gebhart/patrepeval huggingface dataset:
Increased Production of Amyloid Precursor Protein Provides a Substrate for Caspase-3 in Dying Motoneurons (1998)

Biochemical and molecular mechanisms of neuronal cell death are currently an area of intense research. It is well documented that the lumbar spinal motoneurons of the chick embryo undergo a period of naturally occurring programmed cell death (PCD) requiring new gene expression and activation of caspases. To identify genes that exhibit changed expression levels in dying motoneurons, we used a PCR-based subtractive hybridization protocol to identify messages uniquely expressed in motoneurons deprived of trophic support as compared with their healthy counterparts. We report that one upregulated message in developing motoneurons undergoing cell death is the mRNA for amyloid precursor protein (APP). Increased levels of APP and beta-amyloid protein are also detected within dying motoneurons. The predicted peptide sequence of APP indicates two potential cleavage sites for caspase-3 (CPP-32), a caspase activated in dying motoneurons. When peptide inhibitors of caspase-3 are administered to motoneurons destined to undergo PCD, decreased levels of APP protein and greatly reduced beta-amyloid production are observed. Furthermore, we show that APP is cleaved by caspase-3. Our results suggest that differential gene expression results in increased levels of APP, providing a potential substrate for one of the cell death-activated caspases that may ultimately cause the demise of the cell. These results, combined with information on the toxic role of APP and its proteolytic by-product beta-amyloid, in the neurodegenerative disease Alzheimer's, suggest that events of developmental PCD may be reactivated in early stages of pathological neurodegeneration.
Rapid Detection of Urinary Tract Infections Using Isotachophoresis and Molecular Beacons (2011)

We present a novel assay for rapid detection and identification of bacterial urinary tract infections using isotachophoresis (ITP) and molecular beacons. We applied on-chip ITP to extract and focus 16S rRNA directly from bacterial lysate and used molecular beacons to achieve detection of bacteria specific sequences. We demonstrated detection of E. coli in bacteria cultures as well as in patient urine samples in the clinically relevant range 1E6-1E8 cfu/mL. For bacterial cultures we further demonstrate quantification in this range. The assay requires minimal sample preparation (a single centrifugation and dilution), and can be completed, from beginning of lysing to detection, in under 15 min. We believe that the principles presented here can be used for design of other rapid diagnostics or detection methods for pathogenic diseases.
Induction of bacteriocin production in Lactobacillus sake by a secreted peptide (1996)

Lactobacillus sake LTH673 is known to produce a bacteriocin called sakacin P. Production of and immunity to sakacin P were found to depend on the presence of a protease-sensitive component that is produced by L. sake LTH673 itself. This component (called inducing factor [IF]) was purified from culture supernatants and shown to be a basic, nonbacteriocin peptide consisting of 19 amino acids, which in principle is capable of forming a highly amphiphilic helical structure. Circular dichroism studies showed that IF indeed could adopt a helical structure, but only in membrane-mimicking environments. Both purified IF and chemically synthesized IF induced expression of the structural gene for sakacin P and concomitant secretion of the gene product. In addition, IF induced its own production and immunity to sakacin P and related bacteriocins. These results indicate that bacteriocin production by L. sake LTH673 is controlled by an autoinduction pathway in which IF may function as a cell density signal.
Human FLT3/FLK2 receptor tyrosine kinase is expressed at the surface of normal and malignant hematopoietic cells. (1996)

FLT3/FLK2 is a receptor tyrosine kinase (RTK) which is thought to play an important role in early stages of hematopoiesis. Monoclonal antibodies (mAbs) against the extracellular domain of human FLT3 were generated to study the cell surface expression of this class III RTK on normal bone marrow cells and on leukemic blasts from patients with acute leukemias. Functional analysis of five mAbs (SF1 series) revealed that all of them can mimic to variable extents the activity of the FLT3 ligand (FL) upon receptor activation and modulation, while only one mAb weakly inhibited ligand binding. Using flow cytometry, we detected surface expression of FLT3 on cell lines of the myeloid (4/8) and B lymphoid (7/10) lineages. On normal human bone marrow cells, the expression of FLT3 is restricted, in agreement with a presumed function of this receptor at the level of the stem cells and early committed progenitors. Expression of FLT3 was found on a fraction of CD34-positive and CD34-negative cells. Three-color analysis further revealed that most of the CD34 FLT3+ cells coexpress CD117 (KIT) at a high level. Finally, FLT3 is expressed on leukemic blasts of 18/22 acute myeloid leukemias (AML) and 3/5 acute lymphoid leukemias (ALL) of the B lineage, providing a possible application in diagnosis and therapy of these diseases.
The Itch-Producing Agents Histamine and Cowhage Activate Separate Populations of Primate Spinothalamic Tract Neurons (2007)

Itch is an everyday sensation, but when associated with disease or infection it can be chronic and debilitating. Several forms of itch can be blocked using antihistamines, but others cannot and these constitute an important clinical problem. Little information is available on the mechanisms underlying itch that is produced by nonhistaminergic mechanisms. We examined the responses of spinothalamic tract neurons to histaminergic and, for the first time, nonhistaminergic forms of itch stimuli. Fifty-seven primate spinothalamic tract (STT) neurons were identified using antidromic activation techniques and examined for their responses to histamine and cowhage, the nonhistaminergic itch-producing spicules covering the pod of the legume Mucuna pruriens. Each examined neuron had a receptive field on the hairy skin of the hindlimb and responded to noxious mechanical stimulation. STT neurons were tested with both pruritogens applied in a random order and we found 12 that responded to histamine and seven to cowhage. Each pruritogen-responsive STT neuron was activated by the chemical algogen capsaicin and two-thirds responded to noxious heat stimuli, demonstrating that these neurons convey chemical, thermal, and mechanical nociceptive information as well. Histamine or cowhage responsive STT neurons were found in both the marginal zone and the deep dorsal horn and were classified as high threshold and wide dynamic range. Unexpectedly, histamine and cowhage never activated the same cell. Our results demonstrate that the spinothalamic tract contains mutually exclusive populations of neurons responsive to histamine or the nonhistaminergic itch-producing agent cowhage.
CONSTRUE/TIS: A System for Content-Based Indexing of a Database of News Stories (1990)

The Construe news story categorization system assigns indexing terms to news stories according to their content using knowledge-based techniques. An initial deployment of Construe in Reuters Ltd. topic identification system (TIS) has replaced human indexing for Reuters Country Reports, an online information service based on news stories indexed by country and type of news. TIS indexing is comparable to human indexing in overall accuracy but costs much less, is more consistent, and is available much more rapidly. TIS can be justified in terms of cost savings alone, but Reuters also expects the speed and consistency of TIS to provide significant competitive advantage and, hence, an increased market share for Country Reports and other products from Reuters Historical Information Products Division.
DuoBody-CD3xCD20 induces potent T-cell-mediated killing of malignant B cells in preclinical models and provides opportunities for subcutaneous dosing (2020)

Genmab.
β-Cell dysfunction in type II diabetes mellitus (1995)

Non-insulin-dependent diabetes mellitus (NIDDM) is characterized by insulin resistance and β cell dysfunction. Current research is focused on identifying the genetic or functional abnormalities that cause the glucose intolerance, with the long term goal of designing targeted therapies. This review focuses on the p cell and on what defects occur, when, and why. The genetic basis for typical NIDDM is unknown. Mutations in several rare forms of diabetes have been identified during the past couple of years, including two that affect the β cell: glucokinase mutations in families with maturity-onset diabetes of youth and mitochondrial mutations in persons with maternally inherited diabetes (who often, but not invariably, have deafness). Amyloid deposits are a well-known β-cell anatomic finding in NIDDM. There has been considerable speculation that they cause the hyperglycemia by lowering the mass of functional β cells. The latest information from transgenic mice that overexpress human amylin (the protein that makes up the amyloid deposits) in their β cells is consistent with the amyloid deposition occurring after the onset of hyperglycemia. Many studies have looked at insulin secretion in NIDDM, and two types of abnormalities have been found. Early on, the pulsatile pattern of insulin delivery is disrupted. There is considerable interest in the idea that this defect may hold promise as a way to predict persons at risk for NIDDM, After glucose intolerance begins, β-cell glucose responsiveness becomes impaired, further exacerbating the hyperglycemia. Considerable effort is currently directed at identifying the mechanism for this defect. Multiple possibilities have come from rodent models of NIDDM.
Toward a real-time spoken language system using commercial hardware (1990)

We describe the methods and hardware that we are using to produce a real-time demonstration of an integrated Spoken Language System. We describe algorithms that greatly reduce the computation needed to compute the N-Best sentence hypotheses. To avoid grammar coverage problems we use a fully-connected first-order statistical class grammar. The speech-search algorithm is implemented on a board with a single Intel i860 chip, which provides a factor of 5 speedup over a SUN 4 for straight C code. The board plugs directly into the VME bus of the SUN4, which controls the system and contains the natural language system and application back end.
Non-invasive detection of fetal trisomy 21 using fetal epigenetic biomarkers with a high CpG density (2013)

Our findings suggest that the EER may be useful as a potential biomarker for the non-invasive detection of fetal T21, regardless of fetal gender. The MBD method can be used as an effective tool in the detection of methylated fetal specific markers with a high CpG density in maternal plasma.
Glomerular procoagulant activity in human proliferative glomerulonephritis. (1988)

Mechanisms for initiation of glomerular fibrin deposition were studied using renal tissue obtained from two patients with rapidly progressive, crescentic glomerulonephritis. Histological examination showed extensive glomerular monocyte infiltration and fibrin deposition in both patients. Sonicated cell suspensions of isolated glomeruli from these patients contained markedly augmented levels of procoagulant activity (PCA) compared with the levels found in normal glomeruli. This PCA was characterized as tissue factor by its functional dependence on Factors VII and V, independence of Factors VIII and XII, inhibition by concanavalin A and phospholipase C, and association with cell membranes. Its coagulant activity was also inhibited by a specific monoclonal anti-human tissue factor antibody. Tissue factor could be identified in glomeruli from these two patients by indirect immunofluorescence using this antibody. These studies implicate extrinsic pathway activation via tissue factor in intraglomerular deposition of fibrin in these patients. Activated monocytes, known to be a potent source of procoagulant activity and seen in large numbers within glomeruli from these patients, are a likely source of this tissue factor.
Pathophysiology and Related Studies of the No Reflow Phenomenon in Skeletal Muscle (1995)

Although the success rate of microvascular replantation and revascularization procedures has increased steadily since the 1960s, some replanted tissues do not reperfuse despite technically adequate arterial anastomoses. This failure of microvascular perfusion is termed no reflow. Much research has been directed toward discovering the etiology of no reflow since it was first described 25 years ago. Three pathophysiologic processes have been identified as playing a central role in the development of no reflow: intracellular calcium overload, oxygen-free radical medicated damage, and altered arachidonic acid metabolism. The first tissue believed to be injured irreversibly by these processes is the endothelium, which leads to dysfunction of the parenchymal cells. All 3 pathways are interrelated extensively, which allows for pharmacologic intervention at many different steps. Agents that have been shown to be beneficial in preventing no reflow include calcium channel blockers, prostaglandin analogs, thromboxane synthesis inhibitors, vasodilators, thrombolytics, and many antioxidants. Although they have been shown to be effective in various laboratory models, additional investigation is necessary before these treatments can be established in clinical use.
Acetalization with Methanol Using Metal-Organic Frameworks (2011)

Acetalization of aldehydes and ­ketones with methanol using metal-organic frameworks (MOFs) as heterogeneous solid acid catalysts was described. The reaction of aldehydes (16 examples) and ketones (2 examples) with a copper-containing MOF [Cu3(BTC)2] (BTC = 1,3,5-benzenetricarboxylate) gave the corresponding dimethyl acetals in 9-94% yield.
Science, medicine, and the future: Pharmacogenetics (2000)

Individual variation in response to drugs is a substantial clinical problem. Such variation ranges from failure to respond to a drug to adverse drug reactions and drug-drug interactions when several drugs are taken concomitantly. The clinical consequences range from patient discomfort through serious clinical illness to the occasional fatality. One UK study has suggested that about 1 in 15 hospital admissions are due to adverse drug reactions,1 and a recent US study estimated that 106 000 patients die and 2.2 million are injured each year by adverse reactions to prescribed drugs.2
Erythropoietin induces Raf-1 activation and Raf-1 is required for erythropoietin-mediated proliferation (1991)

Erythropoietin mediates the rapid phosphorylation of Raf-1 in the murine cell lines HCD-57 and FDC-P1/ER, which proliferate in response to this cytokine. Phosphorylation occurs at both serine and tyrosine residues and as such is similar to the Raf-1 phosphorylation seen after interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor, and interleukin-2 stimulation in other murine cell lines. Such data suggest that these growth factors may share a common mechanism(s) of Raf-1 phosphorylation. Furthermore, in association with Raf-1 phosphorylation, erythropoietin induces a 2-3-fold increase in Raf-1 kinase activity as measured in immune complex kinase assays in vitro. Finally, a c-raf antisense oligodeoxyribonucleotide, which specifically decreases intracellular Raf-1 levels, also substantially inhibits both erythropoietin and IL-3-directed DNA synthesis. Together, these results provide evidence that activated Raf-1 is a necessary component of erythropoietin and IL-3 growth signaling pathways.
IFN-γ Enhances Production of IFN-α in Human Macrophages but Not in Monocytes (1996)

Monocytes/macrophages are efficient producers of alpha interferons (IFN), and IFN-gamma is a potent activator of these cells. The present study sought to investigate whether IFN-alpha affects the capacity of human monocytes/macrophages to produce IFN-alpha on induction with Sendai virus. Plastic-adherent human peripheral blood monocytes were grown in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) for 3 weeks during which they were transformed into macrophages. At various times, the cultures were pretreated for 24 h with IFN-gamma and induced with Sendai virus for IFN-alpha production. Pretreatment with IFN-gamma had no effect on the production of IFN-alpha during the first days in culture. The production of IFN-alpha was thereafter significantly enhanced by the IFN-gamma pretreatment. Minute amounts of IFN-gamma, < or = 0.1 IU/ml, increased the production of IFN-alpha in macrophages cultured for more than 7 days. The cooperation between IFN-gamma and IFN-alpha in macrophages may play a role in the antiviral defense of the body.
Intranasal Lidocaine for Treatment of Migraine (1996)

<h3>Objective.</h3> —To evaluate the effectiveness of intranasal lidocaine for treatment of acute migraine headache. <h3>Design.</h3> —Prospective, randomized, double-blind, placebo-controlled trial. <h3>Setting.</h3> —Community urgent care department. <h3>Patients.</h3> —A total of 81 patients (67 women and 14 men; median age, 42 years; range, 19-68 years) with a chief complaint of headache who fulfilled criteria of the International Headache Society for migraine participated. Patients were excluded if headache had lasted more than 3 days or if the frequency of severe headache was more than once per week. <h3>Intervention.</h3> —Patients were randomized in a 2:1 ratio to receive a 4% solution of intranasal lidocaine or saline placebo, respectively. <h3>Main Outcome Measures.</h3> —The primary outcome measure was at least 50% reduction of headache within 15 minutes after treatment. Secondary measures include reduction in nausea and photophobia, use of rescue medication, relapse of headache, and change in headache disability scores. <h3>Results.</h3> —Of 53 patients who received intranasal lidocaine, 29 (55%) had at least a 50% reduction of headache compared with 6 (21%) of 28 controls (<i>P</i>=.004). Nausea and photophobia were significantly reduced (<i>P</i>=.03 and<i>P</i>=.001, respectively). Rescue medication for headache relief was needed in 15 (28%) of 53 patients in the lidocaine group vs 20 (71%) of 28 controls (<i>P</i>&lt;.001). Among those with initial relief of headache, relapse of headache occurred in 10 (42%) of 24 in the lidocaine group vs 5 (83%) of 6 in the control group (<i>P</i>=.17), usually within the first hour after treatment. <h3>Conclusions.</h3> —Intranasal lidocaine provides rapid relief of headache in approximately 55% of ambulatory patients with migraine. Relapse of headache is common and occurs early after treatment.
[Proteomic analysis of paclitaxel-induced apoptosis in MCF-7 human breast carcinoma cells]. (2006)

We effectively found the changed proteins in the process of paclitaxel-induced apoptosis in MCF-7 human breast carcinoma cells by proteomic techniques. These up-regulated or down-regulated proteins are important molecules for our further research about the mechanism of paclitaxel-induced apoptosis.
Liver iron concentrations and urinary hepcidin in -thalassemia (2007)

Background and Objectives Patients with β-thalassemia, like those with genetic hemochromatosis, develop iron overload due to increased iron absorption, and their iron burden is further exacerbated by transfusion therapy. Hepcidin, a hepatic hormone, regulates systemic iron homeostasis by inhibiting the absorption of iron from the diet and the recycling of iron by macrophages. In turn, hepcidin release is increased by iron loading and inhibited by erythropoietic activity. Hepcidin deficiency is the cause of iron overload in most forms of hereditary hemochromatosis. We sought to determine hepcidin’s role in the pathogenesis of iron overload in β-thalassemia.Design and Methods We assessed the degree of iron overload in thalassemia intermedia and major patients by measuring hepatic iron concentration in liver biopsy samples and serum ferritin, estimated erythropoietic drive by assaying soluble transferrin receptor and serum erythropoietin levels and correlated these with urinary hepcidin measurements.Results Urinary hepcidin levels in β-thalassemia demonstrate severe hepcidin deficiency in thalassemia intermedia. There was a strong inverse relationship between urinary hepcidin levels and both erythropoietin and soluble transferrin receptor, markers of erythropoietic activity. In contrast, hepcidin levels were elevated in thalassemia major, presumably due to transfusions that reduce erythropoietic drive and deliver a large iron load. Despite similar liver iron concentrations in the two conditions, serum ferritin was much lower in thalassemia intermedia.Interpretation and Conclusions In thalassemia intermedia, high erythropoietic drive causes severe hepcidin deficiency. The lack of hepcidin results in hyperabsorption of dietary iron, but also in iron depletion of macrophages, lowering their secretion of ferritin and, consequently, serum ferritin levels. In contrast, in thalassemia major, transfusions decrease erythropoietic drive and increase the iron load, resulting in relatively higher hepcidin levels. In the presence of higher hepcidin levels, dietary iron absorption is moderated and macrophages retain iron, contributing to higher serum ferritin. In the future, hepcidin measurements may allow a more accurate assessment of the degree of iron overload and the maldistribution of iron in thalassemia.
The effect of aspirin on niacin-induced cutaneous reactions. (1992)

It appears from this pilot study that preceding niacin with 325 mg of aspirin will decrease the warmth and flushing associated with niacin.
Current issues concerning thrombolytic therapy for acute myocardial infarction (1995)

Data are now available from three large-scale randomized trials that directly compare the risks and benefits of thrombolytic agents in acute myocardial infarction. In the interpretation of results from the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico (GISSI-2) trial and its International Extension, the Third International Study of Infarct Survival (ISIS-3), and the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO-1) trial, there are areas of both agreement and controversy. It is generally agreed that the agents most commonly used in the United States--tissue-type plasminogen activator (t-PA), streptokinase and anisoylated plasminogen streptokinase activator complex (APSAC)--all reduce mortality when given to patients with acute evolving myocardial infarction. Further, it is clear that thrombolytic therapy given to such patients presenting up to 12 h after onset of symptoms reduces the mortality rate by approximately 20%, that aspirin therapy for patients presenting up to 24 h reduces the mortality rate by approximately 23% and that the benefits of thrombolytic therapy and aspirin are additive. Finally, and of most importance, the earlier administration as well as the more widespread use of thrombolytic therapy and aspirin would save many more lives. The totality of evidence clearly indicates that streptokinase produces significantly fewer strokes and cerebral hemorrhages than either t-PA or APSAC. Whether or not accelerated t-PA has a small advantage for mortality is less conclusive.(ABSTRACT TRUNCATED AT 250 WORDS)