radical mastectomy (MRM) or breast preservation (BP) was carried out. The demographic data and clinical information were extracted from case records. Seroma formation was studied in relation to age, type of surgery, tumor size, nodal involvement, preoperative chemotherapy, surgical instrument (electrocautery or scalpel), use of pressure garment, and duration of drainage. The multiple logistic regression analysis was performed to estimate odds ratios.

Results
A total of 158 patients with breast cancer were studied. The mean age of the patients was 46.3 years (SD ± 11.9). Seventy-three percent underwent modified radical mastectomy and the remaining 27% received breast preservation surgery. Seroma occurred in 35% of patients. In multivariate logistic regression analysis an association of postoperative seroma formation was noted with modified radical mastectomy (OR = 2.83, 95% CI 1.01–7.90, P = 0.04). No other factor studied was found to significantly effect the seroma formation after breast cancer surgery.

Conclusion
The findings suggest that the type of surgery is a predicting factor for seroma formation in breast cancer patients.
Metallopanstimulin as a marker for head and neck cancer
Authors: Stack Brendan C , Hollenbeak Christopher S , Lee Christopher M , Dunphy Frank R , Lowe Val J , Hamilton Paul D 
Published: January 2005

Abstract
Background
Metallopanstimulin (MPS-1) is a ribosomal protein that is found in elevated amounts in the sera of patients with head and neck squamous cell carcinoma (HNSCC). We used a test, denoted MPS-H, which detects MPS-1 and MPS-1-like proteins, to determine the relationship between MPS-H serum levels and clinical status of patients with, or at risk for, HNSCC.

Patients and methods
A total of 125 patients were prospectively enrolled from a university head and neck oncology clinic. Participants included only newly diagnosed HNSCC patients. Two control groups, including 25 non-smokers and 64 smokers, were studied for comparison. A total of 821 serum samples collected over a twenty-four month period were analyzed by the MPS-H radioimmunoassay.

Results
HNSCC, non-smokers, and smokers had average MPS-H values of 41.5 ng/mL, 10.2 ng/mL, and 12.8 ng/mL, respectively (p = 0.0001).

Conclusion
We conclude that MPS-1 and MPS-1-like proteins are elevated in patients with HNSCC, and that MPS-H appears to be a promising marker of presence of disease and response to treatment in HNSCC patients.
Adoptive immunotherapy of cancer with polyclonal, 108-fold hyperexpanded, CD4+ and CD8+ T cells
Authors: Wang Li-Xin , Huang Wen-Xin , Graor Hallie , Cohen Peter A , Kim Julian A , Shu Suyu , Plautz Gregory E 
Published: January 2005

AbstractT cell-mediated cancer immunotherapy is dose dependent and optimally requires participation of antigen-specific CD4+ and CD8+ T cells. Here, we isolated tumor-sensitized T cells and activated them in vitro using conditions that led to greater than 108-fold numerical hyperexpansion of either the CD4+ or CD8+ subset while retaining their capacity for in vivo therapeutic efficacy. Murine tumor-draining lymph node (TDLN) cells were segregated to purify the CD62Llow subset, or the CD4+ subset thereof. Cells were then propagated through multiple cycles of anti-CD3 activation with IL-2 + IL-7 for the CD8+ subset, or IL-7 + IL-23 for the CD4+ subset. A broad repertoire of TCR Vβ families was maintained throughout hyperexpansion, which was similar to the starting population. Adoptive transfer of hyper-expanded CD8+ T cells eliminated established pulmonary metastases, in an immunologically specific fashion without the requirement for adjunct IL-2. Hyper-expanded CD4+ T cells cured established tumors in intracranial or subcutaneous sites that were not susceptible to CD8+ T cells alone. Because accessibility and antigen presentation within metastases varies according to anatomic site, maintenance of a broad repertoire of both CD4+ and CD8+ T effector cells will augment the overall systemic efficacy of adoptive immunotherapy.
Retroviral transduction of peptide stimulated t cells can generate dual t cell receptor-expressing (bifunctional) t cells reactive with two defined antigens
Authors: Langerman Alexander , Callender Glenda G , Nishimura Michael I 
Published: January 2005

Abstract
Background
Tumors and viruses have developed many mechanisms to evade the immune system, including down-regulation of target antigens and MHC molecules. These immune escape mechanisms may be able to be circumvented by adoptively transferring T cells engineered to express two different T cell receptors, each specific for a different antigen or MHC restriction molecule.

Methods
PBMC from the blood of normal healthy donors were stimulated for three days with an antigenic peptide from cytomegalovirus (CMV) pp65. These CMV reactive cultures were transduced with a encoding the TIL 5 T cell receptor (TCR) that mediates recognition of the dominant epitope of the melanoma antigen MART-1. Following selection for transduced cells, the cultures were evaluated for recognition of CMV pp65 and MART-1 expressing targets.

Results
We were able to rapidly create bifunctional T cells capable of recognizing both CMV pp65 and MART-1 using a combination of HLA-A2 tetramer staining and intracellular staining for interferon-γ. These bifunctional T cells were sensitive to very low levels of antigen, recognize MART-1+ tumor cells, and maintained their bifunctionality for over 40 days in culture.

Conclusion
Bifunctional T cells can be engineered by transducing short term peptide stimulated T cell cultures. These bifunctional T cells may be more effective in treating patients with cancer or chronic virus infections because they would reduce the possibility of disease progression due to antigen and/or MHC loss variants.
HIV-1 nef suppression by virally encoded microRNA
Authors: Omoto Shinya , Ito Masafumi , Tsutsumi Yutaka , Ichikawa Yuko , Okuyama Harumi , Brisibe Ebiamadon Andi , Saksena Nitin K , Fujii Yoichi R 
Published: January 2005

Abstract
Background
MicroRNAs (miRNAs) are 21~25-nucleotides (nt) long and interact with mRNAs to trigger either translational repression or RNA cleavage through RNA interference (RNAi), depending on the degree of complementarity with the target mRNAs. Our recent study has shown that HIV-1 nef dsRNA from AIDS patients who are long-term non-progressors (LTNPs) inhibited the transcription of HIV-1.

Results
Here, we show the possibility that nef-derived miRNAs are produced in HIV-1 persistently infected cells. Furthermore, nef short hairpin RNA (shRNA) that corresponded to a predicted nef miRNA (~25 nt, miR-N367) can block HIV-1 Nef expression in vitro and the suppression by shRNA/miR-N367 would be related with low viremia in an LTNP (15-2-2). In the 15-2-2 model mice, the weight loss, which may be rendered by nef was also inhibited by shRNA/miR-N367 corresponding to suppression of nef expression in vivo.

Conclusions
These data suggest that nef/U3 miRNAs produced in HIV-1-infected cells may suppress both Nef function and HIV-1 virulence through the RNAi pathway.
Years of Life Lost due to exposure: Causal concepts and empirical shortcomings
Authors: Morfeld P 
Published: January 2005

AbstractExcess Years of Life Lost due to exposure is an important measure of health impact complementary to rate or risk statistics. I show that the total excess Years of Life Lost due to exposure can be estimated unbiasedly by calculating the corresponding excess Years of Potential Life Lost given conditions that describe study validity (like exchangeability of exposed and unexposed) and assuming that exposure is never preventive. I further demonstrate that the excess Years of Life Lost conditional on age at death cannot be estimated unbiasedly by a calculation of conditional excess Years of Potential Life Lost without adopting speculative causal models that cannot be tested empirically. Furthermore, I point out by example that the excess Years of Life Lost for a specific cause of death, like lung cancer, cannot be identified from epidemiologic data without assuming non-testable assumptions about the causal mechanism as to how exposure produces death. Hence, excess Years of Life Lost estimated from life tables or regression models, as presented by some authors for lung cancer or after stratification for age, are potentially biased. These points were already made by Robins and Greenland 1991 reasoning on an abstract level. In addition, I demonstrate by adequate life table examples designed to critically discuss the Years of Potential Life Lost analysis published by Park et al. 2002 that the potential biases involved may be fairly extreme. Although statistics conveying information about the advancement of disease onset are helpful in exposure impact analysis and especially worthwhile in exposure impact communication, I believe that attention should be drawn to the difficulties involved and that epidemiologists should always be aware of these conceptual limits of the Years of Potential Life Lost method when applying it as a regular tool in cohort analysis.
Tissue engineering, stem cells, cloning, and parthenogenesis: new paradigms for therapy
Authors: Hipp Jason , Atala Anthony 
Published: January 2005

Abstract
Background
Patients suffering from diseased and injured organs may be treated with transplanted organs. However, there is a severe shortage of donor organs which is worsening yearly due to the aging population. Scientists in the field of tissue engineering apply the principles of cell transplantation, materials science, and bioengineering to construct biological substitutes that will restore and maintain normal function in diseased and injured tissues. Both therapeutic cloning (nucleus from a donor cell is transferred into an enucleated oocyte), and parthenogenesis (oocyte is activated and stimulated to divide), permit extraction of pluripotent embryonic stem cells, and offer a potentially limitless source of cells for tissue engineering applications. The stem cell field is also advancing rapidly, opening new options for therapy. The present article reviews recent progress in tissue engineering and describes applications of these new technologies that may offer novel therapies for patients with end-stage organ failure.
Biochemical prevention and treatment of viral infections – A new paradigm in medicine for infectious diseases
Authors: Le Calvez Hervé , Yu Mang , Fang Fang 
Published: January 2005

AbstractFor two centuries, vaccination has been the dominating approach to develop prophylaxis against viral infections through immunological prevention. However, vaccines are not always possible to make, are ineffective for many viral infections, and also carry certain risk for a small, yet significant portion of the population. In the recent years, FDA's approval and subsequent market acceptance of Synagis, a monoclonal antibody indicated for prevention and treatment of respiratory syncytial virus (RSV) has heralded a new era for viral infection prevention and treatment. This emerging paradigm, herein designated "Biochemical Prevention and Treatment", currently involves two aspects: (1) preventing viral entry via passive transfer of specific protein-based anti-viral molecules or host cell receptor blockers; (2) inhibiting viral amplification by targeting the viral mRNA with anti-sense DNA, ribozyme, or RNA interference (RNAi). This article summarizes the current status of this field.
Effect of oligonucleotide primers in determining viral variability within hosts
Authors: Bracho Maria Alma , García-Robles Inmaculada , Jiménez Nuria , Torres-Puente Manuela , Moya Andrés , González-Candelas Fernando 
Published: January 2005

Abstract
Background
Genetic variability in viral populations is usually estimated by means of polymerase chain reaction (PCR) based methods in which the relative abundance of each amplicon is assumed to be proportional to the frequency of the corresponding template in the initial sample. Although bias in template-to-product ratios has been described before, its relevance in describing viral genetic variability at the intrapatient level has not been fully assessed yet.

Results
To investigate the role of oligonucleotide design in estimating viral variability within hosts, genetic diversity in hepatitis C virus (HCV) populations from eight infected patients was characterised by two parallel PCR amplifications performed with two slightly different sets of primers, followed by cloning and sequencing (mean = 89 cloned sequences per patient). Population genetics analyses of viral populations recovered by pairs of amplifications revealed that in seven patients statistically significant differences were detected between populations sampled with different set of primers.

Conclusions
Genetic variability analyses demonstrates that PCR selection due to the choice of primers, differing in their degeneracy degree at some nucleotide positions, can eclipse totally or partially viral variants, hence yielding significant different estimates of viral variability within a single patient and therefore eventually producing quite different qualitative and quantitative descriptions of viral populations within each host.