gebhart/patrepeval huggingface dataset:
Modulation of human erg K+ channel gating by activation of a G protein‐coupled receptor and protein kinase C (1998)

1. Modulation of the human ether-à-go-go-related gene (HERG) K+ channel was studied in two-electrode voltage-clamped Xenopus oocytes co-expressing the channel protein and the thyrotropin-releasing hormone (TRH) receptor. 2. Addition of TRH caused clear modifications of HERG channel gating kinetics. These variations consisted of an acceleration of deactivation, as shown by a faster decay of hyperpolarization-induced tail currents, and a slower time course of activation, measured using an envelope of tails protocol. The voltage dependence for activation was also shifted by nearly 20 mV in the depolarizing direction. Neither the inactivation nor the inactivation recovery rates were altered by TRH. 3. The alterations in activation gating parameters induced by TRH were demonstrated in a direct way by looking at the increased outward K+ currents elicited in extracellular solutions in which K+ was replaced by Cs+. 4. The effects of TRH were mimicked by direct pharmacological activation of protein kinase C (PKC) with beta-phorbol 12-myristate, 13-acetate (PMA). The TRH-induced effects were antagonized by GF109203X, a highly specific inhibitor of PKC that also abolished the PMA-dependent regulation of the channels. 5. It is concluded that a PKC-dependent pathway links G protein-coupled receptors that activate phospholipase C to modulation of HERG channel gating. This provides a mechanism for the physiological regulation of cardiac function by phospholipase C-activating receptors, and for modulation of adenohypophysial neurosecretion in response to TRH.
Missense and splice site mutations in tau associated with FTDP-17: Multiple pathogenic mechanisms (2001)

Recent identification of mutations in the gene encoding the microtubule-associated protein tau in the inherited frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) has demonstrated that tau dysfunction can lead to neurodegeneration. At least nine missense mutations and one deletion mutation (DeltaK280) have been identified in exons 9 through 13 that encode the microtubule-binding domains of tau. In addition, five mutations have been found close to the 5' splice site of exon 10. The FTDP-17 missense and splice site mutations have multiple effects on the biology and function of tau. It is likely that these varied pathogenic mechanisms explain the wide range of clinical and neuropathologic features observed in the FTDP-17 tauopathies.
Catabolite repression of α amylase gene expression in Bacillus subtilis involves a trans‐acting gene product homologous to the Escherichia coli lacl and galR repressors (1991)

Expression of the alpha-amylase gene of Bacillus subtilis is controlled at the transcriptional level, and responds to the growth state of the cell as well as the availability of rapidly metabolizable carbon sources. Glucose-mediated repression has previously been shown to involve a site near the transcriptional start-point of the amyE gene. In this study, a transposon insertion mutation was characterized which resulted in loss of glucose repression of amyE gene expression. The gene affected by this mutation, which was localized near 263 degrees on the B. subtilis chromosomal map, was isolated and its DNA sequence was determined. This gene, designated ccpA, exhibited striking homology to repressor genes of the lac and gal repressor family. The ccpA gene was found to be allelic to alsA, previously identified as a regulator of acetoin biosynthesis, and may be involved in catabolite regulation of other systems as well.
The chemoresistance of human malignant melanoma (1999)

Malignant melanoma is considered to be a chemotherapy-refractory tumour and the commonly used anticancer drugs do not seem to modify the prognosis of metastatic disease. The cellular resistance mechanisms involved in melanoma chemoresistance have not yet been elucidated. Melanoma-derived cell lines are often markedly chemoresistant. Using the in vitro soft agar culture system to predict tumour cell sensitivity in well-established human melanoma cell lines, a high degree of resistance against all the cytostatic agents studied has been reported, suggesting the presence of intrinsic cellular resistance mechanisms. The relevance of the well-defined resistance mechanisms mediated by P-glycoprotein, multidrug resistance-associated protein (MRP), the glutathione/glutathione S-transferase system and topoisomerase II enzyme are reviewed. Mutated N-Ras oncogene has recently been implicated in melanoma resistance to cisplatin, both in vitro and in vivo, and the role of two other oncogenes, Bcl-2 and p53, which are already involved in the chemoresistance of haematological and solid malignancies, is beginning to be better elucidated. The finding that many chemotherapeutic agents can kill susceptible cells through the apoptosis pathway provides new molecular insight into chemoresistance mechanisms and suggests that apoptosis and/or resistance to apoptosis of melanoma cells should be investigated to better clarify the mechanism of melanoma chemoresistance.
Implantation of Genetically Engineered Fibroblasts into Mice: Implications for Gene Therapy (1987)

In a variety of human genetic diseases, replacement of the absent or defective protein provides significant therapeutic benefits. As a model for a somatic cell gene therapy system, cultured murine fibroblasts were transfected with a human growth hormone (hGH) fusion gene and cells from one of the resulting clonal lines were subsequently implanted into various locations in mice. Such implants synthesized and secreted hGH, which was detectable in the serum. The function of the implants depended on their location and size, and on the histocompatibility of the donor cells with their recipients. The expression of hGH could be modified by addition of regulatory effectors, and, with appropriate immunosuppression, the implants survived for more than 3 months. This approach to gene therapy, here termed "transkaryotic implantation," is potentially applicable to many genetic diseases in that the transfected cell line can be extensively characterized prior to implantation, several anatomical sites are suitable for implantation, and regulated expression of the gene of therapeutic interest can be obtained.
Silica Pattern Formation in Diatoms: Species‐Specific Polyamine Biosynthesis (2006)

Diatoms are eukaryotic, unicellular algae that are well known for the intricate architecture of their silica-based cell walls. Species identification is mainly based on variations of their hierarchically organized silica structures. Particularly striking silica frameworks are found among diatoms that belong to the genus Coscinodiscus. Recent work indicates an important role for long-chain polyamines in guiding silica precipitation as well as in silica-pattern formation. Here we demonstrate that polyamines, even if isolated from closely related diatom species, exhibit substantial structural differences. Structural variations include the overall chain length, the degree of methylation, positions of secondary amino functionalities, and, unexpectedly, site-specific incorporation of a quaternary ammonium functionality. These findings support a specific role for polyamines in creating silica nanostructures.
Disappearing Stem Cells, Disappearing Science (2001)

Soon the Bush administration will decide the fate of human embryonic stem cell (ESC) research at U.S. government-funded institutions, and the outcome of that decision will greatly influence the role of ESC science in human developmental biology around the world. But although the forces that science brings to this field are powerful, the future of ESC research will largely be determined by other interests: politics, organized religion, commerce, the legal community, and patient advocacy groups. The decision-making process needs to develop a policy that is fact-based and serves the best interests of society as well as science.
Identification of gene targets against dormant phase Mycobacterium tuberculosis infections (2007)

Based on our bioinformatics analysis and additional discussion of in-depth biological rationale, several novel anti-TB targets have been proposed as potential opportunities to improve present therapeutic treatments for this disease.
Stimulation of articular cartilage repair in established arthritis by local administration of transforming growth factor-beta into murine knee joints. (1998)

A severe consequence of rheumatoid arthritis is depletion of proteoglycans (PGs) from articular cartilage leading to functional impairment of this tissue. We investigated whether local administration of anabolic factors (transforming growth factors-beta1 and -beta2 [TGF-beta1 and -beta2, respectively] and bone morphogenetic protein-2 (BMP-2) into joints could stimulate cartilage repair during arthritis. A unilateral arthritis was induced in mice by intra-articular injection of zymosan. Starting on Day 4 after the induction of arthritis, three injections of TGF-beta1 (200 ng) were given (Days 4, 6, and 8). On Day 11, articular cartilage PG synthesis was measured by 35S-sulfate incorporation, and histologic knee joint sections were prepared, which were used to analyze cartilage PG content by quantification of safranin O staining. Additionally, histologic sections were used to analyze inflammation and chondrophyte-formation. Local administration of TGF-beta1 did not modify inflammation but clearly stimulated PG synthesis and restored PG content of depleted cartilage. TGF-beta2 appeared to be as potent as TGF-beta1 in the stimulation of cartilage repair, and both TGF-beta isoforms also stimulated the formation of chondrophytes in this rodent model. In contrast to TGF-beta, three intra-articular injections with 200 ng BMP-2 did not stimulate the repair process. In summary, this study demonstrates for the first time that local administration of TGF-beta into arthritic joints stimulates the replenishment of PGs in depleted cartilage.
A high-performance CMOS-SOI antenna switch for the 2.5-5 GHz band (2003)

Taking full advantage of the high resistivity substrate and underlying oxide of silicon-on-insulator (SOI) technology, a high-performance CMOS single-pole double-throw (SPDT) T/R switch for Bluetooth class-II applications has been designed and fabricated in a partially depleted 0.25-μm SOI process. To compare the influence on losses and isolation of the substrate resistivity, the switch has been integrated above standard and high resistivity (20 /spl Omega//spl middot/cm and 1 k/spl Omega//spl middot/cm) substrates. The switch over the standard resistivity substrate exhibits 1 dB of insertion loss and 45dB of isolation at 2.4 GHz. With the high resistivity substrate, the overall performances are strongly improved until 0.7-dB insertion loss and a 54-dB isolation at 2.4 GHz. At 5 GHz, the switch over the high resistivity substrate keeps insertion loss and isolation at 1 and 46 dB, respectively. In both cases, the measured 1-dB input compression point is 12 dBm. The targeted Bluetooth class-II specifications have been fully fitted.
Increased Pregnancy‐Associated Plasma Protein‐A (PAPP‐A) Concentrations in Peritoneal Fluid of Women with Endometriosis (2003)

We conclude that PF levels of PAPP-A vary during the menstrual cycle, and are highest in the secretory phase. We also find that PF PAPP-A levels are significantly increased in women with endometriosis, and that the degree of elevation corresponds to the extent of disease.
Multidrug resistance of DNA-mediated transformants is linked to transfer of the human mdr1 gene. (1986)

Mouse NIH 3T3 cells were transformed to multidrug resistance with high-molecular-weight DNA from multidrug-resistant human KB carcinoma cells. The patterns of cross resistance to colchicine, vinblastine, and doxorubicin hydrochloride (Adriamycin; Adria Laboratories Inc.) of the human donor cell line and mouse recipients were similar. The multidrug-resistant human donor cell line contains amplified sequences of the mdr1 gene which are expressed at high levels. Both primary and secondary NIH 3T3 transformants contained and expressed these amplified human mdr1 sequences. Amplification and expression of the human mdr1 sequences and amplification of cotransferred human Alu sequences in the mouse cells correlated with the degree of multidrug resistance. These data suggest that the mdr1 gene is likely to be responsible for multidrug resistance in cultured cells.
Interleukin 25 regulates type 2 cytokine-dependent immunity and limits chronic inflammation in the gastrointestinal tract (2006)

The cytokine interleukin (IL) 25 has been implicated in the initiation of type 2 immunity by driving the expression of type 2 cytokines such as IL-5 and IL-13, although its role in the regulation of immunity and infection-induced inflammation is unknown. Here, we identify a dual function for IL-25: first, in promoting type 2 cytokine-dependent immunity to gastrointestinal helminth infection and, second, in limiting proinflammatory cytokine production and chronic intestinal inflammation. Treatment of genetically susceptible mice with exogenous IL-25 promoted type 2 cytokine responses and immunity to Trichuris. IL-25 was constitutively expressed by CD4+ and CD8+ T cells in the gut of mouse strains that are resistant to Trichuris, and IL-25-deficient mice on a genetically resistant background failed to develop a type 2 immune response or eradicate infection. Furthermore, chronically infected IL-25(-/-) mice developed severe infection-induced intestinal inflammation associated with heightened expression of interferon-gamma and IL-17, identifying a role for IL-25 in limiting pathologic inflammation at mucosal sites. Therefore, IL-25 is not only a critical mediator of type 2 immunity, but is also required for the regulation of inflammation in the gastrointestinal tract.
Purification and Characterization of a Glucoamylase from Humicola grisea (1995)

A thermostable extracellular glucoamylase from the thermophilic fungus Humicola grisea was purified to homogeneity. Its molecular mass and isoelectric point were 74 kDa and 8.4, respectively. The enzyme contained 5% carbohydrate, showed maximal activities at pH 6.0 and 60(deg)C, and was stable at 55(deg)C and pH 6.0 for 2 h. The K(infm) of soluble starch hydrolysis at 50(deg)C and pH 6.0 was 0.14 mg/ml. The purified enzyme was remarkably insensitive to glucose.
Equalization of Multimode Optical Fiber Systems (1982)

Decision feedback equalization (DFE) may provide a simple way to dramatically increase the bit rate on multimode optical systems. Computer simulations of digital multimode systems with tapped delay-line linear equalization and/or DFE are described. Results indicate that with relatively simple hardware it may be possible to increase by many times the usable bit rate on dispersion-limited optical channels, with a power penalty less than that for multilevel transmission and without the latter's complexity. For example, one could double the bit rate of a two-level system by paying an equalization power penalty of about 3 dB with DFE, whereas doubling the bit rate by going to four levels requires a penalty of 4.8 dB.
Sulfur-containing 1,3-dialkylxanthine derivatives as selective antagonists at A1-adenosine receptors (1989)

Sulfur-containing analogues of 8-substituted xanthines were prepared in an effort to increase selectivity or potency as antagonists at adenosine receptors. Either cyclopentyl or various aryl substituents were utilized at the 8-position, because of the association of these groups with high potency at A1-adenosine receptors. Sulfur was incorporated on the purine ring at positions 2 and/or 6, in the 8-position substituent in the form of 2- or 3-thienyl groups, or via thienyl groups separated from an 8-aryl substituent through an amide-containing chain. The feasibility of using the thienyl group as a prosthetic group for selective iodination via its Hg2+ derivative was explored. Receptor selectivity was determined in binding assays using membrane homogenates from rat cortex [( 3H]-N6-(phenylisopropyl)adenosine as radioligand] or striatum [3H]-5'-(N-ethylcarbamoyl)adenosine as radioligand] for A1- and A2-adenosine receptors, respectively. Generally, 2-thio-8-cycloalkylxanthines were at least as A1 selective as the corresponding oxygen analogue. 2-Thio-8-aryl derivatives tended to be more potent at A2 receptors than the oxygen analogue. 8-[4-[(Carboxy-methyl)oxyl] phenyl]-1,3-dipropyl-2-thioxanthine ethyl ester was greater than 740-fold A1 selective.
Aripiprazole Augmentation for a Patient With Partial Remission of Panic Disorder (2009)

Harada, Tsuyoto MD; Yamada, Kazuo MD, PhD; Sakamoto, Kaoru MD, PhD; Ishigooka, Jun MD, PhD Author Information
Homogeneous silica coating of vitreophobic colloids (1996)

Gold colloids are homogeneously coated with silica via a three-step deposition process; the thickness of the silica layer can be completely controlled, and the particles can be transferred into practically any solvent.
Laboratory Test Handbook (1990)

Laboratory test handbook , Laboratory test handbook , کتابخانه مرکزی دانشگاه علوم پزشکی تهران
Preparation of VT1 and VT2 hybrid toxins from their purified dissociated subunits. Evidence for B subunit modulation of a subunit function (1991)

Verocytotoxins comprise a family of closely related subunit proteins. Two members of this group, VT1 and the immunologically distinct VT2, have been found to share similar physical properties, and yet several differences in their biological activities have been noted. The subunits of these toxins were separated using urea and isolated by high performance liquid chromatography gel filtration. Reconstituted VT1 and VT2 as well as VT1-A:VT2-B and VT2-A:VT1-B hybrid toxins were then prepared. The B subunit was found to determine cell culture specificity, cytotoxic titer, and antibody neutralizability as determined on Vero and MRC-5 cells. Cross-linking isolated B chains revealed 5 species upon sodium dodecyl sulfate-polyacrylamide gel electrophoresis for both VT1-B and VT2-B. Using an in vitro translation system, both toxin A subunits inhibited protein synthesis at concentrations as low as 4 pM. In glycolipid binding assays, VT1 and VT1-B subunits competed equally on a molar basis with 125I-VT1 for the receptor, globotriaosylceramide, however, a 1000-fold excess of VT2 was required. Ligand analysis of direct VT1 and VT2 receptor binding assays revealed a difference in binding affinity constants (Kd of VT1 = 4.6 x 10(-8) M; VT2 = 3.7 x 10(-7) M).
Overall survival benefit with masitinib mesylate in imatinib-naive, locally advanced, or metastatic gastrointestinal stromal tumor (GIST): 4-years follow-up of the French Sarcoma Group phase II trial. (2011)

85 Background: Masitinib is a novel tyrosine kinase inhibitor which, in vitro, has greater activity and selectivity than imatinib (IM) against both wild-type KIT receptor and its mutated form in the juxtamembrane region (IC 50=100 nM versus 200 nM for IM, 3 nM versus 27nM and 40 nM versus 120nM, respectively, for exons 9,11, and 13). This multicenter phase II study evaluated efficacy and safety of masitinib as a first-line treatment of advanced GIST. Methods: IM-naïve patients with inoperable, locally advanced or metastatic GIST received oral masitinib (7.5 mg/kg/day) until progression, refusal or toxicity. Efficacy variables included response rate, best response (RECIST), progression-free survival (PFS) and overall survival (OS). Initial results were previously reported in EJC 2010. We present here the same series with updated PFS and OS (median follow up of 48 months). Results: 30 patients with a median age of 58 years (60% of males) were included from June 2005 to April 2007 in five French institutions. At the cut-off date (31 august 2010), 9 patients are still under treatment with a median treatment duration of 41 months (min=33, max=52). Two additional progressions have been reported for a total of 14 events (13 progressions and 1 death). Updated median PFS is 41 months (95% CI: [17.5; NR]) with PFS rates of 60% [39; 77], 56% [35; 73] and 45% [24; 64] respectively at 2, 3 and 4 years. With 8 patients dead, median OS is not yet reached with OS rates of 90% [72; 97], 87% [68; 95] and 74% [52; 87], respectively, at 2, 3, and 4 years. The main frequent relevant grade 3 toxicities were: rash (10%), neutropenia (7%) and abdominal pain (7%) with one patient presented a grade 4 skin exfoliation. No other relevant long-term toxicities were reported and no more patients discontinued treatment due to suspected toxicity. Conclusions: The long term results observed with masitinib confirm a very interesting activity with prolonged PFS and OS. These results support the head to head comparison with imatinib in the currently ongoing phase III randomized clinical trial in first line locally advanced or metastatic GIST patients. [Table: see text]
pH-associated Brain Injury in Cerebral Ischemia and Circulatory Arrest (1996)

Neuronal injury remains a major limitation in therapies directed toward cardiopulmonary resuscitation and cerebral ischemia. We summarize clinical and experimental information regarding pH-modulated mechanisms of cerebral ischemic injury and the status of antiacidosis therapies relative to the brain. A large body of evidence in animals and humans indicates that cerebral pH can modulate, and perhaps mediate, ischemic brain pathology and influence functional outcome. The importance of low pH and brain bicarbonate levels during reperfusion as a secondary injury remains an open question of therapeutic importance. Under specific conditions, acidosis may be neuroprotective, but this is an area of current controversy. Effective antiacidosis therapy must address the possibility of synergism and competition among multiple injury mechanisms.
Chemical differentiating agents. Differentiation of HL-60 cells by hexamethylenebis[acetamide]analogs (1987)

Hexamethylenebis[acetamide] (HMBA) is an agent in clinical trial that induces differentiation of certain types of tumor cells to nonmalignant phenotypes. In an attempt to discover a more potent compound, a number of bis-functionalized amides, imides, and hydrazine derivatives of HMBA were prepared and evaluated in vitro with the HL-60 human promyelocytic leukemia cell line. Among the compounds evaluated, the 5,5-dimethylhydantoin derivative is almost 10 times more potent than HMBA in inducing differentiation. The bis-imide, diacetyl-HMBA, is both more potent and effective than its parent compound. Six of the 16 compounds evaluated cause at least 20% differentiation. An inverse relationship between the degree of differentiation and the percentage of viable cells is described for HMBA and its analogues.
Initial North American experience with botulinum toxin type a for treatment of anismus (1996)

BTX-A is extremely successful for temporary treatment of anismus that is refractory to BF management. However, because the mechanism of action is short, longer term results are only 50 percent successful. Hopefully, modifications in the strain of BTX-A and dose administered will allow longer periods of success or a repeat trial of BF. Nonetheless, this preliminary report is very encouraging in offering a method of managing this recalcitrant condition.