gebhart/patrepeval huggingface dataset:
[Molecular-target therapy for advanced malignant melanoma]. (2013)

Malignant melanoma is insensitive to chemotherapy, and standard therapy for metastatic melanoma has been dacarbazine for years. Molecular abnormalities of malignant melanoma, mainly of MAP kinase signals such as BRAF mutation, have been clarified, and molecular target therapy for melanoma has been developed recently. Vemurafenib, an inhibitor for mutated BRAF, has shown its efficacy for the first time, with response rate of more than 50%, and an overall improvement in survival compared with dacarbazine in a phase III study. Skin toxicities including squamous cell carcinoma, are the most severe adverse events. Another BRAF inhibitor, dabrafenib, and a MEK inhibitor, trametinib, have shown excellent efficacy in clinical studies. Melanoma also has high immunogenicity, and cytokines or cell immunotherapy have shown some efficacy. Recently, the importance of immune checkpoints which adjust T-cell activation, such as the cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), -B7 or the programmed cell death protein-1(PD1)-PD1 ligand(PDL1), have been clarified. Targeting those immune checkpoints is expected to be effective for enhancing tumor immunity. CTLA-4 antibody ipilimumab has been reported to improve overall survival in two phase III studies. Major adverse events were autoimmune response such as colitis, eruption, liver dysfunction and endocrineopathies. Antibodies to PD1 or PDL1 have shown a higher response rate than those of ipilimumab, and seem to accompany fewer autoimmune responses in phase I studies. These two types of targeting therapy are expected to be standard therapies for melanoma.
Effects of a New Serotonin Antagonist, Ketanserin, in Experimental and Clinical Hypertension (1988)

Ketanserin is an agent whose main pharmacologic action is antagonism of serotonin (5-hydroxytryptamine, 5HT) receptors of the 5HT2 subtype. It also has weak alpha 1-adrenergic blocking properties, which may contribute to the acute blood pressure lowering effects seen in animal models of hypertension. During chronic treatment of hypertension in animals, the 5HT2 antagonistic properties, or a combination of 5HT2 and alpha 1-antagonistic effects, seems to be responsible for ketanserin's hypotensive action. Studies of patients with hypertension have demonstrated the therapeutic effects of ketanserin in monotherapy and combination therapy. In humans, the drug has a terminal half-life of 12-25 hours, and a twice daily dosage will lower blood pressure over the day. Ketanserin is a vasodilator that acts on both resistance and capacitance vessels. Chronic treatment with the drug causes minimal reflex changes in cardiovascular function, as well as sustained blood pressure reduction comparable with the effects of beta-adrenergic blockers or diuretics. In elderly patients, the therapeutic effects of ketanserin appear to be greater, and side effects are less frequent compared with beta-blockers and diuretics. In addition to its antihypertensive action, ketanserin also produces other effects that may be important in reducing cardiovascular morbidity and mortality in patients with hypertension. Some studies have shown a reduction in total and low-density lipoprotein (LDL) cholesterol, and a rise in high-density lipoprotein (HDL) cholesterol. Ketanserin also reduces ex vivo platelet aggregation and inhibits the serotonin-induced platelet release reaction. Worldwide experience with ketanserin in the treatment of hypertension indicates that it is a safe and effective agent for long-term therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
Prolonged Colonization of Mice by Vibrio cholerae El Tor O1 Depends on Accessory Toxins (2007)

Cholera epidemics caused by Vibrio cholerae El Tor O1 strains are typified by a large number of asymptomatic carriers who excrete vibrios but do not develop diarrhea. This carriage state was important for the spread of the seventh cholera pandemic as the bacterium was mobilized geographically, allowing the global dispersion of this less virulent strain. Virulence factors associated with the development of the carriage state have not been previously identified. We have developed an animal model of cholera in adult C57BL/6 mice wherein V. cholerae colonizes the mucus layer and forms microcolonies in the crypts of the distal small bowel. Colonization occurred 1 to 3 h after oral inoculation and peaked at 10 to 12 h, when bacterial loads exceeded the inoculum by 10- to 200-fold, indicating bacterial growth within the small intestine. After a clearance phase, the number of bacteria within the small intestine, but not those in the cecum or colon, stabilized and persisted for at least 72 h. The ability of V. cholerae to prevent clearance and establish this prolonged colonization was associated with the accessory toxins hemolysin, the multifunctional autoprocessing RTX toxin, and hemagglutinin/protease and did not require cholera toxin or toxin-coregulated pili. The defect in colonization attributed to the loss of the accessory toxins may be extracellularly complemented by inoculation of the defective strain with an isogenic colonization-proficient V. cholerae strain. This work thus demonstrates that secreted accessory toxins modify the host environment to enable prolonged colonization of the small intestine in the absence of overt disease symptoms and thereby contribute to disease dissemination via asymptomatic carriers.
Evidence that C1 and C2 propriospinal neurons mediate the inhibitory effects of viscerosomatic spinal afferent input on primate spinothalamic tract neurons (1992)

1. Lumbosacral spinothalamic tract (STT) neurons can be inhibited by noxious pinch of the contralateral hindlimb or either forelimb and by electrical stimulation of cardiopulmonary sympathetic, splanchnic, and hypogastric afferents. A previous study found that spinal transections between C2 and C4 sometimes abolished the inhibitory effect of spinal afferent input and sometimes left it intact. This suggested that propriospinal neurons in the C1 and C2 segments might mediate this effect. To test whether neurons in the C1 and C2 segments were involved in producing this inhibitory effect, the magnitude of the reduction in neural activity was measured in the same STT neuron before and after spinal transection at C1 or between C3 and C7. 2. All neurons were antidromically activated from the contralateral thalamus and thoracic spinal cord. For us to accept a neuron for analysis, the characteristics of the somatic input and the latency and shape of the antidromatic spike produced by spinal cord stimulation had to be the same before and after the spinal transection. Also, spinal transection often causes a marked increase in spontaneous cell activity, which may affect the magnitude of an inhibitory response. To avoid this confounding problem, a cell was accepted for analysis only if it showed marked inhibition of high cell activity evoked by somatic pinch before spinal transection. For analysis 13 STT neurons met these criteria: 6 neurons were in monkeys with C1 transections, and 7 neurons were in animals with transections between C3 and C7.(ABSTRACT TRUNCATED AT 250 WORDS)
Substrate Effects in the Extraction of Diesel Using Supercritical Carbon Dioxide (1992)

Diesel and dodecane have been extracted from various substrates using supercritical CO{2}. The substrates include sand, activated carbon and a zeolite. The extraction efficiencies have been compared in terms of the substrate's surface properties.
Conservation of the sequence of islet amyloid polypeptide in five mammals is consistent with its putative role as an islet hormone. (1989)

Islet amyloid polypeptide (IAPP) is a 37-amino acid peptide found in the pancreatic amyloid deposits of type II (non-insulin-dependent) diabetic patients and insulinomas. We previously reported the nucleotide sequence of a human cDNA, which indicated that IAPP is a C-terminally amidated peptide derived by proteolytic processing of an 89-amino acid precursor. We now report the isolation of cDNA clones coding for cat, rat, mouse, and guinea pig IAPP precursors, obtained using the combination of "amplification of homologous DNA fragments" (AHF) and "rapid amplification of cDNA ends" (RACE). The predicted structure of IAPP precursors from these four mammals revealed that the IAPP moiety of each is derived from an 89- to 93-amino acid precursor by proteolytic processing and is likely to be amidated at the C terminus. The predicted amino acid sequence identities between the IAPP domains of these four mammals and human IAPP were 89% (cat), 84% (rat and mouse), and 78% (guinea pig). Within the IAPP domains, the N-terminal and C-terminal amino acid sequences are very highly conserved among the mammals, as is also the case with a structurally related neuropeptide, calcitonin-gene-related peptide (CGRP), suggesting that IAPP and CGRP interact with similar though not identical receptors. By contrast, the N- and C-terminal propeptides of the IAPP precursor show very little sequence conservation, which suggests that these regions do not represent additional biologically active molecules. Interspecies variations in the amino acid sequence of residues 20-29 of IAPP may account for the presence of amyloid deposits in the islets of humans and cats and their absence in rats and mice.
Nucleic Acid AptamersFrom Selection in Vitro to Applications in Vivo (2000)

Aptamers are nucleic acid ligands which are isolated from combinatorial oligonucleotide libraries by in vitro selection. They exhibit highly complex and sophisticated molecular recognition properties and are capable of binding tightly and specifically to targets ranging from small molecules to complex multimeric structures. Besides their promising application as molecular sensors, many aptamers targeted against proteins are also able to interfere with the proteins' biological function. Recently developed techniques facilitate the intracellular application of aptamers and their use as in vivo modulators of cellular physiology. Using these approaches, one can quickly obtain highly specific research reagents that act on defined intracellular targets in the context of the living cell.
Photoaffinity labeling of the erythropoietin receptor and its identification in a ligand-free form (1991)

Pure human recombinant erythropoietin (EP) was acylated through a primary amino residue with a cross-linking reagent, N-[[3-[[4-[(p-azido-m-[125I]iodophenyl)azo]benzoyl]amino] propanoyl]oxy]-succinimide (Denny-Jaffe reagent), which is photoreactive and cleavable at the azo residue. The resulting conjugated hormone (DJ-EP) was purified from unmodified EP by reverse-phase high-pressure liquid chromatography and maintained its capacity to bind to receptors for EP on erythroid progenitor cells. The receptor for EP was previously identified as two related proteins of 100 and 85 kDa molecular mass by chemical cross-linking to 125I-EP. Recently, D'Andrea and co-workers [(1989) Cell 57, 277-285] cloned a cDNA that codes for a protein of 55-66 kDa, which is thought to be the EP receptor. In this report, cross-linking to the receptor through the monofunctional DJ-EP labeled the same 140- and 125-kDa molecular mass bands (100- and 85-kDa proteins) cross-linked with 125I-EP and disuccinimidyl suberate. Furthermore, cleavage of the azo bond of the DJ-EP receptor complex by sodium dithionite (80 degrees C, 5 min) demonstrated that proteins of 105 and 90 kDa were labeled in ligand-free form by DJ-EP. This result demonstrates that artifactual cross-linking of multiple proteins or other artifacts of cross-linking do not explain the difference in molecular mass of the EP receptor identified by cross-linking and the receptor identified by expression cloning.
Conformal and Small Antenna Designs (1981)

Abstract : Select antennas are described that can be used effectively on conformal surfaces. Most of these antennas are compact, are electrically and physically small, and can be easily integrated into conical and cylindrical bodies. Edge-slot, microstrip, and dielectric rod radiator design techniques are employed in the development of these antennas. Critical design parameters, modes of radiation, empirical data, and theoretical considerations are discussed. The intrinsic properties and characteristics of selected dielectric materials are considered.
Folate-Targeted Hapten Immunotherapy of Adjuvant-Induced Arthritis: Comparison of Hapten Potencies (2009)

We have previously reported that disease symptoms can be greatly ameliorated in rodents with adjuvant-induced arthritis (AIA) by first immunizing the rodents against fluorescein and then treating the animals with folate−fluorescein. In this targeted hapten therapy, folate−fluorescein was shown to decorate folate receptor (FR)-expressing activated macrophages with fluorescein (an immunogenic hapten), leading to binding of antifluorescein antibodies and the consequent elimination of the activated macrophages by Fc receptor-expressing immune cells. In the current study, we compare the therapeutic potencies of a variety of FR-targeted haptens in treating the symptoms of AIA in rats. Rats were immunized with either dinitrophenyl (DNP) or trinitrophenyl (TNP) conjugated to keyhole limpet hemocyanin followed by induction of AIA with heat-inactivated Mycobacterium butyricum. Following development of arthritis, rats were treated with one of five folate−hapten conjugates (folate−DNP1, folate−DNP2, folate−DNP3, folate−FITC, or folate−TNP) at two different doses (30 nmol/kg or 200 nmol/kg) 5×/week for 25 days. Symptoms of AIA in treated rats, including paw swelling, arthritis score, splenomegaly, bone erosion, and FR+ activated macrophage density in inflamed tissues, were quantitated over the course of therapy. Although all folate−hapten conjugates promoted a reduction in disease symptoms, folate−TNP and folate−FITC proved to be more potent than any of the 3 folate−DNP conjugates. We conclude that both folate−TNP and folate−FITC constitute promising haptens for use in FR-targeted immunotherapy of arthritis.
S,X-Acetals in Nucleoside Chemistry. III1. Synthesis of 2′-and 3′-O-Azidomethyl Derivatives of Ribonucleosides (2000)

2'- and 3'-O-azidomethyl derivatives of ribonucleosides were obtained by splitting the corresponding methylthiomethyl derivatives of ribonucleosides with bromine or SO2Cl2 followed by lithium azide treatment.
Dispositivos móveis: Desafios para o marketing (2012)

Abstract The new millennium brought with it the advancement of digital technologies providing the link between people through computers, mobile phones and televisions, thanks to digital connections. You can communicate, research, study, buy and sell, entertain and relate to, creating a society by means of mobile devices. Analyzing this scenario presents the proposition of virtual context as a society, where people cultivate their habits, behaviors and values, creating a space for interactive communication. In this context of relationships, citizens across the universe are provided by mobile devices, creating new forms of relationships with commercial purposes.
Intranasal capsaicin is efficacious in non‐allergic, non‐infectious perennial rhinitis. A placebo‐controlled study (1997)

As involvement of inflammation could not be demonstrated, it is not surprising that capsaicin has no effect on inflammatory mediators. This suggests that inflammatory cells do not play a major part in the pathogenesis of NANIPER.
Analysis of oxosteroids by nano-electrospray mass spectrometry of their oximes (2000)

A method for the analysis of neutral oxosteroids by electrospray mass spectrometry is described. The oxosteroids are converted into their oximes by treatment with hydroxyammonium chloride in aqueous methanol. Intense peaks corresponding to protonated oxime molecules are observed in nano-electrospray mass spectra. The detection limits for the oximes of progesterone, pregnenolone and dehydroepiandrosterone were 2.5, 5 and 25 pg/microL, respectively, approximately 20 times lower than for the underivatised steroids. The signal intensities were proportional to the concentration of the steroids in the range of 500 to 2.5 pg/microL. Fragmentation by collision-induced dissociation (CID) was studied using oximes of 28 model steroids carrying an oxo group at C-3, C-17 or C-20. Some of the steroid oximes were labelled with deuterium or (15)N. Fragment ions were observed which yielded useful structural information. Upon CID, protonated oximes of 3-oxo-Delta(4)-steroids produced abundant ions by cleavage through the B-ring and by loss of the side chain, while protonated oximes of saturated 3-oxosteroids did not give abundant ions by cleavage through the B-ring. Protonated oximes of 20-oxosteroids unsubstituted at C-21, C-17 or C-16 produced a characteristic ion at m/z 86 containing the side chain, C-16 and C-17. Protonated oximes of steroids containing only a 17-oxo group gave fewer ions of diagnostic value. Coupled with the selective isolation of steroid oximes from a biological matrix this method of derivatisation and CID may be used for the analysis of neutral oxosteroids in biological samples.
Differences in therapeutic indexes of combination metronomic chemotherapy and an anti-VEGFR-2 antibody in multidrug-resistant human breast cancer xenografts. (2002)

One of the greatest barriers to the treatment of cancer with chemotherapeutic drugs is acquisition of drug resistance. This includes multidrug resistance mediated by P-glycoprotein (Pgp) to multiple lipophilic natural compounds such as taxanes, doxorubicin (Adriamycin), and vinblastine. The considerable efforts made thus far to reverse this and other types of drug resistance have had very limited success. We report here that a variety of orthotopic human breast cancer xenografts selected for high levels of Pgp and multidrug resistance respond in a significant and durable manner to different continuous low-dose (e.g., one-tenth the maximum tolerated dose of chemotherapy) chemotherapy regimens, when used in combination with an antivascular endothelial cell growth factor (anti-VEGF) receptor-2 (flk-1)-neutralizing antibody (DC101). The Pgp substrates paclitaxel (Taxol), Adriamycin, and vinblastine were all effective using this type of combination treatment, although the chemotherapy protocols showed little or no effect as monotherapies. Similar results were also obtained using cisplatinum (a non-Pgp substrate drug) against cisplatinum-resistant tumors. Evidence of significant tumor cell death by the combination treatment was detected within 3 weeks of initiation of therapy by histopathological analysis, in the absence of shrinkage of tumor mass. There were, however, marked differences in the cumulative toxicity of long-term regimens of Adriamycin and cisplatinum, where toxicity was observed, when compared with the tubulin inhibitors, vinblastine and Taxol, where it was not. We conclude that vascular-targeting protocols involving frequent administration of very low doses of certain chemotherapeutic drugs can provide a stable and safe way to circumvent multidrug resistance in established orthotopically growing tumors, as long as these are used in combination with a second antiangiogenic drug, in this case, anti-VEGFR-2 blocking antibodies.
N‐Tosyloxycarbamates as Reagents in Rhodium‐Catalyzed CH Amination Reactions (2008)

Metal nitrenes for use in C-H insertion reactions were obtained from N-tosyloxycarbamates in the presence of an inorganic base and a rhodium(II) dimer complex catalyst. The C-H amination reaction proceeds smoothly, and the potassium tosylate that forms as a byproduct is easily removed by filtration or an aqueous workup. This new methodology allows the amination of ethereal, benzylic, tertiary, secondary, and even primary C-H bonds. The intramolecular reaction provides an interesting route to various substituted oxazolidinones, whereas the intermolecular reaction gives trichloroethoxycarbonyl-protected amines that can be isolated with moderate to excellent yields and that cleave easily to produce the corresponding free amine. The development, scope, and limitations of the reactions are discussed herein. Isotopic effects and the electronic nature of the transition state are used to discuss the mechanism of the reaction.
Controlled trial of vasopressin plus nitroglycerin vs. vasopressin alone in the treatment of bleeding esophageal varices (1986)

Thirty-nine patients admitted during a 16-month period for acute bleeding from varices confirmed by emergency endoscopy were randomized to receive either continuous intravenous infusions of vasopressin alone (0.66 units per min) (Group I: 19 patients) or vasopressin plus sublingual nitroglycerin (0.6 mg every 30 min for 6 hr) (Group II: 20 patients). The two groups of patients were similar in the type and severity of their cirrhosis. Bleeding was controlled initially in 47% (9/19) of the patients in Group I and 55% (11/20) of the patients in Group II after 6 hr of infusion (not statistically significant). Complete control of bleeding during 24 hr of infusion was achieved in only 4 of 19 patients in Group I (21%) but in 9 of 20 in Group II (45%). This difference is not statistically significant. The total number of patients with complications during infusions were significantly different statistically in the vasopressin and vasopressin-nitroglycerin groups, respectively (17/19 vs. 7/20, p less than 0.001). Major complications requiring immediate cessation of infusions were observed in 6 of 19 of the patients in Group I (32%) and in 2 of 20 in Group II (10%) (p less than 0.05). Mortality (58% in Group I, 55% in Group II) and transfusion requirements were similar in the two groups. This study shows that the addition of sublingual nitroglycerin to intravenous vasopressin does not alter the efficacy of vasopressin alone in controlling hemorrhage from esophageal varices, but it does significantly reduce the complications.