gebhart/patrepeval huggingface dataset:
[Clinical aspects of IgA deficiency]. (1994)

The authors have carried out a retrospective study of 33 selective IgA-deficient patients. They have found the high frequency of respiratory infections, gastrointestinal (celiac disease, giardiasis), and also autoimmune-, allergic- and malignant diseases. They have called the attention to the variety of the clinical picture, the possible consequences of the haemo- and immunotherapy, as well as to the importance of the early diagnosis and examination of family members.
Advances in understanding the cell types and approaches used for generating induced pluripotent stem cells (2014)

Successfully reprogramming somatic cells to a pluripotent state generates induced pluripotent stem (iPS) cells (or iPSCs), which have extensive self-renewal capacity like embryonic stem cells (ESCs). iPSCs can also generate daughter cells that can further undergo differentiation into various lineages or terminally differentiate to reach their final functional state. The discovery of how to produce iPSCs opened a new field of stem cell research with both intellectual and therapeutic benefits. The huge potential implications of disease-specific or patient-specific iPSCs have impelled scientists to solve problems hindering their applications in clinical medicine, especially the issues of convenience and safety. To determine the range of tissue types amenable to reprogramming as well as their particular characteristics, cells from three embryonic germ layers have been assessed, and the advantages that some tissue origins have over fibroblast origins concerning efficiency and accessibility have been elucidated. To provide safe iPSCs in an efficient and convenient way, the delivery systems and combinations of inducing factors as well as the chemicals used to generate iPSCs have also been significantly improved in addition to the efforts on finding better donor cells. Currently, iPSCs can be generated without c-Myc and Klf4 oncogenes, and non-viral delivery integration-free chemically mediated reprogramming methods have been successfully employed with relatively satisfactory efficiency. This paper will review recent advances in iPS technology by highlighting tissue origin and generation of iPSCs. The obstacles that need to be overcome for clinical applications of iPSCs are also discussed.
Enhancing DNA vaccine potency by coadministration of DNA encoding antiapoptotic proteins (2003)

Intradermal vaccination by gene gun efficiently delivers DNA vaccines into DCs of the skin, resulting in the activation and priming of antigen-specific T cells in vivo. DCs, however, have a limited life span, hindering their long-term ability to prime antigen-specific T cells. We reason that a strategy that prolongs the survival of DNA-transduced DCs will enhance priming of antigen-specific T cells and DNA vaccine potency. Here we show that codelivery of DNA encoding inhibitors of apoptosis (BCL-xL, BCL-2, XIAP, dominant negative caspase-9, or dominant negative caspase-8) with DNA encoding model antigens prolongs the survival of transduced DCs. More importantly, vaccinated mice exhibited significant enhancement in antigen-specific CD8 + T cell immune responses, resulting in a potent antitumor effect against antigen-expressing tumors. Among these antiapoptotic factors, BCL-xL demonstrated the greatest enhancement in antigen-specific immune responses and antitumor effects. Thus, coadministration of DNA vaccines with DNA encoding antiapoptotic proteins represents an innovative approach to enhance DNA vaccine potency.
Alpha-melanocyte-stimulating hormone protects against renal injury after ischemia in mice and rats. (1997)

Reperfusion after ischemia induces cytokines, chemoattractant chemokines, adhesion molecules, and nitric oxide (NO). The resultant neutrophil adherence and NO potentiates renal injury. alpha-Melanocyte-stimulating hormone (alpha-MSH) is a potent anti-inflammatory agent that inhibits neutrophil migration and production of neutrophil chemokines and NO. Since neutrophils and NO promote renal ischemic injury, we sought to determine if alpha-MSH inhibits renal injury in a model of bilateral renal ischemia. alpha-MSH significantly reduced ischemia-induced renal damage, measured by changes in renal histology and plasma blood urea nitrogen and creatinine in mice. alpha-MSH significantly decreased tubule necrosis, neutrophil plugging, and capillary congestion. Delay of alpha-MSH treatment for 6 h after ischemia also significantly inhibited renal damage. alpha-MSH also significantly inhibited ischemic damage in rats. To begin to determine the mechanism of action of alpha-MSH, we measured its effects on mediators of neutrophil trafficking and induction of the inducible isoform of NO synthase-II. alpha-MSH inhibited ischemia-induced increases in mRNA for the murine neutrophil chemokine KC/IL-8. alpha-MSH also inhibited induction of mRNA for the adhesion molecule ICAM-1, which is known to be critical in renal ischemic injury. alpha-MSH inhibited nitration of kidney proteins and induction of NO synthase-II. We conclude: (a) alpha-MSH protects against renal ischemia/reperfusion injury; and (b) it may act, in part, by inhibiting the maladaptive activation of genes that cause neutrophil activation and adhesion, and induction of NO synthase.
Estimates of the world‐wide prevalence of cancer for 25 sites in the adult population (2001)

In health services planning, in addition to the basic measures of disease occurrence incidence and mortality, other indexes expressing the demand of care are also required to develop strategies for service provision. One of these is prevalence of the disease, which measures the absolute number, and relative proportion in the population, of individuals affected by the disease and that require some form of medical attention. For most cancer sites, cases surviving 5 years from diagnosis experience thereafter the same survival as the general population, so most of the workload is therefore due to medical acts within these first 5 years. This article reports world-wide estimates of 1-, 2-3- and 4-5-year point prevalence in 1990 in the population aged 15 years or over, and hence describes the number of cancer cases diagnosed between 1986 and 1990 who were still alive at the end of 1990. These estimates of prevalence at 1, 2-3 and 4-5 years are applicable to the evaluation of initial treatment, clinical follow-up and point of cure, respectively, for the majority of cancers. We describe the computational procedure and data sources utilised to obtain these figures and compare them with data published by 2 cancer registries. The highest prevalence of cancer is in North America with 1.5% of the population affected and diagnosed in the previous 5 years (about 0.5% of the population in years 4-5 and 2-3 of follow-up and 0.4% within the first year of diagnosis). This corresponds to over 3.2 million individuals. Western Europe and Australia and New Zealand show very similar percentages with 1.2% and 1.1% of the population affected (about 3.9 and 0.2 million cases respectively). Japan and Eastern Europe form the next batch with 1.0% and 0.7%, followed by Latin America and the Caribbean (overall prevalence of 0.4%), and all remaining regions are around 0.2%. Cancer prevalence in developed countries is very similar in men and women, 1.1% of the sex-specific population, while in developing countries the prevalence is some 25% greater in women than men, reflecting a preponderance of cancer sites with poor survival such as liver, oesophagus and stomach in males. The magnitude of disease incidence is the primary determinant of crude prevalence of cases diagnosed within 1 year so that differences by region mainly reflect variation in risk. In the long-term period however different demographic patterns with long-life expectancy in high-income countries determine a higher prevalence in these areas even for relatively uncommon cancer sites such as the cervix.
Management of Tachyarrhythmias with Dual‐Chamber Pacemakers (1983)

Multiprogrammable dual-demand AV sequential (DVI, MN) pacemakers were implanted in twenty-three patients (in one of them a DVI, MN unit was used as a VVI, MN with the aid of an atrial plug) with supraventricular tachycardias after electrophysiological studies revealed a great variety of AV reentry circuits. The latter included tachycardias involving accessory pathways of the Kent type, manifest or concealed Wolff-Parkinson-White syndromes, nodo-ventricular (Mahaim) tracts, "enhanced" AV node (or extra AV nodal) pathways and dual AV pathways. In addition, multiprogrammable "non-committed" AV sequential (DVI, MN and DDD, M) pacemakers were permanently implanted to treat different forms of ventricular tachyarrhythmias that included: torsade de pointes in the Romano-Ward syndrome and Chagas' cardiomyopathy, ventricular tachycardia which is bradycardia-dependent (in Chagas' cardiomyopathy) and reciprocal beats induced by, and producing severe hemodynamic derangements in a patient with a conventional VVI unit. With small-size multiprogrammable units, arrhythmias may be treated by changing parameters non-invasively. By temporary inhibition, one may analyze the underlying rhythm and pacemaker dependency. In patients without chronic atrial flutter/fibrillation who require pacing and possibly tachyarrhythmia control, our experience with multiprogrammable "non-committed" AV sequential pacing has been very satisfactory. The evolution toward newer pacing modes which provide atrial sensing and tracking (DDD), and thus preserve AV synchrony over a wider range of atrial rates, may contribute even further to successful patient management. This may be applicable to pediatric patients as well.
Non-invasive prenatal assessment of trisomy 21 by multiplexed maternal plasma DNA sequencing: large scale validity study (2011)

Multiplexed maternal plasma DNA sequencing analysis could be used to rule out fetal trisomy 21 among high risk pregnancies. If referrals for amniocentesis or chorionic villus sampling were based on the sequencing test results, about 98% of the invasive diagnostic procedures could be avoided.
Parametric Interaction of Focused Gaussian Light Beams (1968)

A theoretical study is presented on the optimization of second harmonic generation (SHG) and parametric generation (PG) by a laser beam in a uniaxial nonlinear crystal. Numerically computed curves show the dependence of the SHG power, and the reciprocal of the PG threshold power, on the parameter l/b, where l is the optical path length in the crystal and b is the confocal parameter (determined by the focal length of the focusing lens and the minimum radius of the laser beam, assumed to be in the TEM00 mode of an optical resonator). The calculations take full account of diffraction and double refraction. In the absence of double refraction, the optimum focusing condition is found to be l/b=2.84. For PG the optimization of the crystal length l is also discussed, and curves are given showing the dependence of the threshold on l for the case in which signal and idler have the same losses. It is shown that the computed functions are also relevant to the mixing of two Gaussian beams and to parametric amplification. Pump depletion is neglected. Appendices are provided on (1) the theory of Gaussian extraordinary beams and the extension of the theory to cover both positive and negative birefringent crystals, (2) the general definition of nonlinear coefficients, (3) the effective nonlinear coefficient, and (4) details of the computations. The theory of the PG threshold is applied to tellurium and LiNbO3. On the basis of reasonable assumptions about the losses, a PG threshold of 1.0 W is obtained for a pump at 10.6 μ in Te. The optimum length is found to be l=0.14 cm. For LiNbO3 of length l=1 cm the threshold is 22 mW at 0.5147 μ. Also calculated is the quantum efficiency for up-conversion in HgS from 10.6 to 0.6729 μ using the 0.6328 μ He–Ne laser.
Purification and characterization of an O-GlcNAc selective N-acetyl-beta-D-glucosaminidase from rat spleen cytosol. (1994)

Glycosylation of nuclear and cytoplasmic proteins by O-linked N-acetylglucosamine (O-GlcNAc) monosaccharides is an abundant, ubiquitous, and transient post-translational modification. To characterize enzymes involved in removal of these sugars, a neutral and cytoplasmic N-acetyl-beta-D-glucosaminidase (O-GlcNAcase) with strong selectivity for O-GlcNAc-synthetic glycopeptides has been purified over 22,000-fold from rat spleen homogenate. The purified O-GlcNAcase has two major polypeptides of apparent M(r) = 54,000 (alpha subunit) and M(r) = 51,000 (beta subunit). Enzyme activity sediments at M(r) = 106,000 on sucrose gradients, indicating that the native O-GlcNAcase is an alpha beta heterodimer. The O-GlcNAcase also shows substantially stronger relative activity against O-GlcNAc-synthetic glycopeptides than other hexosaminidases. Unlike acidic lysosomal hexosaminidases, O-GlcNAcase is not inhibited by GalNAc or its analogs, has no other detectable glycosidase activities, and does not cross-react with antibodies against acidic hexosaminidases. Subcellular fractionation and latency studies demonstrate the cytoplasmic and nucleoplasmic localization of the enzyme and its ubiquitous presence in tissues. These studies suggest that O-GlcNAcase is involved in the regulated removal of O-GlcNAc from O-GlcNAc-bearing glycoproteins in the nucleoplasmic and cytoplasmic compartments of cells.
A monoclonal antibody specific for a 52,000-molecular-weight human T-cell leukemia virus-associated glycoprotein expressed by infected cells (1985)

A monoclonal antibody, designated HT462, is described which is specific for an antigen expressed in human T-cell leukemia/lymphoma virus (HTLV) preparations and by HTLV-infected cells. In indirect immunofluorescence assays, the antigen was detected on the surface of both HTLV-transformed producer and nonproducer cells, including cells infected in vitro with either HTLV subgroup I (HTLV-I) or HTLV-II. Normal human peripheral blood lymphocytes stimulated with phytohemagglutinin, cord blood T cells cultured with T-cell growth factor, and a variety of HTLV-negative T- and B-cell lines all lacked HT462 antigen expression. The HT462 antigen is a 52,000-molecular-weight glycoprotein, as shown by Western blotting procedures and treatment of viral preparations with neuraminidase, endoglycosidase F, and trypsin. The unglycosylated molecule is approximately 42,000 daltons. That the antigen is virus associated was demonstrated by its banding at the density of HTLV in gradients of metrizamide and by its concomitant synthesis with HTLV gag proteins after short-term culture of primary HTLV-positive leukemic cells. Differential expression of the HT462 antigen and HTLV gag-pol gene products was observed. In one case, low HT462 expression was correlated with the known inability of the particular cell line to produce syncytia in vitro. The properties of the HT462 antigen are most consistent with it being a gene product of the HTLV px region or else a cellular antigen specifically induced after viral infection. We cannot rule out, however, that the antigen is a variant cleavage product of the env gene. The monoclonal HT462 will be useful in further definition of the proteins and functions encoded by the env-px genetic sequence and in studying the biological properties of HTLV-transformed cells. Furthermore, the monoclonal, by recognizing HTLV-transformed nonproducers, will allow a greater spectrum of virus-infected cells to be detected.
Cold Fusion by Electrolysis in a Light Water-Potassium Carbonate Solution with a Nickel Electrode (1993)

The evolution of a large amount of heat, unexplainable by ordinary chemical reactions, was observed in an electrolytic cell with a nickel cathode and a platinum anode in a potassium carbonate-light water solution. The nickel cathode had a specially designed porous structure, based on fundamental knowledge concerning the active hydrogen electrode in alkaline solutions. An increase in the concentration of calcium ions was observed in the electrolyte, which seems to be the result of potassium-hydrogen cold fusion.
The research question and the big picture (1996)

Although epidemiology is reductionist by nature, the author urges for the bigger picture to be kept in mind. (non-author abstract)
Exciton Migration and Cathode Quenching in Organic Light Emitting Diodes (2000)

The quantum efficiency of organic light emitting devices depends on the exciton emission efficiency. Exciton quenching at the metal cathode can be responsible for lowering the device performance. We consider exciton quenching by the metal cathode, taking into account both exciton diffusion and radiationless energy transfer to the metal. The quenching effect in tris(8-hydroxyquinoline)aluminum is analyzed, and ways to improve the device efficiency by suppressing the interaction with the electrode are discussed.
Growth factors in wound healing. Single and synergistic effects on partial thickness porcine skin wounds. (1989)

Several growth factors are potential mediators of wound healing, although their actual roles, interactions, and therapeutic use are not established. Six well-characterized human growth factors were chosen for detailed investigation by topical application to standardized skin wounds in swine: epidermal growth factor (EGF), transforming growth factors alpha and beta (TGF-alpha and TGF-beta), fibroblast growth factor (FGF), insulin-like growth factor-I (IGF-I), and platelet-derived growth factor (PDGF). When applied singly in doses up to 1,500 ng, only TGF-beta produced a marked tissue response, as demonstrated by an increase in the new connective tissue volume, the collagen content and maturity, and increased angiogenesis. However, TGF-beta enhanced inflammation and caused abnormal epithelial differentiation and decreased epithelial volume, the last reversed by addition of IGF-I. Recombinant PDGF-2 homodimer, if given in combination with recombinant IGF-I, caused a similar increase in the new connective tissue volume and collagen content and maturity, but without increased inflammation. In addition, this combination stimulated increased amounts of epithelium with normal differentiation. The synergy of PDGF-2 and IGF-I was optimal at a ratio of 2:1 by weight. Of the six individual factors and nine combinations tested, the combinations of PDGF-2 and IGF-I or PDGF-2 and TGF-alpha were the most potent stimulators of healing in the absence of increased inflammation.
Aggregin: a platelet ADP receptor that mediates activation (1990)

ADP is known to induce platelet shape change, aggregation, and exposure of fibrinogen binding sites as well as inhibit stimulated adenylate cyclase. The platelet is unique in that its purinergic receptor prefers ADP over ATP, which functions as a competitive antagonist. The affinity reagent, 5'-p-fluorosulfonylbenzoyl adenosine (FSBA), has been used to covalently label a single membrane protein, aggregin, on the external platelet surface with mol wt of 100 kDa. Concomitant with incorporation of FSBA, ADP-induced shape change, aggregation, and fibrinogen binding is inhibited. FSBA is also a weak agonist at short times and high concentration, which suggests that prior noncovalent binding to aggregin takes place before covalent modification. Aggregin differs from platelet glycoprotein IIIa in its physical and immunochemical properties. Aggregin is distinct from the receptor coupled to adenylate cyclase. Using FSBA as a probe, platelet aggregation by thromboxane A2 analogs and collagen was shown to be dependent on ADP but not the shape change induced by these agonists. Binding to aggregin is required for epinephrine-induced aggregation. In turn, epinephrine increases the affinity of ADP for its receptor. Thrombin at concentrations greater than 2 nM (0.2 units/ml) stimulates platelet aggregation independent of ADP, but by raising cytoplasmic Ca2+ it activates platelet calpain, which in turn cleaves aggregin. Thus aggregin, in addition to serving as the ADP receptor linked to shape change and aggregation, plays a role in fibrinogen receptor latency that is relieved entirely by ADP binding to or proteolysis of aggregin.
Cocaine Detoxification by Human Plasma Butyrylcholinesterase (1997)

The ability of human plasma butyrylcholinesterase (BChE) to detoxify cocaine in vivo was evaluated. Intravenous administration of BChE, at doses sufficient to increase the plasma levels of the enzyme as much as 800-fold, produced no adverse effects on the cardiovascular, autonomic, or central nervous systems of rats. Most of the enzyme could be recovered in the plasma immediately after administration and remained active with a beta-t(1/2) of 21.6 +/- 2.4 hr. Pretreatment of chloralose-urethane anesthetized rats with BChE, 0.1-7.8 mg/kg, decreased the hypertensive and arrhythmogenic effects produced by cocaine and increased the lethal dose of cocaine by three- to fourfold. Treatment of conscious rats with 1 and 10 mg/kg BChE decreased the incidence of seizures and deaths produced by a prior dose of cocaine (80 mg/kg, i.p.). These results suggest that BChE would provide a safe and highly efficacious treatment for cocaine intoxication.
Role of Leucine 201 of Thermostable D-Amino Acid Aminotransferase from a Thermophile, Bacillus sp. YM-11 (1995)

We studied the catalytic role of leucine 201 residue of the thermostable D-amino acid aminotransferase: the residue was shown crystallographically to be in the vicinity of the active site to interact with the bound pyridoxal phosphate. We replaced the leucine 201 by alanyl or tryptophanyl residues by means of site-directed mutagenesis. The L201A and L201W mutant enzymes showed anomalous kinetic behavior in the overall reaction. The reaction rates of the L201A and L201W mutant enzymes gradually decreased with an increase in the reaction time to become practically zero at a high concentration of substrates. The mutant enzymes were also inactivated in the half reaction with D-alanine, although more slowly than in the overall reaction. The absorption spectra of the mutant enzymes in the presence of D-alanine and alpha-ketoglutarate suggest that the enzyme molecules were mostly in the pyridoxamine form under the conditions employed. These phenomena were explained by assuming two (or more) enzyme species showing kinetically different catalysis for pyridoxamine form of the mutant enzymes, and the rate of conversion from one of these pyridoxamine forms to the pyridoxal form should be very low. The leucine 201 residue probably regulates the function of cofactor during the reaction of D-amino acid aminotransferase.
Toll-like receptor signaling in anti-cancer immunity. (2003)

It is important to augment the anti-cancer host response in cancer treatment. Recent studies suggested that the signaling via Toll-like receptors (TLRs) which are newly identified receptor molecules recognizing many pathogens, are involved in the induction of anti-cancer immunity. Seya et al. demonstrated that maturation of dendritic cells (DCs) and cytokine induction by the cell wall skeleton of Mycobacterium bovis bacillus Calmette-Guerin (BCG-CWS) are induced via both TLR2 and TLR4. Akira et al. discovered a new molecule of TLR family, TLR9, recognizing unmethylated bacterial CpG-DNA, whose clinical use is expected for cancer therapy as a potent inducer of a helper T cell 1 (Th1)-type T-cell response. TLR9-deficient mice did not show any responses to CpG-DNA, including Th 1 cytokine production and maturation of DCs. We have obtained two molecules, a lipoteichoic acid-related molecule isolated from streptococcal agent OK-432, and a plant-derived 55-kDa protein that can induce Th1 response and elicit a strong anti-cancer effect in vivo and in vitro. Our basic experiments demonstrate that TLR4 signaling is intimately involved in anti-cancer immunity induced by these immunopotentiators. Our clinical examination in oral cancer patients also suggests the requirement of both TLR4 and MD-2 in the OK-432-induced anti-cancer host response. Establishment and clinical use of the methodology for human cancer therapy by utilizing TLR signaling is greatly expected.