gebhart/patrepeval huggingface dataset:
Sample size requirements for evaluating a conservative therapy. (1978)

Determination of an adequate sample size for a clinical trial has traditionally involved the specification of type I (false positive) and type II (false negative) error rates, and a difference that one wishes to detect. Because newer therapy has generally been more invasive or more toxic, it is conventional for the type I error to be 0.05 in order that new therapy not be accepted as superior unless its advantages are definitively established. Recently, many new trials have been directed toward showing that a more conservative treatment is equivalent in efficacy to a standard intensive therapy. In this paper, we provide formulas which prescribe the sample size necessary to meet certain criteria specified by the investigator for this alternative type of clinical trial. In addition, the percent increase in total sample size is described when more patients are allocated to one treatment than the other.
Molecular Pathways: Targeting Phosphoinositide 3-Kinase p110-Delta in Chronic Lymphocytic Leukemia (2012)

The advent of targeted therapy, specifically to the B-cell receptor (BCR), has changed the convention for the treatment of chronic lymphocytic leukemia (CLL). The phosphoinositide 3-kinase (PI3K) pathway, activated upstream by the BCR, receptor tyrosine kinases, and cytokine receptors, has been a potential target for a multitude of cancers, but until the recent introduction of isoform-specific inhibitors has not been widely used. In this review, we focus on describing the intricate upstream and downstream signaling, leading to cell survival mediated by PI3K in B cells with a specific focus on the impact and importance of the p110δ isoform (which is localized to hematopoietic cells and regulates distinct cellular functions in B cells). In addition, the clinical advances from targeting p110δ are described, with a focus on clinical outcome, toxicities, and rational combination therapies. The experiences with p110δ in CLL have led to a more fundamental understanding of CLL signaling defects and may be predictive of other BCR-directed therapeutics.
High-performance liquid chromatographic monitoring of carbohydrate fractions in partially hydrolyzed corn starch (1988)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTHigh-performance liquid chromatographic monitoring of carbohydrate fractions in partially hydrolyzed corn starchJean Bouchard, Esteban Chornet, and Ralph P. OverendCite this: J. Agric. Food Chem. 1988, 36, 6, 1188–1192Publication Date (Print):November 1, 1988Publication History Published online1 May 2002Published inissue 1 November 1988https://pubs.acs.org/doi/10.1021/jf00084a016https://doi.org/10.1021/jf00084a016research-articleACS PublicationsRequest reuse permissionsArticle Views219Altmetric-Citations30LEARN 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
Principles and Practice of Solid‐Phase Peptide Synthesis (2002)

Abstract For Abstract see ChemInform Abstract in Full Text.
A New Way of Producing Isomalto-Oligosaccharide Syrup by Using the Transglycosylation Reaction of Neopullulanase (1993)

A new way of producing isomalto-oligosaccharide syrup from starch was developed. Isomalto-oligosaccharides contain one or more alpha-(1-->6)-glucosidic linkages with or without alpha-(1-->4)-glucosidic linkages. The isomalto-oligosaccharide syrups are receiving increased attention as food additives because it is thought that they help prevent dental caries and improve human intestinal microflora, acting as a growth factor for bifidobacteria. The new system for production of isomalto-oligosaccharide syrup is based on the strong alpha-(1-->6)-transglycosylation reaction of neopullulanase. Bacillus subtilis saccharifying alpha-amylase was simultaneously used with neopullulanase to improve the yield of isomalto-oligosaccharides. The yield of isomalto-oligosaccharides was increased to more than 60%, compared with a yield of 45.0% obtained by the conventional system. To reduce the costs, the use of immobilized neopullulanase was investigated. Almost the same yield of isomalto-oligosaccharides was obtained by using immobilized neopullulanase.
Systemic administration of cellular IL-10 induces an effective, specific, and long-lived immune response against established tumors in mice (1996)

Cellular IL-10 (cIL-10), the collective term for human and murine IL-10, has both stimulatory and inhibitory effects on diverse cell types, including costimulation of T cell proliferation, chemoattraction of CD8+ T cells, and stimulation of lymphokine-activated killer cell activity. Human IL-10 (hIL-10) differs from its EBV homolog viral IL-10 (vIL-10) by only 16% at the amino acid level; however, vIL-10 shares with cIL-10 predominantly inhibitory effects, such as macrophage deactivation. We administered cIL-10 systemically to mice bearing established (day 7) sarcomas, melanomas, or colorectal carcinomas. At high doses (20 to 60 micrograms/day x 7 days), cIL-10 induced rejection of tumors, delaying tumor outgrowth or resulting in complete cure. Sublethal irradiation (500 rad) of mice prior to tumor inoculation abrogated the IL-10 effect. Cured mice were immune to subsequent rechallenge with 10-fold higher inoculation with the same, but not a different, tumor. IL-12 also has potent antitumor activity and interacts with IL-10 in both complementary and antagonistic ways; co-administration of both cytokines resulted in additive antitumor activity. To compare cIL-10 vs vIL-10 effects in vivo, we engineered CL8-1 melanoma transfectants bearing the vIL-10 or the murine IL-10 (mIL-10) gene. Local secretion of mIL-10 induced rejection of tumors, while vIL-10 resulted in accelerated outgrowth. Subsequent systemic administration of cIL-10 to mice bearing vIL-10-transduced tumors completely reversed the local suppressive effects, leading to rejection, suggesting distinct pathways for cIL-10 and vIL-10 effects. That cIL-10 can stimulate the acquisition of an effective, specific, and long-lived antitumor immune response in murine models and can reverse the local immunosuppressive effects of vIL-10 indicates a potential role for cIL-10 administration in the biologic therapy of cancer and suggests a broader interpretation of IL-10 biology.
<title>Dual-beam optical coherence tomography and topography of the human eye: a clinical feasibility study</title> (1996)

Partial coherence interferometry, a new optical non-invasive technique, that has been developed for high precision measurements of intraocular distances, has been extended to a 2D imaging instrument, called scanning partial coherence interferometer. Since the improved version of this interferometric technique is capable of performing measurements of intraocular distances at arbitrary angles between vision axis and measurement direction, or along preselected linear or circular scans in equidistant measurement points, tomographic and topographic images can be obtained, containing information about the contour and the thickness profile of different retinal structures, e.g., the retinal thickness, the retinal nerve fiber layer thickness or the thickness of choroidal layers. We report on first preliminary clinical results of measurements of the retinal thickness on healthy subjects. Furthermore the papillary retinal nerve fiber layer thickness distribution of glaucoma patients was obtained and compared with measurements performed on healthy eyes. These results were documented and correlated with topographic maps of the optic disc obtained with a Heidelberg Retina Tomograph and with visual field testing performed by automatic perimetry.
Sensitivity of HER-2/neu antibodies in archival tissue samples: potential source of error in immunohistochemical studies of oncogene expression. (1994)

HER-2/neu oncogene amplification and overexpression of breast cancer tissue has been correlated with poor prognosis in women with both node-positive and node-negative disease. However, several studies have not confirmed this association. Review of these studies reveals the presence of considerable methodological variability including differences in study size, follow-up time, techniques and reagents. The majority of papers with clinical follow-up information are immunohistochemical studies using archival, paraffin-embedded breast cancers, and a variety of HER-2/neu antibodies have been used in these studies. Very little information, however, is available about the ability of the antibodies to detect overexpression following tissue processing for paraffin-embedding. Therefore, a series of antibodies, reported in the literature or commercially available, were evaluated to assess their sensitivity and specificity as immunohistochemical reagents. Paraffin-embedded samples of 187 breast cancers, previously characterized as frozen specimens for HER-2/neu amplification by Southern blot and for overexpression by Northern blot, Western blot, and immunohistochemistry, were used. Two multitumor paraffin-embedded tissue blocks were prepared from the previously analyzed breast cancers as a panel of cases to test a series of previously studied and/or commercially available anti-HER-2/neu antibodies. Immunohistochemical staining results obtained with 7 polyclonal and 21 monoclonal antibodies in sections from paraffin-embedded blocks of these breast cancers were compared. The ability of these antibodies to detect overexpression was extremely variable, providing an important explantation for the variable overexpression rate reported in the literature.
Developing strategies to prevent inhospital cardiac arrest (1994)

Cardiac arrests on the general wards of the hospital are commonly preceded by premonitory signs and symptoms. Strategies to prevent cardiac arrest should include training for nurses and physicians that concentrates on cardiopulmonary stabilization and how to respond to neurologic and respiratory deterioration. Special attention should also be devoted to patients who have been discharged from the ICU who are at greater risk for cardiac arrest after ICU discharge than are other medical patients.
Human fibronectin contains distinct adhesion- and motility-promoting domains for metastatic melanoma cells. (1986)

The active migration of tumor cells through extracellular matrices has been proposed to play a role in certain aspects of metastasis. Metastatic tumor cells migrate in vitro in response to substratum-bound adhesive glycoproteins such as fibronectin. The present studies use affinity-purified proteolytic fragments of fibronectin to determine the nature of adhesion- and/or motility-promoting domains within the protein. Two distinct fragments were identified with cell adhesion-promoting activities. By a number of criteria, the adhesive activity promoted by these two fragments was distinct. One fragment, a 75-kD tryptic fragment purified by monoclonal antibody chromatography, promoted the adhesion, spreading, and haptotactic motility of melanoma cells. Experiments using a synthetic cell attachment peptide in solution indicated that at least part of the attachment activity exhibited by the 75-kD fragment is mediated by the sequence arg-gly-asp-ser. It was not possible to demonstrate migration-stimulating activity using a small (11.5 kD) peptic fragment containing this sequence (Pierschbacher, M.D., E. G. Hayman, and E. Ruoslahti, 1981, Cell, 26:259-267) suggesting that another cell-binding activity within the 75 kD fragment distinct from arg-gly-asp-ser might be required for motility. The second fragment that stimulated melanoma adhesion was a 33-kD tryptic/catheptic carboxyl-terminal heparin-binding fragment, which is localized to the A chain of fibronectin. This fragment promotes adhesion and spreading but not the motility of these cells. Melanoma adhesion to this heparin-binding fragment was sensitive to the effects of cycloheximide, which contrasted adhesion to the haptotaxis-promoting fragment. Importantly, these studies illustrate that haptotaxis in response to fibronectin is not due to simple adhesion gradients of this protein. The results are discussed in light of a model for multiple distinct cell surface constituents mediating cell adhesion and motility on fibronectin.
Crystal structure of human stem cell factor: Implication for stem cell factor receptor dimerization and activation (2000)

Stem cell factor (SCF) plays important roles in hematopoiesis and the survival, proliferation, and differentiation of mast cells, melanocytes, and germ cells. SCF mediates its biological effects by binding to and activating a receptor tyrosine kinase designated c-kit or SCF receptor. In this report we describe the 2.3-A crystal structure of the functional core of recombinant human SCF. SCF is a noncovalent homodimer composed of two slightly wedged protomers. Each SCF protomer exhibits an antiparallel four-helix bundle fold. Dimerization is mediated by extensive polar and nonpolar interactions between the two protomers with a large buried surface area. Finally, we have identified a hydrophobic crevice and a charged region at the tail of each protomer that functions as a potential receptor-binding site. On the basis of these observations, a model for SCF small middle dotc-kit complex formation and dimerization is proposed.
Synthesis and Characterization of Amphiphilic Polyphosphates with Hydrophilic Graft Chains and Cholesteryl Groups as Nanocarriers (2006)

Amphiphilic polyphosphate graft copolymers with varied densities of cholesteryl esters and hydrophilic graft chains were prepared, and the solution properties of the graft copolymers were evaluated. Polyphosphates were synthesized as backbones by ring-opening polymerization of 2-isopropyl-2-oxo-1,3,2-dioxaphospholane (IPP), 2-(2-oxo-1,3,2-dioxaphosphoroyloxyethyl-2-bromoisobutyrate) (OPBB), and 2-choresteryl-2-oxo-1,3,2-dioxaphospholane (ChOP) using triisobutylaluminum as an initiator. Three types of polyphosphates (PIBr(x)Ch(y), x = number of OPBB units in a polymer; y = number of ChOP units in a polymer) such as PIBr4, PIBr6Ch1, and PIBr3Ch2 were obtained. The molecular weights of these polymers were 2.4 x 10(4), 2.4 x 10(4), and 2.6 x 10(4) g/mol, respectively. 2-Methacryloyloxyethyl phosphorylcholine (MPC) was grafted from the OPBB sites in PIBr(x)Ch(y) via atom transfer radical polymerization (ATRP) in EtOH. In each polymer system, the molecular weight of the graft polymer was linear with conversion. Furthermore, the polymer radical concentration remained constant during polymerization; that is, the molecular weights of the graft chains were easily controllable with polymerization time. The solution properties of amphiphilic PIBr(x)Ch(y)-g-PMPCs were investigated by the methods of surface tension measurement, light scattering, and fluorescence probe. The transition point (cmc) of the surface tension of the PIBr(x)Ch(y)-g-PMPCs aqueous solution decreased with an increase in the number of ChOP units in a graft polymer. Particularly, PIBr3Ch2-g-PMPC14.9K formed nanosized associates (R(h) = 7.5 nm) with 2.2 molecules above 0.1 wt %. v79 cells were used to evaluate the cytotoxicity of the graft polymers, but no cytotoxicity was observed. The graft polymers containing cholesteryl groups effectively enhanced the solubility of paclitaxel in an aqueous solution.
Improving chronic disease management (2005)

Chronic disease accounts for nearly 80% of spending on health care, so it is not surprising that a different approach to care delivery is a priority for the NHS. By 2008 all primary care trusts will be expected to have implemented case management approaches alongside existing initiatives such as the expert patient programme (Department of Health, 2004) and so contribute to a reduction in costly unplanned admissions.
Simple agarose gel electrophoretic method for the identification and characterization of plasmid deoxyribonucleic acid (1976)

Agarose gel electrophoresis may be employed effectively for the detection and preliminary characterization of plasmid deoxyribonucleic acid (DNA) present in clinical isolates and laboratory strains of gram-negative microorganisms. The method is sensitive and does not require radioisotopes or ultracentrifugation. The estimation of plasmid mass from the extent of DNA migration in gels compares favorably with results obtained by electron microscopy of plasmid DNA purified by equilibrium density centrifugation. The method has proved to be a useful tool for survey work and the epidemiological investigation of plasmid dissemination, as well as an important adjunct to the genetic analysis of plasmids.
Elimination of infectious human immunodeficiency virus from human T-cell cultures by synergistic action of CD4-Pseudomonas exotoxin and reverse transcriptase inhibitors. (1990)

We have previously described a recombinant protein, designated CD4(178)-PE40, consisting of the human immunodeficiency virus (HIV) envelope glycoprotein-binding region of human CD4 linked to the translocation and ADP-ribosylation domains of Pseudomonas aeruginosa exotoxin A. By virtue of its affinity for gp120 (the external subunit of the HIV envelope glycoprotein), the hybrid toxin selectively binds to and kills HIV-1-infected human T cells expressing surface envelope glycoprotein and also inhibits HIV-1 spread in mixed cultures of infected and uninfected cells. We now report that CD4(178)-PE40 and reverse transcriptase inhibitors exert highly synergistic effects against HIV-1 spread in cultured human primary T cells. Furthermore, combination treatment can completely eliminate infectious HIV-1 from cultures of human T-cell lines. This conclusion is based on protection of a susceptible cell population from HIV-induced killing, complete inhibition of virus protein accumulation, and elimination of HIV DNA (as judged by quantitative polymerase chain reaction analysis). The results highlight the therapeutic potential of treatment regimens involving combination of a virostatic drug that inhibits virus replication plus an agent that selectively kills HIV-infected cells.
Characterization of mammalian receptors for lactoferrin (2002)

Lactoferrin (Lf) has been suggested to have several physiological functions. Specific binding of Lf, indicating the presence of Lf receptors (LfRs), has been observed in various types of mammalian cells such as lymphocytes, hepatocytes, and enterocytes. These LfRs are considered to function as a mediator for some of the functions of Lf. We here review current knowledge of mammalian LfRs characterized in different tissues. We also briefly present evidence for the existence of an LfR provided by our cloning of a human intestinal LfR (HLfR). The entire coding region of the HLfR was cloned by polymerase chain reaction (PCR), and a recombinant HLfR (rHLfR) was expressed in a baculovirus system. The rHLfR was purified by immobilized human Lf (HLf) affinity chromatography, indicating that the rHLfR retained the capacity to bind HLf. The gene was expressed at high levels in fetal small intestine and in adult heart but at lower levels in Caco-2 cells. In summary, we demonstrate the presence of a unique receptor-mediated mechanism for Lf, functioning in the small intestine of the newborn infant and possibly in other tissues of human adults.
Cloning and sequence analysis of cDNA for human renin precursor. (1983)

The primary structure of human renin precursor has been deduced from its cDNA sequence. A library of cDNA clones was constructed from human kidney poly(A)+ RNA by applying the vector/primer method of Okayama and Berg. The library was screened for human renin sequences by hybridization with the previously cloned mouse renin cDNA. Of the 240,000 colonies screened, 35 colonies that were positive for hybridization were isolated. Two recombinant plasmids containing long inserts of about 1,300 and 1,600 base pairs were selected for sequence analysis. The amino acid sequence predicted from the cDNA sequence shows that the human renin precursor consists of 406 amino acids with a pre and a pro segment carrying 20 and 46 amino acids, respectively. A high degree of sequence homology was found upon comparison of the mouse and human renins. Close similarities were also observed in the primary structures of renin and aspartyl proteinases that have known three-dimensional structures, suggesting a similar tertiary structure for renin.
Non-canonical fibroblast growth factor signalling in angiogenesis (2007)

Whereas fibroblast growth factors (FGFs) classically transmit their signals via high-affinity tyrosine kinase receptors (FGFR1-4), recent evidence strongly implicates non-tyrosine kinase receptors (NTKR) or cell-surface FGFR-interacting proteins as important players in FGF signalling. Although NTKR have lower affinity for FGFs in comparison with cognate tyrosine kinase receptors, because of their high abundance they can effectively bind FGFs and produce unique biological effects independent of FGFRs. A prime example of such NTKR is the syndecan family of plasma membrane proteoglycans and, in particular, syndecan-4, which transmits FGF signalling via a protein kinase Calpha pathway. Another NTKR, alpha(v)beta(3) integrin, functions as an FGF signalling modulator by binding both FGF2 and FGFR1. Yet another NTKR, neural cell adhesion molecule (NCAM), can serve as an FGFR ligand and assemble an FGFR signalling complex in the absence of FGFs. Furthermore, N-cadherin, which has been reported to associate with FGFR, appears to activate FGFR in both ligand (FGF)-dependent and ligand-independent manners. Finally, gangliosides are implicated as a co-receptor system of FGFs. The biological consequence of non-canonical FGF signalling tends to be less discernable compared to the canonical FGFR activation because of the overlap between these two pathways; nevertheless, non-canonical signalling is important and sometimes essential for cellular functions. Given the diversity of FGF activities through embryonic development to adult physiology, the existence of the non-canonical signalling system may account for the different cellular response to the FGF input in different biological contexts. In this review, we will discuss recent findings related to non-canonical FGF signalling with emphasis on the endothelial biology and angiogenesis.
Development of a Miniaturized Glucose Monitoring System by Combining a Needle-Type Glucose Sensor With Microdialysis Sampling Method: Long-term subcutaneous tissue glucose monitoring in ambulatory diabetic patients (1994)

Glycemic excursions could be monitored precisely in the subcutaneous tissue by this microdialysis sampling method with a needle-type glucose sensor in ambulatory diabetic patients.