gebhart/patrepeval huggingface dataset:
In vivo Transfer of a Thrombopoietic Factor. (1961)

Injection of plasma from rabbit donors made thrombocytopenic by Myleran or anti-platelet serum into 15 unstressed rabbit recipients raised platelet counts to 166% of control levels 4 days following transfer. These results are highly significant (p<0.001) when compared to the mild thrombocytopenia produced in 15 rabbits receiving plasma from normal donors or when compared to the daily variations in platelet levels of 9 uninjected rabbits. The response of normal and splenectomized recipients was similar. These results suggest that plasma contains stimulatory and inhibitory factors which regulate platelet levels.
Cytoplasmic DNA innate immune pathways (2011)

The innate immune system is responsible for detecting microbial invasion of the cell and for stimulating host defense countermeasures. These anti-pathogen procedures include the transcriptional activation of powerful antiviral genes such as the type I interferons (IFNs) or the triggering of inflammatory responses through interleukin-1 (IL-1) production. Over the past decade, key cellular sensors responsible for triggering innate immune signaling pathways and host defense have started to be resolved and include the Toll-like receptor (TLR), RIG-I-like helicase, and the cytoplasmic nucleotide-binding oligermerization domain-like receptor families. These sensors recognize non-self pathogen-associated molecular patterns such as microbial lipopolysaccharides and nucleic acids. For example, TLR9 has evolved to detect CpG DNA commonly found in bacteria and viruses and to initiate the production of IFN and other cytokines. In contrast, AIM2 (absent in melanoma 2) has been shown to be essential for mediating inflammatory responses involving IL-1β following the sensing of microbial DNA. Recently, a molecule referred to as STING (stimulator of IFN genes) was demonstrated as being vital for recognizing cytoplasmic DNA and for activating the production of innate immune genes in response to a variety of DNA pathogens and even certain RNA viruses. Comprehending the mechanisms of intracellular DNA-mediated innate immune signaling may lead to the design of new adjuvant concepts that will facilitate vaccine development and may provide important information into the origins of autoimmune disease.
An Immunogenic Polysaccharide-Protein Conjugate (1970)

Summary A galactomannan isolated from the dermatophyte Epidermophyton floccosum was covalently linked to bovine γ, globulin by reaction with 2, 4,6-trichloro-s-triazine (cyanuric chloride). This polysaccharide-protein conjugate induced humoral antibody formation in the rabbit. The antibodies gave precipitin reactions with the polysaccharide, with the conjugate and with the 7 globulin. Absorption of the antiserum with γ globulin left. a preparation of antibodies that were specific for the polysaccharide. Hyperimmunized rabbits also developed cutaneous hypersensitivity to the polysaccharide.
Amino Ketones. III.* β-Tetrahydroisoquinolino Ketones and Derivatives. Reaction with Grignard Reagents1 (1944)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAmino Ketones. III.* β-Tetrahydroisoquinolino Ketones and Derivatives. Reaction with Grignard Reagents1Norman H. Cromwell and John S. BurchCite this: J. Am. Chem. Soc. 1944, 66, 6, 872–873Publication Date (Print):June 1, 1944Publication History Published online1 May 2002Published inissue 1 June 1944https://pubs.acs.org/doi/10.1021/ja01234a007https://doi.org/10.1021/ja01234a007research-articleACS PublicationsRequest reuse permissionsArticle Views63Altmetric-Citations5LEARN 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
Transmission Resonances on Metallic Gratings with Very Narrow Slits (1999)

Transmission metallic gratings with very narrow and deep enough slits can exhibit transmission resonances for wavelengths larger than the period of the grating. By using a transfer matrix formalism and a quasianalytical model based on a modal expansion, we show that there are two possible ways of transferring light from the upper surface to the lower one: by the excitation of coupled surface plasmon polaritons on both surfaces of the metallic grating or by the coupling of incident plane waves with waveguide resonances located in the slits. Both mechanisms can lead to almost perfect transmittance for those particular resonances.
Identification of Brain-Derived Neurotrophic Factor as a Novel Functional Protein in Hepatocellular Carcinoma (2005)

This study aims to identify a novel molecule that may contribute to hepatocarcinogenesis in a rat orthotopic hepatocellular carcinoma model. The hepatocellular carcinoma model was generated by injection of tumor cells into the left lobe of the liver. Proteomic approaches, including ProteinChip and two-dimensional electrophoresis, were used to identify proteins from serially collected rat serum samples. By both ProteinChip and two-dimensional electrophoresis techniques, the level of a 27-kDa protein was found to be augmented in serum samples during tumor development, decreased after left lobectomy, and reincreased at the time of tumor recurrence. The protein was identified to be brain-derived neurotrophic factor (BDNF). By using specific primers and monoclonal antibody, the expression pattern of BDNF was confirmed in tumor tissue but not in the adjacent nontumorous liver tissue. In addition, the truncated isoform of BDNF receptor-tyrosine protein kinase receptor B was only found in tumor tissue. An in vitro study showed that exogenous BDNF could induce tumor cell proliferation predominantly in relatively small numbers of inoculated cells. Administration of BDNF to tumor cell lines induced significantly increased expression of heat shock protein 90 (Hsp90) and cyclin D1, and blocking the activity of Hsp90 could reverse the up-regulation of cyclin D1 induced by BDNF. The present study revealed that BDNF and its receptor were uniquely expressed in tumor tissue and cell lines of hepatocellular carcimona but not in nontumorous liver tissue and normal cell line. BDNF could stimulate tumor cell proliferation in a Hsp90-dependent manner.
Fatty acid synthetase and its mRNA are induced by progestins in breast cancer cells. (1987)

The growth of hormone-dependent breast cancer cell lines (MCF7 and T47D) is inhibited in vitro by progestins which also induce several proteins. We have cloned cDNA sequences corresponding to one of them, a 250-kDa protein, and have shown that the corresponding mRNA is also rapidly induced by progestins (Chalbos D., Westley B., May F.E.B., Alibert C., and Rochefort H. (1986) Nucleic Acids Res. 14, 965-982). We show here that the 250-kDa protein is very similar, if not identical, to fatty acid synthetase: fatty acid synthetase is regulated to the same extent by progestins, the 250-kDa protein is specifically immunoprecipitated by antibodies to fatty acid synthetase, and fatty acid synthetase covalently labeled by [14C]pantothenate is immunoprecipitated by antibodies to the 250-kDa protein. The induction of fatty acid synthetase by progestin in cancer cells thus provides another model for studying the mechanism regulating steroid transcription in human cells. Since fatty acid synthetase regulation by progestins appears to be the opposite in cancer and normal mammary cells, this observation may also be a clue for understanding the role of progestins in mammary carcinogenesis.
Overexpression of cdk4/cyclin D1, a possible mediator of apoptosis and an indicator of prognosis in human primary lung carcinoma (2004)

The relation between expression of cell cycle-regulator molecules and apoptosis was examined in surgical specimens and cultured human lung carcinoma cell lines. Immunohistochemical analysis for 133 cases revealed 2 types of staining pattern. The first group consisted of 95 cases (71.4%) characterized by apoptotic cells showing intensely positive staining for cdk4 and cyclin D1 but negative for other proteins (type A). In the second group (type B), comprising 38 cases (28.6%), apoptotic cells exhibited intense positive staining for any cyclins and cdks. Most of the latter cases had lost expression of Rb protein. When tumor cells retrieved from paraffin-embedded tissue were examined by flow cytometry, higher proportions of cells expressing only cdk4 or cyclin D1 in type A cases and of cells expressing any cyclin or cdk in type B cases showed a subdiploid DNA content. In survival analysis using the LI of apoptotic cells and cyclin/cdk-positive cells, the high-apoptosis/high-cyclin D1 group showed the poorest prognosis. Furthermore, forced overexpression of only cdk4 or cyclin D1 induced apoptosis in cultured cells with normal Rb protein, whereas overexpression of any cyclin or cdk induced apoptosis in cells defective for Rb protein. In conclusion, upregulation of cdk4/cyclin D1 may be a primary and critical factor in induction of apoptosis in human lung carcinomas in vivo. Moreover, inactivation of Rb protein renders cells more prone to apoptosis by abnormal expression of any cell-cycle protein.
The blood compatibility of chitosan and N‐acylchitosans (1985)

A segment of silk polyfilament suture [No. 2-0(USP)], ca. 10 cm long, was coated with a thin membrane (2-6 micron) of chitosan, N-acetylchitosan, or N-hexanoylchitosan. The suture was directly inserted into the lumen of dog's peripheral veins. The in vivo blood compatibility of these membranes was macroscopically determined from the blood coagulum formed on the membrane surface at 2 h. An intense thick blood coagulum formed on the chitosan membrane surface and a thin blood coagulum formed on N-acetylchitosan membrane surface, but no blood coagulum formed on N-hexanoylchitosan membrane surface.
Aggressiveness and hyperactive behaviour as related to adrenaline excretion (1989)

The central question concerns the relationship between aspects of behaviour and physiological reactions. Measures of sympathetic‐adrenal activity in terms of adrenaline excretion in a normal and a stressful situation as well as teacher ratings of behaviour were analysed for a representative group of 86 boys aged 13. Adrenaline excretion was in both situations significantly negatively related to ratings of aggressiveness, motor restlessness, and concentration difficulties and also to the sum of the latter two, used as an indicator of hyperactive behaviour. The association between hyperactive behaviour and adrenaline excretion persisted in the stressful situation when aggressiveness was controlled, whereas there was no significant relationship between aggressiveness and adrenaline output when hyperactive behaviour was controlled. Furthermore, hyperactive boys differed significantly from non‐hyperactive boys in displaying lower adrenaline excretion in both situations. The results are discussed in terms of low sympathetic‐adrenal reactivity to external demands as a risk factor and as a possible indicator of vulnerability for social and/or pervasive conduct disturbances.
Phenotype variation and newcomers in ion channel disorders (1997)

Ion channels are part of a large family of macromolecules whose functions include the control and maintenance of electrical potential across cell membranes, secretion and signal transduction. Close inspection of the physiological processes involved in channel function and the secondary structure of various ion channels has served as a basis for subdividing ion channels into a number of superfamilies. The voltage-gated ion channels are one of these superfamilies. Recent work has shown that mutations in various ion channel genes are responsible for a number of neuromuscular and neurological disorders. Correlation of the various mutations with the clinical phenotype is providing us with insight into the pathophysiology of these channel proteins. Interestingly, different mutations within the same gene may cause quite distinct clinical disorders, while mutations in different channel genes may result in very similar phenotypes (genetic heterogeneity). Examples of phenotypic variation and genetic heterogeneity are presented in the context of the periodic paralytic disorders of skeletal muscle, episodic ataxia, migraine, long QT syndrome and paroxysmal dyskinesia. Some of these disorders are known to be caused by mutations in ion channel genes, while in the episodic movement disorders, ion channel genes are considered excellent candidate genes.
Prediction of Node-Negative Breast Cancer Outcome by Histologic Grading and S-Phase Analysis by Flow Cytometry (2001)

Histologic evaluation and reporting of invasive breast cancer has effectively used Nottingham combined histologic grade (NCHG). This approach to predict outcome in invasive breast cancer has not been tested in multicenter cooperative trials. Histologic slides from selected breast cancer cases entered on node-negative Eastern Cooperative Oncology Group trials were assigned grades. Two pathologists evaluated cases for NCHG defined from differentiation, mitotic index, and nuclear grade. The study population consisted of separate samples from low- and high-risk strata, where low risk was estrogen receptor positive with a tumor size of less than 3 cm and high risk was estrogen receptor negative or tumor size greater than or equal to 3 cm. The rate of agreement was generally good, with 80% of cases classified the same for mitotic count and 76% of the cases classified the same for combined grade. There were no cases disagreeing from the lowest to the highest of the three categories. The median follow-up is 11.6 years, but for analysis of survival, this was truncated at 5 years. Mitotic index and combined grade as assessed by both pathologists showed significant associations with survival. High combined histologic grade was predictive for response to cyclophosphamide/methotrexate/5-fluorouracil (CMF) with survival differences at 5 years of 30% in the treated high-grade patients over the untreated patients. Overall, it is clear that pathologists can have close agreement in assignment of combined histologic grades, with highly significant prediction in univariate and borderline significance in multivariate analysis in prognostication of time to recurrence as well as survival. Thus, stratification used in these trials was highly prognostic as hoped, leaving a role for histologic grading in these relatively large tumors, more powerful than S-phase analysis in this series. In the subgroups of high-risk patients randomized between CMF and observation, there was a suggestion that the high-combined-grade group was predictive of treatment efficacy. We conclude that a combined histologic grade with defined criteria may be reliably assigned by practiced pathologists using readily available criteria, and that the measure may be of use in prognostication and prediction of therapeutic responsiveness when done in a technically ideal fashion.
Obstructive sleep apnea: a stand-alone risk factor for chronic kidney disease (2011)

High prevalence of CKD is present in severe OSA patients without hypertension or diabetes. Significantly positive correlations were found between severity of OSA and renal function impairment.
Monoclonal antibodies of three different immunoglobulin G isotypes produced by immunization with a synthetic peptide or native protein protect mice against challenge with Plasmodium yoelii sporozoites (1993)

Passive transfer of monoclonal antibodies (MAbs) against malaria circumsporozoite (CS) proteins protects animals against malaria. Active immunization with synthetic or recombinant peptides induces a level of polyclonal antibodies to sporozoites comparable to those found after passive immunization but does not provide comparable protection. In the Plasmodium yoelii system, synthetic or recombinant peptide-induced antibodies have never been shown to protect. The current studies were designed to determine whether immunogen structure (native protein versus synthetic peptide) or immunoglobulin G (IgG) subclass of antibodies was responsible for the absolute differences between protective, passively transferred MAbs and nonprotective, actively induced polyclonal antibodies. In this study we produced two MAbs, QGP-S1 (IgG1) and QGP-S2 (IgG2b), by immunization with a synthetic peptide based on the P. yoelii CS major repeat, (QGPGAP)4, conjugated to keyhole limpet hemocyanin. These MAbs were compared tp NYS1 (IgG3), an anti-CS protein MAb previously produced by immunization with irradiated P. yoelii sporozoites, which recognizes (QGP GAP)2. QGP-S1 and QGP-S2 passively transferred protection. However, when compared with NYS1, there was a hierarchy of protection, NYS1 > QGP-S1 > QGP-S2. There was no correlation between antibody level at challenge as determined by immunofluorescent antibody test against sporozoites or enzyme-linked immunosorbent assay against (QGPGAP)2 or apparent antibody avidity for (QGPGAP)2 by sodium thiocyanate elution assay. The data demonstrate that a synthetic peptide can induce protective antibodies and that a specific antibody subclass is not required for protection. Work to determine whether antibody affinity or fine specificity can explain the hierarchy of protection among the MAbs is under way.
Cloning, Expression, and Nutritional Regulation of the Mammalian Δ-6 Desaturase (1999)

Arachidonic acid (20:4(n-6)) and docosahexaenoic acid (22:6(n-3)) have a variety of physiological functions that include being the major component of membrane phospholipid in brain and retina, substrates for eicosanoid production, and regulators of nuclear transcription factors. The rate-limiting step in the production of 20:4(n-6) and 22:6(n-3) is the desaturation of 18:2(n-6) and 18:3(n-3) by Delta-6 desaturase. In this report, we describe the cloning, characterization, and expression of a mammalian Delta-6 desaturase. The open reading frames for mouse and human Delta-6 desaturase each encode a 444-amino acid peptide, and the two peptides share an 87% amino acid homology. The amino acid sequence predicts that the peptide contains two membrane-spanning domains as well as a cytochrome b5-like domain that is characteristic of nonmammalian Delta-6 desaturases. Expression of the open reading frame in rat hepatocytes and Chinese hamster ovary cells instilled in these cells the ability to convert 18:2(n-6) and 18:3(n-3) to their respective products, 18:3(n-6) and 18:4(n-3). When mice were fed a diet containing 10% fat, hepatic enzymatic activity and mRNA abundance for hepatic Delta-6 desaturase in mice fed corn oil were 70 and 50% lower than in mice fed triolein. Finally, Northern analysis revealed that the brain contained an amount of Delta-6 desaturase mRNA that was several times greater than that found in other tissues including the liver, lung, heart, and skeletal muscle. The RNA abundance data indicate that prior conclusions regarding the low level of Delta-6 desaturase expression in nonhepatic tissues may need to be reevaluated.
Purification of PDGF-AB and PDGF-BB from human platelet extracts and identification of all three PDGF dimers in human platelets (1990)

We have developed a panel of monoclonal antibodies to platelet-derived growth factor (PDGF) which have variable specificities for the three dimeric forms of the molecule (AA, AB, and BB). We have used these antibodies to detect and immunoaffinity purify the individual dimers from human platelet rich plasma. Extracts of outdated platelet preparations were initially chromatographed over CM-Sepharose and then passed over the Sepharose-coupled monoclonal antibodies in series in selectively isolate the three dimeric forms of PDGF. The PDGF eluted from the affinity columns was subsequently further purified by reversed-phase HPLC. From 300 units of outdated platelet preparations, we purified 58 micrograms of PDGF-BB and 140 micrograms of PDGF-AB. Using the monoclonal antibodies to develop PDGF dimer-specific ELISAs, it was observed that all three PDGF dimer forms are present in fresh human platelet extracts and that the ratios of the three dimer forms vary depending upon the extraction conditions used. The identification of all three PDGF dimer forms in human platelets point to the need to view PDGF isolated from human platelets by conventional techniques as a mixture of all three forms and not solely as PDGF-AB.
The Accumulation of Dendritic Cells in the Lung Is Impaired in CD18−/− But Not in ICAM-1−/− Mutant Mice (2000)

Bone marrow-derived dendritic cell (DC) precursors migrate via the blood stream to peripheral tissues to adopt their sentinel function. To identify factors facilitating their emigration to the lung, mutant mice deficient in E-selectin, P-selectin, E/P-selectin, ICAM-1, or CD18 and their respective controls were examined. DCs and monocytes/macrophages were immunolabeled with M5/114 and MOMA-2 mAbs, respectively, and quantified morphometrically. Of these genotypes, the numbers of DC and MOMA-2+ cells were significantly less only in the lungs of CD18-/- mice by 68 and 35% in alveolar walls and by 28 and 26% in venous walls, respectively. DCs were reduced by 30 and 41% around large and small airways, respectively, but the number of MOMA-2+ cells in these locations was not significantly different from controls. Ablation of a single gene may be associated with augmented expression of other, related gene products. Therefore, we examined the expression of VCAM-1. Increased numbers of arteries exhibited continuous luminal VCAM-1 staining in both CD18-/- and ICAM-1-/- mutants. VCAM-1 expression was absent in pulmonary capillaries and unchanged in veins. These data suggest that under nonperturbing conditions, CD18-mediated adhesion is required for the full complement of DC precursors to accumulate in the lungs. However, the defect in CD18-/- mice is partial, suggesting that CD18-independent adhesion occurs. The alternative pathway may involve VLA-4/VCAM-1 in arteries and venules but not in capillaries. The smaller defect in ICAM-1-/- mice suggests that the CD11/CD18 complex recognizes ligands other than ICAM-1 at some sites.
Noncovalent Modification of Chymotrypsin Surface Using an Amphiphilic Polymer Scaffold:  Implications in Modulating Protein Function (2005)

We report here on a new amphiphilic homopolymer that binds noncovalently to proteins. This polymer not only binds to the target protein chymotrypsin with submicromolar affinity but also stabilizes the native structure of the protein. Since the polymer-protein binding process is based on electrostatic interaction, the bound protein can be released from the polymer surface and reactivated either by increasing the ionic strength or by adding complementary cationic surfactants. The electrostatic binding of polymer to the protein results in a marked change in the substrate specificity of chymotrypsin.