gebhart/patrepeval huggingface dataset:
Metabolic manipulation in ischaemic heart disease, a novel approach to treatment (2004)

Antianginal drugs that exert their anti-ischaemic effects primarily by altering myocardial metabolism have recently attracted attention. They have the potential to relieve symptoms in patients with refractory angina who are already on "optimal" medical therapy and have disease that is not amenable to revascularisation, making these drugs an attractive addition to therapy, particularly for the elderly population. In some cases, they may even be used as first-line treatment. These drugs increase glucose metabolism at the expense of free-fatty-acid metabolism, enhancing oxygen efficiency during myocardial ischaemia. Whilst they have been demonstrated to reduce ischaemia in several clinical trials, their use remains limited. This review aims to draw attention to these "metabolic" antianginal drugs while surveying the evidence supporting their use and mode of action. Four metabolic antianginal drugs are reviewed: perhexiline, trimetazidine, ranolazine, and etomoxir. We also discuss the metabolic actions of glucose-insulin-potassium and beta-blockers and describe myocardial metabolism during normal and ischaemic conditions. The potential of these metabolic agents may extend beyond the treatment of ischaemia secondary to coronary artery disease. They offer significant promise for the treatment of symptoms occurring due to inoperable aortic stenosis, hypertrophic cardiomyopathy, and chronic heart failure.
中、加两国青少年回答“个别差异问卷”的跨文化研究 (1990)

对857名加拿大维多利亚和900名中国上海的早期和中期青少年实施佩维奥和哈希曼的个别差异问卷(修订版)调查。结果在加拿大样组中重复发现了他们研究中的三个表象因素和三个言语因素,在中国样组中则重复出现主要的表象因素和言语因素。然而,两样组均表现出思维的表象方式超出言语方式,这和佩维奥和哈希曼研究中关于加拿大成人思维偏爱言语而非表象的结果不同。
Microtubule-Affinity Regulating Kinase (MARK) Is Tightly Associated with Neurofibrillary Tangles in Alzheimer Brain: A Fluorescence Resonance Energy Transfer Study (2000)

Paired helical filaments, the main structural components of the neurofibrillary tangles in Alzheimer disease, consist of phosphorylated tau protein. Because the levels and degree of phosphorylation are significantly higher in paired helical filament (PHF)-derived tau than in normal adult tau, and because phosphorylation of tau severely disrupts microtubule stability, it is postulated that tau phosphorylation is an important step in PHF formation. The kinases and/or phosphatases that act in vivo to help induce such a pathological state of tau, however, are not yet known. In this study we implicate the non-proline directed kinase MARK in PHF-tau phosphorylation, by virtue of its close intermolecular association with the phosphorylated Ser262 epitope on PHF-tau as assessed by fluorescence resonance energy transfer. Moreover, because this tight enzyme-substrate association is observed in neurofibrillary tangles in Alzheimer tissue, we suggest that PHF-tau phosphorylation may occur to some extent on assembled PHF filaments.
The Significance of Volatile Sulfur Compounds in Food Flavors (2011)

Volatile sulfur compounds are important contributors to the characteristic flavors and off-flavors of many foods. As a class, sulfur-containing flavor volatiles have low sensory detection thresholds, are present in low concentration and are often chemically labile, which can present measurement challenges. Advances in analytical separation techniques and instrumentation have enabled understandings of their occurrence and contributions to their relative sensory significance.
Treatment of Brain Metastases (2015)

Brain metastases (BMs) occur in 10% to 20% of adult patients with cancer, and with increased surveillance and improved systemic control, the incidence is likely to grow. Despite multimodal treatment, prognosis remains poor. Current evidence supports use of whole-brain radiation therapy when patients present with multiple BMs. However, its associated cognitive impairment is a major deterrent in patients likely to live longer than 6 months. In patients with oligometastases (one to three metastases) and even some with multiple lesions less than 3 to 4 cm, especially if the primary tumor is considered radiotherapy resistant, stereotactic radiosurgery is recommended; if the BMs are greater than 4 cm, surgical resection with or without postoperative whole-brain radiation therapy should be considered. There is increasing evidence that systemic therapy, including targeted therapy and immunotherapy, is effective against BM and may be an early choice, especially in patients with sensitive primary tumors. In patients with progressive systemic disease, limited treatment options, and poor performance status, best supportive care may be appropriate. Regardless of treatment goals, use of corticosteroids or antiepileptic medications is helpful in symptomatic patients. In this review, we provide a summary of current therapy, as well as developments in the treatment of BM from solid tumors.
Bioactive oligosaccharide natural products (2014)

Covering up to December 2013. Oligosaccharide natural products target a wide spectrum of biological processes including disruption of cell wall biosynthesis, interference of bacterial translation, and inhibition of human α-amylase. Correspondingly, oligosaccharides possess the potential for development as treatments of such diverse diseases as bacterial infections and type II diabetes. Despite their potent and selective activities and potential clinical relevance, isolated bioactive secondary metabolic oligosaccharides are less prevalent than other classes of natural products and their biosynthesis has received comparatively less attention. This review highlights the unique modes of action and biosynthesis of four classes of bioactive oligosaccharides: the orthosomycins, moenomycins, saccharomicins, and acarviostatins.
Formation of hemoglobin adducts upon treatment of F344 rats with the tobacco-specific nitrosamines 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone and N'-nitrosonornicotine. (1987)

[5-3H]4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone ([5-3H]NNK), [C3H3]NNK, and [5-3H]N'-nitrosonornicotine ([5-3H]NNN) were administered to F344 rats by i.p. injection. Levels of tritium present per milligram globin, 24 h after treatment were 720 fmol (0.1% of dose) for [5-3H]NNK, 640 fmol for [C3H3]NNK, and 370 fmol for [5-3H]NNN. Tritium was detectable in globin 7-8 weeks after treatment with [5-3H]NNK or [5-3H]NNN. Approximately 10-15% of the bound tritium in the globin of rats treated with [5-3H]NNK was released upon incubation of the globin with dilute NaOH or HCl. The released material was identified as 4-hydroxy-1-(3-pyridyl)-1-butanone; it was detectable in globin for 6 weeks (t1/2 = 9.1 days) after administration of [5-3H]NNK. 4-Hydroxy-1-(3-pyridyl)-1-butanone was also formed upon NaOH treatment of globin isolated from rats injected with [5-3H]NNN or [5-3H]4-(carbethoxynitrosamino)-1-(3-pyridyl)-1-butanone. The formation of 4-hydroxy-1-(3-pyridyl)-1-butanone under these conditions is consistent with a mechanism by which 4-(3-pyridyl)-4-oxobutyldiazohydroxide is produced upon metabolic alpha-hydroxylation of NNK or NNN and binds to globin of hemoglobin, yielding an adduct which is readily hydrolyzed by acid or base. Support for this mechanism was obtained by in vitro experiments. Levels of 4-hydroxy-1-(3-pyridyl)-1-butanone released upon base treatment of globin were 50 times greater after incubation of rat hemoglobin with [5-3H]4-(carbethoxynitrosamino)-1-(3-pyridyl)-1-butanone than with either [5-3H]NNK or [5-3H]4-hydroxy-1-(3-pyridyl)-1-butanone. The results of this study suggest methods that might be applicable for assessing the molecular dosimetry of NNK and NNN in individuals exposed to tobacco and tobacco smoke.
T cell subset-dependent modulation of immunity to Borrelia burgdorferi in mice. (1995)

The possible involvement of specific T cells in resolution of infections with Borrelia burgdorferi (Bb), the causative agent of human Lyme disease, has not been adequately studied. To investigate the potential role of T cell subsets in resistance, we have depleted mice of CD4+ and CD8+ T cell subsets in vivo by the administration of specific mAbs and have examined outcomes after infection with Bb. Our results indicate that CD4+ T cells are required for immunologic control of spirochete levels, because their depletion in both susceptible C3H/HeN and resistant BALB/c mice increased the severity of arthritis and the numbers of spirochetes found in joints and skin, as compared with Bb-infected mice treated with a control mAb. In contrast, the CD8+ T cell compartment, particularly in susceptible C3H/HeN mice, appears to promote the disease process, possibly by interfering with the generation of protective immunity, as abrogation of this subset in vivo led to a reduction in both arthritis and in spirochete levels found in joints and skin when compared with Bb-infected control mice. Our inability to establish a correlation between resistance and Bb-specific IgG Ab levels in these mice raises the possibility that Ab-independent mechanisms are important in protection. These findings suggest that the final outcome in Bb-infected hosts may be the net effect of antagonistic influences exerted by CD4+ and CD8+ T cell subsets.
Continuous Production of Butanol by Clostridium acetobutylicum Immobilized in a Fibrous Bed Bioreactor (2004)

We explored the influence of dilution rate and pH in continuous cultures of Clostridium acetobutylicum. A 200-mL fibrous bed bioreactor was used to produce high cell density and butyrate concentrations at pH 5.4 and 35°C. By feeding glucose and butyrate as a cosubstrate, the fermentation was maintained in the solventogenesis phase, and the optimal butanol productivity of 4.6 g/(L h) and a yield of 0.42 g/g were obtained at a dilution rate of 0.9 h-1 and pH 4.3. Compared to the conventional acetone-butanol-ethanol fermentation, the new fermentation process greatly improved butanol yield, making butanol production from corn an attractive alternative to ethanol fermentation.
Controlled Production of Monodisperse Double Emulsions by Two-Step Droplet Breakup in Microfluidic Devices (2004)

A microfluidic device having both hydrophobic and hydrophilic components is exploited for production of multiple-phase emulsions. For producing water-in-oil-in-water (W/O/W) dispersions, aqueous droplets ruptured at the upstream hydrophobic junction are enclosed within organic droplets formed at the downstream hydrophilic junction. Droplets produced at each junction could have narrow size distributions with coefficients of variation in diameter of less than 3%. Control of the flow conditions produces variations in internal/external droplet sizes and in the internal droplet number. Both W/O/W emulsions (with two types of internal droplets) and oil-in-water-in-oil emulsions were prepared by varying geometry and wettability in microchannels.
Apple Pomace: A Potential Substrate for Production of β-Glucosidase by Aspergillus Foetidus (1994)

Of the three Aspergillus species examined, Aspergillus foetidus NRRL 337 was found to produce more β-glucosidase activity on apple pomace than Aspergillus niger NRRL 599 and Aspergillus fumigatus P1061. The enzyme was purified 12-fold by ultrafiltration and gel filtration with a yield of 490 g/kg. The partially purified enzyme exhibited its optimal activity at 65°C and was most active at pH 4.6. The Km value for p-nitrophenol β D-glucopyranoside (PNPG) was 0.87 mmol/L. The enzyme had a molecular weight of 275 kDa as estimated by gel filtration with Sephadex G-200.
Application of fluorescence lifetime imaging microscopy to the investigation of intracellular PDT mechanisms (1997)

The potential for the application of fluorescence lifetime imaging (FLIM) microscopy to studies of photosensitization mechanisms in photodynamic therapy (PDT) has been investigated. The fluorescence microscope incorporates a standard inverted optical microscope, a picosecond pulsed dye-laser excitation source, and an intensified CCD camera detector capable of being gated on a sub-nanosecond timescale. Fluorescence lifetime images resulting from multi-component analysis of sub-nanosecond gated fluorescence images of monolayer V79-4 Chinese hamster lung fibroblasts stained with disulphonated aluminium phthalocyanine (AlPcS2), a photosensitizer used in PDT, are presented. The results of these measurements are discussed in terms of the intracellular localization of the sensitizer. Preliminary results from multi-component FLIM of V79-4 cells multiply stained with AlPcS2 and a potential intracellular pH lifetime probe, 5(+6)-carboxynaphthofluorescein, are also presented.
Neuropilin-1 Expression on Regulatory T Cells Enhances Their Interactions with Dendritic Cells during Antigen Recognition (2008)

The interaction of T cells with dendritic cells (DCs) determines whether an immune response is launched or not. Recognition of antigen leads to formation of immunological synapses at the interface between the cells. The length of interaction is likely to determine the functional outcome, because it limits the number of MHC class II-peptide complexes that can be recruited into the synapse. Here, we show that regulatory T (Treg) cells and naive helper T (Th) cells interact differently with DCs in the absence of proinflammatory stimuli. Although differences in T cell receptor repertoire might contribute, Foxp3-induced phenotypic differences play a major role. We found that Neuropilin-1 (Nrp-1), which is expressed by most Treg cells but not naive Th cells, promoted prolonged interactions with immature DCs (iDCs), resulting in higher sensitivity to limiting amounts of antigen. This is likely to give Treg cells an advantage over naive Th cells, with the same specificity leading to a "default" suppression of immune responses in the absence of "danger signals."
A Constitutively Active Mutant PTH-PTHrP Receptor in Jansen-Type Metaphyseal Chondrodysplasia (1995)

A single heterozygous nucleotide exchange in exon M2 of the gene encoding the parathyroid hormone-parathyroid hormone-related peptide (PTH-PTHrP) receptor was identified in a patient with Jansen-type metaphyseal chondrodysplasia, which changes a strictly conserved histidine residue at position 223 in the receptor's first intracellular loop to arginine. Constitutive, ligand-independent adenosine 3',5'-monophosphate accumulation was observed in COS-7 cells expressing the mutant PTH-PTHrP receptor but not in cells expressing the wild-type receptor. This finding explains the severe ligand-independent hypercalcemia and hypophosphatemia, and most likely the abnormal formation of endochondral bone, in this rare form of short-limbed dwarfism.
Variation in the duration of arousal in obstructive sleep apnea. (2005)

Arousals were greater in apneas than in hypopneas. Apneas and events >20 s with a minSaO(2) <86% were associated more frequently with arousal >11 s.
NFAT signaling in neural development and axon growth (2007)

The NFAT (nuclear factor of activated T-cells) family of transcription factors functions as integrators of multiple signaling pathways by binding to chromatin in combination with other transcription factors and coactivators to regulate genes central for many developmental systems. Recent experimental evidence has shown that the calcineurin/NFAT signaling pathway is important in axonal growth and guidance during vertebrate development. In fact, studies with triple NFATc2/c3/c4 mutant mice demonstrate that the extension and organization of sensory axon projection and commissural axon growth are both dependent upon NFAT activity. Neurotrophin and L-type calcium channel signaling modulate intracellular calcium levels to regulate the nuclear import and transcriptional activity of NFAT by activating the phosphatase calcineurin. The rephosphorylation and subsequent export of NFAT from the nucleus is mediated by several kinases, including GSK-3beta, which contribute to the fine tuning of NFAT transcriptional activity in neurons. However, currently, no direct transcriptional targets for NFAT have been identified in a chromatin environment in the nervous system. Undiscovered are also the binding partners of NFAT that might combinatorially regulate specific genes important for neuronal development. This review will discuss the current knowledge related to NFAT signaling in the nervous system development and the potential for future research directions.
Unique circumferential peripheral keratitis in relapsing polychondritis (2017)

This is the first report of a case of RP causing unique circumferential peripheral keratitis. This keratitis occurred despite use of focal and systemic steroids and showed improvement with general recovery. This may indicate that stabilization of general condition is important for recovery from keratitis in RP.
Structural and functional characterization of Factor VIII-Δ II, a new recombinant Factor VIII lacking most of the B-domain (1991)

A recombinant Factor VIII (Factor VIII-delta II) consists of a unique polypeptide chain of 165 kDa deleted from the major part of the B-domain and from the cleavage site at Arg-1648-Glu-1649 found in plasma-derived Factor VIII. It was expressed in mammalian cells in serum-free medium containing von Willebrand factor and purified by a one-step immunopurification. The recombinant Factor VIII was characterized as a single active peak when subjected to f.p.l.c., in contrast with the plasma-derived molecule. Its coagulant activity was decreased in the presence of EDTA, suggesting that a bivalent ion is required, as for plasma-derived Factor VIII. The activation by thrombin and the inactivation by activated protein C were studied and the resulting molecular forms were analysed by f.p.l.c. and SDS/PAGE. The results clearly demonstrate that, despite the structural differences between plasma-derived and recombinant Factor VIII, activation and inactivation of Factor VIII-delta II generate proteolysed complexes similar to that described for plasma-derived Factor VIII. Thus this deleted recombinant Factor VIII, which is processed similarly to plasma-derived Factor VIII, should be normally integrated in the regulation system of Factor X activation in the blood-coagulation cascade.
Learning New Tricks from Old Dogs: β-Adrenergic Receptors Teach New Lessons on Firing Up Adipose Tissue Metabolism (2004)

The three beta AR (beta-adrenergic receptor) subtypes (beta(1)AR, beta(2)AR, and beta(3)AR) are members of the large family of G protein-coupled receptors, each of which is coupled to G alpha s and increases in intracellular cAMP levels. In white adipose tissues, catecholamine activation of the beta ARs leads to the mobilization of stored fatty acids and regulates release of several adipokines, whereas in brown adipose tissue they stimulate the specialized process of adaptive nonshivering thermogenesis. Noteworthy, in most models of obesity the beta AR system is dysfunctional, and its ability to stimulate lipolysis and thermogenesis are both impaired. Nevertheless, selective agonists for the beta(3)AR, a subtype that is found predominantly in adipocytes, have been able to prevent or reverse obesity and accompanying insulin resistance in animal models. Whether this is a viable therapeutic option for human obesity is much debated with regard to the existence of brown adipocytes in humans or their ability to be recruited. Nevertheless, probing the physiological changes in adrenoceptor function in rodent obesity, as well as the process by which beta(3)AR agonists promote a thermogenic shift in fuel use, have yielded unexpected new insights into beta AR signaling and adipocyte physiology. These include the recent discovery of an essential role of p38 MAPK in mediating adaptive thermogenesis, as well as the accessory role of the ERK MAPK pathway for the control of lipolysis. Because these metabolic events were traditionally ascribed solely to the cAMP/protein kinase A system, the integration of these signaling mechanisms may pose new therapeutic directions in the quest to counter the obesity epidemic in our midst.
Calcineurin Links Ca2+Dysregulation with Brain Aging (2001)

Brain aging is associated with altered Ca(2+) regulation. However, many Ca(2+) signal transduction mechanisms have not been explored in the aged brain. Here, we report that cytosolic expression and activity of the Ca(2+)-dependent protein phosphatase calcineurin (CaN) increases in the hippocampus during aging. CaN changes were paralleled by increased activation, but not expression, of CaN-regulated protein phosphatase 1 and a reduction in the phosphorylation state of CaN substrates involved in cell survival (i.e., Bcl-2-associated death protein and cAMP response element-binding protein). The age-related increase in CaN activity was not attributable to the inability of CaN to translocate to the membrane and was reduced by blocking L-type Ca(2+) channels. Finally, increased CaN activity correlated with memory function as measured with the Morris water escape task. The results suggest that altered regulation of CaN is one of the processes that could link Ca(2+) dyshomeostasis to age-related changes in neural function and cognition.
Removal of 3‐MCPD esters and related substances after refining by adsorbent material (2010)

Abstract Possibilities of a removal of 3‐chloro‐1,2‐propanediol fatty acid esters (3‐MCPD esters) and related substances from palm oil were investigated using different adsorption materials. Some of them are already applied for the improvement of frying oils with respect to reducing polar components. For this purpose nine different commercially available inorganic adsorbent materials were chosen and screened with respect to their ability to reduce the contents of 3‐MCPD esters and related substances in a refined palm oil. Two of the materials, a calcinated zeolite and a synthetic magnesium silicate, were found to be able to reduce the contents of these substances in a range of up to 40%. Further investigations revealed that the ‘related substances’ which had been identified mainly as glycidyl esters, were removed but not the 3‐MCPD esters. Especially the zeolite was able to lower the concentration of these substances relatively fast in a broad range of treatment temperatures. No adverse effects were detected for this material with respect to sensory properties and oxidative stability of the palm oil after the treatment. Practical applications : The successful removal of the health relevant 3‐MCPD esters and related substances may open additional possibilities for the manufacturing of palm oils containing these substances, for example for infant foods. The advantage of such an approach is that these procedures may be easily implemented in a short time frame. In contrast, influencing of precursor contents and formation pathways, like changes in culture and harvesting of palm fruits or modifications of refining processes, requires more fundamental research and may have several impacts on the manufacturing procedures.