The research presented in this paper involves the application of the joint probability method to the estimation of extreme water levels resulting from astronomical tides and surge residuals and the ...investigation of the effects of tide–surge interactions on extreme water levels. The distribution of tide peaks was analysed from field records (<20 years) and a 46-year dataset of monthly maximum tidal amplitudes. Large surges were extracted from both field records and a numerical model hindcast covering the 48 largest storm events in the Irish Sea over the period 1959–2005. Extreme storm surges and tides were independently modelled using the generalised extreme value statistical model, and derived probability distributions were used to compute extreme water levels. An important, and novel, aspect of this research is an analysis of tide–surge interactions and their effects on total water level; where interactions exist, they lead to lower total water levels than in the case of independency. The degree of decrease varies with interaction strength, magnitude of surge peak at a particular phase of tide and the distribution of peaks over a tidal cycle. Therefore, including interactions in the computation of extreme levels may provide very useful information at the design stage of coastal protection systems.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, SIK, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
A confocal Ca 2+ imaging technique has been used to detect ATP release from individual sympathetic varicosities on the same nerve terminal
branch. Varicose nerve terminals and smooth muscle cells in ...mouse vas deferens were loaded with the Ca 2+ indicator Oregon Green 488 BAPTA-1. Field (nerve) stimulation evoked discrete, focal increases in Ca 2+ in smooth muscle cells adjacent to identified varicosities. These focal increases in Ca 2+ have been termed âneuroeffector Ca 2+ transientsâ (NCTs). NCTs were abolished by α,β-methylene ATP (1 μM), but not by nifedipine (1 μM) or prazosin (100 n m ), suggesting that NCTs are generated by Ca 2+ influx through P2X receptors without a detectable contribution from L-type Ca 2+ channels or α 1 -adrenoceptor-mediated pathways. Action potential-evoked ATP release was highly intermittent (mean probability 0.019 ± 0.002;
range 0.001-0.10) at 1 Hz stimulation, even though there was no failure of action potential propagation in the nerve terminals.
Twenty-eight per cent of varicosities failed to release transmitter following more than 500 stimuli. Spontaneous ATP release
was very infrequent (0.0014 Hz). No Ca 2+ transient attributable to noradrenaline release was detected even in response to 5 Hz stimulation. There was evidence of
local noradrenaline release as the α 2 -adrenoceptor antagonist yohimbine increased the probability of occurrence of NCTs by 55 ± 21 % during trains of stimuli at
1 Hz. Frequency-dependent facilitation preferentially occurred at low probability release sites. The monitoring of NCTs now
allows transmitter release to be detected simultaneously from each functional varicosity on an identified nerve terminal branch
on an impulse-to-impulse basis.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The effects of endothelin‐1 (ET‐1) on guinea‐pig lower oesophageal sphincter (LOS) circular smooth muscle were investigated by using intracellular microelectrodes and isometric tension recording ...techniques.
ET‐1 produced biphasic mechanical responses; an initial transient relaxation followed by a sustained contraction. The initial relaxation was not inhibited by either tetrodotoxin (TTX, 1 μM) or L‐NG‐nitroarginine (L‐NOARG, 100 μM). The sustained contraction was greatly attenuated by nifedipine (1 μM).
ET‐1 (1 – 30 nM) induced a concentration‐dependent hyperpolarisation that was unaffected by TTX or L‐NOARG. The ETA receptor antagonist, BQ123 (0.3 μM) abolished the ET‐1‐induced hyperpolarisation, whereas the ETB receptor antagonist, BQ788 (0.3 μM) had no detectable effect. Sarafotoxin S6c (10 nM) did not change the membrane potential.
The ET‐1‐induced hyperpolarisation was abolished by apamin (0.1 μM). Interestingly, apamin abolished the ET‐1‐induced transient relaxation but potentiated the sustained contraction.
In Ca2+‐free Krebs solution, the ET‐1‐induced hyperpolarisation was greatly attenuated and returned to the control value when the tissue was reperfused with Krebs solution containing Ca2+. The ET‐1‐induced hyperpolarisation was insensitive to nifedipine but was attenuated by SK&F 96365 (1 ‐ {β‐3‐(4 ‐ methoxy ‐ phenyl)propoxy ‐ 4 ‐ methoxyphenethyl} ‐ 1H‐imidazole hydrochloride, 50 μM), an inhibitor of receptor‐mediated Ca2+ entry. The residual component of the ET‐1‐induced hyperpolarisation was sensitive to thapsigargin (1 μM).
These results demonstrate that, in guinea‐pig LOS circular smooth muscle, ET‐1 hyperpolarizes the membrane by activating apamin‐sensitive K+ channels, mainly as a result of receptor‐mediated Ca2+ entry and partly by Ca2+ release from intracellular stores. The hyperpolarisation triggers the initial transient relaxation, which acts to oppose the sustained contraction.
British Journal of Pharmacology (2002) 135, 197–205; doi:10.1038/sj.bjp.0704426
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
We describe the radiographic and pathologic findings of small flat umbilicated tumors of the colon detected on double-contrast barium enema examinations performed in a Western population.
Unlike ...those reported by Japanese authors, the small flat umbilicated tumors of the colon in our patients were usually hyperplastic polyps, previously called "inverted hyperplastic polyps." Nevertheless, colonoscopy with excisional biopsy is warranted for such tumors detected on double-contrast barium enema examinations because of the small possibility that these tumors represent adenoma or even early adenocarcinoma.
Electrically‐evoked contractions in different regions of the rabbit isolated pulmonary artery have been investigated using stimulation parameters generally assumed to stimulate nerves selectively.
In ...extrapulmonary artery, trains of stimuli (10 Hz; pulse width 0.1 ms) evoked monophasic contractions. In contrast, a biphasic contraction was evoked in the intrapulmonary artery consisting of an initial fast component followed by a secondary very long‐lasting component.
The contraction in the extrapulmonary artery was prazosin‐sensitive (1 μM) whereas that in the intrapulmonary artery was prazosin‐resistant.
α,β‐Methylene ATP (1 μM), atropine (1 μM), losartan (1 μM), BIBO3304 (1 nM) or nifedipine (1 μM) had no effect on the biphasic contraction of the intrapulmonary artery. Bretylium (2 μM) abolished the contraction of extrapulmonary artery but only partially inhibited the initial component in the intra region with no effect on the second component.
Tetrodotoxin (0.3–1 μM), abolished the contraction of extrapulmonary artery but only partially reduced the electrically‐evoked contraction of intrapulmonary artery.
Removal of the endothelium and application of sulphisoxazole (0.6–22 μM) had no effect.
Varying the resting tone on the arteries, or applying gadolinium, had no effect on contractions.
Using confocal microscopy and calcium imaging, reproducible whole cell calcium transients were evoked in individual smooth muscle cells in intact preparations but only when direct muscle stimulation was used (pulse width of 5–10 ms). No detectable changes in calcium were elicited when brief pulse widths were used (0.1–2 ms).
Together, these data suggest that noradrenaline is the neurotransmitter inducing contraction in extrapulmonary artery. Noradrenaline and sympathetic nerves appear to play a less important role in the intrapulmonary artery. The tetrodoxin‐resistant component is not mediated by ATP, NPY, acetylcholine, angiotensins, ET‐1, stretch‐activation or Ca2+ influx through L‐type Ca2+ channels. Smooth muscle cells do not appear to be damaged by the stimulation protocol. The mechanism underlying the long lasting contraction of intrapulmonary artery evoked by brief electrical stimuli remains to be elucidated.
British Journal of Pharmacology (2002) 137, 488–496. doi:10.1038/sj.bjp.0704863
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
The synovium in rheumatoid arthritis (RA) is characterized by an increase in lining layer thickness and infiltration of inflammatory cells into the sublining area. Fibroblasts in the lining layer ...develop the appearance of "transformed cells", under the influence of proto-oncogenes involved in the regulation of the cell cycle. Fibroblast and macrophage-derived cytokines such as IL-1 and TNF-alpha are present abundantly in the rheumatoid synovium and stimulate these cells to produce destructive enzymes. Other cytokines such as IL-4 and IL-10 represent a physiological attempt to reverse the inflammatory process. Adhesion molecules facilitate both the migration of cells to the joint as well as the attachment of synovium to bone and cartilage. Joint destruction is mediated by enzymes such as serine proteases, matrix metalloproteinases (MMPs) and the cathepsins. Treatments directed against various components of the inflammatory cascade have shown promise. Inhibition of MMPs or adhesion molecules, blockade of IL-1 or TNF-alpha and the use of anti-Fas antibodies to induce apoptosis offer new possibilities for the treatment of RA. More recently, the employment of genes with antiarthritic properties has shown therapeutic potential.
A confocal Ca
2+
imaging technique has been used to detect ATP release from individual sympathetic varicosities on the same nerve terminal branch. Varicose nerve terminals and smooth muscle cells in ...mouse vas deferens were loaded with the Ca
2+
indicator Oregon Green 488 BAPTA‐1. Field (nerve) stimulation evoked discrete, focal increases in Ca
2+
in smooth muscle cells adjacent to identified varicosities. These focal increases in Ca
2+
have been termed ‘neuroeffector Ca
2+
transients’ (NCTs). NCTs were abolished by α,β‐methylene ATP (1 μM), but not by nifedipine (1 μM) or prazosin (100 n
m
), suggesting that NCTs are generated by Ca
2+
influx through P2X receptors without a detectable contribution from L‐type Ca
2+
channels or α
1
‐adrenoceptor‐mediated pathways. Action potential‐evoked ATP release was highly intermittent (mean probability 0.019 ± 0.002; range 0.001‐0.10) at 1 Hz stimulation, even though there was no failure of action potential propagation in the nerve terminals. Twenty‐eight per cent of varicosities failed to release transmitter following more than 500 stimuli. Spontaneous ATP release was very infrequent (0.0014 Hz). No Ca
2+
transient attributable to noradrenaline release was detected even in response to 5 Hz stimulation. There was evidence of local noradrenaline release as the α
2
‐adrenoceptor antagonist yohimbine increased the probability of occurrence of NCTs by 55 ± 21 % during trains of stimuli at 1 Hz. Frequency‐dependent facilitation preferentially occurred at low probability release sites. The monitoring of NCTs now allows transmitter release to be detected simultaneously from each functional varicosity on an identified nerve terminal branch on an impulse‐to‐impulse basis.
Full text
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
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