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121.
Gregory K. Pike Jonathan J. Abramson Guy Salama 《Journal of muscle research and cell motility》1989,10(5):337-349
Summary The local anaesthetics, tetracaine and procaine have previously been found to block, induce or potentiate Ca2+ release from the sarcoplasmic reticulum (SR) of skeletal muscle depending on the preparation, experimental conditions and design. We now show that low concentrations of tetracaine and procaine block SR Ca2+ release whereas high concentrations induce release from the SR of amphibian and mammalian skinned fibres. Both actions depend on pCa, such that a shift in pCa can alter their effect from blocking to releasing Ca2+. In skinned fibres with Ca2+-loaded SR, tetracaine (1mm) produced a tonic contraction with a time to half-peak of 15–20 s and a magnitude reaching 80% of maximum force. Ca2+ release by tetracaine or procaine occured at pCa 6.5 and was not blocked by Ruthenium Red (RR) (25 m). This action of tetracaine was attributed to SR Ca2+ release rather than to a displacement of bound Ca2+ because fibres lacking a functional SR due to pre-treatment with quercetin (100 m), A 23187 (100 g ml–1) or Triton X-100 (1%) did not contract after additions of tetracaine. Lower concentrations of tetracaine (0.5mm) and procaine (10mm) blocked contractions due to caffeine (at pCa 6.73), sulphydryl oxidizing agents, or Ca2+-induced Ca2+ release (CICR). The inhibition of CICR as a function of pCa was difficult to measure quantitatively since lowering pCa to elicit CICR twitches was sufficient to initiate tetracaine-induced tonic contractions.Experiments with isolated SR vesicles showed that 1mm tetracaine inhibited CICR, over a wide range of pCa but 3–5mm tetracaine induced rapid Ca2+ release. The opposite effects of tetracaine and procaine depend mostly on their concentration in SR vesicles and/or pCa in skinned fibres. Blockade of release seems to occur via the CICR pathway, and induction of release through an increase in SR membrane permeability.Abbreviations SR
sarcoplasmic reticulum
- HEPES
N-2-hydroxy-ethylpiperazine-N1-2-ethanesulphonic acid
- EGTA
ethylene glycol bis (-aminoethyl ether)-N,N,N1,-N1-tetraacetic acid
- CICR
Ca2+-induced Ca2+ release
- MOPS
morpholinopropane sulphonic acid
- RR
Ruthenium Red 相似文献
122.
Comparative Analysis of Apoptosis and Inflammation Genes of Mice and Humans 总被引:4,自引:0,他引:4
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John C. Reed Kutbuddin Doctor Ana Rojas Juan M. Zapata Christian Stehlik Loredana Fiorentino Jason Damiano Wilfried Roth Shu-ichi Matsuzawa Ruchi Newman Shinichi Takayama Hiroyuki Marusawa Famming Xu Guy Salvesen RIKEN GER Group GSL Members Adam Godzik 《Genome research》2003,13(6B):1376-1388
Apoptosis (programmed cell death) plays important roles in many facets of normal mammalian physiology. Host-pathogen interactions have provided evolutionary pressure for apoptosis as a defense mechanism against viruses and microbes, sometimes linking apoptosis mechanisms with inflammatory responses through NFκB induction. Proteins involved in apoptosis and NFκB induction commonly contain evolutionarily conserved domains that can serve as signatures for identification by bioinformatics methods. Using a combination of public (NCBI) and private (RIKEN) databases, we compared the repertoire of apoptosis and NFκB-inducing genes in humans and mice from cDNA/EST/genomic data, focusing on the following domain families: (1) Caspase proteases; (2) Caspase recruitment domains (CARD); (3) Death Domains (DD); (4) Death Effector Domains (DED); (5) BIR domains of Inhibitor of Apoptosis Proteins (IAPs); (6) Bcl-2 homology (BH) domains of Bcl-2 family proteins; (7) Tumor Necrosis Factor (TNF)-family ligands; (8) TNF receptors (TNFR); (9) TIR domains; (10) PAAD (PYRIN; PYD, DAPIN); (11) nucleotide-binding NACHT domains; (12) TRAFs; (13) Hsp70-binding BAG domains; (14) endonuclease-associated CIDE domains; and (15) miscellaneous additional proteins. After excluding redundancy due to alternative splice forms, sequencing errors, and other considerations, we identified cDNAs derived from a total of 227 human genes among these domain families. Orthologous murine genes were found for 219 (96%); in addition, several unique murine genes were found, which appear not to have human orthologs. This mismatch may be due to the still fragmentary information about the mouse genome or genuine differences between mouse and human repertoires of apoptotic genes. With this caveat, we discuss similarities and differences in human and murine genes from these domain families. 相似文献
123.
Savage ND Harris SH Rossi AG De Silva B Howie SE Layton GT Lamb JR 《European journal of immunology》2002,32(10):2905-2914
The generation of a productive primary immune response is dependent on the ability of na?ve T lymphocytes to recirculate through peripheral lymph organs to encounter specific antigen. The process of na?ve CD4(+) T cell entry into lymph nodes correlates with cell surface expression of L-selectin (CD62L), which mediates early tethering and rolling events to endothelium prior to entry. Here, we demonstrate that surface expression of CD62L enhances CD4(+) T cell activation in vitro. The synthetic hydroxamate metalloproteinase inhibitor (BB-3103), specifically inhibits activation-induced shedding of CD62L from CD4(+) T cells by TCR cross-linking and lowers proliferation in part by reducing rapid tyrosine phosphorylation of zeta-associated protein 70 kDa (ZAP-70) and by increasing cytosolic free Ca(2+) concentration mobilization. BB-3103 also inhibited the proliferative response of both murine CD4(+) Th1 and Th2 subsets in vitro but the inhibitory effects were sustained only in Th2-type cells. Similarly, BB-3103 mediated prolonged inhibition of allergen-dependent peripheral T cell proliferation in atopic dermatitis patients but not in healthy controls. Analysis of CD62L expression on murine CD4(+) T cell subsets revealed that surface expression was maintained on Th1 cells but not Th2 cells. The differential effects of BB-3103 on primed effector CD4(+) T cells may provide new insights into generating therapeutic agents capable of redressing the Th2/Th1 imbalance in allergic diseases. 相似文献
124.
Jannot AS Meziani R Bertrand G Gérard B Descamps V Archimbaud A Picard C Ollivaud L Basset-Seguin N Kerob D Lanternier G Lebbe C Saiag P Crickx B Clerget-Darpoux F Grandchamp B Soufir N Melan-Cohort 《European journal of human genetics : EJHG》2005,13(8):913-920
The occuloalbinism 2 (OCA2) gene, localized at 15q11, encodes a melanosomal transmembrane protein that is involved in the most common form of human occulo-cutaneous albinism, a human genetic disorder characterized by fair pigmentation and susceptibility to skin cancer. We wondered whether allele variations at this locus could influence susceptibility to malignant melanoma (MM). In all, 10 intragenic single-nucleotide polymorphisms (SNPs) were genotyped in 113 patients with melanomas and in 105 Caucasian control subjects with no personal or family history of skin cancer. By comparing allelic distribution between cases and controls, we show that MM and OCA2 are associated (p value=0.030 after correction for multiple testing). Then, a recently developed strategy, the 'combination test' enabled us to show that a combination formed by two SNPs was most strongly associated to MM, suggesting a possible interaction between intragenic SNPs. In addition, the role of OCA2 on MM risk was also detected using a logistic model taking into account the presence of variants of the melanocortin 1 receptor gene (MC1R, a key pigmentation gene) and all pigmentation characteristics as melanoma risk factors. Our data demonstrate that a second pigmentation gene, in addition to MC1R, is involved in genetic susceptibility to melanoma. 相似文献
125.
Shelef K Diamond GM Diamond GS Liddle HA 《Journal of consulting and clinical psychology》2005,73(4):689-698
In this study, the authors examined the relation between adolescent and parent therapeutic alliances and treatment outcome among 65 substance-abusing adolescents receiving multidimensional family therapy. Observer ratings of parent alliance predicted premature termination from treatment. Observer ratings, but not self-report, of adolescent alliance predicted adolescents' substance abuse and dependency symptoms at posttreatment, as well as days of cannabis use at 3-month follow-up. The association between adolescent alliance and substance abuse and dependency symptoms at posttreatment was moderated by the strength of the parent alliance. Results reveal the unique and interactive effects of the 2 alliances on treatment outcome and emphasize the need for a systemic and well-articulated approach to developing and maintaining the multiple alliances inherent to family therapy. 相似文献
126.
In a series of experiments, we investigated the effects of pulsed low-level microwave irradiation on amphetamine-induced hyperthermia in the rat. Rats were irradiated in a 2,450-MHz cylindrical waveguide exposure system at 1 mW/cm2, 2 s pulses, 500 pps, average SAR of 0.6 W/kg. Acute (45 min) exposure to microwaves attenuated amphetamine-induced hyperthermia. This effect was blocked by pretreatment of the animals with the narcotic antagonist naloxone. In another experiment, rats were subjected to ten daily sessions of microwave exposure (45 min/session). On day 11, amphetamine-induced hyperthermia was studied in the animals immediately after a session of either microwave or sham exposure. Similar to the acute effect, amphetamine-induced hyperthermia was attenuated in rats irradiated with microwaves (unconditioned effect). In the sham-irradiated animals we observed a potentiation of the amphetamine-induced hyperthermia, which was a conditioned effect of microwaves. Thus, the conditioned effect (potentiation) was opposite in direction to the unconditioned effect (attenuation). No tolerance developed to the unconditioned effect after subchronic exposure. Furthermore, both conditioned and unconditioned effects of microwaves on amphetamine-induced hyperthermia could be blocked by treatment with naloxone. These data suggest that (1) microwave irradiation may activate endogenous opioids, which in turn alter the actions of psychoactive drugs, and (2) the effect of microwaves on drug action can be classically conditioned.
Offprint requests to: H. Lai 相似文献
127.
Amadou Kane Edmond Ekué Creppy Angelika Roth Robert Röschenthaler Guy Dirheimer 《Archives of toxicology》1986,58(4):219-224
The distribution of a single low dose of [3H]ochratoxin A (OTA) in different tissues of male Wistar rats, after administration by intubation, was investigated after 5 h, 24 h and 48 h. This dose corresponds to concentrations encountered in naturally contaminated feed (4 ppm). The distribution of [3H]-label varied with the time elapsed after administration; at 5 h the highest specific label was found in the stomach contents and in decreasing order in: intestinal contents, lung, liver, kidney, heart, fat, intestine, testes, and the lowest in muscles, spleen and brain. With exception of brain, fat, stomach and lung, all tissues showed maximum levels at 24 h, after which time the label decreased steadily, whereas in fat it increased.After a 12-week feeding experiment, with doses of 288.8 g/kg corresponding to an intake of 4 ppm in feed each 48 h, the DNA in liver and kidneys was investigated for damage. By the alkaline elution method combined with micro-spectrofluorimetric determinations of DNA, evidence for DNA single-strand breaks was obtained. These findings support reports on the carcinogenic action of OTA. 相似文献
128.
John Gordon Graeme Guy Leonie Walker Paul Nathan Ruth Exley Mike Clemens 《Medical oncology (Northwood, London, England)》1986,3(3-4):269-273
The autocrine growth profile of human B lymphocytes transformed with Epstein-Barr virus (EBV) was found to comprise three distinct components: a B-cell growth factor (BCGF); an interleukin-1 (IL-1)-like activity; an activity requiring cell-to-cell contact for its action. Observations on the inhibition of the EBV-carrying Daudi lymphoma line by α-interferon indicated that loss of response to these autostimulatory factors was underlying growth cessation. Furthermore, a putative for BCGF was found to be down-regulated on B cells stimulated with non-transforming mitogens but constitutively expressed following EBV-transformation. Taken together with recent evidence that normal B cells produce autostimulatory factors, these findings suggest that the special feature of autocrine growth by EBV-immortalized cells is a maintenance of what should normally be a transient phenotype, possibly through deregulation of receptor expression. This hypothesis is discussed. 相似文献
129.
Prediction of drug disposition kinetics in skin and plasma following topical administration 总被引:1,自引:0,他引:1
The development of a physically based pharmacokinetic model for percutaneous absorption is described. The simulation includes four first-order rate constants assigned the following significance: (a) absorption across the stratum corneum; (b) diffusion through the viable tissue; (c) a retardation process which retains penetrant in the stratum corneum (and hence provides a means to mathematically produce a "reservoir" effect, for example); and (d) uptake from the skin into the systemic circulation and subsequent elimination from the body. The kinetic equations of the model are solved and expressions are obtained for the concentration of penetrant within the stratum corneum (and available to subsequently partition into the viable epidermis) and the plasma concentration of the administered substance, as a function of time. Using example values for the four rate parameters, disposition profiles for the penetrant in skin and plasma were derived. The cases considered cover slow and fast stratum corneum penetrants, substances which are excreted rapidly or slowly from the body, and absorbing molecules with a variety of relative stratum corneum-viable tissue affinities. The results suggest a framework for the prediction of pharmaceutically and clinically relevant information following the topical administration of therapeutic agents for local or systemic effect. 相似文献
130.
Maria Ruiz-Castell Gwenaëlle Le Coroller Jean-Francois Landrier Djedgiga Kerkour Bernard Weber Guy Fagherazzi Brice M. R. Appenzeller Michel Vaillant Torsten Bohn 《Nutrients》2021,13(1)
Metabolic syndrome (MetS) characteristics include chronic inflammation and elevated oxidative stress. This study assessed associations between circulating concentrations of micronutrients/phytochemicals and inflammatory/oxidative stress markers with MetS and MetS components. Adults (N = 606) from the European Health Examination Survey in Luxembourg (2013–2015) were randomly selected. We performed a multivariable logistic regression model using the least absolute shrinkage and selection operator to identify MetS-associated variables. Participants with MetS had higher concentrations of C-reactive protein (CRP), 8-iso-prostaglandin F2α, leptin, insulin, and vitamins E/A, but lower concentrations of adiponectin, beta-carotene, and oxidized low-density lipoprotein. A one-unit increase in log-CRP was associated with 51% greater odds of MetS (OR = 1.51 (95% CI: 1.16, 1.98)). Adults with a one-unit increase in log-leptin were 3.1 times more likely to have MetS (3.10 (2.10, 4.72)). Women with a one-unit increase in vitamin A were associated with 3% increased odds of MetS (1.03 (1.01, 1.05)), while those with a one-unit increase in log-adiponectin were associated with 82% decreased odds (0.18 (0.07, 0.46)). Chronic inflammation best characterized adults with MetS, as CRP, adiponectin, and leptin were selected as the main MetS determinants. Micronutrients did not seem to affect MetS, except for vitamin A in women. 相似文献