gebhart/patrepeval huggingface dataset:
Endovascular Treatment of Acute Stroke: Evolution and Selection of Techniques and Instruments Based on Thrombus Imaging (2015)

Mechanical thrombectomy provides higher recanalization rates than intravenous or intra-arterial thrombolysis. Finally this has been shown to translate into improved clinical outcome in six multicentric randomized controlled trials. However, within cohorts the clinical outcomes may vary, depending on the endovascular techniques applied. Systems aiming mainly for thrombus fragmentation and lacking a protection against distal embolization have shown disappointing results when compared to recent stent-retriever studies or even to historical data on local arterial fibrinolysis. Procedure-related embolic events are usually graded as adverse events in interventional neuroradiology. In stroke, however, the clinical consequences of secondary emboli have so far mostly been neglected and attributed to progression of the stroke itself. We summarize the evolution of instruments and techniques for endovascular, image-guided, microneurosurgical recanalization in acute stroke, and discuss how to avoid procedure-related embolic complications.
Immunohistochemical evaluation of carcinoembryonic antigen, secretory component, and epithelial IgA in ulcerative colitis with dysplasia. (1982)

Immunofluorescence staining for carcinoembryonic antigen, secretory component, and epithelial IgA was evaluated semiquantitatively in routine formalin-fixed mucosal biopsy samples from five patients with ulcerative colitis who had undergone colectomy because of carcinomas. Selected areas were given fluorescence intensity scores without knowledge of whether dysplasia or reactive hyperplasia was present as judged by another observer from conventional histopathological features in adjacent sections. The two types of lesion did not differ significantly with regard to the expression of the three marker antigens. In a prospective study based on cold ethanol-fixed mucosal biopsy samples, lesions from 11 ulcerative colitis patients with dysplasia were compared blindly with lesions from six patients with reactive hyperplasia and with samples obtained endoscopically from eight normal controls. The range of disease-associated fluorescence intensity scores was wide, but staining for all markers tended to be brighter in reactive hyperplasia than in dysplasia (P less than 0.01). In the controls, the fluorescence intensity score tended to be lower for carcinoembryonic antigen but was significantly (P less than 0.01) higher for secretory component and epithelial IgA than in both types of lesion. Moreover, staining for secretory component and epithelial IgA in the lesions seemed to be inversely related to the grade of dysplasia and the degree of inflammation. No such trend was seen for carcinoembryonic antigen. The wide ranges of individual fluorescence scores precluded the possibility of applying carcinoembryonic antigen, secretory component, and epithelial IgA as immunohistochemical markers to differentiate between dysplasia and reactive hyperplasia in routine diagnostic work.
Characterization of a new subpopulation of mouse CD8α+ B220+ dendritic cells endowed with type 1 interferon production capacity and tolerogenic potential (2002)

We describe a new B220+ subpopulation of immaturelike dendritic cells (B220+ DCs) with low levels of expression of major histocompatibility complex (MHC) and costimulatory molecules and markedly reduced T-cell stimulatory potential, located in the thymus, bone marrow, spleen, and lymph nodes. B220+ DCs display ultrastructural characteristics resembling those of human plasmacytoid cells and accordingly produce interferon-alpha after virus stimulation. B220+ DCs acquired a strong antigen-presenting cell capacity on incubation with CpG oligodeoxynucleotides, concomitant with a remarkable up-regulation of MHC and costimulatory molecules and the production of interleukin-12 (IL-12) and IL-10. Importantly, our data suggest that nonstimulated B220+ DCs represent a subset of physiological tolerogenic DCs endowed with the capacity to induce a nonanergic state of T-cell unresponsiveness, involving the differentiation of T regulatory cells capable of suppressing antigen-specific T-cell proliferation. In conclusion, our data support the hypothesis that B220+ DCs represent a lymphoid organ subset of immature DCs with a dual role in the immune system-exerting a tolerogenic function in steady state but differentiating on microbial stimulation into potent antigen-presenting cells with type 1 interferon production capacity.
Fabry disease: isolation of a cDNA clone encoding human alpha-galactosidase A. (1985)

Fabry disease is an X-linked inborn error of metabolism resulting from the deficient activity of the lysosomal hydrolase, alpha-galactosidase A (alpha-Gal A; alpha-D-galactoside galactohydrolase, EC 3.2.1.22). To investigate the structure, organization, and expression of alpha-Gal A, as well as the nature of mutations in Fabry disease, a clone encoding human alpha-Gal A was isolated from a lambda gt11 human liver cDNA expression library. To facilitate screening, an improved affinity purification procedure was used to obtain sufficient homogeneous enzyme for production of monospecific antibodies and for amino-terminal and peptide microsequencing. On the basis of an amino-terminal sequence of 24 residues, two sets of oligonucleotide mixtures were synthesized corresponding to adjacent, but not overlapping, amino acid sequences. In addition, an oligonucleotide mixture was synthesized based on a sequence derived from an alpha-Gal A internal tryptic peptide isolated by reversed-phase HPLC. Four positive clones were initially identified by antibody screening of 1.4 X 10(7) plaques. Of these, only one clone (designated lambda AG18) demonstrated both antibody binding specificity by competition studies using homogeneous enzyme and specific hybridization to synthetic oligonucleotide mixtures corresponding to amino-terminal and internal amino acid sequences. Nucleotide sequencing of the 5' end of the 1250-base-pair EcoRI insert of clone lambda AG18 revealed an exact correspondence between the predicted and known amino-terminal amino acid sequence. The insert of clone lambda AG18 appears to contain the full-length coding region of the processed, enzymatically active alpha-Gal A, as well as sequences coding for five amino acids of the amino-terminal propeptide, which is posttranslationally cleaved during enzyme maturation.
Interleukin-7 is a critical growth factor in early human T-cell development (1996)

Abstract Highly purified human CD34+ fetal liver stem cells differentiate to mature T cells when seeded in vitro into isolated fetal thymic lobes of severe combined immunodeficient (SCID) mice followed by fetal thymus organ culture (FTOC). Here, this chimeric human-mouse FTOC was used to address the role of interleukin-7 (IL-7) and of the alpha chain of the IL-7 receptor (IL-7R alpha) in early human T-cell development. We report that addition of either the monoclonal antibody (MoAb) M25, which neutralizes both human and mouse IL-7, or the MoAb M21, which recognizes and blocks exclusively the human high-affinity alpha-chain of the IL-7R, results in a profound reduction in human thymic cellularity. Analysis of lymphoid subpopulations indicates that a highly reduced number of cells undergo maturation from CD34+ precursor cells toward CD4+CD3-CD1+ progenitor cells and subsequently toward CD4+CD8+ thymocytes. Our results reveal a critical role for IL-7 during early human thymocyte development, and may explain the absence or highly reduced levels of T cells in patients with X-linked SCID. The molecular defect in these patients has been shown to be a mutation in the gamma chain of the IL-2R. Although this gamma chain is not only present in the IL-2R, but also forms an essential part of other cytokine receptors, including IL-4, IL-7, IL-9, IL-13, and IL-15, the T- cell defect in these patients can be explained by the fact that IL-7 is not able to transduce its signal by the molecular defect of the common gamma (gamma c) chain and that IL-7 is indispensable for T-cell development.
Effect of Resistive Loading on Variational Activity of Breathing (1998)

To examine the effect of resistive loading on variational activity of breathing, we studied 18 healthy subjects breathing at rest and with inspiratory resistive loads of 3 and 6 cm H2O/L/s, applied randomly for 1 h each. Compared with resting breathing, a resistive load of 3 cm H2O/L/s decreased the total variational activity of expiratory time (TE) and minute ventilation (V I), whereas a load of 6 cm H2O/L/s increased the total variational activity of inspiratory time (TI). Compared with the load of 3 cm H2O/L/s, the load of 6 cm H2O/L/s increased total variational activity of tidal volume (VT), TI, TE, and V I. Partitioning of the total variational activity revealed that these alterations were due to changes in the random uncorrelated fraction. Compared with rest, both the resistive loads of 3 and 6 cm H2O/L/s increased the number of breath lags displaying significant serial correlations ("short-term memory") of TI. Compared with rest, the load of 3 cm H2O/L/s increased the autocorrelation coefficient at a lag of one breath for VT and the load of 6 cm H2O/L/s increased the correlated fraction of variational activity of VT. Thus, three measures of correlated behavior-autocorrelation coefficient at a lag of 1 breath, "short-term memory," and the correlated fraction of total variational activity- increased with loading. In conclusion, resistive loading changed total variational activity according to the size of the load: the random fraction decreased with the smaller load but increased with the larger load; in contrast, correlated behavior increased with both loads. The different behaviors of random and correlated variability with loading may reflect different physiologic influences on respiratory control.
Targeted Protein Surface Sensors as a Tool for Analyzing Small Populations of Proteins in Biological Mixtures (2014)

Optical cross-reactive sensor arrays (the so-called chemical "noses/tongues") have recently been demonstrated as a powerful tool for high-throughput protein detecting and analysis. Nevertheless, applying this technology to biomarker detection is complicated by the difficulty of non-selective sensors to operate in biological mixtures. Herein we demonstrate a step toward circumventing this limitation by using self-assembled fluorescent receptors consisting of two distinct recognition motifs: specific and non-specific. When combined in an array, binding cooperatively between the specific and non-specific protein binders enables the system to discriminate among closely related isoform biomarkers even in the presence of serum proteins or within human urine.
Causal Modeling Using Network Ensemble Simulations of Genetic and Gene Expression Data Predicts Genes Involved in Rheumatoid Arthritis (2011)

Tumor necrosis factor α (TNF-α) is a key regulator of inflammation and rheumatoid arthritis (RA). TNF-α blocker therapies can be very effective for a substantial number of patients, but fail to work in one third of patients who show no or minimal response. It is therefore necessary to discover new molecular intervention points involved in TNF-α blocker treatment of rheumatoid arthritis patients. We describe a data analysis strategy for predicting gene expression measures that are critical for rheumatoid arthritis using a combination of comprehensive genotyping, whole blood gene expression profiles and the component clinical measures of the arthritis Disease Activity Score 28 (DAS28) score. Two separate network ensembles, each comprised of 1024 networks, were built from molecular measures from subjects before and 14 weeks after treatment with TNF-α blocker. The network ensemble built from pre-treated data captures TNF-α dependent mechanistic information, while the ensemble built from data collected under TNF-α blocker treatment captures TNF-α independent mechanisms. In silico simulations of targeted, personalized perturbations of gene expression measures from both network ensembles identify transcripts in three broad categories. Firstly, 22 transcripts are identified to have new roles in modulating the DAS28 score; secondly, there are 6 transcripts that could be alternative targets to TNF-α blocker therapies, including CD86--a component of the signaling axis targeted by Abatacept (CTLA4-Ig), and finally, 59 transcripts that are predicted to modulate the count of tender or swollen joints but not sufficiently enough to have a significant impact on DAS28.
Characterization of Apomictic BC7 and BC8 Pearl Millet: Meiotic Chromosome Behavior and Construction of an ASGR‐carrier Chromosome‐specific Library (2010)

Apospory in Pennisetum squamulatum Fresen is inherited as a single‐locus dominant trait. Molecular analysis has identified the apospory‐specific genomic region (ASGR), a large segment of one chromosome that is necessary and sufficient to confer apomixis. To transfer apospory from P. squamulatum to pearl millet [ P. glaucum (L.) R. Br.], advanced backcrosses were generated. Here we report the characterization of apomictic BC 7 and BC 8 generations. A BC 7 –derived genotype has two P. squamulatum chromosomes, while BC 8 –derived apomictic lines inherited only the ASGR chromosome that confers apospory to pearl millet. Morphologically, no significant differences were observed between backcross generations for plant height, leaf length, leaf width, and first internode and inflorescence lengths. However, the BC 7 and BC 8 lines differed significantly with regard to pollen viability, flowering time, and seed set. Pollen viability increased to 81% in the BC 8 lines compared with 37% in BC 7 . The frequency of aposporous embryo sacs was lower in BC 8 (79%) lines compared to BC 7 (93%). Meiotic behavior of chromosomes during metaphase I and anaphase I showed that BC 8 typically had a single univalent, identified as the ASGR chromosome by FISH (fluorescence in situ hybridization) and GISH (genomic in situ hybridization). Utilizing its unique behavior during meiosis the ASGR chromosome was microdissected and a chromosome‐specific library was constructed and sequenced. Analysis of sequences identified both novel and previously known ASGR‐linked sequences.
Oxidative modifications of glyceraldehyde 3-phosphate dehydrogenase regulate metabolic reprogramming of stored red blood cells (2016)

Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) plays a key regulatory function in glucose oxidation by mediating fluxes through glycolysis or the pentose phosphate pathway (PPP) in an oxidative stress-dependent fashion. Previous studies documented metabolic reprogramming in stored red blood cells (RBCs) and oxidation of GAPDH at functional residues upon exposure to pro-oxidants diamide and H2O2 Here we hypothesize that routine storage of erythrocyte concentrates promotes metabolic modulation of stored RBCs by targeting functional thiol residues of GAPDH. Progressive increases in PPP/glycolysis ratios were determined via metabolic flux analysis after spiking (13)C1,2,3-glucose in erythrocyte concentrates stored in Additive Solution-3 under blood bank conditions for up to 42 days. Proteomics analyses revealed a storage-dependent oxidation of GAPDH at functional Cys152, 156, 247, and His179. Activity loss by oxidation occurred with increasing storage duration and was progressively irreversible. Irreversibly oxidized GAPDH accumulated in stored erythrocyte membranes and supernatants through storage day 42. By combining state-of-the-art ultra-high-pressure liquid chromatography-mass spectrometry metabolic flux analysis with redox and switch-tag proteomics, we identify for the first time ex vivo functionally relevant reversible and irreversible (sulfinic acid; Cys to dehydroalanine) oxidations of GAPDH without exogenous supplementation of excess pro-oxidant compounds in clinically relevant blood products. Oxidative and metabolic lesions, exacerbated by storage under hyperoxic conditions, were ameliorated by hypoxic storage. Storage-dependent reversible oxidation of GAPDH represents a mechanistic adaptation in stored erythrocytes to promote PPP activation and generate reducing equivalents. Removal of irreversibly oxidized, functionally compromised GAPDH identifies enhanced vesiculation as a self-protective mechanism in ex vivo aging erythrocytes.
Proteome analysis: Biological assay or data archive? (1998)

In this review we examine the current state of proteome analysis. There are three main issues discussed: why it is necessary to study proteomes; how proteomes can be analyzed with current technology; and how proteome analysis can be used to enhance biological research. We conclude that proteome analysis is an essential tool in the understanding of regulated biological systems. Current technology, while still mostly limited to the more abundant proteins, enables the use of proteome analysis both to establish databases of proteins present, and to perform biological assays involving measurement of multiple variables. We believe that the utility of proteome analysis in future biological research will continue to be enhanced by further improvements in analytical technology.
Ex Vivo Expansion of Frozen Cord Blood Products without Selection. (2004)

Abstract Ex vivo expansion of cord blood products (CB) has been proposed as an approach to increase the number of cells available from a single CB unit. We and others have reported the requirement of CD34 selection for optimal expansion of CB products, however, the selection of frozen CB products results in significant losses of CD34+ cells with a median recovery of 43% (range 6 to 203%, N=40) and low purities resulting in decreased expansion. Therefore we explored approaches to expand CB without prior selection and have described the use of co-culture of CB mononuclear cells (MNC) on mesenchymal stem cells (MSC). In the present study we have evaluated the expansion of clinical CB products (provided by Duke University CB Bank CB). MNC were obtained after ficol separation of RBCs and 10% of the CB product was cultured on preformed layers of MSC in T150 flasks containing 50ml of defined media (Sigma Aldrich) plus 100 ng/ml each of rhSCF, rhG-CSF and rhTpo. After 6 days of culture, the non adherent cells were transferred to a Teflon bag and a further 50 ml of media and GFs added to the flask. Again at day 10, non adherent cells were transferred to the Teflon bag and media and growth factors replaced. At day 12 to 13 of incubation the cells were harvested, washed and total nucleated cell (TNC) counts and progenitor assays performed. In three separate experiments we have achieved greater than 20 fold expansion of TNC with a median of 22, and a median expansion of GM-CFC of 37 fold. Morphologic analysis demonstrated the expanded cells contained high levels of mature neutrophils and neutrophil precursors. In vivo studies in NOD/SCID mice also demonstrated that the expanded cells maintained in vivo engraftment potential. Clinical studies are being designed to evaluate the in vivo potential of CB MNC products expanded on MSC.
Pedicle Fat Grafts for the Prevention of Scar Formation After Laminectomy (1979)

The formation of scar tissue always follows lumbar disc surgery and usually causes no difficulty. Reoperation may be necessary because of disc reherniation or because of the scar tissue itself. Reoperation is tedious and dangerous because of the presence of scar formation. Beginning in February 1975, the authors performed laminotomies in 107 dogs in an attempt to study the possibility of prevention of scar tissue formation about the dural sac and nerve roots. Gelfoam and Gelfilm were found to increase scar formation. Micropore tape and plastics such as polyethylene, mylar, and woven and smooth silastic were tried without complete success. Free fat grafts gave better protection than other substances, but it was found that pedicle grafts of fat gave more complete prevention of scar. The living pedicle fat grafts also prevented the usual closure of the laminotomy. The technique of pedicle fat grafts has also been used with success in 36 human patients to date.
Inhibition of α4 Integrin Protects Against Transient Focal Cerebral Ischemia in Normotensive and Hypertensive Rats (2001)

These data demonstrate that inhibition of alpha4 integrin can protect the brain against ischemic brain injury and implicate endogenous alpha4 integrin in the pathogenesis of acute brain injury. The mechanism by which alpha4 integrin inhibition offers cerebroprotection is independent of blood pressure modulation and is likely due to inhibition of leukocyte function.
T-cell antigen receptor binding sites for the microbial superantigen staphylococcal enterotoxin A. (1992)

We have examined the interaction of the microbial superantigen staphylococcal enterotoxin A (SEA) with peptides corresponding to overlapping regions of the T-cell antigen receptor beta chain variable region V beta 3. SEA is known to stimulate murine T cells bearing certain V beta elements, among them V beta 3. Five peptides were synthesized representing amino acids 1-24, 20-44, 39-60, 57-77, and 74-95 of V beta 3. We demonstrate here that soluble V beta 3-bearing beta chains can bind to a complex of SEA and major histocompatibility complex class II and that the synthetic peptide V beta 3-(57-77) blocked this interaction. The peptide V beta 3-(57-77) also inhibited SEA-induced interferon-gamma production and SEA-induced proliferation of B10.BR spleen cells. Conversely, the peptide corresponding to amino acids 57-77 of V beta 8.2, a V beta element that is not recognized by SEA, decreased staphylococcal enterotoxin C-2-induced proliferation but did not affect SEA-induced proliferation. The peptide inhibition of SEA-induced function was due at least in part to inhibition of V beta 3-bearing T-cell activity, since the percentage of T cells reactive with an anti-V beta 3 monoclonal antibody was significantly reduced by V beta 3-(57-77). These data suggest that the region of V beta 3 encompassing amino acids 57-77 is an area that displays the appropriate sequence and conformation for binding of the SEA molecule and blocking of the resultant interaction with the T-cell antigen receptor.