gebhart/patrepeval huggingface dataset:
Low Production of Interferon γ Is Related to Disease Progression in HIV Infection: Evidence from a Cohort of 347 HIV-Infected Individuals (1997)

A total of 347 HIV-seropositive individuals attending the Department of Infectious Diseases at Rigshospitalet in Copenhagen and 110 age- and sex-matched healthy controls not at risk for HIV infection were included in this study. Interferon gamma (IFN-gamma) production was measured in whole blood of 223 HIV-seropositive individuals (68 had developed AIDS at enrollment) and 99 healthy sex- and age-matched controls 4.5 hr after challenge with phytohemagglutinin. HIV-infected individuals for whom IFN-gamma production was measured were followed with a median follow-up time of 2.89 years (range, 0.02-4.54 years) from the date of enrollment. Survival analysis was performed considering three different end points: (1) a CD4 count below 100 cells/mm3, (2) an AIDS diagnosis defined according to the 1993 Centers for Disease Control definition, and (3) death. The production of IFN-gamma was highly increased in the blood of HIV-infected individuals without AIDS, but decreased in the blood of AIDS patients (both compared to controls). In the HIV-infected individuals, the total production of IFN-gamma was positively correlated with the number of CD8+ T lymphocytes and with the number of CD16+/CD56+ natural killer cells and negatively correlated with serum levels of beta2-microglobulin. Low levels of IFN-gamma production were associated with an increased risk of experiencing a CD4 count below 100 cells/m3 and death, analyzed in both univariate analysis and in multivariate analysis adjusting for CD4 counts and age. Thus, changes in production of IFN-gamma seem to be truly related to the risk for disease progression in HIV infection.
Expression of the human MHC, HLA-DQW6 genes alters the immune response in C57BL/6 mice. (1990)

In an attempt to obtain direct evidence for the critical role of HLA class II molecules in regulating the immune response, genomic genes for alpha- and beta-chains of HLA-DQw6 from HLA-Dw12 haplotype were introduced into the C57BL/6 (B6) strain of mouse and a line of HLA-DQw6 transgenic mouse was obtained. Tissue specificity of the expression of the transgenes was much the same as that of murine I-Ab genes. DQw6 molecules were expressed on B cells and macrophages in spleen cells and about 30 to 40% of the I-Ab+ spleen cells were positive for DQw6. The HLA-DQw6 transgenic B6 mouse became tolerant to the DQw6 molecules, as evidenced by the MLR and antibody production specific to the DQw6 molecules. The HLA-DQw6 transgenic B6 mouse showed a strong immune response to streptococcal cell wall antigen (SCW), whereas the B6 mouse was a low responder to SCW. The SCW-specific T cell line was established from the transgenic mouse and this T cell line recognized SCW in the context of HLA-DQw6 molecules expressed on the mouse L cell transfectant or on human monocytes. The proliferative response to SCW of primed lymph node T cells and the SCW-specific T cell line derived from the transgenic mice was inhibited by anti-HLA-DQ mAb. Thus, it is clear that the HLA-DQw6 genes acted as major histocompatibility genes in these transgenic mice.
Drug Delivery Systems. 2. Camptothecin 20-O-Poly(ethylene glycol) Ester Transport Forms (1996)

ADVERTISEMENT RETURN TO ISSUEPREVLetterNEXTDrug Delivery Systems. 2. Camptothecin 20-O-Poly(ethylene glycol) Ester Transport FormsRichard B. Greenwald, Annapurna Pendri, Charles Conover, Carl Gilbert, Ross Yang, and Jing XiaView Author Information Enzon Inc., 20 Kingsbridge Road, Piscataway, New Jersey 08854-3969 Cite this: J. Med. Chem. 1996, 39, 10, 1938–1940Publication Date (Web):May 10, 1996Publication History Received17 January 1996Published online10 May 1996Published inissue 1 January 1996https://pubs.acs.org/doi/10.1021/jm9600555https://doi.org/10.1021/jm9600555rapid-communicationACS PublicationsCopyright © 1996 American Chemical SocietyRequest reuse permissionsArticle Views1094Altmetric-Citations81LEARN 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-AlertscloseSupporting Info (1)»Supporting Information Supporting Information SUBJECTS:Hydrolysis,Lactones,Organic compounds,Plasma,Rodent models Get e-Alerts
Precursors of colony-forming cells in humans can be distinguished from colony-forming cells by expression of the CD33 and CD34 antigens and light scatter properties. (1989)

We determined whether human marrow cells that directly form colonies in vitro could be distinguished from cells that generate or become CFC only after LTMC in the presence of irradiated marrow stromal cells. In previous studies, an anti-CD33 antibody, L4F3, and complement (C') were used to lyse nearly all CFC in marrow, and the remaining cells generated CFC in LTMC. In the present studies, marrow cells were treated with L4F3 + C' and the remaining CD33- cells were separated into CD34+ and CD34- populations and placed in LTMC. Only the CD34+ cells were found to generate significant numbers of CFC. To compare the CD33-CD34+ and CD33+CD34+ cells, we isolated each cell population using two-color FACS. Only LTMCs of the CD33-CD34+ cells generated CFC for greater than 5 wk. In contrast, cells that expressed both the CD33 and CD34 antigens, which contained most of the CFC, generated few CFC in LTMC. Fractionation of marrow cells based on right angle and forward light scattering suggested that precursors for CFC have low right angle and low forward light scattering properties. The CD33-CD34+ marrow cells were therefore further fractionated based on light scatter characteristics. Cells with low right angle and low forward light scatter formed few or no colonies on direct culture, yet generated greater numbers of CFC after 4 wk of LTMC than did cells with low right angle and high forward light scatter. Most (87-98%) CFC generated in the LTMCs that were initiated with CD33-CD34+ cells were found to express the CD33 antigen. Thus, hematopoietic progenitors with differing proliferative and differentiative potentials can be directly separated on the basis of their expression of CD33 and CD34 cell surface antigens and their light scatter properties.
Functional Inactivation of the Retinoblastoma Protein Requires Sequential Modification by at Least Two Distinct Cyclin-cdk Complexes (1998)

The retinoblastoma protein (pRb) acts to constrain the G1-S transition in mammalian cells. Phosphorylation of pRb in G1 inactivates its growth-inhibitory function, allowing for cell cycle progression. Although several cyclins and associated cyclin-dependent kinases (cdks) have been implicated in pRb phosphorylation, the precise mechanism by which pRb is phosphorylated in vivo remains unclear. By inhibiting selectively either cdk4/6 or cdk2, we show that endogenous D-type cyclins, acting with cdk4/6, are able to phosphorylate pRb only partially, a process that is likely to be completed by cyclin E-cdk2 complexes. Furthermore, cyclin E-cdk2 is unable to phosphorylate pRb in the absence of prior phosphorylation by cyclin D-cdk4/6 complexes. Complete phosphorylation of pRb, inactivation of E2F binding, and activation of E2F transcription occur only after sequential action of at least two distinct G1 cyclin kinase complexes.
High-throughput RNAi screening in vitro: From cell lines to primary cells (2005)

Small interfering RNAs (siRNAs) are being used to induce sequence-specific gene silencing in cultured cells to study mammalian gene function. Libraries of siRNAs targeting entire human gene classes can be used to identify genes with specific cellular functions. Here we describe high-throughput siRNA delivery methods to facilitate siRNA library screening experiments with both immortalized and primary cells. We adapted chemical reverse transfection for immortalized adherent cell lines in a 96-well format. The method is fast, robust, and exceptionally effective for many cell types. For primary cells and immortalized cells that are recalcitrant to lipofection-based methods, we developed electropermeabilization (electroporation) conditions that facilitate siRNA delivery to a broad range of cell types, including primary human T-cells, hMSC, NHA, NDHF-Neo, HUVEC, DI TNC1, RPTEC, PC12, and K562 cells. To enable high-throughput electropermeabilization of primary cells, we developed a novel 96-well electroporation device that provides highly efficient and reproducible delivery of siRNAs. The combination of high-throughput chemical reverse transfection and electroporation makes it possible to deliver libraries of siRNAs to virtually any cell type, enabling gene function analysis and discovery on a genome scale.
Role of receptor for advanced glycation end-products and signalling events in advanced glycation end-product-induced monocyte chemoattractant protein-1 expression in differentiated mouse podocytes (2005)

These results suggest that AGEs and CML induce MCP-1 expression in podocytes through activation of RAGE and generation of intracellular ROS. NF-kappaB and Sp1 regulate MCP-1 gene transcription.
Mobile Gene Cassettes and Integrons in Evolution (1999)

Integrons and the site-specific recombination systems encoded by them provide a simple mechanism for the addition of new genes to bacterial chromosomes. Although there is substantial divergence among the four known integron-encoded integrases, they all recognize the recombination sites, known as 59-base elements, that are associated with genes that are packaged in gene cassettes. In contrast, the integron-associated recombination sites, attl sites, are preferentially recognized by the cognate integrase.
Spontaneous Tumorigenesis in Mice Overexpressing the p53-Negative Regulator Mdm4 (2010)

High levels of the critical p53 inhibitor Mdm4 is common in tumors that retain a wild-type p53 allele, suggesting that Mdm4 overexpression is an important mechanism for p53 inactivation during tumorigenesis. To test this hypothesis in vivo, we generated transgenic mice with widespread expression of Mdm4. Two independent lines of transgenic mice, Mdm4(Tg1) and Mdm4(Tg15), developed spontaneous tumors, the most prevalent of which were sarcomas. To determine whether overexpression of Mdm4 also cooperated with p53 heterozygosity to induce tumorigenesis, we generated Mdm4(Tg1) p53(+/-) mice. These mice had significantly accelerated tumorigenesis and a distinct tumor spectrum with more carcinomas and significantly fewer lymphomas than p53(+/-) or Mdm4(Tg1) mice. Importantly, the remaining wild-type p53 allele was retained in most Mdm4(Tg1) p53(+/-) tumors. Mdm4 is thus a bona fide oncogene in vivo and cooperates with p53 heterozygosity to drive tumorigenesis. These Mdm4 mice will be invaluable for in vivo drug studies of Mdm4 inhibitors.
Protein synthesis during acquisition of long-term facilitation is needed for the persistent loss of regulatory subunits of the Aplysia cAMP-dependent protein kinase. (1990)

Depending on the number or the length of exposure, application of serotonin can produce either short-term or long-term presynaptic facilitation of Aplysia sensory-to-motor synapses. The cAMP-dependent protein kinase, a heterodimer of two regulatory and two catalytic subunits, has been shown to become stably activated only during long-term facilitation. Both acquisition of long-term facilitation and persistent activation of the kinase is blocked by anisomycin, an effective, reversible, and specific inhibitor of protein synthesis in Aplysia. We report here that 2-hr exposure of pleural sensory cells to serotonin lowers the concentration of regulatory subunits but does not change the concentration of catalytic subunits, as assayed 24 hr later; 5-min exposure to serotonin has no effect on either type of subunit. Increasing intracellular cAMP with a permeable analog of cAMP together with the phosphodiesterase inhibitor isobutyl methylxanthine also decreased regulatory subunits, suggesting that cAMP is the second messenger mediating serotonin action. Anisomycin blocked the loss of regulatory subunits only when applied with serotonin; application after the 2-hr treatment with serotonin had no effect. In the Aplysia accessory radula contractor muscle, prolonged exposure to serotonin or to the peptide transmitter small cardioactive peptide B, both of which produce large increases in intracellular cAMP, does not decrease regulatory subunits. This mechanism of regulating the cAMP-dependent protein kinase therefore may be specific to the nervous system. We conclude that during long-term facilitation, new protein is synthesized in response to the facilitatory stimulus, which changes the ratio of subunits of the cAMP-dependent protein kinase. This alteration in ratio could persistently activate the kinase and produce the persistent phosphorylation seen in long-term facilitated sensory cells.
kang fu xun lian zhi liao xiao er jian zu de tan tao (2013)

目的:探讨治疗小儿尖足的有效方法与对策。方法:对我院门诊治疗的90例有尖足的患儿采用了以运动疗法为主要康复训练手段并配合其他综合治疗方法,每个月为1个小疗程,3个月为1个大疗程,治疗1～8个疗程。结果:经治疗本组走路姿势明显好转或接近正常者89例,轻度足外翻1例,下肢肌张力及足背屈角均正常或接近正常。结论:康复训练加楔形垫进行主动蹲立位训练来治疗小儿尖足,是非常有效的方法。
A novel mechanism for achieving transgene persistence in vivo after somatic gene transfer into hepatocytes. (1992)

Infusion of hepatocyte-specific DNA-protein complexes into rats leads to transient recombinant gene expression in liver. The eventual deterioration of gene expression is due in part to instability of the targeted DNA. In a previous report, we noted retention of transgene sequences in liver and persistent recombinant gene expression when the animals were subjected to partial hepatectomy following in vivo gene transfer. In an attempt to define the mechanism(s) responsible for persistent gene expression following partial hepatectomy, we characterized the molecular state of the retained, liver-associated transgenes. Southern blot analysis of DNA from liver tissues harvested various times after in vivo gene transfer and partial hepatectomy (10 min to 11 weeks) demonstrated high levels of transgene DNA (100-10,000 copies/cell). The predominant form of this DNA appeared to be episomal based on analyses of uncut DNA or DNA restricted by an endonuclease with one site in the plasmid. Livers from several animals contained a small proportion of transgene sequences of unknown structure. The existence of episomal DNA in liver was confirmed in experiments in which intact plasmid was rescued from total hepatocyte DNA by transformation of bacteria. Both strands of DNA in the liver-associated plasmid retained a bacterial pattern of methylation suggesting that the plasmid had not replicated in the eukaryotic cell. These results are consistent with the hypothesis that the majority of transgene sequences are retained as stabilized plasmids. The specific form of DNA which is transcriptionally active was not identified in these studies. This represents a new mechanism for retaining foreign DNA in eukaryotic cells in vivo and has implications both for the development of somatic gene therapies and the pathogenesis of viral diseases.
Issues on the size and outline of killer defects and their influence on yield modeling (2002)

Yield prediction models and critical area calculations based on on defects modeled as circular disks. But, the observation of real defects provides mostly irregular defect outlines. For this reason, we investigate the influence of real defect outlines on determining defect size distributions for yield prediction. To collect data on defects, checkerboard test structures were manufactured that enable a precise localization of defects inside large chip areas. Furthermore, we introduce a methodology to calculate a general defect size distribution that includes variety of real defect outlines. So, this realistic size distribution will be compared to defect size distributions based on known yield models to describe defect outlines.
Human Nuclease/Helicase DNA2 Alleviates Replication Stress by Promoting DNA End Resection (2012)

In precancerous and cancerous lesions, excessive growth signals resulting from activation of oncogenes or loss of tumor suppressor genes lead to intensive replication stress, which is recognized by a high level of replication-associated DNA double-strand breaks (DSB). However, the molecular mechanism by which cells alleviate excessive replication stress remains unclear. In this study, we report that the human nuclease/helicase DNA2 facilitates homologous recombination to repair replication-associated DNA DSBs, thereby providing cells with survival advantages under conditions of replication stress. The nuclease activity of DNA2 was required for DSB end resection, which allowed subsequent recruitment of RPA and RAD51 to repair DSBs and restart replication. More importantly, DNA2 expression was significantly increased in human cancers and its expression correlated with patient outcome. Our findings therefore indicate that enhanced activity of DSB resection likely constitutes one mechanism whereby precancerous and cancerous cells might alleviate replication stress.
Pyrrolopyridine Inhibitors of Mitogen-Activated Protein Kinase-Activated Protein Kinase 2 (MK-2) (2007)

A new class of potent kinase inhibitors selective for mitogen-activated protein kinase-activated protein kinase 2 (MAPKAP-K2 or MK-2) for the treatment of rheumatoid arthritis has been prepared and evaluated. These inhibitors have IC50 values as low as 10 nM against the target and have good selectivity profiles against a number of kinases including CDK2, ERK, JNK, and p38. These MK-2 inhibitors have been shown to suppress TNFalpha production in U397 cells and to be efficacious in an acute inflammation model. The structure-activity relationships of this series, the selectivity for MK-2 and their activity in both in vitro and in vivo models are discussed. The observed selectivity is discussed with the aid of an MK-2/inhibitor crystal structure.
The Use of 4D Seismic in Reservoir Management (2001)

F-01 THE USE OF 4D SEISMIC IN RESERVOIR MANAGEMENT J MARCUS MARSH GRAEME BAGLEY ANDREW LEWIS JOHN MCGARRITY 1 Summary In mid 1999 BP acquired a 3-D survey over the West of Shetland area specifically for time-lapse interpretation of the reservoir dynamic behavior over the component fields. This was described at the EAGE meeting last year i . This formed a turning point in BP’s use of 4-D from experimentation to commercial use. The results were very useful in field management and well planning. Before that it had acquired a number of repeat 3-D seismic surveys which in addition to
Sequence analysis of M2 mRNA of bovine respiratory syncytial virus obtained from an F-M2 dicistronic mRNA suggests structural homology with that of human respiratory syncytial virus (1992)

The nucleotide sequences of the F and M2 mRNAs of strain A51908 of bovine respiratory syncytial virus (BRSV) were determined by sequencing cDNA of an intracellular dicistronic mRNA. Comparison of the F mRNA sequence with those of other BRSV strains showed that there was extensive sequence identity at both the nucleotide (95% identity) and amino acid (94% identity) levels. Alignment of the nucleotide and encoded amino acid sequences of M2 mRNA of BRSV with those of human respiratory syncytial virus (HRSV) M2 mRNA showed 69% identity at the nucleotide level and 80% identity at the amino acid level. The general features of BRSV F and M2 proteins are similar to those described previously for the HRSV proteins. The M2 mRNA of BRSV also contained a second internal, overlapping open reading frame (ORF) similar to one reported for HRSV. The predicted products of the second ORFs of BRSV and HRSV shared 43% amino acid identity. As described for HRSV, the 3'-terminal end of the M2 mRNA overlaps with the 5' end of the L gene by 68 nucleotides. The identity between the N-terminal regions of the L proteins of BRSV and HRSV is 75%. In addition, the intergenic sequence of the F-M2 gene junction of BRSV was determined.
Vascular permeability factor, a key regulator of endothelial cell function and tumour angiogenesis (1995)

We have developed a sensitive and quantitative RT-PCR assay for the determination of tissue factor (TF) mRNA levels in human cells.An in vitro synthesized internal standard RNA was used to correct for differences in reverse transcription or amplification of various RNA samples.The PCR products were quantitated by hybridization.The sensitivity was such that less than 0.2 g of total endothelial RNA sufficed to measure its TF mRNA content.The RT-PCR assay was used to determine TF mRNA levels in endothelial cells treated with a factor from human melanoma cells and/or TNF.In this way the amount of TF mRNA could be induced to a level that was at least 80-fold higher than that in non-induced cells.This increase was in the same order of magnitude as the induction of measured TF activity. Chapter 5Vascular permeability factor, or vascular endothelial growth factor (VPF/VEGF), is an important factor in the regulation of vascular growth and vascular permeability.VPF is a secreted, dimeric protein and has eight cysteine residues conserved with platelet-derived growth factor (PDGF).To study the role of some of these cysteine residues in maintaining the structure and function of VPF, we replaced the codons for the 2 1 , 3 rd , 4 th , and 5 th cysteine by serine codons, and expressed the mutant proteins in a mammalian expression system.Cysteine residues 2 and 4 in VPF were found to be directly involved in anti-parallel interchain disulfide bonds, as in PDGF.VPF mutants lacking one of these cysteines were severely impaired in their S-linked dimerization, whereas upon coexpression of both mutants the ability to form dimers was restored.The VPF mutants lacking cysteine residue 2 or 4 also competed poorly for receptor binding of labelled VPF and had low biological activity, but these defects were also complemented by coexpressing the two mutants, indicating that for efficient receptor binding and activation VPF needs to be a covalent dimer, unlike PDGF-BB.Furthermore, cysteine residue 5 was found to be essential for VPF dimerization and activity, whereas the mutant lacking cysteine residue 3 was only mildly affected in its ability to dimerize and had partial biological activity.
Anterior Corneal Dystrophy of American Dutch Belted Rabbits: Biomicroscopic and Histopathologic Findings (1987)

Spontaneously occurring anterior corneal opacities were present in related, juvenile American Dutch belted rabbits. Slit lamp biomicroscopy revealed focal opacities of epithelium, basement membrane, and subepithelial corneal stroma. Lesions were characterized histologically by thin and disorganized surface epithelium, thickened and intensely staining epithelial basement membrane, fimbriated and irregular basement membrane-stromal juncture, and disorganized subepithelial stroma. Biomicroscopic and histopathologic features of anterior corneal dystrophy of American Dutch belted rabbits appear similar to those of human anterior corneal dystrophies.