gebhart/patrepeval huggingface dataset:
Production and secretion of immunoglobulins in the gastrointestinal tract. (1987)

Two decades ago it was shown that the major immunoglobulin (Ig) present in human secretions is a dimeric IgA covalently bound to an epithelial glycoprotein of about 80 kD, now called the secretory component (SC). Pentameric IgM is likewise actively enriched in most exocrine fluids and is associated with SC, although not in a covalently stabilized complex. Three findings explain the selective translocation of polymeric Ig (pIg) into exocrine fluids: (1) preferential local production; (2) J-chain-expressing capacity of pIg-producing immunocytes; and (3) SC-mediated epithelial transport. Human hepatocytes lack SC and the human liver, therefore, cannot act as an efficient "IgA pump". This is in contrast to the rat liver which shows a remarkable capacity for transport of dimeric IgA from blood into the bile. The J chain of pIg and the epithelial SC represent the "lock and key" in the glandular transport of secretory IgA (SIgA) and SIgM. It has recently been shown that SC is synthesized as a transmembrane protein of about 95 kD and constitutes the actual pIg surface receptor. Complexing between ligand and receptor in the plasma membrane is followed by endocytosis. The completed SIgA and SIgM molecules are then translocated in cytoplasmic vesicles through the epithelial cell to the gland lumen along with an excess of free SC. The main function of SIgA is to exert immune exclusion; that is, by intimate cooperation with innate nonspecific defense factors it decreases penetration of soluble antigens and inhibits epithelial colonization of bacteria and viruses. Especially in selective IgA deficiency, SIgM may exert a similar protective function since its synthesis is markedly increased in the intestinal mucosa. Leakage of IgG into exocrine fluids is enhanced by mucosal irritation. Although IgG should not be considered as a SIg, it may contribute to immune exclusion. This is seen especially in the respiratory tract where IgG is less easily subjected to proteolytic degradation than in the intestinal juice. In contrast, by activating complement, IgG antibodies may at the same time be phlogistic and accelerate mucosal penetration of antigens. IgG may thus contribute to persistent immunopathology in mucosal disease. The same is true for IgE antibodies which may be carried into mucous membranes and secretions by mast cells and cause their degranulation with local histamine release. Traces of IgD may likewise be found in the secretions but without obvious biologic significance. Regulation of secretory immunity takes place both in organized lymphoepithelial structures, such as the Peyer's patches, and adjacent to the glands in the lamina propria.(ABSTRACT TRUNCATED AT 400 WORDS)
Umbilical cord blood expansion with nicotinamide provides long-term multilineage engraftment (2014)

Gamida Cell Ltd.
WNT-1 Signaling Inhibits Apoptosis by Activating β-Catenin/T Cell Factor–Mediated Transcription (2001)

Wnt signaling plays a critical role in development and oncogenesis. Although significant progress has been made in understanding the downstream signaling cascade of Wnt signaling, little is known regarding Wnt signaling modification of the cell death machinery. Given that numerous oncogenes transform cells by providing cell survival function, we hypothesized that Wnt signaling may inhibit apoptosis. Here, we report that cells expressing Wnt-1 were resistant to cancer therapy-mediated apoptosis. Wnt-1 signaling inhibited the cytochrome c release and the subsequent caspase-9 activation induced by chemotherapeutic drugs, including both vincristine and vinblastine. Furthermore, we found that Wnt-1-mediated cell survival was dependent on the activation of beta-catenin/T cell factor (Tcf) transcription. Inhibition of beta-catenin/Tcf transcription by expression of the dominant-negative mutant of Tcf-4 blocked Wnt-1-mediated cell survival and rendered cells sensitive to apoptotic stimuli. These results provide the first demonstration that Wnt-1 inhibits cancer therapy-mediated apoptosis and suggests that Wnt-1 may exhibit its oncogenic potential through a mechanism of anti-apoptosis.
Invasion dynamics and potential spread of the invasive alien plant speciesAgeratina adenophora(Asteraceae) in China (2006)

ABSTRACT Ageratina adenophora (Sprengel) R. King &amp; H. Robinson (= Eupatorium adenophorum Sprengel) is one of the worst invasive alien species in China. Since A . adenophora was first noticed in Yunnan Province of China in the 1940s, its rapid spread has caused an ecological problem in south‐western China. Understanding its historical invasion pattern and its potential for further spread is needed to plan the management of the species. We reconstructed the historical process of its invasion and analysed its ecological preferences in the invaded region. After a lag phase of 20 years (1940–60), A . adenophora spread rapidly throughout the south and middle subtropical zones in Yunnan, Guizhou, Sichuan, and Guangxi, China, with an average expansion rate of 20 km per year. It spread relatively slowly in north subtropical areas, with an average expansion rate of 6.8 km per year. It has not established in warm temperate areas within the invaded regions. Although range expansion in Yunnan stopped after 1990, the expansion of its range into neighbouring provinces indicates that A . adenophora has not reached the full potential of its distribution and its range is still rapidly expanding within China. We applied ecological niche modelling (GARP — Genetic Algorithm for Rule‐set Prediction) to predict potential invasion areas in mainland China on the basis of occurrence points within colonized areas where A . adenophora has reached equilibrium. The predictions, confirmed by the range of values of four key environmental parameters, generally match the parameters of the geography and ecology in the invaded region. Southern and south‐central China have climatic conditions suggestive of a high potential for invasion by A . adenophora . Climatic conditions in northern and western China appear unsuitable for A . adenophora . Urgent measures should be taken to prevent this species from further spreading into the vast areas of potential habitat in southern and south‐central China.
Estimation of Global Ventricular Activation Sequences by Noninvasive Three‐Dimensional Electrical Imaging: Validation Studies in a Swine Model During Pacing (2008)

The present experimental results demonstrate that the noninvasive 3DCEI approach can localize the IS and estimate AS with good accuracy in an in vivo setting under control, paced, and/or diseased conditions.
Epidemiology of anxiety disorders in the 21st century (2015)

Anxiety disorders, including panic disorder with or without agoraphobia, generalized anxiety disorder, social anxiety disorder, specific phobias, and separation anxiety disorder, are the most prevalent mental disorders and are associated with immense health care costs and a high burden of disease. According to large population-based surveys, up to 33.7% of the population are affected by an anxiety disorder during their lifetime. Substantial underrecognition and undertreatment of these disorders have been demonstrated. There is no evidence that the prevalence rates of anxiety disorders have changed in the past years. In cross-cultural comparisons, prevalence rates are highly variable. It is more likely that this heterogeneity is due to differences in methodology than to cultural influences. Anxiety disorders follow a chronic course; however, there is a natural decrease in prevalence rates with older age. Anxiety disorders are highly comorbid with other anxiety disorders and other mental disorders.
Effects of Intravenous, Subcutaneous, and Intranasal Administration of Growth Hormone (GH)-Releasing Hormone-40 on Serum GH Concentrations in Normal Men* (1985)

In addition to stimulating GH release in normal subjects, GH-releasing hormone-40 (GHRH-40) stimulates GH secretion in some adults and children with GH deficiency. Recognizing that GHRH-40 may have potential as a therapeutic agent for the treatment of GH deficiency, we examined the effects of iv, sc, and intranasal (in) GHRH-40 administration on GH secretion and measured the plasma levels of immunoreactive GHRH achieved after the administration of the peptide via these different routes. Normal men were given vehicle or GHRH-40 iv (0.003, 0.01, 0.03, and 0.1 micrograms/kg; n = 10), sc (1, 3.3, and 10 micrograms/kg; n = 8), or in (3, 10, 30, and 100 micrograms/kg; n = 5). No subject had any symptoms after administration of vehicle or GHRH-40. During the 2-h period after iv administration of GHRH-40, the maximal increment in serum GH levels above basal (nanograms per ml; mean +/- SD) after the 0.1 micrograms/kg dose was 15.5 +/- 10.4 compared to 2.4 +/- 4.1 after vehicle (P = 0.0017). During the 3-h period after sc administration, when compared to the maximal increment in serum GH above basal after vehicle alone (10.2 +/- 12.9), the maximal increments above basal in serum GH were increased after both the 3.3 micrograms/kg (26.2 +/- 23.1; P = 0.022) and 10 micrograms/kg (63.6 +/- 53.5; P = 0.0003) doses. During the 3-h period after in administration, when compared to the maximal increment in serum GH above basal after vehicle alone (2.8 +/- 6.4), the maximal increments above basal in GH were higher after both the 30 micrograms/kg (18.5 +/- 10.4; P = 0.0053) and 100 micrograms/kg (21.7 +/- 8.1; P = 0.0028) doses. In addition, significant dose-response relationships were documented between the maximal increments above basal in serum GH and GHRH-40 administered by all routes. The mean (+/- SEM) peak plasma level of IR-GHRH (nanograms per ml) achieved after administration of 10 micrograms/kg GHRH-40, iv, as reported previously (66.6 +/- 17.6), was approximately 60- and 500-fold higher than the mean levels in the current study after administration of the same dose sc (1.11 +/- 0.39) or in (0.14 +/- 0.02), respectively. In summary, although GHRH-40 stimulates GH release when administered iv, sc, or in, significantly higher doses were required using the sc and in routes to achieve responses comparable to those obtained with iv administration.
A Comprehensive Resource of Interacting Protein Regions for Refining Human Transcription Factor Networks (2010)

Large-scale data sets of protein-protein interactions (PPIs) are a valuable resource for mapping and analysis of the topological and dynamic features of interactome networks. The currently available large-scale PPI data sets only contain information on interaction partners. The data presented in this study also include the sequences involved in the interactions (i.e., the interacting regions, IRs) suggested to correspond to functional and structural domains. Here we present the first large-scale IR data set obtained using mRNA display for 50 human transcription factors (TFs), including 12 transcription-related proteins. The core data set (966 IRs; 943 PPIs) displays a verification rate of 70%. Analysis of the IR data set revealed the existence of IRs that interact with multiple partners. Furthermore, these IRs were preferentially associated with intrinsic disorder. This finding supports the hypothesis that intrinsically disordered regions play a major role in the dynamics and diversity of TF networks through their ability to structurally adapt to and bind with multiple partners. Accordingly, this domain-based interaction resource represents an important step in refining protein interactions and networks at the domain level and in associating network analysis with biological structure and function.
Effects of gentamicin on sphingomyelinase activity in cultured human renal proximal tubular cells. (1987)

We have previously shown that cultured human proximal tubular cells (PT) incubated with gentamicin contain numerous "myeloid bodies." This morphological change was accompanied by the storage of phosphatidylcholine and sphingomyelin. In order to delineate the biochemical mechanisms responsible for the accumulation of sphingomyelin in cells incubated with gentamicin, we pursued detailed studies on the activity of sphingomyelinase. Characterization studies on sphingomyelinase revealed that this enzyme has a bimodal pH optima in PT cells. Optimum activity was observed at pH 5.6 (designated as acid sphingomyelinase, A-SMase) and at pH 7.4 (designated as neutral sphingomyelinase, N-SMase). The activity of both the enzymes increased proportionately in control cells as a function of days of incubation. The activity of A-SMase was 16% lower in cells incubated with gentamicin as compared to control. The most striking observation was a gradual decline in the activity of N-SMase in cells incubated with gentamicin. Thus, following 21 days of incubation of cells with 0.3 mM gentamicin, the N-SMase was 2.7-fold lower than control cells. Mg2+ stimulated and Triton X-100 inhibited the activity of N-SMase. Whereas Mg2+ had no effects, Triton X-100 stimulated the activity of the A-SMase in PT cells. Moreover, A-SMase was relatively more heat-resistant than the N-SMase. The Km values for sphingomyelin using A-SMase in control cells and cells incubated with gentamicin were 0.07 X and 0.016 X 10(-7) M, respectively, whereas the Km values for sphingomyelin using N-SMase in control cells and cells incubated with gentamicin were 1.8 X and 1.5 X 10(-7) M, respectively. These findings suggest that gentamicin exerts a competitive inhibition of the A-SMase in PT cells. In contrast, gentamicin exerts a noncompetitive inhibition of the N-SMase in PT cells. Subcellular fractionation studies revealed that A-SMase was exclusively localized in the "lysosome-rich" fraction, whereas most, if not all, the N-SMase was localized in the microsomal fraction and "plasma-membrane"-rich fraction in cultured PT cells. Cells incubated with gentamicin for 21 days contained 25% lower activity of A-SMase associated with the lysosomal fraction as compared to control. In contrast, N-SMase activity in the microsomal and plasma membrane fraction was one-half as compared to control. We conclude that gentamicin-mediated decrease in sphingomyelinase activity may be responsible for the storage of sphingomyelin in cultured human PT cells.(ABSTRACT TRUNCATED AT 400 WORDS)
Upregulation of IL-10 gene expression in porcine peripheral blood mononuclear cells by porcine reproductive and respiratory syndrome virus (2003)

Several lines of evidence suggest that porcine reproductive and respiratory syndrome virus (PRRSV) may have immunomodulatory effects on the host immune system. To determine the effect of PRRSV on cytokine production, a multiplex PCR was established. This allowed a semi-quantitative analysis of IFN-gamma, IL-2, IL-4, IL-10 and glyceraldehyde 3-phosphate dehydrogenase (GAPDH) gene expression levels from porcine peripheral blood mononuclear cells (PBMCs). These results showed that both live and inactivated PRRSV predominantly upregulated IL-10 gene expression in porcine PBMCs. In addition, when PBMCs from pigs immunized previously with classical swine fever virus (CSFV) vaccine were cultivated with the recall antigen, CSFV, in the presence of PRRSV, significant upregulation of IL-10 gene expression and reduction of IFN-gamma gene expression were observed. These findings indicated that the presence of PRRSV in the culture could affect recall antigen response. This study implies that the induction of IL-10 production may be one of the strategies used by PRRSV to modulate host immune responses.
A review of pharmacological therapy for glaucoma (2005)

Glaucoma is a chronic or acute disease in which optic nerve damage occurs in a characteristic way. In primary open angle glaucoma (POAG), the manifestations of the optic nerve damage include visible excavation that develops in the optic nerve head and regions of the retina lose ability to detect all the elements that go into the total sensory prod-uct called vision.1, 2 When these regions worsen and enlarge to coalesce, the result is blindness.The intraocular pressure (IOP) has a causative role in producing the damage. All eyes have an in-ternal pressure to keep them inﬂated, perhaps 17 mmHg on the average, ± 5 mmHg standard devia-tion. In at least two thirds of the eyes that suffer glaucomatous damage, the intraocular pressure is high, at least a bit above the pressure found in 95% of the non-glaucomatous population. The cut-off is in the region of 20 to 22 mmHg used by most deﬁnitions.2 However, a normal or even low intra-ocular pressure can be harmful to some eyes, and when it is, the person has normal or low tension glaucoma. The traditional treatment of glaucoma has logically been to lower the intraocular pres-sure, to prevent further damage to the optic nerve, though previous damage is not undone.
Epiregulin as a Major Autocrine/Paracrine Factor Released From ERK- and p38MAPK-Activated Vascular Smooth Muscle Cells (2003)

Epiregulin is released from VSMCs primed by atherogenic factors and acts as a major autocrine/paracrine factor for VSMC dedifferentiation. It may be involved in the progression of vascular remodeling such as atherosclerosis.
Inhibition of translation by IFIT family members is determined by their ability to interact selectively with the 5′-terminal regions of cap0-, cap1- and 5′ppp- mRNAs (2013)

Ribosomal recruitment of cellular mRNAs depends on binding of eIF4F to the mRNA's 5'-terminal 'cap'. The minimal 'cap0' consists of N7-methylguanosine linked to the first nucleotide via a 5'-5' triphosphate (ppp) bridge. Cap0 is further modified by 2'-O-methylation of the next two riboses, yielding 'cap1' (m7GpppNmN) and 'cap2' (m7GpppNmNm). However, some viral RNAs lack 2'-O-methylation, whereas others contain only ppp- at their 5'-end. Interferon-induced proteins with tetratricopeptide repeats (IFITs) are highly expressed effectors of innate immunity that inhibit viral replication by incompletely understood mechanisms. Here, we investigated the ability of IFIT family members to interact with cap1-, cap0- and 5'ppp- mRNAs and inhibit their translation. IFIT1 and IFIT1B showed very high affinity to cap-proximal regions of cap0-mRNAs (K1/2,app ∼9 to 23 nM). The 2'-O-methylation abrogated IFIT1/mRNA interaction, whereas IFIT1B retained the ability to bind cap1-mRNA, albeit with reduced affinity (K1/2,app ∼450 nM). The 5'-terminal regions of 5'ppp-mRNAs were recognized by IFIT5 (K1/2,app ∼400 nM). The activity of individual IFITs in inhibiting initiation on a specific mRNA was determined by their ability to interact with its 5'-terminal region: IFIT1 and IFIT1B efficiently outcompeted eIF4F and abrogated initiation on cap0-mRNAs, whereas inhibition on cap1- and 5'ppp- mRNAs by IFIT1B and IFIT5 was weaker and required higher protein concentrations.
In vivo characterization of endogenous proliferating cells in adult rat subcortical white matter (1996)

Proliferating cells in adult rat subcortical white matter were characterized in vivo using stereotactic injections of a replication-deficient retrovirus containing the construct for beta galactosidase (BAG); BAG was deposited into the cingulum at the level of the septal nuclei. Morphological profiles, generated using Xgal substrate to visualize labeled cells, revealed a population of simple, immature cells. The antigenic profile, generated immunohistochemically with cell-specific markers 2 or 30 days post injection (dpi), showed a population of cells that primarily expressed nestin or an oligodendrocyte-specific glutathione-S-transferase isoform, Yp (GST-Yp) at 2 dpi and nestin, GST-Yp or Rip at 30 dpi. Occasionally, labeled cells differentiated in vivo into myelinating oligodendrocytes 30 dpi. Labeled cells did not express the astrocyte markers GFAP, GST-Yb, or S100 beta at 2 or 30 dpi. Comparisons of cell distribution 2 and 30 dpi indicated the non-migratory nature of these cells. Cell distribution patterns and nearest neighbor analyses confirmed the emergence of clusters of labeled cells 30 dpi, which bromodeoxyuridine (BrdU) incorporation studies suggested arose from continued proliferation of some labeled cells. In vivo characterization of proliferating cells in the adult revealed a non-migratory, primarily undifferentiated population of cells.
Examination of a CpG Island Methylator Phenotype and Implications of Methylation Profiles in Solid Tumors (2006)

The CpG island methylator phenotype (CIMP), thoroughly described in colorectal cancer and to a lesser extent in other solid tumors, is important in understanding epigenetics in carcinogenesis and may be clinically useful for classification of neoplastic disease. Therefore, we investigated whether this putative phenotype exists in exposure-related solid tumors, where somatic gene alterations and enhanced clonal growth are selected for by carcinogens, and examined the ability of methylation profiles to classify malignant disease. We studied promoter hypermethylation of 16 tumor suppressor genes and 3 MINT loci (acknowledged classifiers of CIMP) in 344 bladder cancers, 346 head and neck squamous cell carcinomas (HNSCC), 146 non-small-cell lung cancer (NSCLC), and 71 malignant pleural mesotheliomas (MPM). We employed rigorous statistical methods to examine the distribution of promoter methylation and the usefulness of these profiles for disease classification. In bladder cancer, HNSCC, and NSCLC, there was a significant correlation (P < 0.0001) between methylation of the three MINT loci and methylation index, although the distribution of methylated loci varied significantly across these disease. Although there was a significant (P < 0.001) association between gene methylation profile and disease, rates of misclassification of each disease by their methylation profile ranged from 28% to 32%, depending on the classification scheme used. These data suggest that a form of CIMP exists in these solid tumors, although its etiology remains elusive. Whereas the gene profiles of hypermethylation among examined loci could not unequivocally distinguish disease type, the existence of CIMP and the relative preponderance of hypermethylation in these cancers suggest that methylation analysis may be clinically useful as a targeted screening tool.
Polyisobutylene‐based urethane foams. II. Synthesis and properties of novel polyisobutylene‐based flexible polyurethane foams (1989)

Abstract Novel polyisobutylene‐based flexible polyurethane foams (PIB–PUF) have been prepared manually by the prepolymer method using three‐arm star hydroxyl‐terminated polyisobutylenes (PIB–triols) and toluene diisocyanate (TDI). Solvent extraction and IR spectroscopy of PIB–PUFs indicated essentially complete crosslinking. Conventional polyether‐based polyrethane foams (PE–PUFs) and polybutadiene‐based polyurethane foams (PBD–PUFs) have also been prepared by the same method and select physical‐mechanical properties of all these urethane foams, such as tensile strength, elongation, resilience, water permeability, hot air stability, and hydrolytic stability, have been examined and compared. Although the density of PIB–PUF is lower than that of PE–PUF, its tensile strength is superior to the latter. Elongation of PIB–PUF is almost the same as those of the other foams. The PIB–PUF exhibits low resilience which indicates good damping properties. Due to the hydrophobicity of the soft segment, PIB–PUF exhibits very low water permeability. The hydrolytic and hot air stability of PIB–PUFs are outstanding. Attempts have been made to determine gas permeabilities; however, due to the open‐cell nature of the foams, these studies could not be completed. The new PIB‐based urethane foams combine excellent thermal, environmental, barrier, and mechanical properties, unmatched by conventional PUFs.