gebhart/patrepeval huggingface dataset:
MHC class I chain-related protein A antibodies and shedding are associated with the progression of multiple myeloma (2008)

Monoclonal gammopathy of undetermined significance (MGUS) is a common disorder of aging and a precursor lesion to full-blown multiple myeloma (MM). The mechanisms underlying the progression from MGUS to MM are incompletely understood but include the suppression of innate and adaptive antitumor immunity. Here, we demonstrate that NKG2D, an activating receptor on natural killer (NK) cells, CD8(+) T lymphocytes, and MHC class I chain-related protein A (MICA), an NKG2D ligand induced in malignant plasma cells through DNA damage, contribute to the pathogenesis of MGUS and MM. MICA expression is increased on plasma cells from MGUS patients compared with normal donors, whereas MM patients display intermediate MICA levels and a high expression of ERp5, a protein disulfide isomerase linked to MICA shedding (sMICA). MM, but not MGUS, patients harbor circulating sMICA, which triggers the down-regulation of NKG2D and impaired lymphocyte cytotoxicity. In contrast, MGUS, but not MM, patients generate high-titer anti-MICA antibodies that antagonize the suppressive effects of sMICA and stimulate dendritic cell cross-presentation of malignant plasma cells. Bortezomib, a proteasome inhibitor with anti-MM clinical efficacy, activates the DNA damage response to augment MICA expression in some MM cells, thereby enhancing their opsonization by anti-MICA antibodies. Together, these findings reveal that the alterations in the NKG2D pathway are associated with the progression from MGUS to MM and raise the possibility that anti-MICA monoclonal antibodies might prove therapeutic for these disorders.
Poxviruses as vectors for cancer immunotherapy. (2003)

Despite advances in chemotherapy and surgical techniques, patients with cancer often develop local recurrence or metastatic spread. Recent advances in molecular biology, coupled with new insights in tumor immunology, have led to the design of novel antitumor vaccines. Poxviruses are a large family of DNA viruses that provide an effective and safe vector system for vaccine development. The poxvirus strategy has been successfully documented in animal models, and has been used to express both tumor-associated antigens and immune stimulatory molecules. In this review, we focus on recent advances in the use of poxvirus-based vaccines as cancer therapeutic agents.
Yeast DNA diesterase for 3′-fragments of deoxyribose: purification and physical properties of a repair enzyme for oxidative DNA damage. (1988)

The DNA strand breaks resulting from exposure to the free radicals generated by ionizing radiation or oxidizing agents are refractory to DNA repair synthesis because of deoxyribose fragments that block their 3' termini. The restoration of normal 3'-OH nucleotide primers is the essential first step in the excision repair of these radical-induced strand breaks. We have used a synthetic DNA substrate containing 3'-phosphoglycolaldehyde esters to identify and purify to physical homogeneity the major yeast diesterase that removes such nucleotide fragments. Yeast 3'-phosphoglycolaldehyde diesterase had Mr = 40,500 upon sodium dodecyl sulfate-polyacrylamide gel electrophoresis. A similar molecular weight estimate from gel filtration indicated that the active species is a nearly globular monomer. Purification of the enzyme removed a tightly bound metal, but the activity of the purified enzyme could be restored by the addition of Co2+, Mn2+, Ni2+, or Zn2+, with Co2+ the most effective cofactor. Even 3 microM Co2+ stimulated near-maximal activity, and this metal also conferred significant thermal stability on the purified protein. This is a novel enzyme, whose N-terminal amino acid sequence does not show any significant similarity to published sequences, and which is not the product of any gene in the RAD52 epistasis group.
Isolation and identification of clozapine metabolites in patient urine. (2001)

Biotransformation products of the atypical neuroleptic clozapine were isolated from urine samples of three schizophrenic patients by solid-phase extraction, liquid-liquid extraction for the separation of unpolar and polar metabolites, and thin-layer chromatography followed by final purification by high-performance liquid chromatography. Their structures were elucidated by mass spectrometry and (1)H NMR spectroscopy and in some cases by enzymatic deconjugation. Besides the known metabolites desmethylclozapine, clozapine N-oxide, 8-deschloro-8-hydroxyclozapine, and 8-deschloro-8-hydroxydesmethylclozapine, the unpolar fraction contained 7-hydroxyclozapine and a compound in which the piperazine ring of clozapine was partially degraded to an ethylenediamine derivative. Novel metabolites identified in the polar fraction were the sulfate and glucuronide conjugates of 7-hydroxyclozapine N-oxide, 8-deschloro-8-hydroxyclozapine-O-glucuronide, and the O-glucuronide of N-hydroxydesmethylclozapine; further conjugates were tentatively identified as 9-hydroxydesmethylclozapine-O-sulfate and 6-hydroxyclozapine-O-sulfate. In addition, the previously described conjugates 7-hydroxydesmethylclozapine-O-sulfate, 7-hydroxyclozapine-O-glucuronide and -O-sulfate, 8-deschloro-8-hydroxydesmethylclozapine-O-glucuronide, and the quaternary ammonium glucuronide of clozapine were detected.
Cytokines in Alzheimer's Disease and Vascular Dementia (2008)

The levels of interleukin 1beta, interleukin 6, and interleukin 10 were elevated in the serum of patients with dementia. No statistically significant correlation was recorded in the interleukin levels among patients with Alzheimer's disease and vascular dementia. Also, no significant correlation was observed in the interleukin levels in the serum and the severity of dementia. However, a significant correlation was found between IL-6 and tumor necrosis factor-alpha (TNF-alpha) levels and age. The levels of IL-1beta and IL-6 were positively correlated with hypertension, and IL-2 levels were negatively correlated. No correlation was found between depressive symptoms and levels of cytokines in the serum.
Preparation and characterization of LiFePO<inf>4</inf>/Ag nanocomposites for application in Li-ion batteries (2011)

In this study, LiFePO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">4</sub> materials were prepared by using solid-state method. The prepared LiFePO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">4</sub> was further mixed with aqueous AgNO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3</sub> and glucose solution to obtain the LiFePO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">4</sub> /Ag nanocomposite materials through the reduction reaction. The results show that the prepared LiFePO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">4</sub> /Ag materials have an orthorhombic olivine-type structure and a small amount of impurity Li <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3</sub> PO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">4</sub> or Li <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3</sub> Fe <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> (PO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">4</sub> ) <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> was present in the product. Raman and TEM analysis shows that the addition of silver can induce more conductive grapheme and reduce the primary particle size of LiFePO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">4</sub> .
Novel Subtype of Type IIs Restriction Enzymes (2000)

BfiI recognizes the non-palindromic nucleotide sequence 5-ACTGGG-3 and cleaves complementary DNA strands 5/4 nucleotides downstream of the recognition sequence. The genes coding for the BfiI restriction-modification (R-M) system were cloned/sequenced and biochemical characterization of BfiI restriction enzyme was performed. The BfiI R-M system contained three proteins: two N4-methylcytosine methyltransferases and a restriction enzyme. Sequencing of bisulfite-treated methylated DNA indicated that each methyltransferase modifies cytosines on opposite strands of the recognition sequence. The N-terminal part of the BfiI restriction enzyme amino acid sequence revealed intriguing similarities to an EDTA-resistant nuclease of Salmonella typhimurium. Biochemical analyses demonstrated that BfiI, like the nuclease of S. typhimurium, cleaves DNA in the absence of Mg 2 ions and hydrolyzes an artificial substrate bis(p-nitrophenyl) phosphate. However, unlike the nonspecific S. typhimurium nuclease, BfiI restriction enzyme cleaves DNA specifically. We propose that the DNA-binding specificity of BfiI stems from the C-terminal part of the protein. The catalytic N-terminal subdomain of BfiI radically differs from that of type II restriction enzymes and is presumably similar to the EDTA-resistant nonspecific nuclease of S. typhimurium; therefore, BfiI did not require metal ions for catalysis. We suggest that BfiI represents a novel subclass of type IIs restriction enzymes that differs from the archetypal FokI endonuclease by the fold of its cleavage domain, the domain location, and reaction mechanism.
Affinity purification of human tissue factor: interaction of factor VII and tissue factor in detergent micelles. (1986)

Tissue factor, a known initiator of blood coagulation, was found to be active in Triton X-100. A system consisting of tissue factor, factor VIIa, calcium ions, and coagulation factor X generated activated factor X at an appreciable rate. Based on this observation, we coupled human and bovine factor VII to a solid support. Each column bound tissue factor, solubilized in Triton X-100, in a species-specific manner. These interactions required calcium ions; when the columns were washed with detergent containing calcium ions, no tissue factor was eluted. When calcium ions were omitted from the eluant, tissue factor emerged as a sharp peak. Human tissue factor was extracted from an acetone brain powder into 2% Triton X-100. This extract, made 10 mM in CaCl2, was passed over a factor VII column. Human factor VII (1.2 mg) was coupled to 30 ml of Affi-Gel 15. This column bound approximately equal to 15 micrograms of human tissue factor. The eluted material was approximately equal to 25% pure. Final purification was achieved by gel filtration after chymotryptic digestion of contaminants. The tissue factor activity was stable to this treatment. The molecular weight determined by sodium dodecyl sulfate/PAGE (approximately equal to 46,000) was also unchanged by chymotrypsin. The final material was a single band on PAGE, demonstrated similar resistance to tryptic and chymotryptic digestion as bovine tissue factor, and had approximately the same specific coagulant activity as the previously purified bovine material. Tissue factor was also purified from human placenta, yielding a similar protein. A partial 28-residue sequence of the latter has been obtained.
Promoter hypermethylation-mediated inactivation of multiple Slit-Robo pathway genes in cervical cancer progression (2006)

Taken together, these findings suggest that epigenetic alterations of Slit-Robo pathway genes (i) play a role in CC development, (ii) further delineation of molecular basis of promoter methylation-mediated gene regulation provides a potential basis for epigenetic-based therapy in advanced stage CC, and (iii) form epigenetic signatures to identify precancerous lesions at risk to progression.
A Convenient Source of Cfu‐S Inhibitors: the Fetal Calf Liver* (1984)

The presence of a bone-marrow stem-cell inhibitor able to prevent CFU-s entry into DNA synthesis after cytosine arabinoside (Ara-C) treatment has been detected in 7-month-old fetal calf liver. The inhibitory fraction was obtained through ultrafiltration of a delipidated tissue extract powder and purified by BioGel-P-2 chromatography. The elution pattern on Sephadex G10 is similar to that of the bone-marrow inhibitory extract previously obtained from fetal calf bone marrow. It corresponds to a low-molecular-weight molecule (MW less than 2000), devoid of species specificity and having no inhibitory effect on GM-CFC proliferation.
Synthesis of 4'-substituted nucleosides and their biological evaluation (1999)

4'-C-Ethynyl-beta-D-arabino- and 4'-C-ethynyl-beta-D-2'-deoxy-ribo-pentofuranosyl pyrimidines were synthesized. Most of these 4'-ethynyl nucleosides showed interesting biological activities.
Demagnetizing Factors of the General Ellipsoid (1945)

Charts and tables of the demagnetizing factors of prolate and oblate spheroids are readily available; however, demagnetizing factors of ellipsoids of three different axes are incompletely tabulated and laborious to calculate. This article presents charts and tables which make possible easy determination of the demagnetizing factor for any principal axis of an ellipsoid of any shape. Formulas for the demagnetizing factors of the general ellipsoid are included together with supplementary formulas which cover a large number of special cases.
Synthesis of 3-(triethylstannyl)propanoic acid: An organotin mass label for DNA (1993)

The synthesis of 3-(triethylstannyl)propanoic acid (TESPA), an organometallic reporter group that enables the mass labeling of oligonucleotides with stable isotopes of tin, is described. Synthesized from commercially available isotopically-enriched SnO2 in a five step process, the NHS ester of TESPA is produced with an overall yield of 40%. This simplification of the standard synthetic scheme, with two less synthetic steps and a coincident 60% yield increase, is accomplished through the use of the reagent N-(acryloxy)succinimide and the free radical initiator AMPN. The conditions for the attachment of the reporter group to priming oligonucleotides and the subsequent HPLC isolation of the labeled primers are also detailed.
Sjögren's syndrome. Proposed criteria for classification (1986)

The term "Sjögren's syndrome" (SS) is frequently used to describe the occurrence of keratoconjunctivis sicca and xerostomia in association with an autoimmune disorder. However, well-defined criteria for the classification of SS have not been established, and this diagnosis is being applied to a wide spectrum of conditions, ranging from clear "autoimmune" disease in some patients, to sicca complaints without evidence of a systemic immune process in elderly patients. Here, we review the clinical and laboratory features of patients referred for evaluation of sicca symptoms. In particular, we emphasize the need for care in choosing the site for minor salivary gland biopsy, and we describe the histologic features that aid in the evaluation of these biopsy specimens. In an attempt to identify a population of patients whose conditions might have a common etiopathogenesis and, thus, a common treatment program, we propose the following criteria for a diagnosis of SS: 1) objective evidence of keratoconjunctivis sicca, as documented by rose bengal or fluorescein dye staining; 2) objective evidence of diminished salivary gland flow; 3) minor salivary gland biopsy, obtained through normal mucosa, with the specimen containing at least 4 evaluable salivary gland lobules, and having an average of at least 2 foci/4 mm2; 4) evidence of a systemic autoimmune process, as manifested by the presence of autoantibodies, such as rheumatoid factor and/or antinuclear antibody. The diagnosis of "definite SS" would be made when all 4 criteria are met; the diagnosis of "possible SS" would be made when 3 criteria are present. Specific exclusions for this diagnosis are preexisting lymphoma, graft-versus-host disease, sarcoidosis, and acquired immunodeficiency disease.(ABSTRACT TRUNCATED AT 250 WORDS)
Phenotypic and molecular characterization of the claudin-low intrinsic subtype of breast cancer (2010)

These results should help to improve our understanding of the biologic heterogeneity of breast cancer and provide tools for the further evaluation of the unique biology of claudin-low tumors and cell lines.
Separation of Grape and Wine Proanthocyanidins According to Their Degree of Polymerization (1998)

A method was developed for the fractionation of grape and wine proanthocyanidins according to their degree of polymerization. The grape and wine proanthocyanidins were fractionated on C18 Sep-Pak cartridges into three fractions by different organic solvents. The combination of TLC, analytic HPLC, and degradation with toluene-α-thiol confirmed that these three fractions contained, respectively, monomeric flavan-3-ols (catechins), oligomeric proanthocyanidins, and polymeric proanthocyanidins. The mean degrees of polymerization for oligomeric and polymeric proanthocyanidins in red wine were, respectively, 4.8 and 22.1, and those in the seed extract, 9.8 and 31.5. The method proposed is very interesting for the study of grape and wine proanthocyanidins according to their degree of polymerization, and a further quantification is also possible. Keywords: Grape; wine; catechins; proanthocyanidins; C18 Sep-Pak cartridge; fractionation
Protection from Natural Killer Cell-Mediated Lysis by HLA-G Expression on Target Cells (1996)

The outermost layer of the human placenta is devoid of classical class I human leukocyte antigens (HLA-A, HLA-B, and HLA-C) and class II proteins (HLA-DR, HLA-DQ, and HLA-DP). Although this prevents recognition by maternal T lymphocytes, the lack of class I molecules leaves these cells susceptible to attack by natural killer (NK) cells. However, trophoblast cells directly in contact with the maternal tissues express the class I molecule HLA-G, which may be involved in protecting the trophoblast from recognition by NK cells. Here evidence is provided that expression of HLA-G is sufficient to protect otherwise susceptible target cells from lysis by activated NK1 and NK2 cell lines and clones that are specific for distinct groups of HLA-C alleles. The receptors on NK cells that recognize HLA-G are also identified.
Antitumor Therapy Mediated by 5-Fluorocytosine and a Recombinant Fusion Protein Containing TSG-6 Hyaluronan Binding Domain and Yeast Cytosine Deaminase (2009)

Matrix attachment therapy (MAT) is an enzyme prodrug strategy that targets hyaluronan in the tumor extracellular matrix to deliver a prodrug converting enzyme near the tumor cells. A recombinant fusion protein containing the hyaluronan binding domain of TSG-6 (Link) and yeast cytosine deaminase (CD) with an N-terminal His(x6) tag was constructed to test MAT on the C26 colon adenocarcinoma in Balb/c mice that were given 5-fluorocytosine (5-FC) in the drinking water. LinkCD was expressed in Escherichia coli and purified by metal-chelation affinity chromatography. The purified LinkCD fusion protein exhibits a K(m) of 0.33 mM and V(max) of 15 microM/min/microg for the conversion of 5-FC to 5-fluorouracil (5-FU). The duration of the enzyme activity for LinkCD was longer than that of CD enzyme at 37 degrees C: the fusion protein retained 20% of its initial enzyme activity after 24 h, and 12% after 48 h. The LinkCD fusion protein can bind to a hyaluronan oligomer (12-mer) at a K(D) of 55 microM at pH 7.4 and a K(D) of 5.32 microM at pH 6.0 measured using surface plasmon resonance (SPR). To evaluate the antitumor effect of LinkCD/5-FC combination therapy in vivo, mice received intratumoral injections of LinkCD on days 11 and 14 after C26 tumor implantation and the drinking water containing 10 mg/mL of 5-FC starting on day 11. To examine if the Link domain by itself was able to reduce tumor growth, we included treatment groups that received LinkCD without 5-FC and Link-mtCD (a functional mutant that lacks cytosine deaminase activity) with 5-FC. Animals that received LinkCD/5-FC treatment showed significant tumor size reduction and increased survival compared to the CD/5-FC treatment group. Treatment groups that were unable to produce 5-FU had no effect on the tumor growth despite receiving the fusion protein that contained the Link domain. The results indicate that a treatment regime consisting of a fusion protein containing the Link domain, the active CD enzyme, and the prodrug 5-FC is sufficient to produce an antitumor effect. Thus, the LinkCD fusion protein is an alternative to antibody-directed prodrug enzyme therapy (ADEPT) approaches for cancer treatment.
Pro-gastrin-releasing peptide(31-98) is a specific tumor marker in patients with small cell lung carcinoma. (1994)

Gastrin-releasing peptide (GRP) is a specific and an actively secreted product of small cell lung carcinoma (SCLC) cells. Based on this observation, we attempted to develop a new approach for early detection of SCLC and for monitoring therapeutic response in SCLC patients. Recombinant human ProGRP(31-98), a region common to three types of human ProGRP molecules, was synthesized, and a convenient radioimmunoassay system was developed; in this assay, the minimum detectable amount in serum was 10 pM when 0.1 ml of unextracted serum was used. Serum levels of immunoreactive ProGRP(31-98) were measured in 247 normal subjects, 180 patients with nonmalignant pulmonary diseases, 231 patients with non-SCLC, and 140 patients with SCLC. The percentages of subjects with the level greater than 10 pM in normal subjects and patients with nonmalignant pulmonary diseases and with non-SCLC were 1.2, 2.2, and 3.0%, respectively. In contrast, 76% of patients with SCLC had elevated levels; the positive rates in SCLC patients with limited and extensive diseases were 73 and 79%, respectively, indicating that the serum Pro-GRP(31-98) level could serve as a reliable tumor marker in SCLC patients, even at a relatively early stage of this disease. Moreover, changes in the serum ProGRP(31-98) showed excellent correlation with the therapeutic responses in SCLC patients. These results indicate that the determination of serum ProGRP(31-98) levels plays an important role in the diagnosis and treatment of SCLC patients.
Incorporation of reporter molecule-labeled nucleotides by DNA polymerases. II. High-density labeling of natural DNA (2003)

The modification of nucleic acids using nucleotides linked to detectable reporter or functional groups is an important experimental tool in modern molecular biology. This enhances DNA or RNA detection as well as expanding the catalytic repertoire of nucleic acids. Here we present the evaluation of a broad range of modified deoxyribonucleoside 5'-triphosphates (dNTPs) covering all four naturally occurring nucleobases for potential use in DNA modification. A total of 30 modified dNTPs with either fluorescent or non-fluorescent reporter group attachments were systematically evaluated individually and in combinations for high-density incorporation using different model and natural DNA templates. Furthermore, we show a side-by-side comparison of the incorporation efficiencies of a family A (Taq) and B (Vent(R) exo-) type DNA polymerase using the differently modified dNTP substrates. Our results show superior performance by a family B-type DNA polymerase, Vent(R) exo-, which is able to fully synthesize a 300 bp DNA product when all natural dNTPs are completely replaced by their biotin-labeled dNTP analogs. Moreover, we present systematic testing of various combinations of fluorescent dye-modified dNTPs enabling the simultaneous labeling of DNA with up to four differently modified dNTPs.