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1.
The effects of M1 and M2 cholinoceptors on stimulated water transport in the urinary bladder of the common frogRana temporaria L. are described. In the presence of pirenzepine, a selective M1 cholinoceptor antagonist, carbachol stimulated water transport. Activation of M2 cholinoceptors by oxotremorine in concentrations of 0.5–5.0 μM inhibited water transport, whereas their activation by this compound in higher concentrations (10–100 μM) stimulated it. The use of the phospholipase C inhibitor neomycin (0.5 mM) and the calmodulin inhibitor W-7 (1 mM) indicated that activation of M2 cholinoceptors switches on phospholipid-Ca2+-calmodulin-dependent mechanisms. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 120, N o 9, pp. 252–254, September, 1995 (Presented by P. V. Sergeev, Member of the Russian Academy of Medical Sciences)  相似文献   

2.
This study examines the effects of the intracellular protein FKBP12.6 on action potential and associated K+ currents in isolated adult rabbit ventricular cardiomyocytes. FKBP12.6 was over-expressed by ~6 times using a recombinant adenovirus coding for human FKBP12.6. This over-expression caused prolongation of action potential duration (APD) by ~30%. The amplitude of the transient outward current (I to) was unchanged, but rate of inactivation at potentials positive to +40 mV was increased. FKBP12.6 over-expression decreased the amplitude of the inward rectifier current (I K1) by ~25% in the voltage range −70 to −30 mV, an effect prevented by FK506 or lowering intracellular [Ca2+] below 1 nM. Over-expression of an FKBP12.6 mutant, which cannot bind calcineurin, prolonged APD and affected I to and I K1 in a similar manner to wild-type protein. These data suggest that FKBP12.6 can modulate APD via changes in I K1 independently of calcineurin binding, suggesting that FKBP12.6 may affect APD by direct interaction with I K1.  相似文献   

3.
A detailed mapping of the γ-aminobutyric acid (GABA)A receptor subunits (α1, α2, α3 and β2+3) in the infralimbic/ventral prelimbic region (IL/vPL) of the rat frontal cortex was carried out using subunit-specific antibodies. The α1 and β2+3 subunit antibodies immunostained all layers of the IL/vPL region. Layers II and III displayed immunostaining of cell bodies whereas I, V and VI showed predominantly neuropil staining. The size of the α1-positive cell bodies corresponded to that of small interneurons (range, 20–55 μm2; mean ± SEM, 37 ± 5.5 μm2) as well as pyramidal cells or large interneurons (range, 87–135 μm2; mean ± SEM, 103.4 ± 9.7 μm2). However, β2+3 antibody immunostained only small cell bodies. Immunoreactivity for α2 was restricted to layers I and II, whereas α3 and α5 subunit expression was seen only in layer VI. The antibody to the α2 subunit immunostained small cell bodies (range, 29–63 μm2; mean ± SEM, 32 ± 4.5 μm2) in layer II, resembling interneurons. Conversely, both α3 and α5 antibodies immunostained large cell bodies (range, 94–151 gmm2; mean ± SEM, 115.7 ± 13.4 μm2), consistent with pyramidal cell labelling in layer VI.  相似文献   

4.
We examined the effects of niflumic acid (NFA), a chloride channel blocker, on the hyperpolarization-activated current (Ih) in newt rod photoreceptors. At 100 μM, NFA delayed the activation of Ih induced by hyperpolarizing voltage pulses to −83 mV from a holding potential of −43 mV, and reduced the steady-state current. However, reduction by NFA was weakened when Ih was activated by hyperpolarizing steps to −123 mV, suggesting that these effects were voltage-dependent. The suppressive effects of NFA on Ih were accompanied by a negative shift in activation voltage. NFA also delayed the relaxation of Ih tail currents, showing that this drug also inhibited deactivation of the current. The reversal potential and the fully activated conductance were not affected. These observations suggest that NFA reduces Ih by modifying the gating kinetics of the underlying channels. The suppressive actions of NFA remained when intracellular Ca2+ was strongly chelated, and the failure of suppression by NFA in inside-out patches suggests that the agent may act on the Ih channel from the extracellular side. These results, obtained in rod photoreceptors, are consistent with similar effects of NFA on If in cardiac myocytes, suggesting that both currents share similar pharmacological properties.  相似文献   

5.
Introduction. Expression of adhesion molecules such as α v β 3 integrin has been associated with the metastatic potential of tumor cells. The purpose of this study was to determine whether α v β 3 expression correlated with the metastatic potential of human osteosarcoma cells. Materials and methods. We developed a series of sublines (LM2–LM7) from human osteosarcoma SAOS parental cells, with progressively increasing potential to form lung metastases in nude mice after intravenous injection. SAOS parental and LM2 cells were poorly metastatic, but LM7 cells resulted in visible metastatic lung nodules by 6–8 weeks. We quantified α v β 3 integrin expression using flow cytometry. Results. α v β 3 expression correlated with the metastatic potential of the cells, with LM7 cells showing the highest expression. LM7 cell adhesion to vitronectin decreased after treatment with echistatin, a RGD-containing peptide antagonist of α v β 3. LM7 cells demonstrated higher chemotactic activity than SAOS cells to a homogenate made from lung tissue. This chemotactic activity was also inhibited by echistatin. These data indicated that α v β 3 was critical for the migration of LM7 cells to the lung homogenate. Chemotaxis to a liver homogenate was the same for LM7 and SAOS cells. Migration of LM7 cells through lung endothelial cells was higher than that through liver endothelial cells, and echistatin again inhibited this migration. Conclusions. α v β 3 integrin expression may play a role in the metastatic potential of osteosarcoma cells by enhancing the ability of the cells to migrate specifically to the lung. α v β 3 integrin may therefore be a potential new target for osteosarcoma.This revised version was published online in August 2005 with a corrected cover date.  相似文献   

6.
Summary The differences inP O 2readings between gas and blood were studied with a Clark-type electrode in the range of 38.5 to 713 mm HgP O 2.The tonometered blood samples were taken in two different ways. The results showed that the gas-blood ratior b(equilibrating gasP O 2reading/equilibrated bloodP O 2reading) depended not only on the sampling method but also on theP O 2range: it varied from 1.005 to 1.032 for aP O 2of 96.5 mm Hg, and from 1.040 to 1.081 for aP O 2of 713 mm Hg according to the sampling procedure.A theoretical analysis demonstrated that the variation ofr bwith the bloodP O 2can be attributed to the influence of the degree of oxygen saturation of the hemoglobin on theP O 2gradient existing in the blood diffusion boundary layer adhering to the electrode membrane.This work was supported by grants from the High Authority of the European Coal and Steel Community and from the Fonds de la Recherche Scientifique Médicale, Belgium.  相似文献   

7.
We previously reported that there were three copies of ATP1 coding for F1- and two copies of ATP3 coding for F1- on the left and right arm of chromosome II, respectively. In this study, we present evidence that there are three closely linked copies of ATP2 encoding the subunit of the F1F0-ATPase complex on the right arm of chromosome X in several laboratory strains, including Saccharomyces cerevisiae strain S288C, although it was reported by the yeast genome project that ATP2 is a single-copy gene. Chromosome X fragmentation, long-PCR, chromosome-walking and ATP2-disruption analysis using haploid wild-type strains and prime clone 70645 showed that the three copies of ATP2 are present on the right arm of chromosome X, like those of ATP1 on chromosome II. Each was estimated to be approximately 4 kb apart. We designated the ATP2 proximal to the centromere as ATP2a, the middle one as ATP2b and the distal one as ATP2c. The region containing the three ATP2s is composed of two repeated units of approximately 7 kb; that is, both ends (ATP2a, ATP2c) accompanying the ATP2-neighboring ORFs are the same. A part of YJR119c, YJR120w, YJR122w (CAF17) and YJR123w (RP55), which were reported by the yeast genome project, are contained in the ATP2 repeated units; and the middle ATP2 of the three ATP2s, ATP2b, is located between the two repeated units. Expression of all three copies of ATP2 (ATP2a, ATP2b, ATP2c) was confirmed because a single or double ATP2-disruptant could grow on glycerol, but a triple ATP2-disruptant could not. In addition, of the three copies of ATP1 and ATP2, even if only one copy of the ATP1 and ATP2 genes remained, the cells grew on glycerol.  相似文献   

8.
The gene for mast cell chymase (CMA1) is an ideal candidate for investigating genetic predisposition to atopic asthma, as it is an important mediator of inflammation and remodeling in the asthmatic lung. Various studies have examined the association between –1903 G/A polymorphism and allergic phenotypes, but inconsistent results have been obtained. We investigated the association of this SNP and a novel (TG)n(GA)m repeat polymorphism (accession no. BV210164) 254 bp downstream of the gene with asthma and its associated traits in a case-control study in two independent cohorts recruited from the Indian population. A significant association was observed for the (TG)n(GA)m repeat with asthma (p<0.05) in both the cohorts. Although no association was observed for the –1903 G/A SNP with asthma, a significant association was observed between the genotypes and serum IgE levels (p=0.003 and 0.0004 for cohort A and B). When haplotypes were compared between patients and controls, the haplotype G_43 was found at higher frequency in controls (p=0.05). Also, on comparing major haplotypes (>5%) with respect to log total serum IgE levels, a significant difference was obtained (p=0.018 and p=0.046 for cohorts A and B). These results suggest that the CMA1 gene contributes to asthma susceptibility and may be involved in regulating IgE levels in atopic asthma.  相似文献   

9.
Incubation of mouse and chicken splenocytes with amino acid or peptide preparationsin vitro increases cell resistance to benzene and aflatoxin B1. Short-term (15 days) treatment of chicken with an amino acid mixture (aviamine) in combination with benzene also increased splenocyte resistance to toxinin vitro. By contrast, aviamine in combination with aflatoxin B1 sharply decreased cell resistance to toxin. Glutamic acid possessed no such properties. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 128, No. 10, pp. 419–421, October, 1999  相似文献   

10.
APCO2 electrode working on the principle of electrical conductivity is described. The calibration curve can be linearized according to the formula . This linearity has been tested in thePCO2 range of 0.93–9.33 kPa (7–70 Torr). For the experiments electrodes are used which have conductivity values of about 50 nS and drifts of maximally 5%/h at aPCO2 of 5.33 kPa (40 Torr). The response time (T 90) is about 20 s. The temperature sensitivity is 2.4 nS/1 K between 298K–310K. The standard error of the measurements is =0.33 nS. With these electrodes tissuePCO2 can be measured on the surface of various organs.  相似文献   

11.
Background: Asthma is a chronic inflammatory disease of the airways. The chemokines are potent chemoattractants for eosinophils and other types of cells associated with allergic inflammation. AA-2414, a new thromboxane A2 receptor antagonist, reduces bronchial hyperresponsiveness in asthmatic subjects, but its mechanism of action is unclear. Objective: We tested the hypothesis that the beneficial effects of AA-2414 in asthma result from reduction in the number of inflammatory cells infiltrating the airway associated with inhibition of chemokine release. Methods: We studied bronchial biopsy specimens from 31 asthmatic subjects before and after oral treatment with AA-2414 (80 mg/day) or matched placebo for 4 months in a double-blind manner. Biopsy specimens were examined by immunohistochemistry. Each subject recorded symptom score and peak expiratory flow (PEF). Lung function and bronchial responsiveness to methacholine were measured before and after treatment. Results: After treatment, significant improvements in symptom score (P < .05), PEF (P < .01), diurnal variation of PEF (P < .01), and bronchial responsiveness (P < .01) were observed in the AA-2414 group compared with the placebo group. These improvements were accompanied by a significant decrease in the number of submucosal EG2+ eosinophils (P < .05). There was also a reduction in the number of cells expressing RANTES (P < .05) and macrophage inflammatory protein (MIP)-1α (P < .05) in the epithelium and of cells expressing monocyte chemotactic protein-3 (P < .01), RANTES (P < .05), MIP-1α (P < .01), and eotaxin (P < .01) in the submucosa in the AA-2414 treatment group. A significant correlation was found between the number of EG2+ eosinophils and numbers of monocyte chemotactic protein-3+ (rs = 0.52, P < .005), MIP-1α+ (rs = 0.34, P < .05), and eotaxin+ cells (rs = 0.47, P < .01) in the submucosa. There was a significant negative correlation between the increase in bronchial responsiveness and the change in number of submucosal EG2+ cells (rs = –0.65, P < .001). Conclusions: These findings suggest that AA-2414 treatment of patients with asthma may inhibit activated eosinophil infiltration in part by modulating the expression of chemokines in bronchial tissues. (J Allergy Clin Immunol 1999;103:1054-61.)  相似文献   

12.
A binding site for the repressor protein BP1, which contains a tandem (AT)x(T)y repeat, is located approximately 530 bp 5 to the human -globin gene (HBB). There is accumulating evidence that BP1 binds to the (AT)9(T)5 allele more strongly than to other alleles, thereby reducing the expression of HBB. In this study, we investigated polymorphisms in the (AT)x(T)y repeat in 57 individuals living in Thailand, including three homozygotes for the hemoglobin E variant (HbE; 26Glu->Lys), 22 heterozygotes, and 32 normal homozygotes. We found that (AT)9(T)5 and (AT)7(T)7 alleles were predominant in the studied population and that the HbE variant is in strong linkage disequilibrium with the (AT)9(T)5 allele, which can explain why the E chain is inefficiently synthesized compared to the normal A chain. Moreover, the mildness of the HbE disease compared to other hemoglobinopathies in Thai may be due, in part, to the presence of the (AT)9(T)5 repeat on the HbE chromosome. In addition, a novel (AC)n polymorphism adjacent to the (AT)x(T)y repeat (i.e., (AC)3(AT)7(T)5) was found through the variation screening in this study.MIM and accession numbers and URLs for data presented herein are as follows: Online Mendelian Inheritance of Man (OMIM), (for HBB [MIM 141900]). GenBank, (accession number [NG_000007.2] reference sequence information).  相似文献   

13.
The study comparesin vitro effect of different contrast media on complement activity and eicosanoid content. Ionic agents (Bilignost>Iodamide>Triombrast>Hexabrix) exert pronounced complement-activating effect, while nonionic agents markedly increase blood content of arachidonic acid metabolites. The complement-activating effect of contrast media did not correlate with their ability to elevate blood content of prostaglandin F and leukotrienes C4 and B4. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 125, No. 6, pp. 637–640, June, 1998  相似文献   

14.
Summary Static relationships between arterial, transcutaneous[/p] and end-tidal PCO2 (P aCO2, P tc CO 2, P etCO2) as well as the dynamic relationship between P etCO2 and P tcCO2 were studied during moderate bicycle ergometer exercise with and without external C02 loading. The exercise pattern consisted of 5-min intervals of constant power at 40 W and 100 W and 900 s of randomised changes between these two power levels. The external CO2 loading was achieved by means of controlled variations of inspiratory gas compositions aimed at a constant P etCO2 of 6.5 kPa (49 mm Hg). The PetO2 was regulated at 17.3 kPa (130 mm Hg). Under steady-state conditions all PCO2 parameters showed close linear relationships. P aCO2/P tcCO2 was near to identity while the P etCO2 systematically overestimated changes in P aCO2. No relationship showed a significant influence of the exercise intensity. Transients of P tcCO2 are considerably slower than P etCO2 transients. The dynamic relationship between both parameters was found to be independent of whether internal or external C02 loadings were applied. It is concluded that the combination of P etCO2 and P tcCO2 measurements allows an improved non-invasive assessment of P aCO2. While P etC02 better reflects the transients, P tcCO2 can be employed to determine slow changes of the absolute P aCO2.  相似文献   

15.
The purpose of this article was to establish whether previously reported oxygen-to-mass ratios, used to predict flat and hill-climbing cycling performance, extend to similar power-to-mass ratios incorporating other, often quick and convenient measures of power output recorded in the laboratory [maximum aerobic power (W MAP), power output at ventilatory threshold (W VT) and average power output (W AVG) maintained during a 1 h performance test]. A proportional allometric model was used to predict the optimal power-to-mass ratios associated with cycling speeds during flat and hill-climbing cycling. The optimal models predicting flat time-trial cycling speeds were found to be (W MAP m −0.48)0.54, (W VT m −0.48)0.46 and (W AVG m −0.34)0.58 that explained 69.3, 59.1 and 96.3% of the variance in cycling speeds, respectively. Cross-validation results suggest that, in conjunction with body mass, W MAP can provide an accurate and independent prediction of time-trial cycling, explaining 94.6% of the variance in cycling speeds with the standard deviation about the regression line, s=0.686 km h−1. Based on these models, there is evidence to support that previously reported -to-mass ratios associated with flat cycling speed extend to other laboratory-recorded measures of power output (i.e. Wm −0.32). However, the power-function exponents (0.54, 0.46 and 0.58) would appear to conflict with the assumption that the cyclists’ speeds should be proportional to the cube root (0.33) of power demand/expended, a finding that could be explained by other confounding variables such as bicycle geometry, tractional resistance and/or the presence of a tailwind. The models predicting 6 and 12% hill-climbing cycling speeds were found to be proportional to (W MAP m −0.91)0.66, revealing a mass exponent, 0.91, that also supports previous research.  相似文献   

16.
The cyt-12-12 mutant of Neurospora crassa is characterized by slow growth and a deficiency of spectrophotometrically-detectable cytochromes aa 3 and c. Using a sib-selection procedure we have isolated the cyt-12 + allele from a cosmid library of N. crassa genomic DNA. Characterization of the cyt-12 + allele reveals that it encodes the structural gene for cytochrome c. DNA sequence analysis of the cyt-12-12 allele revealed a mutation in the cytochrome c coding sequence that results in replacement of a glycine residue, which is invariant in the cytochrome c of other species, with an aspartic acid. Genetic analysis confirms that cyt-12-12 is allelic with the previously-characterized cyc-1-1 mutant, which was also shown to affect the single locus encoding cytochrome c in N. crassa. We suggest that the amount of functional cytochrome c present in mitochondria influences the level of cytochrome aa 3 .  相似文献   

17.
Summary In 11 adult cats, lightly anesthetized with chloralose-urethane, blood from both common carotid arteries was led into a plastic chamber of 15–20 ml and returned to the carotids at a point 1.5 cm more cranial. By doing so arterial blood was assumed to pool within the chamber and lose itsP CO 2 oscillations which are normally known to exist as a result of the respiratory cycle. In control periods blood bypassed the chamber, thus maintaining respiratoryP CO 2 oscillations. Spontaneous ventilation was measured spirometrically. The animals were breathing pure O2.Results. 1. When the sinus (carotid) nerves were intact or sectioned there was no significant difference in ventilation before or after switching from non-oscillating to oscillatingPa CO 2. 2. When the vertebral arteries were ligated a drop in ventilation occurred after turning to oscillatingPa CO 2 which was followed by a slight rise above control values after 30–50 sec. This phenomenon was independent of sinus nerve integrity. Thus in hyperoxie condition the smallPa CO 2 oscillations known to occur in phase with respiration do not seem to provide a respiratory stimulus to resting ventilation above that generated by the mean level ofPa CO 2. The ventilatory depression after vertebral artery ligation must at this time remain unexplained.  相似文献   

18.
Agonists of κ1-opiate receptors injected in brain ventricle potentiate arrhythmogenic effect of adrenaline. Antagonist of κ1-opiate receptors norbinaltorphimine or ganglioblocker hexamethonium completely abolish proarrythmic effects of κ1-agonists. Norbinaltorphimine possesses intrinsic antiarrhythmic activity. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 123, No. 6, pp. 656–658, June, 1997  相似文献   

19.
Zusammenfassung Die Verteilung des Sauerstoffdrucks auf der Oberfläche und in der Wand des isolierten, hämoglobinfrei perfundierten stillgestellten und leer schlagenden Meerschweinchenherzens wurde untersucht. Für das schlagende Herz wurden zu diesem Zweck spezielle Miniaturformen von Platinstichelektroden entwickelt.In der Wand des ruhenden Herzens besteht ein Gradient des mittleren Sauerstoffdrucks mit einem im äußeren Drittel steilen, dann flachen Abfall zum Endokard hin. Bei Perfusion mit oxygeniertem Medium besteht in der äußersten Myokardschicht von 100 ein O2-Diffusionsaustausch mit der umgebenden Atmosphäre. Bei Verhinderung dieser Diffusion durch Abdeckung der Oberfläche erhöhen sich diepO2-Werte auf der Oberfläche auf ungefähr das Doppelte. Bei freier Diffusion beträgt der Sauerstoffverlust (ohne Berücksichtigung der Vorhöfe und extramuralen Gefäße) 4,3% der Ruheatmung. Die auf der (abgedeckten) Oberfläche des Myokards gemessenenpO2-Werte zeigen eine statistische Normalverteilung mit Maximum im Bereich des venösenpO2.Das Epikard des Meerschweinchenherzens ist gefäßarm und hat eine mittlere Dicke von 20 . An Basis und Spitze verdickt es sich auf 80 bzw. 120 . Der dadurch beipO2-Oberflächenmessungen bedingte Druckabfall beträgt im Mittel 1 Torr.Die Verteilung derpO2-Werte in der Wand des leerschlagenden Herzens zeigt keinen einheitlichen Gradienten. Das mittlerepO2-Niveau liegt wesentlich höher als beim ruhenden Herzen. Aus diesem Befund wird geschlossen, daß in der Wand des schlagenden Herzens eine weitgehend homogene Durchblutung besteht.Bei sämtlichen gemessenenpO2-Serien liegt das Maximum der Häufigkeitsverteilung derpO2-Werte unterhalb des coronarvenösenpO2. Es wird angenommen, daß diese Verteilungsform bei Perfusion mit oxygeniertem, hämoglobinfreiem Medium im wesentlichen durch einen Sauerstoff-Diffusionsshunt im Gewebe zustande kommt. Die Möglichkeiten, aus solchenpO2-Häufigkeitsverteilungen auf Einzelheiten der Vorgänge bei Sauerstofftransfer und-verbrauch im Gewebe zu schließen, werden diskutiert.Teile dieser Arbeit wurden auf der 35. Tagung der Deutschen Physiologischen Gesellschaft auszugsweise vorgetragen [Pflügers Arch.307, 24 (1969)].  相似文献   

20.
On reaching the respiratory compensation point (RCP) during rapidly increasing incremental exercise, the ratio of minute ventilation (VE) to CO2 output (VCO2) rises, which coincides with changes of arterial partial pressure of carbon dioxide (P aCO2). Since P aCO2 changes can be monitored by transcutaneous partial pressure of carbon dioxide (PCO2,tc) RCP may be estimated by PCO2,tc measurement. Few available studies, however, have dealt with comparisons between PCO2,tc threshold (T AT) and lactic, ventilatory or gas exchange threshold (V AT), and the results have been conflicting. This study was designed to examine whether this threshold represents RCP rather than V AT. A group of 11 male athletes performed incremental excercise (25 W · min–1) on a cycle ergometer. The PCO2,tc at (44°C) was continuously measured. Gas exchange was computed breath-by-breath, and hyperaemized capillary blood for lactate concentration ([la]b) and P aCO2 measurements was sampled each 2 min. The T AT was determined at the deflection point of PCO2,tc curve where PCO2,tc began to decrease continuously. The V AT and RCP were evaluated with VCO2 compared with oxygen uptake (VO2) and VE compared with the VCO2 method, respectively. The PCO2,tc correlated with P aCO2 and end-tidal PCO2. At T AT, power output [P, 294 (SD 40) W], VO2 [4.18 (SD 0.57)l · min–1] and [la] [4.40 (SD 0.64) mmol · l–1] were significantly higher than those at V AT[P 242 (SD 26) W, VO2 3.56 (SD 0.53) l · min–1 and [la]b 3.52 (SD 0.75), mmol · l–1 respectively], but close to those at RCP [P 289 (SD 37) W; VO2 3.97 (SD 0.43) l · min and [la]b 4.19 (SD 0.62) mmol · l–1, respectively]. Accordingly, linear correlation and regression analyses showed that P, VO2 and [la]b at T AT were closer to those at RCP than at V AT. In conclusion, the T AT reflected the RCP rather than V AT during rapidly increasing incremental exercise.  相似文献   

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