gebhart/patrepeval huggingface dataset:
Uptake and binding of radiolabelled phenylarsine oxide in 3T3-L1 adipocytes (1990)

Phenylarsine oxide (PAO), a trivalent arsenical, has been shown to inhibit insulin-stimulated glucose transport in 3T3-L1 adipocytes, implicating vicinal dithiols in signal transmission [Frost & Lane (1985) J. Biol. Chem. 260, 2646-2652]. To assist in the direct identification of a PAO-binding protein which might be involved in this process, we have synthesized [3H]acetylaminophenylarsine oxide [( 3H]APAO) from the amino derivative of phenylarsine oxide (NPAO). To assess the inhibitory effect of the product, a dual-labelling experiment was performed which showed that [3H]APAO inhibited insulin-stimulated 2-deoxy[1-14C]glucose transport in 3T3-L1 adipocytes with a Ki of 21 microM, identical with that of the parent compound, NPAO. Further characterization revealed that over a wide concentration range, uptake of the labelled arsine oxide was linear. Although the dithiol reagent 2,3-dimercaptopropanol (DMP) reversed PAO-induced inhibition of transport, it had no effect on the uptake of [3H]APAO. In a simple fractionation experiment approx. 50% of the radioactivity was associated with the cytosolic fraction and 50% with the total membrane fraction. Identification of radiolabelled proteins by non-reducing SDS/PAGE revealed fraction-specific binding, although many proteins were observed. Covalent modification was time-dependent and could be reversed by addition of DMP. These data further support a role for vicinal dithiols in insulin-stimulated glucose transport. Additionally, the probe described may offer a new means with which to identify the inhibitory protein or, more globally, to investigate mechanisms of action of vicinal dithiol-containing proteins.
Oversecretion of IL‐18 in haemophagocytic lymphohistiocytosis: a novel marker of disease activity (1999)

We investigated the significance of interleukin (IL)-18 levels in the pathophysiology of haemophagocytic lymphohistiocytosis (HLH). IL-18 levels were significantly elevated in all nine patients with active HLH compared with those of healthy controls. Serial determination of IL-18 levels in three cases, showed a gradual decrease compared with those of IL-12, interferon (IFN)-gamma or soluble Fas ligand (sFasL) in the course of clinical improvement, and seemed to be elevated until complete disappearance of disease activity. IL-18 and IFN-gamma (CC 0.711, P = 0.018), and IFN-gamma and sFasL (CC 0.849, P = 0.0049) levels were significantly correlated. On the other hand, correlation between IL-12 and IFN-gamma, IL-18 and sFasL, or IL-18 and IL-12 was not observed. IL-18, IFN-gamma and sFasL levels significantly correlated with disease activity such as fever and alanine transaminase (ALT) levels. IL-18 mRNA expression was enhanced in spleen, but not in peripheral blood mononuclear cells (MNC), bone marrow MNC, liver from patients of active HLH, or the tumour from a patient with lymphoma-associated haemophagocytic syndrome (LAHS). These results suggest that IL-18 may play important roles in the pathogenesis of HLH, particularly through induction of Th1 cells. IL-18 measurement may be useful for the diagnosis and for the detection of smouldering disease activity.
Duodenal administered seal oil for patients with subjective food hypersensitivity: an explorative open pilot study (2010)

Short-term duodenal administration of n-3 polyunsaturated fatty acid (PUFA)-rich seal oil may improve gastrointestinal complaints in patients with subjective food hypersensitivity, as well as joint pain in patients with inflammatory bowel disease (IBD). The aim of the present explorative pilot study was to investigate whether 10-day open treatment with seal oil, 10 mL self-administrated via a nasoduodenal tube 3 times daily, could also benefit nongastrointestinal complaints and quality of life (QoL) in patients with subjective food hypersensitivity. Twenty-six patients with subjective food hypersensitivity, of whom 25 had irritable bowel syndrome (IBS), were included in the present study. Before and after treatment and 1 month posttreatment, patients filled in the Ulcer Esophagitis Subjective Symptoms Scale (UESS) and the Gastrointestinal Symptom Rating Scale (GSRS) for gastrointestinal symptoms and subjective health complaints (SHC) inventory for nongastrointestinal symptoms in addition to short form of the Nepean dyspepsia index (SF-NDI) for evaluation of QoL. Compared with baseline, gastrointestinal, as well as nongastrointestinal, complaints and QoL improved significantly, both at end of treatment and 1 month posttreatment. The consistent improvements following seal oil administration warrant further placebo-controlled trials for confirmation of effect.
Pluripotency of Bovine Embryonic Cell Line Derived from Precompacting Embryos (2001)

We report herein the establishment of three bovine pluripotent embryonic cell lines derived from 8-16-cell precompacting embryos. Two cell lines were cultured for 10 passages and underwent spontaneous differentiation. One cell line (Z2) has been cultured continuously for over 3 years and has remained undifferentiated. These cells express cell surface markers that have been used routinely to characterize embryonic stem (ES) and embryonic germ (EG) cells in other species such as stage-specific embryonic antigens SSEA-1, SSEA-3, and SSEA-4, and c-Kit receptor. In the absence of a feeder layer, these cells differentiated into a variety of cell types and formed embryoid bodies (EBs). When cultured for an extended period of time, EBs differentiated into derivatives of three EG layers - mesoderm, ectoderm, and endoderm - which were characterized by detection of specific cell surface markers. Our results indicate that the Z2 cell line is pluripotent and resembles an ES cell line. To our knowledge, this is the first bovine embryonic cell line that has remained pluripotent in culture for more than 150 passages.
The potential of mustard (Brassica juncea (L.) Coss) as an edible oil crop on the Canadian Prairies (1991)

The performance of mustard (Brassica juncea (L.) Coss) was compared with that of canola (B. napus L. and B. rapa L.) on the western prairies. Mustard had a higher yield and protein content and was intermediate in maturity. Improvement in oil content will probably be required. Key words: Mustard, Brassica juncea, edible oil crop
Effects of lobaplatin as a single agent and in combination with TRAIL on the growth of triple-negative p53-mutated breast cancers in vitro (2012)

Lobaplatin as a single agent and in combination with tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) is investigated in in-vitro models of p53-negative triple-negative breast cancers (TNBCs) and compared with a model of oestrogen receptor-positive p53-positive breast cancer. In addition, the induction of programmed cell death by lobaplatin is further explored. By using cell viability assays and western blotting, the cytotoxic effects of lobaplatin alone and in combination with TRAIL are compared with cisplatin in HCC 1806, HCC 1937, and MCF 7 cells. The multicaspase inhibitor z-VAD-fmk and necrostatin, an inhibitor of necroptosis, are used to demonstrate the mechanism of cell death caused by lobaplatin. Lobaplatin displayed antitumour activity in all three cell lines, which increased time dependently. Cotreatment of lobaplatin and TRAIL induced an increase in cytotoxicity by 30-50% in the different cell lines. The pan-caspase inhibitor z-VAD-fmk as well as necrostatin could weaken but not abolish the cytotoxic effect of lobaplatin and cisplatin. Lobaplatin showed substantial cytotoxic effects in two in-vitro models of p53-mutated TNBC. Cotreatment with TRAIL and platinum agents resulted in increased antitumour activity in the TNBC cell lines investigated. Cell death subsequent to treatment with cisplatin and lobaplatin occurred because of apoptosis. However, caspase-independent mechanisms of programmed cell death were also involved. It was also demonstrated that platinum compounds could induce necroptosis, although to a minor extent.
Multipotent stem cell involvement in megakaryoblastic leukemia: cytologic and cytogenetic evidence in 15 patients (1989)

Cytologic and cytogenetic results obtained from patients fulfilling the FAB criteria for the diagnosis of acute nonlymphocytic leukemia (ANLL) of megakaryocytic lineage (ANLL-M7) are reported. Eleven cases were de novo ANLL-M7, of whom three presented with acute myelofibrosis. Four cases were megakaryoblastic transformations of chronic myelogenous leukemia (two cases), refractory anemia with excess of blasts (one case), and polycythemia vera (one case). Four patients showed a minority of granular blasts, with occasional Auer rods in one. Positive myeloperoxidase and/or sudan black-B stainings and CD13 positivity in these cases were consistent with the presence of a myeloid involvement. Morphologic evidence of associated myelodysplastic features was detected in all evaluable patients with de novo ANLL-M7. These cytologic findings indicate that ANLL-M7 may frequently represent a multilineage proliferation. Cytogenetic studies revealed -7/7q- and +8, alone or in combination with additional aberrations, in three cases each. Rearrangements involving bands 3q21 or 3q26 were seen in two patients and +21, as an additional aberration, in one. Other structural rearrangements all observed in a single patient were inv(16)(p13q22) at megakaryoblastic relapse with bone marrow eosinophilia, t(13;20)(q13 or 14;q11), del(20)(q11), and der(7)t(7;17)(p14;q22). Most breakpoints of these aberrations are located at bands frequently rearranged in malignant myeloid stem cell disorders. A review of 31 cases of the literature showed a frequent occurrence of -7/7q- and -5/5q- in ANLL- M7. Many of the chromosome aberrations so far described in ANLL-M7 appear to be shared by a spectrum of myeloid neoplasias and may be related to mechanisms conferring proliferative advantage to undifferentiated stem cells.
Identification of novel blood proteins specific for mammalian hibernation. (1992)

Mammalian hibernation is a unique physiological adaptation that allows the sustainment of life under extremely low body temperatures. In the chipmunk, we found four proteins related specifically to hibernation. These proteins started to diminish in concentration in the blood before and disappeared during hibernation. These proteins reappeared in the blood as hibernation ceased and remained during nonhibernation. The complete or partial amino acid sequences of the four proteins showed that three (27-, 25-, and 20-kDa) were previously unknown, whereas another (55-kDa) is highly homologous with alpha 1-antitrypsin. The three novel proteins are homologous, indicating that they are a family. In the NH2-terminal regions of these proteins, a collagen-like amino acid sequence is present, whereas in their COOH-terminal regions, two sequences, Ser-Ala-Phe-Ala-Val-Lys and Val-Trp-Leu-Glu, are conserved. Analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis under nonreducing conditions and gel permeation chromatography under denaturating conditions revealed that the four proteins form a 140-kDa complex in the plasma fraction. The novel proteins were detected in blood of another hibernator, the ground squirrel, but not in rodent nonhibernators, namely tree squirrels and rats. The present finding is the first identification of a hibernation-specific protein. The presence of specific proteins in hibernators suggests the involvement of genetic factors in the control of hibernation. These proteins provide valuable tools for understanding molecular mechanisms of mammalian hibernation.
Emerging PEGylated drugs (2009)

PEGylation is a pharmaceutical technology that involves the covalent attachment of polyethylene glycol (PEG) to a drug to improve its pharmacokinetic, pharmacodynamic, and immunological profiles, and thus, enhance its therapeutic effect. Currently, PEGylation is used to modify proteins, peptides, oligonucleotides, antibody fragments, and small organic molecules. Research groups are striving to improve the consistencies of PEGylated drugs and to PEGylate commercialized proteins and small organic molecules. Furthermore, the PEGylations of novel medications, like oligonucleotides and antibody fragments, are being pursued to improve their bioavailabilities. This active research in the PEGylation field and the continued growth of the biopharmaceutical market predicts that PEGylated drugs have a bright future.
Aph2, a Protein with a zf-DHHC Motif, Interacts with c-Abl and Has Pro-apoptotic Activity (2002)

c-Abl is a non-receptor tyrosine kinase implicated in DNA damage-induced cell death and in growth factor receptor signaling. To further understand the function and regulation of c-Abl, a yeast two-hybrid screen was performed to identify c-Abl-interacting proteins. Here we report the identification of Abl-philin 2 (Aph2), encoding a novel protein with a unique cysteine-rich motif (zf-DHHC) and a 53-amino acid stretch sharing homology with the creatine kinase family. The zf-DHHC domain is highly conserved from yeast to human. Two proteins containing this motif, Akr1p and Erf2p, have been characterized in Saccharomyces cerevisiae, both implicated in signaling pathways. Deletion analysis by two-hybrid assays revealed that the N-terminal portion of Aph2 interacts with the C terminus of c-Abl. Aph2 was demonstrated to interact with c-Abl by co-immunoprecipitation assays. Aph2 is expressed in most tissues tested and is localized in the cytoplasm, mainly in the endoplasmic reticulum (ER). The sequences required for ER location reside in the N terminus and the zf-DHHC motif of Aph2. It has been reported that a portion of c-Abl is localized in the ER. We demonstrate here that Aph2 and c-Abl are co-localized in the ER region. Overexpression of Aph2 leads to apoptosis as justified by TUNEL assays, and the induction of apoptosis requires the N terminus. Co-expression of c-Abl and Aph2 had a synergistic effect on apoptosis induction and led to a decreased expression of both proteins, suggesting either that these two proteins are mutually down-regulated or that cells expressing both c-Abl and Aph2 rapidly disappeared from the culture. These results suggest that Aph2 may be involved in ER stress-induced apoptosis in which c-Abl plays an important role.
Partial Purification and Properties of Neuraminidase fromBifidobacterium lactentis (1981)

Bifidobacterium lactentis 659 a gram-positive, nonsporeforming anaerobic bacterium originally isolated from the feces of breast-fed infants produces neuraminidase after enzyme induction with 2mM N-acetylmannosamine added to the culture medium. Bacteria were transferred and grown in a medium containing casein hydrolysate, lactose, sodium acetate, amino acids, vitamins, salts and 2% human milk for 48 h at 37 degrees C under N2/CO2 atmosphere. Two subcultures derived from the original strain B. lactentis 659 were investigated separately because of different growth characteristics. However, their taxonomic identity was not doubtful. Neuraminidase was liberated from the bacterial sediments by ultrasonic treatment in 0.15M NaCl and was isolated by 60% ammonium sulfate precipitation, dialysis, concentration, and column chromatography on Sepharose CL-6B and Sephadex G-100. The enzyme exhibits a molecular weight of 38000 and a pH optimum in the range of pH 5--6 in barbital/acetate buffers. Starch gel electrophoresis and neuraminidase-specific staining with NeuAc alpha 2 leads to (3-methoxyphenyl) glycoside revealed two major and three minor enzyme bands. Michaelis constants (Km) were determined to be 7.1 mM for the (alpha 2 leads to 3) linkage of II3NeuAc-Lac, 7.5mM for the (alpha 2 leads to 6) linkage of II6Neu-Ac-Lac and 15mM for the (alpha 2 leads to 8) linkage in II3(leads from 2NeuAc8)2-Lac. Among the different groups of naturally occurring NeuAc-containing substrates, i.e. glycoproteins, gangliosides and oligosaccharides, B. lactentis neuraminidase cleaves oligosaccharides preferentially without remarkable differences between (alpha 2 leads to 3) and (alpha 2 leads to 6) linkages. Globular glycoproteins and mucins are poor substrates and gangliosides are practically not affected. In contrast, enzyme activity towards synthetic NeuAc glycosides is very high. The enzyme is activated by 50% with 50mM Ca2 and inhibited by 20mM EDTA accordingly. In general, B. lactentis neuraminidase shows a substrate specificity pattern similar to those found in other non-pathogenic and non-invasive representatives of the human bacterial flora. The potential biological role of intestinal Bifidobacteria will be discussed.
SLAM++: Simultaneous Localisation and Mapping at the Level of Objects (2013)

We present the major advantages of a new 'object oriented' 3D SLAM paradigm, which takes full advantage in the loop of prior knowledge that many scenes consist of repeated, domain-specific objects and structures. As a hand-held depth camera browses a cluttered scene, real-time 3D object recognition and tracking provides 6DoF camera-object constraints which feed into an explicit graph of objects, continually refined by efficient pose-graph optimisation. This offers the descriptive and predictive power of SLAM systems which perform dense surface reconstruction, but with a huge representation compression. The object graph enables predictions for accurate ICP-based camera to model tracking at each live frame, and efficient active search for new objects in currently undescribed image regions. We demonstrate real-time incremental SLAM in large, cluttered environments, including loop closure, relocalisation and the detection of moved objects, and of course the generation of an object level scene description with the potential to enable interaction.
Oral Administration of Dihomo‐γ‐Linolenic Acid Prevents Development of Atopic Dermatitis in NC/Nga Mice (2007)

Disorders of the metabolism of essential fatty acids (EFAs) are related to atopic dermatitis (AD). Concentrations of dihomo-gamma-linolenic acid (DGLA), an EFA, in the serum of AD patients are lower than those in healthy volunteers. Recently we developed a fermented DGLA oil, and examined whether oral administration of DGLA prevents development of dermatitis in NC/Nga mice, which spontaneously develop human AD-like skin lesions. NC/Nga mice were fed a diet either containing or not containing DGLA for 8 weeks under in air-uncontrolled conventional circumstances. Clinical skin severity scores were significantly lower in mice fed DGLA than in mice not fed it. Scratching behavior and plasma total IgE levels were also reduced in the DGLA group, in association with histological improvement. DGLA suppressed clinical severity of skin lesions dose-dependently, with an increase in DGLA contents in phospholipids of skin, spleen, and plasma. Discontinuation of DGLA administration resulted in the onset of dermatitis and a decrease in DGLA contents in skin, spleen, and plasma. These findings indicate that oral administration of DGLA effectively prevents the development of AD in NC/Nga mice, and that DGLA in phospholipids is a compound of key importance in the development and prevention of dermatitis.
Experimental Support for the "Hydrophobic Zipper" Hypothesis (1994)

4024MetricsTotal Downloads40Last 6 Months6Last 12 Months14Total Citations24Last 6 Months0Last 12 Months0View all metrics
Bacillus Calmette-Guérin Interacts with the Carboxyl-Terminal Heparin Binding Domain of Fibronectin: Implications for BCG-Mediated Antitumor Activity (1994)

Intravesical bacillus Calmette-Guérin (BCG) has been shown to be an effective treatment for superficial transitional cell carcinoma of the bladder. The mechanisms by which BCG achieves this effect remain unclear. Reports have attributed an important role to fibronectin both in the initial attachment of BCG to bladder surfaces and in the limitation of tumor cell motility. In the present study, using limited protease cathepsin B degradation followed by Western blot analyses with antibodies to various domains of the fibronectin molecule, we showed that BCG appears to bind to fibronectin near the carboxyl terminal and adjacent to the heparin binding domain. Furthermore a 51-chromium release assay with human bladder cancer cell line T24 as target cells and lymphokine activated killer (LAK) cells as effector cells showed that fibronectin was needed for tumor cytotoxicity by the LAK cells. By using antibodies and peptides to various domains of the fibronectin molecule, the heparin binding domain, but not the cell binding domain, carboxyl terminal region, or the amino terminal region of the fibronectin molecule, was identified as essential to tumor cell lysis by the LAK cells. Flow cytometric analysis showed that both peripheral blood lymphocytes and the LAK cells express fibronectin receptors VLA-3, VLA-4 and VLA-5 on their surfaces. However, the numbers of receptors are not significantly different in the two cell populations. We conclude that, by binding near the carboxyl terminal region and adjacent to the heparin-binding domain of the fibronectin molecule, BCG may protect this region of the molecule from tumor proteases, and may thus allow the antitumor activity of the host immune cells to take place.
Discrimination of sepsis and systemic inflammatory response syndrome by determination of circulating plasma concentrations of procalcitonin, protein complement 3a, and interleukin-6 (2000)

Our data show that the determination of PCT, IL-6, and C3a is more reliable to differentiate between septic and SIRS patients than the variables CRP and elastase, routinely used at the intensive care unit. The determination of PCT and C3a plasma concentrations appears to be helpful for an early assessment of septic and SIRS patients in intensive care.
Generation of a humanized anti-glypican 3 antibody by CDR grafting and stability optimization (2010)

Glypican 3 (GPC3), a glycosylphosphatidylinositol-anchored heparan sulfate proteoglycan, is expressed in a majority of hepatocellular carcinoma tissues. The murine monoclonal antibody GC33 that specifically binds to the COOH-terminal part of GPC3 causes strong antibody-dependent cellular cytotoxicity against hepatocellular carcinoma cells and exhibits strong antitumor activity in the xenograft models. To apply GC33 for clinical use, we generated a humanized GC33 from complementarity-determining region grafting with the aid of both the hybrid variable region and two-step design methods. The humanized antibody bound to GPC3 specifically and induced antibody-dependent cellular cytotoxicity as effectively as a chimeric GC33 antibody. To improve stability of the humanized GC33, we further optimized humanized GC33 by replacing the amino acid residues that may affect the structure of the variable region of a heavy chain. Substitution of Glu6 with Gln in the heavy chain significantly improved the stability under high temperatures. GC33 also has the risk of deamidation of the -Asn-Gly- sequence in the complementarity-determining region 1 of the light chain. As substitution of Asn diminished the antigen binding, we changed the neighboring Gly to Arg to avoid deamidation. The resulting humanized anti-GPC3 antibody was as efficacious as chimeric GC33 against the HepG2 xenograft and is now being evaluated in clinical trials.