gebhart/patrepeval huggingface dataset:
Expression of ETV6/TEL is associated with prognosis in non-small cell lung cancer. (2015)

The ETV6/TEL gene is a member of the ETS family of transcription factors that has been mainly studied in hematological diseases. This study provides the first investigation of ETV6 expression in non-small cell lung cancer (NSCLC). In this study, ETV6 expression was immunohistochemically studied in 170 consecutive patients with NSCLC. The association between ETV6 expression and clinicopathological parameters was evaluated. Kaplan-Meier survival analysis and Cox proportional hazards models were used to estimate the effect of ETV6 expression on survival. ETV6 expression was observed in 135 of the 170 (79.4%) patients. ETV6 expression was positive for nuclear staining. From the clinicopathological standpoint, the expression of ETV6 was significantly correlated with age (P=0.014). The overall survival was significantly enhanced in the group with a low expression of ETV6 compared with the group with a high expression of ETV6 (five-year survival rates, 56.53% versus 29.88%; P=0.002), and the same finding was obtained for disease-free survival (five-year survival rates, 52.24% versus 30.47%; P=0.001). Multivariable analysis confirmed that ETV6 expression increased the hazard of death after adjusting for other clinicopathological factors (hazard ratio, 2.002; 95% confidence interval, 1.303-3.074; P=0.002). Our study demonstrated that ETV6 was markedly involved in the development of NSCLC and could serve as a potential prognostic marker for this deadly disease.
Leukocyte analysis and differentiation using high speed microfluidic single cell impedance cytometry (2009)

Miniature high speed label-free cell analysis systems have yet to be developed, but have the potential to deliver fast, inexpensive and simple full blood cell analysis systems that could be used routinely in clinical practice. We demonstrate a microfluidic single cell impedance cytometer that performs a white blood cell differential count. The device consists of a microfluidic chip with micro-electrodes that measure the impedance of single cells at two frequencies. Human blood, treated with saponin/formic acid to lyse erythrocytes, flows through the device and a complete blood count is performed in a few minutes. Verification of cell dielectric parameters was performed by simultaneously measuring fluorescence from CD antibody-conjugated cells. This enabled direct correlation of impedance signals from individual cells with phenotype. Tests with patient samples showed 95% correlation against commercial (optical/Coulter) blood analysis equipment, demonstrating the potential clinical utility of the impedance microcytometer for a point-of-care blood analysis system.
Efficient coupling of glycopeptides to proteins with a heterobifunctional reagent (1989)

A heterobifunctional linking reagent containing a masked aldehydo group and acyl hydrazide was synthesized for coupling of glycopeptides and other amino-containing compounds to proteins. After conversion to acyl azide, the reagent reacts with the amino group of a glycopeptide, and the modified glycopeptide is deacetalized with a weak acid to unmask the aldehydo group, which is then conjugated to bovine serum albumin (BSA) by reductive alkylation with pyridine-borane. The overall reaction scheme proceeds under relatively mild conditions. When the protein amino group was in a large excess (greater than 6-fold) of the aldehyde reagent, the efficiency of conjugation was as high as 88% even at submicromole levels. As a test case for application of this reagent, 6-aminohexyl beta-D-galactopyranoside (Gal-AH) was attached to the linking reagent and conjugated to BSA at various aldehyde-to-protein molar ratios ranging from 25 to 200. The level of O-galactosyl residue incorporated into BSA by this reagent far exceeded that observed in a similar reductive alkylation involving S-galactoside reagents [Lee, R. T., & Lee, Y. C. (1980) Biochemistry 19, 156-163]. By use of the present conjugating procedure, as many as 112 mol of Gal-AH residues were incorporated per mole of BSA, which represents near total modification of the amino groups. Some binding characteristics of the new BSA derivatives were studied in the mammalian hepatic galactose/N-acetylgalactosamine specific lectin system along with other types of BSA derivatives (containing S-galactosyl residues). In general, the behavior of the new derivatives was similar to that of other types. For instance, the affinity increased exponentially at low sugar substitution levels (up to 30 mol of galactosyl residues/mol of BSA), and the slope of exponential increase and affinity at a given sugar substitution level was similar to those of other types.
Rational design of inducible CRISPR guide RNAs for de novo assembly of transcriptional programs (2017)

CRISPR-based transcription regulators (CRISPR-TRs) have transformed the current synthetic biology landscape by allowing specific activation or repression of any target gene. Here we report a modular and versatile framework enabling rapid implementation of inducible CRISPR-TRs in mammalian cells. This strategy relies on the design of a spacer-blocking hairpin (SBH) structure at the 5' end of the single guide RNA (sgRNA), which abrogates the function of CRISPR-transcriptional activators. By replacing the SBH loop with ligand-controlled RNA-cleaving units, we demonstrate conditional activation of quiescent sgRNAs programmed to respond to genetically encoded or externally delivered triggers. We use this system to couple multiple synthetic and endogenous target genes with specific inducers, and assemble gene regulatory modules demonstrating parallel and orthogonal transcriptional programs. We anticipate that this 'plug and play' approach will be a valuable addition to the synthetic biology toolkit, facilitating the understanding of natural gene circuits and the design of cell-based therapeutic strategies.
Presence of cutaneous interferon-a producing cells in patients with systemic lupus erythematosus (2001)

Systemic lupus erythematosus (SLE) patients have increased levels of interferon-alfa (IFN-alpha) in the circulation but a reduced number of functionally intact natural IFN-alpha producing cells (IPC) in peripheral blood. In search for tissue localisation of activated IPC, we investigated skin biopsies from SLE patients for the occurrence of such cells. Eleven SLE patients with inflammatory skin lesions and six healthy controls were biopsied. An immunohistochemical technique (IH) and in situ hybridisation (ISH) were used to detect intracellular IFN-alpha protein and IFN-alpha mRNA, respectively. In all 11 biopsies from SLE lesions, a high number of IPC were detected by IH. In the nonlesional SLE biopsies we could also demonstrate IPC in 10/11 patients. In 6/11 SLE patients, IFN-alpha mRNA containing cells could be detected in the specimens. A low number of IPC were detected in 1/6 healthy controls by IH, but no ISH positive cells were seen. Our results demonstrate that SLE patients have active IPC in both dermal lesions and in noninflammatory skin. A recruitment of IPC from blood to peripheral tissues may explain the low number of circulating natural IPC in SLE patients. Because the type I IFN system is involved in the SLE disease process, these results are of interest for the understanding of the pathogenesis in SLE.
2-Chloro-4-[[(1R,2R)-2-hydroxy-2-methyl-cyclopentyl]amino]-3-methyl-benzonitrile: A Transdermal Selective Androgen Receptor Modulator (SARM) for Muscle Atrophy (2015)

A transdermal SARM has a potential to have therapeutic benefit through anabolic activity in muscle while sparing undesired effects of benign prostate hyperplasia (BPH) and liver-mediated decrease in HDL-C. 2-Chloro-4-[(2-hydroxy-2-methyl-cyclopentyl)amino]-3-methyl-benzonitrile 6 showed the desired muscle and prostate effects in a preclinical ORX rat model. Compound 6 had minimal effect on HDL-C levels in cynomolgus monkeys and showed human cadaver skin permeability, thus making it an effective tool for proof-of-concept studies in a clinical setting.
Hemodynamic effects of exogenous nitric oxide in ovine transitional pulmonary circulation (1992)

To determine the hemodynamic effects of exogenous nitric oxide (NO) on the immature pulmonary circulation, we studied the response to NO inhalation in 19 mechanically ventilated late-gestation ovine fetuses in three separate protocols. In protocol 1, we examined the relative effects of 1) mechanical ventilation while maintaining fetal arterial O2 tension (PaO2) constant [fractional inspired O2 concentration (FIO2) less than 0.10)], 2) NO inhalation [5-20 parts per million (ppm)] at fetal PaO2, and 3) high FIO2 (1.00) (n = 7). NO increased left pulmonary artery blood flow (Qlpa) in a dose-dependent fashion, from 254 +/- 62 (baseline) to 398 +/- 49 ml/min with 20 ppm NO (P less than 0.001). The response of Qlpa to a FIO2 equal to 1.00 was not different from NO alone. Systemic arterial pressure was not affected by NO. In protocol 2 we studied the effects of prolonged NO inhalation (2 h, 20 ppm) during mechanical ventilation with low FIO2 (n = 4). NO increased Qlpa from 267 +/- 92 to 468 +/- 75 ml/min at 10 min of NO inhalation (P less than 0.001). The increase in Qlpa was sustained during the entire 2-h study period. In protocol 3 we measured left ventricular output (LVO), systemic vascular resistance (SVR), and ductus arteriosus shunting using radiolabeled microspheres (n = 8) during baseline mechanical ventilation and 20 ppm NO inhalation. LVO and SVR were not significantly different in the two study periods; however, the percentage of LVO that reached the lungs (predominantly left-to-right shunting across the ductus arteriosus) increased from 18 +/- 5 to 43 +/- 4% during NO inhalation.(ABSTRACT TRUNCATED AT 250 WORDS)
Cyanobacterial conversion of carbon dioxide to 2,3-butanediol (2013)

Conversion of CO(2) for the synthesis of chemicals by photosynthetic organisms is an attractive target for establishing independence from fossil reserves. However, synthetic pathway construction in cyanobacteria is still in its infancy compared with model fermentative organisms. Here we systematically developed the 2,3-butanediol (23BD) biosynthetic pathway in Synechococcus elongatus PCC7942 as a model system to establish design methods for efficient exogenous chemical production in cyanobacteria. We identified 23BD as a target chemical with low host toxicity, and designed an oxygen-insensitive, cofactor-matched biosynthetic pathway coupled with irreversible enzymatic steps to create a driving force toward the target. Production of 23BD from CO(2) reached 2.38 g/L, which is a significant increase for chemical production from exogenous pathways in cyanobacteria. This work demonstrates that developing strong design methods can continue to increase chemical production in cyanobacteria.
[Synthesis and anti-ulcer activity of some new compounds with arylthiomethyl-pyridine structure]. (1988)

We report the results of the antiulcer activity of some arylthiomethylpyridine compounds. Some of these showed gastroprotective activity against 96% ethanol-induced gastric lesions greater than Omeprazole. However they possess antiulcer properties lower than the reference compound against Indomethacin-induced gastric ulcers.
Rapid Signaling of Estrogen in Hypothalamic Neurons Involves a Novel G-Protein-Coupled Estrogen Receptor that Activates Protein Kinase C (2003)

Classically, 17beta-estradiol (E2) is thought to control homeostatic functions such as reproduction, stress responses, feeding, sleep cycles, temperature regulation, and motivated behaviors through transcriptional events. Although it is increasingly evident that E2 can also rapidly activate kinase pathways to have multiple downstream actions in CNS neurons, the receptor(s) and the signal transduction pathways involved have not been identified. We discovered that E2 can alter mu-opioid and GABA neurotransmission rapidly through nontranscriptional events in hypothalamic GABA, proopiomelanocortin (POMC), and dopamine neurons. Therefore, we examined the effects of E2 in these neurons using whole-cell recording techniques in ovariectomized female guinea pigs. E2 reduced rapidly the potency of the GABAB receptor agonist baclofen to activate G-protein-coupled, inwardly rectifying K+ channels in hypothalamic neurons. These effects were mimicked by the membrane impermeant E2-BSA and selective estrogen receptor modulators, including a new diphenylacrylamide compound, STX, that does not bind to intracellular estrogen receptors alpha or beta, suggesting that E2 acts through a unique membrane receptor. We characterized the coupling of this estrogen receptor to a Galpha(q)-mediated activation of phospholipase C, leading to the upregulation of protein kinase Cdelta and protein kinase A activity in these neurons. Moreover, using single-cell reverse transcription-PCR, we identified the critical transcripts, PKCdelta and its downstream target adenylyl cyclase VII, for rapid, novel signaling of E2 in GABA, POMC, and dopamine neurons. Therefore, this unique Gq-coupled estrogen receptor may be involved in rapid signaling in hypothalamic neurons that are critical for normal homeostatic functions.
Plasminogen activator inhibitor from human endothelial cells. Purification and partial characterization (1987)

An inhibitor of plasminogen activator was purified to apparent homogeneity from human umbilical vein endothelial cell conditioned medium. The purification was achieved by a speedy and simple two-step procedure, without the use of denaturants. The purified protein was a single-chain glycoprotein with apparent molecular mass of 48 kDa. The purified inhibitor had a specific activity of 8500 U/mg protein and the activity could be stimulated about fourteenfold by treatment with denaturants. An antiserum to the purified inhibitor was raised in rabbits. It recognised plasminogen activator inhibitor from platelets and plasma as well as from cultured endothelial cells. The immunoglobulin fraction of the antiserum neutralised the functional activity of the inhibitor from all these sources.
Complications of Intravesical Therapy for Urothelial Cancer of the Bladder (2006)

Although intravesical therapy is generally safe, local and systemic side effects occur and it is important to be aware of them. Identifying complications early, preventing them when possible and managing them efficiently are critical. Most complications are preventable. Knowing the risks and benefits of chemotherapeutic and immunotherapeutic agents may decrease the short-term and long-term toxicity of these agents. Adherence to guidelines may prevent inappropriate use, which can lead to unnecessary complications, resulting in bladder dysfunction and even cystectomy.
Chromosome and oncogene studies in human rectal and colon carcinomas. (1992)

Cytogenetic examinations of 48 rectal and 17 colon carcinomas and analyses of proto-oncogene activation on 67 of the former and 8 of the latter tumors were performed. Besides a general considerable heterogeneity of chromosome counts, some chromosomes were found to contribute non-randomly to hypersomies (# 2, 3, 7, 9, 19, 20 and 6) and to hyposomies (# 14, 15, Y, 21, and 18) in this material. Chromosomal markers non-randomly involved breakpoint clusters on 17p11, 13q11, 7p, 1p11, and 1p36 and on the centromeric regions of chromosomes 1, 8, 14, 15 and 21. Cytogenetic equivalents of gene amplification ("double minutes") were present in only rather small cell fractions (less than 20%) of 50% of the studied tumors. Using a cDNA technique and a battery of respective probes, proto-oncogene overexpression was screened for in the tumor samples, but also in 24 samples of inconspicuous mucosae of tumor patients and in two mucosae of healthy individuals. Simultaneous overexpression of several proto-oncogenes was the most characteristic finding in the tumor cells. However several of the mucosa samples obtained from tumor patients also just exhibited clear signals of proto-oncogene overexpression, which were not found in epithelial cells from non-tumor patients.
Paroxysmal cold haemoglobinuria as a tardive complication of idiopathic myelofibrosis (2004)

Paroxysmal cold haemoglobinuria (PCH) is an autoimmune haemolytic anaemia caused by the Donath-Landsteiner antibody. It is classically described in association with chronic syphilis or after acute viral infections. We describe the first case of PCH presented as a late manifestation of advanced myelofibrosis associated with antiphospholipid syndrome, that promptly responded to high dosage of prednisone.
Cancer Anorexia-Cachexia Syndrome: Current Issues in Research and Management (2002)

Cachexia is among the most debilitating and life-threatening aspects of cancer. Associated with anorexia, fat and muscle tissue wasting, psychological distress, and a lower quality of life, cachexia arises from a complex interaction between the cancer and the host. This process includes cytokine production, release of lipid-mobilizing and proteolysis-inducing factors, and alterations in intermediary metabolism. Cachexia should be suspected in patients with cancer if an involuntary weight loss of greater than five percent of premorbid weight occurs within a six-month period. The two major options for pharmacological therapy have been either progestational agents, such as megestrol acetate, or corticosteroids. However, knowledge of the mechanisms of cancer anorexia-cachexia syndrome has led to, and continues to lead to, effective therapeutic interventions for several aspects of the syndrome. These include antiserotonergic drugs, gastroprokinetic agents, branched-chain amino acids, eicosapentanoic acid, cannabinoids, melatonin, and thalidomide--all of which act on the feeding-regulatory circuitry to increase appetite and inhibit tumor-derived catabolic factors to antagonize tissue wasting and/or host cytokine release. Because weight loss shortens the survival time of cancer patients and decreases performance status, effective therapy would extend patient survival and improve quality of life.
Isolation of Dengue Viruses from Peripheral Blood Leukocytes of Patients with Hemorrhagic Fever (1980)

Dengue viruses were isolated by a plaque technique in LLC-MK2 cells from washed peripheral blood leukocytes of patients with hemorrhagic fever. In comparison with plasma, the use of peripheral blood leukocytes permitted greater than three times the recovery rate of viruses, allowed for the isolation of strains of virus from patients with high serum levels of antibody to dengue virus, and extended the period of detectable viremia. The use of peripheral blood leukocytes was especially useful for isolation of viruses from patients with hemorrhagic fever, in whom antibody titers were generally quite high during the acute phase of the disease. This method is recommended for use by laboratories with access to the appropriate acute-phase specimens. Of the peripheral blood leukocytes, adherent monocytes appeared to be the cells most likely affected; however, involvement of atypical lymphocytes, which are commonly found in patients with hemorrhagic fever, or polymorphonuclear leukocytes could not be excluded by this study. Only a small number of infected centers could be identified by infectious-center assays, but the marked augmentation of recovery of virus with the use of peripheral blood leukocytes indicated the presence in patients of a subpopulation of cells that permit dengue virus infection.
High-power near-diffraction-limited tapered amplifiers at 1064 nm for optical intersatellite communications (1998)

The realization of high-power tapered amplifiers at 1064 nm on a low-modal gain structure is presented. More than 1.5-W continuous-wave optical output power at 3-A injection current is achieved with only 13-mW input optical power and a near-diffraction-limited output beam quality. The use of a low-modal gain structure in conjunction with a very low AR-coating value avoids the addition of cavity spoilers. The implementation of such amplifiers in an optical intersatellite communication system is studied. The devices showed excellent resistance to 160-krad proton irradiation. Preliminary aging tests on broad-area laser diodes demonstrate extrapolated lifetimes as long as 20000 h at 50/spl deg/C.
Efficacy and Toxicity Management of 19-28z CAR T Cell Therapy in B Cell Acute Lymphoblastic Leukemia (2014)

We report on 16 patients with relapsed or refractory B cell acute lymphoblastic leukemia (B-ALL) that we treated with autologous T cells expressing the 19-28z chimeric antigen receptor (CAR) specific to the CD19 antigen. The overall complete response rate was 88%, which allowed us to transition most of these patients to a standard-of-care allogeneic hematopoietic stem cell transplant (allo-SCT). This therapy was as effective in high-risk patients with Philadelphia chromosome-positive (Ph(+)) disease as in those with relapsed disease after previous allo-SCT. Through systematic analysis of clinical data and serum cytokine levels over the first 21 days after T cell infusion, we have defined diagnostic criteria for a severe cytokine release syndrome (sCRS), with the goal of better identifying the subset of patients who will likely require therapeutic intervention with corticosteroids or interleukin-6 receptor blockade to curb the sCRS. Additionally, we found that serum C-reactive protein, a readily available laboratory study, can serve as a reliable indicator for the severity of the CRS. Together, our data provide strong support for conducting a multicenter phase 2 study to further evaluate 19-28z CAR T cells in B-ALL and a road map for patient management at centers now contemplating the use of CAR T cell therapy.
Assessment of Recombinant Adenoviral Vectors for Hepatic Gene Therapy (1993)

Recombinant adenoviral vectors have recently been used to transfer genes into a number of different cell types in vitro and in vivo. A recombinant adenoviral vector bearing the Escherichia coli beta-galactosidase (beta-gal) gene was used to quantitate the frequency of hepatocyte transduction in the mouse after direct viral infusion into the portal vein. When 10(10) adenoviral particles were infused, over 95% of the hepatocytes were transduced in vivo as determined by x-gal staining. The transduction protocol is relatively safe in that there is no detectable helper virus production in transduced animals and that very few extrahepatic cells are transduced by this method. There is also no evidence of significant liver pathology unless substantially greater quantities of virus are used. However, the transduced hepatocytes do not appear to persist in vivo because the percentage of hepatocytes expressing beta-gal declined over time. Four months after the procedure, 0.5-10% of the hepatocytes contain detectable beta-gal activity in vivo. The change in beta-gal-positive cells correlates with decreasing amounts of adenoviral DNA. Thus, current recombinant adenoviral vectors may have clinical applications in gene therapy for acute hepatic disorders.