gebhart/patrepeval huggingface dataset:
Protonation of 2,4-diaminopyrimidines. I. Dissociation constants and substituent effects (1969)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTProtonation of 2,4-diaminopyrimidines. I. Dissociation constants and substituent effectsBarbara Roth and Justina Z. StrelitzCite this: J. Org. Chem. 1969, 34, 4, 821–836Publication Date (Print):April 1, 1969Publication History Published online1 May 2002Published inissue 1 April 1969https://pubs.acs.org/doi/10.1021/jo01256a011https://doi.org/10.1021/jo01256a011research-articleACS PublicationsRequest reuse permissionsArticle Views567Altmetric-Citations74LEARN 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
Comparison of the Directigen Flu A+B Test, the QuickVue Influenza Test, and Clinical Case Definition to Viral Culture and Reverse Transcription-PCR for Rapid Diagnosis of Influenza Virus Infection (2003)

The diagnostic performances of the clinical case definition of influenza virus infection based on the combination of fever and cough and of two rapid influenza diagnostic tests, the Directigen Flu A+B test (Directigen; BD Diagnostic Systems, Sparks, Md.) and the QuickVue influenza test (QuickVue; Quidel, San Diego, Calif.), were compared to those of viral culture and an in-house reverse transcription (RT)-PCR during the 2000-2001 flu season. Two hundred consecutive nasopharyngeal aspirates were analyzed from 192 patients, including 122 adults and 70 children. Viral culture identified influenza virus A in 16 samples and influenza virus B in 55 samples, whereas RT-PCR identified influenza virus A in 21 samples and influenza virus B in 64 samples. When RT-PCR was used as the reference standard, the likelihood ratios for a positive test were 40.0 for Directigen, 8.6 for QuickVue, and 1.4 for the combination of fever and cough, whereas the likelihood ratios for a negative test were 0.22, 0.16, and 0.48, respectively. Our study suggests that (i). the poor specificity (35 to 58%) and the poor positive predictive value (41 to 60%) of the clinical case definition of influenza preclude its use for prediction of influenza virus infections during epidemics, especially when infection control decision making in the hospital setting is considered; (ii). Directigen has a higher diagnostic yield than QuickVue but is associated with a larger number of invalid results; (iii). the sensitivities of the rapid diagnostic tests are significantly lower with samples from adults than with samples from children, with the rates of false-negative results reaching up to 29%; and (iv). RT-PCR detects more cases of influenza than viral culture, and this greater accuracy makes it a more useful reference standard.
Receptor Radionuclide Therapy with 90 Y-DOTATOC in Patients with Medullary Thyroid Carcinomas (2004)

This retrospective analysis is consistent with the literature, regarding a low response rate in medullary thyroid cancers treated with 90Y-DOTATOC. Patients with smaller tumors and higher uptake of the radiopeptide tended to respond better. Studies with 90Y-DOTATOC administered in earlier phases of the disease will help to evaluate the ability of this treatment to enhance survival. New more specific peptides and new isotopes will also represent the key of a better treatment of MTC.
Surface hydration: Principles and applications toward low-fouling/nonfouling biomaterials (2010)

Surface resistance to nonspecific protein adsorption, cell/bacterial adhesion, and biofilm formation is critical for the development and performance of biomedical and analytical devices. Significant needs and efforts have been made in the development of biocompatible and bioactive materials for antifouling surfaces, but much of the work retains an empirical flavor due to the complexity of experiments and the lack of robust theoretical models. In this review, two major classes of nonfouling materials (i.e. hydrophilic and zwitterionic materials) and associated basic nonfouling mechanisms and practical examples are discussed. Highly hydrated chemical groups with optimized physical properties of the surface, along with appropriate surface coating methods, are the keys to developing effective and stable nonfouling materials for long-term biomedical applications. The zwitterionic polymers are promising nonfouling biomaterials due to the simplicity of synthesis, ease of applicability, abundance of raw materials, and availability of functional groups.
Assembly and Functionalization of DNA−Polymer Microcapsules (2009)

We report the synthesis and characterization of DNA-grafted poly(N-isopropylacrylamide) (PNIPAM) micelles, their assembly into multilayered thin films, and the subsequent generation and poly(ethylene glycol) (PEG) functionalization of DNA-PNIPAM microcapsules. Multilayer films were assembled by sequentially depositing DNA-grafted PNIPAM micelles containing the cDNA sequences polyA(30) or polyT(30) (i.e., PNIPAM-A(30) or PNIPAM-T(30)). DNA-polymer microcapsules were obtained by the alternate deposition of PNIPAM-A(30) and PNIPAM-T(30) onto silica particles, followed by removal of the template core. Upon removal of the silica core particle, shrinkage of between 30 and 50% was observed for the microcapsules. The presence of PNIPAM within the DNA-polymer hybrid film reduces the permeability of the microcapsules to macrosolutes (e.g., dextran) compared with microcapsules made solely of DNA. The hydrophobic core of the DNA-grafted PNIPAM micelles was designed to contain alkyne "click" groups, which were exploited to covalently couple azide-bearing low-fouling PEG to the DNA-PNIPAM microcapsules. The combination of hydrophobic and reactive "click" nanodomains, along with the degradability of DNA, offers a multifunctional and versatile DNA-polymer capsule system that is envisioned to find applications in the controlled delivery of therapeutics.
Discrimination in the metabolism of orally dosed ergocalciferol and cholecalciferol by the pig, rat and chick (1982)

Vitamin D-deficient pigs, rats and chicks were repleted with four daily oral doses of crystalline ergocalciferol (vitamin D2) and cholecalciferol (vitamin D3) containing equal concentrations of each. At 24 h after the last dose, the plasma of each species was analysed for vitamin D and 25-hydroxyvitamin D by standard methods. The mean (+/- S.D.) ratios of plasma cholecalciferol to ergocalciferol concentration were 1.5 +/- 0.1 (pig). 1.7 +/- 0.1 (rat) and 6.3 +/- 1.2 (chick). The mean ratios of plasma 25-hydroxycholecalciferol to 25-hydroxyergocalciferol concentration were 4.0 +/- 0.1 (pig), 0.4 +/- 0.02 (rat) and 10.7 +/- 3.4 (chick). The mean plasma cholecalciferol/ergocalciferol ratios for the 24,25-dihydroxy-, 25,26-dihydroxy- and 1,25-dihydroxy-derivatives in the pig were 2.6 +/- 0.6, 5.8 +/- 1.3 and 5.8 +/- 0.8 respectively. This is the first evidence that mammals other than the New World monkey, like birds, discriminate between ergocalciferol and cholecalciferol. These data, therefore, suggest that species discrimination between the different forms of vitamin D is probably a general phenomenon in mammals. Moreover, this is the first indication of a species (rat) that discriminates against a cholecalciferol metabolite in favour of an ergocalciferol metabolite. Species discrimination against particular forms of vitamin D may be important to the choice of experimental animal models for studying the regulation of vitamin D metabolism and may also be an important consideration in dietary vitamin supplementation.
Cardiac Myosin-Binding Protein-C Phosphorylation and Cardiac Function (2005)

The role of cardiac myosin binding protein-C (cMyBP-C) phosphorylation in cardiac physiology or pathophysiology is unclear. To investigate the status of cMyBP-C phosphorylation in vivo, we determined its phosphorylation state in stressed and unstressed mouse hearts. cMyBP-C phosphorylation is significantly decreased during the development of heart failure or pathologic hypertrophy. We then generated transgenic (TG) mice in which the phosphorylation sites of cMyBP-C were changed to nonphosphorylatable alanines (MyBP-C(AllP-)). A TG line showing &40% replacement with MyBP-C(AllP-) showed no changes in morbidity or mortality but displayed depressed cardiac contractility, altered sarcomeric structure and upregulation of transcripts associated with a hypertrophic response. To explore the effect of complete replacement of endogenous cMyBP-C with MyBP-C(AllP-), the mice were bred into the MyBP-C(t/t) background, in which less than 10% of normal levels of a truncated MyBP-C are present. Although MyBP-C(AllP-) was incorporated into the sarcomere and expressed at normal levels, the mutant protein could not rescue the MyBP-C(t/t) phenotype. The mice developed significant cardiac hypertrophy with myofibrillar disarray and fibrosis, similar to what was observed in the MyBP-C(t/t) animals. In contrast, when the MyBP-C(t/t) mice were bred to a TG line expressing normal MyBP-C (MyBP-CWT), the MyBP-C(t/t) phenotype was rescued. These data suggest that cMyBP-C phosphorylation is essential for normal cardiac function.
Detection by polymerase chain reaction of residual cells with the bcl-2 translocation is associated with increased risk of relapse after autologous bone marrow transplantation for B-cell lymphoma (1993)

Although molecular biologic techniques can now detect minimal numbers of residual cancer cells in patients in complete clinical remission, the clinical significance of minimal residual disease has never been conclusively established. If the detection of minimal residual disease predicts which patients will relapse, then therapy could be altered based upon the detection of these cells. The t(14;18) can be detected by polymerase chain reaction (PCR) amplification in 50% of patients with B-cell non-Hodgkin's lymphoma and allows detection of one lymphoma cell in up to 1 million normal cells. To determine the clinical significance of the detection of minimal residual lymphoma cells in the bone marrow (BM) PCR amplification was used to detect the presence of residual lymphoma cells after autologous BM transplantation (ABMT) in serial BM samples from 134 patients with B-cell lymphoma in whom a bcl-2 translocation could be detected. PCR analysis was performed on a total of 542 BM samples obtained while these patients were in complete remission. Disease-free survival was markedly increased in patients with no PCR-detectable lymphoma cells in the marrow compared with those in whom residual lymphoma cells were detected (P < .00001), and the presence of detectable lymphoma cells was associated with a 48-fold increase in the risk of relapse. Of the 77 patients (57%) with no PCR-detectable lymphoma cells in their most recent BM sample, none have relapsed. In contrast, all 33 patients (25%) who have relapsed had PCR-detectable lymphoma cells detected in their BM before clinical relapse occurred. In 19 patients (14%), residual lymphoma cells in the BM were detected early following transplantation and subsequently were no longer detectable, although these patients received no further therapy. In these patients, residual lymphoma cells may already have been irreversibly damaged by the high-dose therapy or an endogenous immune mechanism may be capable of eliminating residual lymphoma cells in some patients. Therefore, although the detection of minimal residual disease by PCR following ABMT in patients with lymphoma identifies those patients at high risk of relapse, the presence of residual minimal disease early after transplantation may not be associated with poor prognosis in a small subset of patients. Confirmatory studies will be required to determine more definitively the role of minimal disease detection to identify which patients require additional therapy.
A Research Trail Over Half a Century (1995)

The author describes his major research activities from the time of his PhD thesis work (1937-1940) on properties of erythrocyte membranes to the present. His involvement in research on circulatory shock during World War II led to a continuing interest in the physiology and pharmacology of smooth muscle and cardiac muscle. From 1956 to 1978, his main areas of research were photorelaxation of blood vessels, factors influencing contractility of cardiac muscle, peripheral adrenergic mechanisms, and receptor theory. The major findings of his and his collaborators in these areas are described. He then recounts how an accidental finding in an experiment in 1978 on preparations of rabbit aorta eventually led to the discovery of endothelium dependent relaxation and the endothelium-derived relaxing factor (EDRF); and how additional findings led him to propose in 1986 that EDRF is nitric oxide.
Magnetic resonance molecular imaging of the HER-2/neu receptor. (2003)

The HER-2/neu receptor is a member of the epidermal growth factor family and is amplified in multiple cancers. It is under intense investigation both as a prognostic marker and for therapy, using monoclonal antibodies targeted against the receptor. We have developed a novel two-component gadolinium-based MR contrast agent to image the HER-2/neu receptor. Positive T1 contrast in MR images was generated by the specific binding of avidin-gadolinium complexes to tumor cells prelabeled with a biotinylated anti-HER-2/neu antibody. Significant intensity enhancement was observed in HER-2/neu-expressing cell lines and in vivo in a breast cancer model. Potential applications of this approach may include determination of the HER-2/neu status for prognosis and for selecting tumors for monoclonal antibody therapy.
Influence of Gastric Inhibitory Polypeptide Antiserum on Glucose-Induced Insulin Secretion in Rats (1982)

The action of gastric inhibitory polypeptide (GIP) antiserum on glucose tolerance and insulin secretion after an intraduodenal glucose load (600 mg/kg) was examined in anesthetized rats. In control experiments the insulin secretion was nearly doubled when glucose was administered intraduodenally, as compared to an iv glucose load to simulate the blood glucose curve after the intraduodenal glucose administration. After injection of GIP antiserum, the glucose curve resulting from the intraduodenal glucose load was slightly elevated and the insulin response was significantly reduced. No free GIP could be measured in the plasma of antibody-treated rats. However, the GIP antiserum did not offset the incretin effect of the intraduodenal glucose load completely. In control experiments the same amount of GIP antibody completely blocked the insulinotropic effect of exogenous porcine GIP (0.6 microgram/kg . h). In nonanesthetized rats serial oral glucose tolerance tests were performed for 14 days after injection of the GIP antiserum. Despite the blockage of endogenous GIP, the glucose tolerance did not change significantly in the antibody-treated group of rats as compared to a control group. These data indicate that GIP is not the exclusive incretin and that additional gut factors with insulinotropic activity exist.
Evidence-Based Data From Animal and Human Experimental Studies on Pain Relief With Antidepressants: A Structured Review (2000)

Overall, the results of this structured review support the above hypothesis.
Anti-herpes Virus Activity of Fabaceous Triterpenoidal Saponins. (2000)

Anti-herpes simplex virus type 1 (HSV-1) activity of oleanane-type triterpenoidal saponins obtained from some fabaceous plants were examined. Among sophoradiol glycosides, the order of potency was kaikasaponins III>I>>sophoradiol monoglucuronide. It was suggested that the trisaccharide group showed greater action than the disaccharide group. Neither the monoglucuronide of sophoradiol nor that of soyasapogenol B showed activity. Among the trisaccharide group of soyasapogenol B, the order of activity was azukisaponin V>soyasaponin II>astragaloside VIII>>soyasaponin I. Therefore, the saponin having a glucosyl unit in the central sugar moiety seemed to show greater action. In comparison with the activities for a group having the same trisaccharide, the potency of the sapogenol moieties was found to be in the order of soyasapogenol E>sophoradiol>>soyasapogenol B. Hence, the carbonyl group at C-22 would be more effective than the hydroxyl group in anti-HSV-1 activity, while the hydroxyl group at C-24 could reduce the activity.
Febuxostat, a novel nonpurine selective inhibitor of xanthine oxidase: A twenty‐eight–day, multicenter, phase II, randomized, double‐blind, placebo‐controlled, dose‐response clinical trial examining safety and efficacy in patients with gout (2005)

Treatment with febuxostat resulted in a significant reduction of sUA levels at all dosages. Febuxostat therapy was safe and well tolerated.
Biodegradable Pin Fixation of Osteochondral Fragments of the Knee (1996)

The authors present 3 cases of osteochondritis and 2 cases of osteochondral fracture of the knee. These cases were treated with a bioabsorbable ultra high strength poly (L-lactide) pin, which has the highest mechanical strength value of any nonfiber reinforced poly (L-lactide) reported previously. Three of the patients were male, and 2 were females; their ages ranged from 12 to 21 years. The followup period ranged from 2 years to 7 years 9 months (mean, 4.1 years). Two to 4 poly (L-lactide) pins with a diameter of 2 mm were used to fix the osteochondral fragments or the transplanted autogenous osteochondral grafts. In all cases, satisfactory bone union was obtained, and no inflammatory reaction was observed during the entire followup periods. The ranges of motion were normal, and there was no pain in any of the cases. It is concluded that the poly (L-lactide) pin is safe and useful in the repair of osteochondral fractures of the knee and in fixing grafted osteochondral fragments.
The Primate Erythrocyte Complement Receptor (CR1) as a Privileged Site: Binding of Immunoglobulin G to Erythrocyte CR1 Does Not Target Erythrocytes for Phagocytosis (1997)

The primate erythrocyte (E) complement receptor, CR1, is a transmembrane glycoprotein located in clusters on the surface of E. In vivo studies have demonstrated that during processing and clearance of complement-opsonized immune complexes, large amounts of immunoglobulin G (IgG) can be bound to primate E via CR1 with no E loss or lysis. However, when comparable amounts of IgG are bound to other sites on E, in many cases the E are cleared from the circulation by the mononuclear phagocytic system. Therefore, due to its role in immune complex processing, CR1 may represent a privileged site on the primate E. To delineate further this property of E CR1, we performed in vitro phagocytosis assays in the absence of complement and examined the ingestion of E, opsonized at various sites with IgG, by peripheral blood monocytes. When either human or rhesus monkey E were opsonized at sites other than CR1, with between 1,000 and 15,000 IgG per E, substantial phagocytosis of E was evident. However, when comparable amounts of IgG were bound exclusively via CR1, little, if any, phagocytosis was observed. The key to the low phagocytic level of E opsonized via CR1 may be related to the requirements of a "zipper mechanism" for phagocytosis first annunciated by Griffin et al. Based on their findings, we suggest that due to the presence of preexisting clusters of CR1 on the E membrane, large amounts of IgG can be bound to E under conditions that preclude circumferential engagement (and phagocytosis) of the entire E by Fc receptors on the monocyte.
Inhibition of complement activation on the surface of cells after incorporation of decay-accelerating factor (DAF) into their membranes. (1984)

Decay-accelerating factor (DAF), extracted from the stroma of human erythrocytes, was purified to homogeneity and incorporated into the membrane of sheep red cell complement intermediates, where its functional properties were analyzed. Incorporation of DAF into the cell membranes was temperature dependent, took place on pronase- or trypsin-treated erythrocytes, and did not depend on prior deposition of antibody, C1 or C4. Serum lipoproteins (high and low density) effectively inhibited DAF incorporation, but had no effect on the activity of DAF after its association with the cell membrane. The incorporated DAF could not be removed from the red cell surface by repeated washings in the presence of high salt concentration but was solubilized when the stroma were extracted with 0.1% Nonidet P-40. The presence of DAF in the membrane of EA did not affect the deposition of C1 and C4, but as few as 10(2) DAF molecules per cell profoundly inhibited the assembly of C3 and C5 convertases of both the classical and alternative pathways. The DAF inhibitory effect on EAC14 or EAC43 was not overcome by supplying an excess of C2 or factor B, but the alternative pathway C3 convertase could be assembled in the presence of Ni++, or nonphysiological concentrations of Mg++, which enhances the binding affinity of factor B for C3b. The DAF effect on EAC14 or EAC143 was entirely reversed by treating the cells with specific anti-DAF antibodies, showing that DAF did not alter the structure of C4b or C3b. Taken together, the experimental evidence suggests that DAF interacts directly with membrane-bound C3b or C4b and prevents subsequent uptake of C2 and factor B. DAF can function only within the cell membrane. Indeed, the decay dissociation of the C4b2a enzyme on DAF-containing sheep intermediates was not changed by varying the cell concentration. DAF-treated EA had no influence on the decay of nontreated EAC142 present in the same mixture. Moreover, the inhibitory activity of intact human erythrocytes on C4b2a was not blocked by antibodies to DAF, but was abolished by antibodies to the C3b/C4b receptor (CR1). When incorporated into the membrane of rabbit erythrocytes, human DAF inhibited their lysis by human complement. In conclusion, on the basis of these and previous results, it appears that DAF plays a central role in preventing the amplification of the complement cascade on host cell surfaces.(ABSTRACT TRUNCATED AT 400 WORDS)
NMR relaxation in tissues with weak magnetic inhomogeneities (2000)

A theory is presented for describing the effect on the transverse NMR relaxation rate of microscopic spatial inhomogeneities in the static magnetic field. The theory applies when the inhomogeneities are weak in magnitude and the nuclear spins diffuse a significant distance in comparison with a length scale characterizing the inhomogeneities. It is shown that the relaxation rate is determined by a temporal correlation function and depends quadratically on the magnitude of the inhomogeneities. For the case of unrestricted diffusion, a simple algebraic approximation for the temporal correlation function is derived. The theory is illustrated by applying it to a model of randomly distributed magnetized spheres. The theory is also used to fit experimental data for the dependence of the relaxation rate on the interecho time for a Carr-Purcell-Meiboom-Gill pulse sequence. The experimental systems considered are in vitro red blood cell suspensions and samples of human gray matter and rat liver. Magn Reson Med 44:144-156, 2000.