bluuebunny/crossref_metadata_2025_split huggingface dataset:
Maintenance of size and function of influenza virus hemagglutinin specific transgenic T‐cell clone during life
Authors: Radu D. L. , Weksler M. E. , Bona C. A. 
Published: May 2007

AbstractImmunization induces less protective immunity against infectious diseases in old compared to young subjects. We have studied the effect of age on the in vitro and in vivo function of murine transgenic T cells expressing a receptor for influenza hemagglutinin 110‐120 peptide. During aging the transgenic T cells undergo the age‐associated shift from naive to memory phenotype but maintain, despite thymic involution, their number as well as their cytokine production and proliferative responses induced by the hemagglutinin 110‐120 peptide in vitro. The maintenance of the size and functions of transgenic T cells during the aging may be related to low expression of CTLA‐4 molecules known to exhibit a negative regulatory effect subsequent to interaction with costimulatory molecules as well as of stimulation of T cells by unknown cross reactive endogenous factors but not by nominal antigen since innate immunity prevents natural infection with influenza virus of murine species. This suggests that the impaired immunity induced by immunization in old subjects reflects defects in the development and maintenance of T cell memory and not in the expression of effector activity.
Apoptosis in human embryo development: 3. Fas‐induced apoptosis in brian primary cultures
Authors: Nat Roxana , Radu E. , Regalia T. , Popescu L. M. 
Published: May 2007

AbstractFas (APO‐1/CD95) is an important apoptotic mediator for both immune and nervous systems. In the present study, we have investigated the expression and function of Fas in human embryonic/fetal brain primary cultures from 12 human embryos and fetuses with gestational ages between 5 to 22 weeks. Anti‐Fas fluorescent antibody was used for labeling of Fas positive cells and for quantitation of Fas expression in brain cultures. To demonstrate that Fas receptor is functional in human embryonic/fetal brain cells, anti‐Human‐Fas monoclonal antibody (0.5 μg/ml) was used to induce apoptosis in brain primary cultures. Apoptosis was investigated by flow‐cytometry and fluorescent microscopy using TUNEL and annexin V labeling. Fas was found to be expressed in the embryonic/fetal human primary brain cultures, on neuronal and glial cells or their precursors, varying with gestational ages. Cross‐linking of Fas induced apoptosis in brain cultures indicating that Fas receptor functions as a death receptor. We also showed that cell death triggered through Fas receptor was caspase dependent, hence it was blocked by a selective caspase‐8 inhibitor (IETD‐fmk).These results suggest that Fas is involved in neuronal apoptosis in the developing human brain.
Classification of thymic epithelial neoplasms: a controversial issue coming to an end?
Authors: Kuo Tseng‐Tong 
Published: May 2007

AbstractThe classification of thymic epithelial neoplasms has been one of the most controversial issues in tumor pathology. There are two opposing schools of pathologists holding different views regarding the classification of thymic epithelial neoplasms. One school of pathologists believe that histological classification of thymomas is not possible or useful. Another school of pathologists believe that thymomas can be histologically subclassified despite their complex histomorphology and that these histological subtypes correlate with their aggressiveness and clinical behavior. A compromised histological classification has been established by World Health Organization (WHO) to designate thymic epithelial neoplasms with letters and numbers. This classification should be adopted internationally to facilitate the communication among concerned pathologists and oncologists. A simple histological classification of thymomas based on cytomorphology and supported by cytokeratin expressions is proposed and compared to the WHO and Müller‐Hermelink's histogenetic classifications.
Cytochromes P450 and experimental models of drug metabolism
Authors: Zuber R. , Anzenbacherová Eva , Anzenbacher P. 
Published: May 2007

AbstractFor the development of new drugs, evaluation of drug‐drug interactions with already known compounds, as well as for better understanding of metabolism pathways of various toxicants and pollutants, we studied the drug metabolism mediated by cytochromes P450. The experimental approach is based on animal drug‐metabolising systems. From the ethical as well as rational reasons, the selection of an appropriate system is crucial. Here, it is necessary to decide on the basis of expected CYP system involved. For CYP1A‐mediated pathways, all the commonly used experimental models are appropriate except probably the dog. On the contrary, the dog seems to be suitable for modelling of processes depending on the CYP2D. With CYP2C, which is possibly the most large and complicated subfamily, the systems based on monkey (Maccacus rhesus) may be a good representative. The CYP3A seems to be well modelled by pig or minipig CYP3A29. Detailed studies on activities with individual isolated CYP forms are needed to understand in full all aspects of inter‐species differences and variations.
APOE polymorphism and clinical duration determine regional neuropathology in Swedish APP670, 671 mutation carriers: implications for late‐onset Alzheimer's disease
Authors: Bogdanovic N. , Corder Elizabeth , Lannfelt L. , Winblad B. 
Published: May 2007

AbstractNeurofibrillary changes throughout the brain were investigated for three relatives who carried the Swedish APP670,671 mutation which causes overproduction of Aβ40 and Aβ42. They differed in terms of APOE genotype, age at the onset of dementia, and disease duration (P1: ɛ2/3, age 57, 11 years; P2: ɛ2/3, age 61, 5 years; P3: ɛ4/4, age 44, 12 years). For each subject, paraffin‐embedded sections from diverse anatomically and cytoarchitectonically well‐preserved regions were stained using the modified Bielschowsky method. Neurofibrillary tangles (NFT) and neuritic plaques (NP) were counted, and the area occupied by plaque estimated (%NP). In addition, sections from the medial frontal gyrus were stained with monoclonal antibodies to APOE. The regional patterns of neurofibrillary changes were consistent with those for late‐onset AD. Longer disease duration was associated with further accumulations in earlier‐affected areas, with superficial cortical layers consistently containing higher %NP than deep layers. APOE ɛ4/4 was associated with deeper limbic and frontal NFT, with an excess of NP (especially in the outer parietal cortex) which stained heavily for APOE ‐ as well as with very early onset. APP670,671 mutation carriers demonstrate regional brain neurofibrillary changes characteristic of late‐onset Alzheimer's disease with evidence for more Aβ deposition for ɛ4/4 than ɛ2/3. This raises the possibility that early Braak Stage I‐II lesions might also follow this pattern of promotion.
Apoptosis in the immune system: 1. Fas‐induced apoptosis in monocytes‐derived human dendritic cells
Authors: Nat Roxana , Radu E. , Regalia T. , Popescu L. M. 
Published: May 2007

AbstractDendritic cells (DC) are cells of the hematopoietic system specialized in capturing antigens and initiating T cell‐mediated immune responses. We show here that human DC generated from adherent peripheral blood mononuclear cells (PBMC) after in vitro stimulation with granulocyte macrophage colony stimulating factor (GM‐CSF) and interleukin‐4 (IL‐4) express Fas antigen (APO‐1, CD95) and can undergo apoptosis upon triggering of Fas by monoclonal antibodies. Immature monocytes‐derived dendritic cells (MDDC) upregulate CD86 and HLA‐DR expression and develop dendrites and veiled processes. Flow cytometry analysis revealed CD95 expression in approx. 40% of these MDDC and incubation with anti‐CD95 mAb (0.5μg/ml) induced apoptosis when compared to untreated controls. The extent of apoptosis induced by the agonist anti‐Fas antibody strongly related to the percentage of cells expressing CD 95. Upon tumor necrosis factor α (TNF‐α) additional stimulation, MDDC assumed a characteristic mature dendritic cells morphology showing prolonged veils, CD83 expression, and high levels of HLA‐DR. These cells have downregulated their Fas receptors (to approx. 20%) and undergo apoptosis to a lesser extent when treated with anti‐CD 95, as demonstrated by the hardly noticeable effect of this antibody on the viability of cultured cells as compared to controls. Thus, upon TNF‐α induced maturation, MDDC became resistant to Fas‐induced apoptosis. The apoptotic episodes surrounding the earlier stage of DC differentiation appeared to be mediated by Fas. In contrast, a Fas independent pathway is probably responsible for the apoptotic events associated with terminally differentiated DC.
The adenylosuccinate synthetase‐1 gene is activated in the hypertrophied heart
Authors: Wen H. Y. , Xia Y. , Young M. E. , Taegtmeyer H. , Kellems R. E. 
Published: May 2007

AbstractAdenylosuccinate synthetase 1 (ADSS1) functions as an important component in adenine nucleotide biosynthesis and is abundant in the heart. Here we report that the Adssl gene is up‐regulated in two in vivo rodent models of surgically induced cardiac hypertrophy. In addition, we examined an in vitro hypertrophy system of rat neonatal cardiomyocytes treated with angiotensin II to study Adssl gene regulation. We show that this stimulus triggers a signaling cascade that results in the activation of the Adssl gene. The induction of Adssl gene expression was blocked by cyclosporin A in vitro, suggesting that calcineurin, a calmodulin activated phosphatase, is involved in this signaling pathway. Consistent with this view we provide evidence that the induction of Adss1 by angiotension II requires the presence of an NFAT binding site located 556 base pairs upstream of the Adssl transcription start site. We propose that ADSS1 plays a role in the development of cardiac hypertrophy through its function in adenine nucleotide biosynthesis.
Comparative study of some energetic and steric parameters of the wild type and mutants HIV‐1 protease: a way to explain the viral resistance
Authors: Avram Speranta , Movileanu L. , Mihailescu D. , Flonta Maria‐Luiza 
Published: May 2007

AbstractBecause, in vivo, the HIV‐1 PR (HIV‐1 protease) present a high mutation rate we performed a comparative study of the energetic behaviors of the wild type HIV‐1 PR and four type of mutants: Val82/Asn; Val82/Asp; Gln7/Lys, Leu33/Ile, Leu63/Ile; Ala71/Thr, Val82/Ala. We suggest that the energetic fluctuation (electrostatic, van der Waals and torsion energy) of the mutants and the solvent accessible surface (SAS) values can be useful to explain the viral resistance process developed by HIV‐1 PR. The number and localization of enzyme mutations induce important modifications of the van der Waals and torsional energy, while the electrostatic energy has an insignificant fluctuation. We showed that the viral resistance can be explored if the solvent accessible surfaces of the active site for the mutant structures are calculated. In this paper we have obtained the solvent accessible surface for a group of 15 mutants (11 mutants obtained by Protein Data Bank (PDB) file, 4 mutants modeled by CHARMM software) and for the wild type HIV‐1 PR). Our study try to show that the number and localization of the mutations are factors which induce the HIV‐1 PR viral resistance. The larger solvent accessible surface could be recorded for the point mutant Val 82/Phe.
Potentiation of angiogenic response by ischemic and hypoxic reconditioning of the heart
Authors: Maulik Nilanjana , Das D. K. 
Published: May 2007

AbstractThis review is intended to discuss the newly discovered role of preconditioning which should make it an attractive therapeutic stimulus for repairing the injured myocardium. We recently found that apart from rendering the myocardium tolerant to ischemic reperfusion injury, preconditioning also potentiates angiogenesis. Our study demonstrated for the first time that both ischemic and hypoxic preconditioning triggered myocardial angiogenesis at the capillary and arteriolar levels which nicely corroborated with the improved myocardial contractile function.Hypoxic preconditioning resulted in the stimulation of VEGF, the most potent angiogenic factor known to date. In concert, endothelial cell specific tyrosine kinase receptors, Tie 1, Tie 2 and Flt‐1 and Flk‐1 were also significantly enhanced in the preconditioned myocardium. The redox‐regulated transcription factor NFkB was found to play an essential role in the preconditioning regulation of angiogenesis
Regulation of apoptosis by the ubiquitin and proteasome pathway
Authors: Wójcik Cezary 
Published: May 2007

AbstractRegulated proteolysis plays important roles in cell physiology as well as in pathological conditions. In most of the cases, regulated proteolysis is carried out by the ubiquitin‐ and proteasome‐dependent proteolytic system, which is also in charge of the bulk of cytoplasmic proteolysis. However, apoptosis or the process of programmed cell death is regulated by a different proteolytic system, i.e. by caspases, a family of specialized cysteine proteases. Nevertheless, there is plenty of evidence of a crosstalk between the apoptotic pathways and the ubiquitin and proteasome system, whose function in apoptosis appears to be very complex. Proteasome inhibitors induce apoptosis in multiple cell types, while in other they are relatively harmless or even prevent apoptosis induced by other stimuli. Proteasomes degrade specific proteins during apoptosis, but on the other hand some components of the proteasome system are degraded by caspases. The knowledge about the involvement of the ubiquitin‐ and proteasome‐dependent system in apoptosis is already clinically exploited, since proteasome inhibitors are being tested as experimental drugs in the treatment of cancer and other pathological conditions, where manipulation of apoptosis is desirable.
The study of CTLA‐4 and vitamin D receptor polymorphisms in the Romanian type 1 diabetes population
Authors: Guja C. , Marshall S. , Welsh K. , Merriman M. , Smith A. , Todd J. A. , Ionescu‐Tîrgoviste C. 
Published: May 2007

AbstractSeveral studies suggested that part of the genetic susceptibility for Type 1 diabetes (TIDM) is encoded by some polymorphisms of CTLA‐4 gene (2q33) and of Vitamin D Receptor gene (VDR; 12q12‐14). Our aim was to assess their contribution to TIDM genetic susceptibility in the Romanian population. We typed CTLA‐4 49 A/G and VDR FokI (F/f), ApaI (A/a) and TaqI (T/t) polymorphisms by Sequence Specific Primer PCR (SSP‐PCR) in 204 Romanian diabetic families (756 individuals: 212 TIDM probands and 544 unaffected parents and siblings). We studied alleles transmission using the Transmission Disequilibrium Test (TDT). We found an increased transmission of CTLA‐4 49G allele to diabetics (54.8%, p=0.11). The transmission of F (56.1%, p=0.063), a (55.7%, p=0.061) and T (51.8%, p=0.37) alleles of VDR gene to diabetics was increased but did not reach statistical significance. In conclusion we found the same increased transmission of CTLA‐4 49 G allele to diabetics as previously reported. VDR FoqI F allele seems to be predisposing while TaqI T allele seems to be protective.
Image processing, diagnostic information extraction and quantitative assessment in pathology
Authors: Santinelli Alfredo , Mazzucchelli Roberta , Colanzi Paola , Tinca Antonela , Montironi Rodolfo 
Published: May 2007

AbstractAs we enter the information age we hold strong beliefs in the benefits of digital technology applied to pathology: numerical representation offers objectivity. Digital knowledge may indeed lead to significant information discovery, and, processing systems might be designed to allow a true evolution of capabilities. Questions arise whether the methodology underlying quantitative analysis provides the information that we need and whether it is appropriate for some of the problems encountered in diagnostic and prognostic histopathology. While one certainly would not dispute the value of statistical procedures, the clinical needs call for individual patient targeted prognosis.
Megamitochondria formation ‐ physiology and pathology
Authors: Wakabayashi T. 
Published: May 2007

AbstractMitochondria undergo structural changes simultaneously with their functional changes in both physiological and pathological conditions. These structural changes of mitochondria are classified into two categories: simple swelling and the formation of megamitochondria (MG). Data have been accumulated to indicate that free radicals play a crucial role in the mechanism of the MG formation induced by various experimental conditions which are apparently various. These include ethanol‐, chloramphenicol‐ and hydrazine‐induced MG formation. Involvement of free radicals in the mechanism of MG formation is showed by the fact that MG formation is successfully suppressed by free radical scavengers such as α‐tocopherol, coenzyme Q10, and 4‐OH‐TEMPO. Detailed mechanisms and pathophysiological meanings of MG formation still remain to be investigated. However, a body of evidence strongly suggests that enormous changes in physicochemical and biochemical properties of the mitochondrial membranes during MG formation take place and these changes are favorable for membrane fusion. A recent report showed that continous exposure of cells with MG to free radicals induces apoptosis, finding which suggests that MG formation is an adaptative process to unfavorable environments at the level of intracellular organelles. Mitochondria try to decrease intracellular reactive oxygen species (ROS) levels by decreasing the consume of oxygen via MG formation. If mitochondria succeed to suppress intracellular ROS levels, MG return to normal both structurally and functionally, and they restore the ability to actively synthesize ATP. If cells are additionally exposed to excess amounts of free radicals, MG become swollen, membrane potential of mitochondria (ΔΨm) decreases, cytochrome c is released from mitochondria, leading to activation of caspases and apoptosis is induced.
Activated c‐Met signals through PI3K with dramatic effects on cytoskeletal functions in small cell lung cancer
Authors: Maulik G. , Madhiwala P. , Brooks S. , Ma P. C. , Kijima T. , Tibaldi E. V. , Schaefer E. , Parmar K. , Salgia R. 
Published: May 2007

AbstractSmall cell lung cancer (SCLC) is an aggressive illness with early metastases. There are several receptor tyrosine kinases (RTKs) overexpressed in SCLC, including c‐Met. c‐Met contains an external semaphorin‐like domain, a cytoplasmic juxtamembrane domain, tyrosine kinase domain and multiple tyrosines that bind to adapter molecules. We have previously reported that c‐Met is abundantly expressed in the NCI‐H69 SCLC cell line and now have determined the downstream effects of stimulating c‐Met via its ligand hepatocyte growth factor (HGF). Utilizing unique phospho‐specific antibodies generated against various tyrosines of c‐Met, we show that Y1003 (binding site for c‐Cb1 and a negative regulatory site), Y1313 (binding site for PI3K), Y1230/Y1234/Y1235 (autophosphorylation site), Y1349 (binding site for Grb2), Y1365 (important in cell morphogenesis) are phosphorylated in response to HGF (40 ng/ml, 7.5 min) in H69 cells. Since multiple biological and biochemical effects are transduced through the PI3K pathway, we determine the role of PI3K in the c‐Met/HGF stimulation pathway. We initially determined that by inhibiting PI3K with LY294002 (50μM over 72 hours), there was at least a 55% decrease in viability of H69 cells. Since H69 SCLC cells form clusters in cell culture, we determined the effects of HGF and LY294002 on cell motility of the clusters by time‐lapse video microscopy. In response to HGF, SCLC moved much faster and formed more clusters, and this was inhibited by LY294002. Finally, we determined the downstream signal transduction of HGF stimulation of c‐Met with and without inhibition of c‐Met (with geldanamycin, an anisamycin antibiotic that inhibits c‐Met in SCLC) or PI3K (with LY294002). We show that association of c‐Met with PI3K and GAB2 is diminished by inhibiting c‐Met. In summary, activation of the c‐Met pathway targets the PI3K pathway in SCLC and this may be an important therapeutic target.
Dantrolene protects neurons against kainic acid induced apoptosis in vitro and in vivo
Authors: Popescu B. O. , Oprica M. , Sajin Maria , Stanciu Cristina L. , Bajenaru O. , Predescu Andreea , Vidulescu Cristina , Popescu L. M. 
Published: May 2007

AbstractApoptotic cell death induced by kainic acid (KA) in cultures of rat cerebellar granule cells (CGC) and in different brain regions of Wistar rat pups on postnatal day 21 (P21) was studied. In vitro, KA (100–500 μM) induced a concentration‐dependent loss of cell viability in MTT assay and cell death had apoptotic morphology as studied by chromatin staining with propidium iodide (PI). In vivo, twenty‐four hours after induction of status epilepticus (SE) by an intraperitoneal KA injection (5 mg/kg) we quantified apoptotic cells in hippocampus (CA1 and CA3), parietal cortex and cerebellum using PI staining and terminal deoxynucleotidyl transferase‐mediated dUTP nick end labeling (TUNEL) technique. We report that dantrolene, a specific ryanodine receptor antagonist, was able to significantly reduce the apoptotic cell death in CGC cultures and in hyppocampal CA1 and parietal cortex regions. Our finding can be valuable for neuroprotective therapy strategies in patients with repeated generalized seizures or status epilepticus.
Ex vivo differentiation of umbilical cord blood progenitor cells in the presence of placental conditioned medium
Authors: Chivu Mihaela , Diaconu Carmen C. , Brasoveanu Lorelei , Alexiu Irina , Bleotu Coralia , Banceanu G. , Miscalencu D. , Cernescu C. 
Published: May 2007

AbstractHematopoetic stem cells (HSC) are the progenitors for the lympho‐hematopoietic system, with long lifespan and high proliferation potential. Transplantation of HSC from bone marrow or peripheral blood represents a standard therapy in severe hematological conditions. A possible alternative source of HSC is the umbilical cord blood, prepared by various separation procedures followed by expansion in cultures supplemented with hematopoietic growth factors. In order to check the effects of placental conditioned medium (PCM) from placental cells culture upon viability of HSC, we added plasma, PCM, dimetil sulfoxyde or hemin in HSC cultures. Flow cytometry or direct scoring of solid cultures using CD45+, CD34+, CD71+ and CD14+ fluorescent‐labeled monoclonal antibodies evaluated the effects upon cell proliferation and colony forming ability of HSC cultures, versus controls. PCM produced the highest proliferation, followed by plasma, DMSO and hemin. PCM improved the survival time and maintained a higher proportion of immature cells. PCM stimulates the differentiation towards myeloid lineage progenitor cells (>90% being CD45+), increasing the percentage of CD14+, granulocites /monocytes precursors. It is highly suggestive that PCM contains growth factors or cytokines, which regulate the development of HSC. Characterization of these factors is in progress.