gebhart/patrepeval huggingface dataset:
Database of mRNA gene expression profiles of multiple human organs (2005)

Genome-wide expression profiling of normal tissue may facilitate our understanding of the etiology of diseased organs and augment the development of new targeted therapeutics. Here, we have developed a high-density gene expression database of 18,927 unique genes for 158 normal human samples from 19 different organs of 30 different individuals using DNA microarrays. We report four main findings. First, despite very diverse sample parameters (e.g., age, ethnicity, sex, and postmortem interval), the expression profiles belonging to the same organs cluster together, demonstrating internal stability of the database. Second, the gene expression profiles reflect major organ-specific functions on the molecular level, indicating consistency of our database with known biology. Third, we demonstrate that any small (i.e., n approximately 100), randomly selected subset of genes can approximately reproduce the hierarchical clustering of the full data set, suggesting that the observed differential expression of >90% of the probed genes is of biological origin. Fourth, we demonstrate a potential application of this database to cancer research by identifying 19 tumor-specific genes in neuroblastoma. The selected genes are relatively underexpressed in all of the organs examined and belong to therapeutically relevant pathways, making them potential novel diagnostic markers and targets for therapy. We expect this database will be of utility for developing rationally designed molecularly targeted therapeutics in diseases such as cancer, as well as for exploring the functions of genes.
Chronic Benign Cervical Pain Syndromes (1992)

The results of surgical intervention for chronic benign pain syndromes are generally poor. In this review, pertinent ablative and modulatory techniques are reviewed, with specific reference to their utility for benign pain syndromes. With the possible exception of facet rhizotomy, the ablative modalities have little role in the management of benign pain syndromes. The more extensive techniques of cordotomy, dorsal root entry zone lesioning, ganglionectomy, and rhizotomy, have erratic results and high rates of complication. No long-term studies exist to support the use of facet rhizotomy. It is minimally invasive, however, and has little morbidity. In patients with benign refractory posterior column pain, facet rhizotomy may be worth consideration. Modulatory devices may have a role in benign pain syndromes. While the use of indwelling epidural catheters remains investigational, dorsal column stimulation has been widely studied. In representative reports, significant pain relief has been observed in up to 60% of patients (mean follow-up of two years). In the carefully selected patient, this may represent a valuable therapeutic adjunct.
Converting Tissue-type Plasminogen Activator into a Zymogen (1996)

In striking contrast to most other members of the chymotrypsin family of serine proteases, tissue-type plasminogen activator (t-PA) is not synthesized and secreted as a true zymogen. The zymogenicity, or ratio of the catalytic efficiencies of the mature, two-chain enzyme and the single-chain precursor, is only 5-10 for t-PA. This exceptional property of t-PA, however, is not shared by urokinase (u-PA), a plasminogen activator that is very closely related to t-PA. The molecular basis of this important functional distinction between these two intimately related serine proteases has not been previously investigated. Based on observation of the recently described structures of the protease domains of two-chain t-PA and u-PA, and molecular modeling of the corresponding single-chain enzymes, we propose that the presence or absence of an acidic residue at position 144 (chymotrypsin numbering system) is the primary determinant of the distinct zymogenicities of the two enzymes. Consistent with this hypothesis, mutation of histidine 144 of t-PA to an acidic residue, as in u-PA, selectively suppressed the activity of single-chain t-PA and thereby significantly enhanced the enzyme's zymogenicity. A variant of t-PA containing an aspartate residue at position 144, for example, exhibited a zymogenicity of 150, compared to a value of 9 for wild type t-PA and 250 for u-PA.
BIACORE: an affinity biosensor system for characterization of biomolecular interactions (1999)

Conference Article| February 01 1999 BIACORE: an affinity biosensor system for characterization of biomolecular interactions M. Malmqvist M. Malmqvist 1Biacore AB, Rapsgatan 7, S-75450 Uppsala, Sweden Search for other works by this author on: This Site PubMed Google Scholar Biochem Soc Trans (1999) 27 (2): 335–340. https://doi.org/10.1042/bst0270335 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share MailTo Twitter LinkedIn Cite Icon Cite Get Permissions Citation M. Malmqvist; BIACORE: an affinity biosensor system for characterization of biomolecular interactions. Biochem Soc Trans 1 February 1999; 27 (2): 335–340. doi: https://doi.org/10.1042/bst0270335 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsBiochemical Society Transactions Search Advanced Search Keywords: BIA, biomolecular interaction analysis This content is only available as a PDF. © 1999 Biochemical Society1999 Article PDF first page preview Close Modal You do not currently have access to this content.
Characterization and expression of a cDNA encoding the human androgen receptor. (1989)

We report the isolation of a cDNA that encodes the complete human androgen receptor. The cDNA predicts a protein of 917 amino acids with a molecular weight of 98,918. Introduction of the cDNA into heterologous mammalian cells caused expression of high levels of a protein that binds dihydrotestosterone with the affinity, specificity, and sedimentation properties characteristic of the native human androgen receptor. Comparisons with the amino acid sequence of previously cloned steroid hormone receptors revealed a high degree of sequence conservation with the progesterone, glucocorticoid, and mineralocorticoid receptors in the putative hormone and DNA-binding domain regions.
Is follicular fluid steroid content representative of follicular steroid secretion? (1989)

Nine oestrogen-active (E-A) and seven oestrogen-inactive (E-I) bovine follicles were superfused for 10 h. Levels of oestradiol (E2), testosterone (T) and progesterone (P4) were measured in superfusate and follicular fluid. No correlation between intrafollicular steroid concentrations of E2, T and P4 and the amount of these steroids detected in the superfusate was found in oestrogen-active follicles, i.e. follicular fluid E2, T or P4 levels did not allow for any prediction of superfusate E2, T and P4 concentrations and vice versa. In contrast, E-I follicles showed a close correlation between intrafollicular and superfusate T and P, but not E2 levels. It is speculated that an alteration in intrafollicular regulatory mechanisms might explain the different findings for these two classes of follicles.
Alginate fibres: an overview of the production processes and applications in wound management (2007)

Abstract Alginate fibers are made from sodium alginate, which is a natural polymer extracted from brown seaweeds. Over the last two decades, alginate fibers have become well established in the wound management industry where their ion‐exchange and gel‐forming abilities are particularly useful for the treatment of exuding wounds. In order to deliver functional performances for advanced wound management products, many improvements have been made in recent years to enhance the absorption and gel‐forming capabilities and the anti‐microbial properties of alginate fibers. In addition, attempts have been made to use alginate fibers as a carrier to deliver zinc, silver and other active ingredients that are beneficial to wound healing. This paper reviews the development in the production of various fibers from alginate, and summarizes the production processes for calcium alginate, calcium/sodium alginate, sodium alginate, zinc alginate, silver alginate and other types of alginate fibers containing novel functional ingredients. Copyright © 2007 Society of Chemical Industry
Average velocity of ultrasound in the human female breast (1973)

A technique for measuring the in vivo average velocity of ultrasound in the human female breast was developed and applied to determine the range of such values in the breast of normal subjects in the approximate age ranges 20 to 80 years and in subjects with selected breast pathologies. Reasonable correlation of the velocity values with breast tissue type, as determined by x ray (mammography), was obtained, indicating that ultrasonic velocity data provide useful information on the main tissue constituents in the breast and that this technique should allow safe, long-term study of changes that may occur in the composition of such tissues.
Generation, Characterization, and in Vivo Studies of Humanized Anticarcinoma Antibody CC49 (1995)

Monoclonal antibody (MAb) CC49 reacts with tumor-associated glycoprotein (TAG)-72, a human pancarcinoma antigen. In clinical trials, radiolabeled CC49 has shown excellent tumor localization; however, many of the patients receiving MAb CC49 develop a human antimouse antibody response. In an attempt to prevent this antiimmunoglobulin response, we have developed a humanized CC49 (HuCC49) by grafting the MAb CC49 hypervariable regions onto the variable light (VL) and variable heavy (VH) frameworks of the human MAbs LEN and 21/28' CL, respectively, while retaining those murine framework residues that may be required for the integrity of the antigen combining-site structure. The HuCC49 MAb was compared with native murine CC49 (nCC49) and chimeric CC49 (cCC49), using a variety of assays. SDS-PAGE analysis under nonreducing conditions showed that the HuCC49 MAb has virtually identical mobility to that of cCC49. Under reducing conditions, the HuCC49 yielded two bands of approximately 25-28 and approximately 50-55 kDa, characteristic of heavy and light immunoglobulin chains. In competition radioimmunoassays, HuCC49 completely inhibited the binding of 125I-labeled nCC49 to TAG-72, although 23- to 30-fold more HuCC49 was required to achieve a level of competition similar to those of cCC49 and nCC49. The relative affinity of HuCC49 was 2- to 3-fold less than those of the cCC49 and nCC49 MAbs, respectively. The plasma clearance in mice of HuCC49 was virtually identical to that of cCC49. Biodistribution studies demonstrated equivalent tumor-targeting of HuCC49 and cCC49 to human colon carcinoma xenografts. These studies thus suggest that HuCC49 and genetically modified molecules, such as sFv and domain-deleted immunoglobulins developed by using the HuCC49 variable region as a cassette, may be potentially useful in both diagnostic and therapeutic clinical trials in patients with TAG-72-positive tumors.
Interferon-alpha-2b enhances the natural killer activity of patients with transitional cell carcinoma of the bladder (1993)

Recombinant IFN-alpha can enhance the nonmajor histocompatibility-restricted cytotoxic activity of PBMNC from patients with TCC of the bladder.
Ribozyme Knockdown of the γ-Subunit of Rod cGMP Phosphodiesterase Alters the ERG and Retinal Morphology in Wild-Type Mice (2005)

Ribozyme-mediated somatic knockdown of wild-type PDEgamma mRNA in vivo can efficiently reduce the target RNA leading to a loss in rod photoreceptors and in rod-mediated ERG amplitudes, thus generating an animal model of retinal degeneration resembling human RP in an essentially normal adult retina. This vector ribozyme technique should be applicable to other genes associated with RP and perhaps also to mRNAs of phototransduction genes not yet associated with RP. Application of this approach may be age and species independent.
Intramyocardial Delivery of Basic Fibroblast Growth Factor-Impregnated Gelatin Hydrogel Microspheres Enhances Collateral Circulation to Infarcted Canine Myocardium. (2001)

The present study examined whether basic fibroblast growth factor (bFGF)-impregnated acidic gelatin hydrogel microspheres (AGHM) would enhance collateral development to the infarct area in dogs with coronary occlusion. Studies were conducted in 28 dogs with a 2-week occlusion of the proximal left anterior descending coronary artery (LAD). The dogs were divided into 3 groups according to treatment: Group A treated with bFGF-impregnated AGHM in the infarct area; Group B with free-form bFGF; Group C with AGHM alone. Coronary angiography (n=15; Group A, 7 dogs; Group B, 5 dogs; Group C, 3 dogs) and a regional myocardial blood flow study (n=13; Group A, 6 dogs; Group B, 4 dogs; Group C, 3 dogs) were repeated at a 2-week interval. Coronary angiography revealed that in Group A, antegrade flow in the LAD distal to the occlusion, which was assessed by Thrombolysis in Myocardial Infarction (TIMI) grade, was significantly increased after treatment. In contrast, in Groups B and C, the treatment did not change the flow grade in the LAD. In Group A, the regional myocardial blood flow in the collateral dependent area was significantly increased after treatment, and the regional myocardial blood flow reserve after adenosine injection was also significantly increased. These measurements remained after treatment in Groups B and C. The immunohistochemical study with factor VIII-related antigen revealed an increase of vascular density in the ischemic region in Group A. Intramyocardial delivery of bFGF-impregnated AGHM, but not free-form bFGF, improves the collateral circulation to the infarct area of a coronary occlusion in dogs.
Thirteen Years of Building Constraint-Based In Silico Models of Escherichia coli (2003)

The recent flood of genomic ([13][1]), transcriptomic ([29][2]), and other high-throughput data ([21][3], [33][4], [45][5]) makes the need to interpret this information in a systemic fashion increasingly pressing. The construction of in silico models represents a way to interpret these data and
pH-sensitive immunoliposomes as an efficient and target-specific carrier for antitumor drugs. (1986)

pH-sensitive immunoliposomes composed of dioleoylphosphatidyl-ethanolamine and oleic acid (8:2) significantly enhanced the cytotoxic effect of the entrapped drug 1-beta-D-arabinofuranosylcytosine (ara-C) to target L-929 cells, as compared to free drug, drug encapsulated in antibody-free liposomes, or in pH-insensitive immunoliposomes. These pH-sensitive immunoliposomes were ineffective against nontarget A-31 cells. The enhanced cytotoxic effect could be blocked by excess free antibody or excess drug-free immunoliposomes. Pretreatment of target cells with the weak bases chloroquine or NH4Cl, which raise the internal pH of cellular acidic organelles such as endosomes and lysosomes, inhibited the cell killing activity of ara-C encapsulated in the pH-sensitive immunoliposomes. Since it is known that ara-C is rapidly inactivated in the lysosomes, our results suggest that the release of ara-C from the pH-sensitive immunoliposomes occurs in a prelysosomal compartment, i.e., the endosome. Parallel experiments using methotrexate as a cytotoxic drug confirm the enhanced ability of the pH-sensitive liposomes for cytoplasmic drug delivery over that of free drug. These results indicate that pH-sensitive immunoliposomes can be used as an efficient and target-specific carrier for antitumor drugs.
Characterization of De Novo Synthesized GPCRs Supported in Nanolipoprotein Discs (2012)

The protein family known as G-protein coupled receptors (GPCRs) comprises an important class of membrane-associated proteins, which remains a difficult family of proteins to characterize because their function requires a native-like lipid membrane environment. This paper focuses on applying a single step method leading to the formation of nanolipoprotein particles (NLPs) capable of solubilizing functional GPCRs for biophysical characterization. NLPs were used to demonstrate increased solubility for multiple GPCRs such as the Neurokinin 1 Receptor (NK1R), the Adrenergic Receptor â2 (ADRB2) and the Dopamine Receptor D1 (DRD1). All three GPCRs showed affinity for their specific ligands using a simple dot blot assay. The NK1R was characterized in greater detail to demonstrate correct folding of the ligand pocket with nanomolar specificity. Electron paramagnetic resonance (EPR) spectroscopy validated the correct folding of the NK1R binding pocket for Substance P (SP). Fluorescence correlation spectroscopy (FCS) was used to identify SP-bound NK1R-containing NLPs and measure their dissociation rate in an aqueous environment. The dissociation constant was found to be 83 nM and was consistent with dot blot assays. This study represents a unique combinational approach involving the single step de novo production of a functional GPCR combined with biophysical techniques to demonstrate receptor association with the NLPs and binding affinity to specific ligands. Such a combined approach provides a novel path forward to screen and characterize GPCRs for drug discovery as well as structural studies outside of the complex cellular environment.
MHC-Antigens: Constituents of the Envelopes of Human and Simian Immunodeficiency (1987)

Immunoelectron microscopy was applied to study the antigenic make-up of human and simian immunodeficiency viruses (HIV, SIV) grown in cells expressing either MHC class I (Molt-3) or MHC class I and II (H9) antigens. A variety of antibodies directed against the surface glycoprotein gp120 of HIV and against MHC class I and II antigens were employed. Consistent with earlier observations on the loss of HIV envelope components, gp120 was only weakly demonstrable on the mature virion. MHC class I determinants were present regularly in small amounts on HIV and SIV. Class II antigens, e.g. HLA-DR were found in high density on HIV and SIV grown in H9 cells, but were absent, as expected, on virus grown in Molt-3 cells. These cellular surface antigens are constituents of the virion. The presence of MHC class II antigens in virus preparations used for diagnostic purposes might explain some of the false positive results in HIV serology. Possible biological implications of these virus associated cellular antigens for the pathogenicity of HIV are discussed.
Iterative Saturation Mutagenesis on the Basis of B Factors as a Strategy for Increasing Protein Thermostability (2006)

Efficiency counts: A new method of directed evolution for increasing the thermostability of proteins saves time and effort. In an illustrative study, iterative cycles of saturation mutagenesis were performed at those sites in a lipase that display high B factors.
Use of the alr Gene as a Food-Grade Selection Marker in Lactic Acid Bacteria (2002)

Both Lactococcus lactis and Lactobacillus plantarum contain a single alr gene, encoding an alanine racemase (EC 5.1.1.1), which catalyzes the interconversion of D-alanine and L-alanine. The alr genes of these lactic acid bacteria were investigated for their application as food-grade selection markers in a heterologous complementation approach. Since isogenic mutants of both species carrying an alr deletion (Deltaalr) showed auxotrophy for D-alanine, plasmids carrying a heterologous alr were constructed and could be selected, since they complemented D-alanine auxotrophy in the L. plantarum Deltaalr and L. lactis Deltaalr strains. Selection was found to be highly stringent, and plasmids were stably maintained over 200 generations of culturing. Moreover, the plasmids carrying the heterologous alr genes could be stably maintained in wild-type strains of L. plantarum and L. lactis by selection for resistance to D-cycloserine, a competitive inhibitor of Alr (600 and 200 micro g/ml, respectively). In addition, a plasmid carrying the L. plantarum alr gene under control of the regulated nisA promoter was constructed to demonstrate that D-cycloserine resistance of L. lactis is linearly correlated to the alr expression level. Finally, the L. lactis alr gene controlled by the nisA promoter, together with the nisin-regulatory genes nisRK, were integrated into the chromosome of L. plantarum Deltaalr. The resulting strain could grow in the absence of D-alanine only when expression of the alr gene was induced with nisin.
Immunotherapy of Metastatic Malignant Melanoma by a Vaccine Consisting of Autologous Interleukin 2-Transfected Cancer Cells: Outcome of a Phase I Study (1999)

We performed a phase I trial to evaluate the safety and tolerability of repeated skin injections of IL-2-transfected autologous melanoma cells into patients with advanced disease. Cell suspensions, propagated from excised metastases, were IL-2 gene transfected by adenovirus-enhanced transferrinfection and X-irradiated prior to injection. Vaccine production was successful in 54% of the patients. Fifteen patients (37%) received two to eight skin vaccinations of either 3 x 10(6) (intradermal) or 1 x 10(7) (half intradermal, half subcutaneous) transfected melanoma cells per vaccination (secreting 140-17,060 biological response modifier program units of IL-2/10(6) cells/24 hr). Analyses of safety and efficacy were carried out in 15 and 14 patients, respectively. Overall, the vaccine was well tolerated. All patients displayed modest local reactions (erythema, induration, and pruritus) and some experienced flu-like symptoms. Apart from newly appearing (4 of 14) and increasing (5 of 14) anti-adenovirus and newly detectable anti-nuclear antibody titers (1 of 15), recipients developed de novo or exhibited increased melanoma cell-specific delayed-type hypersensitivity (DTH) reactions (8 of 15) and vitiligo (3 of 15) and showed signs of tumor regression (3 of 15). This supports the idea of a vaccine-induced or -amplified anti-cancer immune response. None of the patients exhibited complete or partial regressions, but five of them experienced periods of disease stabilization. Three of these individuals received more than the four planned vaccinations and their mean survival time was 15.7 +/- 3.5 months as compared to 7.8 +/- 4.6 months for the entire patient cohort. These data indicate that IL-2-producing, autologous cancer cells can be safely administered to stage IV melanoma patients and could conceivably be of benefit to patients with less advanced disease.
Disabled infectious single cycle-herpes simplex virus (DISC-HSV) as a vector for immunogene therapy of cancer. (2002)

Disabled infectious single cycle-herpes simplex viruses (DISC-HSV) have been shown to be safe for use in humans and may be considered efficacious as vectors for immunogene therapy in cancer. Preclinical studies show that DISC-HSV is an efficient delivery system for cytokine genes and antigens. DISC-HSV infects a high proportion of cells, resulting in rapid gene expression for at least 72 h. The DISC-HSV-mGM-CSF vector, when inoculated into tumors, induces tumor regression in a high percentage of animals, concomitant with establishing a cytotoxic T-cell response, which is MHC class I restricted and directed against peptides of known tumor antigens. The inherent properties of DISC-HSV makes it a suitable vector for consideration in human immunogene therapy trials.