gebhart/patrepeval huggingface dataset:
IL-2 activated cell-mediated immunotherapy: control of minimal residual disease in malignant disorders by allogeneic lymphocytes and IL-2. (1990)

The present experiments were designed to investigate whether it might be possible to combine their therapeutic benefits of autologous BMT and allogeneic BMT following administration of T-lymphocyte depleted marrow allografts with additional immunotherapy following BMT. The tumor model used for investigating graft vs leukemia (GVL) effects was the murine B-cell leukemia (BCL1), a spontaneous, nonimmunogenic, highly lethal leukemia of BALB/c origin. Immunotherapy with high dose recombinant human interleukin-2 (IL2) (10(5) Cetus units x 3/day intraperitoneally (IP) for 5 days) produced significant anti-tumor effects in BCL1-bearing mice. BALB/c mice inoculated with 10(3) BCL1 leukemia cells received were treated on day -1 with cyclophosphamide 100 mg/kg and transplanted with normal syngenic BM cells on day 0. High-dose IL2 (100,000 Cetus Units x 3/day IP x 5 consecutive days) was initiated on day +1, +7, or +21 following BMT. Optimal time for administration of IL2 was noted at 3 weeks post-BMT with 90% of the mice surviving with no evidence of disease greater than 1 year. An experimental model designed to study GVL effects in a state of minimal residual disease following T-cell depleted allogeneic BMT indicated that mice receiving low dose of BCL1 challenge (10(4] were successfully treated by either IL2 (2 x 10(4) Cetus units x 2/day IP x 3 days), allogeneic spleen cells (10(6) on day +1, 10(7) on day +5 and 5 x 10(7) on day +9) alone and certainly following a combination of both.(ABSTRACT TRUNCATED AT 250 WORDS)
5-Aminosalicylic Acid in the Treatment of Crohn's Disease: A 16-Week Double-Blind, Placebo-Controlled, Multicentre Study with Pentasa® (1987)

The response to 5-aminosalicylic acid (5-ASA) in mild and moderately active Crohn's disease localized in the small bowel was studied in a randomized, double-blind, placebo-controlled trial in four centres. Sixty-seven patients were included, of whom 30 were treated with 1500 mg slow-release 5-ASA/day (Pentasa) for a scheduled period of 16 weeks. In the 5-ASA group 40% of the patients improved, versus 30% of the placebo-treated group ('intent to treat' basis; p greater than 0.1). Four of the patients treated with 5-ASA left the study owing to disease deterioration, versus 10 of the placebo-treated patients (p greater than 0.2). Seventeen patients were secondarily excluded, and the remaining 50 patients (23 receiving 5-ASA) were reevaluated in greater detail. No statistically significant differences in outcome were shown. Three patients (one given 5-ASA) were withdrawn from the study because of presumed side effects, but no serious adverse reactions were recorded. The present results indicate that 5-ASA, at least in the dosage used, is not superior to placebo. Nevertheless, trends towards a beneficial effect in Crohn's disease in the small bowel justify further clinical trials with a larger dosage of 5-ASA.
Correlation of TCR diversity with immune reconstitution after cord blood transplant. (2012)

6631 Background: Umbilical cord blood is an important source of hematopoietic stem cells for allogeneic transplants used to treat hematologic disorders and malignancies. Stem cells from cord blood has several advantages over other sources (peripheral blood or marrow) including reduced incidence of graft-versus-host disease (GvHD) which allows less strict donor-patient HLA-type matching requirements. However, hematopoietic recovery (both myeloid and platelet engraftment) and immune reconstitution is significantly delayed in CBT patients resulting in patients remaining at high risk of infection for an extended period of time. Though the high risk of infections to patients is well-documented and recognized, physicians lack an objective means to monitor each patient’s progress toward functional reconstitution of the adaptive immune system. Our project aims to test if our measure of TCR diversity is a better proxy of immune reconstitution in CBT patients. Methods: To do this, we compare our proposed measure of immune reconstitution, TCRB CDR3 sequence diversity and richness over time, against the observed clinical course of severe infection in patients who have received CBT. Previously, peripheral blood mononuclear cells (PBMC) were collected and cyropreserved from 35 CBT recipients at six time points, pre-transplant, and 28, 56, 100, 180, and 365 days post-transplant. Concordantly, clinical outcomes for these patients were collected for up to four years post-transplant. We use a t-test to test if size of TCR repertoire differs between CBT patients with non-relapse related mortality and all other CBT patients. Results: Our TCR sequencing method was successful at measuring immune reconstitution, and TCR diversity is predictive of subsequent mortality from severe infection by 56 days post-transplant. Conclusions: TCR repertoire sequencing is a viable method to monitor immune reconstitution.
Renal disease pathophysiology and treatment: contributions from the rat (2016)

The rat has classically been the species of choice for pharmacological studies and disease modeling, providing a source of high-quality physiological data on cardiovascular and renal pathophysiology over many decades. Recent developments in genome engineering now allow us to capitalize on the wealth of knowledge acquired over the last century. Here, we review rat models of hypertension, diabetic nephropathy, and acute and chronic kidney disease. These models have made important contributions to our understanding of renal diseases and have revealed key genes, such as Ace and P2rx7, involved in renal pathogenic processes. By targeting these genes of interest, researchers are gaining a better understanding of the etiology of renal pathologies, with the promised potential of slowing disease progression or even reversing the damage caused. Some, but not all, of these target genes have proved to be of clinical relevance. However, it is now possible to generate more sophisticated and appropriate disease models in the rat, which can recapitulate key aspects of human renal pathology. These advances will ultimately be used to identify new treatments and therapeutic targets of much greater clinical relevance.
Journey to the Center of the Cell: Role of the Receptosome (1981)

Fibroblasts contain a specific internalization pathway that carries hormones as well as some proteins and viruses from the cell surface to the cell interior. Initially, the ligands bind to mobile receptors that are randomly distributed on the cell surface. Next the ligand-receptor complexes are trapped and concentrated in specialized regions of the membrane termed bristle-coated pits. From the pit a smooth-walled vesicle containing the ligand forms and carries the ligand to the cell interior. Because of its role in receptor-mediated endocytosis, this vesicle has been termed a "receptosome."
The transcription factor ATF5: role in neurodevelopment and neural tumors (2008)

We review recent findings regarding the properties of ATF5 and the major roles that this transcription factor plays in development of the nervous system and in survival of neural tumors. ATF5 is a widely expressed basic leucine zipper protein that has been subject to limited characterization. It is highly expressed in zones of neuroprogenitor cell proliferation. In vitro and in vivo studies indicate that it functions there to promote neuroprogenitor cell expansion and to suppress their differentiation into neurons or glia. ATF5 expression is down-regulated by trophic factors and this is required for their capacity to promote neuroprogenitor cell cycle exit and differentiation into either neurons, oligodendroglia or astrocytes. ATF5 is also highly expressed in a number of tumor types, including neural tumors such as neuroblastomas, medulloblastomas and glioblastomas. Examination of the role of ATF5 in glioblastoma cells indicates that interference with its expression or activity causes them to undergo apoptotic death. In contrast, normal astrocytes and neurons do not appear to require ATF5 for survival, indicating that it may be a selective target for treatment of glioblastomas and other neural neoplasias. Further studies are needed to identify the transcriptional targets of ATF5 and the mechanisms by which its expression is regulated in neuroprogenitors and tumors.
Reducing the quantum-computing overhead with complex gate distillation (2015)

In leading fault-tolerant quantum computing schemes, accurate transformation are obtained by a two-stage process. In a first stage, a discrete, universal set of fault-tolerant operations is obtained by error-correcting noisy transformations and distilling resource states. In a second stage, arbitrary transformations are synthesized to desired accuracy by combining elements of this set into a circuit. Here, we present a scheme which merges these two stages into a single one, directly distilling complex transformations. We find that our scheme can reduce the total overhead to realize certain gates by up to a few orders of magnitude. In contrast to other schemes, this efficient gate synthesis does not require computationally intensive compilation algorithms, and a straightforward generalization of our scheme circumvents compilation and synthesis altogether.
A novel PTEN gene promoter mutation and untypical Cowden syndrome. (2013)

Cowden syndrome (CS), an autosomal dominant disorder, is one of a spectrum of clinical disorders that have been linked to germline mutations in the phosphatase and tensin homolog (PTEN) gene. Although 70-80% of patients with CS have an identifiable germline PTEN mutation, the clinical diagnosis presents many challenges because of the phenotypic and genotypic variations. In the present study, we sequenced the exons and the promoter of PTEN gene, mutations and variations in the promoter and exons were identified, and a PTEN protein expression negative region was determined by immunohistochemistry (IHC). In conclusion, a novel promoter mutation we found in PTEN gene may turn off PTEN protein expression occasionally, leading to the disorder of PTEN and untypical CS manifestations.
Extraction of high-quality genomic DNA from different plant orders applying a modified CTAB-based method (2019)

Reliable measurement of DNA concentration and purity is important for almost all molecular genetics studies. Different plant species have varying levels of polysaccharides, polyphenols, and other secondary metabolites which combine with nucleic acids during DNA isolation and further affect the quality of the extracted DNA. The current extraction protocol is based upon the conventional cetyl trimethylammonium bromide (CTAB) method with further modifications for the extraction of DNA from variable plant seeds and crops belonging to seven different orders. The principle modifications currently employed for DNA extraction involved the use of higher CTAB concentration and higher levels of 2-β-mercaptoethanol. Additionally, higher concentrations of sodium chloride and potassium acetate were added simultaneously with absolute ice cold isopropanol for the precipitation of DNA free from polysaccharides. The prescribed modifications in the present method establish a quick and efficient standardized protocol for DNA extraction from different plant orders. The current extraction protocol, therefore, can be of great value for molecular analysis involving large numbers of different plant samples from different orders. These modifications consistently produced pure and high-quality DNA suitable for further molecular analysis. Successful PCR amplification with random amplified polymorphic DNA primer, NPTII gene, and the complete digestion of the isolated DNA with the HindIII restriction enzyme validated the quality of the isolated DNA. Moreover, it reflects the efficiency of the protocol and proves its suitability for further applications for the assessment of food safety, detection of genetically modified (GM) crops, and conservation of biodiversity.
Ethanol Vapor Is an Efficient Inducer of the alc Gene Expression System in Model and Crop Plant Species (2002)

We have demonstrated that low concentrations of ethanol vapor efficiently induce the alc gene expression system in tobacco (Nicotiana tabacum cv Samsun NN), potato (Solanum tuberosum cv Solara), and oilseed rape (Brassica napus cv Westar). For many situations, this may be the preferred method of induction because it avoids direct application of comparatively high concentrations of an ethanol solution. Although induction was seen with less than 0.4 microM ethanol vapor, maximal induction of the chloramphenicol acetyl transferase gene was achieved after 48 h in leaves of tobacco plants enclosed with 4.5 microM ethanol vapor. In the absence of ethanol, there is no detectable gene expression. Treatment of potato tubers with ethanol vapor results in uniform beta-glucoronidase (GUS) expression. Vapor treatment of a single oilseed rape leaf resulted in induction of GUS in the treated leaf only and (14)C-ethanol labeling in tobacco confirmed that the inducer was not translocated. In contrast, enclosure of the roots, aerial parts, or whole plant with ethanol vapor resulted in induction of GUS activity in leaves and roots. The data reported here broaden the utility of the alc system for research and crop biotechnology.
Activation of the protein tyrosine phosphatase SHP2 via the interleukin-6 signal transducing receptor protein gp130 requires tyrosine kinase Jak1 and limits acute-phase protein expression (1998)

Stimulation of the interleukin-6 (IL-6) signalling pathway occurs via the IL-6 receptor-glycoprotein 130 (IL-6R-gp130) receptor complex and results in the regulation of acute-phase protein genes in liver cells. Ligand binding to the receptor complex leads to tyrosine phosphorylation and activation of Janus kinases (Jak), phosphorylation of the signal transducing subunit gp130, followed by recruitment and phosphorylation of the signal transducer and activator of transcription factors STAT3 and STAT1 and the src homology domain (SH2)-containing protein tyrosine phosphatase (SHP2). The tyrosine phosphorylated STAT factors dissociate from the receptor, dimerize and translocate to the nucleus where they bind to enhancer sequences of IL-6 target genes. Phosphorylated SHP2 is able to bind growth factor receptor bound protein (grb2) and thus might link the Jak/STAT pathway to the ras/raf/mitogen-activated protein kinase pathway. Here we present data on the dose-dependence, kinetics and kinase requirements for SHP2 phosphorylation after the activation of the signal transducer, gp130, of the IL-6-type family receptor complex. When human fibrosarcoma cell lines deficient in Jak1, Jak2 or tyrosine kinase 2 (Tyk2) were stimulated with IL-6-soluble IL-6R complexes it was found that only in Jak1-, but not in Jak 2- or Tyk2-deficient cells, SHP2 activation was greatly impaired. It is concluded that Jak1 is required for the tyrosine phosphorylation of SHP2. This phosphorylation depends on Tyr-759 in the cytoplasmatic domain of gp130, since a Tyr-759-->Phe exchange abrogates SHP2 activation and in turn leads to elevated and prolonged STAT3 and STAT1 activation as well as enhanced acute-phase protein gene induction. Therefore, SHP2 plays an important role in acute-phase gene regulation.
Inhibition of hypoxia-inducible factor 1 activity by nitric oxide donors in hypoxia (1998)

Nitric oxide (NO) is known to have various biologic and pathophysiologic effects on organisms. The molecular mechanisms by which NO exerts harmful effects are unknown, although various O2 radicals and ions that result from reactivity of NO are presumed to be involved. Here we report that adaptive cellular response controlled by the transcription factor hypoxia-inducible factor 1 (HIF-1) in hypoxia is suppressed by NO. Induction of erythropoietin and glycolytic aldolase A mRNAs in hypoxically cultured Hep3B cells, a human hepatoma cell line, was completely and partially inhibited, respectively, by the addition of sodium nitroprusside (SNP), which spontaneously releases NO. A reporter plasmid carrying four hypoxia-response element sequences connected to the luciferase structural gene was constructed and transfected into Hep3B cells. Inducibly expressed luciferase activity in hypoxia was inhibited by the addition of SNP and two other structurally different NO donors, S-nitroso-L-glutathione and 3-morpholinosydnonimine, giving IC50 values of 7.8, 211, and 490 microM, respectively. Inhibition by SNP was also observed in Neuro 2A and HeLa cells, indicating that the inhibition was not cell-type-specific. The vascular endothelial growth factor promoter activity that is controlled by HIF-1 was also inhibited by SNP (IC50 = 6.6 microM). Induction generated by the addition of cobalt ion (this treatment mimics hypoxia) was also inhibited by SNP (IC50 = 2.5 microM). Increased luciferase activity expressed by cotransfection of effector plasmids for HIF-1alpha or HIF-1alpha-like factor in hypoxia was also inhibited by the NO donor. We also showed that the inhibition was performed by blocking an activation step of HIF-1alpha to a DNA-binding form.
The Reactive Site of Trypsin Inhibitors (1966)

Virgin soybean trypsin inhibitor has 1 NH2-terminal aspartic acid or asparagine residue and no COOH-terminal residues that can be released by carboxypeptidase B. Upon incubation with 1 mole % of trypsin for 24 hours at pH 3.75, virgin inhibitor is converted to a modified inhibitor which has 2 NH2 terminals aspartic acid or asparagine and isoleucine. Approximately 1 mole of arginine is released from it by the action of carboxypeptidase B. Reduction and carboxymethylation of virgin inhibitor leads to formation of one major fragment as judged by Sephadex chromatography; the same treatment of modified inhibitor leads to formation of two fragments. The sum of the amino acid compositions of these two fragments accurately corresponds to the amino acid composition of soybean trypsin inhibitor. The smaller fragment is composed of approximately 64 amino acids and has NH2-terminal aspartic acid or asparagine residue and a COOH-terminal arginine residue. It is concluded that the modification reaction consists of conversion of single chain inhibitor to two chains held by a single disulfide bond by tryptic cleavage of a single Arg-Ile bond located approximately between residues 64 and 65. Evidence is also presented that modification of chicken ovomucoid consists of conversion of single chain to two chain protein by cleavage of a single Arg-Ala bond. The fragments may be held by a disulfide bond or bonds. Compilation of considerable amount of evidence obtained by others suggests that part of the reactive site of many, or possibly all, naturally occurring trypsin inhibitors consists of a trypsin-accessible Arg-X or Lys-X bond contained within a disulfide loop.
Nitrate biosynthesis in man. (1981)

Nitrate metabolism was investigated in long-term metabolic studies in healthy young men. Under conditions of constant low ingestion of nitrate (less than 180 mumol/day per subject), the amount of nitrate excreted in urine was an average of 4-fold greater than the amount ingested. Balance studies with 15NO3- showed that the source of the excess nitrate in urine was the endogenous biosynthesis of nitrate, rather than the emptying of a body pool. Nitrate biosynthesis occurred when nitrate ingestion was high as well as low, and the amounts synthesized appeared to be independent of intake and comparable to the amounts ingested from normal diets. Analysis of the 15NO3- data also revealed that half of ingested nitrate was recovered as urinary nitrate. Because nitrate in urine is the net result of (i) intake, (ii) endogenous synthesis, and (iii) metabolic losses, the magnitude of the losses is such that, despite ongoing synthesis, the amount of nitrate in the urine of people consuming most diets will be less than the amount ingested.
Identification of Hexon-Specific CD4 and CD8 T-Cell Epitopes for Vaccine and Immunotherapy (2007)

Adenoviral infections in the immunocompromised host are associated with significant morbidity and mortality. Although the adoptive transfer of adenovirus-specific T cells may prevent and treat such infections, the T-cell immune response to the multiplicity of adenovirus serotypes and subspecies that infect humans has not been well characterized, impeding the development of such approaches. We have, therefore, analyzed the specificities of T-cell responses to the viral capsid hexon antigen, since this structure is highly conserved in human pathogens. We screened 25 human cytotoxic T-cell lines with adenovirus specificity to extensively characterize their responses to adenoviral hexon and to identify a panel of novel CD4(+) and CD8(+) T-cell epitopes. Using a peptide library spanning the entire sequence of the hexon protein, we confirmed the responsiveness of these cytotoxic T-cell lines to seven peptides described previously and also identified 33 new CD4- or CD8-restricted hexon epitopes. Importantly, the majority of these epitopes were shared among different adenovirus subspecies, suggesting that T cells with such specificities could recognize and be protective against multiple serotypes, simplifying the task of effective adoptive transfer or vaccine-based immunotherapy for treating infection by this virus.
VOLUNTARY ACCELERATION OF THE HEART BEAT (1918)

Favill and White<sup>1</sup>have recently studied a person having the ability to increase the rate of the heart at will. This was the fourteenth of such persons to be reported (see Footnote 2). Electrocardiograms have been made of three of these persons, but only in the studies of Favill and White were the effects of atropin on the ability to accelerate observed. These authors, with others who have studied similar instances, were led to believe that the action of the accelerator nerves was the chief factor in the mechanism of this type of acceleration. The following observations are reported in order to add another case to the series and because certain differences in results were obtained from those previously recorded. The subject is a young medical student who is entirely healthy and is apparently free from all physical and neurotic defects. He has had no cardiovascular symptoms whatever and physical
Synthesis and chemistry of 7-amino-4-(trifluoromethyl)coumarin and its amino acid and peptide derivatives (1980)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis and chemistry of 7-amino-4-(trifluoromethyl)coumarin and its amino acid and peptide derivativesEugene R. Bissell, Alexander R. Mitchell, and Robert E. SmithCite this: J. Org. Chem. 1980, 45, 12, 2283–2287Publication Date (Print):June 1, 1980Publication History Published online1 May 2002Published inissue 1 June 1980https://pubs.acs.org/doi/10.1021/jo01300a003https://doi.org/10.1021/jo01300a003research-articleACS PublicationsRequest reuse permissionsArticle Views1304Altmetric-Citations75LEARN 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