gebhart/patrepeval huggingface dataset:
The role of the WSXWS equivalent motif in growth hormone receptor function. (1994)

Members of the cytokine receptor family have a consensus WSXWS sequence (WS motif) in the extracellular domain. With the interleukin-2, erythropoietin, and prolactin receptors, alteration of the WS sequence disrupts ligand binding and receptor signaling. The structural basis for these effects is unclear. To examine the role of the WS equivalent sequence (Y222GEFS226) in the function of the growth hormone receptor, each residue was mutated to alanine or to the WS consensus sequence. Although we used stable cell lines expressing all of these mutants, we show only three mutants, Y222A, G223A, and S226A, which display lower ligand affinity. Using conformation-specific monoclonal antibodies, we show that Y222A and S226A receptors have structural perturbations, which result in decreased signal transduction. This was shown by a decreased ability of growth hormone to stimulate protein synthesis and to transactivate the c-fos promoter with these mutants. The crystal structure of the ligand-occupied extracellular domain of growth hormone receptor indicates that Tyr222 and Ser226 have important interactions within the second beta-barrel domain, providing a structural basis for our results. The WS segment is not involved in sequence-specific accessory protein interaction, as mutation of residues Gly223, Glu224, and Phe225 does not alter receptor function.
High‐Frequency Gastric Electrical Stimulation for the Treatment of Gastroparesis: A Meta‐Analysis (2009)

Results show substantial benefits for high-frequency GES in the treatment of gastroparesis. However, caution is necessary in interpreting the results, primarily because of the limitations of uncontrolled studies. Further controlled studies are required to confirm the clinical benefits of high-frequency GES.
Comparison of topical sucralfate and silver sulfadiazine cream in second degree burns in rats. (2013)

Sucralfate is known to have multiple beneficial effects on wound healing. Using topical sucralfate accelerates the burn wound healing process in comparison with both the control and SSD groups and can be used as an adjunctive or alternative agent in the future.
Glycative stress from advanced glycation end products (AGEs) and dicarbonyls: An emerging biological factor in cancer onset and progression (2016)

In recent years, glycative stress from exogenous or endogenous advanced glycation end products (AGEs) and highly reactive dicarbonyls has gained great attention for its putative effects on cancer development. AGEs are a group of compounds formed from the complex chemical reaction of reducing sugars with compounds containing an amino group. AGEs bind to and activate the receptor for AGEs (RAGE), which is a predominant modulator of inflammation-associated cancer, and AGEs induce reactive oxygen species that are an important regulator of the hallmarks of cancer. Dicarbonyls, which are formed during glycolysis, lipid oxidation, or protein degradation, include glyoxal, methylglyoxal, and 3-deoxyglucosone and are regarded as major precursors of AGEs. These dicarbonyls not only fuel the AGE pool in living organisms but also evoke carbonyl stress, which may contribute to the carbonylative damage of carbohydrates, lipids, proteins, or DNA. Carbonylative damage then leads to many lesions, some of which are implicated in the pathogenesis of cancer. In this review, studies regarding the effects of AGEs and dicarbonyls on cancer onset or progression are systematically discussed, and the utilization of AGE inhibitors and dicarbonyl scavengers in cancer therapy are noted.
Generation of Antibodies to the Urokinase Receptor (uPAR) by DNA Immunization of uPAR Knockout Mice: Membrane‐Bound uPAR is Not Required for an Antibody Response (2003)

The urokinase receptor (uPAR) is a glycolipid-anchored cell surface glycoprotein that plays a central role in extracellular proteolysis during tissue remodeling processes including cancer invasion. Furthermore, uPAR is found on the surface of both dendritic cells (DCs) and T cells, and has been proposed to play a role in DC-induced T-cell activation and, therefore, in the induction of an immune response. In order to investigate the possibility of using DNA immunization for the generation of poly- and monoclonal antibodies to uPAR, we injected wild-type mice and mice deficient in uPAR (uPAR knockouts) intramuscularly with plasmid DNA encoding a carboxy-terminal truncated soluble form of the human uPAR. Multiple injections of 100 micro g of DNA resulted in a strong and specific antibody response in all mice irrespective of genotype. Antisera with a maximum titre of 32,000 were obtained, comparable with that obtained after immunization with recombinant uPAR. The subclass distribution of uPAR-specific antibodies in the sera demonstrated the induction of a mixed TH1/TH2 response, irrespective of the genotype of the mice. Our results demonstrate the possibility of generating high titre antibodies to uPAR by DNA immunization of wild-type as well as uPAR knockout mice, and that cell surface uPAR is not indispensable for the generation of a humoral immune response.
Liposomal Pemetrexed: Formulation, Characterization and <i>in Vitro</i> Cytotoxicity Studies for Effective Management of Malignant Pleural Mesothelioma (2015)

Pemetrexed (PMX) is a newly developed multi-targeted anti-folate with promising clinical activity in many solid tumors including malignant pleural mesothelioma (MPM). However, PMX does not show sufficient anti-tumor activity in vivo when used alone either due to inefficient delivery of adequate concentrations to tumor tissue or dose-limiting side effects. In order to overcome these problems and to achieve potent anti-tumor activity, PMX was encapsulated into a liposomal delivery system. In the present study, various formulations of liposomal PMX were prepared. The effect of formulation parameters on the encapsulation efficiency of PMX within liposomes was evaluated. In addition, the influence of drug release rate on the in vitro cytotoxicity was investigated. Encapsulation of PMX within liposomes was remarkably increased by the incorporation of cholesterol within liposomal membranes and by increasing the total lipid concentration. Encapsulation efficiency was found to be unaffected by the type of phospholipid used or the inclusion of a cation lipid, DC-6-14. Interestingly, encapsulation of PMX within "fluid" liposomes was found to allow efficient release of PMX from liposomes resulting in a potent in vitro cytotoxicity against MPM MSTO-211H cell line. On the other hand, entrapment of PMX within "solid" liposomes substantially hindered PMX release from liposomes, and thus PMX failed to exert any in vitro cytotoxicity. These results suggest that encapsulation of PMX within "fluid" liposomes might represent a novel strategy to enhance the therapeutic efficacy of PMX while minimizing the side effect encountered by the non selective delivery of free PMX to various body tissues.
Prevalence of theFMR1 mutation in Taiwan assessed by large-scale screening of newborn boys and analysis of DXS548-FRAXAC1 haplotype (2005)

If carrier women could be identified in time and take appropriate measures, fragile X syndrome (FXS) can be prevented. Wide screening of women to be or in their early pregnancy was considered a good approach to identify carriers without misdetection. Nevertheless, we argued against the cost-effectiveness of implementing such a screening program in Taiwan, due to the lower carrier rate found in our pilot study. To reliably estimate the prevalence of mutant FMR1 gene in Taiwan, we anonymously screened 10,046 newborn boys using bloodspot polymerase chain reaction (PCR). Among them, the sample from one boy, who was most likely had FXS, failed repeatedly in PCR amplification. The estimated prevalence of premutation (55-200 CGG repeats) and intermediate alleles (45-54 CGG repeats) was 1:1,674 (n = 6) and 1:143 (n = 70), respectively. All these estimates were constantly lower than that reported in Caucasian populations, with variable statistic significance. Furthermore, when comparing analyses of the distribution of alleles at the two most often investigated microsatellite loci, DXS548 and FRAXAC1, between 100 control and 28 unrelated fragile X chromosomes, we found no apparent founder haplotype prevalent among the fragile X patients. Because a few founder haplotypes were reportedly prevalent in two thirds of fragile X alleles in Caucasians and in Chinese from Central China, we thus suggested that lack of founder fragile X chromosomes might result in a relatively low prevalence of mutant FMR1 gene in a population, as observed in Taiwan.
Fiber optics sensors for ultrasonic virtual biopsy (2003)

Recent progresses in optoacoustics let us foresee the possibility to realize a strongly miniaturized transducer constituted by two optical fibers: a first fiber, with a heavily absorbing film on its extremity, to generate broadband ultrasounds; another fiber, with a Fabry-Perot cavity mounted, or deposed, on its tip, to optically detect ultrasonic echoes. The proposed transducer is characterized by high cutoff frequency, wide bandwidth, high electromagnetic compatibility and no electrical wiring. Due to these virtues, the transducer may result greatly useful for diagnostic applications, allowing for higher echographic resolution and microstructural tissue characterization. In addition, the transducer miniaturization would make possible its insertion in the human body for a direct investigation of focal lesions with minimal invasivity. Thus, a path toward virtual biopsy may be traced.
Expression of ICAM-1 and VCAM-1 and Monocyte Adherence in Arteries Exposed to Altered Shear Stress (1995)

Local shear stresses generated by blood flow exert direct mechanical effects on adhesion of circulating leukocytes to vascular endothelium, but their effects on expression of endothelial-leukocyte adhesion molecules have not been determined. Shear stress in rabbit carotid arteries was increased by 170% or decreased by 73% in 5 days by surgical manipulations. En face immunofluorescence staining with the monoclonal antibody Rb1/9 revealed that vascular cell adhesion molecule-1 (VCAM-1) expression was greatly increased under low shear stress, but the distribution of staining was patchy. Thus, 71.4 +/- 7.8% of fields were VCAM-1 positive versus 2.4 +/- 0.47% of fields in control arteries. Frequently, large regions showed consistent but heterogeneous staining. Occasionally, small islands of cells were labeled intensely. Monocytes, detected by use of the monocyte-specific antibody HAM 56, adhered to endothelium under low shear stress; 64.5 +/- 8.2% of the monocytes colocalized with detectable VCAM-1, although many (83.2 +/- 2.8%) VCAM-1-positive regions were devoid of monocytes. VCAM-1 expression also increased significantly but to a lesser extent when shear stress was approximately doubled. Thus, 8.7 +/- 1.5% of fields were VCAM-1 positive under high shear versus 2.5 +/- 0.87% under normal shear stress. No monocytes were detected at high shear stress. At normal shear stresses, intercellular adhesion molecule-1 (ICAM-1), detected by use of the monoclonal antibody Rb2/3, was extensively distributed; thus, 53.5 +/- 5.5% of fields contained ICAM-1-positive cells. The junctional regions of the cells were heavily stained.(ABSTRACT TRUNCATED AT 250 WORDS)
Kinetics of Core Histones in Living Human Cells (2001)

Histones H2A and H2B form part of the same nucleosomal structure as H3 and H4. Stable HeLa cell lines expressing histones H2B, H3, and H4 tagged with green fluorescent protein (GFP) were established; the tagged molecules were assembled into nucleosomes. Although H2B-GFP was distributed like DNA, H3-GFP and H4-GFP were concentrated in euchromatin during interphase and in R-bands in mitotic chromosomes. These differences probably result from an unregulated production of tagged histones and differences in exchange. In both single cells and heterokaryons, photobleaching revealed that H2B-GFP exchanged more rapidly than H3-GFP and H4-GFP. About 3% of H2B exchanged within minutes, whereas approximately 40% did so slowly (t(1/2) approximately 130 min). The rapidly exchanging fraction disappeared in 5,6-dichloro-1-beta-d-ribofuranosylbenzimidazole and so may represent H2B in transcriptionally active chromatin. The slowly exchanging fraction was probably associated with chromatin domains surrounding active units. H3-GFP and H4-GFP were assembled into chromatin when DNA was replicated, and then >80% remained bound permanently. These results reveal that the inner core of the nucleosome is very stable, whereas H2B on the surface of active nucleosomes exchanges continually.
Isolation of Clostridium botulinum Type G and Identification of Type G Botulinal Toxin in Humans: Report of Five Sudden Unexpected Deaths (1981)

Clostridium botulinum type G has not been identified until now from humans or animals; it has been isolated only twice, from soil samples in Argentina. Type G organisms were isolated from necropsy specimens in four adults and an 18-week-old infant. Type G botulinal toxin was demonstrated in the serum of three of these individuals. The toxic dose in mice ranged from 2 to 7 50% lethal doses/ml. These persons died suddenly and unexpectedly at home, without any pathologic evidence to account for the cause of death in four cases. Symptoms in two individuals were similar to those observed in food-borne botulism. Thus, a prompt postmortem search for toxin and organisms of C. Botulinum in blood and feces may be worthwhile in determining the etiology of unexplained deaths. More microbiologic, physiologic, and toxicologic data are needed to clarify the role of C. botulinum in the pathogenesis of sudden unexpected death in infants and adults.
A double-blind placebo-controlled comparison of the efficacy and safety of 50, 100, and 200 micrograms of misoprostol QID in the prevention of ibuprofen-induced gastric and duodenal mucosal lesions and symptoms. (1989)

Ibuprofen, a commonly proscribed nonsteroidal anti-inflammatory drug that is also available in many countries, including the United States, without a prescription, is known to cause hemorrhage and erosion of the gastroduodenal mucosa. This study was conducted to compare the efficacy of 200, 100, and 50 micrograms of misoprostol and placebo administered qid for 6 days, with a final dose on the morning of the 7th day, in the prevention of gastric and duodenal lesions induced by the concurrent administration of 800 mg of ibuprofen qid. A total of 120 healthy subjects with endoscopically normal gastric and duodenal mucosae were enrolled in the study. The endoscopic examination was repeated 2 h after the final dose on day 7, and the mucosae were graded on a 0 to 4+ scale. In the stomach, all three misoprostol groups were significantly more protective than placebo and did not differ significantly from each other. In the duodenum, the endoscopic scores of the 200- and 100-micrograms misoprostol groups, but not the 50-micrograms group differed significantly from placebo. The 200- and 100-microgram groups did not differ significantly from each other, but both differed from the 50-micrograms group for duodenal mucosal injury. Subjective symptoms thought to be primarily attributable to the NSAID (e.g., pain, indigestion/heartburn and nausea) were recorded by each subject in a diary. Subjects in the 200-micrograms misoprostol group attained the greatest degree of mucosal protection and had a significantly higher incidence of indigestion/heartburn and abdominal pain than the placebo group. One can conclude that misoprostol in both antisecretory (200- and 100-micrograms) and non-antisecretory (50-micrograms) doses protects the gastric mucosa from injury from high anti-inflammatory doses of ibuprofen (3200 mg/day). Only the antisecretory doses (100 and 200 micrograms qid) were effective in the duodenum, suggesting that acid suppression is necessary for mucosal protection to occur in the duodenum.
Opioid Insights (2004)

Opioid analgesics are an irreplaceable component of pharmacotherapy of numerous pain-producing conditions. Clinicians and patients must contend with the imperfect nature of this class of drugs, trying to balance benefits and burdens on a continual basis. New literature related to evidence-based selection of opioids and the neurobiological phenomenon of opioid induced hyperalgesia are reviewed. A matrix describing critical elements in the selection of opioid analgesics, both for initial therapy and for opioid rotation, is presented.
KRAS Mutation Status Is Predictive of Response to Cetuximab Therapy in Colorectal Cancer (2006)

The anti-epidermal growth factor receptor (anti-EGFR) cetuximab has been proven to be efficient in metastatic colorectal cancer. The molecular mechanisms underlying the clinical response to this drug remain unknown. Genetic alterations of the intracellular effectors involved in EGFR-related signaling pathways may have an effect on response to this targeted therapy. In this study, tumors from 30 metastatic colorectal cancer patients treated by cetuximab were screened for KRAS, BRAF, and PIK3CA mutation by direct sequencing and for EGFR copy number by chromogenic in situ hybridization. Eleven of the 30 patients (37%) responded to cetuximab. A KRAS mutation was found in 13 tumors (43%) and was significantly associated with the absence of response to cetuximab (KRAS mutation in 0% of the 11 responder patients versus 68.4% of the 19 nonresponder patients; P = 0.0003). The overall survival of patients without KRAS mutation in their tumor was significantly higher compared with those patients with a mutated tumor (P = 0.016; median, 16.3 versus 6.9 months). An increased EGFR copy number was found in 3 patients (10%) and was significantly associated with an objective tumor response to cetuximab (P = 0.04). In conclusion, in this study, KRAS mutations are a predictor of resistance to cetuximab therapy and are associated with a worse prognosis. The EGFR amplification, which is not as frequent as initially reported, is also associated with response to this treatment.
Dimerization of the Interferon Type I Receptor IFNaR2–2 Is Sufficient for Induction of Interferon Effector Genes but Not for Full Antiviral Activity (1999)

We constructed chimeric receptors wherein the extracellular domain of the erythropoietin receptor (EpoR) was fused to the transmembrane and intracellular domains of the interferon (IFN) type I receptor subunits, IFNaR1 or IFNaR2-2. Transfection into 2fTGH and Tyk2-deficient 11,1 cells showed that EpoR/IFNaR2-2 alone was able to transduce a signal upon stimulation with erythropoietin (Epo), as judged by induction of the interferon type I-inducible 6-16 promoter. In contrast, protection against infection with encephalomyocarditis virus or vesicular stomatitis virus was reduced or absent, respectively. To further investigate the role of IFNaR1 in the induction of an antiviral state, we analyzed the Epo- versus IFNalpha-induced transcription of a set of genes, involved in antiviral protection. Up to 24 h after stimulation with Epo or IFNalpha, comparable transcription of the p56, dsRNA-dependent protein kinase, 2'-5'A synthetase, and MxA genes was seen. However, at later time points, only in the case of Epo induction, a sharp decrease of mRNA levels was observed. Western blotting analysis of dsRNA-dependent protein kinase showed a similar pattern at the protein level. Taken together, our results imply a role for IFNaR1 in the induction of sustained mRNA and protein levels that are likely required for optimal antiviral activity.
Growth factors and stromal support generate very efficient retroviral transduction of peripheral blood CD34+ cells from Gaucher patients (1995)

We have achieved high-efficiency gene transfer into nonmobilized peripheral blood (PB) CD34+ cells from patients with Gaucher's disease using a clinically acceptable retroviral supernatant transduction protocol. In our studies, bone marrow (BM) and PB CD34+ cells were transduced using a high titer (10(8) particles/mL) retroviral supernatant once a day for 4 consecutive days in the presence of interleukin-3 (IL-3), IL-6, and stem cell factor (SCF), with or without an irradiated allogeneic BM stromal layer. The growth factors alone resulted in 29% +/- 10% gene transfer of PB CD34+ clonogenic cells in contrast with 71% +/- 17% gene transfer efficiency using stroma with the growth factors; a 2.5-fold increase. The increase in gene transfer efficiency was less prominent when BM CD34+ cells were used (40% +/- 16% without and 57% +/- 8% with stroma, a 1.5-fold increase). The overall transduction efficiency of both PB and BM CD34+ cells was lower when the cells were transduced over a stromal cell layer without added growth factors. The combination of IL-3, IL-6, and SCF with stroma transduced 75% of primitive long-term culture initiating cells (PB LTC-ICs) in comparison with 34% of LTC-ICs when IL-3, IL-6, and SCF were used without stromal support. Using this clinically acceptable supernatant/cytokines/stroma transduction protocol, correction of the glucocerebrosidase (GC) deficiency in the progeny cells of PBLTC-ICs from Gaucher's-disease patients has been accomplished. Efficient transduction of the PB CD34+ cells using this transduction protocol may allow repeated delivery of "GC-corrected" hematopoietic stem and progenitor cells to Gaucher's-disease patients.
Homogeneous Production of Feline Interferon in Silkworm by Replacing Single Amino Acid Code in Signal Peptide Region in Recombinant Baculovirus and Characterization of the Product. (1993)

In a previous paper we reported that we constructed a recombinant baculovirus named BmFeIFN1 which produced recombinant feline interferon (FeIFN) in silkworm after infection. High purification of FeIFN in body fluid from the larvae revealed that two kinds of FeIFN were produced by the BmFeIFN1. The difference between the two in the NH2-terminal amino acid sequence was clarified, and two kinds of processing at different sites in FeIFN precursor were suggested. Changing one residue of the amino acid sequence in deduced signal peptide by site directed mutagenesis of encoding cDNA led to the production of homogeneous FeIFN whose NH2-terminal three amino acid sequence was identical to the conserved sequence of human interferon-alpha. We designated the FeIFN produced as rFeIFN. Amino acid sequence analysis revealed that rFeIFN consisted of 170 amino acid residues. The COOH-terminal amino acid of the rFeIFN is Glu which is located at one amino acid residue upstream to the COOH-terminal amino acid deduced from the nucleotide sequence. Positive periodic acid Schiff reaction, undetectability of Asn at position 79 by automated protein sequencer, and detectability of N-acetylglucosamine not N-acetylgalactosamine suggested that rFeIFN was N-glycosylated. rFeIFN was stable at pH 1.5 at 4 degrees C for at least 50 days, and had an antiviral action on feline calicivirus or feline herpesvirus in vitro. Its isoelectric point was pI 6.5. Comparing the structure and biosynthesis of rFeIFN with those of HuIFNs, rFeIFN may be classified as omega-type.