Hyperplasia in multiple smooth muscle tissues in transgenic mice expressing a temperature-sensitive SV40 T-antigen under the control of smooth muscle alpha-actin regulatory sequences.
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Control of smooth muscle cell (SMC) proliferation is of fundamental importance in the development and pathology of the vasculature. To derive vascular SMC with conditional inactivation of negative cell cycle regulatory proteins in the context of smooth muscle protein expression, a 3.4 kb fragment of the mouse SMC alpha-actin promoter was used to target a temperature-sensitive mutant SV40 T antigen (tsA58) to smooth muscle in transgenic mice. Mice with this genotype display a heritable phenotype of abnormal SMC proliferation in the central tail artery, vasa deferentia, seminal vesicles, prostate, and uterus, with the latter resembling uterine leiomyomatosis and prostatic hypertrophy. Neither the aorta nor other viscera manifested abnormal proliferation. Cultures from aorta, vas deferens, seminal vesicle, and kidney tissue were characterized with regard to protein expression, stability, and matrix remodelling capacity. The alpha-actin content/cell was up to 3-4-fold higher, as well as more stable than in primary SMC cultures, suggesting successful selection for propagation of cells expressing this differentiation marker. All cells displayed enhanced growth at the permissive temperature. As an initial functional assessment, the cells were compared to non-transformed mouse aortic SMC with respect to the ability to remodel collagen gel matrices, and demonstrated conservation of this physiologic function. This in vivo analysis of the SMC alpha-actin promoter supports a broader range of smooth muscle-directed expression activity than previously recognized, and establishes the feasibility of its use to direct transgene expression to vascular as well as genito-urinary smooth muscle. The targeted expression of the tsA58 T antigen has yielded transgenic animals with several manifestations of smooth muscle hyperplasia; these animals have in turn permitted the derivation of several murine SMC lines with phenotypic stability and conditionally-modulated proliferation. These cells will allow expansion of derivative transfected smooth muscle cell lines under permissive conditions, as well as oncogene inactivation at the restrictive temperature when desired for functional studies. (+info)
Efficacy of nedocromil 2% versus fluorometholone 0.1%: a randomised, double masked trial comparing the effects on severe vernal keratoconjunctivitis.
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AIMS: To compare the efficacy of topical nedocromil 2% with fluorometholone 0.1% in vernal keratoconjunctivitis (VKC). METHODS: In a double masked random design, 24 patients with severe vernal keratoconjunctivitis were placed at random on nedocromil 2% eye drops in one eye and fluorometholone 0.1% in the fellow eye. At the end of the 2 week treatment period, the patient crossed over the eye drops (if asymptomatic in one eye), or continued with nedocromil sodium in both eyes (if asymptomatic in both eyes). All patients were examined weekly and ocular surface temperature recorded for a period of 6 weeks. RESULTS: Improvement in the watering, discharge, conjunctival hyperaemia, papillary hypertrophy, and Trantas' dots was noted in both groups, but overall fluorometholone was significantly more effective than nedocromil. Eyes treated with fluorometholone showed a significant decrease in ocular surface temperature compared with nedocromil treated eyes (p = 0.03). CONCLUSIONS: Both nedocromil and fluorometholone were effective in ameliorating the signs and symptoms of vernal keratoconjunctivitis. No adverse effects were noted in the nedocromil group. (+info)
Day-specific probabilities of clinical pregnancy based on two studies with imperfect measures of ovulation.
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Two studies have related the timing of sexual intercourse (relative to ovulation) to day-specific fecundability. The first was a study of Catholic couples practising natural family planning in London in the 1950s and 1960s and the second was of North Carolina couples attempting to become pregnant in the early 1980s. The former identified ovulation based on the ovulatory shift in the basal body temperature, while the latter used urinary assays of hormones. We use a statistical model to correct for error in identifying ovulation and to re-estimate the length of the fertile window and day-specific fecundabilities. We estimate the same 6-day fertile interval in both studies after controlling for error. After adjusting for error both data sets showed the highest estimate of the probability of pregnancy on the day prior to ovulation and both fell close to zero after ovulation. Given that the fertile interval is before ovulation, methods that anticipate ovulation by several days (such as the assessment of cervical mucus) would be particularly useful for couples who want to time their intercourse either to avoid or facilitate conception. (+info)
Intra-oral temperature variation over 24 hours.
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This study aimed to investigate temperature variation at archwire sites adjacent to the maxillary right central incisor and first premolar, its correlation with ambient temperature, and the influence of inter-racial variation. Twenty young adult male subjects were randomly selected (13 Asian, seven Caucasian). Thermocouples were attached to the labial archwire component of custom-made orthodontic retainers at the two intra-oral sites. A third thermocouple measured ambient temperature. A data-logger recorded temperatures at 5-second intervals over a 24-hour period. Temperatures ranged from 5.6 to 58.5 degrees C at the incisor and from 7.9 to 54 degrees C at the premolar, with medians of 34.9 degrees C and 35.6 degrees C, respectively. Ambient temperature correlated poorly with the intra-oral temperatures. The Asian and Caucasian groups had significantly different temperature distributions. On average during the 24-hour period, temperatures at the incisor site were in the range of 33-37 degrees C for 79 per cent of the time, below it for 20 per cent, and above it for only 1 per cent of the time. Corresponding figures for the premolar site were 92, 6, and 2 per cent. At both archwire sites the most frequent temperatures were in the range of 35-36 degrees C. The data presented demonstrate that the temperature at sites on an archwire in situ varies considerably over a 24-hour period and that racial differences may exist. This information should be considered during the manufacture and use of temperature-sensitive orthodontic materials, in particular nickel-titanium archwires and springs. (+info)
O(2) cost of contractility but not of mechanical energy increases with temperature in canine left ventricle.
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We investigated the effects of myocardial temperature on left ventricular (LV) mechanoenergetics in the excised, cross-circulated canine heart. We used the framework of the LV contractility (E(max))-pressure-volume area (PVA; a measure of total mechanical energy)-myocardial oxygen consumption (VO(2)) relationship. We have shown this framework to be useful to integrative analysis of the mechanoenergetics of a beating heart. In isovolumic contractions at a constant pacing rate, increasing myocardial temperature from 30 to 40 degrees C depressed E(max) and increased the oxygen cost of E(max), which was enhanced by dobutamine, in a linear manner. However, the slope of the VO(2)-PVA relation (reciprocal of contractile efficiency) and its VO(2) intercept remained constant. Q(10) values of E(max), the oxygen cost of E(max), and the oxygen cost of PVA were 0.4, 2.1 and 1.0, respectively, around normothermia. We conclude that the temperature-dependent processes of cross-bridge cycling and Ca(2+) handling integratively depress E(max) and augment its oxygen cost without affecting the oxygen cost of PVA as myocardial temperature increases by 10 degrees C around normothermia. (+info)
Thermoregulatory responses to cold water at different times of day.
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This study examined how time of day affects thermoregulation during cold-water immersion (CWI). It was hypothesized that the shivering and vasoconstrictor responses to CWI would differ at 0700 vs. 1500 because of lower initial core temperatures (T(core)) at 0700. Nine men were immersed (20 degrees C, 2 h) at 0700 and 1500 on 2 days. No differences (P > 0.05) between times were observed for metabolic heat production (M, 150 W. m(-2)), heat flow (250 W. m(-2)), mean skin temperature (T(sk), 21 degrees C), and the mean body temperature-change in M (DeltaM) relationship. Rectal temperature (T(re)) was higher (P < 0.05) before (Delta = 0.4 degrees C) and throughout CWI during 1500. The change in T(re) was greater (P < 0. 05) at 1500 (-1.4 degrees C) vs. 0700 (-1.2 degrees C), likely because of the higher T(re)-T(sk) gradient (0.3 degrees C) at 1500. These data indicate that shivering and vasoconstriction are not affected by time of day. These observations raise the possibility that CWI may increase the risk of hypothermia in the early morning because of a lower initial T(core). (+info)
Control of cutaneous blood vessels in psoriatic plaques.
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The aim of this study was to compare local blood flow in psoriatic plaques before and after provocations known to alter cutaneous vascular resistance, in order to determine whether plaque hyperemia is caused by a failure of normal vascular control mechanisms. Cutaneous blood flow was recorded using a laser Doppler flowmeter over plaque skin (plaque site) and clinically normal skin (nonplaque site) on the opposite arm, at least 5 cm away from the nearest plaque. It is important to note that most of the laser Doppler signal comes from the subpapillary plexus of the skin and only a small portion (2%-10%) is produced by capillary blood flow. In the psoriatic plaques the basal flux was between nine and 13 times greater than nonplaque skin. The biologic zero (a signal independent of perfusion, which also persists after complete proximal arterial occlusion) was also significantly greater at plaque sites compared with nonplaque sites. Sympathetic and local vasoconstriction in psoriatic skin was shown to be intact and responses to vasodilator tests were likewise intact, i.e., there was no failure of response to normal vascular control mechanisms, albeit some quantitative differences. Tests of vasodilatation indicated that, although basal flux is high in plaque compared with nonplaque skin, arterioles supplying plaque skin can dilate further, i.e., lesional arterioles are not normally maximally dilated but have a basal constrictor tone. Interestingly, the red cell flux at maximum dilatation in nonplaque skin is less than even the basal flux in plaque skin. This means that in plaque skin either there are more arterioles than in nonplaque skin, or there is chronic, structural widening of the existing arterioles in plaque skin. (+info)
Field test of a paradigm: hysteresis of heart rate in thermoregulation by a free-ranging lizard (Pogona barbata).
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The discovery that changes in heart rate and blood flow allow some reptiles to heat faster than they cool has become a central paradigm in our understanding of reptilian thermoregulation. However, this hysteresis in heart rate has been demonstrated only in simplistic laboratory heating and cooling trials, leaving its functional significance in free-ranging animals unproven. To test the validity of this paradigm, we measured heart rate and body temperature (Tb) in undisturbed, free-ranging bearded dragons (Pogona barbata), the species in which this phenomenon was first described. Our field data confirmed the paradigm and we found that heart rate during heating usually exceeded heart rate during cooling at any Tb. Importantly, however, we discovered that heart rate was proportionally faster in cool lizards whose Tb was still well below the 'preferred Tb range' compared to lizards whose Tb was already close to it. Similarly, heart rate during cooling was proportionally slower the warmer the lizard and the greater its cooling potential compared to lizards whose Tb was already near minimum operative temperature. Further, we predicted that, if heart rate hysteresis has functional significance, a 'reverse hysteresis' pattern should be observable when lizards risked overheating. This was indeed the case and, during heating on those occasions when Tb reached very high levels (> 40 degrees C), heart rate was significantly lower than heart rate during the immediately following cooling phase. These results demonstrate that physiological control of thermoregulation in reptiles is more complex than has been previously recognized. (+info)