gebhart/patrepeval huggingface dataset:
Normal alveolar epithelial lining fluid contains high levels of glutathione (1987)

The epithelial cells on the alveolar surface of the human lower respiratory tract are vulnerable to toxic oxidants derived from inhaled pollutants or inflammatory cells. Although these lung cells have intracellular antioxidants, these defenses may be insufficient to protect the epithelial surface against oxidants present at the alveolar surface. This study demonstrates that the epithelial lining fluid (ELF) of the lower respiratory tract contains large amounts of the sulfhydryl-containing antioxidant glutathione (GSH). The total glutathione (the reduced form GSH and the disulfide GSSG) concentration of normal ELF was 140-fold higher than that in plasma of the same individuals, and 96% of the glutathione in ELF was in the reduced form. Compared with nonsmokers, cigarette smokers had 80% higher levels of ELF total glutathione, 98% of which was in the reduced form. Studies of cultured lung epithelial cells and fibroblasts demonstrated that these concentrations of reduced glutathione were sufficient to protect these cells against the burden of H2O2 in the range released by alveolar macrophages removed from the lower respiratory tract of nonsmokers and smokers, respectively, suggesting that the glutathione present in the alveolar ELF of normal individuals likely contributes to the protective screen against oxidants in the extracellular milieu of the lower respiratory tract.
Protein inference: a review (2012)

Assembling peptides identified from tandem mass spectra into a list of proteins, referred to as protein inference, is a critical step in proteomics research. Due to the existence of degenerate peptides and 'one-hit wonders', it is very difficult to determine which proteins are present in the sample. In this paper, we review existing protein inference methods and classify them according to the source of peptide identifications and the principle of algorithms. It is hoped that the readers will gain a good understanding of the current development in this field after reading this review and come up with new protein inference algorithms.
Complete amino acid sequence of the delta heavy chain of human immunoglobulin D. (1982)

We have determined the amino acid sequence of the variable (V) region of the delta heavy (H) chain of human IgD isolated from the plasma of myeloma patient WAH. This V region is unusual in its amino end group (arginine) and in its length (129 residues). The length is due to 10 insertions in the third complementarity-determining region (CDR3). A computer search showed that no reported CDR3-joining region (-JH) sequences are identical and that they appear to be unrelated to the constant (C) region sequences of immunoglobulins. The V region sequence together with our previous results for the C region give the complete sequence of the human delta chain WAH, which has 512 amino acid residues and a Mr congruent to 65,000. The human delta chain has four domains (V, C delta 1, C delta 2, and C delta 3) and a long hinge region; by comparison, the mouse delta chain lacks a continuous segment of 135 residues, including half the hinge region and the entire C delta 2 domain. The human and mouse delta chains also differ in the number, kind, and location of GlcN and GalN glycans and probably in conformation and quaternary structure. These and other considerations suggest that there may be multiple forms of both secreted and membrane-bound IgD that differ in size, structure, and function.
A nontransferring dry adhesive with hierarchical polymer nanohairs (2009)

We present a simple yet robust method for fabricating angled, hierarchically patterned high-aspect-ratio polymer nanohairs to generate directionally sensitive dry adhesives. The slanted polymeric nanostructures were molded from an etched polySi substrate containing slanted nanoholes. An angled etching technique was developed to fabricate slanted nanoholes with flat tips by inserting an etch-stop layer of silicon dioxide. This unique etching method was equipped with a Faraday cage system to control the ion-incident angles in the conventional plasma etching system. The polymeric nanohairs were fabricated with tailored leaning angles, sizes, tip shapes, and hierarchical structures. As a result of controlled leaning angle and bulged flat top of the nanohairs, the replicated, slanted nanohairs showed excellent directional adhesion, exhibiting strong shear attachment (approximately 26 N/cm(2) in maximum) in the angled direction and easy detachment (approximately 2.2 N/cm(2)) in the opposite direction, with a hysteresis value of approximately 10. In addition to single scale nanohairs, monolithic, micro-nanoscale combined hierarchical hairs were also fabricated by using a 2-step UV-assisted molding technique. These hierarchical nanoscale patterns maintained their adhesive force even on a rough surface (roughness <20 microm) because of an increase in the contact area by the enhanced height of hierarchy, whereas simple nanohairs lost their adhesion strength. To demonstrate the potential applications of the adhesive patch, the dry adhesive was used to transport a large-area glass (47.5 x 37.5 cm(2), second-generation TFT-LCD glass), which could replace the current electrostatic transport/holding system with further optimization.
Activation of transient receptor potential A1 by a non‐pungent capsaicin‐like compound, capsiate (2012)

Taken together, these results indicate that capsinoids activate TRPA1 by an as yet unknown mechanism, and TRPA1 could be involved in physiological phenomena associated with capsinoid treatment.
An Efficient Synthesis of Benzene Fused Six-, Seven- and Eight-membered Rings Containing Nitrogen and Sulfur by Benzyne Ring Closure Reaction (2004)

3,4-Dihydro-2-H-benzo [1,4]thiazines (3a-c), 2,3,4,5-tetrahydro[b]- [1,4]thiazapines (3d-f) and 2,3,4,5-tetrahydro-2H-benzo [b][1,4]thiazocines (3g-i) were prepared by the cyclization of the respective 2-bromophenylsulfanyl derivatives of ethylamine (1a-c), propylamine (2d-f) and butylamine (2g-i).A major portion of our research for the past several years has been concerned with the use of benzyne chemistry in preparing new heterocycles.For example, we have prepared new heterocycles by nucleophilic addition to arynes possessing charged substituents, 1 by the reaction of benzyne with Barton esters, 2 and by Diels-Alder's cycloaddition reactions involving 4-haloarynes with furan, 3 selenoureas, 4 and N,N-diethylthiocarbamic acid S-o-tolyl esters. 5Recently, we turned our attention to the use of
Naked DNA delivered intraportally expresses efficiently in hepatocytes. (1996)

Naked plasmid DNA in hypertonic solutions was injected intraportally in mice whose hepatic veins were transiently occluded. High levels of luciferase expression and beta-galactosidase expression in 1% of the hepatocytes throughout the entire liver were achieved using 100 micrograms of the respective plasmid vector. Two days after the intraportal injection of 100 micrograms of pCMVGH, the mean hGH serum concentration was 65 ng/ml +/- 26 (n = 7) which is approximately 50-fold above normal baseline levels. These unprecedented levels of foreign gene expression from naked plasmid DNA document the ability of parenchymal cells in vivo to take up naked DNA following intravascular delivery.
Anxiety does not predict response to duloxetine in major depression: results of a pooled analysis of individual patient data from 11 placebo-controlled trials (2009)

Duloxetine was more effective than placebo in achieving response and remission in both anxious and nonanxious patients. Anxious status did not affect the magnitude of the drug effect.
Zoledronic Acid Treatment of 5T2MM-Bearing Mice Inhibits the Development of Myeloma Bone Disease: Evidence for Decreased Osteolysis, Tumor Burden and Angiogenesis, and Increased Survival (2003)

Multiple myeloma is characterized by the growth of plasma cells in the bone marrow and the development of osteolytic bone disease. Myeloma cells are found closely associated with bone, and targeting this environment may therefore affect both the bone disease and the growth of myeloma cells. We have investigated the effect of the potent bisphosphonate, zoledronic acid, on the development of bone disease, tumor burden, and disease-free survival in the 5T2MM model of myeloma. 5T2MM murine myeloma cells were injected intravenously into C57BL/KaLwRij mice. After 8 weeks, all animals had a paraprotein. Animals were treated with zoledronic acid (120 microg/kg, subcutaneously, twice weekly) or vehicle, from the time of tumor cell injection or from paraprotein detection for 12 or 4 weeks, respectively. All animals injected with tumor cells developed osteolytic lesions, a decrease in cancellous bone volume, an increase in osteoclast perimeter, and a decrease in bone mineral density. Zoledronic acid prevented the formation of lesions, prevented cancellous bone loss and loss of bone mineral density, and reduced osteoclast perimeter. Zoledronic acid also decreased paraprotein concentration, decreased tumor burden, and reduced angiogenesis. In separate experiments, Kaplan-Meier analysis demonstrated a significant increase in survival after treatment with zoledronic acid when compared with control (47 vs. 35 days). A single dose of zoledronic acid was also shown to be effective in preventing the development of osteolytic bone disease. These data show that zoledronic acid is able to prevent the development of osteolytic bone disease, decrease tumor burden in bone, and increase survival in a model of established myeloma.
Uricases as Therapeutic Agents to Treat Refractory Gout: Current States and Future Directions (2012)

Treatment of refractory gout remains a challenge on drug development. While pegloticase, a recombinant mammalian uricase modified with monomethoxyl-poly(ethylene glycol) (mPEG) is effective in treating refractory gout, after continued treatment for three months biweekly at a therapeutic dose of 0.14 mg/kg body weight, it elicits an immune response against mPEG in nearly 20% of patients. For continued treatment of refractory gout PEGylated uricases at monthly therapeutic doses below 4 μg/kg body weight have promise. To formulate uricases to achieve monthly therapeutic regimens requires pharmacodynamics simulation and experimentation including: (a) molecular engineering of uricases based on rational design and evolution biotechnology in combination to improve their inherent catalytic efficiency, thermostability and selectivity for urate over xanthine and; (b) optimization of the number and distribution of accessible reactive amino acid residues in native uricases for site-specific PEGylation with PEG derivatives with lower of immunogenicity than mPEG to retain activity, minimize immunogenicity and enhance the pharmacokinetics of the PEGylated uricase. These issues are briefly reviewed as a means to stimulate the development of safer uricase formulations for continued treatment of refractory gout.
The association between depressive and cognitive symptoms in amnestic mild cognitive impairment (2008)

This study reveals differences between the pattern of cognitive impairment for a-MCI/D+ and a-MCI subgroups particularly at the level of executive capacities. In terms of memory functioning, the differences between the subgroups were more subtle; more studies are needed in order to better characterize the memory impairment of a-MCI/D+ and a-MCI patients.
Identification of γ-AApeptides with potent and broad-spectrum antimicrobial activity (2011)

We report the identification of a new class of antimicrobial peptidomimetics-γ-AApeptides with potent and broad-spectrum activity, including clinically-relevant strains that are unresponsive to most antibiotics. They are also not prone to select for drug-resistance.
Effects of Calcium and Phosphorus Supplementation on Calcium Retention and Fat Absorption in Preterm Infants Fed Pooled Human Milk (1986)

Fat, phosphorus, and calcium balance studies were performed in normal very low birth weight infants (BW less than or equal to 1,500 g) fed either normal or calcium- and phosphorus-supplemented pooled pasteurized human milk. Calcium and phosphorus supplements were 27 mg/dl and 24.5 mg/dl, respectively, throughout the study. Measured calcium and phosphorus intake in the supplemented group averaged 90 +/- 6 mg/kg/day and 62 mg/kg/day, respectively, compared to 47 +/- 7 mg/kg/day and 24 +/- 6 mg/kg/day in the nonsupplemented group. The percent of fat, calcium, and phosphorus absorption was similar in the two groups: respectively, 71 +/- 23%, 73 +/- 13%, and 93 +/- 2% in the supplemented group compared to 75 +/- 11%, 71 +/- 14%, and 92 +/- 4% in the nonsupplemented group. Calcium and phosphorus retention reached 62 +/- 12 mg/kg/day and 53 +/- 4 mg/kg/day in the supplemented group against 21 +/- 10 mg/kg/day and 21 +/- 5 mg/kg/day in the nonsupplemented group. These data support the notion that calcium, in addition to phosphorus supplementation in pooled human breast milk, improves both calcium and phosphorus retention in preterm infants.
Antimicrobial effects of α-MSH peptides (2000)

The presence of the ancient anti-inflammatory peptide alpha-melanocyte-stimulating hormone [alpha-MSH (1-13), SYSMEHFRWGKPV] in barrier organs such as gut and skin suggests a role in the nonspecific (innate) host defense. alpha-MSH and and its carboxy-terminal tripeptide (11-13, KPV) were determined to have antimicrobial influences against two major and representative pathogens: Staphylococcus aureus and Candida albicans. alpha-MSH peptides significantly inhibited S. aureus colony formation and reversed the enhancing effect of urokinase on colony formation. Antimicrobial effects occurred over a broad range of concentrations including the physiological (picomolar) range. Small concentrations of alpha-MSH peptides likewise reduced viability and germ tube formation of the yeast C. albicans. Antimicrobial influences of alpha-MSH peptides could be mediated by their capacity to increase cellular cAMP. Indeed, this messenger was significantly augmented in peptide-treated yeast and the potent adenylyl cyclase inhibitor dideoxyadenosine (ddAdo) partly reversed the killing activity of alpha-MSH peptides. Reduced killing of pathogens is a detrimental consequence of therapy with anti-inflammatory drugs. Because alpha-MSH has potent anti-inflammatory effects we determined influences of alpha-MSH on C. albicans and S. aureus killing by human neutrophils. alpha-MSH peptides did not reduce killing but rather enhanced it, likely as a consequence of the direct antimicrobial activity. alpha-MSH peptides that combine antipyretic, anti-inflammatory, and antimicrobial effects could be useful in treatment of disorders in which infection and inflammation coexist.
Purification, characterization, and immunological properties of fumarase from Euglena gracilis var. bacillaris (1985)

A rapid three-step procedure utilizing heat treatment, ammonium sulfate fractionation, and affinity chromatography on Matrex gel Orange A purified fumarase (EC 4.2.1.2) 632-fold with an 18% yield from crude extracts of Euglena gracilis var. bacillaris. The apparent molecular weight of the native enzyme was 120,000 as determined by gel filtration on Sephacryl S-300. The preparation was over 95% pure, and the subunit molecular weight was 60,000 as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, indicating that the enzyme is a dimer composed of two identical subunits. The pH optimum for E. gracilis fumarase was 8.4. The Km values for malate and fumarate were 1.4 and 0.031 mM, respectively. Preparative two-dimensional gel electrophoresis was used to further purify the enzyme for antibody production. On Ouchterlony double-immunodiffusion gels, the antifumarase serum gave a sharp precipitin line against total E. gracilis protein and purified E. gracilis fumarase. It did not cross-react with purified pig heart fumarase. On immunoblots of purified E. gracilis fumarase and crude cell extracts of E. gracilis, the antibody recognized a single polypeptide with a molecular weight of approximately 60,000, indicating that the antibody is monospecific. This polypeptide was found in E. gracilis mitochondria. The antibody cross-reacted with an Escherichia coli protein whose molecular weight was approximately 60,000, the reported molecular weight of the fumA gene product of E. coli, but it failed to cross-react with proteins found in crude mouse cell extracts, Bacillus subtilis extracts, or purified pig heart fumarase.
Synthesis and biologic evaluation of the dopamine analog N-acetyldopamine in experimental leukemia in mice. (1981)

N-Acetyldopamine is a relatively nontoxic analog of dopamine that has shown significant antitumor activity in experimental L1210 and P388 leukemias. A convenient two-step chemical synthesis of this derivative provided a sufficient quantity of material to study the effects of the administration of this drug by a more frequent schedule. The antitumor activity in the L1210 and P388 systems was significantly improved when N-acetyldopamine was administered to (C57BL/6J x DBA/2)F1 (B6D2F1) mice three times daily for 4 days. Long-term survivors appeared, which indicated tumor kills in excess of 10(5) cells. The effects of dopamine and N-acetyldopamine on the incorporation of radioactively labeled thymidine (dThd) by proliferating tissues (tumor, bone marrow, and gastrointestinal mucosa) were examined in tumor-bearing B6D2F1 mice. The dThd incorporation into tumor cells was selectively inhibited in both the L1210 and P388 leukemias with less inhibition of bone marrow and gastrointestinal mucosa cells. One hour after a dose of 400 mg N-acetyldopamine/kg, dThd incorporation was completely suppressed by both P388 and L1210 tumor cells with minimal effects on bone marrow or gastrointestinal mucosa cells. The synthetic method reported here is applicable to the preparation of various derivatives for study.
Roles of a 67-kDa polypeptide in reversal of protein synthesis inhibition in heme-deficient reticulocyte lysate. (1988)

During heme deficiency in reticulocyte lysates, the heme-regulated protein synthesis inhibitor, HRI, phosphorylates the alpha subunit of eukaryotic initiation factor 2 (eIF-2) and thus inhibits protein synthesis. Two factors, eIF-2 and a reticulocyte-lysate supernatant factor that we term RF, reverse this inhibition. We now report the following. (i) An active eIF-2 preparation contained, in addition to the three subunits (alpha, beta, and gamma), a 67-kDa polypeptide. Pretreatment of eIF-2 with polyclonal antibodies against either isolated alpha subunit or 67-kDa polypeptide almost completely inhibited the reversal activity. Upon further fractionation, three-subunit eIF-2 and the 67-kDa polypeptide were resolved. Neither the three-subunit eIF-2 nor the 67-kDa polypeptide alone was active in protein synthesis inhibition reversal. The activity was, however, restored by combining both the three-subunit eIF-2 and the 67-kDa polypeptide. (ii) Active RF preparations contained eIF-2 alpha (unphosphorylated) and beta subunits and the 67-kDa polypeptide. As with eIF-2, prior treatment of the RF preparation with antibodies to either the alpha subunit or the 67-kDa polypeptide almost completely inhibited the reversal activity. The RF preparation devoid of eIF-2 gamma subunit did not form ternary complex (Met-tRNA(fMet).eIF-2.GTP). The eIF-2 gamma subunit in the free form was isolated, and addition of this isolated gamma subunit to RF promoted significant ternary-complex formation. (iii) Purified HRI efficiently phosphorylated the alpha subunit in the three subunit eIF-2. However, the extent of such phosphorylation was significantly reduced when eIF-2 containing the 67-kDa polypeptide was used. The 67-kDa polypeptide apparently protected eIF-2 alpha subunit from HRI-catalyzed phosphorylation but did not inhibit HRI activity. Based on these results, we suggest that the protein synthesis inhibition reversal activity in both eIF-2 and RF is due to the same components--namely, eIF-2 alpha subunit and the 67-kDa polypeptide. The 67-kDa polypeptide protects eIF-2 alpha subunit from HRI-catalyzed phosphorylation and may also be a necessary component of the functioning eIF-2 molecule.
Plk Phosphorylation Regulates the Microtubule-Stabilizing Protein TCTP (2002)

The mitotic polo-like kinases have been implicated in the formation and function of bipolar spindles on the basis of their respective localizations and mutant phenotypes. To date, this putative regulation has been limited to a kinesin-like motor protein, a centrosomal structural protein, and two microtubule-associated proteins (MAPs). In this study, another spindle-regulating protein, the mammalian non-MAP microtubule-binding and -stabilizing protein, the translationally controlled tumor protein (TCTP), was identified as a putative Plk-interacting clone by a two-hybrid screen. Plk phosphorylates TCTP on two serine residues in vitro and cofractionates with the majority of kinase activity toward TCTP in mitotic cell lysates. In addition, these sites were demonstrated to be phosphorylated in vivo. Overexpression of a Plk phosphorylation site-deficient mutant of TCTP induced a dramatic increase in the number of multinucleate cells, rounded cells with condensed ball-like nuclei, and cells undergoing cell death, similar to both the reported anti-Plk antibody microinjection and the low-concentration taxol treatment phenotypes. These results suggest that phosphorylation decreases the microtubule-stabilizing activity of TCTP and promotes the increase in microtubule dynamics that occurs after metaphase.
Decrease in serum levels of advanced glycation end-products by short-term lifestyle modification in non-diabetic middle-aged females. (2009)

The present findings suggest lifestyle modification as a promising approach to reducing circulating AGE levels even in healthy middle-aged females with neither overt diabetes nor renal dysfunction.
Naloxone ameliorates the pathophysiologic changes which lead to and attend an acute stroke in stroke-prone/SHR. (1984)

Stroke-prone, spontaneously hypertensive rats (SP/SHR) were fed a low protein (8%) fish diet + 1% saline at the time of weaning; some were treated with Naloxone (0.4 mg/100 gms bw/sc/2 X daily/5 days per week). Naloxone-treated animals did not develop high blood pressure or strokes. Sixty-two days after feeding the low protein fish diet, blood pressure levels reached 260-300 mmHg and all of the non-treated animals exhibited acute and severe strokes; Naloxone treatment was again initiated for half of the SP/SHR. By Day 4 (post stroke), all of the non-treated SP/SHR were dead; Naloxone-treated SP/SHR survived until Day 12 (post stroke). Naloxone-treatment during the post-stroke period caused significant reduction of blood pressure, ACTH, and beta-endorphin levels concomitant with reduced cerebral edema and clearance of hepatic lipid infiltration. It is suggested that anti-opiate treatment may ameliorate the severe hypertension-inducing effects of a low protein fish diet and thereby prevent the appearance of strokes in SP/SHR as well as palliate the cerebral edema and fatty liver which characteristically appear in the immediate post-stroke period in fish-fed SP/SHR. The central mechanism of this palliative effect may be through reduced hypothalamic-pituitary-adrenal activity.