gebhart/patrepeval huggingface dataset:
Circulatory and metabolic effects of beta-adrenergic blockade in the hyperinsulinemic ovine fetus (1993)

Offspring of women with poorly controlled diabetes exhibit hypoxemia, elevated catecholamine concentration at birth, and an increased incidence of fetal death. Experimental fetal hyperinsulinemia results in increased catecholamine concentration and hemodynamic changes including increased combined ventricular output and vasodilation of select fetal organs. We hypothesized that insulin-induced catecholamine-mediated beta-adrenergic stimulation supports some of these hemodynamic changes in the hyperinsulinemic ovine fetus. To study this, 24 chronically instrumented fetal sheep receiving insulin for 24 h were exposed to beta-(propranolol),beta 1-(metoprolol), and beta 2-(ICI 118,551) adrenergic blockade. Insulin infusion resulted in hyperinsulinemic-hypoglycemia, a surge in epinephrine and norepinephrine concentration, and increases in the combined ventricular output and regional blood flow to the heart, adrenal glands, kidney, gastrointestinal tract, liver, fat, muscle, carcass, and placenta. In the hyperinsulinemic state, beta-adrenergic blockade was associated with significant reductions in the combined ventricular output and blood flow to fat, carcass, lungs, and the placenta; beta 1-blockade was associated with reductions in the combined ventricular output and blood flow to the lungs; and beta 2-adrenergic blockade was associated with reductions in blood flow to muscle and lungs. Because beta-adrenergic blockade was associated with reductions in placental blood flow during hyperinsulinemia, oxygen and glucose metabolism were also compromised. We conclude that in the hyperinsulinemic-hypoglycemic normoxemic ovine fetus, insulin-induced catecholamine-mediated hemodynamic changes are modulated in part by beta-adrenergic receptor stimulation.
BMP-2-Mediated Regeneration of Large-Scale Cranial Defects in the Canine: An Examination of Different Carriers (2011)

Treatment with 0.2 mg/ml rhBMP-2 in an absorbable collagen sponge with MasterGraft Granules showed the least amount of ectopic bone formation and the most compact bone formation within the defect, and produced reasonably consistent bony thickness across the defect. Future studies should focus on spatial regulation of rhBMP-2 to minimize unwanted bone formation.
Cytokeratins mediate epithelial innate defense through their antimicrobial properties (2012)

Epithelial cells express antimicrobial proteins in response to invading pathogens, although little is known regarding epithelial defense mechanisms during healthy conditions. Here we report that epithelial cytokeratins have innate defense properties because they constitutively produce cytoprotective antimicrobial peptides. Glycine-rich C-terminal fragments derived from human cytokeratin 6A were identified in bactericidal lysate fractions of human corneal epithelial cells. Structural analysis revealed that these keratin-derived antimicrobial peptides (KDAMPs) exhibited coil structures with low α-helical content. Synthetic analogs of these KDAMPS showed rapid bactericidal activity against multiple pathogens and protected epithelial cells against bacterial virulence mechanisms, while a scrambled peptide showed no bactericidal activity. However, the bactericidal activity of a specific KDAMP was somewhat reduced by glycine-alanine substitutions. KDAMP activity involved bacterial binding and permeabilization, but the activity was unaffected by peptide charge or physiological salt concentration. Knockdown of cytokeratin 6A markedly reduced the bactericidal activity of epithelial cell lysates in vitro and increased the susceptibility of murine corneas to bacterial adherence in vivo. These data suggest that epithelial cytokeratins function as endogenous antimicrobial peptides in the host defense against infection and that keratin-derived antimicrobials may serve as effective therapeutic agents.
The clinical spectrum of renal osteodystrophy in 57 chronic hemodialysis patients: a correlation between biochemical parameters and bone pathology findings. (1991)

Fifty-nine chronic hemodialysis patients who had been on dialysis for an average of 77 months underwent bone biopsies and the pathologic findings were correlated with biochemical and demographic data. All but two had evidence of renal osteodystrophy, 23 with osteitis fibrosa (OF), 19 with osteomalacia and/or adynamic disease (OM/AD), and 15 with mixed osteodystrophy (MOD). Patients in each group were similar with regard to age, sex distribution, duration of dialysis, unstimulated serum aluminum, calcium and phosphorus. Patients with osteitis fibrosa (OF) had statistically higher DFO stimulated aluminum, alkaline phosphatase and PTHC levels than the other two groups although there was marked individual variation. The bone biopsies were also evaluated for the amount of aluminum deposited in the osteoid seam. All 23 of the patients with OF and 11 of the 15 patients with MOD had no, mild, or minimal aluminum deposition but 12 of the 19 patients with OM/AD had moderate to marked aluminum deposition. Patients with minimal to mild aluminum deposition were similar in age, duration of dialysis, sex distribution, unstimulated and DFO stimulated aluminum levels, calcium, phosphorus, alkaline phosphatase to those with moderate to marked deposition but had significantly higher parathormone levels. All patients had been treated in a similar fashion regarding diet, oral phosphate binders and vitamin D; therefore, the observed differences in bone pathology were not readily explicable. However, patients who were found to have osteitis fibrosa and those with minimal to mild aluminum deposition had significantly higher parathormone levels when compared with patients in the other groups at the inception of dialysis.
Molecular characterization of clear cell renal cell carcinoma identifies CSNK2A1, SPP1 and DEFB1 as promising novel prognostic markers (2016)

The prognosis associated with clear cell renal carcinoma (ccRCC) can vary widely and novel molecular prognostic markers are needed to assess prognosis at an earlier stage. Several gene products have been investigated for this purpose, but none of them have been implemented in clinical practice. Here we hypothesized that we, using TaqMan® Array, could identify superior prognostic messenger RNA (mRNA)s in long-term follow-up. Messenger RNA level of 19 candidate genes was investigated in 97 patients with ccRCC. Three genes impacted significantly on prognosis in both univariate and multivariate analysis. In univariate analysis, CSNK2A1 was a strong indicator of a poor overall survival (OS) (HR = 5.01, p < 0.001), disease specific survival (DSS) (HR = 6.21, p = 0.007) and progression free survival (PFS) (HR = 5.93, p = 0.005). High expression of SPP1 was associated to poor PFS (HR = 4.41, p = 0.04). DEFB1 was associated with a better PFS (HR = 0.24, p = 0.006). In multivariate analysis, CSNK2A1 was associated to a worse OS (HR = 3.56, p = 0.008) and PFS (HR = 3.84, p = 0.005), whereas SPP1 was an independent predictor of a worse PFS (HR = 3.46, p = 0.007) and DEFB1 of a better PFS (HR = 0.37, p = 0.027). These results show that with TaqMan®) Array we could identify three superior gene products related to prognosis. Further studies are needed to elucidate the pathways and roles of these genes in renal cacer development.
Hepatitic variant of graft-versus-host disease after donor lymphocyte infusion (2002)

Graft-versus-host disease (GVHD) of the liver is characterized by bile duct damage and portal lymphocytic infiltrate. We report acute hepatitislike presentation of GVHD after donor lymphocyte infusion (DLI). Between April 1998 and September 2001, 73 patients received 94 DLI treatments. Liver GVHD developed after DLI in 22 (30%) patients whose median age was 43 years (range, 21 to 61 years). Onset of liver dysfunction was at 35 days (range, 11 to 406 days) after DLI. Fifteen patients underwent liver biopsy, and the diagnosis of liver GVHD was confirmed in 13 (87%) patients. After viral hepatitis and recent drug exposure were excluded, 11 (50%) patients were given a diagnosis of a hepatitic variant of GVHD based on histologic evidence of lobular hepatitis (n = 5), elevation of maximum serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) level more than 10 times the upper normal limit (n = 9), or both. There was a significant difference in maximum ALT (P =.002) and AST (P =.01) level between the hepatitic-variant and classical GVHD groups. GVHD progressed in 14 (64%) patients, and 10 patients died after a median follow-up of 221 days (range, 31-1284 days). These observations suggest that GVHD that occurs after DLI may have distinct clinical features. Hepatitic-variant GVHD should be considered in the differential diagnosis in DLI recipients with unexplained hepatitis.
ChemInform Abstract: Synthesis and Chiroptical Properties of 5,7‐Dioxobicyclo[2.2.2]oct‐2‐ene and Bicyclo[2.2.2]octane‐2,5‐dione. (1986)

Abstract Synthesis and Chiroptical Properties of 5,7‐Dioxobicyclo[2.2.2loct‐2‐ ene and Bicyclo[2.2.2loctane‐2,5‐dione.
l-Lactide Macromonomer Synthesis Initiated by New Cyclic Tin Alkoxides Functionalized for Brushlike Structures (2001)

l-Lactide macromonomers with an incorporated double bond were successfully synthesized by controlled ring-opening polymerization initiated by two new cyclic tin alkoxides (1,1-di-n-butyl-stanna-2,7-dioxacyclo-4-heptene and 9,9,20,20-tetrabutyl-8,10,19,21-tetraoxa-9,20-distanna-dispiro[5.5.5.5]docosa-2,14-diene). Initiators and crude reaction mixtures were characterized by NMR. 1H NMR analysis showed that the initiators were completely reacted in the polymerization and that both tin−oxygen bonds were reactive and participated in propagation. The polymerizations were performed in chloroform at 60 °C, and the molecular weight was effectively controlled by adjusting the monomer-to-initiator ratio. The molecular weight distribution was narrow (<1.1) for both high and low molecular weights (3000−72 000 g/mol). A plot of Mn vs conversion was linear up to a conversion of 98%, showing a system propagating in a controlled manner. The kinetic investigation showed that all of the polymerizations were first order in monomer and that no termination reactions occurred during polymerization.
Consistency Degrees of Theories in Łukasiewicz Fuzzy andn-Valued Propositional Logic Systems (2010)

By means of theory of truth degrees of formulas, according to deduction theorems and completeness theorems, the new concepts of consistency degrees and polar index for general theories in Łukasewicz fuzzy and<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mi>n</mml:mi></mml:math>-valued propositional logic systems are introduced. Moreover, sufficient and necessary conditions for a theory<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mi>Γ</mml:mi></mml:math>to be consistent, inconsistent, and fully divergent are obtained. Finally, some important properties of truth degrees of formulas are proposed.
Interleukin-6 Inhibits Apoptosis and Tumour Necrosis Factor Induced Proliferation of B-Chronic Lymphocytic Leukaemia (1996)

There is now good evidence that tumour necrosis factor [TNF] stimulates DNA synthesis of B-chronic lymphocytic leukaemia (B-CLL) cells. The malignant clone produces TNF, and addition of exogenous TNF up-regulates the TNF mRNA in B-CLL cells. Interleukin-6 (rIL-6) may also be important in this growth loop. We studied the interaction of TNF and IL-6 in the regulation of DNA synthesis (3H-TdR uptake), cytokine release and cell survival in CLL cells in vitro. Addition of TNF (100 U/ml over 5 days) enhanced DNA synthesis from 718 +/- 284 (mean cpm +/- SE) to 2730 +/- 545 compared to cells cultured in medium alone (n = 16, p < 0.01). TNF-alpha induced DNA synthesis was inhibited in all cases studied by the addition of anti-TNF monoclonal antibody (5 micrograms/ml) to cell cultures. Spontaneous IL-6 protein release was enhanced in the presence of TNF (100 U/ml and 250 U/ml) by CLL cells at 48 hours of culture 143.6% and 172% (p < 0.05, n = 6). At 120 hours of culture, the increase was 323% and 412.5% (4 of 7 cases) of the control respectively. IL-6 (100 U/ml or greater) increased spontaneous DNA synthesis (3H-TdR uptake) but, in the presence of high concentrations of TNF-alpha, inhibited TNF induced DNA synthesis in a dose dependent manner. Cell survival was reduced in the presence of anti-IL-6 mAb, while IL-6 was able to protect CLL cells from spontaneous apoptosis. These results suggest that IL-6 in an autocrine manner may inhibit DNA synthesis but prolongs survival in CLL cells. Increased serum IL-6 levels were detected in 27 of 50 cases of CLL, the mean level being significantly higher in Rai Stage III and IV cases compared to Rai Stage O-II cases.
Iloprost preserves renal oxygenation and restores kidney function in endotoxemia-related acute renal failure in the rat (2009)

Iloprost significantly restored kidney function of endotoxemic rats to baseline values. This beneficial effect of iloprost on renal function might be addressed to an improvement in intrarenal oxygenation.
The herpes simplex virus type 1 temperature-sensitive mutant ts1222 has a single base pair deletion in the small subunit of ribonucleotide reductase. (1988)

The herpes simplex virus type 1 (HSV-1) temperature-sensitive (ts) mutant, ts1222, has a defect within the gene specifying the small subunit of ribonucleotide reductase. Sequence determination of the lesion revealed that the mutant DNA had a single base pair deletion at the 3' end of the gene. The mutation altered the translational reading frame such that the codons of all but one of the last 15 amino acids of the protein were changed and the termination codon removed. Although ts1222 did not induce detectable amounts of enzyme activity at both 31 degrees and 39.5 degrees, it replicated as well as wild-type virus at 31 degrees in exponentially growing tissue culture cells under one step growth conditions. At 39.5 degrees, however, ts1222 behaved as a ts mutant. These findings suggest that at low temperatures the virus-coded enzyme is dispensable for virus growth in actively dividing tissue culture cells but at high temperatures the enzyme is essential for virus replication. Under these conditions altered properties of the host cell contribute to the ts phenotype of the mutant. In the presence of hydroxyurea, which inactivates both the cellular and virus ribonucleotide reductases, growth of the mutant at 31 degrees was inhibited more than wild-type virus replication. Growth of the mutant at the permissive temperature was also sensitive to high concentrations of thymidine whereas wild-type virus multiplication was resistant to the nucleoside. It is therefore likely that ts1222 is dependent on the cellular ribonucleotide reductase for growth at this temperature. In serum-starved cells, growth of the mutant virus at 31 degrees was severely impaired. Thus, like thymidine kinase, the HSV-coded ribonucleotide reductase is required for virus multiplication in resting tissue culture cells.
Transport and anchoring of beta-lactamase to the external surface of Escherichia coli. (1992)

The outer membrane of Gram-negative bacteria presents an effective barrier that restricts the release of proteins from the cell. Virtually all extracellular proteins of Gram-negative bacteria are exported by specialized systems requiring the action of several gene products. We have constructed a tripartite fusion consisting of (i) the signal sequence and first nine N-terminal amino acids of the mature major Escherichia coli lipoprotein, (ii) amino acids 46-159 of the outer membrane protein OmpA, and (iii) the complete mature beta-lactamase (EC 3.5.2.6) sequence. This protein had an enzymatically active beta-lactamase and was found predominantly in the outer membrane. Immunofluorescence microscopy, the accessibility of the fusion protein to externally added proteases, and the rates of hydrolysis of nitrocefin and penicillin G by whole cells demonstrated that a substantial fraction (20-30%) of the beta-lactamase domain of the fusion protein was exposed on the external surface of E. coli. In cells grown at 24 degrees C the localization of beta-lactamase on the cell surface was almost quantitative (greater than 80% of the enzymatically active protein was exposed to the extracellular fluid) as determined by nitrocefin and penicillin G hydrolysis and trypsin accessibility. These results demonstrated that a soluble protein, beta-lactamase, can be transported through--and become anchored on--the outer membrane by fusion to the proper targeting and localization signals.
Joint transmitter-receiver optimization for multi-input multi-output systems with decision feedback (1994)

The joint transmit-receive optimization problem for multiuser communication systems with decision feedback is investigated. It is shown that minimization of the geometric mean-squared error (defined as the determinant of the error covariance matrix) leads to a tractable transmitter optimization problem for general multi-input multi-output decision-feedback systems. Several computational results are included that highlight system performance for a variety of useful transmission scenarios.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Phase 1 Study in Patients With Metastatic Melanoma of Immunization With Dendritic Cells Presenting Epitopes Derived From the Melanoma-Associated Antigens MART-1 and gp100 (2000)

Dendritic cells (DCs) have been shown to enhance anti-tumor immune responses in several preclinical models. Furthermore, DC-like function can be elicited from peripheral blood monocytes cultured in vitro with interleukin-4 and granulocyte-macrophage colony-stimulating factor. For this reason, a phase 1 study was initiated at the Surgery Branch of the National Cancer Institute to test the toxicity and biological activity of the intravenous administration of peripheral blood monocyte-derived DCs. The DCs were generated by 5- to 7-day incubation in interleukin-4 (1,000 U/mL) and granulocyte-macrophage colony-stimulating factor (1,000 U/mL) of peripheral blood monocytes obtained by leukapheresis. Before administration, the DCs were pulsed separately with the HLA-A*0201-associated melanoma epitopes MART-1(27-35) and gp-100-209-2M. The DCs were administered four times at 3-week intervals. A first cohort of patients (n = 3) was treated with 6 x 10(7) DCs and a second cohort (n = 5) with 2 x 10(8) DCs (in either case, one half of the DCs were pulsed with MART-1(27-35) and the other half was pulsed with gp-100-209-2M). In a final cohort under accrual (n = 2) 2 x 10(8) DCs were administered in combination with interleukin-2 (720,000 IU/kg every 8 hours). The recovery of DCs after in vitro culture ranged from 3% to 35% (mean, 15%) of the original peripheral blood monocytes. Administration of DCs caused no symptoms at any of the doses, and the concomitant administration of interleukin-2 did not cause toxicity other than that expected for interleukin-2 alone. Monitoring of patients' cytotoxic T lymphocyte reactivity before and after treatment revealed enhancement of cytotoxic T lymphocyte reactivity only in one of five patients tested. Of seven patients evaluated for response, one had a transient partial response with regression of pulmonary and cutaneous metastases. A relatively large number of DCs can be safely administered intravenously. The poor clinical outcome of this study perhaps could be explained by the type of protocol used for DC maturation, the route of administration, or both. For this reason, this clinical protocol was interrupted prematurely, whereas other strategies for DC preparation and route of administration are being investigated at the authors' institution.
Expression cloning of the Golgi CMP-sialic acid transporter. (1996)

Translocation of nucleotide sugars across the membrane of the Golgi apparatus is a prerequisite for the synthesis of complex carbohydrate structures. While specific transport systems for different nucleotide sugars have been identified biochemically in isolated microsomes and Golgi vesicles, none of these transport proteins has been characterized at the molecular level. Chinese hamster ovary (CHO) mutants of the complementation group Lec2 exhibit a strong reduction in sialylation of glycoproteins and glycolipids due to a defect in the CMP-sialic acid transport system. By complementation cloning in the mutant 6B2, belonging to the Lec2 complementation group, we were able to isolate a cDNA encoding the putative murine Golgi CMP-sialic acid transporter. The cloned cDNA encodes a highly hydrophobic, multiple membrane spanning protein of 36.4 kDa, with structural similarity to the recently cloned ammonium transporters. Transfection of a hemagglutinin-tagged fusion protein into the mutant 6B2 led to Golgi localization of the hemagglutinin epitope. Our results, together with the observation that the cloned gene shares structural similarities to other recently cloned transporter proteins, strongly suggest that the isolated cDNA encodes the CMP-sialic acid transporter.
Optical Measuring Methods for the Investigation of High-Pressure Homogenisation (2016)

High-pressure homogenisation is a commonly used technique to produce emulsions with droplets in the micro to nano scale. Due to the flow field in the homogenizer, stresses are transferred to the interface between droplets and continuous phase. Cohesive forces within droplets interact with external stresses. To exceed the cohesive forces, high process pressures are necessary, which might cause a complex flow pattern and large flow velocities. Additionally, the pressure drop can induce cavitation. Inline measurements are a challenge, but necessary to understand droplet break-up in a high-pressure homogenizer. Recently, different optical methods have been used to investigate the flow conditions as well as the droplet deformation and break-up in high-pressure homogenisation, such as high speed imaging, particle and micro particle image velocimetry. In this review, those optical measuring methods are considered critically in their applications and limitations, achievable results and further developments.
Novel fucolipids of human adenocarcinoma: characterization of the major Ley antigen of human adenocarcinoma as trifucosylnonaosyl Ley glycolipid (III3FucV3FucVI2FucnLc6). (1986)

A series of glycolipid antigens with Ley determinant (Fuc alpha 1----2Gal beta 1----4(Fuc alpha 1----3)GlcNAc) defined by monoclonal antibody AH6 (Abe, K., McKibbin, J. M., and Hakomori, S. (1983). J. Biol. Chem. 258, 11793-11797) have been detected in human colonic carcinoma cases. Three Ley-active components have been identified as follows. The simplest compound was characterized as Ley hexaosylceramide (lactodifucohexaosylceramide, III3FucIV2FucnLc4), which was previously isolated and was found as the major component in six out of eight cases of colonic adenocarcinoma but as only a very minor component in two cases. The second component was a very minor component in all eight cases, and its structure was identified by 1H NMR spectroscopy as an extended Ley (lactodifucooctaosylceramide, V3FucVI2FucnLc6; Structure 1 below). The third, major component, common in all eight cases, has been identified as trifucosyl Ley (lactotrifucononaosylceramide, III3FucV3FucVI2FucnLc6, Structure 2 below) based on 1H NMR spectroscopy, methylation analysis, and direct-probe electron-impact mass spectrometry. (formula; see text)