gebhart/patrepeval huggingface dataset:
Dipole interactions in axonal microtubules as a mechanism of signal propagation (1997)

The microtubules (MTs) of nerve cells are stable relative to their counterparts in the rest of the body. This stability allows them to participate in cellular signaling processes. Each of the MT's subunits, dimers of tubulin protein, has an electric dipole moment that contributes to the overall polarity of the structure. We propose that the orientation of the individual dipoles may be flipped due to a conformational change of the tubulin dimer if energy is supplied through guanosine tri-phosphate hydrolysis or via physical interactions. Thus the MT lattice may be viewed as an electric dipole lattice with some overall polarization upon which signals, in the form of dipole patterns, may be propagated through dipole interactions that induce conformational changes. As a nerve impulse propagates along a neuron (nerve cell), the neuronal MTs are subjected to a large transient electric field that interacts with the MT lattices. Based on the recent conjecture of information processing and/or energy transport by MTs, we have used a Monte Carlo technique to model the interactions between the MT's subunits and to investigate the response of the lattice to nerve impulses. Our model of these interactions addresses the problem of thermal fluctuations in the dipole lattice and demonstrates how the nerve impulse may cause a signal to propagate along the MTs within the axon.
Treatment of persistent dry cough: if possible, treat the cause; if not, treat the cough. (1999)

Persistent dry cough is a common presenting symptom which may be associated with considerable morbidity. In the majority of patients, systematic investigation reveals an underlying cause, usually asthma, postnasal drip, gastrooesophageal reflux or various combinations of these conditions. Intensive treatment of the underlying cause usually leads to improvement or resolution of the cough. However, in a minority of patients, no underlying cause is identified despite appropriate investigation. In these patients with idiopathic persistent dry cough, cough sensitivity to inhaled tussigens is enhanced, suggesting that increased sensitivity of airway sensory nerves is important in pathogenesis. An ideal antitussive would reduce this increased sensitivity to normal levels without significant adverse effects but currently available antitussives fall short of this expectation. This review discusses the currently available antitussive therapy and explores potential avenues for the development of future novel antitussive therapies.
The innate immune system in demyelinating disease (2012)

Demyelinating diseases such as multiple sclerosis are chronic inflammatory autoimmune diseases with a heterogeneous clinical presentation and course. Both the adaptive and the innate immune systems have been suggested to contribute to their pathogenesis and recovery. In this review, we discuss the role of the innate immune system in mediating demyelinating diseases. In particular, we provide an overview of the anti-inflammatory or pro-inflammatory functions of dendritic cells, mast cells, natural killer (NK) cells, NK-T cells, γδ T cells, microglial cells, and astrocytes. We emphasize the interaction of astroctyes with the immune system and how this interaction relates to the demyelinating pathologies. Given the pivotal role of the innate immune system, it is possible that targeting these cells may provide an effective therapeutic approach for demyelinating diseases.
Fasting plasma amino acid levels in cancer patients (1985)

The concentration in plasma of 15 fasting amino acids were measured in 14 control volunteers and 55 cancer patients. In addition, 16 patients (7 with, 9 without total parenteral nutrition [TPN] ) with metastatic sarcoma had sequential amino acid profiles measured during 6 weeks of ablative chemotherapy. In four cancer patient groups (lymphoma, sarcoma, osteosarcoma and metastatic sarcoma) with no or minimal weight loss, most plasma amino acid levels were similar to controls. Proline levels were significantly reduced in the lymphoma and sarcoma patients. Esophageal cancer patients with 20% body weight loss had a marked reduction in total and individual amino acid levels (except branched chain amino acids) compared to controls and all others. The metastatic sarcoma patients who received parenteral nutrition had higher levels of plasma lysine and tyrosine during chemotherapy than controls; however, TPN failed to change the majority of amino acid levels. It appears that plasma amino acid levels except proline were well maintained in cancer patients without weight loss. Esophageal cancer patients with weight loss demonstrated marked reduction in all circulating amino acids except branched chain. Parenteral nutrition did not significantly alter the amino acid profile of cancer patients undergoing chemotherapy.
ChemInform Abstract: Glycals in Stereospecific Synthesis. Part 5. Chiral Synthons for (14R, 15R)‐Lipoxine B (IX) and (‐)‐cis‐Disparlure (VI) from 6‐Substituted 6‐ Deoxy‐D‐galactoses. (1991)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Kinetics of grafting acrylonitrile onto starch (1973)

Abstract Acrylonitrile (AN) was graft copolymerized onto gelatinized and granular wheat starch in aqueous media in the presence of ceric ammonium nitrate initiator at 91‐364 anhydroglucose units (AGU) per cerium (IV) and at 1.08‐4.33 AN to AGU ratios. Molecular weights and dispersities of polyacrylonitrile side chains were determined by gel‐permeation chromatography. Conversion‐time plots of AN polymerizations in both gelatinized and granular starch systems show characteristics common to heterogeneous polymerizations that could be explained on the basis of buried polymer radicals. The rates of polymerizations were directly related to the square root of the corrected cerium(IV) concentration and to the 1.3 power of the AN concentration. Graft copolymerization of AN onto starch, at least during initial stages, is not suitably explained by a kinetic scheme involving termination by polymer radical with cerium(IV) ion.
Nucleic Acid Amplification Technologies Application to Disease Diagnosis (1996)

Guide to current information on various nucleic acid amplification technologies for clinical laboratory diagnosis. For biomedical scientists.
Methods for Quantification of in vivo Changes in Protein Ubiquitination following Proteasome and Deubiquitinase Inhibition (2012)

Ubiquitination plays a key role in protein degradation and signal transduction. Ubiquitin is a small protein modifier that is adducted to lysine residues by the combined function of E1, E2, and E3 enzymes and is removed by deubiquitinating enzymes. Characterization of ubiquitination sites is important for understanding the role of this modification in cellular processes and disease. However, until recently, large-scale characterization of endogenous ubiquitination sites has been hampered by the lack of efficient enrichment techniques. The introduction of antibodies that specifically recognize peptides with lysine residues that harbor a di-glycine remnant (K-ε-GG) following tryptic digestion has dramatically improved the ability to enrich and identify ubiquitination sites from cellular lysates. We used this enrichment technique to study the effects of proteasome inhibition by MG-132 and deubiquitinase inhibition by PR-619 on ubiquitination sites in human Jurkat cells by quantitative high performance mass spectrometry. Minimal fractionation of digested lysates prior to immunoaffinity enrichment increased the yield of K-ε-GG peptides three- to fourfold resulting in detection of up to ~3300 distinct K-GG peptides in SILAC triple encoded experiments starting from 5 mg of protein per label state. In total, we identify 5533 distinct K-ε-GG peptides of which 4907 were quantified in this study, demonstrating that the strategy presented is a practical approach to perturbational studies in cell systems. We found that proteasome inhibition by MG-132 and deubiquitinase inhibition by PR-619 induces significant changes to the ubiquitin landscape, but that not all ubiquitination sites regulated by MG-132 and PR-619 are likely substrates for the ubiquitin-proteasome system. Additionally, we find that the proteasome and deubiquitinase inhibitors studied induced only minor changes in protein expression levels regardless of the extent of regulation induced at the ubiquitin site level. We attribute this finding to the low stoichiometry of the majority ubiquitination sites identified in this study.
Loss of nuclear p16 protein expression is not associated with promoter methylation but defines a subgroup of aggressive endometrial carcinomas with poor prognosis. (2000)

The p16INK4aa (CDKN2) tumor suppressor gene is altered in several tumor types, but the frequency and mechanism of inactivation are largely unknown for endometrial carcinomas. We therefore wanted to assess the pattern and prognostic impact of p16 protein expression and promoter region methylation in a population-based series of 316 endometrial carcinoma patients with long-term and complete follow-up. Nuclear staining of p16 protein was related to clinicopathological variables, tumor markers, patient survival, and the presence of promoter region methylation. Absent/minimal nuclear staining for p16 protein was found in 14% of the tumors. Methylation of the p16 promoter region was found in only one tumor (0.7%) in a subset of 138 cases studied. This tumor lacked nuclear p16 protein expression as well. Loss of nuclear p16 staining was significantly associated with increased age, high FIGO (International Federation of Gynecology and Obstetrics) stage, serous papillary or clear cell histological types, high histological grade, aneuploidy, low estradiol and progesterone receptor concentrations, high expression of Ki-67, high intratumor microvessel density, and strong nuclear p53 protein expression. The 5-year survival was 47% for patients with absent/minimal nuclear p16 expression (n = 39) compared with 81% for patients with moderate/high nuclear p16 expression (n = 247; P < 0.0001). In Cox proportional hazards regression analysis, nuclear p16 expression showed an independent prognostic impact in addition to FIGO stage, age, Ki-67 expression, and microvessel density, with an adjusted hazard ratio of 2.9 (95% confidence interval, 1.3-6.5). The other variables lost their prognostic impact when nuclear p16 staining was added to the Cox model. In conclusion, loss of nuclear p16 protein expression was associated with aggressive endometrial carcinomas and high proliferative activity (Ki-67) and was found to represent a strong and independent prognostic indicator. Methylation of the promoter region seems to be an uncommon mechanism of p16 inactivation in endometrial carcinoma.
Pharmacokinetic interaction of cytochrome P450 3A-related compounds with rhodamine 123, a P-glycoprotein substrate, in rats pretreated with dexamethasone. (2001)

The effect of pretreatment with dexamethasone (DEX) on drug-drug interactions between rhodamine 123 (Rho123), a P-glycoprotein (P-gp) substrate, and midazolam, a cytochrome P450 (CYP) 3A substrate, or verapamil, a P-gp/CYP3A substrate, was studied in rats. Rats were pretreated with DEX (100 mg/kg/day, oral) for 2 days. Western blot analysis with a monoclonal antibody for P-gp, C219, revealed that DEX pretreatment increased P-gp level in the intestine 1.9-fold, but not in the liver. In vitro metabolism study of erythromycin in microsomal suspensions indicated the 9.7-fold increase of CYP3A activity in the liver, but not in the intestine, by DEX pretreatment. In an in vivo study, DEX pretreatment increased P-gp-mediated exsorption clearance of Rho123 from blood to the intestinal lumen approximately 2-fold, but not biliary clearances, in good agreement with the results of Western blot analysis. In untreated rats, midazolam (100 microM) or verapamil (30 or 100 microM) added in the intestinal perfusate (single perfusion) decreased the exsorption clearance and biliary clearance of Rho123 by approximately 30 to 50%. In DEX-pretreated rats, however, the inhibitory potency of midazolam in the liver significantly decreased compared with that in untreated rats, although the potency in the intestine did not change. The inhibitory potency of verapamil decreased both in the intestine and liver by DEX pretreatment. In conclusion, it was demonstrated that DEX pretreatment affects not only P-gp-mediated disposition of Rho123 but also pharmacokinetic interactions of P-gp/CYP3A-related compounds with Rho123, probably because concentrations of substrates/inhibitors at target sites such as the intestine and liver are varied.
The Significance of Nasal Protease Inhibitor Concentrations in House Dust Allergy (1978)

In 57 patients with house dust allergy and 20 controls protease inhibitor concentrations in nasal secretions were measured before and after antigen challenge. A correlation was found between low inhibitor levels and long duration of disease. Furthermore, significant differences of inhibitor concentrations could be demonstrated between patients with strong or moderate reactions to antigen provocation, and between patients with isolated rhinitis or a combination of rhinitis and bronchial asthma. The clinical significance of the results will be discussed with special regard to different biochemical mechanisms in the pathophysiology of seasonal and perennial immediate-type rhinitis.
The Genetics of Type 2 Diabetes: A Realistic Appraisal in 2008 (2008)

Although substantial progress in our knowledge of the genetic basis of type 2 diabetes is taking place, these new discoveries represent but a small proportion of the genetic variation underlying the susceptibility to this disorder. Major work is still required to identify the causal variants, test their role in disease prediction and ascertain their therapeutic implications.
Advances in DNA sequence specific agents : A research annual (1992)

List of Contributors. Preface Part I: Methods used to evaluate the molecular basis for sequence specificity. Part II: Sequence Specificity of DNA Interactive Drugs.
Crystallization experiments with 2-enoyl-CoA hydratase, using an automated `fast-screening' crystallization protocol (1994)

A convenient method for screening crystallization conditions using an automated fast-screen protocol has been implemented and tested on an enoyl-CoA hydratase. The crystallization solutions for the initial screening and subsequent optimizations are prepared using a crystallization robot. Enoyl-CoA hydratase (E.C. 4.2.1.17), purified from rat-liver mitochondria, is one of the enzymes from the beta-oxidation pathway of fatty-acid metabolism; it catalyzes the reversible hydration of 2-trans-enoyl-CoA's to L-3-hydroxy-acyl-CoA's. Different crystal forms, diffracting to 3.0 A, were obtained.
The contribution of collagen crosslinks to bone strength (2012)

Collagen crosslinking is a major post-translational modification of collagen which has important roles in determining the biomechanical competence of bone. Crosslinks can be divided into enzymatic lysil oxidase-mediated and non-enzymatic glycation-induced (advanced glycation end products, AGE) molecules. In addition, collagen in bone can also undergo spontaneous isomerization and racemization of the aspartic acid residues with the C-telopeptide (CTX), leading to the formation of two isomers namely α (newly formed collagen) and β (matured isomerized collagen) CTX. Several in vitro and ex vivo studies, relating the bone content of these crosslinks with bone strength, have shown that they contributed to the mechanical competence of trabecular and cortical bone—mainly on the post-yield properties—in part independent of the bone mineral content. In addition, AGEs such as pentosidine have been reported to alter the formation and propagation of microdamage by making the bone more brittle. The bone content of AGEs and isomerization can also be modified by antiresorptive and anabolic therapies. They may thus explain part of the antifracture efficacy of these treatments. The main challenge consists in the transposition of these in vitro/ex vivo studies to clinical applications for the development of a non-invasive biomarker, as none of currently identified collagen crosslinks (both enzymatic and nonenzymatic) is bone specific. Nevertheless, serum or urine levels of pentosidine and the ratio of α/β CTX have been reported to predict fracture risk in postmenopausal women, in men and in patients with type 2 diabetes.
The assessment of pain and plasma β-endorphin immunoactivity in burned children (1985)

The need for better analgesia during burn dressing changes (BDCs) in acutely burned children led us to assess pain during BDC with a large 0-10 thermometer-like scale which was well accepted and appeared to reflect the varying degrees of pain that patients experienced. Pain scores were obtained at least once each minute throughout 33 BDCs in 15 patients of 8-17 years. Plasma levels of beta-endorphin immunoactivity (iB-EP) were measured at 5 intervals before and after BDC; mean values (+/- S.E.M.) ranged from 30.5 +/- 4.63 pg/ml (before BDC and analgesic) to 19.2 +/- 3.02 pg/ml (immediately following BDC). The mean pain score (MPS) for each BDC was inversely related to the iB-EP levels of that day (P less than 0.001 with 4 of the 5 iB-EP determinations). The MPS varied directly with the extent of burn injury and inversely with weight; the 2 variables together predicted MPS as well as the iB-EP alone (r2 = 43 and 36% respectively).
Annotation-directed run-time specialization in C (1997)

We present the design of a dynamic compilation system for C. Directed by a few declarative user annotations specifying where and on what dynamic compilation is to take place, a binding time analysis computes the set of run-time constants at each program point in each annotated procedure's control flow graph; the analysis supports program-point-specific polyvariant division and specialization. The analysis results guide the construction of a specialized run-time specializer for each dynamically compiled region; the specializer supports various caching strategies for managing dynamically generated code and supports mixes of speculative and demand-driven specialization of dynamic branch successors. Most of the key cost/benefit trade-offs in the binding time analysis and the run-time specialize are open to user control through declarative policy annotations. Our design is being implemented in the context of art existing optimizing compiler.
Label-Free, Single-Molecule Detection with Optical Microcavities (2007)

Current single-molecule detection techniques require labeling the target molecule. We report a highly specific and sensitive optical sensor based on an ultrahigh quality (Q) factor (Q > 10(8)) whispering-gallery microcavity. The silica surface is functionalized to bind the target molecule; binding is detected by a resonant wavelength shift. Single-molecule detection is confirmed by observation of single-molecule binding events that shift the resonant frequency, as well as by the statistics for these shifts over many binding events. These shifts result from a thermo-optic mechanism. Additionally, label-free, single-molecule detection of interleukin-2 was demonstrated in serum. These experiments demonstrate a dynamic range of 10(12) in concentration, establishing the microcavity as a sensitive and versatile detector.
Genetic Control of Immune Response to Recombinant Antigens Carried by an AttenuatedSalmonella typhimuriumVaccine Strain:Nramp1Influences T-Helper Subset Responses and Protection against Leishmanial Challenge (1998)

Attenuated strains of Salmonella typhimurium have been widely used as vehicles for delivery and expression of vaccine antigens in murine models of infectious disease. In mice, early bacterial replication following infection with S. typhimurium is controlled by the gene (Nramp1, formerly Ity/Lsh/Bcg) encoding the natural-resistance-associated macrophage protein (Nramp1). Nramp1 regulates macrophage activation and has multiple pleiotropic effects, including regulation of tumor necrosis factor alpha, interleukin 1beta (IL-1beta), and major histocompatibility complex class II molecules, all of which influence antigen processing and presentation. Nramp1 also has a direct effect on antigen processing, possibly by regulating the activity of proteases in the late endosomal compartment. Hence, there are multiple ways (regulation of bacterial load or recombinant antigen dose, class II molecule expression, costimulatory or adjuvant activity, and antigen processing) that Nramp1 might influence responses to recombinant salmonella vaccines. To test the hypothesis that Nramp1 influences responses to vaccination, congenic mouse strains have been used to analyze immune responses to recombinant antigens (tetanus toxoid antigen and leishmanial gp63) carried by live attenuated S. typhimurium aroA aroD mutants. Results show that congenic mice carrying the wild-type (S. typhimurium resistance) Nramp1 allele mount a predominantly T-helper-1 (IL-2 and gamma interferon) response to vaccination and show enhanced resolution of lesions following challenge infection with Leishmania major. In contrast, mice carrying mutant (S. typhimurium susceptibility) Nramp1 mount a T-helper-2 (immunoglobulin E and IL-4) response and show exacerbated lesion growth upon challenge.
Comparison of Interleukin-1β Expression by In Situ Hybridization in Monoclonal Gammopathy of Undetermined Significance and Multiple Myeloma (1999)

We investigated whether interleukin-1β (IL-1β) is differentially expressed in plasma cells from monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM) patients because IL-1β appears to play a major role in the development of lytic bone lesions, the major clinical feature distinguishing MGUS from myeloma. In situ hybridization (ISH) for IL-1β was performed using bone marrow aspirates from 51 MM, 7 smoldering MM, 21 MGUS, and 5 normal control samples. Using the ISH technique IL-1β mRNA was detectable in the plasma cells from 49 of 51 patients with active myeloma and 7 of 7 patients with smoldering myeloma. In contrast, 5 of 21 patients with MGUS and 0 of 5 normal controls had detectable IL-1β message. Bone lesions were present in 40 of the 51 MM patients analyzed, and all 40 patients had IL-1β mRNA by ISH. These results show that greater than 95% of MM patients but less than 25% of MGUS patients are positive for IL-1β production. In the future, continued follow-up of IL-1β positive and negative MGUS patients should determine whether aberrant expression of plasma cell IL-1β is predictive of those MGUS patients that will eventually progress to active myeloma.