gebhart/patrepeval huggingface dataset:
The combined use of an immunotoxin and a radioimmunoconjugate to treat disseminated human B-cell lymphoma in immunodeficient mice. (2000)

Immunoconjugates (ICs) consist of a targeting moiety and a toxic moiety and have the specificity that traditional cancer therapy lacks. At appropriate doses, ICs are safe and effective in treating various cancers in experimental animals and in humans. However, because cures are rarely achieved using single agents, regimens involving combinations of agents with different mechanisms of action must be evaluated. In this study, we explored the efficacy and toxicity of a combination of two IC therapies, radioimmunotherapy (RIT) and immunotoxin (IT) therapy, to treat advanced, disseminated human lymphoma in immunodeficient mice. We proposed to use the bystander effect of RIT to reduce large tumor burdens, followed by an IT to eliminate residual tumor cells. Our results indicate that, when used alone, both RIT and IT therapy were safe and effective, but not curative. When the two therapies were combined, efficacy and toxicity became dependent on the temporal order of administration. Thus, with the doses used in this study, when RIT was administered after IT therapy, the regimen was curative. In contrast, when RIT was administered before IT therapy, the combination was highly toxic or even lethal. Both RIT and IT therapy induced pulmonary vascular leak, but with different kinetics. When RIT was given prior to IT therapy, the pulmonary vascular leak became life-threatening but not when the two agents were administered in the reverse order.
Different packing of external residues can explain differences in the thermostability of proteins from thermophilic and mesophilic organisms (2007)

Supplementary data are available at Bioinformatics online.
Differential Expression of Two O-Methyltransferases in Lignin Biosynthesis in Zinnia elegans (1995)

Caffeic acid 3-O-methyltransferase (CAOMT) and caffeoyl-coenzyme A 3-O-methyltransferase (CCoAOMT) are involved in different methylation pathways in lignin biosynthesis. We previously showed that only the CCoAOMT was markedly induced during lignification in in vitro differentiating tracheary elements (TEs) of Zinnia elegans. To further examine the expression patterns of CAOMT in lignification, we isolated a cDNA clone for Zinnia CAOMT. RNA gel blot analysis showed that the expression of the CAOMT gene did not correlate well with lignification during in vitro TE differentiation from Zinnia-isolated mesophyll cells. Tissue-print hybridization showed that, in the young internodes, the CAOMT mRNA signal was much more evident in phloem fibers than in xylem, whereas the CCoAOMT mRNA signal was predominantly present in differentiating xylem regions. In the older internode, both the CAOMT and CCoAOMT mRNAs markedly accumulated in phloem fibers and differentiating xylem regions. Immunocytochemical localization showed that the CAOMT protein staining was much more evident in phloem fibers and xylem fibers than in xylem TEs. These results indicate that the expression of these two O-methyltransferases is differentially regulated during lignification in different cell types in Zinnia. We suggest that all the intermediates in the CAOMT-mediated methylation pathway might become substrates for the CCoAOMT-mediated methylation pathway after coenzyme A ligation when these two pathways occur in the same lignifying cell types.
Long-Term Regulation of ENaC Expression in Kidney by Angiotensin II (2003)

We carried out semiquantitative immunoblotting of kidney to identify apical sodium transporter proteins whose abundances are regulated by angiotensin II. In NaCl-restricted rats (0.5 mEq Na/200 g BW/d), the type 1 angiotensin II receptor (AT1 receptor) antagonist, candesartan, (1 mg/kg of body weight per day SC for 2 days) markedly decreased the abundance of the alpha subunit of the epithelial sodium channel (ENaC). This subunit has been shown to be rate-limiting for assembly of mature ENaC complexes. In addition, systemic infusion of angiotensin II increased alphaENaC protein abundance in rat kidney cortex. The decrease in alphaENaC protein abundance in response to AT1 receptor blockade was associated with a fall in alphaENaC mRNA abundance (real-time RT-PCR), consistent with transcriptionally mediated regulation. The effect of AT1 receptor blockade on alphaENaC expression was not blocked by spironolactone, suggesting a direct role of the AT1 receptor in regulation of alphaENaC gene expression. Candesartan administration was also found to increase the abundances of the beta and gamma subunits. The increase in beta and gammaENaC protein abundance was not associated with a significant increase in the renal abundances of the corresponding mRNAs, suggesting a posttranscriptional mechanism. Immunocytochemistry confirmed the increase in beta and gammaENaC protein abundance and demonstrated candesartan-induced ENaC internalization in collecting duct cells. The results support the view that the angiotensin II receptor regulates ENaC abundance, consistent with a role for angiotensin II in regulation of collecting duct function.
Vagus Nerve Stimulation for Treatment of Partial Seizures: 1. A Controlled Study of Effect on Seizures (1994)

Vagus nerve stimulation (VNS) was shown to reduce seizure frequency in refractory epilepsy patients in two pilot studies. Based on these results, a multicenter, prospectively randomized, parallel, double-blind study of patients with refractory partial seizures was initiated. After a 12-week baseline period, identical vagus nerve stimulators were implanted and patients randomized to either a high or low 14-week VNS treatment paradigm. The primary objective was to demonstrate that high VNS (therapeutic parameters) was more effective in reducing partial seizure frequency than was low VNS (less or noneffective parameters). Patients continued receiving antiepileptic drugs (AEDs) with plasma concentrations held constant throughout the study. We report results of the first 67 patients to exit the 14-week acute phase. After 14 weeks of VNS, 31 patients receiving high VNS experienced a mean seizure frequency percentage reduction of 30.9%, which was statistically significant as compared with the mean seizure frequency percentage reduction of 11.3% in 36 patients receiving low VNS (p = 0.029, t test; p = 0.036, Wilcoxon rank-sum test). In addition to the significant intragroup p-values, mean seizure frequency percentage change reached statistical significance for high VNS (p < 0.001) but not low VNS (p = 0.072) as compared with baseline. Twelve of 31 (38.7%) patients receiving high VNS achieved at least 50% reduction in seizure frequency whereas 7 of 36 (19.4%) patients receiving low VNS experienced at least 50% reduction after 14 weeks. The implant procedure and VNS therapy were well tolerated. Our study confirmed the effectiveness of VNS as treatment for epilepsy patients with refractory partial seizures.
Modeling, Design, Fabrication, and Performance of Rectangular &#x003BC;-Coaxial Lines and Components (2006)

A miniature non-uniform copper-air rectangular coaxial line with the inner conductor supported by periodic dielectric straps is demonstrated. The overall height of the line is 310mum with the outer conductor cross-section being 250mumtimes250mum. The measured loss is 0.22dB/cm at 26GHz, while the isolation between two parallel lines with a center-to-center separation of 700mum is better than 60dB. Several quasi-planar components are designed and fabricated on the same wafer, and presented here are a branch-line hybrid and a transmission line resonator. The through and coupled port transmissions for the hybrid at 26GHz are -3.25dB and -3.35dB respectively, with phase misbalance below 0.2deg. The transmission line resonator has an unloaded Q-factor of 110 at 25GHz
Cancer-Protective Properties of High-Selenium Broccoli (2001)

Selenium (Se) from high-Se garlic reduces the incidence of chemically induced mammary tumors, and Se from high-Se broccoli reduces colon cancer. However, the ability of Se from high-Se broccoli to protect against mammary cancer has not been tested. Also, the sprout form of broccoli contains many secondary plant compounds that are known to reduce cancer risk, but the anticarcinogenic activity of broccoli sprouts has not been investigated. The present studies examined the ability of high-Se broccoli or high-Se broccoli sprouts to protect against chemically induced mammary or colon cancer. In one experiment, Sprague--Dawley rats that consumed diets containing 3.0 microg of Se/g supplied as high-Se broccoli had significantly fewer mammary tumors than rats fed 0.1 microg of Se as selenite with or without the addition of regular broccoli. In the second experiment, Fisher F-344 rats fed 2.0 microg of Se/g of diet supplied as either high-Se broccoli florets or high-Se broccoli sprouts had significantly fewer aberrant colon crypts than rats fed 0.1 or 2 microg of Se/g of diet supplied as selenite with or without the addition of low-Se broccoli. These data demonstrate that the cancer-protective effect of Se in high-Se broccoli extends to mammary cancer and the protective forms of broccoli against colon cancer include high-Se broccoli sprouts.
Combination therapy with paclitaxel and thalidomide inhibits angiogenesis and growth of human colon cancer xenograft in mice. (2003)

The results of this study underscore the therapeutic efficacy of concomitant use of paclitaxel and thalidomide in the treatment of highly vascular colorectal tumors in a xenograft model.
A phase I study of high-dose interleukin-2 in combination with interferon-alpha 2b. (1990)

Our group and others have conducted phase II trials of high-dose interleukin-2 (IL-2) or IL-2 with the adoptive transfer of in vitro activated lymphocytes in patients with advanced malignancies. Although durable complete and partial responses were seen in patients with renal cell carcinoma and metastatic melanoma, overall response rates were low and toxicity was substantial. In preclinical models, the combination of IL-2 and interferon-alpha has synergistic antitumor activity. Based on these data, and our prior experience with high-dose IL-2 (Cetus), we conducted a trial to determine the maximum tolerated dose of IL-2 (0.4, 0.8, and 1.2 mg/m2) administered together with a fixed dose of interferon-alpha 2b (3 x 10(6) u/m2) intravenously every 8 h on days 1-5 and 15-19. Patients were monitored in the intensive care unit and given pressor support for hypotension as needed. Twenty-four patients were entered (6, 10, and 8 at each IL-2 dose, respectively; 14 renal cell carcinoma, 7 melanoma, 2 colon, and 1 hepatoma). The median age was 56 years, the male to female ratio was 19:5, and performance status was 0 or 1 (Eastern Cooperative Oncology Group) in all patients. Toxicity was similar at all dose levels, but the onset was earlier in the treatment course as the dose of IL-2 was escalated in successive cohorts; therefore, more doses were withheld at the higher dose levels. The major toxicities resulting in the interruption or stopping of treatment were hypotension requiring pressors, dyspnea, and neurotoxicity. Grade 1 or 2 fever, nausea and vomiting, fatigue, and cutaneous reactions were common at all dose levels.(ABSTRACT TRUNCATED AT 250 WORDS)
Elevated Levels of Interleukin-6 in Unstable Angina (1996)

Our study demonstrates that raised levels of interleukin-6 are common in unstable angina, correlate with C-reactive protein, and are associated with prognosis, thus confirming the importance of the cytokine pathway for the production by the liver of acute-phase proteins and strengthening the importance of inflammation in this syndrome. Further studies are required to elucidate better the role of interleukins in unstable angina.
Fibrin gel as a three dimensional matrix in cardiovascular tissue engineering (2000)

Objective: In tissue engineering, three-dimensional biodegradable scaffolds are generally used as a basic structure for cell anchorage, cell proliferation and cell differentiation. The currently used biodegradable scaffolds in cardiovascular tissue engineering are potentially immunogenic, they show toxic degradation and inammatory reactions. The aim of this study is to establish a new three-dimensional cell culture system within cells achieve uniform distribution and quick tissue development and with no toxic degradation or inammatory reactions. Methods: Human aortic tissue is harvested from the ascending aorta in the operation room and worked up to pure human myobroblasts cultures. These human myobroblasts cultures are suspended in brinogen solution and seeded into 6-well culture plates for cell development for 4 weeks and supplemented with different concentrations of aprotinin. Hydroxyproline assay and histological studies were performed to evaluate the tissue development in these brin gel structures. Results: The light microscopy and the transmission electron microscopy studies for tissue development based on the three-dimensional brin gel structures showed homogenous cell growth and conuent collagen production. No toxic degradation or inammatory reactions could be detected. Furthermore, brin gel myobroblasts structures dissolved within 2 days in medium without aprotinin, but medium supplemented with higher concentration of aprotinin retained the three-dimensional structure and had a higher collagen content (P , 0:005) and a better tissue development. Conclusions: A three-dimensional brin gel structure can serve as a useful scaffold for tissue engineering with controlled degradation, excellent seeding effects and good tissue development.
Molecular characterisation, expression and localisation of human neurokinin‐3 receptor (1992)

The complete amino acid sequence of the human neurokinin-3 receptor was deduced by DNA sequence analysis of human genomic fragments. Comparison of the predicted primary structure with those for the human neurokinin receptors 1 and 2 shows a highly conserved pattern of seven hydrophobic regions with maximum divergence occurring at the amino- and carboxy-termini. The position of intron-exon junctions are identical to those in other reported neurokinin genes. Using a chimeric genomic-cDNA gene, the human NK-3 receptor was expressed in Xenopus laevis oocytes where it mediates membrane conductance changes in response to its agonist, neurokinin B. More significantly, expression of the gene in mammalian cells resulted in detection of receptor binding as well as neurokinin-stimulated calcium mobilization and arachidonic acid release, all displaying the pharmacological characteristics expected of a neurokinin-3 receptor. By using the polymerase chain reaction we have shown that mRNA for the human neurokinin-3 receptor is expressed predominantly in the central nervous system.
Central Hypothyroidism Associated with Retinoid X Receptor–Selective Ligands (1999)

Hypothyroidism may develop in patients with cutaneous T-cell lymphoma who are treated with high-dose bexarotene, most likely because the retinoid X receptor-selective ligand suppresses thyrotropin secretion.
Targeted deletions created in yeast vectors by recombinational excision (1999)

We have developed a simple method for creating defined deletions in yeast vectors by utilizing the ability of Saccharomyces cerevisiae to perform homologous recombination. Two complementary single-stranded oligonucleotides are designed so that the 5' and 3' halves of the resulting double-stranded oligonucleotide are homologous to the 5' and 3' side of a desired deletion junction, respectively. The sequence to be deleted is cleaved by restriction endonuclease digestion, followed by co-transformation of the linearized plasmid and the oligonucleotide into yeast. By homologous recombination in vivo, a subset of the plasmids will recircularize and simultaneously acquire the deletion as defined by the oligonucleotide.
A rapid colorimetric AFP monoclonal antibody test for the diagnosis of preterm rupture of the membranes. (1987)

Premature rupture of the membranes is a common and serious complication of pregnancy. Despite the prevalence and severity of sequelae, current diagnostic techniques are less than ideal. We studied 48 women with preterm rupture of the membranes with a rapid, colorimetric monoclonal alpha-fetoprotein (AFP) antibody test. Sensitivity was 98% for AFP testing compared to 77% for nitrazine and 62% for ferning. The differences in sensitivity were greater when membranes were ruptured for longer than 12 hours. In all 31 patients without rupture of the membranes, AFP testing was negative. Neither urine nor semen affected AFP testing, whereas blood did. Alpha-fetoprotein testing may be a significant addition to current methods in the diagnosis of preterm rupture of the membranes.
The use of DNA viruses as vectors for gene therapy. (1994)

The need for efficient transfer of potentially therapeutic genes to defined cell populations has stimulated the development of vectors based on viruses. To date, most effort has been spent on the RNA-containing retroviruses. These viruses, however, possess a number of disadvantages including an inability to infect nondividing cells as well as having potential for oncogenicity and insertional mutagenesis of host cell genes due to random chromosomal integration. These disadvantages have led to the development of vectors based on DNA-containing viruses such as adenovirus, herpes simplex virus and parvovirus. These viruses possess a number of attributes favourable to their use in gene therapy. Adenoviruses, for example, were first considered as potential vectors for the genetic treatment of lung conditions due to their natural affinity for respiratory epithelium. However, other features including their ability to be prepared at high titres, to direct high levels of foreign gene expression and their extrachromosomal existence has resulted in their development for the treatment of numerous other diseases. In many studies, adenovirus vectors have been shown to efficiently infect target cell populations and to express proteins at therapeutic levels in the absence of significant toxicity. The ability of herpes simplex virus to reside in neurons in a latent state that does not appear to affect normal cellular physiology has sparked interest in this virus as a potential vector in the treatment of neurological disorders. A subgroup of parvoviruses, namely the adeno-associated viruses, have a prediliction for integration at a defined chromosomal location and may represent a safer alternative to retroviruses.
Signaling Pathways of the TREM-1- and TLR4-Mediated Neutrophil Oxidative Burst (2009)

The triggering receptor expressed on myeloid cells 1 (TREM-1) is involved in the innate inflammatory response to microbial infections. Activation and expression of TREM-1 by polymorphonuclear neutrophils (PMN) occurs in concert with Toll-like receptors (TLR) such as TLR4 for bacterial lipopolysaccharide. However, it is currently unclear how this is mediated on a molecular level. Using pharmacological inhibitors and Western blot analysis we demonstrate that phosphatidyl inositide 3-kinase, phospholipase C and the mitogen-activated kinase p38MAPK are essential for the TREM-1- and TLR4-induced oxidative burst of human PMN. The activation of protein kinase B and extracellular signal-related kinase show characteristic phosphorylation patterns upon single or co-ligation indicating individual activation pathways of both receptors. Taken together, we provide new insights into the mechanisms how TREM-1 and TLR interact creating synergistic activation in PMN. These results shed a new light on our understanding of how the innate inflammatory responses are regulated and might contribute to the development of future concepts for the treatment of severe inflammatory conditions such as sepsis.
Two Distinct Pathways Support Gene Correction by Single-Stranded Donors at DNA Nicks (2016)

Nicks are the most common form of DNA damage. The mechanisms of their repair are fundamental to genomic stability and of practical importance for genome engineering. We define two pathways that support homology-directed repair by single-stranded DNA donors. One depends upon annealing-driven strand synthesis and acts at both nicks and double-strand breaks. The other depends upon annealing-driven heteroduplex correction and acts at nicks. Homology-directed repair via these pathways, as well as mutagenic end joining, are inhibited by RAD51 at nicks but largely independent of RAD51 at double-strand breaks. Guidelines for coordinated design of targets and donors for gene correction emerge from definition of these pathways. This analysis further suggests that naturally occurring nicks may have significant recombinogenic and mutagenic potential that is normally inhibited by RAD51 loading onto DNA, thereby identifying a function for RAD51 in maintenance of genomic stability.
Theory of Microphase Separation in Block Copolymers (1980)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTTheory of Microphase Separation in Block CopolymersLudwik LeiblerCite this: Macromolecules 1980, 13, 6, 1602–1617Publication Date (Print):November 1, 1980Publication History Published online1 May 2002Published inissue 1 November 1980https://pubs.acs.org/doi/10.1021/ma60078a047https://doi.org/10.1021/ma60078a047research-articleACS PublicationsRequest reuse permissionsArticle Views23266Altmetric-Citations3194LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Amino acid sequence of the variable regions of heavy chains from two idiotypically cross-reactive human IgM anti-.gamma.-globulins of the Wa group (1981)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAmino acid sequence of the variable regions of heavy chains from two idiotypically cross-reactive human IgM anti-.gamma.-globulins of the Wa groupDavid W. Andrews and J. Donald CapraCite this: Biochemistry 1981, 20, 20, 5822–5830Publication Date (Print):September 29, 1981Publication History Published online1 May 2002Published inissue 29 September 1981https://pubs.acs.org/doi/10.1021/bi00523a027https://doi.org/10.1021/bi00523a027research-articleACS PublicationsRequest reuse permissionsArticle Views20Altmetric-Citations12LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Free Omental Flap for Partial Breast Reconstruction after Breast-Conserving Surgery (2012)

Therapeutic, IV.