gebhart/patrepeval huggingface dataset:
Value of magnetic resonance angiography for the detection of intracranial aneurysms in autosomal dominant polycystic kidney disease. (1993)

The association of intracranial aneurysms with autosomal dominant polycystic kidney disease (ADPKD), the 30-day mortality rate exceeding 50% for aneurysmal rupture, the effectiveness of surgical repair of unruptured aneurysms with a low surgical risk, and the development of noninvasive imaging techniques for their detection have led physicians to consider the value of screening patients with ADPKD for unruptured intracranial aneurysms. The sensitivity and specificity of high-resolution computed tomography and magnetic resonance imaging for the diagnosis of small intracranial aneurysms have been disappointing. To determine the value of magnetic resonance angiography (MRA), 85 patients with ADPKD without symptoms related to an intracranial aneurysm and 2 patients with ADPKD presenting with a subarachnoid hemorrhage or a suspected aneurysmal leak were studied. MRA was performed with the Multisequence Vascular Package (GE Medical Systems) with use of three-dimensional time-of-flight and three-dimensional phase-contrast techniques, and postprocessing maximum intensity projection images were generated to eliminate the problem of overlapping vessels. Asymptomatic intracranial aneurysms were detected in 6 (22%) of 27 patients with and 3 (5%) of 56 patients without a family history of intracranial aneurysm or subarachnoid hemorrhage (P = 0.02, information missing in 2 patients) and in the 2 patients who presented with a symptomatic aneurysm. A stepwise logistic regression analysis indicated that a family history of intracranial aneurysm or subarachnoid hemorrhage was independently associated with the presence of intracranial aneurysms. All of the aneurysms were < or = 6.5 mm in diameter.(ABSTRACT TRUNCATED AT 250 WORDS)
Glucocorticoid-induced apoptosis (1995)

Glucocorticoids are potent immunosuppressants that exert their effects primarily by inducing apoptosis in lymphocytes. Despite considerable research, the mechanism by which glucocorticoids induce apoptosis in lymphocytes remains unknown, although the necessity of the glucocorticoid receptor is not disputed. There is evidence that glucocorticoid receptors induce apoptosis by stimulating transcription of specific genes that ate currently being characterised. Conversely, recent data suggest that the lethal effects of glucocorticoids are exerted through suppression of gene transcription. In addition, other studies suggest that oxygen radicals and antiapoptosis genes may participate in modulating glucocorticoid-induced apoptosis. We propose a new model in which redundant systems of gene stimulation and repression ensure an apoptotic response after glucocorticoid treatment.
Changing patterns of transcriptional and post-transcriptional control of liver-specific gene expression during rat development. (1987)

Genes coding for unique or tissue-specific (differentiated) functions in the liver are induced at different times during development. It has generally been felt that transcriptional control represents the dominant mechanism for regulating expression of these genes. We have determined the relative transcription rates and mRNA steady-state levels for a series of genes specifically or preferentially expressed in rat liver and find examples of transcriptional control (albumin, alpha-fetoprotein, alpha 1-antitrypsin, tyrosine aminotransferase, transferrin, and cytochrome P450, TF-1) and post-transcriptional control (alpha 1-acid glycoprotein, apolipoproteins A-1 and E, malic enzyme, and ATP citrate lyase), as well as "mixed" regulation (ligandin and cytochrome P450, R17). Examples have been identified in which the predominant mode for regulating expression of preferentially expressed genes changes from transcriptional to post-transcriptional at different stages of liver development and some members of multigene families (cytochrome P450s and apolipoprotein genes) also show independent and sometimes contrasting modes of regulation. Therefore, it appears that regulation of specific gene expression in the liver is a dynamic process, far more complex than heretofore suspected, and a much greater contribution of post-transcriptional regulation accounts for changes in expression of genes representing major functions of the liver.
Preparation of inside-out vesicles of pig lymphocyte plasma membrane (1976)

Between 30 and 50% of pig lymphocyte plasma membrane vesicles were not bound by concanavalin A (Con A)-Sepharose. Various results suggest that the Con A-unretarded fraction represents "inside-out" membrane vesicles. First, an alternative cell surface ligand, anti-lymphocytic serum, gave a similar fractionation to Con A. Second, lack of binding by Con A was not due to lack of carbohydrate or to masking of carbohydrate by extraneous protein, because the unfractionated membrane and the unretarded fraction had similar carbohydrate and polypeptide compositions. Third although the carbohydrate of the unretarded membrane vesicles was accessible to 125I-labelled Con A and to release by soluble trypsin, it was not accessible to ferritin-Con A or trypsin-Sepharose. Fourth, antisera against the external surface of the Con A-unretarded vesicles strongly agglutinated the unretarded membrane, but caused negligible agglutination of whole lymphocytes. When attached to Sepharose these antisera bound all of the Con A-unretarded fraction, but failed to bind the membrane that adhered to Con A-Sepharose.
Regulation of Na+/Glucose Cotransporters (1997)

Na+/glucose cotransporters (SGLTs) are expressed in the small intestine and the proximal renal tubule, where they play a central role in the absorption of glucose and galactose from food and the reabsorption of glucose from the glomerular filtrate. The regulation of intestinal sugar absorption occurs over two distinct time scales, one over days and the other over minutes. This review focuses on the mechanisms involved in the shorter-term regulation. Recent studies of the mouse intestine in vitro demonstrated that Na+/glucose cotransport is increased two- to eightfold within minutes by the application of forskolin, an agent that increases intracellular cyclic AMP levels. Here we explore how cyclic AMP may upregulate Na+/glucose cotransport. Our strategy was to express cloned SGLT1s in Xenopus laevis oocytes and then use electrophysiological methods to measure (i) the kinetics of Na+/glucose cotransport, (ii) the number of cotransporters in the plasma membrane, and (iii) the net rate of exo- and endocytosis before and after activation of protein kinases. To evaluate the role of cotransporter phosphorylation, we have examined the effect of protein kinase activation on various SGLT1 isoforms and other cotransporters. In oocytes expressing rabbit SGLT1, the activation of protein kinase A (PKA) increased the maximum rate of Na+/glucose cotransport by 30%, and the activation of protein kinase C (PKC) decreased the maximum rate of transport by 60%. Changes in maximum transport rates were accompanied by proportional changes in the number of cotransporters in the plasma membrane and by changes in the area of the membrane. We conclude that PKA and PKC regulate rabbit SGLT1 activity by modulating the number of cotransporters in the plasma membrane and that this occurs through regulation of exocytosis and endocytosis. Given the size of intracellular transport vesicles containing SGLT1, 100-120 nm in diameter, and the density of cotransporters in these vesicles, 10-20 per vesicle, we estimate that the net rate of SGLT1 vesicle exocytosis is about 10,000 s-1 and that this rate increases 100-fold after activation of PKA. The effect of PKA is independent of the presence or absence of consensus sites for phosphorylation on SGLT1. Surprisingly, the effects of PKA or PKC depend critically on the sequence of the contransporter being expressed in the oocyte, e.g. activation of PKC inhibited rabbit and rat SGLT1, but stimulated human SGLT1. This dependency suggests that the regulation of vesicle trafficking by protein kinases depends upon the structure of the cotransporter expressed in the oocyte. Similar considerations apply to other classes of cotransporters, such as the neurotransmitter and dipeptide cotransporters. Our working hypothesis is that the regulation of cotransporter expression by protein kinases occurs largely by regulated exo- and endocytosis, and that the effect of the protein kinases is indirect and determined by critical domains in the cotransporter.
Beneficial Effects of Testosterone Replacement for the Nonmotor Symptoms of Parkinson Disease (2002)

A daily dose of transdermal testosterone gel improved testosterone deficiency symptoms in men with PD. Although there were trends in improvement in other nonmotor and motor symptoms of PD, future placebo control studies will need to be powered to answer these important questions. Whether testosterone deficiency is simply a comorbidity in PD or whether it plays a role in the pathogenesis of disease also remains for future study.
Stem Cell Therapy in Perspective (2003)

he concept of regenerative medicine using the body's own stem cells and growth factors to repair tissues may become a reality as new basic science works and initial clinical experiences have "teamed-up" in an effort to develop alternative therapeutic strategies to treat the diseased myocardium. In particular, revealing the signals that mediate cellular growth and differentiation may provide novel tools designed for myocardial regeneration in patients sustaining ischemic cardiomyopathy syndromes. We attempt herein to provide a critical overview of recent developments of myocardial cell transplantation strategies.
590. Higher aliphatic compounds. Part XI. A synthesis of DL-ricinoleic acid (1957)

A. S. Bailey, V. G. Kendall, P. B. Lumb, J. C. Smith and C. H. Walker, J. Chem. Soc., 1957, 3027 DOI: 10.1039/JR9570003027
Induction of Endogenous Virus and of Thymidine Kinase by Bromodeoxyuridine in Cell Cultures Transformed by Friend Virus (1974)

Thymidine kinase positive (TK(+)) N type cell lines that had been transformed by spleen focus-forming virus were established by transformation with NB tropic Friend virus complex. Thymidine kinase deficient (TK(-)) cell clones were isolated. Some of these cell clones release 1000- to 100,000-fold reduced amounts of Friend virus complex as compared to the TK(+) parental cell clone. TK(-) clones were grown in medium without BrdUrd. Some of these TK(-) clones can be induced to release endogenous helper virus and transforming spleen focus-forming virus on reexposure to 10(-6)-10(-4) M BrdUrd. The induced Friend virus complex is of N host range as expected with induced endogenous virus in N-type cells. Before the induction of the endogenous virus spleen focus-forming virus complex, an induction of thymidine kinase (ATP:thymidine 5'-phosphotransferase, EC 2.7.1.75) activity is observed. The latter is possibly a prerequisite for the induction of endogenous virus in TK(-) cells. Induction of thymidine kinase activity and of endogenous virus is transient and always correlated. The role of BrdUrd and another thymidine analogue, azidothymidine, in interfering with C-type virus release in virus positive cells is discussed. Azidothymidine is unable to induce endogenous virus. Induction of endogenous virus by BrdUrd and inhibition of virus release in virus positive cells is apparently not caused by the same mechanism.
Partial activation of naive CD4 T cells and tolerance induction in response to peptide presented by resting B cells (1997)

Tolerance is thought to occur when Ag is presented to T cells in the absence of costimulatory interactions from APC accessory molecules. Of the professional APC, the resting B cell may be the main tolerizing cell in vivo. We have analyzed several aspects of activation of naive transgenic CD4 cells stimulated with resting or activated B cells presenting peptide Ag. Similar results were obtained with stimulation from peptide presenting fibroblast APC lacking or expressing B7-1 with intracellular adhesion molecule-1. TCR ligation with little or no accessory molecule coreceptor engagement induced efficient blastogenesis; up-regulation of CD25, CD44, CD69, CD95 and CD71; and down-regulation of CD62L over a 48-h period. Accessory molecule help enhanced the expression of CD25, CD44, CD69, and CD71, but to very modest degrees. Only two molecules, CD40 ligand and IL-2, were found to be extremely dependent on accessory molecule help, with little or no expression evident with peptide presented on resting B cells or class II-positive fibroblasts. T cells induced on resting B cells expanded minimally over 3 days, and this was followed by extensive cell death and hyporesponsiveness of the resulting cells. These studies suggest that under tolerizing conditions, such as Ag presentation by resting B cells, much of the naive CD4 response is induced efficiently. Partial activation, however, may be the overall result due to the lack of CD40 ligand expression, which may regulate costimulatory activity in APC and, in turn, may contribute to limiting the production of IL-2 required for T cell expansion and survival.
Replacement of the Active-Site Cysteine Residues of DsbA, a Protein Required for Disulfide Bond Formation in vivo (1994)

DsbA is a periplasmic protein of Escherichia coli that was identified genetically as being involved in the formation of disulfide bonds in secreted proteins. Its active site contains one accessible and one buried cysteine residue, separated in the primary structure by only two other residues. These cysteine residues can form a very unstable disulfide bond that is 10(3)-fold more reactive toward thiols than normal. Moreover, the mixed disulfide between the accessible cysteine residue and glutathione is 10(4)-fold more reactive than normal. Site-directed mutagenesis was carried out to replace either one or both cysteine residues by serine. Cys30 is shown to be the accessible thiol, while Cys33 is shielded from the solvent. Even though the thiol group of Cys30 is exposed and reactive, it formed a very unstable mixed disulfide with glutathione. This disulfide bond was 2.17 +/- 0.02 kcal mol-1 less stable in the native conformation than when DsbA was unfolded. If the native conformation destabilizes the mixed disulfide, the mixed disulfide must destabilize the folded conformation to the same extent. This was confirmed by demonstrating that the folded conformation of the mixed disulfide form of the mutant DsbA was 2.7 +/- 0.9 kcal mol-1 less stable than that of the reduced form; these stability effects originated almost exclusively in the folded conformation. Replacing the cysteine residues by serine destabilized the folded conformation of the reduced protein to varying extents. This suggests that the thiol groups are involved in interactions that stabilize the folded conformation, which would cause any disulfide bonds, either inter- or intramolecular, that involve these groups to be unstable.
Biotechnological advances in goat reproduction. (1997)

Goat selection and reproduction have resulted from using conventional methods of natural mating and artificial insemination. Genetic improvements resulting from these are usually slow. Innovative developments in biotechnology rapidly propagate superior genes, offering hope for modeling and designing animals to fit market and environmental requirements. Use of Tris, citric acid, fructose, egg yolk, and glycerol extender has enabled goat sperm to be stored successfully for several years before being used in cervical or laparoscopic insemination. Laparoscopic recovery of goat embryos to reduce adhesions from repeat surgeries has great potential in improving embryo production for direct transfer or for future transfer after cryopreservation. Goat kids have been produced, as a result of experiments to refine techniques of in vitro maturation and fertilization of recovered oocytes, with successful culture and transfer of embryos. In vitro fertilization technology is also essential for cloning goat embryos and for gene transfer. Transgenic goats have already been produced due to new genes being expressed from biologically active molecules altering the phenotype of the transferred goat. The introduced gene is capable of transmission between generations. The goat's diversified commercial value and convenient size make it a benefactor to new technology for rapid genetic improvement as a supplement to conventional selection methods.
In vitro anti-human immunodeficiency virus (HIV) activities of transition state mimetic HIV protease inhibitors containing allophenylnorstatine (1993)

Transition state mimetic tripeptide human immunodeficiency virus (HIV) protease inhibitors containing allophenylnorstatine [(2S,3S)-3-amino-2-hydroxy-4-phenylbutyric acid] were synthesized and tested for activity against HIV in vitro. Two compounds, KNI-227 and KNI-272, which were highly potent against HIV protease with little inhibition of other aspartic proteases, showed the most potent activity against the infectivity and cytopathic effect of a wide spectrum of HIV strains. As tested in target CD4+ ATH8 cells, the 50% inhibitory concentrations of KNI-227 against HIV type 1 LAI (HIV-1LAI), HIV-1RF, HIV-1MN, and HIV-2ROD were 0.1, 0.02, 0.03, and 0.1 microM, respectively, while those of KNI-272 were 0.1, 0.02, 0.04, and 0.1 microM, respectively. Both agents completely blocked the replication of 3'-azido-2',3'-dideoxythymidine-sensitive and -insensitive clinical HIV-1 isolates at 0.08 microM as tested in target phytohemagglutinin-activated peripheral blood mononuclear cells. The ratios of 50% cytotoxic concentrations to 50% inhibitory concentrations for KNI-227 and KNI-272 were approximately 2,500 and > 4,000, respectively, as assessed in peripheral blood mononuclear cells. Both compounds blocked the posttranslational cleavage of the p55 precursor protein to generate the mature p24 Gag protein in stably HIV-1-infected cells. The n-octanol-water partition coefficients of KNI-227 and KNI-272 were high, with log Po/w values of 3.79 and 3.56, respectively. Degradation of KNI-227 and KNI-272 in the presence of pepsin (1 mg/ml, pH 2.2) at 37 degrees C for 24 h was negligible. Current data warrant further careful investigations toward possible clinical application of these two novel compounds.
Neural Networks Based on Information Fusion Using for Avoiding Obstacle Robot (2009)

The paper describes an indoor autonomous wheel robot which could move safely in an obstacle environment. The environment may involve any number of arbitrary shape and size obstacles, and the path may be very complex. We describe an approach to solving the motion-planning for mobile robot control by using neural networks based on information fusion technique. In the article, the physics model of the mobile robot was set up, and the sensors used in the avoiding obstacle of the mobile robot were selected. As the indoor environment information couldn't be exact by single sensor, we proposed that using a multi-sensor system for the mobile robot avoiding obstacle. At last, we selected multiple ultrasonic sensors and infrared sensors. In order to predigest the calculation, the measurement data are to be classified and selected. The fuzzy neuron network information fusion based on the T-S model is used to avoid obstacle for the mobile robot, which fully utilized the information coming from the sensors. Finally, the experiment with the autonomous robot proved that the method is really feasible and efficient.
Post-translational modification of p53 protein in response to DNA damage (2000)

grantor: University of Toronto
Metabolic remodeling of the tumor microenvironment: Migration stimulating factor (MSF) reprograms myofibroblasts toward lactate production, fueling anabolic tumor growth (2012)

Migration stimulating factor (MSF) is a genetically truncated N-terminal isoform of fibronectin that is highly expressed during mammalian development in fetal fibroblasts, and during tumor formation in human cancer-associated myofibroblasts. However, its potential functional role in regulating tumor metabolism remains unexplored. Here, we generated an immortalized fibroblast cell line that recombinantly overexpresses MSF and studied their properties relative to vector-alone control fibroblasts. Our results indicate that overexpression of MSF is sufficient to confer myofibroblastic differentiation, likely via increased TGF-b signaling. In addition, MSF activates the inflammation-associated transcription factor NFκB, resulting in the onset of autophagy/mitophagy, thereby driving glycolytic metabolism (L-lactate production) in the tumor microenvironment. Consistent with the idea that glycolytic fibroblasts fuel tumor growth (via L-lactate, a high-energy mitochondrial fuel), MSF fibroblasts significantly increased tumor growth, by up to 4-fold. Mechanistic dissection of the MSF signaling pathway indicated that Cdc42 lies downstream of MSF and fibroblast activation. In accordance with this notion, Cdc42 overexpression in immortalized fibroblasts was sufficient to drive myofibroblast differentiation, to provoke a shift towards glycolytic metabolism and to promote tumor growth by up to 2-fold. In conclusion, the MSF/Cdc42/NFκB signaling cascade may be a critical druggable target in preventing "Warburg-like" cancer metabolism in tumor-associated fibroblasts. Thus, MSF functions in the metabolic remodeling of the tumor microenvironment by metabolically reprogramming cancer-associated fibroblasts toward glycolytic metabolism.
The Effects of 4-Aminopyridine on Neurological Deficits in Chronic Cases of Traumatic Spinal Cord Injury in Dogs: A Phase I Clinical Trial (1991)

A Phase I trial of 4-aminopyridine (4-AP) was carried out in 39 dogs referred to the veterinary teaching hospital with naturally occurring traumatic paraplegia or paraparesis. The rationale for the study was provided by the observation that 4-AP restores conduction in demyelinated nerve fibers in experimental spinal cord injury. Most injuries (77%) resulted from degenerative disk disease, occurring at or near the thoracolumbar junction, and producing chronic, complete paraplegia. Neurological examination of each dog was recorded on videotape before and at intervals after administration of 4-AP. The drug was administered systemically in total doses between 0.5 and 1 mg/kg body weight. Three areas of neurological status changed significantly at 15-45 minutes following administration of 4-AP: (a) striking improvements in hindlimb placing occurred in 18 animals; (b) increased awareness of painful stimuli to the hindlimb in 10 animals; (c) partial recovery of the cutaneus trunci muscle reflex of the back skin in 9 animals. These effects reversed within a few hours of administration. Other animals (36%) showed no change in neurological signs except a slight enhancement of hindlimb reflex tone. Significant side effects were seen in 6 dogs receiving higher intravenous doses, with elevation of body temperature and apparent anxiety, leading to mild seizures in 3 of the animals. These seizures were controlled with diazepam. The results indicate that conduction block may contribute significantly to functional deficits in closed-cord injuries and that potassium channel blockade may prove to be a valid, if limited approach to therapeutic intervention in chronic paraplegia and paraparesis.