gebhart/patrepeval huggingface dataset:
Activity of the glycosylating enzyme, core 2 GlcNAc (beta1,6) transferase, is higher in polymorphonuclear leukocytes from diabetic patients compared with age-matched control subjects: relevance to capillary occlusion in diabetic retinopathy. (2000)

The exact mechanism for capillary occlusion in diabetic retinopathy is still unclear, but increased leukocyte-endothelial cell adhesion has been implicated. We examined the possibility that posttranslational modification of surface O-glycans by increased activity of core 2 transferase (UDP-Glc:Galbeta1-3GalNAcalphaRbeta-N-acetylglucoaminyltr ansferase) is responsible for increased adhesion of leukocytes to vascular endothelium in diabetes. The mean activity of core 2 transferase in polymorphonuclear leukocytes isolated from type 1 and type 2 diabetic patients was higher compared with age-matched control subjects (1,638 +/- 91 [n = 42] vs. 249 +/- 35 pmol x h(-1) x mg(-1) protein [n = 24], P = 0.00013; 1,459 +/- 194 [n = 58] vs. 334 +/- 86 [n = 11], P = 0.01). As a group, diabetic patients with retinopathy had significantly higher mean activity of core 2 transferase compared with individuals with no retinopathy. There was a significant association between enzyme activity and severity of retinopathy in type 1 and type 2 diabetic patients. There was a strong correlation between activity of core 2 transferase and extent of leukocyte adhesion to cultured retinal capillary endothelial cells for diabetic patients but not for age-matched control subjects. Results from transfection experiments using human myelocytic cell line (U937) demonstrated a direct relationship between increased activity of core 2 transferase and increased binding to cultured endothelial cells. There was no relationship between activity of core 2 transferase and HbA(1c) (P = 0.8314), serum advanced glycation end product levels (P = 0.4159), age of the patient (P = 0.7896), and duration of diabetes (P = 0.3307). On the basis that branched O-glycans formed by the action of core 2 transferase participate in leukocyte adhesion, the present data suggest the involvement of this enzyme in increased leukocyte-endothelial cell adhesion and the pathogenesis of capillary occlusion in diabetic retinopathy.
Enhancement of the antiallodynic and antinociceptive efficacy of spinal morphine by antisera to dynorphin A (1–13) or MK-801 in a nerve-ligation model of peripheral neuropathy (1997)

Neuropathic pains arising from peripheral nerve injury can result in increased sensitivity to both noxious and non-noxious stimuli and are accompanied by a number of neuroplastic alterations at the level of the spinal cord including upregulation of neurotransmitters including dynorphin, cholecystokinin and neuropeptide Y. Additionally, such pain states appear to be associated with activation of excitatory amino acid receptors including the N-methyl-D-aspartate (NMDA) receptor. Neuropathic pains have often been classified as 'opioid resistant' in both clinical and laboratory settings. As it is known that dynorphin produces 'non-opioid' effects through interaction with NMDA receptors and this peptide is upregulated after peripheral nerve injury, the present studies were undertaken to determine the possible importance of this substance in the neuropathic state. Nerve injury was produced in rats by tight ligation of the L5 and L6 spinal roots of the sciatic nerve. Catheters were inserted for the intrathecal (i.t.) delivery of drug to the lumbar spinal cord. Tactile allodynia was determined by measuring responses to probing the plantar surface of the affected limb with von Frey filaments, and acute nociception was determined in the 55 degrees C hot-water tail-flick test in nerve-ligated and sham-operated subjects. Intrathecal administration of MK-801 or antisera to dynorphin A (1-13) did not alter the tactile allodynia associated with nerve-ligation injury or the baseline tail-flick latency in either sham-operated or nerve-injured animals. As previously reported, i.t. morphine did not alter tactile allodynia and showed reduced potency and efficacy to block the tail-flick reflex in nerve-injured animals. Co-administration, however, of i.t. morphine with MK-801, or i.t. antisera to dynorphin A (1-13) given prior to morphine elicited both a full antiallodynic response and a complete block of the tail-flick reflex in nerve-injured animals. These results suggest that tonic activation of NMDA receptors, following peripheral nerve injury, is involved with the attenuation of the effectiveness of spinal morphine in a model of neuropathic pain. Additionally, this tonic NMDA activity may be mediated, in part, by increased levels of endogenous dynorphin associated with peripheral nerve injury.
The Presence of Novel Amino Acids in the Cytoplasmic Domain of Stem Cell Factor Results in Hematopoietic Defects inSteel17H Mice (1999)

Stem cell factor (SCF) is expressed as an integral membrane growth factor that may be differentially processed to produce predominantly soluble (S) (SCF248) or membrane-associated (MA) (SCF220) protein. A critical role for membrane presentation of SCF in the hematopoietic microenvironment (HM) has been suggested from the phenotype of the Steel-dickie(Sld) mice, which lack MA SCF, and by studies performed in our laboratory (and by others) using long-term bone marrow cultures and transgenic mice expressing different SCF isoforms.Steel17H (Sl17H) is an SCF mutant that demonstrates melanocyte defects and sterility in males but not in females. The Sl17H allele contains a intronic mutation resulting in the substitution of 36 amino acids (aa’s) in the SCF cytoplasmic domain with 28 novel aa’s. This mutation, which affects virtually the entire cytoplasmic domain of SCF, could be expected to alter membrane SCF presentation. To investigate this possibility, we examined the biochemical and biologic properties of the Sl17H-encoded protein and its impact in vivo and in vitro on hematopoiesis and on c-Kit signaling. We demonstrate that compound heterozygous Sl/Sl17H mice manifest multiple hematopoietic abnormalities in vivo, including red blood cell deficiency, bone marrow hypoplasia, and defective thymopoiesis. In vitro, both S and MA Sl17H isoforms of SCF exhibit reduced cell surface expression on stromal cells and diminished biological activity in comparison to wild-type (wt) SCF isoforms. These alterations in presentation and biological activity are associated with a significant reduction in the proliferation of an SCF-responsive erythroid progenitor cell line and in the activation of phosphatidylinositol 3-Kinase/Akt and mitogen-activated protein-Kinase signaling pathways. In vivo, transgene expression of the membrane-restricted (MR) (SCFX9/D3) SCF in Sl/Sl17H mutants results in a significant improvement in peripheral red blood cell counts in comparison toSl/Sl17H mice.
Donor lymphocyte infusion for the treatment of leukemia relapse after HLA-mismatched/haploidentical T-cell-replete hematopoietic stem cell transplantation (2007)

In this study, we tested the efficacy and safety of donor lymphocyte infusion (DLI) with granulocyte colony-stimulating factor (G-CSF) priming in patients who relapsed after haploidentical hematopoietic stem cell transplantation (HSCT). Twenty patients received DLI at a median of 177 days after HSCT. Eight patients survived in complete remission for a median of 1118 days. The 2-year probability of leukemia-free survival was 40%. Acute graft-versus-host disease (GVHD) grade 3-4 occurred in six patients after DLI. GVHD prophylaxis reduced the incidence of acute GVHD. Our primary data showed that G-CSF-primed DLI with GVHD prophylaxis was a potentially effective therapeutic option for patients who relapsed after haploidentical HSCT.
Stimuli‐Responsive Polymeric Systems for Biomedical Applications (2008)

Abstract Smart polymeric‐based devices and surfaces that reversibly alter their physico‐chemical characteristics in response to their environment are the center of many studies related to the development of materials and concepts in a broad‐range of biomedical fields. Although the initial interests were more focused in systems for the delivery of therapeutic molecules, other applications have been raised in topics ranging from actuators to biomaterials for tissue engineering and regenerative medicine. The general aspects of the different types of stimuli that can be used to modulate the response are reviewed mainly for the case of hydrogels and surfaces, based on natural‐origin or biodegradable macromolecules. Thermosensitive or light responsive surfaces that can modulate cell adhesion or protein adsorption are addressed as well as less conventional smart surfaces, such as substrates onto which biomineralization may be triggered. Injectable liquids that turn to gels by the action of heating (sol‐gel thermo‐reversible hydrogels) or by changing pH or the ionic milieu (bioinspired self‐assembling systems) may find great applicability as temporary scaffolds in non invasive procedures to deliver drugs or cells to particular places in the body. Examples of systems that recognize independently or simultaneously more than one stimulus will also be presented. Besides the typical response to temperature and pH, recent developments on materials that react to biochemical stimuli, including specific enzymes, antibodies or cells, are also highlighted.
Progress in antisense therapeutics. (1995)

Antisense technology offers the potential to create compounds specific enough to support highly isotypically selective pharmacology (i.e., pharmacologic agents specific enough to affect only one isotype in a multigene family of related proteins). However, enthusiasm about the potential of the technology has been appropriately tempered by questions about its ability to deliver on its promise. The fundamental issue is: Can oligonucleotides that have acceptable drug properties be created? This review discusses recent progress that helps to define the pharmacokinetic, pharmacologic, and toxicologic properties of phosphorothioate oligonucleotides. Progress in the medicinal chemistry of oligonucleotides that has resulted in a wide range of new chemical classes is also described.
The Rel/NF-κB Family Directly Activates Expression of the Apoptosis Inhibitor Bcl-x L (2000)

The transcription factors of the Rel/NF-kappaB family are key regulators of immune and inflammatory responses and contribute to lymphocyte proliferation, survival, and oncogenesis. The absolute correlation between the antiapoptotic and oncogenic activities of the Rel/NF-kappaB oncoprotein v-Rel emphasizes the importance of characterizing the death antagonists under NF-kappaB control. Our recent finding that the prosurvival Bcl-2 homolog Bfl-1 (also called A1) is a direct transcriptional target of NF-kappaB raised the issue of whether NF-kappaB is a specific or global regulator of death antagonists in the Bcl-2 family. Here, we demonstrate that NF-kappaB differentially regulates the expression of particular Bcl-2-related death inhibitors and that it directly activates the expression of Bcl-x(L). While Bcl-x(L) was significantly upregulated by c-Rel and RelA, Bcl-2 was not. Importantly, stimuli that activate endogenous NF-kappaB factors also upregulated bcl-x gene expression and this effect was antagonized by an inhibitor of NF-kappaB activity. The expression of bcl-x suppressed apoptosis in the presence or absence of NF-kappaB activity. Functional analysis of the bcl-x promoter demonstrated that it is directly controlled by c-Rel. These results establish that NF-kappaB directly regulates the expression of distinct prosurvival factors in the Bcl-2 family, such as Bcl-x(L) and Bfl-1/A1. These findings raise the possibility that some of these factors may contribute to oncogenesis associated with aberrant Rel/NF-kappaB activity.
Hereditary C1q deficiency and systemic lupus erythematosus (1994)

We describe a 27-year-old women with systemic lupus erythematosus, C1q deficiency and cytomegalovirus retinitis. She suffered from severe SLE, with cutaneous and CNS involvement, and died of CNS disease aged 28. Review of 29 other published cases of C1q deficiency shows that SLE in these patients is often severe (five with CNS disease, ten with glomerulonephritis). The results of autoantibody studies in this and another patient with C1q deficiency and SLE are presented--both patients had autoantibodies to the extractable nuclear antigens, Sm, RNP and Ro, and one patient had high titres of antibodies to dsDNA. One of the patients had previously been treated with fresh frozen plasma, and antibodies to C1q were present in his serum. Homozygous C1q deficiency is associated with a very high prevalence of severe SLE with the full panoply of autoantibodies characteristic of this disease.
Phenotypic Susceptibilities to Tenofovir in a Large Panel of Clinically Derived Human Immunodeficiency Virus Type 1 Isolates (2002)

Tenofovir is a nucleotide analogue human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) inhibitor, and its oral prodrug, tenofovir disoproxil fumarate, has recently been approved for the treatment of HIV-1 infection in the United States. The objective of this study was to characterize the in vitro susceptibility profiles of a large panel of clinically derived HIV-1 isolates for tenofovir. The distribution of tenofovir susceptibilities in over 1,000 antiretroviral-naive, HIV-1-infected individuals worldwide was determined using the Virco Antivirogram assay. In addition, phenotypic susceptibilities to tenofovir and other RT inhibitors were determined in a panel of nearly 5,000 recombinant HIV-1 clinical isolates from predominantly treatment-experienced patients analyzed as a part of routine drug resistance testing. Greater than 97.5% of isolates from treatment-naive patients had tenofovir susceptibilities <3-fold above those of the wild-type controls by the Antivirogram. The clinically derived panel of 5,000 samples exhibited a broad range of antiretroviral drug susceptibilities, including 69, 43, and 16% having >10-fold-decreased susceptibilities to at least one, two, and three antiretroviral drug classes, respectively. Greater than 88% of these 5,000 clinical isolates were within the threefold susceptibility range for tenofovir, and >99% exhibited <10-fold-reduced susceptibilities to tenofovir. Decreased susceptibility to tenofovir was not directly associated with resistance to other RT inhibitors; r(2) values of log-log linear regression plots of susceptibility to tenofovir versus susceptibility to other RT inhibitors were <0.4. The results suggest that the majority of treatment-naive and treatment-experienced individuals harbor HIV that remains within the normal range of tenofovir susceptibilities and may be susceptible to tenofovir disoproxil fumarate therapy.
In the Beginning: The Washington Supreme Court a Century Ago (1989)

This Article will discuss (1) the politics that influenced the drafting of the judicial article (article IV) in the constitutional convention; (2) the election of the first five members of the bench and the backgrounds of those inaugural judges; (3) the particular approach toward judicial review adopted by these five jurists (activism-restraint); and (4) the personal relations among these members of the supreme court. This Article will provide a personal perspective of the first five judges and their court.
Fault and the Suicide Victim: When Third Parties Assume a Suicide Victim’s Duty of Self-Care (1997)

We formulate a biofilm reactor model with suspended bacteria that accounts for thermodynamic growth inhibition. The reactor model is a chemostat style model consisting of a single replenished growth promoting substrate, a single reaction product, suspended bacteria, and wall attached bacteria in the form of a bacterial biofilm. We present stability conditions for the washout equilibrium using standard techniques, demonstrating that analytical results are attainable even with the added complexity from thermodynamic inhibition. Furthermore, we numerically investigate the longterm behaviour. In the computational study, we investigate model behaviour for select parameters and two commonly used detachment functions. We investigate the effects of thermodynamic inhibition on the model and find that thermodynamic inhibition limits substrate utilization/production both inside the biofilm and inside the aqueous phase, resulting in less suspended bacteria and a thinner biofilm.
Cardiovascular responses to long-term blockade of nitric oxide synthesis. (1993)

The goal of this study was to determine if there is a basal release of nitric oxide that affects long-term arterial pressure regulation in dogs. Studies were conducted over a 23-day period in eight conscious dogs with indwelling catheters. Nitric oxide synthesis was blocked by continuous intravenous infusion of nitro-L-arginine-methyl ester at 37.1 nmol/kg per minute for 11 days. Arterial pressure increased to 120 +/- 4% of control on the first day, decreased for a few days, and then increased to a maximum value of 122 +/- 6% of control on day 7. Bradycardia was sustained throughout the entire nitro-arginine period. Blockade of nitric oxide synthesis was evidenced by attenuated pressure and flow responses to systemic acetylcholine infusion. The pressor response to phenylephrine was increased for only 1 day, and the hypotensive effects of nitroprusside were enhanced. Also, the variability of arterial pressure was significantly increased during nitro-arginine. Sodium and water balances were positive the first day of nitro-arginine infusion but were unchanged for the entire nitro-arginine period. In conclusion, the data suggest that blockade of the basal release of nitric oxide in dogs causes an increase in the long-term level of arterial pressure without any sustained sodium or water retention.
SUPERCOILED CIRCULAR DNA-PROTEIN COMPLEX IN Escherichia coli : PURIFICATION AND INDUCED CONVERSION TO AN OPEN CIRCULAR DNA FORM (1969)

The 23S twisted circular form of ColE(1) DNA has been isolated from Escherichia coli as a tightly associated DNA-protein complex with a sedimentation coefficient of approximately 24S. Treatment of this complex with pronase, trypsin, sodium dodecyl sulfate, Sarkosyl, or heat results in a conversion to a slower sedimenting form of 17S or 18S, as determined by centrifugation in neutral sucrose gradients. These treatments do not alter the sedimentation properties of noncomplexes supercoiled ColE(1) DNA even in the presence of the ColE(1)-protein complex. Electron microscopic analyses indicate that the decrease in sedimentation rate of the ColE(1)-protein complex after treatment with these various agents is largely owing to an induced transition of ColE(1) DNA from the supercoiled to the open circular state.
Holographic interferometer to test optical surfaces (1975)

A new interferometric method for testing optical surfaces is given. It is related to Murty's Fresnel zone plate interferometer and suggests the fruitful applications of holography to this branch of optics. In this paper a theoretical model that explains both interferometers is developed. Experimental results and pertinent comments are included.
Introduction (2011)

Ever since humans learned to harness power from sources other than what their own muscles could provide, several important changes have occurred in the way in which societies are able to conduct civilized life. Modern agriculture and urban life are almost totally dependent on people's ability to control natural forces that are far greater than their muscles could exert. We can almost say that one of the main propellants of modern society is the increased availability of nonmuscle energy.
The Liver X Receptor (LXR) and Hepatic Lipogenesis (2006)

The liver X receptors, LXRalpha (NR1H3) and LXRbeta (NR1H2), are ligand-activated transcription factors that belong to the nuclear hormone receptor superfamily. LXRs play a critical role in cholesterol homeostasis and bile acid metabolism. In addition, oral administration of LXR agonists to mice results in elevated hepatic fatty acid synthesis and steatosis and increased secretion of triglyceride-rich very low density lipoprotein resulting in hypertriglyceridemia. This increased hepatic lipogenesis has been largely attributed to the LXR-dependent up-regulation of sterol regulatory element-binding protein 1c (SREBP-1c) expression. However, it has been reported that treating Srebp-1c null mice with the synthetic LXR agonist T0901317 still results in enhanced expression of many lipogenic genes, suggesting additional mechanisms by which LXR can enhance hepatic lipogenesis. In this report, we identify the carbohydrate response element-binding protein (ChREBP) as an LXR target that independently enhances the up-regulation of select lipogenic genes. The ChREBP promoter contains functional LXR-binding sites that confer receptor-dependent binding and transactivation. We show that T0901317 treatment of mice is associated with up-regulation of the ChREBP target gene, liver-type pyruvate kinase. Therefore, activation of LXR not only increases ChREBP mRNA via enhanced transcription but also modulates ChREBP activity. This establishes LXR as a master lipogenic transcription factor, as it directly regulates both SREBP-1c and ChREBP to enhance hepatic fatty acid synthesis.
Developmental changes of connexin40 and connexin43 mRNA distribution patterns in the rat heart (1996)

Gap junctions have been demonstrated ultrastructurally in cardiac regions where connexin40 (Cx40) and connexin43 (Cx43) protein could not be detected immunohistochemically. We investigated therefore the distribution of their mRNAs with more sensitive techniques. Methods: In situ hybridizations with Cx40 and Cx43 cRNA probes were performed on sections of rat hearts from 9 embryonic days (ED 9) to adults. Results: From ED 13, Cx40 and Cx43 mRNA are detectable in atria and ventricles, but not in their flanking myocardium (inflow tract, atrioventricular canal and outflow tract). Even though Cx40 and Cx43 mRNA eventually become expressed in the inflow tract, they remain undetectable in the sinoatrial node, the atrioventricular canal (including atrioventricular node) and outflow tract. Expression of Cx40 is maximal in the fetal period and declines towards birth. Cx40 expression in the left and right ventricles evolves independently, its mRNA disappearing 4 days earlier from the right than from the left ventricle, and earlier from the free wall than from the trabeculations. Expression of Cx43 mRNA increases during development and changes postnatally from uniform to punctate. Prenatally, Cx43 mRNA was strongest in the subepicardial layer of the ventricular free wall. Nevertheless, we did not detect protein in this layer. Conclusions: Cardiac regions without detectable Cx40 or Cx43 mRNA either have extremely low levels of expression or express a different connexin. The temporally separate disappearance of Cx40 mRNA from the fetal ventricles implies that left and right ventricles mature independently with respect to gap-junctional communication. The division of the developing heart in compartments where Cx40 and Cx43 mRNA can and cannot be detected, implies pretranslationally regulated gene expression. The postnatally observed subcellular redistribution of Cx43 mRNA coincides with a reported increase in protein expression.
Outcome after relapse of acute lymphoblastic leukemia in adult patients included in four consecutive risk-adapted trials by the PETHEMA Study Group (2010)

The prognosis of adult patients with acute lymphoblastic leukemia who relapse is poor. Those aged less than 30 years with a first complete remission lasting longer than 2 years have reasonable possibilities of becoming long-term survivors while patients over this age or those who relapse early cannot be successfully rescued using the therapies currently available.