gebhart/patrepeval huggingface dataset:
Regulation of muscarinic acetylcholine receptor number in cultured neuronal cells by chronic membrane depolarization. (1987)

The effect of chronic membrane depolarization on the regulation of muscarinic acetylcholine receptor (mAChR) number was studied in neuroblastoma cells (clone N1E-115). Receptor number was determined by a filter binding assay using 3H-quinuclidinyl benzilate (QNB) in membrane and crude cellular homogenates. Incubation with 50 microM veratridine (VTN), an activator of voltage-sensitive Na+ channels, induced a 50-200% increase in mAChR number at 24 hr, which was inhibited 80% by TTX. Scatchard analysis showed that affinity of the mAChR for 3H-QNB was not affected by VTN. Upon withdrawal of VTN, mAChR number returned to control levels within 20 hr. Chronic membrane depolarization caused by incubation in medium containing 60 mM K+ induced a TTX-insensitive 50% increase in mAChR number at 24 hr. AChE activity was unaffected by chronic membrane depolarization. The VTN-induced increase in mAChR number was not blocked by coincubation with cycloheximide or tunicamycin, both inhibitors of de novo mAChR synthesis. The rate of mAChR degradation was reduced in the presence of 50 microM VTN, with the apparent half-life increased from approximately 18 hr (control) to approximately 40 hr (VTN). Although treatment with either 1 mM 8Br-cAMP or 1 mM 8Br-GMP failed to increase mAChR number, treatment with either the inorganic Ca2+ channel blocker Co2+ (1 mM) or the organic Ca2+ channel antagonist D600 (10-100 microM) produced 40-80% increases in mAChR number. The combination of VTN and either D600 or Co2+ failed to induce a greater increase in mAChR number than incubation with VTN alone.(ABSTRACT TRUNCATED AT 250 WORDS)
Potential of ileal bile acid transporter inhibition as a therapeutic target in Alagille syndrome and progressive familial intrahepatic cholestasis (2020)

Alagille syndrome (ALGS) and progressive familial intrahepatic cholestasis (PFIC) are rare, inherited cholestatic liver disorders that manifest in infants and children and are associated with impaired bile flow (ie cholestasis), pruritus and potentially fatal liver disease. There are no effective or approved pharmacologic treatments for these diseases (standard medical treatments are supportive only), and new, noninvasive options would be valuable. Typically, bile acids undergo biliary secretion and intestinal reabsorption (ie enterohepatic circulation). However, in these diseases, disrupted secretion of bile acids leads to their accumulation in the liver, which is thought to underlie pruritus and liver-damaging inflammation. One approach to reducing pathologic bile acid accumulation in the body is surgical biliary diversion, which interrupts the enterohepatic circulation (eg by diverting bile acids to an external stoma). These procedures can normalize serum bile acids, reduce pruritus and liver injury and improve quality of life. A novel, nonsurgical approach to interrupting the enterohepatic circulation is inhibition of the ileal bile acid transporter (IBAT), a key molecule in the enterohepatic circulation that reabsorbs bile acids from the intestine. IBAT inhibition has been shown to reduce serum bile acids and pruritus in trials of paediatric cholestatic liver diseases. This review explores the rationale of inhibition of the IBAT as a therapeutic target, describes IBAT inhibitors in development and summarizes the current data on interrupting the enterohepatic circulation as treatment for cholestatic liver diseases including ALGS and PFIC.
Prophylactic Alpha Interferon Treatment Increases the Therapeutic Index of Oncolytic Vesicular Stomatitis Virus Virotherapy for Advanced Hepatocellular Carcinoma in Immune-Competent Rats (2005)

Vesicular stomatitis virus (VSV) is a negative-strand RNA virus with intrinsic oncolytic specificity due to substantially attenuated antiviral responses in many tumors. We have recently reported that recombinant VSV vector can be used as an effective oncolytic agent to safely treat multifocal hepatocellular carcinoma (HCC) in the livers of immune-competent rats via hepatic artery infusion. When administered at doses above the maximum tolerated dose (MTD), however, the animals suffered from neurotoxicity and/or acute lethal hepatotoxicity. Since VSV is extremely sensitive to the antiviral actions of alpha/beta interferon (IFN-alpha/beta) in normal cells, we tested if prophylactic treatment with rat IFN-alpha would enhance VSV safety without compromising treatment efficacy in tumor-bearing rats. We found that VSV retained its replication potential in human and rat HCC cells after preincubation with relatively high doses of rat and human IFN-alpha in vitro, and its MTD in tumor-bearing rats treated systemically with rat IFN-alpha at 66 IU/g body weight (BW), equivalent to a human IFN-alpha dose that is currently prescribed for patients with viral hepatitis, was elevated by more than 1/2 log unit. Furthermore, we demonstrate that intratumoral replication of VSV was not attenuated by administration of 66 IU/g BW rat IFN-alpha, as tumor response and survival advantage in VSV-treated rats in the presence or absence of rat IFN-alpha were equivalent. The results suggest that prophylactic rat IFN-alpha treatment elevates the therapeutic index of hepatic arterial VSV therapy for multifocal HCC in rats. Since human IFN-alpha is currently in clinical use, its prophylactic application should be considered in future clinical translational protocols for VSV-mediated oncolytic virotherapy as a novel therapeutic modality in patients with advanced HCC, as well as other types of cancer.
Beta-adrenoceptor antagonists in neuropsychiatry: an update. (1988)

Although beta-adrenoceptor antagonists such as propranolol have been used in neuropsychiatry for more than 20 years, their indications, extent of efficacy, and place in therapy remain unclear. In this overview, which concentrates on the recent literature, four indications for use of the drugs are reviewed, with particular reference to efficacy, mode of action, and clinical utility. The indications are anxiety disorders, including performance anxiety; schizophrenia; aggressive behavior; and akathisia. The author concludes that beta-blockers are useful in some forms of anxiety disorder, perhaps those characterized by somatic symptoms and by performance anxiety, and that akathisia seems to be responsive to those drugs. However, the use of high doses of beta-blockers in schizophrenia remains unestablished, and insufficient data are available with respect to their use in aggressive behavior.
Circumventing the immune response to adenovirus-mediated gene therapy. (1996)

Adenovirus-mediated gene transfer experiments have demonstrated an exceptional efficiency of virus uptake and gene expression in a variety of in vivo models. Unfortunately, the efficiency of gene delivery is not accompanied by long-term gene expression. Maximal gene expression peaks during the first week of infection followed by a rapid decline to near baseline levels within several weeks. Data from several laboratories implicate host cellular and humoral immune responses as being responsible for the limited duration of expression and for the inability to successfully readminister a gene using adenovirus vectors. In this study we have examined two strategies which, independently or in combination, circumvent aspects of the host immune response against adenovirus-mediated gene therapy. The first strategy explores induction of immune tolerance in the experimental host as a method to increase the duration of gene expression and as a method to allow readministration of adenovirus expression vectors. Our second strategy is directed at the need to readminister adenoviral vectors to immune competent adult animals. We have demonstrated that a sequential exposure of rats to at least two other adenovirus serotypes does not compromise our ability to successfully administer an Ad5-based CAT expression vector. The characterization of serotype-specific neutralizing response indicates that the construction and use of Ad expression vectors from different serotypes will facilitate a useful adenovirus-based strategy allowing multiple administrations of a target gene.
A retroviral packaging cell line for pseudotype vectors based on glioma‐infiltrating progenitor cells (2007)

This proof-of-principle study shows that primary adult progenitor cells with tumor-infiltrating capacity can be genetically modified to stably produce retroviral LCMV pseudotype vectors. These BM-TIPC may be a useful tool to enhance specificity and efficacy of gene transfer to gliomas in patients.
High-speed waveguide electro-optic polarization modulator (1982)

By careful electrode design we have achieved a 1.7-GHz modulation bandwidth for a Ti:LiNbO(3) integrated-optic TE ? TM mode-converter modulator. Because of the wavelength selectivity of this modulator, it is an attractive device for simultaneously providing multiplexing and signal encoding in future wavelength-multiplexed single-mode light-wave systems.
A Phosphatidylinositol-3 Kinase Binds to Platelet-Derived Growth Factor Receptors through a Specific Receptor Sequence Containing Phosphotyrosine (1991)

Platelet-derived growth factor (PDGF) stimulates autophosphorylation of the PDGF receptor and association of the receptor with several cytoplasmic molecules, including phosphatidylinositol-3 kinase (PI3 kinase). In this study we examined the association of PI3 kinase with immunoprecipitated autophosphorylated PDGF receptor in vitro. The PI3 kinase from cell lysates bound to the wild-type receptor but not to a mutant receptor that had a deletion of the kinase insert region. A protein of an apparent size of 85 kDa bound to the receptor, consistent with previous observations that a protein of this size is associated with PI3 kinase activity. In addition, 110- and 74-kDa proteins bound to the phosphorylated receptor. Dephosphorylated receptors lost the ability to bind PI3 kinase activity as well as the 85-kDa protein. A 20-amino-acid peptide composed of a sequence in the kinase insert region that included one of the autophosphorylation sites of the receptor (tyrosine 719) as well as a nearby tyrosine (Y708) blocked the binding of PI3 kinase to the receptor, but only when the peptide was phosphorylated on tyrosine residues. A scrambled version of the peptide did not block PI3 kinase binding to the receptor even when it was phosphorylated on tyrosine. These tyrosine-phosphorylated peptides did not block binding of phospholipase C-gamma or GTPase-activating protein to the receptor. In separate experiments (receptor blots), soluble radiolabeled receptor bound specifically to an 85-kDa protein present in sodium dodecyl sulfate-polyacrylamide gel electrophoresis-fractionated 3T3 cell lysates that were transferred to nitrocellulose paper. The binding was blocked by the same tyrosine-phosphorylated peptides that prevented binding of PI3 kinase activity to immobilized receptors. These findings show that the PDGF receptor binds directly to an 85-kDa protein and to a PI3 kinase activity through specific sequences in the kinase insert region. The association of a 110-kDa protein with the receptor also involve these sequences, suggesting that this protein may be a subunit of the PI3 kinase. Phosphotyrosine is an essential structure required for the interactions of these proteins with the PDGF receptor.
Recent Trends in Multifunctional Liposomal Nanocarriers for Enhanced Tumor Targeting (2013)

Liposomes are delivery systems that have been used to formulate a vast variety of therapeutic and imaging agents for the past several decades. They have significant advantages over their free forms in terms of pharmacokinetics, sensitivity for cancer diagnosis and therapeutic efficacy. The multifactorial nature of cancer and the complex physiology of the tumor microenvironment require the development of multifunctional nanocarriers. Multifunctional liposomal nanocarriers should combine long blood circulation to improve pharmacokinetics of the loaded agent and selective distribution to the tumor lesion relative to healthy tissues, remote-controlled or tumor stimuli-sensitive extravasation from blood at the tumor's vicinity, internalization motifs to move from tumor bounds and/or tumor intercellular space to the cytoplasm of cancer cells for effective tumor cell killing. This review will focus on current strategies used for cancer detection and therapy using liposomes with special attention to combination therapies.
Serum-free growth of human mammary epithelial cells: rapid clonal growth in defined medium and extended serial passage with pituitary extract. (1984)

A serum-free medium with bovine pituitary extract as the only undefined supplement has been developed for long-term culture of human mammary epithelial cells. This medium supports serial subculture of normal cells for 10-20 passages (1:10 splits) without conditioning or special substrates, and it supports rapid clonal growth with plating efficiencies up to 35%. It consists of an optimized basal nutrient medium, MCDB 170, supplemented with insulin, hydrocortisone, epidermal growth factor, ethanolamine, phosphoethanolamine, and bovine pituitary extract. Replacement of pituitary extract with prostaglandin E1 and ovine prolactin yields a defined medium that supports rapid clonal growth and serial subculture for three or four passages. Cultures initiated in these media from normal reduction mammoplasty tissue remain diploid and maintain normal epithelial morphology, distribution of cell-associated fibronectin, expression of keratin fibrils, and a low level of expression of milk fat globule antigen. Large cell populations can now be generated and stored frozen, permitting multiple experiments over a period of time with cells from a single donor. These media greatly extend the range of experiments that can be performed both conveniently and reproducibly with cultured normal and tumor-derived human mammary epithelial cells.
Effect of Glycosaminoglycans on Thrombin- and Atroxin-Induced Fibrin Assembly and Structure (1989)

This study was performed to quantitate the impact of several glycosaminoglycans (GAG) on fibrin assembly and structure. Gel formation was monitored as the increase in optical density at 633 nm subsequent to thrombin (2 NIH u/ml) or atroxin (0.10 mg/ml) addition to solutions of buffered fibrinogen (1 mg/ml) or plasma. Gel absorbance was measured as a function of wavelength (400 to 800 nm) and gel fiber diameter and mass/length ratio (mu) were calculated. Chondroitin sulfate A (CSA) shortened the lag phase, enhanced the maximal rate of turbidity increase, and increased the final gel turbidity of fibrin gels formed by thrombin or atroxin. CSA (16 mg/ml) increased fiber mu from 1.3 to 3.1 x 10(13) dalton/cm and fiber radius from 6.0 to 8.6 x 10(-6) cm in thrombin-induced gels. Mu increased from 0.7 to 2.7 x 10(13) dalton/cm and fiber radius from 4 to 7.8 x 10(-6) cm for atroxin-induced gels. Above 16 mg/ml, CSA caused fibrinogen precipitation in purified solutions but not in plasma. CSA inhibited thrombin-induced plasma clotting of plasma but effects in atroxin-mediated plasma gels paralleled those seen in purified solutions. Chondroitin sulfate B (CSB)-induced changes in fibrin were similar but slightly less dramatic than those seen with CSA. Mu increased from 0.9 to 2.0 x 10(13) dalton/cm for atroxin-induced fibrin gels and from 0.8 to 2.3 x 10(13) dalton/cm for atroxin-induced gels. Low molecular weight heparin (Mr = 5100) slowed fibrin assembly and reduced fiber size by 50% in thrombin-induced gels. Changes in mu of atroxin-induced gels were much less pronounced (less than 20%).(ABSTRACT TRUNCATED AT 250 WORDS)
Dendritic cells and IFN-alpha-producing cells are two functionally distinct non-B, non-monocytic HLA-DR+ cell subsets in human peripheral blood. (1989)

At least two distinct HLA-DR+ cell subsets lacking surface markers specific for B cells, monocytes or other known lineages are present in human peripheral blood. One subset is non-adherent to plastic, produces interferon-alpha (IFN-alpha) when incubated with cytomegalovirus-infected target cells and provides an accessory function required for natural killer (NK) cell-mediated lysis of such cells. These non-adherent HLA-DR+ cells express the surface antigen recognized by antibody anti-D44 and do not stimulate mixed leucocyte reaction (MLR). The other HLA-DR+ cell subset is loosely adherent to plastic, produces only minimal levels of IFN-alpha when incubated with cytomegalovirus-infected target cells and does not provide the accessory function required for NK cell-mediated lysis of such cells. These HLA-DR+ cells stimulate a strong MLR, do not express D44 antigen and meet the criteria of dendritic cells (DC) morphologically and functionally.
The Hospital Physician Advisor: A Handbook for the Practicing Physician (1991)

Physician Advisor Consultant Services 16040 Lefingzuell Road #68 Whittier, CA 90603 1990, 86 pages, $32.50
The Effect of Beta Blockade on Stress-Induced Cognitive Dysfunction in Adolescents (1991)

Test anxiety is severely disabling to students whose fear of examinations causes cognitive dysfunction that paralyzes their thinking the way stage fright impairs actors ability to act. In studies using subjective evaluations among actors and musicians, beta-blockade relieved stage fright and has been used informally to treat test anxiety in students without objective measures of effectiveness. The Scholastic Aptitude Test (SAT) was chosen as an objective test instrument to confirm the effect of beta-blockade on test anxiety and performance. Thirty-two high school students who had already taken the SAT before enrolling in this study and who had stress-induced cognitive dysfunction on exams were given 40 mg of propranolol one hour before they retook those tests. Mean SAT scores with beta-blockade were 130 points higher than on the initial SAT done before entering the study without medication (p = less than .01). A single dose of propranolol immediately before the SAT permitted improved performance in students prone to cognitive dysfunction due to test anxiety.
Power-aware partitioned cache architectures (2001)

Article Share on Power-aware partitioned cache architectures Authors: S. Kim Dept. of Computer Science and Engineering, Pennsylvania State University, PA Dept. of Computer Science and Engineering, Pennsylvania State University, PAView Profile , N. Vijaykrishnan Dept. of Computer Science and Engineering, Pennsylvania State University, PA Dept. of Computer Science and Engineering, Pennsylvania State University, PAView Profile , M. Kandemir Dept. of Computer Science and Engineering, Pennsylvania State University, PA Dept. of Computer Science and Engineering, Pennsylvania State University, PAView Profile , A. Sivasubramaniam Dept. of Computer Science and Engineering, Pennsylvania State University, PA Dept. of Computer Science and Engineering, Pennsylvania State University, PAView Profile , M. J. Irwin Dept. of Computer Science and Engineering, Pennsylvania State University, PA Dept. of Computer Science and Engineering, Pennsylvania State University, PAView Profile , E. Geethanjali Dept. of Computer Science and Engineering, Pennsylvania State University, PA Dept. of Computer Science and Engineering, Pennsylvania State University, PAView Profile Authors Info & Claims ISLPED '01: Proceedings of the 2001 international symposium on Low power electronics and designAugust 2001Pages 64–67https://doi.org/10.1145/383082.383095Published:06 August 2001Publication History 24citation412DownloadsMetricsTotal Citations24Total Downloads412Last 12 Months5Last 6 weeks0 Get Citation AlertsNew Citation Alert added!This alert has been successfully added and will be sent to:You will be notified whenever a record that you have chosen has been cited.To manage your alert preferences, click on the button below.Manage my AlertsNew Citation Alert!Please log in to your account Save to BinderSave to BinderCreate a New BinderNameCancelCreateExport CitationPublisher SiteGet Access
Sperm plasma membrane breakdown during Drosophila fertilization requires Sneaky, an acrosomal membrane protein (2006)

Fertilization typically involves membrane fusion between sperm and eggs. In Drosophila, however, sperm enter eggs with membranes intact. Consequently, sperm plasma membrane breakdown (PMBD) and subsequent events of sperm activation occur in the egg cytoplasm. We previously proposed that mutations in the sneaky (snky) gene result in male sterility due to failure in PMBD. Here we support this proposal by demonstrating persistence of a plasma membrane protein around the head of snky sperm after entry into the egg. We further show that snky is expressed in testes and encodes a predicted integral membrane protein with multiple transmembrane domains, a DC-STAMP-like domain, and a variant RING finger. Using a transgene that expresses an active Snky-Green fluorescent protein fusion (Snky-GFP), we show that the protein is localized to the acrosome, a membrane-bound vesicle located at the apical tip of sperm. Snky-GFP also allowed us to follow the fate of the protein and the acrosome during fertilization. In many animals, the acrosome is a secretory vesicle with exocytosis essential for sperm penetration through the egg coats. Surprisingly, we find that the Drosophila acrosome is a paternally inherited structure. We provide evidence that the acrosome induces changes in sperm plasma membrane, exclusive of exocytosis and through the action of the acrosomal membrane protein Snky. Existence of testis-expressed Snky-like genes in many animals, including humans, suggests conserved protein function. We relate the characteristics of Drosophila Snky, acrosome function and sperm PMBD to membrane fusion events that occur in other systems.
Proteomic studies support the use of multi‐product immunoassays to monitor host cell protein impurities (2005)

In the biopharmaceutical industry, recombinant protein drugs are commonly produced in Chinese hamster ovary (CHO) cells. During the development process, removal of CHO cell-derived proteins from the biopharmaceutical product is monitored using multi-product immunoassays. Such immunoassays are developed by raising antibodies to a single CHO cell protein preparation. However, these assays are utilized to monitor CHO cell protein impurities during the recovery of products from different CHO cell lines. To address whether underlying differences between CHO cell lines result in sufficient protein expression changes to exclude the suitability of multi-product immunoassays, a comparative proteomics study of three independently generated CHO cell lines was performed. Statistical analysis of over 1000 proteins resolved by 2-D PAGE demonstrated that the protein expression profiles of three different CHO cell lines exhibit very few differences in protein expression. Only 11 qualitative changes in protein expression and 26 quantitative changes greater than two-fold were observed. Identification of protein spots by mass spectrometry revealed that many of the observed changes were due to post-translational modifications rather than expression of novel proteins in each cell line. These results suggest that multi-product immunoassays are suitable for monitoring host cell proteins in biopharmaceuticals produced in different CHO cell lines.
The molecular biology of bovine immunodeficiency virus: a comparison with other lentiviruses (2004)

Bovine immunodeficiency virus (BIV) was first isolated in 1969 from a cow, R-29, with a wasting syndrome. The virus isolated induced the formation of syncytia in cell cultures and was structurally similar to maedi-visna virus. Twenty years later, it was demonstrated that the bovine R-29 isolate was indeed a lentivirus with striking similarity to the human immunodeficiency virus. Like other lentiviruses, BIV has a complex genomic structure characterized by the presence of several regulatory/accessory genes that encode proteins, some of which are involved in the regulation of virus gene expression. This manuscript aims to review biological and, more particularly, molecular aspects of BIV, with emphasis on regulatory/accessory viral genes/proteins, in comparison with those of other lentiviruses.