gebhart/patrepeval huggingface dataset:
Idebenone as a Novel Therapeutic Approach for Duchenne Muscular Dystrophy (2015)

Progressive loss of pulmonary function leads to early morbidity and mortality in Duchenne muscular dystrophy (DMD) due to both expiratory impairment with ineffective airway clearance, and inspiratory impairment leading to nocturnal and daytime hypoventilation and respiratory failure. Glucocorticoid steroids have become a mainstay of DMD therapy with well-documented efficacy on muscle strength and respiratory function. However, the side-effect profile restricts their long-term use, particularly in non-ambulant patients. Idebenone improves secondary mitochondrial dysfunction caused by dystrophin deficiency, intracellular calcium accumulation and increased reactive oxygen species (ROS). Idebenone-mediated improved bioenergetics leads to enhanced adenosine triphosphate (ATP) production and reduced ROS. Based on this rationale, idebenone has been investigated clinically for efficacy on reducing respiratory function decline in exploratory phase II (DELPHI) and confirmatory phase III (DELOS) trials. Idebenone significantly reduced the loss of respiratory function in 8–18-year-old DMD patients who were not using concomitant glucocorticoids. These results indicate that idebenone can modify the natural course of respiratory disease progression in DMD, which is relevant in clinical practice where loss of respiratory function continues to be a predominant cause of early morbidity and mortality in DMD.
Tailored Design and Synthesis of Heparan Sulfate Oligosaccharide Analogues Using Sequential One‐Pot Multienzyme Systems (2013)

Heparan sulfate analogues: Highly efficient one-pot multienzyme (OPME) chemoenzymatic systems for the activation and transfer of N-acetylglucosamine (GlcNAc) and glucuronic acid (GlcA) have been developed. They were applied to the sequential tailored synthesis of N-sulfated analogues of heparan sulfate oligosaccharides, which could be potential therapeutics. As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Positive Selection Vectors to Generate Fused Genes for the Expression of His-Tagged Proteins (1998)

Epitope tagging simplifies detection, characterization and purification of proteins. Gene fusion to combine the coding region of a well-characterized epitope with the coding region for a protein of interest generally requires several subcloning steps. Alternatively, a PCR strategy can be used to generate such a chimeric gene. In addition to its simplicity, this approach allows one to limit the size of the multiple cloning sites present in conventional expression vectors, thus reducing the introduction of artifactual amino-acid sequences into the fused protein. In this communication, we describe new vectors that allow PCR cloning and selection of chimeric genes coding for N- or C-terminal His-tagged proteins. These vectors are based on the control of cell death CcdB direct selection technology and are well adapted to the cloning of blunt-ended PCR products that were generated by using thermostable polymerases that provide proofreading activity.
Purification, characterization, and the complete amino acid sequence of porcine pancreatic deoxyribonuclease. (1986)

Porcine pancreatic DNase has been purified to homogeneity. The polypeptide exhibits a single band of Mr = 34,000 on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The enzyme is a glycoprotein containing glucosamine. The results of end group analyses show leucine at the NH2 terminus and alanine at the COOH terminus. The enzymatic properties of the purified porcine DNase are very similar to those of bovine and ovine DNases. The sequence data on the tryptic and chymotryptic peptides derived from CNBr fragments of porcine DNase, along with the results of automated Edman degradation of the intact polypeptide and of the two largest CNBr fragments, indicate the complete amino acid sequence of porcine DNase to be as follows:L-R- I-A-F-N-I-R-T-F-G-E-T-K-M-S-N-A-T-S-N-Y-I-V-R-I-L-S-R-Y-D-I-A-L-I-Q- E-V-R-D-S-H-L-T-A-V-G-K-L-L-N-E-L-N-Q-D-D-P-N-N-Y-H-H-V-V-S-E-P-L-G-R- S-T-Y-K-E-R-Y-L-F-V-F-R-P-N-Q-V-S-V-L-D-S-Y-L-Y-D-D-G-C-E-P-C-G-N-D-T- F-N-R-E-P-S-V-V-K-F-S-S-P-F-T-Q-V-K-E-F-A-I-V-P-L-H-A-A-P-S-D-A-A-A-E- I-N-S-L-Y-D-V-Y-L-N-V-R-Q-K-W-D-L-Q-D-I-M-L-M-G-D-F-N-A-G-C-S-Y-V-T- T-S-H-W-S-S-I-R-L-R-E-S-P-P-F-Q-W-L-I-P-D-T-A-D-T-T-V-S-S-H-T-C-A-Y- D-R-I-V-V-A-G-P-L-L-Q-R-A-V-V-P-D-S-A-A-P-F-D-F-Q-A-A-F-G-L-S-Q-E-T- A-L-A-I-S-D-H-Y-P-V-E-V-T-L-K-R-A. The polypeptide consists of 262 amino acid residues. One of the two disulfide loops links Cys-101 and Cys-104 and the other Cys-173 and Cys-209. Two carbohydrate side chains are attached at Asn-18 and Asn-106.
Comparison of a Production Process in a Membrane-Aerated Stirred Tank and up to 1000-L Airlift Bioreactors Using BHK-21 Cells and Chemically Defined Protein-Free Medium (2003)

The applicability of a protein-free medium for the production of recombinant human interleukin-2 with baby hamster kidney cells in airlift bioreactors was investigated. For this purpose, a BHK-21 cell line, adapted to grow and produce in protein-free SMIF7 medium without forming spheroids in membrane-aerated bubble-free bioreactors, was used as the producer cell line. First, cultivation of the cells was established at a 20-L scale using an internal loop airlift bioreactor system. During the culturing process the medium formulation was optimized according to the specific requirements associated with cultivation of mammalian cells under protein-free conditions in a bubble-aerated system. The effects of the addition of an antifoam agent on growth, viability, productivity, metabolic rates, and release of lactate dehydrogenase were investigated. Although it was possible to establish cultivation and production at a 20-L scale without the use of antifoaming substances, the addition of 0.002% silicon-oil-based antifoaming reagent improved the cultivation system by completely preventing foam formation. This reduced the release of lactate dehydrogenase activity to the level found in bubble-free aerated stirred tank membrane bioreactors and led to a reduction in generation doubling times by about 5 h (17%). Using the optimized medium formulation, cells were cultivated at a 1000-L scale, resulting in a culture performance comparable to the 20-L airlift bioreactor. For comparison, cultivations with protein-containing SMIF7 medium were carried out at 20- and 1000-L scales. The application of protein supplements did not lead to a significant improvement in the cultivation conditions. The results were also compared with experiments performed in a bubble-free aerated stirred tank membrane bioreactor to evaluate the influence of bubbles on the investigated culture parameters. The data implied a higher metabolic activity of the cells in airlift bioreactors with a 150% higher glucose consumption rate. The results of this study clearly demonstrate the applicability of a protein-free chemically defined medium for the production of recombinant proteins with BHK cells in airlift bioreactors.
In vivo gene therapy for alpha-fetoprotein-producing hepatocellular carcinoma by adenovirus-mediated transfer of cytosine deaminase gene. (1997)

The alpha-fetoprotein (AFP) gene is normally expressed in fetal liver and is transcriptionally silent in adult liver but overexpressed in human hepatocellular carcinoma (HCC). Here, we demonstrate that replication defective recombinant adenoviral vectors, containing the human AFP promoter/enhancer, can be used to express the Escherichia coli cytosine deaminase (CD) gene (AdAFPCD) and the beta-galactosidase gene (AdAF-PlacZ) in AFP-producing HCC cell lines. Expression of the CD gene by adenovirus from the AFP promoter/enhancer (AdAFPCD) induced cells sensitive to 5-fluorocytosine (5FC) in the AFP-producing cells but not in the AFP-nonproducing cells. Transduction by an adenoviral vector harboring an ubiquitous strong promoter and CD gene showed enzymatic activity and 5FC killing in all cell lines. When AdAFPlacZ was injected into the s.c. established hepatoma in vivo, expression of the beta-galactosidase gene was confined to AFP-producing HCC xenografts. Moreover, HCC xenografts regressed by transduction with AdAFPCD and subsequently with 5FC treatment in vivo. These findings suggest that utilization of the AFP promoter/enhancer in an adenoviral vector can confer selective expression of a heterologous suicide gene in hepatocellular carcinoma cells in vitro and in vivo.
DISTANT MIGRATION OF SILICONE GEL FROM A RUPTURED BREAST IMPLANT (1978)

A complication of augmentation mammaplasty is presented in which the bag of a gel-filled implant ruptured and the thin gel migrated through subcutaneous planes as far as the groin. We feel that when a rupture of a gel-filled prosthesis becomes evident, it should be replaced as soon as possible if such migration is to be prevented (particularly if the gel is of the thinner and less-cohesive variety).
Biopolymers codelivering engineered T cells and STING agonists can eliminate heterogeneous tumors (2017)

Therapies using T cells that are programmed to express chimeric antigen receptors (CAR T cells) consistently produce positive results in patients with hematologic malignancies. However, CAR T cell treatments are less effective in solid tumors for several reasons. First, lymphocytes do not efficiently target CAR T cells; second, solid tumors create an immunosuppressive microenvironment that inactivates T cell responses; and third, solid cancers are typified by phenotypic diversity and thus include cells that do not express proteins targeted by the engineered receptors, enabling the formation of escape variants that elude CAR T cell targeting. Here, we have tested implantable biopolymer devices that deliver CAR T cells directly to the surfaces of solid tumors, thereby exposing them to high concentrations of immune cells for a substantial time period. In immunocompetent orthotopic mouse models of pancreatic cancer and melanoma, we found that CAR T cells can migrate from biopolymer scaffolds and eradicate tumors more effectively than does systemic delivery of the same cells. We have also demonstrated that codelivery of stimulator of IFN genes (STING) agonists stimulates immune responses to eliminate tumor cells that are not recognized by the adoptively transferred lymphocytes. Thus, these devices may improve the effectiveness of CAR T cell therapy in solid tumors and help protect against the emergence of escape variants.
A Forward-Adjoint Operator Pair Based on the Elastic Wave Equation for Use in Transcranial Photoacoustic Computed Tomography (2017)

Photoacoustic computed tomography (PACT) is an emerging imaging modality that exploits optical contrast and ultrasonic detection principles to form images of the photoacoustically induced initial pressure distribution within tissue. The PACT reconstruction problem corresponds to an inverse source problem in which the initial pressure distribution is recovered from measurements of the radiated wavefield. A major challenge in transcranial PACT brain imaging is compensation for aberrations in the measured data due to the presence of the skull. Ultrasonic waves undergo absorption, scattering and longitudinal-to-shear wave mode conversion as they propagate through the skull. To properly account for these effects, a wave-equation-based inversion method should be employed that can model the heterogeneous elastic properties of the skull. In this work, a forward model based on a finite-difference time-domain discretization of the three-dimensional elastic wave equation is established and a procedure for computing the corresponding adjoint of the forward operator is presented. Massively parallel implementations of these operators employing multiple graphics processing units (GPUs) are also developed. The developed numerical framework is validated and investigated in computer19 simulation and experimental phantom studies whose designs are motivated by transcranial PACT applications.
Variable domain-linked oligosaccharides of a human monoclonal IgG: structure and influence on antigen binding (1999)

The variable-domain-attached oligosaccharide side chains of a human IgG produced by a human-human-mouse heterohybridoma were analysed. In addition to the conserved N-glycosylation site at Asn-297, an N-glycosylation consensus sequence (Asn-Asn-Ser) is located at position 75 in the variable region of its heavy chain. The antibody was cleaved into its antigen-binding (Fab) and crystallizing fragments. The oligosaccharides of the Fab fragment were released by digestion with various endo- and exoglycosidases and analysed by anion-exchange chromatography and fluorophore-assisted carbohydrate electrophoresis. The predominant components were disialyl- bi-antennary and tetra-sialyl tetra-antennary complex carbohydrates. Of note is the presence in this human IgG of oligosaccharides containing N-glycolylneuraminic acid and N-acetylneuraminic acid in the ratio of 94:6. Furthermore, we determined N-acetylgalactosamine in the Fab fragment of this antibody, suggesting the presence of O-linked carbohydrates. A three-dimensional structure of the glycosylated variable (Fv) fragment was suggested using computer-assisted modelling. In addition, the influence of the Fv-associated oligosaccharides of the CBGA1 antibody on antigen binding was tested in several ELISA systems. Deglycosylation resulted in a decreased antigen-binding activity.
31 Translation Initiation on Picornavirus RNA (2000)

The animal picornaviruses are a large family of viruses which is currently subdivided into six genera (Table 1). They are non-enveloped viruses with a positive-strand RNA genome some 8000 nucleotides in length. Replication occurs entirely within the cytoplasm, as witnessed by the fact that they can replicate efficiently in enucleated cells (Follett et al. 1975). There is a 3′ poly(A) tail that is encoded rather than being added in a template-independent process by a poly(A) polymerase. At the 5′ end there is a covalently linked small virus-encoded protein, VPg (also known as 3B). It is believed that soon after entry into the infected cell, this protein is cleaved off by cellular activities, so that the RNA is effectively translated as an uncapped mRNA. Certainly, VPg is not essential for infectivity, since full length in vitro synthesized RNA (without VPg) is infectious. There is a single open reading frame coding for a polyprotein (Fig. 1), which is rapidly processed to give the individual capsid proteins and viral nonstructural proteins. The common features of picornavirus 5′-untranslated regions (UTRs) are that they are very long (610 to >1200 nucleotides depending on the species); they have numerous AUG triplets, most of which are not conserved even between different isolates of the same virus (Poyry et al. 1992); and they are predicted to fold into complex secondary structures. These characteristics, together with the fact that the RNA is not capped, imply that the RNAs cannot possibly be translated efficiently by the conventional scanning mechanism. Initiation...
Tuning the Preference of Thiodigalactoside- and Lactosamine-Based Ligands to Galectin-3 over Galectin-1 (2013)

Inhibitors for galectin-1 and -3 were synthesized from thiodigalactoside and lactosamine by derivatization of the galactose C3. Introduction of 4-phenyl-1H-1,2,3-triazol-1-yl substituents at the thiodigalactoside C3 by CuAAC, targeting arginine-arene interactions, increased the affinity to 13 nM but yielded little selectivity. The bulkier 4-(4-phenoxyphenyl)-1H-1,2,3-triazol-1-yl substituent, however, increased the preference for galectin-3 over galectin-1 to more than 200-fold. Modeling showed more arginine-arene interactions for galectin-3 than for galectin-1. Introducing 4-phenoxyaryl groups on lactosamine had a similar effect.
Place de la chirurgie dans le traitement de la maladie de Crohn (2002)

The authors compare their experience in the surgical treatment of Crohn's disease with the results from several large series in the literature, Over 25 years 533 intestinal operations in adults were performed, including a first operation in 348 patients (177 women, 171 men, median age: 33 years, range: 15-80 years), with no mortality. The main indications for intestinal resection limited to macroscopic disease were symptomatic strictures (45.7%) and fistulas (37 %). As observed in other series reported, recurrences assessed as reoperations have been frequent, with a cumulative resection rate of 11% after 5 years, 29% after 10 years, 41% after 15 years and 70% after 20 years. However, 10-year cumulative reoperation rate was nil after coloproctectomy + ileostomy. In 18 patients, including 8 with previous surgery, 68 stricturoplasties were performed, associated with ileocolic and/or segmental jejuno-ileal resections in 15. After stricturoplasty, the reoperation rate was 33% over a median followup of 33.5 months (8-144). The confirmation of the high risk of recurrence after conservative surgery for Crohn's disease, which can only be reduced by cessation of smoking, urges the need to pursue randomized trials about post-surgical chemoprevention. If effective and safe, chemoprevention could allow even more conservative surgery, such as ileal-pouch anastomosis in patients with satisfactory anal sphincter function.
Radioimmunotherapy after chemotherapy compared to chemotherapy alone in the treatment of advanced ovarian cancer: a matched analysis. (1998)

Ovarian cancer has an overall five-year survival of around 30% in spite of complete remissions being obtained after optimal surgery and platinum-based chemotherapy. Previous studies have indicated a survival advantage for patients treated with radiolabelled monoclonal antibodies (radioimmunotherapy). We report here on the survival of patients who received single-dose intraperitoneal radioimmunotherapy after having achieved complete remission with standard management. Twenty-five patients with epithelial ovarian cancer, stages Ic-IV, received adjuvant intraperitoneal radioimmunotherapy following completion of conventional chemotherapy. On achieving complete remission they receive once 25 mg of HMFG1 labelled with 18 mCi/m2. Controls for cases were sought from the database of the North Thames ovary group (NTOG). Controls were selected on the basis of stage, histological grade and type, and age of patient at diagnosis. Kaplan-Meier survival plots were constructed for cases and controls and subjected to statistical analysis with the log-rank test. Additionally, using a database of 84 NTOG patients known to be disease-free at the end of chemotherapy, estimated survival curves were constructed using Cox's proportional hazards regression model. Close matches were found for 20 of the 25 patients. Median survival has not been reached at a median follow-up of 59 months for cases and 27 months for controls. Survival at five years is 80% for cases and 55% for controls (p=0.0035). The Cox model estimates long-term (10-year) survival of 70% for patients who received radioimmunotherapy, compared to 32% for those that did not (p=0.003). All patients developed serological evidence of human anti-mouse antibody (HAMA). This study shows a likely survival benefit for patients with ovarian cancer who receive intraperitoneal radioimmuno-therapy in the adjuvant setting.
Resource-based relative-value scale expansion: implications for performance and quality of care. (1997)

The diffusion or RBRVS to multiple payers may have a profound impact on the distribution of services provided, how these services are delivered, and the quality of care provided. Providers may respond to RBRVS by reducing some types of services, while increasing others, and using new resource combinations. Managed-care payers are likely to continue using RBRVS for negotiating fee schedules or for allocating payments for bundled service packages and capitation and sub-capitation products among physicians. As larger shares of physicians' incomes are driven by RBRVS, the underlying incentives become more critical. Nevertheless, RBRVS will remain an important payment approach in the future. The impact on quality and delivery of physician services from broader use of RBRVS cannot be measured adequately until future empirical studies are undertaken.
The Cause and management of aneurysms (1990)

Focuses on principle aneurysm sites. Includes coverage of investigative approaches, conservation, and surgical management.
Vitamin A Supplementation for Retinitis Pigmentosa (1993)

We welcome the opportunity to address the comments of Drs Massof and Finkelstein<sup>1</sup>in their editorial that accompanies our article<sup>2</sup>in the June 1993 issue of theArchives. The editorialists inaccurately state that our conclusion was based on a single aspect of the cone electroretinogram (ERG). In fact, our conclusion regarding the beneficial effect of vitamin A supplementation for retinitis pigmentosa (RP) was based on two objective tests of retinal function—the 30-Hz (flicker) ERG and the 0.5-Hz (single flash) ERG. The 30-Hz ERG provides a measure of cone function, and the 0.5-Hz ERG, a measure of cone and rod function in combination. We reported that patients receiving 15 000 IU/d of vitamin A had a significantly slower rate of decline of remaining ERG amplitude on average than those not receiving this supplement, not only for 30-Hz responses (<i>P</i>=.01) but also for 0.5-Hz responses (<i>P</i>=.04). The editorialists
Long-term tamoxifen therapy to control or to prevent breast cancer: laboratory concept to clinical trials. (1988)

The successful evaluation of tamoxifen as an antiestrogenic therapy for advanced breast cancer in the early 1970's, has resulted in its availability in more than 70 countries around the world. Currently the drug development process is focusing attention upon long-term adjuvant therapy and the future prospect of chemosuppression. Progress at this stage, however, must be cautious. Trials conducted using women with stage I disease have a high proportion of women who may never have a recurrence. At this point, the risk is justified because the toxicity of tamoxifen is low and disease recurrence is invariably very difficult or impossible to control. Future studies in the general population must be carefully weighed to ensure that the hazards do not exceed the benefits. The pharmacology of tamoxifen seems to be a balance of estrogenic and antiestrogenic effects. Longer treatments with the drug must be carefully monitored. Uterine tissue should be examined to ensure that excessive stimulation does not occur. This is particularly true in the light of the recent report that a human uterine carcinoma, transplanted into athymic mice, can grow more rapidly during tamoxifen therapy (Satyaswaroop et al., 1984; Clark and Satyaswaroop, 1985). In fact, we have recently confirmed this observation in a collaborative study with Dr. Satyaswaroop. We have demonstrated that when athymic mice are transplanted in one axilla with an MCF-7 breast tumor and the human endometrial tumor in the other, tamoxifen causes the endometrial tumor to grow, but not the breast tumor. This again illustrates the target site specific effects of tamoxifen. If, in the long run, the estrogenic side effects of tamoxifen are too severe then there is a case for the development of a non-estrogenic antiestrogen. Clearly this may provide benefit for short term (1-2 years) therapy and avoid any estrogen-like stimulation of tumor growth. Similarly, the concern about antithrombin III depression will be avoided. On the negative side, however, the concerns about atherosclerosis and osteoporosis will again have to be addressed with a new generation of agents.