gebhart/patrepeval huggingface dataset:
Impact of Variation Near MC4R on Whole‐body Fat Distribution, Liver Fat, and Weight Loss (2009)

Polymorphisms near the melanocortin-4 receptor (MC4R) gene locus are associated with body weight. Recent studies have shown that they influence insulin sensitivity and incidence of the metabolic syndrome. Thus, we hypothesized that the candidate single-nucleotide polymorphism (SNP) rs17782313 near MC4R additionally influences body fat distribution and its change during lifestyle intervention. To test this, 343 German subjects were genotyped for SNP rs17782313. Body composition was assessed using magnetic resonance technique. Subjects were characterized by an oral glucose tolerance test (OGTT). A subgroup of 242 subjects participated in a 9-month lifestyle intervention. In the overall cohort, the C allele was associated with a higher BMI (P=0.0013), but had no impact on glucose tolerance or insulin sensitivity (all P>or=0.10). There was an effect of the SNP on total body fat (P=0.022) and nonvisceral fat (P=0.017), but not on liver fat and visceral fat (all P>or=0.33). In the subgroup undergoing lifestyle intervention, SNP rs17782313 had no impact on changes in body weight or fat distribution. Despite an association with BMI and nonvisceral adipose tissue, the SNP rs17782313 did not influence visceral adipose tissue. Thus, this candidate SNP for human obesity may preferentially affect the accumulation of subcutaneous adipose tissue. Furthermore, the variation near MC4R has no effect on success of weight loss during lifestyle intervention.
Localization of neuregulin isoforms and erbB receptors in myelinating glial cells (2003)

Neuregulins (NRGs) are growth factors present in neurons and glial cells of the central and peripheral nervous systems and play a role in the survival, proliferation, and differentiation of these cells. We now report the localization of the two major isoforms of NRG (alpha and beta) and their receptors (erbB) in cultured Schwann cells and oligodendrocytes isolated from neonatal rat pups. Immunocytochemistry and Western blots for NRG and erbB receptors in defined subcellular fractions were utilized to assess cellular localization. Less differentiated oligodendrocytes contain both NRG isoforms in the cell bodies but not the processes, while only NRG-1beta was found in the nucleus. In contrast, more differentiated oligodendrocytes contained neither isoform in the nucleus while both isoforms were colocalized in the cytoplasm and cell processes. In Schwann cells, both NRG-1beta and NRG-1alpha were colocalized in the cytoplasm and processes. The Schwann cell nucleus had weak immunoreactivity for both NRG-1 isoforms, although NRG-1beta was predominant. ErbB2 and erbB3 receptors, which transduce the NRG-1 signal in Schwann cells, were found throughout the cytoplasm and in the processes and were also localized in the cell nucleus. The nuclear localization of NRG-1 isoforms and/or erbB receptors in both cell types was confirmed by Western blotting of nuclear and cytoplasmic extracts. Stimulation of Schwann cells with mitotic agents increased NRG-1beta expression in the nucleus and dramatically suppressed NRG-1alpha expression throughout the cell. The functional implications of this differential localization in myelinating cells are discussed.
Multisite stimulation for correction of cardiac asynchrony (2000)

Cardiac electrical stimulation as primary or adjunctive treatment of congestive heart failure is entering its second decade of existence. Initial trials of conventional DDD pacing1-5 were followed by bifocal right ventricular stimulation.6 The concept of multisite stimulation for haemodynamic support was introduced in 1994.7 8 Various studies have already reported the benefits of this method,9 10 or are in progress.11 

The transition from conventional DDD pacing to multisite stimulation was not fortuitous. Successive “advances” in the design of cardiac pacing systems have aimed at correcting anomalies in the sequence of cardiac chamber activation, as well as in the synchronisation of the various phases of myocardial contraction and relaxation. The phenomenon of asynchrony is a consequence of progressive, global or focal degradation of the myocardium. One can easily visualise interstitial fibrosis gradually replacing areas of normal myocardium, and causing heterogeneous propagation of cardiac electrical activity. Such heterogeneity combines, to various degrees, three consecutive atrioventricular, interventricular, and intraventricular asynchrony levels. Among various analytical and modelling methods, Doppler echocardiography is preferred for its ease of application in day to day practice.12 

The oldest concept, that of desynchronised atrioventricular sequential activation, applies only to sinus rhythm. It is the product of a mismatch between end of atrial systole and onset of ventricular systole, sometimes facilitated by a disorder of atrioventricular conduction or QRS prolongation. It may be simply described as an abbreviated ventricular filling time with respect to the complete cardiac cycle, and, on occasion, by early passive ventricular filling flow superimposed on atrial systole dependent flow. Dual chamber pacing, by linking ventricular to atrial activation, normalises flow patterns of ventricular filling, provided atrial contraction …
Phase II trial of weekly intravenous vinorelbine in first-line advanced breast cancer chemotherapy. (1993)

Our data confirm that Navelbine has major single-agent antitumor activity as front-line therapy in advanced breast cancer. Given its excellent tolerance profile and low toxicity, it should be considered for inclusion in first-line combination chemotherapy regimens.
3,6-Bis-(2-pyridyl)-pyridazine as supramolecular (co)initiator for DL-lactide polymerization (2003)

The synthesis of a new hydroxy functionalized dipyridylpyridazine by a Diels-Alder reaction between 5-hexyn-1-ol and dipyridyltetrazine was reported. An aluminum alkoxide was generated in situ from this functional ligand to initiate the controlled ring opening polymn. of of DL-lactide resulting in a macroligand with a mol. wt. of 3,900 Dalton. 1H-NMR spectroscopy revealed that indeed the ligand was incorporated in the polymer. The stepwise addn. of tetrakis(acetonitrile)copper(I) hexafluorophosphate to the macroligand was investigated with UV-Vis spectroscopy. Upon addn. of tetrakis(acetonitrile)copper(I) hexafluorophosphate an absorption band at 440 nm appeared and maximal absorption was obtained after addn. of 1 equiv copper(I). Both the absorption max. and the full complexation at 1 equiv of Cu(I) are typical for these grid-like complexes. [on SciFinder (R)]
Histological validation of myocardial microstructure obtained from diffusion tensor magnetic resonance imaging (1998)

Diffusion tensor magnetic resonance imaging (MRI) is a possible new means of elucidating the anatomic structure of the myocardium. It enjoys several advantages over traditional histological approaches, including the ability to rapidly measure fiber organization in isolated, perfused, arrested hearts, thereby avoiding fixation and sectioning of artifacts. However, quantitative validation of this MRI method has been lacking. Here, fiber orientations estimated in the same locations in the same heart using both diffusion tensor MRI and histology are compared in a total of two perfused rabbit hearts. Fiber orientations were statistically similar for both methods and differed on average by 12 degrees at any single location. This is similar to the 10 degrees uncertainty in fiber orientation achieved with histology. In addition, imaging studies performed in a total of seven hearts support a level of organization beyond the myofiber, the recently described laminar organization of the ventricular myocardium.
c‐erbB‐2 anti‐sense phosphorothioate oligodeoxynucleotides inhibit growth and serum‐induced cell spreading of p185c‐erbB‐2‐overexpressing ovarian carcinoma cells (1995)

Overexpression of the c-erbB-2 proto-oncogene product (p185c-erbB-2) occurs frequently in different types of human cancer and is correlated with a significantly decreased survival in ovarian cancer patients. The effect of c-erbB-2 anti-sense phosphorothioate oligodeoxynucleotides (S-ODNs) was examined on the ovarian cancer cell line SK-OV-3. p185c-erbB-2 levels were specifically reduced by a single-dose application of 5 microM c-erbB-2 anti-sense S-ODNs. This was accompanied by a 60% inhibition of anchorage-dependent cell growth. More strikingly, c-erbB-2 anti-sense S-ODNs almost completely abrogated serum-induced cell spreading. A control of complementary sense oligodeoxynucleotides did not show significant inhibitory effects on cell growth or on cell spreading. The inhibition of cell spreading was imitated by a monoclonal antibody (9G6) targeting the extracellular domain of p185c-erbB-2 and by the tyrosine kinase inhibitor erbstatin. The inhibitory activity of these 2 compounds was lost after a few hours, while the inhibition of serum-induced cell spreading by anti-sense S-ODNs was still present after 24 hr. Our results show that c-erbB-2 anti-sense S-ODNs effectively inhibit the mitogenic and spreading activity of p185c-erbB-2 in ovarian cancer cells. Thus, anti-sense strategies have the potential of providing new strategies for the therapy of ovarian cancer.
Diagnosing breast cancer by using Raman spectroscopy (2005)

We employ Raman spectroscopy to diagnose benign and malignant lesions in human breast tissue based on chemical composition. In this study, 130 Raman spectra are acquired from ex vivo samples of human breast tissue (normal, fibrocystic change, fibroadenoma, and infiltrating carcinoma) from 58 patients. Data are fit by using a linear combination model in which nine basis spectra represent the morphologic and chemical features of breast tissue. The resulting fit coefficients provide insight into the chemical/morphological makeup of the tissue and are used to develop diagnostic algorithms. The fit coefficients for fat and collagen are the key parameters in the resulting diagnostic algorithm, which classifies samples according to their specific pathological diagnoses, attaining 94% sensitivity and 96% specificity for distinguishing cancerous tissues from normal and benign tissues. The excellent results demonstrate that Raman spectroscopy has the potential to be applied in vivo to accurately classify breast lesions, thereby reducing the number of excisional breast biopsies that are performed.
Common lymphoid progenitors rapidly engraft and protect against lethal murine cytomegalovirus infection after hematopoietic stem cell transplantation (2003)

Abstract Lymphoid deficiency after allogeneic hematopoietic cell transplantation (HCT) results in increased susceptibility to infection; however, transplantation of mature lymphocytes frequently results in a serious complication known as graft-versus-host disease (GVHD). Here we demonstrate in mice that both congenic as well as allogeneic transplantation of low numbers of highly purified common lymphoid progenitors (CLPs)—a rare population of lymphoid-lineage-committed bone marrow cells—accelerates immune reconstitution after lethal irradiation and rescue with hematopoietic stem cells (HSCs). After congenic transplantation, 3 × 103 CLPs protected against murine cytomegalovirus (MCMV) infection at a level roughly equivalent to 107 unfractionated lymph node cells. In the allogeneic model of matched unrelated donor HSC transplantation, cotransplantation of 3 × 103 CLPs protected thymus-bearing as well as thymectomized hosts from MCMV infection and attenuated disease severity. Immunohistochemistry in combination with antibody depletion of T and natural killer (NK) cells confirmed that CLP-derived as well as residual host lymphocytes contribute to antiviral protection. Importantly, transplantation of allogeneic CLPs provided a durable antiviral immunity without inducing GVHD. These data support the potential for composing grafts with committed progenitors to reduce susceptibility to viral infection following HCT.
Cytosolic phospholipase A2α activation induced by S1P is mediated by the S1P3 receptor in lung epithelial cells (2008)

Cytosolic phospholipase A(2)alpha (cPLA(2)alpha) activation is a regulatory step in the control of arachidonic acid (AA) liberation for eicosanoid formation. Sphingosine 1-phosphate (S1P) is a bioactive lipid mediator involved in the regulation of many important proinflammatory processes and has been found in the airways of asthmatic subjects. We investigated the mechanism of S1P-induced AA release and determined the involvement of cPLA(2)alpha in these events in A549 human lung epithelial cells. S1P induced AA release rapidly within 5 min in a dose- and time-dependent manner. S1P-induced AA release was inhibited by the cPLA(2)alpha inhibitors methyl arachidonyl fluorophosphonate (MAFP) and pyrrolidine derivative, by small interfering RNA-mediated downregulation of cPLA(2)alpha, and by inhibition of S1P-induced calcium flux, suggesting a significant role of cPLA(2)alpha in S1P-mediated AA release. Knockdown of the S1P3 receptor, the major S1P receptor expressed on A549 cells, inhibited S1P-induced calcium flux and AA release. The S1P-induced calcium flux and AA release was associated with sphingosine kinase 1 (Sphk1) expression and activity. Furthermore, Rho-associated kinase, downstream of S1P3, was crucial for S1P-induced cPLA(2)alpha activation. Our data suggest that S1P acting through S1P3, calcium flux, and Rho kinase activates cPLA(2)alpha and releases AA in lung epithelial cells. An understanding of S1P-induced cPLA(2)alpha activation mechanisms in epithelial cells may provide potential targets to control inflammatory processes in the lung.
CpG ODN can re-direct the Th bias of established Th2 immune responses in adult and young mice (2001)

Induction of an appropriate immune response is essential for successful immunization. For example, Th1 type immune responses are necessary for the control of intracellular infections whereas Th2 type responses are more useful for the control of extracellular infections. Immunostimulatory CpG ODN (oligonucleotides containing unmethylated cytosine and guanine dinucleotides in specific base contexts) act as potent adjuvants and have been shown to induce Th1 type immune responses with a number of different antigens. This study investigates the effect of CpG ODN on the Th bias of immune responses generated against the hepatitis B major surface antigen (HBsAg) in adult (6-8 weeks old) and young (<1 week old) BALB/c mice. It also investigates the potential of CpG DNA to reverse a pre-established Th2 response generated as an adult or as a neonate, following re-exposure to HBsAg in adult life. Both adult and young mice immunized with HBsAg/CpG ODN had a Th1 biased immune response (strong cytotoxic T-lymphocyte (CTL) induction, IgG2a>>IgG1). In contrast, mice immunized with HBsAg/alum had a Th2 type immune response (poor CTL, IgG1>>IgG2a). More importantly, when animals were immunized with HBsAg/alum and boosted with HBsAg/CpG ODN, the CpG ODN were able to re-direct the Th2 response pre-established by alum, whereas the animals receiving the primary immunization with HBsAg/CpG ODN and later boosted with HBsAg/alum maintained their Th1 bias, even after the boost with alum. These data suggest that CpG ODN have the ability to augment both humoral and cell mediated immune responses and override the Th2 bias created by alum, even in very young animals, which are known to have a Th2 biased immune system.
Single DNA molecule stretching in sudden mixed shear and elongational microflows (2006)

High-throughput stretching and monitoring of single DNA molecules in continuous elongational flow offers compelling advantages for biotechnology applications such as DNA mapping. However, the polymer dynamics in common microfluidic implementations are typically complicated by shear interactions. These effects were investigated by observation of fluorescently labeled 185 kb bacterial artificial chromosomes in sudden mixed shear and elongational microflows generated in funneled microfluidic channels. The extension of individual free DNA molecules was studied as a function of accumulated fluid strain and strain rate. Under constant or gradually changing strain rate conditions, stretching by the sudden elongational component proceeded as previously described for an ideal elongational flow (T. T. Perkins, D. E. Smith and S. Chu, Science, 1997, 276, 2016): first, increased accumulated fluid strain and increased strain rate produced higher stretching efficiencies, despite the complications of shear interactions; and second, the results were consistent with unstretched molecules predominantly in hairpin conformations. More abrupt strain rate profiles did not deliver a uniform population of highly extended molecules, highlighting the importance of balance between shear and elongational components in the microfluidic environment for DNA stretching applications. DNA sizing with up to 10% resolution was demonstrated. Overall, the device delivered 1000 stretched DNA molecules per minute in a method compatible with diffraction-limited optical sequence motif mapping and without requiring laborious chemical modifications of the DNA or the chip surface. Thus, the method is especially well suited for genetic characterization of DNA mixtures such as in pathogen fingerprinting amidst high levels of background DNA.
Induction of cytotoxic T lymphocytes by intramuscular immunization with plasmid DNA is facilitated by bone marrow-derived cells. (1996)

Striated muscle is the predominant site of gene expression after i.m. immunization of plasmid DNA, but it is not clear if myocytes or professional antigen-presenting cells (APCs) of hematopoietic origin present the encoded antigens to class I major histocompatibility complex (MHC)-restricted cytotoxic T lymphocytes (CTL). To address this issue, CTL responses were assessed in mice engrafted with immune systems that were partially MHC matched with antigen-producing muscle cells. Spleen cells (sc) from immunocompetent F1 H-2bxd mice were infused into H-2b or H-2d mice carrying the severe combined immunodeficiency (scid) mutation, creating F1sc-->H-2b and F1sc-->H-2d chimeras, respectively. Immunization with DNA plasmids encoding the herpes simplex virus gB or the human immunodeficiency virus gp120 glycoproteins elicited antiviral CTL activity. F1sc-->H-2d chimeras responded to an H-2d-restricted gp120 epitope but not an H-2b restricted gB epitope, whereas F1sc-->H-2b chimeras responded to the H-2b but not the H-2d restricted epitope. This pattern of epitope recognition by the sc chimeras indicated that APCs of recipient (scid) origin were involved in initiation of CTL responses. Significantly, CTL responses against epitopes presented by the mismatched donor class I molecules were elicited if F1 bone marrow cells and sc were transferred into scid recipients before or several days to weeks after DNA immunization. Thus, bone marrow-derived APCs are sufficient for class I MHC presentation of viral antigens after i.m. immunization with plasmid DNA. Expression of plasmid DNA by these APCs is probably not a requirement for CTL priming. Instead, they appear to present proteins synthesized by other host cells.
Experimental implantation of epiretinal retina implants (EPI-RET) with an IOL-type receiver unit (2007)

The purpose of this paper is to investigate the surgical feasibility of implantation and long-term structural outcome of retina implant devices with an anterior IOL receiver, a connecting microcable and posterior segment epiretinal microcontacts. Implantation of epiretinal retina (EPI-RET) implants was performed as a one-step surgical procedure including phacoemulsification and pars plana vitrectomy in two adult rabbits. Implants were mechanically stabilized in an anterior position by the lens capsule and in the posterior segment by microtacks with a soft contact collar. Follow-up (6 and 9 months) included regular clinical examination, anterior and posterior segment photography and finally pathohistological evaluation. Implantation was uneventful in case 1 and complicated by vitreous space haemorrhage in case 2. At the end of follow-up, the retina was partially detached in animal 1 and subtotally detached in animal 2. Common features of tissue reaction in both cases were the formation of cyclitic membranes extending around and posterior to the anterior IOL receiver. In addition to that severe proliferations developed around microcables, microcontacts and microtacks forming a tissue capsule around posterior segment foreign materials. Retinal areas in contact to implant devices presented a severe structural damage and disorganization. Results of this preliminary trial suggest that the application of epiretinal prostheses with large diameter IOL receivers may be a critical issue and can give rise to an unfavourable outcome. Further systematic investigation ought to be performed involving a larger number of animals, modified implants and perhaps other species.
Infiltration of COX-2–expressing macrophages is a prerequisite for IL-1β–induced neovascularization and tumor growth (2005)

Inflammatory angiogenesis is a critical process in tumor progression and other diseases. The inflammatory cytokine IL-1beta promotes angiogenesis, tumor growth, and metastasis, but its mechanisms remain unclear. We examined the association between IL-1beta-induced angiogenesis and cell inflammation. IL-1beta induced neovascularization in the mouse cornea at rates comparable to those of VEGF. Neutrophil infiltration occurred on day 2. Macrophage infiltration occurred on days 4 and 6. The anti-Gr-1 Ab-induced depletion of infiltrating neutrophils did not affect IL-1beta- or VEGF-induced angiogenesis. The former was reduced in monocyte chemoattractant protein-1-deficient (MCP-1(-/-)) mice compared with wild-type mice. After day 4, clodronate liposomes, which kill macrophages, reduced IL-1beta-induced angiogenesis and partially inhibited VEGF-induced angiogenesis. Infiltrating macrophages near the IL-1beta-induced neovasculature were COX-2 positive. Lewis lung carcinoma cells expressing IL-1beta (LLC/IL-1beta) developed neovasculature with macrophage infiltration and enhanced tumor growth in wild-type but not MCP-1(-/-) mice. A COX-2 inhibitor reduced tumor growth, angiogenesis, and macrophage infiltration in LLC/IL-1beta. Thus, macrophage involvement might be a prerequisite for IL-1beta-induced neovascularization and tumor progression.
The Eastern Church (2009)

Extracted from Arthur Penrhyn Stanley's Lectures on the History of the Eastern Church, this initial essay lays out his general perceptions of the Eastern Church. He considers the divisions of the church, the historical epochs into which it falls, and the general characteristics and the advantage of studying them