gebhart/patrepeval huggingface dataset:
RNAi screen of the protein kinome identifies checkpoint kinase 1 (CHK1) as a therapeutic target in neuroblastoma (2011)

Neuroblastoma is a childhood cancer that is often fatal despite intense multimodality therapy. In an effort to identify therapeutic targets for this disease, we performed a comprehensive loss-of-function screen of the protein kinome. Thirty kinases showed significant cellular cytotoxicity when depleted, with loss of the cell cycle checkpoint kinase 1 (CHK1/CHEK1) being the most potent. CHK1 mRNA expression was higher in MYC-Neuroblastoma-related (MYCN)-amplified (P < 0.0001) and high-risk (P = 0.03) tumors. Western blotting revealed that CHK1 was constitutively phosphorylated at the ataxia telangiectasia response kinase target site Ser345 and the autophosphorylation site Ser296 in neuroblastoma cell lines. This pattern was also seen in six of eight high-risk primary tumors but not in control nonneuroblastoma cell lines or in seven of eight low-risk primary tumors. Neuroblastoma cells were sensitive to the two CHK1 inhibitors SB21807 and TCS2312, with median IC(50) values of 564 nM and 548 nM, respectively. In contrast, the control lines had high micromolar IC(50) values, indicating a strong correlation between CHK1 phosphorylation and CHK1 inhibitor sensitivity (P = 0.0004). Furthermore, cell cycle analysis revealed that CHK1 inhibition in neuroblastoma cells caused apoptosis during S-phase, consistent with its role in replication fork progression. CHK1 inhibitor sensitivity correlated with total MYC(N) protein levels, and inducing MYCN in retinal pigmented epithelial cells resulted in CHK1 phosphorylation, which caused growth inhibition when inhibited. These data show the power of a functional RNAi screen to identify tractable therapeutical targets in neuroblastoma and support CHK1 inhibition strategies in this disease.
Preventing Adverse Drug Events in Hospitalized Patients (1994)

Prospective surveillance of computer-based medical records for known drug allergies and appropriate drug administration rates can reduce the number of type B ADEs. Early ADE detection and notification of physicians permit drug and dosage changes that reduce the progression of mild and moderate ADEs to more severe conditions.
(NZW x BXSB)F1 mouse. A new animal model of idiopathic thrombocytopenic purpura. (1988)

A decrease in thrombocyte count was observed in (NZW x BXSB)F1 (W/B F1) mice at the age of greater than 5 mo, whereas megakaryocyte counts were found to increase in such mice. FACS analyses revealed the presence of both platelet-associated antibodies (PAA) and circulating antiplatelet antibodies. There is a correlation between the presence of these antibodies and the degree of thrombocytopenia. The transplantation of normal bone marrow cells from BALB/c nu/nu mice to W/B F1 mice was found to have preventative and curative effects on thrombocytopenia; the mice showed normal platelet counts and no evidence of circulating antiplatelet antibodies. These results indicate that thrombocytopenia in W/B F1 mice is due to the presence of antibodies to platelets. We therefore think that W/B F1 mice serve as a useful animal model of idiopathic thrombocytopenic purpura (ITP) not only for elucidating the mechanism of the development of antiplatelet antibodies, but also for characterizing autoantibodies to platelets.
Chemical Vapor Deposition of Three Aminosilanes on Silicon Dioxide: Surface Characterization, Stability, Effects of Silane Concentration, and Cyanine Dye Adsorption (2010)

Covalently bonded monolayers of two monofunctional aminosilanes (3-aminopropyldimethylethoxysilane, APDMES, and 3-aminopropyldiisopropylethoxysilane, APDIPES) and one trifunctional aminosilane (3-aminopropyltriethoxysilane, APTES) have been deposited on dehydrated silicon substrates by chemical vapor deposition (CVD) at 150 °C and low pressure (a few Torr) using reproducible equipment. Standard surface analytical techniques such as x-ray photoelectron spectroscopy (XPS), contact angle goniometry, spectroscopic ellipsometry, atomic force microscopy, and time-of-flight secondary ion mass spectroscopy (ToF-SIMS) have been employed to characterize the resulting films. These methods indicate that essentially constant surface coverages are obtained over a wide range of gas phase concentrations of the aminosilanes. XPS data further indicate that the N1s/Si2p ratio is higher after CVD with the trifunctional silane (APTES) compared to the monofunctional ones, with a higher N1s/Si2p ratio for APDMES compared to that for APDIPES. AFM images show an average surface roughness of 0.12- 0.15 nm among all three aminosilane films. Stability tests indicate that APDIPES films retain most of their integrity at pH 10 for several hours and are more stable than APTES or APDMES layers. The films also showed good stability against storage in the laboratory. ToF-SIMS of these samples showed expected peaks, such as CN(-), as well as CNO(-), which may arise from an interaction between monolayer amine groups and silanols. Optical absorption measurements on adsorbed cyanine dye at the surface of the aminosilane films show the formation of dimer aggregates on the surface. This is further supported by ellipsometry measurements. The concentration of dye on each surface appears to be consistent with the density of the amines.
Tissue-specific cytokine release from human extra-placental membranes stimulated by lipopolysaccharide in a two-compartment tissue culture system (2009)

The amnion and choriodecidua exhibited distinct patterns of response to LPS with evidence of inflammatory signaling across the layers of the gestational membranes. These results suggest a complicated network of signaling within the gestational membranes, in which cytokine- and tissue-specific responses to inflammatory stimulation may have important implications for maintaining pregnancy in the challenge of microbial invasion of the uterine compartment.
Secretory products of macrophages. (1987)

Numbers refer to selected reports of the indicated action. t NO, reportedly not observed. -, No observations reported, to my knowledge.
Knockout of maternal CD163 protects fetuses from infection with porcine reproductive and respiratory syndrome virus (PRRSV) (2017)

After infection of the porcine dam at about 90 days of gestation, porcine reproductive and respiratory syndrome virus (PRRSV) crosses the placenta and begins to infect fetuses. Outcomes of include abortion, fetal death and respiratory disease in newborn piglets. CD163 is the receptor for the virus. In this study, CD163-positive fetuses, recovered between 109 days of gestation or 20 days after maternal infection, were completely protected from PRRSV in dams possessing a complete knockout of the CD163 receptor. The results demonstrate a practical means to eliminate PRRSV-associated reproductive disease, a major source of economic hardship to agriculture.
Protein-loaded microspheres prepared by sequential adsorption of dextran sulphate and protamine on melamine formaldehyde core (2009)

Polyelectrolyte multilayer microspheres were fabricated by layer-by-layer self-assembly of a dextran sulphate and a protamine on melamine formaldehyde cores, followed by the partial decomposition of the core. Effects of pH on the encapsulation of proteins and enzymes with different physico-chemical properties (insulin, aprotinin, peroxidase, glucose oxidase (GOD), catalase (Cat)) in the prepared microspheres were then studied. This method of protein encapsulation demonstrated a high loading capacity and efficiency. The protein incorporation and release was regulated by the pH of the solution. Encapsulated enzymes retained a high specific activity depending on the amount of protein incorporated. Bienzyme system GOD/Cat immobilized in the microspheres was suitable for the glucose content assay.
PLASTIC REPAIR OF CONJUNCTIVAL DEFECTS WITH FETAL MEMBRANES (1940)

Conjunctiva has to be replaced when a large enough area is destroyed so as to cause a high degree of symblepharon or entropion or when the socket is too small to carry a prosthesis. Most common causes of its destruction are chemical and thermic burns and trachoma. Rare causes are malignant tumor, pemphigus, tuberculous ulcer, mechanical injury and amyloid and hyaline degeneration. Conjunctiva can be replaced primarily immediately after its loss. This has to be done after the removal of the necrotic conjunctiva. Denig<sup>1</sup>introduced the method by which necrotic conjunctiva is removed immediately after the chemical burn and the defect is covered with mucous membrane. However, the conjunctiva usually has to be replaced when symblepharon has already developed. Veasey<sup>1a</sup>revised the materials which are or have been used to cover the defects of the conjunctiva. These consist of grafts of conjunctiva, of the inner surface of the
A novel 205-kilodalton testis-specific serine/threonine protein kinase associated with microtubules of the spermatid manchette. (1993)

To identify proteins which interact with and potentially modulate the function of microtubules during spermatogenesis, we prepared a total testis MAP (microtubule-associated protein) antiserum and used it to isolate cDNA clones from a mouse testis cDNA expression library. Antibodies affinity purified by using one expression clone recognized a 205-kDa protein, termed MAST205, which colocalizes with the spermatid manchette. Sequencing of full-length cDNA clones encoding MAST205 revealed it to be a novel serine/threonine kinase with a catalytic domain related to those of the A and C families. The testis-specific MAST205 RNA increases in abundance during prepuberal testis development, peaking at the spermatid stage. The microtubule-binding region of MAST205 occupies a central region of the molecule including the kinase domain and sequences C terminal to this domain. Binding of MAST205 to microtubules requires interaction with other MAPs, since it does not bind to MAP-free tubulin. A 75-kDa protein associated with immunoprecipitates of MAST205 from extracts of both whole testis and testis microtubules becomes phosphorylated in in vitro kinase assays. This 75-kDa substrate of the MAST205 kinase may form part of the MAST205 protein complex which binds microtubules. The MAST205 protein complex may function to link the signal transduction pathway with the organization of manchette microtubules.
Pharmacological Management to Reduce Exacerbations in Adults With Asthma (2004)

Inhaled corticosteroids are the single most effective therapy for adult patients with asthma. However, for those unable or unwilling to take corticosteroids, the use of leukotriene modifiers/receptor agonists appears reasonable. Long-acting beta2 agonists may be added to corticosteroids for those who remain symptomatic despite low-dose steroid therapy. Anti-IgE therapy may be considered as adjunctive therapy for young adults with asthma who have clear evidence of allergies and elevated serum IgE levels.
Empowering Targeted Therapy: Lessons from Rituximab (2004)

Rituximab, a monoclonal antibody directed against the B cell-specific protein CD20, has revolutionized lymphoma treatment by providing a highly effective form of therapy with relatively mild toxic side effects. Effective as a single agent against some forms of B cell lymphoma, rituximab also has a chemosensitizing effect, enhancing the efficacy of chemotherapy against other forms of the disease. Although the mechanisms whereby rituximab achieves its effects remain incompletely understood, these seem to involve at least three distinct phenomena: (i) antibody-dependent cell-mediated cytotoxicity, (ii) complement-mediated cell lysis, and (iii) stimulation of apoptosis in target cells. The latter occurs through interaction of complexes of rituximab and CD20 in lipid rafts, with elements of a signaling pathway involving Src kinases. Effector molecules trigger various gene expression events, leading to sensitization of malignant cells to proapoptotic stimuli. Lessons learned from the research on rituximab may be applied to the rational development of antibody-based therapies against other forms of cancer.
Retinoids in the treatment of skin aging: an overview of clinical efficacy and safety (2006)

Aging of skin is an intricate biological process consisting of two types. While intrinsic or chronological aging is an inevitable process, photoaging involves the premature aging of skin occurring due to cumulative exposure to ultraviolet radiation. Chronological and photoaging both have clinically differentiable manifestations. Various natural and synthetic retinoids have been explored for the treatment of aging and many of them have shown histological and clinical improvement, but most of the studies have been carried out in patients presenting with photoaged skin. Amongst the retinoids, tretinoin possibly is the most potent and certainly the most widely investigated retinoid for photoaging therapy. Although retinoids show promise in the treatment of skin aging, irritant reactions such as burning, scaling or dermatitis associated with retinoid therapy limit their acceptance by patients. This problem is more prominent with tretinoin and tazarotene whereas other retinoids mainly represented by retinaldehyde and retinol are considerably less irritating. In order to minimize these side effects, various novel drug delivery systems have been developed. In particular, nanoparticles have shown a good potential in improving the stability, tolerability and efficacy ofretinoids like tretinoin and retinol. However, more elaborate clinical studies are required to confirm their advantage in the delivery of topical retinoids.
Prasugrel: A Novel Thienopyridine Antiplatelet Agent. A Review of Preclinical and Clinical Studies and the Mechanistic Basis for Its Distinct Antiplatelet Profile (2007)

Prasugrel (CS-747, LY640315) is a novel member of the thienopyridine class of oral antiplatelet agents that includes ticlopidine and clopidogrel. Like other thienopyridines, prasugrel is a prodrug that is inactive in vitro. Prasugrel's distinct chemical structure permits efficient conversion to its active metabolite with a less rigorous dependence on specific cytochrome P-450 enzymes. Prasugrel is rapidly converted in vivo to an active metabolite (R-138727) that binds specifically and irreversibly to the platelet P2Y 12 purinergic receptor inhibiting ADP-mediated platelet activation and aggregation. Preclinical studies indicated that prasugrel is approximately 10- and 100-fold more potent at inhibiting ex vivo platelet aggregation and in vivo thrombus formation than clopidogrel and ticlopidine, respectively. Early clinical data in healthy subjects confirmed the greater platelet inhibition and consistency with prasugrel compared to clopidogrel. While the active metabolites of prasugrel and clopidogrel resulted in similar levels of platelet inhibition in vitro, the amount of each active metabolite generated in vivo was quite different-prasugrel (60 mg) resulting in an approximately 12-fold greater exposure to its active metabolite compared with clopidogrel (300 mg). This observation provides a mechanistic basis for the faster, greater, and more consistent inhibition of platelet aggregation observed with prasugrel. Clinical studies in patients with cardiovascular disease confirmed the potent antiplatelet effect of prasugrel compared with clopidogrel. Collectively, these phase 1/1b studies and a phase 2 study (JUMBO-TIMI 26) aided in dose selection for the recently completed phase 3 trial (TRITON-TIMI 38) in patients with acute coronary syndrome undergoing percutaneous coronary intervention.
A note on "On single-scanline camera calibration" [and reply] (1995)

In this correspondence, the single-scanline camera model proposed in the original paper (R. Horaud, R. Mohr and B. Lorecki, ibid., vol. 8, no. 1, p. 71-5, 1993) is modified to include a lens distortion coefficient. The authors say that, by this modification, the calibration approach presented will become more practical. The original authors accept that the improvement is sensible but say that the argument is not rigorous and suggest better approaches to some aspects.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Measurement of C-reactive protein and the erythrocyte sedimentation rate in general practice (1995)

In clinical situations with suspected inflammatory diseases, the CRP test appears often to yield more useful results than the ESR. The NycoCard:::CRP test is suitable for use in general practice.
Antiestrogen Action in the Medial Basal Hypothalamus and Pituitary of Immature Female Rats: Insights Concerning Relationships among Estrogen, Dopamine, and Prolactin* (1986)

We have examined the effects of nonsteroidal antiestrogens (AEs) and estradiol (E) on dopamine (DA) levels and turnover rates in the medial basal hypothalamus (MBH) and on serum and pituitary PRL to gain insight into DA-PRL-E/AE interrelationships. In 21-day-old female rats, E was found to increase MBH DA levels and turnover and serum PRL concentrations in a time- and concentration-dependent manner. Changes were observed by 1 day, and after 3 days of E treatment (1 microgram/day), MBH DA levels increased 2-fold (to 1300 pg/mg tissue), and DA turnover rates increased 5-fold (to 1170 pg/mg tissue . h). The AEs tamoxifen, monohydroxytamoxifen, CI628, and LY117018 (50 micrograms/day for 3 days) weakly stimulated uterine weight gain and significantly suppressed the uterotropic action of E. The AEs LY117018, monohydroxytamoxifen, CI628, and tamoxifen competed with E for binding to the MBH estrogen receptor and displayed relative binding affinities of 190%, 185%, 6.7%, and 1.4%, with E set at 100%; these affinities are similar to those found for uterine estrogen receptors. The AEs increased DA turnover rates only 2-fold, and they antagonized the E-induced 5-fold increase in DA turnover rates very successfully. In animals treated with bromocriptine, E and AE failed to increase the low serum PRL levels, yet they evoked significant (approximately 2-fold) increases in DA turnover rates and nearly 2-fold increases in MBH DA content. Hence, a part of the actions of E and AE on MBH DA appears to be exerted independently of changes in circulating PRL and may occur by direct action of these compounds on the estrogen receptor system present in the MBH. In addition, these studies reveal that AEs behave as partial estrogen agonists/antagonists in terms of their effects on MBH DA turnover.
Are cross-species measures of sensorimotor gating useful for the discovery of procognitive cotreatments for schizophrenia? (2006)

Prepulse inhibition of startle (PPI), a measure of sensorimotor gating used to identify antipsychotics, is reduced in schizophrenia patients and in rodents treated with dopamine agonists or glutamate antagonists. The National Institute of Mental Health (NIMH)-funded Measurement And Treatment Research to Improve Cognition in Schizophrenia (MATRICS) program has initiated a new era in the development of procognitive cotreatments in schizophrenia, independently of treating positive symptoms. Although PPI is not a cognitive process per se, such abnormalities in attention may be predictive of or lead to cognitive deficits. Since first-generation antipsychotics block PPI deficits induced by dopamine agonists, this model cannot identify cognitive enhancers for use as cotreatments with antipsychotics. PPI deficits caused by glutamate antagonists, like the exacerbation of symptoms they produce in patients, are insensitive to dopamine antagonists, but reduced by clozapine. Similarly, both PPI and cognitive deficits in schizophrenia patients are insensitive to first-generation antipsychotics, but attenuated by clozapine. Hence, treatment-induced reversals of glutamate antagonist effects on PPI may provide animal and human models to identify treatments of cognitive deficits in patients already treated with existing antipsychotics.
Purification and characterization of recombinant human thyrotropin (TSH) isoforms produced by Chinese hamster ovary cells: the role of sialylation and sulfation in TSH bioactivity (1993)

The biological significance of glycosylation variants of pituitary glycoprotein hormones remains controversial because of the indirect methods usually employed to determine carbohydrate composition or structure as well as the use of unreliable biological/immunological ratio to determine bioactivity. We have previously characterized recombinant human TSH (rhTSH) secreted by Chinese hamster ovary cells attached to microcarrier beads in a large scale bioreactor after stable transfection of hCG alpha and hTSH beta minigenes. In the present study rhTSH has been used as a model to determine structure-function relationships of different isoforms of glycoprotein hormones. We have now produced greater than 200 mg rhTSH using a hollow fiber bioreactor. The highly purified rhTSH produced in the hollow fiber bioreactor (rhTSH-N) as well as rhTSH commercially produced in a large scale bioreactor (rhTSH-G) were quantitated by immunoassays, receptor binding assay, and amino acid analysis and further characterized by a variety of physico-biochemical methods, including chromatofocusing and carbohydrate analysis. rhTSH-G, rhTSH-N, as well as pituitary human TSH (phTSH) have been separated by chromatofocusing on a Mono P column into several isoforms with different pI values. Compositional analysis of the fractions showed higher sialic acid content in the more acidic rhTSH-G fractions. phTSH acidic isoforms showed higher total sulfate and sialic acid contents than the more basic fractions. The bioactivities of various TSH isoforms based on rigorous quantitation of mass by amino acid analysis determined in three different FRTL-5 cell bioassays showed that the more basic and less sialylated fractions of rhTSH-G were more active than the more acidic fractions. In contrast to the in vitro data, highly sialylated and acidic rhTSH-G isoforms showed longer plasma half-lives and higher in vivo bioactivity than the basic forms. These results indicate that secreted rhTSH, similar to intrapituitary phTSH, exists as a mixture of charge isoforms that are related at least in part to the degree of sialylation. The degree of sialylation, highly dependent on the bioreactor production conditions, appears to be the major factor affecting the charge heterogeneity, MCR, and bioactivity of rhTSH.
Molecular and Biochemical Aspects of the PD-1 Checkpoint Pathway (2016)

The PD-1 pathway plays an essential role in maintaining immunologic self-tolerance. However, cancers can subvert the role of this pathway and blind the immune system to their presence. The molecular details of the pathway are discussed.
Expression of Fcγr1 (CD64) on Polymorphonuclear Leucocytes during Progression to Acquired Immunodeficiency Syndrome in Perinatally Human Immunodeficiency Virus‐Infected Children (2000)

CD64, the high-affinity receptor in the family of FCgamma receptors, is not expressed constitutively in polymorphonuclear leucocytes (PMN). CD64 is expressed by PMNs in the late stages of human immunodeficiency virus (HIV) infection in adults. We followed the expression of CD64 on PMNs in perinatally HIV-infected children during disease progression. Peripheral blood leucocytes (PBL) from 45 perinatally HIV-infected paediatric patients and 13 healthy age-matched controls were analysed using cytofluorimetry after reaction with a fluorophore-labelled monoclonal antibody (MoAb) to CD64. In parallel, we examined the expression of CD32, CD16, CD11b and the human neutrophil-specific BH2-Ag using fluorophore-labelled MoAbs. We found that up to 79.5% of the PMNs in children in class C3 express CD64. Most importantly, we observed a continuous and significant increase in the appearance of CD64+ PMNs as a function of CDC classification (P < 0.001) but no changes in the expression of CD32, CD16, CD11b and BH2-Ag. This suggests that following the expression of CD64 on PMNs can be useful in evaluating the progression of HIV infection in perinatally HIV-infected children.