gebhart/patrepeval huggingface dataset:
Neomycin Mimics the Effects of High Extracellular Calcium Concentrations on Parathyroid Function in Dispersed Bovine Parathyroid Cells* (1991)

We examined the effects of the polycationic antibiotic, neomycin, on the function of dispersed bovine parathyroid cells. Neomycin caused a reversible, dose-dependent inhibition of low calcium (Ca++)-stimulated PTH release, with half-maximal inhibition at 30 microM. Maximal inhibition (with 200 microM neomycin) was not additive with the suppressive effects of high (2 mM) Ca++. Neomycin also inhibited dopamine-stimulated cAMP accumulation by 90-98% at 100-200 microM, with a half-maximal effect at 40-50 microM. This action was reversible and was blocked by preincubating the cells overnight with 0.5 microgram/ml pertussis toxin. In addition to its suppressive effects on cAMP metabolism and PTH release, neomycin stimulated the accumulation of inositol phosphates and produced a transient increase in the cytosolic Ca++ concentration (Cai) in fura-2-loaded parathyroid cells. The neomycin-evoked spike in Cai persisted despite removal of extracellular Ca++, indicating that it arises from intracellular Ca++ stores. Exposure of cells to elevated magnesium (Mg++) concentrations elicited a similar spike in Cai but blocked the spike in Cai in response to subsequent addition of neomycin and vice versa. Thus, Mg++ and neomycin mobilize Ca++ from the same intracellular store(s). These results indicate that a polycation, neomycin, closely mimics the effects of polyvalent cations on parathyroid function, suggesting that both agents regulate parathyroid function via similar biochemical pathways.
IL-17 and IL-4 producing CD8+ T cells in tumor draining lymph nodes of breast cancer patients: positive association with tumor progression. (2013)

As the first study to investigate various effector subtypes of CD8+ lymphocytes in TDLNs of patients with breast cancer, our data collectively suggests a positive association between IL-17- and IL-4-producing CD8+ T cell percentages (Tc2 and Tc17) in TDLNs with breast cancer progression. Although the number of Tc1 cells seems not to be affected by cancer progression, down-regulation of IFN-γ by these cells seems to be associated with tumor metastasis to TDLNs. These findings may have implications in cancer immunotherapy based on CD8+ effector subsets.
Caspase-1 Regulates the Inflammatory Process Leading to Autoimmune Demyelination (1999)

T cell-mediated inflammation is considered to play a key role in the pathogenic mechanisms sustaining multiple sclerosis (MS). Caspase-1, formerly designated IL-1beta-converting enzyme, is crucially involved in immune-mediated inflammation because of its pivotal role in regulating the cellular export of IL-1beta and IL-18. We studied the role of caspase-1 in experimental autoimmune encephalomyelitis (EAE), the animal model for MS. Caspase-1 is transcriptionally induced during EAE, and its levels correlate with the clinical course and transcription rate of proinflammatory cytokines such as TNF-alpha, IL-1beta, IFN-gamma, and IL-6. A reduction of EAE incidence and severity is observed in caspase-1-deficient mice, depending on the immunogenicity and on the amount of the encephalitogenic myelin oligodendrocyte glycoprotein (MOG) peptide used. In caspase-1-deficient mice, reduced EAE incidence correlates with defective development of anti-MOG IFN-gamma-producing Th1 cells. Finally, pharmacological blockade of caspase-1 in Biozzi AB/H mice, immunized with spinal cord homogenate or MOG35-55 peptide, by the caspase-1-inhibitor Z-Val-Ala-dl -Asp-fluoromethylketone, significantly reduces EAE incidence in a preventive but not in a therapeutic protocol. These results indicate that caspase-1 plays an important role in the early stage of the immune-mediated inflammatory process leading to EAE, thus representing a possible therapeutic target in the acute phase of relapsing remitting MS.
REACTIONS OF ATOMS AND FREE RADICALS IN SOLUTION. XXX. DIMERIZATION OF FREE RADICALS PRODUCED FROM OLEFINS (1953)

ADVERTISEMENT RETURN TO ISSUEPREVArticleREACTIONS OF ATOMS AND FREE RADICALS IN SOLUTION. XXX. DIMERIZATION OF FREE RADICALS PRODUCED FROM OLEFINSM. S. KHARASCH, DANIEL SCHWARTZ, and W. NUDENBERGCite this: J. Org. Chem. 1953, 18, 3, 337–344Publication Date (Print):March 1, 1953Publication History Published online1 May 2002Published inissue 1 March 1953https://pubs.acs.org/doi/10.1021/jo01131a018https://doi.org/10.1021/jo01131a018research-articleACS PublicationsRequest reuse permissionsArticle Views59Altmetric-Citations7LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Endothelial Dysfunction in Men With Small LDL Particles (2000)

Small LDL particles are associated with impaired in vivo endothelial function independent of HDL and LDL cholesterol and triglyceride concentrations. LDL size may therefore mediate adverse effects of hypertriglyceridemia on vascular function.
Pharmacokinetic aspects of levofloxacin 500 mg once daily during sequential intravenous/oral therapy in patients with lower respiratory tract infections (2002)

Levofloxacin is considered an effective antibiotic in the treatment of community-acquired lower respiratory tract infections (LRTIs). A study was carried out on 17 in-patients to assess the pharmacokinetics of a 500 mg once-daily switch intravenous (i.v.)/oral regimen of levofloxacin in the treatment of LRTI patients. Blood samples were collected under steady-state conditions at appropriate intervals. Levofloxacin plasma concentrations were analysed by means of HPLC and pharmacokinetic parameters were estimated using the WinNonlin pharmacokinetic software package. A lower clearance of levofloxacin (<2 mL/min/kg), conditioning both a longer elimination half-life (approximately 9 h) and a larger AUC(0-tau) (approximately 80 mg/L x h), was observed for both routes in our patients than in healthy volunteers. These differences may be explained considering that levofloxacin is excreted mainly as unchanged drug by the renal route, and most of our patients (71%) were very elderly subjects whose renal function physiologically declines with age. The almost complete (> or =99%) absolute oral bioavailability suggests that a comparable exposure to the iv regimen may be achieved after oral administration. The overall clinical success rate was 94.1%.
Analysis of a recombinant mouse hepatitis virus expressing a foreign gene reveals a novel aspect of coronavirus transcription (1997)

We have inserted heterologous genetic material into the nonessential gene 4 of the coronavirus mouse hepatitis virus (MHV) in order to test the applicability of targeted RNA recombination for site-directed mutagenesis of the MHV genome upstream of the nucleocapsid (N) gene and to develop further genetic tools for site-directed mutagenesis of structural genes other than N. Initially, a 19-nucleotide tag was inserted into the start of gene 4a of MHV strain A59 with the N gene deletion mutant Alb4 as the recipient virus. In further work, the entire gene for the green fluorescent protein (GFP) was inserted in place of gene 4, creating the currently largest known RNA virus. The expression of GFP was demonstrated by Western blot analysis of infected cell lysates; however, the level of GFP expression was not sufficient to allow detection of fluorescence of viral plaques. Northern blot analysis of transcripts of GFP recombinants showed the expected alteration of the pattern of the nested MHV subgenomic mRNAs. Surprisingly, though, GFP recombinants also produced an RNA species that was the same size as wild-type mRNA4. Analysis of the 5' end of this species revealed that it was actually a collection of mRNAs originating from 10 different genomic fusion sites, none possessing a canonical intergenic sequence. The finding of these aberrant mRNAs suggests that long-range RNA or the ribonucleoprotein structure of the MHV genome can sometimes be the sole determinant of the site of initiation of transcription.
Aggregated α-Synuclein Mediates Dopaminergic NeurotoxicityIn Vivo (2007)

Mutations in the synaptic protein alpha-synuclein cause rare genetic forms of Parkinson's disease. Alpha-synuclein is thought to play a critical role in more common sporadic cases of Parkinson's disease as well because the protein aggregates in the hallmark intraneuronal inclusions of the disorder, Lewy bodies. To test the role of protein aggregation in the pathogenesis of Parkinson's disease, we expressed a form of alpha-synuclein with a deletion of amino acids 71-82 that is unable to aggregate in vitro in a transgenic Drosophila model of the disorder. We found no evidence of large aggregates or oligomeric species of alpha-synuclein in these animals and no loss of tyrosine hydroxylase-positive neurons. We also expressed a truncated form of alpha-synuclein that has enhanced ability to aggregate in vitro. This truncated form of alpha-synuclein showed increased aggregation into large inclusions bodies, increased accumulation of high molecular weight alpha-synuclein species, and demonstrated enhanced neurotoxicity in vivo. Our findings thus support a critical role for aggregation of alpha-synuclein in mediating toxicity to dopaminergic neurons in vivo, although the precise role each aggregated form of alpha-synuclein plays in neurotoxicity remains to be determined.
AlGaN/GaN high electron mobility transistors with InGaN back-barriers (2005)

A GaN/ultrathin InGaN/GaN heterojunction has been used to provide a back-barrier to the electrons in an AlGaN/GaN high-electron mobility transistor (HEMT). The polarization-induced electric fields in the InGaN layer raise the conduction band in the GaN buffer with respect to the GaN channel, increasing the confinement of the two-dimensional electron gas under high electric field conditions. The enhanced confinement is especially useful in deep-submicrometer devices where an important improvement in the pinchoff and 50% increase in the output resistance have been observed. These devices also showed excellent high-frequency performance, with a current gain cut-off frequency (f/sub T/) of 153 GHz and power gain cut-off frequency (f/sub max/) of 198 GHz for a gate length of 100 nm. At a different bias, a record f/sub max/ of 230 GHz was obtained.
Matrix metalloproteases and lung disease. (1994)

Development, tissue remodelling, cell migra- tion, inflammation, angiogenesis, and wound healing are just some of the physiological pro- cesses in which the matrix metalloproteases (MMPs), a family of highly homologous endo- peptidases, play a crucial part.'" Collectively the MMPs can cleave most, if not all, the protein constituents of the extracellular matrix including collagen, proteoglycan, laminin, fibronectin, and elastin. In so doing they facilitate cell movement, reorientation, and dispersal. The production and action of the MMPs are subject to strict control, ensuring limited proteolysis of the extracellular matrix during cell migration, tissue remodelling and repair."' Inadequate regulation of MMP production or action has, however, been implicated in a wide range of pathological processes including several lung diseases, rheumatoid arthritis, periodontal and renal diseases, osteoarthritis, fibrotic disorders, and tumour invasion. 7-12 Recent studies elucidating (1) the sequence homologies between members of the MMP family,'3 (2) factors involved in the regulation of MMP expression,'4 15 and (3) mechanisms of MMP activation and inhibition'6 17 have added considerably to our knowledge of the crucial control mechanisms which can tip the balance of MMP action from normal homoeostasis to pathological process. In this review the salient features of the action and regulation of MMPs
Cloning and expression of a gene encoding an interleukin 3 receptor-like protein: identification of another member of the cytokine receptor gene family. (1990)

Using a monoclonal antibody to the interleukin 3 (IL-3) receptor (anti-Aic2), we isolated a cDNA (AIC2B) from a mouse mast cell line which is homologous to the previously characterized gene for the IL-3 receptor (AIC2A). This cDNA encodes a polypeptide of 896 amino acid residues and has 91% amino acid sequence identity with the IL-3 receptor. A consensus sequence defining an additional cytokine receptor family is present in this clone. Compared to the AIC2A clone, the AIC2B cDNA encodes a protein with amino acid substitutions, insertions, and deletions dispersed throughout the entire protein. Oligonucleotide probes specific for each cDNA hybridized with different genomic fragments, indicating that the AIC2A and AIC2B proteins are encoded by two distinct genes. Fibroblasts transfected with the AIC2B cDNA expressed the protein at the cell surface as determined by binding with the anti-Aic2 antibody but did not bind IL-3 or other cytokines, including IL-2, IL-4, granulocyte-macrophage colony-stimulating factor, erythropoietin, and IL-9 (p40) at concentrations between 1 and 10 nM. An S1 nuclease protection assay was used to discriminate between the AIC2A and AIC2B transcripts. We found that the AIC2B gene was coexpressed with the AIC2A gene. These results suggest a potential involvement of AIC2B in cytokine signal transduction.
Structural Analysis of Collagen Fibrils in Rat Skin Based on Small-Angle X-Ray-Diffraction Pattern (1996)

A superhelix structure is proposed to explain the short band period (65 nm) observed in rat skin collagen fibrils in comparison with that of tendon collagen fibrils (67 nm). In the former case, each molecule forms an angle of 12–13° with the fibril axis and almost ten tropocollagen molecules aggregate to form a tilting plane in a bundle or a subfibril. The adjacent bundles may be staggered with respect to each other by a length of ten amino acid residues along the chain axis to form the band structure observed to be normal to the fibril axis. This model is found to be quantitatively consistent with small-angle X-ray diffraction data obtained from uniaxially oriented collagen fibrils in native rat skin as well as a transmission electron microscopic image of freeze-etched fibrils in glycerinated rat skin.
Pour Plates or Streak Plates? (1969)

The pour plate method of counting bacteria is more precise than the streak plate method, but, on the average, it will give a lower count.
Theophylline—an Immunomodulatory Role in Asthma? (1993)

Theophylline, a drug used for the treatment of asthma, is recognized as an immunomodulator affecting T-lymphocytes both in vitro and in vivo. The effect of slow-release theophylline (Uniphyllin Continus) on the late asthmatic response (LAR) has been compared with placebo before and after 5 wk of treatment in a double-blind, randomized, parallel group study. Nineteen volunteers with stable mild asthma successfully completed the study. All were dual responders with a documented late response to inhaled house dust mite extract. The LAR was assessed both in terms of changes in lung function and in peripheral blood T-lymphocyte subsets. The mean (SEM) maximal late fall in FEV1 before and after treatment was 28.8 (4.1)% and 7.8 (2.0)% with theophylline, versus 35.8 (5.1)% and 29.1 (5.0)% with placebo (p = 0.046; Cl, 0.3-26.9). Corresponding figures for specific airway conductance (SGaw) were 46.4 (8.4)% and 7.2 (8.0)% with theophylline versus 46.2 (7.2)% and 44.8 (7.7)% with placebo (p = 0.008; Cl, 11.2 to 64.1). This was achieved at a mean (SD) trough serum theophylline level of only 7.8 (3.5) micrograms/ml. Airway responsiveness to methacholine was not significantly changed 24 h after the initial allergen challenge. There was a trend towards a decrease in baseline responsiveness after treatment with theophylline compared with that after placebo (p = 0.07). Studies of peripheral blood lymphocytes showed a modifying effect of treatment on the allergen-induced changes in CD4 and CD8 counts 48 h after challenge. Previous studies have shown a protective effect of theophylline on the LAR at serum theophylline concentrations within the conventional range for bronchodilation.(ABSTRACT TRUNCATED AT 250 WORDS)
Reversal by NPY, PYY and 3–36 molecular forms of NPY and PYY of intracisternal CRF‐induced inhibition of gastric acid secretion in rats (1996)

1. The Y receptor subtype involved in the antagonism by neuropeptide Y (NPY) of intracisternal corticotropin-releasing factor (CRF)-induced inhibition of gastric acid secretion was studied in urethane-anaesthetized rats by use of peptides with various selectivity for Y1, Y2 and Y3 subtypes: NPY, a Y1, Y2 and Y3 agonist, peptide YY (PYY), a Y1 and Y2 agonist, [Leu31, Pro34]-NPY, a Y1 and Y3 agonist, NPY(3-36) and PYY(3-36), highly selective Y2 agonists and NPY(13-36) a weak Y2 and Y3 agonist. Peptides were injected intracisternally 10 min before intracisternal injection of CRF (10 micrograms) and gastric acid secretion was measured by the flushed technique for 1 h before and 2 h after pentagastrin-(10 micrograms kg-1 h-1, i.v.) infusion which started 10 min after CRF injection. 2. Intracisternal injection of CRF (10 micrograms) inhibited by 56% gastric acid secretion stimulated by pentagastrin. Intracisternal injection of NPY and PYY (0.1-0.5 microgram) did not influence the acid response to pentagastrin but blocked CRF-induced inhibition of pentagastrin-stimulated acid secretion. NPY(3-36) (0.5 microgram) and PYY(3-36) (0.25 and 0.5 microgram) also completely blocked the inhibitory action of CRF on pentagastrin-stimulated acid secretion. 3. [Leu31, Pro34]-NPY (0.5-5 micrograms) and NPY(13-36) (0.5-5 micrograms) injected intracisternally did not modify gastric acid secretion induced by pentagastrin or CRF inhibitory action. 4. The sigma antagonist, BMY 14802 (1 mg kg-1, s.c.) did not influence the acid response to pentagastrin but prevented the antagonism by PYY(3-36) (0.5 microgram) of the CRF antisecretory effect. 5. These results show that both PYY and NPY and the 3-36 forms of PYY and NPY are equipotent in blocking central CRF-induced inhibition of pentagastrin-stimulated gastric acid secretion. The structure-activity profile suggests a mediation through Y2 receptor subtype and the involvement of sigma binding sites.
Synthesis and biological activity of certain alkyl 5-(alkoxycarbonyl)-1H-benzimidazole-2-carbamates and related derivatives: a new class of potential antineoplastic and antifilarial agents (1992)

A series of methyl and ethyl 5-(alkoxycarbonyl)-1H-benzimidazole-2-carbamates (7-19) and methyl 5-carbamoyl-1H-benzimidazole-2-carbamates (24-34) have been synthesized via the reaction of an appropriate alcohol or amine with the acid chloride derivatives 6a or 6b at room temperature. Reaction of an alcohol with acid chloride 6a at reflux temperature afforded transesterified products 20-23 in good yield. Treatment of methyl 5-amino-1H-benzimidazole-2-carbamate with substituted benzoyl chlorides furnished the methyl 5-benzamido-1H-benzimidazole-2-carbamates (36-38). Compounds 9, 16, 20, and 22 demonstrated significant growth inhibition in L1210 cells with IC50's less than 1 microM. Growth inhibition by this series of compounds appears to be associated with mitotic spindle poisoning. All the compounds tested, 9, 10, 19, 20, 22, and 23, caused significant accumulation of L1210 cells in mitosis. Compounds 7, 9, 19, 25, 26, 27, and 36 showed significant in vivo antifilarial activity against adult worms of Brugia pahangi, Litomosoides carinii, and Acanthocheilonema viteae in experimentally infected jirds.
A critical analysis of the hydrino model (2005)

Abstract. Recently, spectroscopic and calorimetric observations of hydrogen plasmas and chemical reactions with them have been interpreted as evidence for the existence of electronic states of the hydrogen atom with a binding energy of more than 13.6 eV. The theoretical basis for such states, that have been dubbed hydrinos, is investigated. We discuss both, the novel deterministic model of the hydrogen atom, in which the existence of hydrinos was predicted, and standard quantum mechanics. Severe inconsistencies in the deterministic model are pointed out and the incompatibility of hydrino states with quantum mechanics is reviewed.
An improved approach to separating startle data from noise (2015)

The improvements made allow researchers to automatically separate startle data from noise, and normalize for an individual animal's mass. These steps ease inter-animal and inter-laboratory comparisons of startle data.
Role of Catheter's Position for Final Results in Intrathecal Drug Delivery. Analysis Based on CSF Dynamics and Specific Drugs Profiles (2013)

Intrathecal drug delivery is an effective and safe option for the treatment of chronic pathology refractory to conventional pain therapies. Typical intrathecal administered drugs are opioids, baclofen, local anesthetics and adjuvant medications. Although knowledge about mechanisms of action of intrathecal drugs are every day more clear many doubt remain respect the correct location of intrathecal catheter in order to achieve the best therapeutic result. We analyze the factors that can affect drug distribution within the cerebrospinal fluid. Three categories of variables were identified: drug features, cerebrospinal fluid (CSF) dynamics and patients features. First category includes physicochemical properties and pharmacological features of intrathecal administered drugs with special attention to drug lipophilicity. In the second category, the variables in CSF flow, are considered that can modify the drug distribution within the CSF with special attention to the new theories of liquoral circulation. Last category try to explain inter-individual difference in baclofen response with difference that are specific for each patients such as the anatomical area to treat, patient posture or reaction to inflammatory stimulus. We conclude that a comprehensive evaluation of the patients, including imaging techniques to study the anatomy and physiology of intrathecal environment and CSF dynamics, could become essential in the future to the purpose of optimize the clinical outcome of intrathecal therapy.