gebhart/patrepeval huggingface dataset:
Haploidentical Stem Cell Transplantation in Children: A Comparison between Positive Selection of Stem Cells and Depletion of T- and B-Cells. (2005)

Abstract Profound depletion of T- and B-cells is a fundamental prerequisite for haploidentical 1–3 loci mismatched stem cell transplantation. Here, we compare hematopoietic engraftment and occurrence of GvHD after positive selection procedures (with anti-CD34 coated or anti-CD133 coated beads, n=64 patients) and after a direct depletion procedure with anti-CD3/anti-CD19 coated microbeads (n=12) in children with leukemias (ALL, AML, CML), lymphomas and nonmalignant diseases. Median purity of stem cells was comparable after CD34+ selection and CD133+ selection, whereas stem cells were only slightly enriched after CD3+/CD19+ depletion (97.5%, 93.4% and 1.02%). Indirect depletion of T-cells by positive selection methods resulted in 10 000 residual CD3+ cells/kg (7000–30 000). Patients with grafts depleted with anti-CD3/anti-CD19 coated microbeads, received 32 000 (7000–160 000) residual T-cells/kg. Those grafts comprised also remarkable amounts of effector cells such as NK-cells (median number: 86 × 106/kg), dendritic cells and monocytes/granulocytes (median number: 700 × 106/kg) with antileukemic activity in vitro. Primary engraftment occurred in 83% of patients with positive selected stem cells. After reconditioning, sustained engraftment was achieved in 98%. In patients with CD3+/CD19+ depleted grafts, primary engraftment was observed in 92% (11/12) and sustained engraftment (after reconditioning) in 100% (12/12). GvHD grade II occurred in 6% (positive selection) and 25% (CD3/CD19 depletion). Only one patient had severe GvHD grade III-IV (CD34+). T-cell recovery was significantly faster in patients with CD3/CD19 depleted grafts. In the group with positive selected grafts, 5 year EFS for patients with ALL CR1-3, myeloic leukemias and nonmalignant diseases was 45%, 22% and 60%, respectively. CD3+/CD19+ depleted grafts were given to patients with refractory disease (AML/MDS, ALL) or with high risk of graft failure. 4/10 patients with leukemias and 2/2 patients with SAA/PNH are disease free (median follow-up: 8 months). Conclusions: Haploidentical transplantation with standard CD34+ or CD133+ selected grafts provides stable long term survival rates. CD3+/CD19+ depletion resulted in better and more reliable engraftment but produced slightly more GvHD than positive selection methods. Our preliminary results indicate, that CD3/CD19 selected grafts may be advantageous regarding engraftment and immunoreconstitution. Since effector cell with potential antileukemic activity are cotransfused, such grafts may be suited in particular for patients with insufficient remission.
Urinary collagen metabolite excretion in amyotrophic lateral sclerosis (2001)

Collagen abnormalities of the spinal cord and the skin have been reported in patients with amyotrophic lateral sclerosis (ALS). The urinary concentrations of the hydroxylysine glycosides, i.e., glucosylgalactosyl hydroxylysine (glu-gal Hyl) and galactosyl hydroxylysine (gal Hyl), indicate the tissue origin of the collagen metabolites and the rate of the degradation of collagen. We measured the urinary levels of glu-gal Hyl and gal Hyl in 12 ALS patients, 10 diseased control subjects with other neurologic or muscular diseases (Control Group A), and 10 healthy control subjects (Control Group B). The urinary level of glu-gal Hyl in ALS patients was significantly lower than in the two control groups. In addition, a significant negative relationship between glu-gal Hyl urinary level and duration of illness was found in ALS patients. There was no marked difference in the urinary level of gal Hyl between ALS patients and the control groups. Our data suggest that the decreased urinary level of glu-gal Hyl may be useful in assessing the alteration in collagen metabolism in ALS and may have a relationship with the progression of ALS.
Transforming Growth Factor-β-stimulated Clone-22 Is a Member of a Family of Leucine Zipper Proteins That Can Homo- and Heterodimerize and Has Transcriptional Repressor Activity (1999)

TGF-beta-stimulated clone-22 (TSC-22) encodes a leucine zipper-containing protein that is highly conserved during evolution. Two homologues are known that share a similar leucine zipper domain and another conserved domain (designated the TSC box). Only limited data are available on the function of TSC-22 and its homologues. TSC-22 is transcriptionally up-regulated by many different stimuli, including anti-cancer drugs and growth inhibitors, and recent data suggest that TSC-22 may play a suppressive role in tumorigenesis. In this paper we show that TSC-22 forms homodimers via its conserved leucine zipper domain. Using a yeast two-hybrid screen, we identified a TSC-22 homologue (THG-1) as heterodimeric partner. Furthermore, we report the presence of two more mammalian family members with highly conserved leucine zippers and TSC boxes. Interestingly, both TSC-22 and THG-1 have transcriptional repressor activity when fused to a heterologous DNA-binding domain. The repressor activity of TSC-22 appears sensitive for promoter architecture, but not for the histone deacetylase inhibitor trichostatin A. Mutational analysis showed that this repressor activity resides in the non-conserved regions of the protein and is enhanced by the conserved dimerization domain. Our results suggest that TSC-22 belongs to a family of leucine zipper-containing transcription factors that can homodimerize and heterodimerize with other family members and that at least two TSC-22 family members may be repressors of transcription.
T-Cell Receptor Vβ Repertoire CDR3 Length Diversity Differs within CD45RA and CD45RO T-Cell Subsets in Healthy and Human Immunodeficiency Virus-Infected Children (2000)

The T-cell receptor (TCR) CDR3 length heterogeneity is formed during recombination of individual Vbeta gene families. We hypothesized that CDR3 length diversity could be used to assess the fundamental differences within the TCR repertoire of CD45RA and CD45RO T-cell subpopulations. By using PCR-based spectratyping, nested primers for all 24 human Vbeta families were developed to amplify CDR3 lengths in immunomagnetically selected CD45RA and CD45RO subsets within both CD4(+) and CD8(+) T-cell populations. Umbilical cord blood mononuclear cells or peripheral blood mononuclear cells obtained from healthy newborns, infants, and children, as well as human immunodeficiency virus (HIV)-infected children, were analyzed. All T-cell subsets from newborn and healthy children demonstrated a Gaussian distribution of CDR3 lengths in separated T-cell subsets. In contrast, HIV-infected children had a high proportion of predominant CDR3 lengths within both CD45RA and CD45RO T-cell subpopulations, most commonly in CD8(+) CD45RO T cells. Sharp differences in clonal dominance and size distributions were observed when cells were separated into CD45RA or CD45RO subpopulations. These differences were not apparent in unfractionated CD4(+) or CD8(+) T cells from HIV-infected subjects. Sequence analysis of predominant CDR3 lengths revealed oligoclonal expansion within individual Vbeta families. Analysis of the CDR3 length diversity within CD45RA and CD45RO T cells provides a more accurate measure of disturbances in the TCR repertoire than analysis of unfractionated CD4 and CD8 T cells.
Human factors guidelines for terminal interface design (1983)

This paper provides a set of guidelines for the design of software interfaces for video terminals. It describes how to optimize screen layouts, interactive data entry, and error handling, as well as many practical techniques for improving man-machine interaction. Emphasis is placed on factors relating to perceptual and cognitive psychology rather than on gross physiological concerns. Ways in which interfaces can be evaluated to improve their user friendliness are also suggested. The author summarizes many ideas that can be found in other, more comprehensive texts on the subject. These guidelines will provide practicing software designers with useful insights into some of today's principal terminal interface design considerations.
New Drug Delivery Systems in Inflammatory Bowel Disease: MMX&#8482; and Tailored Delivery to the Gut (2010)

MMX is a promising new delivery system that can improve efficacy of current and new drugs, augmenting targeting to the affected tract, thereby increasing response and remission rates for those drugs in patients with IBD.
A human histone H2B.1 Variant gene, located on chromosome 1, utilizes alternative 3′ end processing (1992)

A variant human H2B histone gene (GL105), previously shown to encode a 2300 nt replication independent mRNA, has been cloned. We demonstrate this gene expresses alternative mRNAs regulated differentially during the HeLa S3 cell cycle. The H2B-Gl105 gene encodes both a 500 nt cell cycle dependent mRNA and a 2300 nt constitutively expressed mRNA. The 3' end of the cell cycle regulated mRNA terminates immediately following the region of hyphenated dyad symmetry typical of most histone mRNAs, whereas the constitutively expressed mRNA has a 1798 nt non-translated trailer that contains the same region of hyphenated dyad symmetry but is polyadenylated. The cap site for the H2B-GL105 mRNAs is located 42 nt upstream of the protein coding region. The H2B-GL105 histone gene was localized to chromosome region 1q21-1q23 by chromosomal in situ hybridization and by analysis of rodent-human somatic cell hybrids using an H2B-GL105 specific probe. The H2B-GL105 gene is paired with a functional H2A histone gene and this H2A/H2B gene pair is separated by a bidirectionally transcribed intergenic promoter region containing consensus TATA and CCAAT boxes and an OTF-1 element. These results demonstrate that cell cycle regulated and constitutively expressed histone mRNAs can be encoded by the same gene, and indicate that alternative 3' end processing may be an important mechanism for regulation of histone mRNA. Such control further increases the versatility by which cells can modulate the synthesis of replication-dependent as well as variant histone proteins during the cell cycle and at the onset of differentiation.
Analog Signal Acquisition from Computer Optical Disk Drives for Quantitative Chemical Sensing (2006)

Optoelectronic consumer products that are widely employed in the office and home attract attention for optical sensor applications due to (1) their cost advantage over analytical instruments produced only in small quantities, (2) robustness in operation due to the detailed manufacturability improvements, and (3) ease of operation. We demonstrate here a new approach for quantitative chemical/biochemical sensing when analog signals are acquired from conventional optical disk drives, and these signals are used for quantitative detection of optical changes of sensor films deposited on conventional CD and DVD optical disks. Because we do not alter manufacturing process of optical disks, any disk can be employed for deposition and readout of sensor films. The optical disk drives also perform their original function of reading and writing digital content to optical media because no optical modifications are introduced to obtain the analog signal. Such a sensor platform is quite universal and can be applied for chemical and biological quantitative detection, as well as for monitoring of changes of physical properties of regions deposited onto a CD or DVD (e.g., during combinatorial screening of materials). As a model example, we demonstrate the concept using chemical detection of ionic species such as Ca2+ in liquids (e.g., blood, urine, or water). Colorimetric calcium-sensitive sensor films were deposited onto a DVD, exposed to water with different concentrations of Ca2+, and quantified in the optical disk drive. The developed lab-on-DVD system demonstrated a 5 ppm detection limit of Ca2+ determinations, similar or slightly better than that achieved using a conventional fiber-optic portable spectrometer. This detection limit corresponded to a 0.023 absorbance unit resolution, as determined by the measurement of the same colorimetric films with a portable spectrometer. Determinations of Ca2+ unknowns using the lab-on-DVD system demonstrated +/-5 ppm accuracy and 2-5% relative standard deviation precision in predicting 100 ppm Ca2+.
FOXO3a Induces Differentiation of Bcr-Abl-transformed Cells through Transcriptional Down-regulation of Id1 (2006)

Leukemic transformation often requires activation of protein kinase B (PKB/c-Akt) and is characterized by increased proliferation, decreased apoptosis, and a differentiation block. PKB phosphorylates and inactivates members of the FOXO subfamily of Forkhead transcription factors. It has been suggested that hyperactivation of PKB maintains the leukemic phenotype through actively repressing FOXO-mediated regulation of specific genes. We have found expression of the transcriptional repressor Id1 (inhibitor of DNA binding 1) to be abrogated by FOXO3a activation. Inhibition of PKB activation or growth factor deprivation also resulted in strong down-regulation of Id1 promoter activity, Id1 mRNA, and protein expression. Id1 is highly expressed in Bcr-Abl-transformed K562 cells, correlating with high PKB activation and FOXO3a phosphorylation. Inhibition of Bcr-Abl by the chemical inhibitor STI571 resulted in activation of FOXO3a and down-regulation of Id1 expression. By performing chromatin immunoprecipitation assays and promoter-mutation analysis, we demonstrate that FOXO3a acts as a transcriptional repressor by directly binding to the Id1 promoter. STI571 treatment, or expression of constitutively active FOXO3a, resulted in erythroid differentiation of K562 cells, which was inhibited by ectopic expression of Id1. Taken together our data strongly suggest that high expression of Id1, through PKB-mediated inhibition of FOXO3a, is critical for maintenance of the leukemic phenotype.
Interdependent effect of angiotensin‐converting enzyme and platelet‐activating factor acetylhydrolase gene polymorphisms on the progression of immunoglobulin A nephropathy (2002)

In order to investigate the interdependent action of the insertion/deletion polymorphism of the angiotensin-converting enzyme (ACE) gene and polymorphism in exon 11 (C1136-->T; Ala379Val) of the platelet-activating factor acetylhydrolase (PAF-AH) gene, which encodes a functional antagonist of PAF, on the progression of immunoglobulin A (IgA) nephropathy, we analysed both polymorphisms in patients with primary IgA nephropathy, who were followed-up for longer than 3 years. During the follow-up (87.3 +/- 50.0 months), the disease progressed in 38 of the 191 patients (19.9%). The D allele of the ACE gene in the absence of the T allele of the PAF-AH gene did not affect the prognosis [odds ratio (OR), 3.6; 95% confidence interval (CI), 0.8-16.4] and neither did the T allele in the absence of the D allele (OR, 3.0; 95% CI, 0.4-24.2). However, the presence of both was a significant prognostic factor (OR, 6.6; 95% CI, 1.4-31.3). After adjusting for other risk factors, the presence of both proved to be an independent risk factor (OR, 4.5; 95% CI, 1.6-12.7). These results suggest that the interdependent effects of ACE and PAF-AH polymorphisms on the progression of IgA nephropathy might be more important than the effect of the individual polymorphisms.
Human colorectal adenocarcinoma cells: differential nitric oxide synthesis determines their ability to aggregate platelets. (1991)

The existence and role of an L-arginine:nitric oxide (NO) pathway in two human colorectal adenocarcinoma cell lines, SW-480 and SW-620, were investigated. Both cell lines, which derive from the same patient, SW-480 from the primary tumor and SW-620 from its metastatic lesion, were shown to have a cytosolic, Ca(2+)-independent, NADPH-dependent NO synthase, the activity of which was lower in the cytosol of SW-620. These cells were more potent inducers of platelet aggregation. In contrast, SW-480, which had more NO synthase activity, were less potent inducers of platelet aggregation. Pretreatment of both cell lines with NG-monomethyl-L-arginine, an inhibitor of NO synthase, potentiated their proaggregating effect and made them equally active. Exogenous L-arginine, NO, and related nitrovasodilators all inhibited platelet aggregation induced by SW-620. The antiaggregating activity of NO was further potentiated by prostacyclin and by M&B22948, a selective inhibitor of cyclic GMP phosphodiesterase. We propose that the generation of NO by tumor cells inversely correlates with their metastatic potential. Furthermore, we show that the lower activity of NO synthase in metastatic cells is due to the presence in these cells of a low molecular weight inhibitor of the NO synthase. In addition, agents which modulate platelet function by a cyclic GMP-dependent mechanism may be useful in the prevention of tumor metastasis.
Genetic Analysis of the Methanol- and Methylamine-Specific Methyltransferase 2 Genes of Methanosarcina acetivorans C2A (2008)

The entry of methanol into the methylotrophic pathway of methanogenesis is mediated by the concerted effort of two methyltransferases, namely, methyltransferase 1 (MT1) and methyltransferase 2 (MT2). The mtaA1, mtaA2, and mtbA genes of Methanosarcina acetivorans C2A encode putative methanol- or methylamine-specific MT2 enzymes. To address the in vivo roles of these genes in growth and methanogenesis from known substrates, we constructed and characterized mutants with deletions of each of these genes. The mtaA1 gene is required for growth on methanol, whereas mtaA2 was dispensable. However, the mtaA2 mutant had a reduced rate of methane production from methanol. Surprisingly, deletion of mtaA1 in combination with deletions of the genes encoding three methanol-specific MT1 isozymes led to lack of growth on acetate, suggesting that MT1 and MT2 enzymes might play an important role during growth on this substrate. The mtbA gene was required for dimethylamine and monomethylamine (MMA) utilization and was important, but not required, for trimethylamine utilization. Analysis of reporter gene fusions revealed that both mtaA1 and mtbA were expressed on all methanogenic substrates tested. However, mtaA1 expression was induced on methanol, while mtbA expression was down-regulated on MMA and acetate. mtaA2 was expressed at very low levels on all substrates. The mtaA1 transcript had a large 5' untranslated region (UTR) (275 bp), while the 5' UTR of the mtbA transcript was only 28 bp long.
Alteration of the specificity of subtilisin BPN' by site-directed mutagenesis in its S1 and S1' binding sites (1991)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAlteration of the specificity of subtilisin BPN' by site-directed mutagenesis in its S1 and S1' binding sitesPierre R. Bonneau, Thomas P. Graycar, David A. Estell, and J. Bryan JonesCite this: J. Am. Chem. Soc. 1991, 113, 3, 1026–1030Publication Date (Print):January 1, 1991Publication History Published online1 May 2002Published inissue 1 January 1991https://pubs.acs.org/doi/10.1021/ja00003a043https://doi.org/10.1021/ja00003a043research-articleACS PublicationsRequest reuse permissionsArticle Views180Altmetric-Citations52LEARN 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
Proteomimetic Libraries:  Design, Synthesis, and Evaluation of p53−MDM2 Interaction Inhibitors (2006)

The p53-MDM2 interaction regulates p53-mediated cellular responses to DNA damage, and MDM2 is overexpressed in 7% of all cancers. Structure-based computational design was applied to this system to design libraries centered on a scaffold that projects side chain functionalities with distance and angular relationships equivalent to those seen in the MDM2 interacting motif of p53. A library of 173 such compounds was synthesized using solution phase parallel chemistry. The in vitro competitive ability of the compounds to block p53 peptide binding to MDM2 was determined using a fluorescence polarization competition assay. The most active compound bound with K(d) = 12 microM, and its binding was characterized by (15)N-(1)H HSQC NMR.
Priming with T helper cell epitope peptides enhances the antibody response to the envelope glycoprotein of HIV-1 in primates (1991)

The induction of a memory immune response to HIV, mediated by any kind of effector mechanism, requires the induction of T cell help. In previous studies performed in different murine MHC haplotypes, three immunodominant T cell epitopes (T1, T2, and TH4.1) had been identified in the HIV envelope glycoprotein. Moreover, these peptides were proliferative T cell epitopes in humans. In this study, rhesus monkeys, Macaca mulatta, were primed with these three peptides either in combination or given separately. Half of the monkeys had a proliferative response to one or more of the priming peptide(s). Those monkeys who had a T cell proliferative response also had a high antibody response after one boost with a suboptimal dose of the native protein gp 160, whereas three of four control monkeys who had received only the native protein immunization gave no detectable antibody response, and one displayed a very weak response. For reasons that are unclear, antibodies only to the gp41 portion of gp 160 could be detected in the sera. Thus, the peptides can prime Th cells in primates for an enhanced antibody response on first exposure to the whole protein. The three peptides belong to highly conserved and nonglycosylated regions of the envelope protein. The fact that the peptides acted as immunogenic T cell proliferative and helper epitopes in nonhuman primates is very encouraging for including them in future vaccine studies in humans.
Transcranial magnetic stimulation--a new tool for functional imaging of the brain. (1999)

Recent progress in the theory and technology of transcranial magnetic stimulation (TMS) is leading to novel approaches in brain mapping. TMS becomes a powerful functional brain mapping tool when other imaging methods are used to record TMS-evoked activity or when peripheral effects are observed as a function of stimulus location. TMS-evoked activity currently can be recorded by EEG, PET, and fMRI. In addition to providing indices of cortical excitability, these methods allow one to study brain connectivity directly, without the need for behavioral activations. When the coordinate systems in the different imaging modalities are combined, anatomical structures seen in MRI and activation sites determined by PET, fMRI, or MEG/EEG can be used for the selection of target areas in the brain. PET and fMRI can be used to map the spatial distribution of TMS-evoked activity. On the other hand, the combination of TMS and high-resolution EEG may often be the method of choice for basic neuroscience and for clinical diagnosis, for example, in the assessment of brain connectivity in patients suffering from neurodegenerative diseases or head injuries.