gebhart/patrepeval huggingface dataset:
Chemotherapy of human colorectal tumor xenografts in athymic mice with clinically active drugs: 5‐fluorouracile and 1‐3‐bis‐(‐2‐chloroethyl)‐1‐nitrosourea (bcnu). Comparison with doxorubicin derivatives: 4′deoxydoxorubicin and 4′‐0‐methyldoxorubicin (1981)

The effects of single-agent therapy with two clinically useful drugs, 5-fluorouracil (5-FU) and 1-3-bis-(2-chloroethyl)-1-nitrosourea (BCNU) against nine human colorectal tumors (rectum T 157 and T 348, lung metastasis T 84, lymph-node metastasis T 245, colon, T 183, T 219, T 347, T 362 and T 380) transplanted and passed serially in thymic (nude) mice were studied. In addition, chemosensitivity of the tumors to 5-FU and BCNU was compared with the chemosensitivity of the tumors to two new doxorubicin analogues, 4'-deoxydoxorubicin and 4'-0-methyldoxorubicin. BALB/c nude mice were treated intravenously on a weekly basis for 3-4 weeks, starting when the tumor volume became relatively large (advanced stage of tumor treatment). All the tumors showed a 90-100% take rate and stable growth. In these experiments, 77% (5/9) of the colorectal tumors were biologically sensitive to the treatment with 5-FU but the percentage of statistically significant sensitive tumors was 22%, which is in good agreement with the clinical data reported in the literature (21%). In patients, BCNU has been reported to give up to 13% response. In contrast, we have found a 33% statistically significant response rate in our panel of colorectal tumors. The difference could be related to the higher tolerance of nude mice to certain drugs, including BCNU. The results suggest that the two new doxorubicin derivatives, 4'-deoxydoxorubicin and 4'-0-methyldoxorubicin, should be more active in the patient than both of the clinically used drugs, 5-FU and BCNU. Furthermore, there is a good correlation between the results obtained in the experimental system (human tumor/nude mouse) and in human patients with the active drugs, 5-FU and BCNU.
Xyloglucans in different types of cotton (Gossypiumsp.) cells (1993)

The different xyloglucans obtained from the cell walls of cotton fibres, cotton leaves, suspension-cultured cotton cells, and from the culture medium of the latter cells have been characterized by methylation and 13C-NMR. The proportions of the constituent monosaccharides are quite similar—glucose:xylose:galactose:fucose (2–4-2-0:l:0–5-0-3:0–3-0-l) and the xyloglucans all have a main chain of β-l,4-linked D-glucopyranosyl residues to which α-xylopyranosyl-, 2-O-β-galactopyranosyl-α-xylopyranosyl-, and 2-O-α-fucopyranosyl-2-O-β-galactopyranosyl-α-xylopyranosylresidues are attached at C(O)6. An oligosaccharide, which was tentatively identified as the xyloglucan nonasaccharide XG9 (Glc4Xyl3GalFuc), was isolated from the culture medium of suspension-cultured cells.
Calcium homeostasis in intact lymphocytes: cytoplasmic free calcium monitored with a new, intracellularly trapped fluorescent indicator. (1982)

A new, fluorescent, highly selective Ca2+ indicator , "quin2", has been trapped inside intact mouse and pig lymphocytes, to measure and manipulate cytoplasmic free Ca2+ concentrations, [Ca2+]i. Quin2 is a tetracarboxylic acid which binds Ca2+ with 1:1 stoichiometry and an effective dissociation constant of 115 nM in a cationic background mimicking cytoplasm. Its fluorescence signal (excitation 339 nm, emission 492 nm) increases about fivefold going from Ca-free to CA-saturated forms. Cells are loaded with quin2 by incubation with its acetoxymethyl ester, which readily permeates the membrane and is hydrolyzed in the cytoplasm, thus trapping the impermeant quin2 there. The intracellular quin2 appears to be free in cytoplasm, not bound to membranes and not sequestered inside organelles. The fluorescence signal from resting cells indicates a [Ca2+]i of near 120 nM. The millimolar loadings of quin2 needed for accurately calibrated signals do not seem to perturb steady-state [Ca2+]i, but do somewhat slow or blunt [Ca2+]i transients. Loadings of up to 2mM are without serious toxic effects, though above this level some lowering of cellular ATP is observed. [Ca2+]i was well stabilized in the face of large changes in external Ca2+. Alterations of Na+ gradients, membrane potential, or intracellular pH had little effect. Mitochondrial poisons produced a small increase in [Ca2+]i, probably due mostly to the effects of severe ATP depletion on the plasma membrane. Thus intracellulary trapped chelators like quin2 offer a method to measure or buffer [Ca2+]i in hitherto intractable cell types.
Tumor necrosis factor/cachectin stimulates peritoneal macrophages, polymorphonuclear neutrophils, and vascular endothelial cells to synthesize and release platelet-activating factor. (1987)

Murine tumor necrosis factor (mTNF) stimulates production of platelet-activating factor (PAF) by cultured rat peritoneal macrophages in amounts comparable to those formed during treatment with the calcium ionophore A23187 or phagocytosis of zymosan. The cell-associated PAF that was released into the medium was identical to synthetic PAF, as determined with physicochemical, chromatographic, and enzymatic assays. Furthermore, de novo synthesis of PAF by macrophages was demonstrated by the incorporation of radioactive precursors such as [3H]acetyl-coenzyme A or [3H]2-lyso-PAF. Macrophages incubated with mTNF for 4 h synthesized PAF only during the first h of treatment. At this time, the amount of cell-associated PAF was approximately equal to that released into the medium. The cell-associated PAF decreased afterwards, whereas that in the medium did not correspondingly increase, suggesting that some PAF was being degraded. The response of rat macrophages to different doses of mTNF and human TNF (hTNF) was examined. Maximal synthesis of PAF was obtained with 10 ng/ml of mTNF and 50 ng/ml of hTNF. This finding may be explained by a lower affinity of hTNF for TNF receptors of rat cells. The hTNF stimulated production of PAF by human vascular endothelial cells cultured from the umbilical cord vein. The time course of PAF synthesis was slower than that observed with macrophages, with maximal production between 4 and 6 h of treatment. Optimal synthesis of PAF was obtained with 10 ng/ml of hTNF. Only 20-30% of the PAF synthesized by endothelial cells was released into the medium, even after several hours of incubation. Synthesis of PAF in response to TNF was also detected in rat polymorphonuclear neutrophils, but not in human tumor cells and dermal fibroblasts. Therefore, production of PAF is a specialized response that is transient in macrophages continuously treated with TNF, and that appears to be controlled by unidentified regulatory mechanisms.
An Improved Synthesis of 2-, 3-, and 4-(Trifluoromethyl)cyclohexylamines (2012)

An improved synthesis of 2-, 3-, and 4-trifluoromethylcyclohexylamines on a multigram scale via PtO<sub>2</sub>-mediated hydrogenation of the corresponding trifluoromethylanilines in trifluoroacetic acid at room temperature under atmospheric pressure is reported. The hydrogenation occurred with a remarkable stereo­selectivity favoring the formation of <i>cis</i>-isomers.
Spatial and temporal changes in the distribution of proteoglycans during avian neural crest development (1991)

In this study, we describe the distribution of various classes of proteoglycans and their potential matrix ligand, hyaluronan, during neural crest development in the trunk region of the chicken embryo. Different types of chondroitin and keratan sulfate proteoglycans were recognized using a panel of monoclonal antibodies produced against specific epitopes on their glycosaminoglycan chains. A heparan sulfate proteoglycan was identified by an antibody against its core protein. The distribution of hyaluronan was mapped using a biotinylated fragment that corresponds to the hyaluronan-binding region of cartilage proteoglycans. Four major patterns of proteoglycan immunoreactivity were observed. (1) Chondroitin-6-sulfate-rich proteoglycans and certain keratin sulfate proteoglycans were absent from regions containing migrating neural crest cells, but were present in interstitial matrices and basement membranes along prospective migratory pathways such as the ventral portion of the sclerotome. Although initially distributed uniformly along the rostrocaudal extent of the sclerotome, these proteoglycans became rearranged to the caudal portion of the sclerotome with progressive migration of neural crest cells through the rostral sclerotome and their aggregation into peripheral ganglia. (2) A subset of chondroitin/keratan sulfate proteoglycans bearing primarily unsulfated chondroitin chains was observed exclusively in regions where neural crest cells were absent or delayed from entering, such as the perinotochordal and subepidermal spaces. (3) A subset of chondroitin/keratan sulfate proteoglycans was restricted to the perinotochordal region and, following gangliogenesis, was arranged in a metameric pattern corresponding to the sites where presumptive vertebral arches form. (4) Certain keratan sulfate proteoglycans and a heparan sulfate proteoglycan were observed in basement membranes and in an interstitial matrix uniformly distributed along the rostrocaudal extent of the sclerotome. After gangliogenesis, the neural crest-derived dorsal root and sympathetic ganglia contained both these proteoglycan types, but were essentially free of other chondroitin/keratan-proteoglycan subsets. Hyaluronan generally colocalized with the first set of proteoglycans, but also was concentrated around migrating neural crest cells and was reduced in neural crest-derived ganglia. These observations demonstrate that proteoglycans have diverse and dynamic distributions during times of neural crest development and chondrogenesis of the presumptive vertebrae. In general, chondroitin/keratan sulfate proteoglycans are abundant in regions where neural crest cells are absent, and their segmental distribution inversely correlates with that of neural crest-derived ganglia.
Influence of Pravastatin and Plasma Lipids on Clinical Events in the West of Scotland Coronary Prevention Study (WOSCOPS) (1998)

We conclude that the treatment effect of 40 mg/d of pravastatin is proportionally the same regardless of baseline lipid phenotype. There is no CHD risk reduction unless LDL levels are reduced, but a fall in the range of 24% is sufficient to produce the full benefit in patients taking this dose of pravastatin. LDL reduction alone does not appear to account entirely for the benefits of pravastatin therapy.
Nonmelanoma Cancers of the Skin (1992)

BASAL-CELL and squamous-cell cancers of the skin are the most frequent malignant conditions in the white population. About 600,000 new cases are detected each year in the United States.1 Fortunately, only a small proportion lead to death. Nonmelanoma cancers are associated with substantial morbidity, including loss of function and disfigurement, and their treatment is costly. Early detection can reduce morbidity and cost.We will review the epidemiology, recognition, treatment, and prevention of basal-cell and squamous-cell carcinomas, which together account for most nonmelanoma skin cancers (we exclude tumors of the mucous membranes). We shall emphasize risk factors for the development of . . .
Cutaneous and systemic effects of varying doses of brown recluse spider venom in a rabbit model. (2007)

In the model, both the size and depth of the eschar were dose-related. We also observed a dose related elevation in the APTT that corrected with mixing studies. The dose-response relationship suggests direct interference by a component of the venom, rather than an idiosyncratic response. We did not detect a deficiency of commonly measured coagulation factors or evidence of a lupus anticoagulant. Protein C demonstrated a decrease. Although DIC did not occur in this rabbit model, a dose-related elevation in APTT was noted. The finding that the elevation corrected with mixing studies suggests that a plasma factor is essential in the coagulopathy associated with brown recluse envenomation. Further studies to identify this factor could shed light on human coagulopathy following envenomation.
Calcitonin Gene-Related Peptide and Migraine: Implications for Therapy (2004)

It is clearly evident from the literature that headache has troubled mankind from the \ndawn of civilization (Rapoport &amp; Edmeads, 2000). A variety of methods have been \nused throughout the ages in an attempt to alleviate or cure this pain; these may have \nbeen the most appropriate at that time, and were probably seen as “cutting edge”. \nToday they seem at best amusing, and at worst cruel and barbaric. \nThe earliest concepts in migraine were those of the supernatural, with \nmigraine believed to be due to malevolent beings within the head; treatment based on \nthis idea included incantations and application to the head of substances intended to \ndrive out the demons and spirits (Edmeads, \n1991). These were also driven out physically, \nas in the Neolithic period (8500-7000 BC). The \npeople living in this time used the method of \ntrepanation, a kind of neurosurgery, which \ninvolved removing circular chunks of skull so \nthat the spirits causing the headache could \nescape. Over 50% of the trepanned skulls have \nshown evidence of healing, indicating a high \nsurvival rate for this operation. Although the \nscientific rationale behind trepanation is not \nunderstood, it is surprising that this procedure \nwas performed as a treatment for migraine as \nlate as the mid 17th century (Edmeads, 1991; \nRapoport &amp; Edmeads, 2000).
CytochromeP-450 metabolite of arachidonic acid mediates bradykinin-induced negative inotropic effect (2001)

This study focused on the mechanisms of the negative inotropic response to bradykinin (BK) in isolated rat hearts perfused at constant flow. BK (100 nM) significantly reduced developed left ventricular pressure (LVP) and the maximal derivative of systolic LVP by 20-22%. The cytochrome P-450 (CYP) inhibitors 1-aminobenzotriazole (1 mM and 100 microM) or proadifen (5 microM) abolished the cardiodepression by BK, which was not affected by nitric oxide and cyclooxygenase inhibitors (35 microM NG-nitro-L-arginine methyl ester and 10 microM indomethacin, respectively). The CYP metabolite 14,15-epoxyeicosatrienoic acid (14,15-EET; 50 ng/ml) produced effects similar to those of BK in terms of the reduction in contractility. After the coronary endothelium was made dysfunctional by Triton X-100 (0.5 microl), the BK-induced negative inotropic effect was completely abolished, whereas the 14,15-EET-induced cardiodepression was not affected. In hearts with normal endothelium, after recovery from 14,15-EET effects, BK reduced developed LVP to a 35% greater extent than BK in the control. In conclusion, CYP inhibition or endothelial dysfunction prevents BK from causing cardiodepression, suggesting that, in the rat heart, endothelial CYP products mediate the negative inotropic effect of BK. One of these mediators appears to be 14,15-EET.
snRNP protein expression enhances the formation of Cajal bodies containing p80-coilin and SMN (2001)

Splicing snRNPs (small nuclear ribonucleoproteins) are essential sub-units of the spliceosome. Here we report the establishment of stable cell lines expressing fluorescently tagged SmB, a core snRNP protein. Analysis of these stable cell lines has allowed us to characterize the nuclear pathway that leads to snRNP accumulation in nuclear speckles and has identified a limiting nucleolar step in the pathway that can be saturated by overexpression of Sm proteins. After nuclear import, newly assembled snRNPs accumulate first in a subset of Cajal bodies that contain both p80-coilin and the survival of motor neurons protein (SMN) and not in bodies that contain p80-coilin but lack SMN. Treatment of cells with leptomycin B (LMB) inhibits both the accumulation of snRNPs in nuclear bodies and their subsequent accumulation in speckles. The formation of Cajal bodies is enhanced by Sm protein expression and the assembly of new snRNPs. Formation of heterokaryons between HeLa cell lines expressing Sm proteins and primary cells that usually lack Cajal bodies results in the detection of Cajal bodies in primary cell nuclei. Transient over-expression of exogenous SmB alone is sufficient to induce correspondingly transient Cajal body formation in primary cells. These data indicate that the level of snRNP protein expression and snRNP assembly, rather than the expression levels of p80-coilin or SMN, may be a key trigger for Cajal body formation.
Automated star/galaxy discrimination with neural networks (1992)

We discuss progress in the development of automatic star/galaxy discriminators for processing images generated by the University of Minnesota Automated Plate Scanner (APS) for cataloging the first epoch Palomar Sky Survey. Classifications are based on 14 image parameters computed for each object detected by the APS operating in a threshold densitometry mode. It is shown that a number of parameter spaces formed with these vector elements are effective in separating a sample into the two basic populations of stellar and nonstellar objects. An artificial intelligence technique known as a neural network is employed to perform the image classification. We have experimented with a simple linear classifier known as a perceptron, as well as with a more sophisticated backpropagation neural network with the result that we are able to attain classification success rates of 99% for galaxy images with B&lt;=18.5 and above 95% for the magnitude range 18.5&lt;=B&lt;=19.5. The analysis presented here uses a training dataset consisting of 2665 galaxies and 2082 stars, along with a test sample of 936 galaxies and 2378 stars. We have determined the success rate of these classifiers as a function of image diameter and integrated magnitude. Simple numerical experiments have been conducted in an effort to illustrate the robust nature of this method as well as to isolate the most significant image parameters used by the networks in distinguishing image class.
Medicinal Chemistry of Nucleoside Phosphonate Prodrugs for Antiviral Therapy (2011)

Considerable attention has been focused on the development of phosphonate-containing drugs for application in many therapeutic areas. However, phosphonate diacids are deprotonated at physiological pH and thus phosphonate-containing drugs are not ideal for oral administration, an extremely desirable requisite for the treatment of chronic diseases. To overcome this limitation several prodrug structures of biologically active phosphonate analogues have been developed. The rationale behind the design of such agents is to achieve temporary blockade of the free phosphonic functional group until their systemic absorption and delivery, allowing the release of the active drug only once at the target. In this paper, an overview of acyclic and cyclic nucleoside phosphonate prodrugs, designed as antiviral agents, is presented.
Opioid Peptides and Opioid Receptors in Cells of the Immune System (1988)

I Abbreviations used: ACTH, adrenocorticotropic hormone; ADCC, antibody-dependent cellular cytotoxicity; Bma .. total number of binding sites; BREM, bremazocine, an agonist with modest selectivity for K sites; CCK, cholecystokinin; ConA, concanavalin A; DADLE, [D-Ala2,D-LeuS]enkephalin, an agonist somewhat selective for /j �ites; DEX, dextrorphan, inert enantiomer of LEV; DHM, dihydromorphine, a Jl-selective agonist; DIP, dipre­ norphine, a relatively nonselective antagonist; DYN, dynorphin, a peptide product of the dynorphin gene, selective for K sites; EKC, ethylketazocine, a benzomorphan agonist with modest selectivity for K sites; END, endorphin; a peptide product of the pro-opio­ melanocortin gene; <Xand y-endorphin are fragments of fJ-endorphin; fJ-endorphin is selective for e sites; ETO, etorphine, a relatively nonselective agonist; fMLP, formyl-methio­ nyl-leucinyl-phenylalanine; granulo, granulocyte(s); h, human; ICso, concentration of a com­ peting ligand that reduces specific binding of radioligand by 50%; icv, intracerebro­ ventricular; IFN, interferon; ir-, immunoreactive; Kd, K;, equilibrium dissociation con­ stants, determined by binding isotherm or by competition, respectively; LENK, [Leu]en­ kephalin, a minor product of the pro-enkephalin gene, an agonist somewhat selective for {) sites; leuko, leukocyte(s); LEV, levorphanol, a Jl-selective agonist; Iympho, Iymphocyte(s); m, mouse; M.p, macrophage(s); MENK, [Met]enkephalin, major product of the pro-enkephalin gene, a /j-selective agonist; MNC, mononuclear cell(s); mono, monocyte(s); MOR, morphine, a Jl-selective agonist; NA, not applicable; NAL, naloxone, a moderately jl-selective antag­ onist; NK, natural killer; NR, not reported; NTX, naltrexone, a long-lasting Jl-selective antagonist closely related to naloxone; PBL, peripheral blood Iymphocyte(s); PBMNC, peripheral blood mononuclear cell(s); PHA, phytohemagglutinin; PMNL, polymorpho­ nuclear leukocyte(s); r, rat; RIA, radioimmunoassay; spleno, splenocyte; SRBC, sheep red blood cells; VIP, vasoactive intestinal peptide.
Molybdenum Monoaryloxide Pyrrolide Alkylidene Complexes That Contain Mono-ortho-substituted Phenyl Imido Ligands (2012)

Monaryloxide pyrrolide (MAP) molybdenum imido alkylidene complexes of the type Mo(NArX)(CHCMe2R)(Me2Pyr)(OR′) (Me2Pyr = 2,5-dimethylpyrrolide) have been prepared in which NArX is an ortho-substituted phenylimido group (X = Cl (NArCl), CF3 (NArCF3), i-Pr (NAriPr), t-Bu (NArtBu), mesityl (NArM), or TRIP (TRIP = triisopropylphenyl; NArT)) and OR′ = O-2,3,5,6-(C6H5)4C6H (OTPP), O-2,6-(2,4,6-Me3C6H2)2C6H3 (OHMT), or O-2,6-(2,4,6-i-Pr3C6H2)2C6H3 (OHIPT). The object was to explore to what extent relatively “large” NArM or NArT ligands would alter the performance of MAP catalysts in reactions that have been proposed to depend upon the relative size of the imido and OR′ groups. Preliminary studies employing the ring-opening metathesis polymerization of 5,6-dicarbomethoxynorbornadiene as a measure of selectivity suggest that a single phenylimido ortho substituent, even in an NArM or NArT group, does not produce any unique behavior and that the outcome of the ROMP reaction correlates with the overall relative size of the imido and OR′ group. Single-crystal X-ray structures of six species that contain the new NArM or NArT groups are reported.
Silver Clusters and Chemistry in Zeolites (1994)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSilver Clusters and Chemistry in ZeolitesTao Sun and Karl SeffCite this: Chem. Rev. 1994, 94, 4, 857–870Publication Date (Print):June 1, 1994Publication History Published online1 May 2002Published inissue 1 June 1994https://pubs.acs.org/doi/10.1021/cr00028a001https://doi.org/10.1021/cr00028a001research-articleACS PublicationsRequest reuse permissionsArticle Views2527Altmetric-Citations394LEARN 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