gebhart/patrepeval huggingface dataset:
Undifferentiated Murine Embryonic Stem Cells Cannot Induce Portal Tolerance but May Possess Immune Privilege Secondary to Reduced Major Histocompatibility Complex Antigen Expression (2006)

Induction of donor-specific tolerance using embryonic stem (ES) cells followed by transplantation of ES cell-derived tissues from the same allogeneic strain could theoretically engender successful transplantation without immunosuppression. We sought to induce tolerance using bona fide murine ES cells in immunocompetent mice. ES cells were evaluated for the expression of markers restricted to undifferentiated cells [stage-specific embryonic antigen-1 (SSEA-1) and OCT-4] and the ability to form teratomas in immunodeficient mice. BALB/cByJ mice underwent intraportal inoculation with YC5-EYFP ES cells (129 strain; R1-derived) or saline followed by transplantation with 129X1/SvJ, CBA/J, or BALB/cByJ nonvascularized, neonatal cardiac grafts. Mice were sacrificed at graft failure and underwent histologic evaluation of transplanted grafts and lymphoid organs. ES cells and early differentiated progeny underwent real time (RT)-PCR and fluorescence-activated cell sorting (FACS) analysis to detect major histocompatibility complex (MHC) gene transcription and antigen expression. ES cells expressed markers restricted to undifferentiated cells while maintaining the ability to form teratomas in immunodeficient mice. No prolongation of allograft survival or evidence of lymphoid chimerism was observed in immunocompetent recipient mice despite hepatic teratoma formation. MHC class I, class II, and nonclassical antigens were undetectable on ES cells and early differentiated progeny despite the presence of mRNA transcripts. Class I expression was strongly upregulated upon exposure to gamma-interferon. Intraportal inoculation with murine ES cells does not produce lymphoid chimerism or induce donor-specific unresponsiveness to neonatal cardiac grafts in unmanipulated immunocompetent hosts. However, specific differentiated cell types such as ES cellderived dendritic cells, or alternate routes of ES cell administration, may be effective. ES cells appear to have immune privilege, allowing them to form teratomas in immunocompetent mice.
The spray drying of pharmaceuticals (1992)

(1992). The spray drying of pharmaceuticals. Drug Development and Industrial Pharmacy: Vol. 18, No. 11-12, pp. 1169-1206.
Histologic activity of the liver in children with transfusion-associated chronic hepatitis C (1994)

Adults with chronic hepatitis C develop cirrhosis over a period of 6 to 20 years, but there are few reports of this disorder in children. To determine the histologic activity of chronic hepatitis C in children, we examined 31 biopsy specimens from 25 children (age range 3-16 years) with this disease. All patients were seropositive for antibody to hepatitis C virus by second-generation testing, and for HCV-RNA by the polymerase chain reaction. All cases were transfusion-associated. Patients were divided into two groups according to underlying disease: malignant disease or aplastic anemia (Group A, 17 cases) and non-malignant disease (Group B, eight cases). All patients in Group A, but only one in Group B, had received multiple transfusions. All patients in Group A had received intensive courses of cytotoxic and immunosuppressive agents. The histologic diagnosis was made using the standard criteria and Knodell's histology activity index. Chronic persistent hepatitis was more common in Group B (six patients) than in Group A (three patients). Chronic aggressive hepatitis 2B was found only in Group A (five patients). The mean histology activity index score was higher in Group A than in Group B (8.5 vs. 5.7). Six patients (four in Group A and two in group B) subsequently had a liver biopsy. The pathological diagnosis did not change after the second biopsy in any patient in Group B, while two patients in Group A showed a rapid progression of hepatitis. In each category of the histology activity index, periportal necrosis and intralobular necrosis were more severe in Group A than in Group B.(ABSTRACT TRUNCATED AT 250 WORDS)
Molecular cloning of human immune interferon cDNA and its expression in eukaryotic cells (1982)

Starting with mRNA derived from Staphylococcal enterotoxin A induced human splenocytes, dsDNA was synthesized and inserted into unique BamHI site of the eukaryotic expression vector pSV529 (1). A recombinant plasmid containing human immune interferon (IFN-gamma) cDNA was identified by hybridization of plasmid inserted DNA bound onto nitrocellulose filters with mRNA derived from SEA-induced splenocytes, translation of the eluted RNA in Xenopus laevis oocytes and assaying for IFN activity. Plasmids containing the entire human IFN-gamma cDNA sequence were identified by colony hybridization and were sequenced. A unique coding region was identified which predicted a protein of 166 amino acids, the 20 N-terminal amino acids of which presumably represent a signal peptide. After transfection of monkey cells with plasmid DNA isolated from one of the recombinant clones (pHIIF-SV-gamma 1), IFN was excreted into the culture medium. This IFN was not distinguishable from human IFN-gamma by serological criteria or by cell target species specificity.
In Vivo Delivery to Tumors of DNA Complexed with Linear Polyethylenimine (1999)

Synthetic gene delivery vectors have shown promise in several organs, including brain and lung. Tumor cell targeting, however, is still hindered by their low efficacy. A linear polyethylenimine (L-PEI, Exgen 500) was found to be effective in vivo. Our first attempts to use L-PEI for intratumoral gene delivery were not successful, presumably because of poor diffusion of the complexes within the tumor mass after injection with a syringe. Here we show that L-PEI-mediated transfection can be strongly enhanced when the complexes are delivered slowly into a solid tumor mass, using a micropump. Furthermore, L-PE/DNA complexes actively transfect pseudocystic tumor cells when injected into the cyst cavity. In both cases L-PEI induced a significant and long-lasting (> or =15 days) expression of the reporter gene. Finally, even though systemic delivery of L-PEI/DNA complexes leads to high levels of expression in the lung, this method is not adapted for transfection of subcutaneous tumors implanted in the thigh nor for transfection of lung metastases. Altogether, these results show that L-PEI has promising features for transfection of tumor cells, provided that the mode of delivery is adapted.
Persisting atypical and cystic forms of Borrelia burgdorferi and local inflammation in Lyme neuroborreliosis (2008)

The results indicate that atypical extra- and intracellular pleomorphic and cystic forms of Borrelia burgdorferi and local neuroinflammation occur in the brain in chronic Lyme neuroborreliosis. The persistence of these more resistant spirochete forms, and their intracellular location in neurons and glial cells, may explain the long latent stage and persistence of Borrelia infection. The results also suggest that Borrelia burgdorferi may induce cellular dysfunction and apoptosis. The detection and recognition of atypical, cystic and granular forms in infected tissues is essential for the diagnosis and the treatment as they can occur in the absence of the typical spiral Borrelia form.
Cell surface antigens of human renal cancer defined by autologous typing. (1979)

Sera from 28 patients with renal cancer were tested for reactivity with surface antigens of cultured autologous renal cancer cells. Four serological assays were used to survey sera for autologous antibody. Immune adherence, protein A, and C3-mixed hemadsorption assays detected reactivity in a high percentage of patients (80-100%), whereas mixed hemadsorption assays were negative with sera from all but one patient. Reactive sera from six patients were analyzed by absorption tests with autologous, allogeneic, and restricted to autologous renal cancer cells; class 2 antigens, present on certain allogeneic renal and nonrenal cancer cells; and class 3 antigens, found on a wide variety of normal and malignant cell types. The sera of one patient detected class 1, 2, and 3 antigens, the sera of three patients detected class 2 antigens, and the sera of two patients detected class 3 antigens. This analysis of renal cancer, with the recognition of three classes of surface antigens recognized by autologous sera, resembles the results of autologous typing of three other human malignancies: malignant melanoma, acute leukemia, and astrocytoma. Evidence provided by autologous typing of these cancers indicates that class 1 and class 2 antigens are tumor-restricted and that under certain circumstances these antigens are immunogenic for the autologous host.
Structure of Ferric Soybean LeghemoglobinaNicotinate at 2.3 Å Resolution (1997)

Soybean leghemoglobin a is a small (16 kDa) protein facilitating the transport of O(2) to respiring N(2)-fixing bacteria at low free-O(2) tension. The crystal structure of soybean ferric leghemoglobin a nicotinate has been refined at 2.3 A resolution. The final R factor is 15.8% for 6877 reflections between 6.0 and 2.3 A. The structure of soybean leghemoglobin a (143 residues) is closely similar to that of lupin leghemoglobin II (153 residues), the proteins having 82 identical residues when the sequences are aligned. The new structure provides support for the conclusion that the unique properties of leghemoglobin arise principally from a heme pocket considerably larger and more flexible than that of myoglobin, a strongly ruffled heme group, and a proximal histidine orientation more favourable to ligand binding.
Cross-reactions between pneumococci and other streptococci due to C polysaccharide and F antigen (1987)

By serological methods, all 83 known types of Streptococcus pneumoniae could be shown to possess C polysaccharide and F antigen. Cross-reactions due to these two antigens between pneumococci and a broad range of most other commonly encountered streptococci were examined. The presence of an antigen closely similar or identical to pneumococcal C polysaccharide was demonstrated in some strains of Streptococcus mitior. Therefore, we conclude that pneumococci cannot be identified serologically from mixed samples without culture. Streptococcal group C antiserum was found to cross-react with pneumococcal F antigen.
Effects of 17beta-estradiol on cytokine-induced endothelial cell adhesion molecule expression. (1996)

One of the earliest events in atherosclerosis is interaction of circulating mononuclear leukocytes and the endothelium. Endothelial cell (EC) activation by cytokines results in expression of adhesion molecules and production of chemotactic factors, augmenting leukocyte adhesion and recruitment, respectively. The incidence of atherosclerosis in premenopausal women is significantly less than that observed in age-matched males with similar risk profiles. Because estrogen has gene regulatory effects, we investigated whether 17beta-estradiol (E2) can inhibit cytokine-mediated EC adhesion molecule transcriptional activation. Cultured human umbilical vein EC (estrogen receptor-positive) were propagated in gonadal hormone-free medium and were E2-pretreated for 48 h before IL-1 activation. Detected by FACS analysis, E2 strongly (60-80%) inhibited IL-1-mediated membrane E-selectin and vascular cell adhesion molecule-1 induction, and intercellular adhesion molecule-1 hyperinduction. 17alpha-estradiol (an inactive E2 stereoisomer) had no effect. This inhibition correlated with similar reductions in steady state-induced E-selectin mRNA levels, and was abrogated by the E2 antagonist ICI 164,384, demonstrating a specific, estrogen receptor-mediated effect. Nuclear run-offs confirmed suppression at the transcriptional level. The implications of these results for the cardiovascular protective role of estrogen are discussed.
Association between human rhinovirus C and severity of acute asthma in children (2010)

A new and potentially more pathogenic group of human rhinovirus (HRV), group C (HRVC), has recently been discovered. We hypothesised that HRVC would be present in children with acute asthma and cause more severe attacks than other viruses or HRV groups. Children with acute asthma (n = 128; age 2-16 yrs) were recruited on presentation to an emergency department. Asthma exacerbation severity was assessed, and respiratory viruses and HRV strains were identified in a nasal aspirate. The majority of the children studied had moderate-to-severe asthma (85.2%) and 98.9% were admitted to hospital. HRV was detected in 87.5% and other respiratory viruses in 14.8% of children, most of whom also had HRV. HRVC was present in the majority of children with acute asthma (59.4%) and associated with more severe asthma. Children with HRVC (n = 76) had higher asthma severity scores than children whose HRV infection was HRVA or HRVB only (n = 34; p = 0.018), and all other children (n = 50; p = 0.016). Of the 19 children with a non-HRV virus, 13 had HRV co-infections, seven of these being HRVC. HRVC accounts for the majority of asthma attacks in children presenting to hospital and causes more severe attacks than previously known HRV groups and other viruses.
A Trip Through my Life With an Immunological Theme (2002)

In this essay, I make four points about the operation of the immune system. First, thanks to the innate immune system's regulation of the main costimulatory molecules CD80 and CD86, the immune system rarely mistakes a pathogen for a self-antigen. Second, the adaptive immune system consisting of T lymphocytes and B lymphocytes can mistake self for non-self because adaptive immunity is selected in single somatic cells. Third, the adaptive immune system of T lymphocytes and B lymphocytes is always referential to self, as it is selected on self-ligands; it persists in the periphery on self-ligands; and at least for T cells, it is dependent on self-ligands to be able to mount a response. Fourth, it is becoming clear that regulatory or suppressor T cells are our main defense against autoimmunity, as my first boss, Richard Gershon, had predicted. These cells recognize antigen as do all T cells, but they secrete the immunoregulatory cytokines IL-10 and TGF beta.
HIVgp120 activates autoreactive CD4-specific T cell responses by unveiling of hidden CD4 peptides during processing. (1995)

T cells are made tolerant only to those self-peptides that are presented in sufficient amounts by antigen-presenting cells. They ignore cryptic self-determinants, such as either those not generated by processing machinery or generated in insufficient amounts. It is anticipated that mechanisms that either change antigen processing or increase the yield of previously "invisible" peptides may be capable of inducing T cell priming and, if they are self-maintained, may sustain autoimmune diseases. Herein, we demonstrate for the first time a mechanism by which the gp120 human immunodeficiency virus-I, by downregulating plasma membrane CD4 and increasing its processing, unveils hidden CD4 epitopes, inducing an autoimmune-specific T cell response.
Measuring the Effect of Cell Mismatch on Module Output (2006)

Photovoltaic modules are commonly built using solar cells with similar IV characteristics to ensure that mismatch is minimized. Mismatch occurs because the IV characteristics of cells within a module are not identical. When connected in series, cells do not perform at their individual maximum power point. Instead, the cells perform at a combined maximum, which is less than the sum of the individual maximums. Various cell-sorting methods are used by PV module manufacturers. These different sorting strategies, including bin tolerances, have an effect on mismatch in the module. This work explains how cell mismatch in a module can be measured on a finished product using a module IV flash tester, by comparing a Suns-Voc pseudo IV curve to a measured IV curve. Further, this work presents a methodology for accurately measuring mismatch in a module, demonstrates the validity of the method using simulations, and compares the simulations with experimental data. This approach can be used by module manufacturers to characterize the module losses caused by cell mismatch, select a cell-sorting strategy, and optimize the cell-binning tolerance
Review: physical chemistry of solid dispersions (2009)

Abstract Objectives With poorly soluble drug candidates emerging in the drug discovery pipeline, the importance of the solid dispersion formulation approach is increasing. This strategy includes complete removal of drug crystallinity, and molecular dispersion of the poorly soluble compound in a hydrophilic polymeric carrier. The potential of this technique to increase oral absorption and hence bioavailability is enormous. Nevertheless, some issues have to be considered regarding thermodynamic instability, as well in supersaturated solutions that are formed upon dissolution as in the solid state. Key findings After a brief discussion on the historical background of solid dispersions and their current role in formulation, an overview will be given on the physical chemistry and stability of glass solutions as they form supersaturated solutions, and during their shelf life. Conclusions Thorough understanding of these aspects will elicit conscious evaluation of carrier properties and eventually facilitate rational excipient selection. Thus, full exploitation of the solid dispersion strategy may provide an appropriate answer to drug attrition due to low aqueous solubility in later stages of development.
VHF free-free beam high-Q micromechanical resonators (2000)

Free-free-beam flexural-mode micromechanical resonators utilizing nonintrusive supports to achieve measured Qs as high as 8400 at VHF frequencies from 30 to 90 MHz are demonstrated in a polysilicon surface micromachining technology. The microresonators feature torsional-mode support springs that effectively isolate the resonator beam from its anchors via quarter-wavelength impedance transformations, minimizing anchor dissipation and allowing these resonators to achieve high-Q with high stiffness in the VHF frequency range. The free-free-beam micromechanical resonators of this paper are shown to have an order of magnitude higher Q than clamped-clamped-beam versions with comparable stiffnesses.
In vivo glucose metabolism, insulin secretion and, insulin action in Europids with non-insulin-dependent diabetes mellitus (NIDDM) and their first-degree relatives. (1996)

In this review we will mainly concentrate on the most common form of NIDDM in Europe, namely the form linked to overweight, arterial hypertension, dyslipoproteinaemia and coronary heart disease (CHD)-the Insulin Resistance Syndrome (IRS). This form of NIDDM seems to be growing epidemically world wide following the industrial growth or the 'cocacolanization', as it has been mentioned. Around 2-3% of the population in Europe suffers from this disease, but for subjects beyond 60 years of age the prevalence is 5-20%. Thus, we face an enormous economical, social, and humanitarian challenge. Therefore it is important to continue the research on aetiology and pathophysiology of this syndrome. The results of treatment of NIDDM patients (often started at 60 years of age) have been rather disappointing; even properly treated NIDDM patients develop substantial complications, especially macroangiopathy. Coronary heart disease is the main cause of death in these patients and the overall mortality rate in NIDDM patients is 3-4 times higher than in comparable non diabetic-subjects. Furthermore, several complications may already be present at the diagnosis of the disease, which indicate that macroangiopathy may not be secondary to the diabetic state itself, but rather a part of the NIDDM phenotype. Based on these findings it seems obvious that the IRS must be diagnosed in the prediabetic states before macroangiopathy has started or reached a clinically manifest level. In this review, therefore, we will discuss the metabolic background of NIDDM and especially focus on the pathophysiological mechanisms leading to hyperglycaemia, i.e. alterations in glucose effectiveness, insulin action and insulin secretion in prediabetic states.
The Enhanced Tumor Selectivity of an Oncolytic Vaccinia Lacking the Host Range and Antiapoptosis Genes SPI-1 and SPI-2 (2005)

The ability of cancer cells to evade apoptosis may permit survival of a recombinant vaccinia lacking antiapoptotic genes in cancer cells compared with normal cells. We have explored the deletion of two vaccinia virus host range/antiapoptosis genes, SPI-1 and SPI-2, for their effects on the viral replication and their ability to induce cell death in infected normal and transformed cells in vitro. Indeed, in three paired normal and transformed cell types, the SPI-1 and SPI-2 gene-deleted virus (vSP) preferentially replicates in transformed cells or p53-null cells when compared with their normal counterparts. This selectivity may be derived from the fact that vSP-infected normal cells died faster than infected cancer cells. A fraction of infected cells died with evidence of necrosis as shown by both flow cytometry and detection of high-mobility group B1 protein released from necrotic cells into the culture supernatant. When administered to animals, vSP retains full ability to replicate in tumor tissues, whereas replication in normal tissues is greatly diminished. In a model of viral pathogenesis, mice treated with vSP survived substantially longer when compared with mice treated with the wild-type virus. The mutant virus vSP displayed significant antitumoral effects in an MC38 s.c. tumor model in both nude (P < 0.001) and immunocompetent mice (P < 0.05). We conclude that this recombinant vaccinia vSP shows promise for oncolytic virus therapy. Given its enhanced tumor selectivity, improved safety profile, and substantial oncolytic effects following systemic delivery in murine models, it should also serve as a useful vector for tumor-directed gene therapy.
Targeting Interleukin-6: All the Way to Treat Autoimmune and Inflammatory Diseases (2012)

Interleukin (IL)-6, a cytokine featuring redundancy and pleiotropic activity, contributes to host defense against acute environmental stress, while dysregulated persistent IL-6 production has been demonstrated to play a pathological role in various autoimmune and chronic inflammatory diseases. Targeting IL-6 is thus a rational approach to the treatment of these diseases. Indeed, clinical trials of tocilizumab, a humanized anti-IL-6 receptor antibody have verified its efficacy and tolerable safety for patients with rheumatoid arthritis, Castleman's disease and systemic juvenile idiopathic arthritis, resulting in approval of this innovative biologic for treatment of these diseases. Moreover, a considerable number of case reports and pilot studies of off-label use of tocilizumab point to the beneficial effects of tocilizumab for a variety of other phenotypically different autoimmune and chronic inflammatory diseases. Elucidation of the source of IL-6 and of mechanisms through which IL-6 production is dysregulated can thus be expected to lead to clarification of the pathogenesis of various diseases.