gebhart/patrepeval huggingface dataset:
Molecular pathomechanism of distal myopathy with rimmed vacuoles. (2005)

Distal myopathy with rimmed vacuoles (DMRV) and hereditary inclusion body myopathy (HIBM) are now known to be the same disease and are caused by mutations in tile GNE gene that encodes a bifunctional protein with two enzymatic activities: UDP-GlcNAc2-epimerase (GNE) and ManNAc kinase (MNK). GNE catalyzes the rate-limiting step in the sialic acid biosynthesis and MNK catalyzes the next step. So far, we have found homozygous or compound heterozygous mutations in 55 unrelated Japanese DMRV patients. Among them, c.1714G>C (p.V572L) mutation is the most common, accounting for 57% of the mutant alleles. The same mutation was recently identified also in Korean DMRV patients, raising the possibility of the presence of a common founder. We have also found that cardiac involvement is not very rare and is found in 18% of patients, albeit degree of severity widely varies; in some patients, it can result in sudden death. The length of time when patients become non ambulatory is diverse. The severity of clinical symptoms also varies widely, as evidenced by the presence of an asymptomatic homozygote harboring of p.D176V, the second most common mutation among Japanese patients. Patients' fibroblasts and myotubes are hyposialylated and this hyposialylation can be recovered by adding GNE metabolite, ManNAc, or sialic acid per se, NeuAc. Accordingly, the sialylation status in the skeletal muscle tissue is also greatly altered especially in fibers with rimmed vacuoles, suggesting the tight association between hyposialylation and the formation of rimmed vacuoles. However, we still do not know why hyposialylation leads to the formation of rimmed vacuoles. To further elucidate the pathomechanism and to develop a therapy of DMRV, we need to produce mouse model mouse for this disease.
Deferasirox: uncertain future following renal failure fatalities, agranulocytosis and other toxicities (2007)

Cases of fatal, acute, irreversible renal failure and cytopenias, including agranulocytosis and thrombocytopenia, have been disclosed in a postmarketing report on deferasirox, a few months after the European Union authorities and about a year after the FDA proceeded to its accelerated approval. No details on the incidence rate or the cause of these toxicities have yet been reported. Other toxic side effects include skin, gastric, auditory and ocular abnormalities, and hepatitis. Regular serum creatinine, blood counts and other toxicity monitoring as well as withdrawal of deferasirox from the patients affected and those with serum ferritin < 0.5 mg/l was recommended. Toxicity, inability to clear cardiac iron and high cost (60 euros/g) question the future universal role of deferasirox, by comparison with the safety and efficacy records of deferiprone, deferoxamine and their combination in the treatment of transfusional iron overload. Also questioned are the procedures adopted by regulatory authorities and the marketing methods of pharmaceutical companies on orphan drugs, which are of no benefit to thalassaemia patients in developing countries.
From cell image segmentation to differential diagnosis of thyroid cancer (2003)

An approach for cytologic diagnosis of thyroid cancer with the help of automatic morphometry is proposed. This approach is based on a developed computer analyser of images that is aimed at: automated processing and binarization of colour images; automatic raster-to-vector transformation and formation of biological objects; morphometric assessment of biological objects by quantitative parameters characterizing the changes of cell nuclei; building of an expert system to aid the diagnosis of thyroid cancer.
Generation and Growth Mechanism of Metal (Fe, Co, Ni) Nanotube Arrays (2006)

Nanotubes composed of layered or nonlayered materials have been synthesized through various methods, among which template-based electrodeposition technology provides a versatile technique for synthesizing one-dimensional nanostructured materials. However, the growth mechanism of nanotubes using the template method is seldom clarified. Herein, we present the systematic preparation of metal nanotube arrays and put forward the growth mechanism, termed current-directed tubular growth (CDTG), for template-based electrodeposition. There are competitive growth rates for metal atoms entering the crystal lattice, that is, v( parallel) (growth rate parallel to current direction) and v( perpendicular) (growth rate perpendicular to current direction). Metal nanotubes can be obtained at v( parallel)>>v( perpendicular), while nanowires can be obtained at v( parallel) approximately v( perpendicular). The as-synthesized metal (Fe, Co, Ni) nanotubes are constructed from nonlayered materials, which are of body-centered cubic iron structure, hexagonal close packed cobalt structure, and face-centered cubic nickel structure, respectively. The CDTG mechanism is expected to have applications in designing and synthesizing other metal nanotubes and even compound nanotubes via template-based electrodeposition technology.
Participation of lymphocyte activating factor (Interleukin 1) in the induction of cytotoxic T cell responses. (1980)

The initiation of murine alloantigen-specific cytotoxic T cell responses is macrophage dependent. The requirement for macrophages can be replaced in macrophage-depleted cytotoxic T lymphocyte assay by a soluble factor released from phorbol myristic acetate-stimulated mouse peritoneal adherent cells or P388D1 macrophage tumor cells. On the basis of the cell of origin, m.w. (15,000), and elution profiles on DEAE cellulose and polyacrylamide gels, this macrophage-replacing factor for T cell-mediated cytotoxicity was identical to lymphocyte activating factor (LAF). The stimulatory effect of LAF was totally dependent on the presence of the priming alloantigen. The results presented in this report support the hypothesis that macrophage-mediated antigen-induced T cell activation is dependent on two signals, antigen and LAF.
Eróticas heréticas heteroxéneas (1999)

ABO blood group system is the most important blood group system in transfusion and transplantation medicine. Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphomas (NHLs) worldwide. There have been some studies that lymphoma could affect ABO blood group system and thus affect blood transfusion strategy. However, the mechanisms lymphoma affecting ABO blood group system have not been fully elucidated so far. Here, we report a case of a patient who was a 72-year-old Chinese man came to our hospital for medical advice because of cervical lymphadenophathy. The patient was subsequently diagnosed with diffuse large B-cell lymphoma by lymph-node biopsy. His ABO blood group was initially typed as B on November 7, 2020. He was transfusing B type leukocyte poor RBCs (LPR) before we found the patient's ABO blood group discrepancy on December 2, 2020 by forward and reverse typing methods, which the discrepancy was verified by genotyping. The patient began to transfuse O type washed RBCs (WRBC) since then. Compared to transfuse B type leukocyte poor RBCs (LPR), the efficiency of transfusing O type washed RBCs (WRBC) was better. Although hemoglobin level did not greatly improve, indirect bilirubin level evidently decreased. Furthermore, we found B-cell lymphoma affected blood transfusion strategy by producing IgM anti-B antibody in this case. Clinicians should need to be aware of the effect of B-cell lymphoma on blood transfusion strategy.
The two phenylalanines in the GFFKR motif of the integrin α6A subunit are essential for heterodimerization (1997)

The membrane-proximal domain of the integrin alpha subunit contains a conserved motif of five amino acid residues, GFFKR. We deleted this motif from the human alpha6A subunit and found that in COS-7 cells this mutant cannot associate with the beta1 subunit and is retained in the endoplasmic reticulum. Point mutations in the GFFKR motif of the glycine residue or the two highly charged amino acids, or deletion of the lysine and arginine residues, had no effect on the ability of alpha6 to interact with beta1 and to be expressed at the cell surface. In contrast, by replacing either of the two phenylalanines with alanine, or by deletion of both of these residues, alpha6 was incapable of associating with beta1. The alpha6 point mutants that associated with beta1 were expressed in K562 cells and their responsiveness to integrin-activating factors was determined. None of these transfectants bound spontaneously to laminin-1, but binding could be induced by either PMA or the stimulating anti-beta1 antibody TS2/16 to the same extent as that of the wild-type transfectant. The ability of these mutants to initiate focal-contact formation in CHO cells plated on laminin-1 substrates also appeared to be unaltered. Thus the behaviour of alpha6 mutants involving the glycine, lysine or arginine residues was indistinguishable from that of wild-type alpha6 both in inside-out and outside-in signalling. In contrast, deletion of the cytoplasmic domain of alpha6 C-terminal of the GFFKR motif resulted in a loss of responsiveness of alpha6beta1 to PMA stimulation and formation of focal contacts on laminin-1. However, this mutant was targeted to focal contacts formed by other integrins, even when they had not bound ligand. Together, these results suggest that the two phenylalanine residues of the GFFKR motif provide a site for interaction of the alpha6A subunit with beta1, whereas the cytoplasmic domain C-terminal of this motif is involved in the regulation of bidirectional signalling via alpha6Abeta1.
Laser-Resonance Chirality Selection in Single-Walled Carbon Nanotubes (2005)

Laser Resonance Chirality Selection method has been proposed to select single‐walled carbon nanotubes (SWNTs) with specific chirality from mass of SWNTs by intense laser irradiation. Absorption of the exciting laser beam is strongly enhanced for SWNTs with specific chirality when the laser excitation energy is close to the energy separation in the density of states. As a result of the resonance effect, at a certain threshold excitation power density, only these SWNTs can be oxidized and be removed selectively. We have demonstrated with Raman scattering measurements that SWNTs with specific chirality are selectively removed after intense laser irradiation.
Identification of integrin collagen receptors on human melanoma cells (1989)

Integrin receptors may mediate the adhesion of cells to a number of extracellular matrix components. We found that the attachment of human melanoma cells to collagen types I and IV was blocked by antibodies to the integrin beta 1 subunit but not by peptides containing the Arg-Gly-Asp sequence. Ligand affinity chromatography was used to search for integrin-related receptors which mediate adhesion to native collagens. Detergent extracts of surface 125I-iodinated melanoma cells were chromatographed on type I or IV collagen-Sepharose columns. Bound material was eluted and analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. EDTA, but not Arg-Gly-Asp peptides, eluted a mixture of two integrin-related heterodimeric complexes. Each complex contained the integrin beta 1 chain with Mr of 110,000 and a distinct alpha chain with Mr of either 200,000 or 150,000. Immunoprecipitation with specific monoclonal antibodies identified the complexes as very late activation antigen (VLA)-1 (alpha 1 beta 1) and VLA-2 (alpha 2 beta 1), respectively. The binding of these receptors to collagen appeared to be specific because they failed to be retained on fibronectin- or laminin-Sepharose columns. Immunofluorescent staining of cells on collagen substrates with antibodies to VLA-1 and VLA-2 localized these complexes in vinculin-positive adhesion plaques. In contrast, the receptor complexes were not detected in adhesion plaques of cells attached to fibronectin- or laminin-coated substrates. These results indicate that melanoma cells express at least two different integrin-related collagen-binding receptor complexes that appear to mediate cell adhesion to collagen.
Multiple and Plastic Receptors Mediate Tonic GABAAReceptor Currents in the Hippocampus (2005)

Persistent activation of GABAA receptors by extracellular GABA (tonic inhibition) plays a critical role in signal processing and network excitability in the brain. In hippocampal principal cells, tonic inhibition has been reported to be mediated by alpha5-subunit-containing GABAA receptors (alpha5GABAARs). Pharmacological or genetic disruption of these receptors improves cognitive performance, suggesting that tonic inhibition has an adverse effect on information processing. Here, we show that alpha5GABAARs contribute to tonic currents in pyramidal cells only when ambient GABA concentrations increase (as may occur during increased brain activity). At low ambient GABA concentrations, activation of delta-subunit-containing GABAA receptors predominates. In epileptic tissue, alpha5GABAARs are downregulated and no longer contribute to tonic currents under conditions of raised extracellular GABA concentrations. Under these conditions, however, the tonic current is greater in pyramidal cells from epileptic tissue than in pyramidal cells from nonepileptic tissue, implying substitution of alpha5GABAARs by other GABAA receptor subtypes. These results reveal multiple components of tonic GABAA receptor-mediated conductance that are activated by low GABA concentrations. The relative contribution of these components changes after the induction of epilepsy, implying an adaptive plasticity of the tonic current in the presence of spontaneous seizures.
On-line capillary liquid chromatography tandem mass spectrometry on an ion trap/ reflectron time-of-flight mass spectrometer using the sequence tag database search approach for peptide sequencing and protein identification (2000)

Capillary high-performance liquid chromatography has been coupled on-line with an ion trap storage/reflectron time-of-flight mass spectrometer to perform tandem mass spectrometry for tryptic peptides. Selection and fragmentation of the precursor ions were performed in a three-dimensional ion trap, and the resulting fragment ions were pulsed out of the trap into a reflectron time-of-flight mass spectrometer for mass analysis. The stored waveform inverse Fourier transform waveform was applied to perform ion selection and an improved tickle voltage optimization scheme was used to generate collision-induced dissociation. Tandem mass spectra of various doubly charged tryptic peptides were investigated where a conspicuous y ion series over a certain mass range defined a partial amino acid sequence. The partial sequence was used to determine the identity of the peptide or even the protein by database search using the sequence tag approach. Several peptides from tryptic digests of horse heart myoglobin and bovine cytochrome c were selected for tandem mass spectrometry (MS/MS) where it was demonstrated that the proteins could be identified based on sequence tags derived from MS/MS spectra. This approach was also utilized to identify protein spots from a two-dimensional gel separation of a human esophageal adenocarcinoma cell line.
Rosiglitazone Monotherapy in Mild-to-Moderate Alzheimer’s Disease: Results from a Randomized, Double-Blind, Placebo-Controlled Phase III Study (2010)

No evidence of efficacy of 2 mg or 8 mg RSG XR monotherapy in cognition or global function was detected in the APOE-ε4-negative or other analysis populations. The safety and tolerability of RSG XR was consistent with its known pharmacology.
The characterization of endosomal insulin degradation intermediates and their sequence of production (1996)

Insulin degradation within isolated rat liver endosomes was studied in vitro with the aid of three 125I-insulin isomers specifically labelled at tyrosine (A14, B16 and B26). Chloroquine and 1,10-phenanthroline were used to minimize insulin proteolysis during endosome preparation, whereas the manipulation of endosomal processing of insulin in vitro by Co2+ ions (to activate) and 1,10-phenanthroline (to inhibit) permitted the study of degradation intermediates and their time-dependent production. Structural and kinetic analysis of intermediates isolated from both intra- and extra-endosomal compartments allowed the determination of major cleavage sites and the probable sequence of proteolytic events. It was found that 125I-tyrosine is the ultimate labelled degradation product of all iodo-insulin isomers, suggesting that endosomal proteases are able to degrade insulin to the level of its constituent amino acids. 125I-tyrosine was also the only radiolabelled product able to cross the endosomal membrane. Intra-endosomal insulin degradation proceeds via two inter-related cleavage routes after metalloendoprotease cleavage of the B-chain. One pathway results from an initial cleavage in the centre region of the B-chain (B7-19), probably at B14-15, whereas the major route results from a cleavage at B24-25. B24-25 cleavage removes the B-chain C-terminal hexapeptide (B25-30), which is subsequently cleaved by an aminopeptidase activity to produce first the pentapeptide B26-30 and then 125I-tyrosine. The isolation of intact radiolabelled A-chain from the degradation of 125I-[A14]-insulin suggests that further degradation of proteolytic intermediates containing cleaved B-chain proceeds via interchain disulphide reduction. The A-chain is then processed by several cleavages, one of which occurs at A13-14.
Acid- and Base-Induced Proteins during Aerobic and Anaerobic Growth of Escherichia coli Revealed by Two-Dimensional Gel Electrophoresis (1999)

Proteins induced by acid or base, during long-term aerobic or anaerobic growth in complex medium, were identified in Escherichia coli. Two-dimensional gel electrophoresis revealed pH-dependent induction of 18 proteins, nine of which were identified by N-terminal sequencing. At pH 9, tryptophan deaminase (TnaA) was induced to a high level, becoming one of the most abundant proteins observed. TnaA may reverse alkalinization by metabolizing amino acids to produce acidic products. Also induced at high pH, but only in anaerobiosis, was glutamate decarboxylase (GadA). The gad system (GadA/GadBC) neutralizes acidity and enhances survival in extreme acid; its induction during anaerobic growth may help protect alkaline-grown cells from the acidification resulting from anaerobic fermentation. To investigate possible responses to internal acidification, cultures were grown in propionate, a membrane-permeant weak acid which acidifies the cytoplasm. YfiD, a homologue of pyruvate formate lyase, was induced to high levels at pH 4.4 and induced twofold more by propionate at pH 6; both of these conditions cause internal acidification. At neutral or alkaline pH, YfiD was virtually absent. YfiD is therefore a strong candidate for response to internal acidification. Acid or propionate also increased the expression of alkyl hydroperoxide reductase (AhpC) but only during aerobic growth. At neutral or high pH, AhpC showed no significant difference between aerobic and anaerobic growth. The increase of AhpC in acid may help protect the cell from the greater concentrations of oxidizing intermediates at low pH. Isocitrate lyase (AceA) was induced by oxygen across the pH range but showed substantially greater induction in acid or in base than at pH 7. Additional responses observed included the induction of MalE at high pH and induction of several enzymes of sugar metabolism at low pH: the phosphotransferase system components ManX and PtsH and the galactitol fermentation enzyme GatY. Overall, our results indicate complex relationships between pH and oxygen and a novel permeant acid-inducible gene, YfiD.
Effects of sympathetic activation by adrenergic infusions on hemostasis in vivo (2000)

Overactivity of the sympathetic nervous system (SNS) has been related to increased cardiovascular morbidity. Historical reports suggest hastening of blood coagulation following intravenous administration of epinephrine. Given the important role of the hemostatic system in atherosclerosis and thrombosis, it is surprising that short-term adrenergic effects on blood coagulation, fibrinolysis and platelet activity have not been scrutinized closely. To elucidate such effects in vivo, this paper reviews human studies in which alpha- and beta-sympathomimetic agents had been infused. The literature suggests a dose-dependent stimulation of factor VIII clotting activity, von Willebrand factor antigen, tissue-type plasminogen activator, and platelets within a 15- to 40-min infusion of epinephrine. Precise mechanisms underlying hemostatic changes with sympathetic activation remain to some extent speculative. However, there is evidence from adrenoreceptor blockade studies that coagulation and fibrinolysis molecules are released into circulation by stimulation of vascular endothelial beta-adrenoreceptors (most likely beta2-receptors). Combined alpha2- and beta2-adrenoreceptor-related mechanism(s) are responsible for platelet activation. Short-term activation of the SNS effects regular hemostatic activity. While in healthy individuals the hemostatic balance between coagulation and fibrinolysis may be preserved, catecholamine surge may trigger a hypercoagulable state and enhance the odds of overt thrombosis in patients with atherosclerotic disease.
Ligand-induced Formation of p55 and p75 Tumor Necrosis Factor Receptor Heterocomplexes on Intact Cells (1997)

The p55 and p75 tumor necrosis factor receptors are known to mediate their effects on cells through distinct signaling pathways. Under certain circumstances, the two classes of TNF receptors cooperate with each another to produce enhanced cellular responses. The only molecular mechanism proposed thus far to explain this effect is the process of "ligand passing," whereby TNF is concentrated at cell surfaces by binding to p75 and then following dissociation from this receptor class binds with high efficiency to p55. Using the in vivo model of TNF-induced TNF receptor shedding we have uncovered a novel ligand-dependent interaction of the two TNF receptors that occurs upon exposure of cells to TNF. Using TNF receptor-specific monoclonal antibodies that bind TNF receptors in the presence or absence of ligand, we report that TNF induces the formation of heterocomplexes consisting of both p55 and p75 TNF receptors. Whereas immunoprecipitates from untreated or human TNF-treated cells formed with either p55 or p75 TNF receptor-specific monoclonal antibodies contained only the relevant TNF receptor class, anti-p55 or anti-p75 precipitated both receptor types from murine TNF-treated cells. Ligand-induced complex formation was transient, occurred at physiologically relevant concentrations of TNF, and occurred with receptors lacking intracellular domains or that contained irrelevant transmembrane domains. Formation of TNF receptor heterocomplexes may therefore 1) define a novel molecular mechanism of ligand passing and/or 2) contribute to cooperative TNF receptor signaling via the juxtaposition of the intracellular domains of the two receptor classes and the signaling proteins that they recruit.