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31.
Lymphocytes were cloned from animals bearing UV-induced skin tumors. These cells were I-J+, CD4-, CD8-, and had become growth factor independent. Extracts, but not supernatants, of these clones suppressed primary immune reactions in vitro against UV-induced tumors, but not methylcholanthrene-induced tumors. The cells therefore had the functional characteristics of afferent suppressor T cells directed against a common Ag on UV-induced tumors. Surface iodination of the clones revealed an extremely low level expression of molecules that might be TCR or related molecules. 相似文献
32.
Plasma melatonin concentrations were examined following three relatively low intensities of artificial light. Six normal, healthy control subjects were all exposed to (a) 200 lux, (b) 400 lux and (c) 600 lux for a three hour duration from midnight to 0300 h. Blood was also collected on a control night where light intensity was less than 10 lux throughout. Significant suppression of melatonin was observed following light of 400 lux and 600 lux intensity when compared to the control night (p less than 0.05; Mann-Whitney U-test). 200 lux light did not produce a statistically significant melatonin suppression when compared with control samples. Each light intensity produced its own individual maximal melatonin suppression by one hour of exposure. Increased duration of exposure to the light had no further influence on melatonin plasma concentrations. These data confirm a dose response relationship between light and melatonin suppression, and indicate that there is no reciprocal relationship between the effects of light intensity and the duration of exposure on maximal melatonin suppression in man. 相似文献
33.
Vanessa R. Panz Paul Ruff Barry I. Joffe Mary-Anne Kedda Harold C. Seftel 《Human genetics》1996,97(4):438-440
The frequency of DNA polymorphisms in the tyrosine kinase domain (exons 17–21) of the insulin receptor gene was assessed
in 30 black and 30 white South Africans, using single-stranded conformation polymorphism and direct sequencing analysis. A
comparison of the frequencies of the normal versus the combined polymorphic alleles, found only in exon 17, showed a significant
difference between black and white groups (P = 0.037).
Received: 25 May 1995 / Revised: 1 September 1995 相似文献
34.
Abstract: Bradykinin receptors have been subdivided into at least two major pharmacological subtypes, B1 and B2 . The cDNAs encoding functional B2 receptors have recently been cloned, but no molecular information exists at present on the B1 receptor. In this article, we describe experiments examining the possible relationship between the mRNAs encoding the B1 and B2 types of receptor. We showed previously that the Human fibroblast cell line W138 expresses both B1 and B2 receptors. In this report, we describe oocyte expression experiments showing that the B1 receptor in W138 human fibroblast cells is encoded by a distinct mRNA ∼2 kb shorter than that encoding the B2 receptor. We have used an antisense approach in conjunction with the oocyte expression system to demonstrate that the two messages differ in sequence at several locations throughout the length of the B2 sequence. Taken together with the mixed pharmacology exhibited in some expression systems by the cloned mouse receptor, the data indicate that B1 -type pharmacology may arise from two independent molecular mechanisms. 相似文献
35.
Maja Wiprächtiger Melanie Haupt Andreas Froemelt Magdalena Klotz Claudio Beretta Dominik Osterwalder Vanessa Burg Stefanie Hellweg 《Journal of Industrial Ecology》2023,27(1):254-271
Industrial ecology (IE) methodologies, such as input/output or material flow analysis and life cycle assessment (LCA), are often used for the environmental evaluation of circular economy strategies. Up to now, an approach that utilizes these methods in a systematic, integrated framework for a holistic assessment of a geographic region's sustainable circular economy potential has been lacking. The approach developed in this study (IE4CE approach) combines IE methodologies to determine the environmental impact mitigation potential of circular economy strategies for a defined geographic region. The approach foresees five steps. First, input/output analysis helps identify sectors with high environmental impacts. Second, a refined analysis is conducted using material flow and LCA. In step 3, circular strategies are used for scenario design and evaluated in step 4. In step 5, the assessment results are compiled and compared across sectors. The approach was applied to a case study of Switzerland, analyzing 8 sectors and more than 30 scenarios in depth. Carbon capture and storage (CCS) from waste incineration, biogas and cement production, food waste prevention in households, hospitality and production, and the increased recycling of plastics had the highest mitigation potential. Most of the scenarios do not influence each other. One exception is the CCS scenarios: waste avoidance scenarios decrease the reduction potential of CCS. A combination of scenarios from different sectors, including their impact on the CCS scenario potential, led to an environmental impact mitigation potential of 11.9 Mt CO2-eq for 2050, which equals 14% of Switzerland's current consumption-based impacts. 相似文献
36.
Iain M. McIntyre Christopher V. King Stan Skafidis Olaf H. Drummer 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》1993,621(2)
A sensitive method suitable for the determination of tricyclic and other antidepressants in postmortem and clinical specimens is presented. The procedure, which utilizes reversed-phase HPLC combined with dual ultraviolet wavelength detection, enables the separation of 17 commonly prescribed antidepressants and some selected metabolites in a single extraction. Peak purity was confirmed using absorbance ratios at 220 nm and 254 nm wavelengths and revealed little interference from other eluting analytes. The blood detection limit for most antidepressants was 50 ng/ml. The most commonly observed antidepressants in 281 forensic cases analysed over a two-year period with the described method were dothiepin, amitriptyline, nortriptyline and doxepin. 相似文献
37.
38.
O. A. Vanderpuye C. A. Labarrere J. A. McIntyre 《Histochemistry and cell biology》1993,100(3):241-246
Prolyl 4-hydroxylase is a heterodimeric enzyme that is crucial in the biosynthesis of collagen. The subunit of this enzyme is a multifunctional protein which is also known as protein-disulfide isomerase. Immunofluorescence and monoclonal antibody (Mab) 5B5 were used to localize the subunit in human extraembryonic tissues. The strongest sites of 5B5 reactivity were extravillous cytotrophoblasts in the basal plate, uteroplacental arteries and amniochorion, syncytiotrophoblast displayed variable weaker reactivity. Only a small fraction of placental 5B5 antigen was detected as a component of prolyl-4-hydroxylase by affinity chromatography on immobilized polyproline. The results indicate a difference in the expression of an endoplasmic reticulum marker between villous and extravillous trophoblast. The predominance of 5B5 antigen in extravillous trophoblast could be associated with an increased ability to synthesize collagen or other enzymatic reactions associated with prolyl 4-hydroxylase subunit. 相似文献
39.
Alex Graça Contato Vanessa Kaplum Débora Botura Scariot Francielle Pelegrin Garcia Hugo Falzirolli Fábio Vandresen Tânia Ueda-Nakamura Sueli de Oliveira Silva Cleuza Conceição da Silva Celso Vataru Nakamura 《化学与生物多样性》2023,20(7):e202300523
Leishmaniasis is a tropical zoonotic disease. It is found in 98 countries, with an estimated 1.3 million people being affected annually. During the life cycle, the Leishmania parasite alternates between promastigote and amastigote forms. The first line treatment for leishmaniasis are the pentavalent antimonials, such as N-methylglucamine antimoniate (Glucantime®) and sodium stibogluconate (Pentostam®). These drugs are commonly related to be associated with dangerous side effects such as cardiotoxicity, nephrotoxicity, hepatotoxicity, and pancreatitis. Considering these aspects, this work aimed to obtain a new series of limonene-acylthiosemicarbazides hybrids as an alternative for the treatment of leishmaniasis. For this, promastigotes, axenic amastigotes, and intracellular amastigotes of Leishmania amazonensis were used in the antiproliferative assay; J774-A1 macrophages for the cytotoxicity assay; and electron microscopy techniques were performed to analyze the morphology and ultrastructure of parasites. ATZ−S-04 compound showed the best result in both tests. Its IC50, in promastigotes, axenic amastigotes and intracellular amastigotes was 0.35±0.08 μM, 0.49±0.06 μM, and 15.90±2.88 μM, respectively. Cytotoxicity assay determined a CC50 of 16.10±1.76 μM for the same compound. By electron microscopy, it was observed that ATZ−S-04 affected mainly the Golgi complex, in addition to morphological changes in promastigote forms of L. amazonensis. 相似文献
40.
Roger S. McIntyre Mohammad Alsuwaidan Bernhard T. Baune Michael Berk Koen Demyttenaere Joseph F. Goldberg Philip Gorwood Roger Ho Siegfried Kasper Sidney H. Kennedy Josefina Ly-Uson Rodrigo B. Mansur R. Hamish McAllister-Williams James W. Murrough Charles B. Nemeroff Andrew A. Nierenberg Joshua D. Rosenblat Gerard Sanacora Alan F. Schatzberg Richard Shelton Stephen M. Stahl Madhukar H. Trivedi Eduard Vieta Maj Vinberg Nolan Williams Allan H. Young Mario Maj 《World psychiatry》2023,22(3):394-412
Treatment-resistant depression (TRD) is common and associated with multiple serious public health implications. A consensus definition of TRD with demonstrated predictive utility in terms of clinical decision-making and health outcomes does not currently exist. Instead, a plethora of definitions have been proposed, which vary significantly in their conceptual framework. The absence of a consensus definition hampers precise estimates of the prevalence of TRD, and also belies efforts to identify risk factors, prevention opportunities, and effective interventions. In addition, it results in heterogeneity in clinical practice decision-making, adversely affecting quality of care. The US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have adopted the most used definition of TRD (i.e., inadequate response to a minimum of two antidepressants despite adequacy of the treatment trial and adherence to treatment). It is currently estimated that at least 30% of persons with depression meet this definition. A significant percentage of persons with TRD are actually pseudo-resistant (e.g., due to inadequacy of treatment trials or non-adherence to treatment). Although multiple sociodemographic, clinical, treatment and contextual factors are known to negatively moderate response in persons with depression, very few factors are regarded as predictive of non-response across multiple modalities of treatment. Intravenous ketamine and intranasal esketamine (co-administered with an antidepressant) are established as efficacious in the management of TRD. Some second-generation antipsychotics (e.g., aripiprazole, brexpiprazole, cariprazine, quetiapine XR) are proven effective as adjunctive treatments to antidepressants in partial responders, but only the olanzapine-fluoxetine combination has been studied in FDA-defined TRD. Repetitive transcranial magnetic stimulation (TMS) is established as effective and FDA-approved for individuals with TRD, with accelerated theta-burst TMS also recently showing efficacy. Electroconvulsive therapy is regarded as an effective acute and maintenance intervention in TRD, with preliminary evidence suggesting non-inferiority to acute intravenous ketamine. Evidence for extending antidepressant trial, medication switching and combining antidepressants is mixed. Manual-based psychotherapies are not established as efficacious on their own in TRD, but offer significant symptomatic relief when added to conventional antidepressants. Digital therapeutics are under study and represent a potential future clinical vista in this population. 相似文献