gebhart/patrepeval huggingface dataset:
STAT6 Immunohistochemistry Is Helpful in the Diagnosis of Solitary Fibrous Tumors (2014)

Solitary fibrous tumor (SFT) is an uncommon fibroblastic neoplasm. Although histologic characteristics and frequent CD34 expression allow for an accurate diagnosis in the majority of SFT cases, a wide histologic spectrum and an occasional unexpected immunophenotype may pose diagnostic challenges. Molecular analyses have discovered that almost all SFTs harbor an NAB2-STAT6 fusion gene, which is considered specific to this tumor type. Recent studies have suggested that STAT6 immunohistochemistry is a reliable surrogate for detection of the fusion gene. Our aim was to validate these findings by examining a large number of SFT cases and a broad array of 30 different types of non-SFT tumors. A total of 49 SFTs with a range of histologic characteristics and 159 benign or malignant tumors that can mimic SFTs were retrieved and stained for STAT6. All 49 SFTs (100%) showed STAT6 expression that was restricted in the nucleus, mostly in a diffuse and strong manner, irrespective of the tumor sites and histologic patterns. The staining was uniform in most cases but was heterogenous in about 20% of the cases in which zonal staining attenuation was observed, likely reflecting variability in fixation or tissue ischemia. In contrast, only 4 non-SFT tumors (2.5%) exhibited weak nuclear STAT6 expression, whereas the remaining 155 cases showed no staining or often weak reactivity in both the cytoplasm and the nucleus. Therefore, nuclear STAT6 immunoreactivity is a highly sensitive and specific marker of SFTs and can be helpful when diagnosis is inconclusive by conventional methods.
Discovery of Diphenylmethanepropionic and Dihydrostilbeneacetic Acids as Antagonists of the Integrin αvβ3 (2006)

A peptidomimetic inhibitor of the integrin alpha(v)beta(3) has been substantially modified to produce several new nonpeptidic antagonists. These inhibitors are simpler to synthesize and belong to new classes of scaffolds. Some of the compounds served as the initial lead for further optimization, which led to the discovery of potent and selective inhibitors of the integrin alpha(v)beta(3).
The MDR phenotype is associated with the expression of COX-2 and iNOS in a human hepatocellular carcinoma cell line (2002)

The presence of multiple drug resistance (MDR1) and angiogenic phenotypes negatively affect patients' prognosis with cancer even when treated with drugs that are not transported by the MDR1 gene product. It is possible to suggest a link between the MDR1 and angiogenic phenotypes. Because prostaglandins (PGs) and nitric oxide (NO) have been proposed to be involved in angiogenesis in vivo, the production of PGs and NO and the behavior of inducible NO synthase (iNOS), cyclooxygenase 1 (COX-1), and inducible cyclooxygenase (COX-2) were studied in parental drug-sensitive (P5) liver cancer cell lines and in P5-derived MDR1 cells P1(0.5). Immunohistochemical evaluation, Northern and Western blot analysis of COX-2 and iNOS, and assessment of cell proliferation were performed in basal conditions and after the exposure to stimulants or to specific inhibitors of COX-2 and iNOS. The messenger RNA and protein levels of COX-2 and iNOS were in basal conditions higher in P1(0.5) cells than the parental P5 cells. The exposure to lipopolysaccharide (LPS) or epidermal growth factor (EGF) determined an increase of PG and NO production in both cell lines and this increase was strongly reduced by COX-2 inhibitors such as celecoxib (CLX) and nimesulide (NIME). The inhibition of NO production by COX-2 inhibitors suggests cross-talk between COX-2 and iNOS pathways. CLX and NIME also inhibited cell proliferation, but only in MDR1 cells. A specific inhibitor of iNOS, N(6)-(1-iminoethyl)-L-lysine, had only a mild effect on cell proliferation in both cell lines. In conclusion, these data support the hypothesis that the MDR1 and angiogenic phenotypes are linked to each other in human liver cancer cell lines.
Nucleotide sequence of the Streptococcus gordonii PK488 coaggregation adhesin gene, scaA, and ATP-binding cassette (1994)

Human oral viridans group streptococci that coaggregate with Actinomyces naeslundii PK606 express surface proteins related to ScaA, the coaggregation-mediating adhesin of Streptococcus gordonii PK488 (R. N. Andersen, N. Ganeshkumar, and P. E. Kolenbrander, Infect. Immun. 61:981-987, 1993). The nucleotide sequence of the 6,125-bp EcoRI insert of pRA1, containing scaA, the gene encoding ScaA, was determined. Six open reading frames (ORFs) were identified. The orientation of four ORFs, two upstream (ORF 1 and ORF 2) and one downstream (ORF 4) of scaA (ORF 3), indicated transcription in one direction, whereas ORF 5 and ORF 6 were transcribed divergently. Computer analysis of the deduced amino acid sequences identified a consensus binding site for ATP (GxxGxGKS) in the putative 28,054-Da protein encoded by ORF 1. ORF 2 potentially encoded a hydrophobic protein of 29,705 Da with six potential membrane-spanning regions. ScaA was 310 amino acids, 34,787 Da, and contained the lipoprotein consensus sequence LxxC, also reported for the ScaA-related proteins SsaB, FimA, and PsaA from Streptococcus sanguis 12, Streptococcus parasanguis FW213, and Streptococcus pneumoniae R36A, respectively. ORF 4 potentially encoded a 163-amino-acid protein of 17,912 Da, which was nearly identical to the downstream adjacent gene products of ssaB, fimA, and psaA. No significant homology with other proteins was found with the putative ORF 5 gene product, a 229-amino-acid protein of 25,107 Da. ORF 6 was incomplete and encoded a protein larger than 564 amino acids. This putative protein had a consensus Zn2+ binding motif, HExxH, found among bacterial thermolysins and mammalian neutral endopeptidases and was 40% identical to a homologous 210-amino-acid region of human enkephalinase. The genetic organization of ORFs 1, 2, and 3 was similar to those of the bacterial periplasmic-binding protein-dependent transport systems of gram-negative bacteria and binding-lipoprotein-dependent transport systems of gram-positive bacteria, and these genes appeared to encode ABC (ATP-binding cassette) proteins. This report describes a cell-to-cell adherence function associated with an ATP-binding cassette.
Tobacco rattle virus RNA-protein interactions (1976)

Abstract For the purpose of attempting to generalize the rules concerning morphogenesis of helical viruses, the in vitro reconstitution of the CAM strain of TRV was studied. The conditions for reconstitution and the importance of the aggregation state of the protein for initiation and elongation are compar ed with those of TMV. The initiation step consisting of the binding of RNA with the 36S disk of protein was easily accomplished. The polarity and the specificity of encapsidation of TRV RNA by homologous and heterologous viral protein is discussed.
REGULATION OF MHC CLASS II GENES: Lessons from a Disease (1996)

Precise regulation of major histocompatibility complex class II (MHC-II) gene expression plays a crucial role in the control of the immune response. A major breakthrough in the elucidation of the molecular mechanisms involved in MHC-II regulation has recently come from the study of patients that suffer from a primary immunodeficiency resulting from regulatory defects in MHC-II expression. A genetic complementation cloning approach has led to the isolation of CIITA and RFX5, two essential MHC-II gene transactivators. CIITA and RFX5 are mutated in these patients, and the wild-type genes are capable of correcting their defect in MHC-II expression. The identification of these regulatory factors has furthered our understanding of the molecular mechanisms that regulate MHC-II genes. CIITA was found to be a non-DNA binding transactivator that functions as a molecular switch controlling both constitutive and inducible MHC-II expression. The finding that RFX5 is a subunit of the nuclear RFX-complex has confirmed that a deficiency in the binding of this complex is indeed the molecular basis for MHC-II deficiency in the majority of patients. Furthermore, the study of RFX has demonstrated that MHC-II promoter activity is dependent on the binding of higher-order complexes that are formed by highly specific cooperative binding interactions between certain MHC-II promoter-binding proteins. Two of these proteins belong to families of which the other members, although capable of binding to the same DNA motifs, are probably not directly involved in the control of MHC-II expression. Finally, the facts that CIITA and RFX5 are both essential and highly specific for MHC-II genes make possible novel strategies designed to achieve immunomodulation via transcriptional intervention.
Structure-function requirements of parathyroid hormone for stimulation of 1,25-dihydroxyvitamin D3 production by rat renal proximal tubules. (1993)

PTH stimulates synthesis and secretion of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] in renal proximal tubule cells through activation of the protein kinase-A (PKA) or the protein kinase-C (PKC) signaling pathway. The relative contribution of the two transducing systems was explored using PTH fragments with selective activation of either PKA or PKC. Rat renal proximal tubules were isolated by Percoll centrifugation, and PKA and PKC activities were measured after treatment with synthetic fragments and analogs of PTH. Rat PTH-(1-34), [Nle8,Nle15,Tyr34]bovine PTH-(3-34), and human PTH-(13-34) increased PKC activity in a dose-dependent manner. All fragments tested stimulated PKC at physiological concentrations (10(-11)-10(-10) M). Rat PTH-(1-34) (10(-7) M) increased PKA activity 4.5-fold, but other fragments failed to stimulate PKA between 10(-12)-10(-6) M. Human PTH-(28-34) stimulation of PKC was variable from experiment to experiment. All four PTH fragments tested increased 1,25-(OH)2D3 secretion by perifused renal proximal tubules at the lowest concentrations that stimulated PKC activity. The adenylate cyclase inhibitor 2',5'-dideoxyadenosine (10(-4) M) reduced PTH-(1-34)-stimulated PKA activity by 60%, but failed to block the rise in 1,25-(OH)2D3 secretion. The results of these studies demonstrate that PTH fragments that contain the PKC translocating domain stimulate 1,25-(OH)2D3 secretion, whereas elimination of the PKA activation domain does not alter the potency of the analogs' 1,25-(OH)2D3-stimulating activity. These results support the concept that PKC translocation may be required for PTH stimulation of 1,25-(OH)2D3 secretion.
Haptoglobin-related Protein Mediates Trypanosome Lytic Factor Binding to Trypanosomes (2001)

Trypanosome lytic factor (TLF-1) is an unusual high density lipoprotein (HDL) found in human serum that is toxic to Trypanosoma brucei brucei and may be critical in preventing human infections by this parasite. TLF-1 is composed of four major apolipoproteins: apolipoprotein AI, apolipoprotein AII, paraoxonase, and the primate-specific haptoglobin-related protein (Hpr). Hpr is greater than 90% homologous to haptoglobin (Hp), an abundant acute phase serum protein. Killing of trypanosomes by TLF-1 requires cell surface binding, endocytosis, and subsequent lysosomal targeting. Low temperature binding studies reveal two receptors for TLF-1: one that is high affinity/low capacity (K(d) approximately 12 nm, 350 receptors per cell) and another that binds with low affinity/high capacity (K(d) approximately 1 microm, 60,000 receptors per cell). The low affinity binding is competed by nonlytic human HDL and is likely to be apolipoprotein AI-mediated. Purified human Hpr and human Hp bind to trypanosomes, are internalized, and are targeted to the lysosome. Furthermore, Hpr shows competition for TLF-1 binding, and a monoclonal antibody against Hpr prevents both TLF-1 uptake and trypanosome killing. Based on these results, we propose that Hpr mediates the high affinity binding of TLF-1 to T. b. brucei through a haptoglobin-like receptor.
Diagnosis of premenstrual syndrome by a simple, prospective, and reliable instrument: The calendar of premenstrual experiences (1991)

To establish a quantitative method for the diagnosis of premenstrual syndrome (PMS), a simple prospective inventory, the calendar of premenstrual experiences, was constructed. The validity and reliability of this instrument were assessed by administering it throughout two consecutive ovulatory cycles to 36 rigidly screened women with PMS and to 18 controls. To establish concurrent validity, scores on behavioral items were correlated with simultaneously obtained scores on lengthier, well-validated psychiatric inventories designed to measure depression rather than PMS, the Beck Depression Inventory and the Profile of Mood States. The results showed that the calendar of premenstrual experiences luteal phase score distinguished PMS women from controls correctly in 104 of 108 cycles, with a 2.8% false-negative rate and no false positives when used for two consecutive cycles. An upper limit follicular phase score was observed beneath which all PMS and normal control subjects fell, suggesting that a higher score is not consistent with PMS. Correlation coefficients of calendar item scores with Profile of Mood States scale scores were 0.58 for tension, 0.51 for depression, 0.46 for anger, 0.61 for fatigue, and 0.57 for confusion (P less than .0001 for all correlations). The correlation of the calendar depression item with the Beck Depression Inventory score was 0.56 (P less than .0001). The test-retest reliability of the calendar given in the same phase of two consecutive menstrual cycles was high (r = 0.78, P less than .0001). We conclude that this instrument is a valid, reliable, and practical PMS inventory, applicable to clinical and some research settings.
Modeling, simulation and analysis of an uninterruptible power supply (2002)

The uninterruptible power supply (UPS) has become an integral part of modern computer and communication systems to assure a continued and reliable operation by providing an uninterruptible power to such equipment. Various topologies have come to the fore recently with the advent of high frequency switching techniques. This paper considers such a high frequency operated UPS system and it is modeled, simulated and analyzed to provide insight and information for design studies. A framework for the software simulation of a class of UPS is proposed in this paper and its implementation results are given and discussed. The software structure and its implementation are included in the paper. The software is built on a modular basis to enable the simulation of various topologies of UPS that are in vogue and that may emerge in the future.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
High Bone Mineral Density and Fracture Risk in Type 2 Diabetes as Skeletal Complications of Inadequate Glucose Control (2013)

Poor glycemic control in type 2 diabetes is associated with fracture risk, high BMD, and thicker femoral cortices in narrower bones. We postulate that fragility in apparently "strong" bones in ICD can result from microcrack accumulation and/or cortical porosity, reflecting impaired bone repair.
Enhancement of cytotoxicity by electropermeabilization (1998)

Electropermeabilization (EPN), also termed electroporation, is a physical method to overcome the barrier of the cell membrane by applying short and intense electric pulses. It is the basis for a new cancer treatment modality, electrochemotherapy, where uptake of chemotherapeutics is enhanced by EPN. Preclinical and clinical trials have shown that application of electric pulses in vivo is feasible and that electrochemotherapy is highly efficient. The aim of this study was to develop an improved method of screening drugs on electropermeabilized versus non-electropermeabilized cells. In this study we describe an easy protocol which gives high cell viability, good reproducibility and a high rate of cell permeabilization. Cell cytotoxicity is simply determined by the MTT assay. Cell death due to the EPN procedure was less than 4% and more than 90% of cells were permeabilized. For daunorubicin, doxorubicin, etoposide and paclitaxel, no effect of EPN was found. For carboplatin and cisplatin the effect of EPN was a factor 3 and 2.3, respectively, on the IC50 (inhibitory concentration 50%). For bleomycin we found a dramatic effect of EPN of the magnitude of a factor 300 on the IC50. In conclusion, we have established a new, easy and reliable protocol to test new drugs for cytotoxicity with or without the limitations of the cell membrane. Our data support the role of bleomycin as the drug of choice for electrochemotherapy.
Severity of Airflow Limitation Is Associated with Severity of Airway Inflammation in Smokers (1998)

To investigate the relationship between airflow limitation and airway inflammation in smokers, we examined paraffin-embedded bronchial biopsies obtained from 30 smokers: 10 with severe airflow limitation, eight with mild/moderate airflow limitation, and 12 control smokers with normal lung function. Histochemical and immunohistochemical methods were performed to assess the number of inflammatory cells in the subepithelium and the expression of CC chemokines macrophage inflammatory protein (MIP)-1alpha and -1beta in the bronchial mucosa. Compared with control smokers, smokers with severe airflow limitation had an increased number of neutrophils (p < 0.02), macrophages (p < 0.03), and NK lymphocytes (p < 0.03) in the subepithelium, and an increased number of MIP-1alpha+ epithelial cells (p < 0.02). When all smokers were considered together, the value of FEV1 was inversely correlated with the number of neutrophils (r = -0.59, p < 0.002), macrophages (r = -047, p < 0. 012), NK-lymphocytes (r = -0.51, p < 0.006) in the subepithelium, and with the number of MIP-1alpha+ epithelial cells (r = -0.61, p < 0.003). We conclude that in smokers the severity of airflow limitation is correlated with the severity of airway inflammation and that severe airflow limitation is associated with an increased number of neutrophils, macrophages, NK lymphocytes, and MIP-1alpha+ cells in the bronchial mucosa.
High relaxivity linear Gd(DTPA)‐polymer conjugates: The role of hydrophobic interactions (1997)

A series of linear copolymers of DTPA-class Gd3+ conjugates, linked by alpha, omega-alkyldiamides with a varying number (n) of methylenes separating the amide function, were synthesized. Surprisingly, their relaxivities at all fields increased with increasing n. At MRI fields and 35 degrees C, the relaxivities of the n = 10 and n = 12 polymers were unexpectedly high, similar to those of rigid dendrimer-based Gd3+ chelates. The magnetic field dependence of solvent proton 1/T1 was measured for aqueous urea-free and urea-containing polymer solutions. The results for urea-free solutions imply an increase of rigidity (required for high relaxivities) with increasing n, arising from hydrophobic interactions of the methylene groups with solvent. This hypothesis is supported by a large decrease in the relaxivities upon addition of urea, which is known to weaken hydrophobic interactions. The relaxivities are also independent of polymer concentration, indicating that the hydrophobic interactions are intramolecular.
Endocrine changes after burn trauma - A review. (1989)

After burn trauma, a very marked endocrine response occurs. Almost all the known hormones take part in it. Their response influences very much the postburn metabolic changes and participates in the integration of the body's response with the nervous and immune systems. In this review, mainly the changes in various hormone levels are described, as well as the possible role of the acute phase response after burn trauma, and the communications between the endocrine and immune systems, the cells of the latter are able to respond to various hormonal stimuli and to secrete various hormones themselves. Some of the hormones are very sensitive indicators of the burn stress, e.g., the T3 levels (very low), testosterone in males (very low), dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEA-S) (very low), ADH, catecholamines, renin and angiotensin II, cortisol (high), 17-beta-estradiol in males (usually elevated). Other hormones are usually elevated, but not always (ACTH, aldosterone, prolactin, glucagon, immunoreactive insulin, beta-endorphin, rT3, 11-beta-hydroxyandrostenedione), but there are hormones that are unually low (T4, FSH, androstenedione, progesterone--the latter especially in females). Calcitonin, parathyroid hormone, growth hormone are sometimes elevated, as well as LH (measured with RIA methods). TSH is usually normal, the biologically measured LH was reported to be low. The levels of the sensitive indicators of burn stress may be used to evaluate the effect of treatment: if the burn patient is properly treated, the indicators may become earlier normal.
Platelet Membrane Glycoprotein IIb/IIIa: Member of a Family of Arg-Gly-Asp—Specific Adhesion Receptors (1986)

Adhesive interactions of the platelet surface with plasma proteins such as fibrinogen and fibronectin play an important role in thrombosis and hemostasis. The binding of both of these proteins to platelets is inhibited by synthetic peptides containing the sequence Arg-Gly-Asp, which corresponds to the cell adhesion site in fibronectin and is also present in the alpha chain of fibrinogen. An affinity matrix made of an insolubilized heptapeptide containing the Arg-Gly-Asp sequence selectively binds the platelet membrane glycoprotein IIb/IIIa from detergent extracts of platelets. When incorporated into liposome membranes, the isolated protein confers to the liposomes the ability to bind to surfaces coated with fibrinogen, fibronectin, and vitronectin but not to surfaces coated with thrombospondin or albumin. This platelet receptor is related to the previously identified fibronectin and vitronectin receptors in that it recognizes an Arg-Gly-Asp sequence but differs from the other receptors in its wider specificity toward various adhesive proteins. These results establish the existence of a family of adhesion receptors that recognize the sequence Arg-Gly-Asp.