gebhart/patrepeval huggingface dataset:
Branched Chain Amino Acids Cause Liver Injury in Obese/Diabetic Mice by Promoting Adipocyte Lipolysis and Inhibiting Hepatic Autophagy (2016)

The Western meat-rich diet is both high in protein and fat. Although the hazardous effect of a high fat diet (HFD) upon liver structure and function is well recognized, whether the co-presence of high protein intake contributes to, or protects against, HF-induced hepatic injury remains unclear. Increased intake of branched chain amino acids (BCAA, essential amino acids compromising 20% of total protein intake) reduces body weight. However, elevated circulating BCAA is associated with non-alcoholic fatty liver disease and injury. The mechanisms responsible for this quandary remain unknown; the role of BCAA in HF-induced liver injury is unclear. Utilizing HFD or HFD+BCAA models, we demonstrated BCAA supplementation attenuated HFD-induced weight gain, decreased fat mass, activated mammalian target of rapamycin (mTOR), inhibited hepatic lipogenic enzymes, and reduced hepatic triglyceride content. However, BCAA caused significant hepatic damage in HFD mice, evidenced by exacerbated hepatic oxidative stress, increased hepatic apoptosis, and elevated circulation hepatic enzymes. Compared to solely HFD-fed animals, plasma levels of free fatty acids (FFA) in the HFD+BCAA group are significantly further increased, due largely to AMPKα2-mediated adipocyte lipolysis. Lipolysis inhibition normalized plasma FFA levels, and improved insulin sensitivity. Surprisingly, blocking lipolysis failed to abolish BCAA-induced liver injury. Mechanistically, hepatic mTOR activation by BCAA inhibited lipid-induced hepatic autophagy, increased hepatic apoptosis, blocked hepatic FFA/triglyceride conversion, and increased hepatocyte susceptibility to FFA-mediated lipotoxicity. These data demonstrated that BCAA reduces HFD-induced body weight, at the expense of abnormal lipolysis and hyperlipidemia, causing hepatic lipotoxicity. Furthermore, BCAA directly exacerbate hepatic lipotoxicity by reducing lipogenesis and inhibiting autophagy in the hepatocyte.
Isolation and characterization of human breast tumor-derived endothelial cells (2006)

Increasing evidence indicates that tumor-derived endothelial cells (TEC) possess a distinct and unique phenotype in respect to normal endothelial cells and may be able to acquire resistance to drugs. However, few functional studies are available on cultured TEC. In the present study, we obtained TEC from human breast carcinomas and, to dispel the possibility of contaminating tumor cells, we established six different clones that we characterized at a functional level. Breast TEC cell lines and clones did not undergo normal cell senescence in culture and showed constant expression of markers of endothelial activation and angiogenesis. These cells showed increased apoptosis resistance to vincristine and doxorubicin and increased random cell motility, as compared to normal micro-endothelial cells. In addition, breast TEC, at variance to normal endothelial cells, were able to grow and to organize in the absence of serum in capillary-like structures on Matrigel that persisted up to one week. These functional characteristics of breast TEC may be relevant for tumor angiogenesis and may indicate an increased pro-angiogenic activity of endothelial cells within the tumor. Moreover, our data suggest that TEC might be more appropriate for screening antiangiogenic drugs than normal endothelial cells.
Construction of a potential bivalent vaccine strain: introduction of Shigella sonnei form I antigen genes into the galE Salmonella typhi Ty21a typhoid vaccine strain (1981)

Shigella sonnei, an intestinal pathogen, produces a characteristic form I cell surface antigen now known to be plasmid encoded. We considered that the GalE Salmonella typhi Ty21a oral vaccine strain, highly effective against typhoid, might be modified so as to be protective also against shigellosis due to S. sonnei. The plasmid responsible for form I antigen synthesis was therefore conjugally transferred to the galE S. typhi strain. Serological studies revealed that the derivative strain produces the form I antigen in addition to the normal S. typhi somatic antigens. Testing in mice demonstrated that the derivative form I galE S. typhi strain is protective against both S. sonnei and S. typhi challenges. These data suggest that the galE S. Ty21a oral vaccine strain, which presumably stimulates the local immune system in the intestine, may also serve as a useful carrier for other antigenic determinants to protect against different intestinal infections.
Polyelectrolyte complex layers: a promising concept for anti-fouling coatings verified byin-situ ATR-FTIR spectroscopy (1999)

In-situ attenuated total reflection (ATR)-FTIR spectroscopy enabled studies on the interaction between the differently charged model proteins human serum albumin, lysozyme, immunoglobulin G and multilayer assemblies, which were deposited by alternating adsorption of poly(ethyleneimine) and poly(acrylic acid) onto Si crystals. Low adsorbed protein amounts were observed if the top polyelectrolyte layer and the protein were equally charged, whereas enhanced protein adsorption occurred for electrostatic attraction between protein and top polyelectrolyte layer.
Attomolar Detection of Botulinum Toxin Type A in Complex Biological Matrices (2008)

The sensitivity, specificity, speed and simplicity of the BoNT ALISSA should make this method attractive for diagnostic, biodefense and pharmacological applications.
Chemostat Enrichments of Human Feces with Resistant Starch Are Selective for Adherent Butyrate-Producing Clostridia at High Dilution Rates (2000)

Resistant starch (RS) enrichments were made using chemostats inoculated with human feces from two individuals at two dilution rates (D = 0.03 h(-1) and D = 0.30 h(-1)) to select for slow- and fast-growing amylolytic communities. The fermentations were studied by analysis of short-chain fatty acids, amylase and alpha-glucosidase activities, and viable counts of the predominant culturable populations and the use of 16S rRNA-targeted oligonucleotide probes. Considerable butyrate was produced at D = 0. 30 h(-1), which corresponded with reduced branched-chain fatty acid formation. At both dilution rates, high levels of extracellular amylase activity were produced, while alpha-glucosidase was predominantly cell associated. Bacteroides and bifidobacteria predominated at the low dilution rate, whereas saccharolytic clostridia became more important at D = 0.30 h(-1). Microscopic examination showed that within 48 h of inoculation, one particular bacterial morphotype predominated in RS enrichments at D = 0.30 h(-1). This organism attached apically to RS granules and formed rosette-like structures which, with glycocalyx formation, agglomerated to form biofilm networks in the planktonic phase. Attempts to isolate this bacterium in pure culture were repeatedly unsuccessful, although a single colony was eventually obtained. On the basis of its 16S rDNA sequence, this RS-degrading, butyrate-producing organism was identified as being a previously unidentified group I Clostridium sp. A 16S rRNA-targeted probe was designed using this sequence and used to assess the abundance of the population in the enrichments. At 240 h, its contributions to total rRNA in the chemostats were 5 and 23% at D = 0.03 and 0.30 h(-1), respectively. This study indicates that bacterial populations with significant metabolic potential can be overlooked using culture-based methodologies. This may provide a paradigm for explaining the discrepancy between the low numbers of butyrate-producing bacteria that are isolated from fecal samples and the actual production of butyrate.
Septal His‐Purkinje Ventricular Pacing in Canines: A New Endocardial Electrode Approach (1992)

Ventricular activation sequences and cardiac performance are influenced by pacing sites. Stimulation of or close to the specialized atrioventricular (AV) conduction system optimizes paced ventricular function compared to alternative epi- or endocardial muscle conduction sites. This study reports a new endocardial electrode implant approach to approximate septal His-Purkinje ventricular pacing. Five 6-month-old beagles were used. A custom, platinum-iridium, exposed helical screw electrode (Medtronic, Inc.), 4.5-mm long, with a 17.8-mm2 surface area, was designed with a polyurethane covered 4 filar MP35N nickle conductor lead. An 8 French sheath (USCI, Inc.) was modified as introducer to permit simultaneous implant intracardiac pressure and electrogram recordings. Following a thoracotomy, the introducer was inserted through the right atrial appendage and advanced to record optimal His-bundle electrogram while maintaining atrial pressure along the septal tricuspid valve annulus. After electrode implant, ECG demonstrated narrow paced QRS morphology. Mean implant values showed sensed R wave 6.3 mV, slew rate 0.65 V/sec, pacing impedance 319 ohms, and threshold 0.9 V/3.3 mA at 0.5-msec output. Necropsy showed implant above the tricuspid annulus with electrode extension into and contained within the proximal ventricular septum. This study demonstrates that an endocardial septal approach to His-Purkinje ventricular pacing to optimize paced ventricular function is feasible with a new electrode design and precise septal implant technique. Alternative introducer designs may permit transvenous application of this approach.
A Comparison of ePTFE Membranes Alone or in Combination with Platelet‐Derived Growth Factors and Insulin‐Like Growth Factor‐I or Demineralized Freeze‐Dried Bone in Promoting Bone Formation Around Immediate Extraction Socket Implants (1992)

The purpose of this study was to compare bone promotion around implants which were augmented with ePTFE membranes alone or in combination with cortical demineralized freeze-dried bone (DFDB) or the combination of platelet derived growth factor-BB (PDGF) and insulin like growth factor I (PDGF/IGF-I). Membranes were placed over titanium implants which had been inserted into fresh extraction sockets with large buccal dehiscences. Twenty-four implants were placed in 4 dogs. At 18 weeks clinical bone height measurements were taken, the animals were sacrificed, and all specimens retrieved for histologic evaluation. Clinically, a significant gain in bone levels was present in both the ePTFE membrane alone group (P < 0.005) and PTFE plus PDGF/IGF-I group (P < 0.01), but not in the PTFE plus DFDB group. Results from histometric measurements revealed an approximately 2-fold increase in the percentage of implant surface in contact with bone, area of bone adjacent to the implant surface, and in the total length of the implant surface in contact with bone in the dehiscence defects treated with ePTFE plus PDGF/IGF-I compared to the defects receiving ePTFE membranes alone (each P < 0.05). The response to the DFDB was highly variable and it did not significantly improve the efficacy of the PTFE membranes for any parameter measured. The distance from the outer surface of the new bone to the implant surface was statistically significant for ePTFE membranes alone and membranes plus PDGF/IGF-I. The results demonstrated that clinically, ePTFE membranes alone or ePTFE membranes with PDGF/IGF-I were equally effective in promoting bone growth around the implants. Histologic measurements demonstrated that sites treated with ePTFE membranes plus PDGF/IGF-I had the highest bone density compared with sites which received ePTFE membranes alone or with ePTFE membranes and DFDB. The results of this study question the use of DFDB and support the use of ePTFE membranes alone or with PDG-F-BB/IGF-I as potential methods of promoting bone formation around dental implants.
Joint Profit Maximization, Negotiation, and the Determinacy of Price in Bilateral Monopoly (1993)

Many economists teach that joint profit maximization leads to a determinate quantity and indeterminate price of the intermediate good traded. Using isoprofit curves, the Truetts argue that only one price is consistent with rational behavior and the goal of profit maximization.
Inactivation of the Amidotransferase Activity of Carbamoyl Phosphate Synthetase by the Antibiotic Acivicin (2002)

Carbamoyl phosphate synthetase (CPS) from Escherichia coli catalyzes the formation of carbamoyl phosphate from 2 mol of ATP, bicarbonate, and glutamine. CPS was inactivated by the glutamine analog, acivicin. In the presence of ATP and bicarbonate the second-order rate constant for the inactivation of the glutamine-dependent activities was 4.0 x 10(4) m(-1) s(-1). In the absence of ATP and bicarbonate the second-order rate constant for inactivation of CPS was reduced by a factor of 200. The enzyme was protected against inactivation by the inclusion of glutamine in the reaction mixture. The ammonia-dependent activities were unaffected by the incubation of CPS with acivicin. These results are consistent with the covalent labeling of the glutamine-binding site located within the small amidotransferase subunit. The binding of ATP and bicarbonate to the large subunit of CPS must also induce a conformational change within the amidotransferase domain of the small subunit that enhances the nucleophilic character of the thiol group required for glutamine hydrolysis. The acivicin-inhibited enzyme was crystallized, and the three-dimensional structure was determined by x-ray diffraction techniques. The thiol group of Cys-269 was covalently attached to the dihydroisoxazole ring of acivicin with the displacement of a chloride ion.
Cell-specific expression in transgenic plants reveals nonoverlapping roles for chloroplast and cytosolic glutamine synthetase. (1990)

Chloroplast and cytosolic isoforms of glutamine synthetase (GS; EC 6.3.1.2) are encoded by separate nuclear genes in plants. Here we report that the promoters for chloroplast GS2 and cytosolic GS3A of Pisum sativum confer nonoverlapping, cell-specific expression patterns on the beta-glucuronidase (GUS) reporter gene in transgenic tobacco. The promoter for chloroplast GS2 directs GUS expression within photosynthetic cell types (e.g., palisade parenchymal cells of the leaf blade, chlorenchymal cells of the midrib and stem, and photosynthetic cells of tobacco cotyledons). The promoter for chloroplast GS2 retains the ability to confer light-regulated gene expression in the heterologous transgenic tobacco system in a manner analogous to the light-regulated expression of the cognate gene for chloroplast GS2 in pea. These expression patterns reflect the physiological role of the chloroplast GS2 isoform in the assimilation of ammonia generated by nitrite reduction and photorespiration. In contrast, the promoter for cytosolic GS3A directs expression of GUS specifically within the phloem elements in all organs of mature plants. This phloem-specific expression pattern suggests that the cytosolic GS3A isoenzyme functions to generate glutamine for intercellular nitrogen transport. In germinating seedlings, the intense expression of the cytosolic GS3A-GUS transgene in the vasculature of cotyledons reveals a role for cytosolic GS in the mobilization of seed storage reserves. The distinct, cell-specific patterns of expression conferred by the promoters for chloroplast GS2 and cytosolic GS3A indicate that the corresponding GS isoforms perform separate metabolic functions.
Plasma Brain Natriuretic Peptide — An Independent Predictor of Cardiovascular Mortality in Acute Heart Failure (1999)

A plasma BNP level has independent and at least short-term prognostic significance in patients admitted with acute heart failure. This non-invasive and readily available blood test should be considered for risk stratification in patients with acute heart failure.
Single-step polymerase chain reaction for combined gene detection and epidemiological typing in three bacterial models (2006)

We describe a new polymerase chain reaction (PCR) for combined gene detection and epidemiological typing (COGEDET), which allows bacterial typing and gene detection in a one-step assay. This assay, in which target gene-specific primers are used under low-stringency annealing conditions, was evaluated on 32 Staphylococcus aureus strains using toxic shock syndrome toxin 1 (tst) primers, 30 Clostridium difficile strains using toxin A (toxA) primers, and 30 Escherichia coli strains using cytotoxic necrotizing factor (cnf) primers. Typing performances with COGEDET were compared to those of conventional random amplification polymorphic DNA (RAPD), and gene detection performances, to those of conventional PCR followed by Southern blot hybridization. Concordances between conventional PCR/Southern blot and COGEDET were 96.9, 100 and 96.7% for the detection of the tst, toxA and cnf genes, respectively. Discriminatory indexes for the conventional RAPD and COGEDET techniques were similar in the three bacterial species tested. These results show that the COGEDET assay can replace two separate assays for typing and genes detection respectively, thus saving both technicians' time and reagents.
LAP degradation product reflects plasma kallikrein-dependent TGF-β activation in patients with hepatic fibrosis (2014)

Byproducts of cytokine activation are sometimes useful as surrogate biomarkers for monitoring cytokine generation in patients. Transforming growth factor (TGF)-β plays a pivotal role in pathogenesis of hepatic fibrosis. TGF-β is produced as part of an inactive latent complex, in which the cytokine is trapped by its propeptide, the latency-associated protein (LAP). Therefore, to exert its biological activity, TGF-β must be released from the latent complex. Several proteases activate latent TGF-β by cutting LAP. We previously reported that Camostat Mesilate, a broad spectrum protease inhibitor, which is especially potent at inhibiting plasma kallikrein (PLK), prevented liver fibrosis in the porcine serum-induced liver fibrosis model in rats. We suggested that PLK may work as an activator of latent TGF-β during the pathogenesis of liver diseases in the animal models. However, it remained to be elucidated whether this activation mechanism also functions in fibrotic liver in patients. Here, we report that PLK cleaves LAP between R(58) and L(59) residues. We have produced monoclonal antibodies against two degradation products of LAP (LAP-DP) by PLK, and we have used these specific antibodies to immunostain LAP-DP in liver tissues from both fibrotic animals and patients. The N-terminal side LAP-DP ending at R(58) (R(58) LAP-DP) was detected in liver tissues, while the C-terminal side LAP-DP beginning at L(59) (L(59) LAP-DP) was not detectable. The R(58) LAP-DP was seen mostly in α-smooth muscle actin-positive activated stellate cells. These data suggest for the first time that the occurrence of a PLK-dependent TGF-β activation reaction in patients and indicates that the LAP-DP may be useful as a surrogate marker reflecting PLK-dependent TGF-β activation in fibrotic liver both in animal models and in patients.
Effects of a nitric oxide synthase inhibitor in humans with septic shock (1994)

Low doses of L-NMMA cause a widespread increase in vascular tone and raise blood pressure in patients with septic shock. Overproduction of nitric oxide appears to be an important mechanism in septic shock in patients, and inhibition of nitric oxide synthesis might provide a novel therapeutic approach to this condition. However, L-NMMA produced a fall in cardiac output and it is possible that this would worsen tissue perfusion. Larger studies examining the effects of L-NMMA on mortality and morbidity are now required.
Utilization of monoclonal antibodies to evaluate the involvement of Campylobacter jejuni in proliferative ileitis in Syrian hamsters (Mesocricetis auratus) (1987)

The role of Campylobacter jejuni in the pathogenesis of proliferative ileitis in Syrian hamsters was evaluated with monoclonal antibodies of different specificities. Monoclonal antibodies were produced with two different specificities: one for all members of the genus Campylobacter tested (antibody 8322-2E6) and one for C. jejuni and Campylobacter coli (antibodies 841-2A11, 841-4C6, and 841-5B1). Heal sections from healthy hamsters, from hamsters with naturally occurring proliferative ileitis, and from hamsters with experimentally induced proliferative ileitis were examined by using fluorescein isothiocyanate-labeled, Campylobacter sp.-specific 8322-2E6 and tetramethylrhodamine isothiocyanate-labeled C. jejuni-C. coli-specific 841-2A11 for direct dual-labeling immunofluorescence. Organisms which stained with the C. jejuni-C. coli-specific monoclonal antibody were observed in the ileal lumens and along the distal tips of the villi of hamsters with either experimentally induced or naturally occurring proliferative ileitis. In contrast, organisms identified by the Campylobacter sp.-specific monoclonal antibody were present deep within the villus lumens and crypts and intracellularly within the apical portions of the epithelial cells. No organisms stained with the C. jejuni-C. coli-specific monoclonal antibody were observed in ileal sections from control hamsters; an occasional intracellular organism stained with the Campylobacter sp.-specific monoclonal antibody was observed in 2 of 10 control hamsters. Thus, at least two immunologically distinct patterns were identified in ileal sections from hamsters with proliferative ileitis. On the basis of these results, we conclude that the organism seen intracellularly in ileal sections from hamsters with proliferative ileitis is a member of the genus Campylobacter but that it probably is not C. jejuni or C. coli.
Inflammatory Skin Diseases, T Cells, and Immune Surveillance (1999)

Skin is the primary interface between the body and the environment. The spectrum of insults to which skin is susceptible includes disorders caused by chemical and microbial agents, thermal and electromagnetic radiation, and mechanical trauma. The most damaging consequence of the disruption of skin is invasion by pathogenic microorganisms, and the need for an effective means of protection against this challenge has been a fundamental force behind the evolution of the immune system. The translation of insults into cutaneous inflammation (innate immunity) and the recruitment of memory T lymphocytes that have clonally expanded in response to antigens encountered at the . . .
Preparation and Preservation of Red Cells (1998)

New options for the preparation and storage of red blood cells are available and undergo continuous evaluation.