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Selected AbstractsDevelopment of an Improved Technique for the Perfusion of the Isolated Caudal Lobe of Sheep LiverEXPERIMENTAL PHYSIOLOGY, Issue 5 2000A. M. Ali The study was designed to develop an improved technique for perfusing the isolated caudal lobe of sheep liver. Twenty caudal lobes were perfused for 3-4 h, in a non-recirculating mode, with Krebs-Henseleit bicarbonate buffer. The perfusion system was designed to give a constant flow. The hepatic viability and functional normality of the perfused lobe were assessed by measuring the perfusion flow rate, pH, K+ efflux, O2 uptake, substrate uptake, gluconeogenesis from propionate and amino acids, and ureagenesis from ammonia and amino acids. Liver tissue was sampled for histological examination, as well as for the determination of liver glycogen and wet: dry weight ratio. The perfusion flow rate and pH were both stable throughout the perfusion. The potassium concentration in the effluent perfusate did not increase during the perfusion, suggesting that there was no loss of viability or hypoxia. The perfused lobe extracted more than 50% of the O2 supply. The rate of oxygen consumption was comparable to the rate reported in vivo. The initial glycogen content was reduced by about 40% after 4 h perfusion. The wet: dry weight ratio was 3.6, consistent with the absence of tissue oedema. Urea production was stimulated when NH4Cl (0.3 mM) was added to the medium but there was no significant increase in urea release when alanine (0.15 mM), glutamine (0.2 mM) or lysine (0.2 mM) was added. Urea production, however, increased by about 171% when a physiological mixture of amino acids was added. Propionate (0.5 mM), alanine and glutamine stimulated glucose production but not lysine or the complete amino acid mixture. Glutamine release was lower than that reported in the rat liver. Changing the direction of flow also revealed an apparent difference between livers from sheep and rats in their metabolism of ammonia. The improved technique offers a simple practical and inexpensive approach to many problems in ruminant physiology and nutritional biochemistry. [source] On the kinetics of voltage formation in purple membranes of Halobacterium salinariumFEBS JOURNAL, Issue 19 2000Richard W. Hendler The kinetics of the bacteriorhodopsin photocycle, measured by voltage changes in a closed membrane system using the direct electrometrical method (DEM) of Drachev, L.A., Jasaitus, A.A., Kaulen, A.D., Kondrashin, A.A., Liberman, E.A., Nemecek, I.B., Ostroumov, S.A., Semenov, Yu, A. & Skulachev, V.P. (1974) Nature249, 321,324 are sixfold slower than the kinetics obtained in optical studies with suspensions of purple membrane patches. In this study, we have investigated the reasons for this discrepancy. In the presence of the uncouplers carbonyl cyanide m -chlorophenylhydrazone or valinomycin, the rates in the DEM system are similar to the rates in suspensions of purple membrane. Two alternative explanations for the effects of uncouplers were evaluated: (a) the ,back-pressure' of the ,µ,H+ slows the kinetic steps leading to its formation, and (b) the apparent difference between the two systems is due to slow major electrogenic events that produce little or no change in optical absorbance. In the latter case, the uncouplers would decrease the RC time constant for membrane capacitance leading to a quicker discharge of voltage and concomitant decrease in photocycle turnover time. The experimental results show that the primary cause for the slower kinetics of voltage changes in the DEM system is thermodynamic back-pressure as described by Westerhoff, H.V. & Dancshazy, Z. (1984) Trends Biochem. Sci.9, 112,117. [source] Corporate Sustainability Performance and Idiosyncratic Risk: A Global PerspectiveFINANCIAL REVIEW, Issue 2 2009Darren D. Lee G11; G30; Q56 Abstract Does investing in sustainability leaders affect portfolio performance? Analyzing two mutually exclusive leading and lagging global corporate sustainability portfolios (Dow Jones) finds that (1) leading sustainability firms do not underperform the market portfolio, and (2) their lagging counterparts outperform the market portfolio and the leading portfolio. Notably, we find leading (lagging) corporate social performance (CSP) firms exhibit significantly lower (higher) idiosyncratic risk and that idiosyncratic risk might be priced by the broader global equity market. We develop an idiosyncratic risk factor and find that its inclusion significantly reduces the apparent difference in performance between leading and lagging CSP portfolios. [source] Suppression of HCV-specific T cells without differential hierarchy demonstrated ex vivo in persistent HCV infectionHEPATOLOGY, Issue 6 2003Kazushi Sugimoto Hepatitis C virus (HCV) has a high propensity for persistence. To better define the immunologic determinants of HCV clearance and persistence, we examined the circulating HCV-specific T-cell frequency, repertoire, and cytokine phenotype ex vivo in 24 HCV seropositive subjects (12 chronic, 12 recovered), using 361 overlapping peptides in 36 antigenic pools that span the entire HCV core, NS3-NS5. Consistent with T-cell-mediated control of HCV, the overall HCV-specific type-1 T-cell response was significantly greater in average frequency (0.24% vs. 0.04% circulating lymphocytes, P = .001) and scope (14/36 vs. 4/36 pools, P = .002) among the recovered than the chronic subjects, and the T-cell response correlated inversely with HCV titer among the chronic subjects (R = ,0.51, P = .049). Although highly antigenic regions were identified throughout the HCV genome, there was no apparent difference in the overall HCV-specific T-cell repertoire or type-1/type-2 cytokine profile relative to outcome. Notably, HCV persistence was associated with a reversible CD4-mediated suppression of HCV-specific CD8 T cells and with higher frequency of CD4+CD25+ regulatory T cells (7.3% chronic vs. 2.5% recovered, P = .002) that could directly suppress HCV-specific type-1 CD8 T cells ex vivo. In conclusion, we found that HCV persistence is associated with a global quantitative and functional suppression of HCV-specific T cells but not differential antigenic hierarchy or cytokine phenotype relative to HCV clearance. The high frequency of CD4+CD25+ regulatory T cells and their suppression of HCV-specific CD8 T cells ex vivo suggests a novel role for regulatory T cells in HCV persistence. [source] Influence of environmental stress on skin tone, color and melanogenesis in Japanese skinINTERNATIONAL JOURNAL OF COSMETIC SCIENCE, Issue 1 2005K. Kikuchi Introduction It is needless to say that one of the most potent environmental stress for melanogenesis of the human skin is the effect of ultraviolet (UV) light from the sunlight. Characteristic skin aging as a result of this UV light is recognized as photoaging. Clinical features in photoaging are wrinkles, skin laxity, coarseness, leathery, yellowing, lentigenes, mottled pigmentation, telangiectasia, sebaceous hypertrophy and purpura. There is an apparent difference in clinical features in photoaging among different races, i.e. between Caucasians, African American and Asians that include Japanese. Not only photo skin type but also environmental factors, such as climate, latitude, altitude and their habit of sunbathing, smoking and skin care influence the characteristic development of their photoaging. Racial difference in photoaging Caucasians tend to develop skin laxity and fine wrinkles more than Asians [1]. Asians tend to produce coarser wrinkles than the Caucasians although their development is rather late in life. There is also a difference in the skin color. Pigmentation is an earliest and prominent skin changes in Asians [1] and it increases with age [2]. In contrast, pigmentation is not apparent in the Caucasians although redness probably because of an increase in cutaneous vascularization becomes prominent in middle aged Caucasians [2]. Chung reported that seborrheic keratosis is a major pigmentary lesion in men, whereas hyperpigmented macules are prominent features in women in Koreans [3]. Melanogenesis pigmentation disorders in Japanese Ephelides (freckles) are commonly found in those with photo skin type I who have fair skin and red eyes and blond hair. They are also found in the Japanese. Clinical feature reveals that multiple small pigmentary macules on sun-exposed areas mainly on the mid-portion of the face. These lesions seem to be familial, becoming apparent even in early childhood after sun exposure. Melasma is an acquired pigmentary disorder commonly found in middle aged Japanese women characterized by irregular brown macules and patches on the sun-exposed areas on the face typically as bilaterally present macules on the cheeks. An increase in sex hormones as a result of pregnancy and intake of contraceptive pills is one of the etiological factors to develop melasma. Sun exposure also worsens it. Nevus of Ota is also a common pigmentary disorder found in the Japanese. It is usually unilateral, blue-brown to slate-gray pigmentary macules on the eyelid and cheek that appear in early childhood or in puberty. Acquired dermal melanocytosis is also a pigmentary disorder, in which dermal melanocytes are found as shown in nevus of Ota, characterized by bilateral brown to blue-gray macules on the forehead, temple, eyelid and malar areas in middle aged Japanese women. This tends to be misdiagnosed as melasma. Solar lentigo is an acquired pigmented macule induced by sun exposure. Solar lentigines are usually multiple, circumscribed brown macules. There are two types of solar lentigo. One is a small macular type, characterized by multiple, small brown macules whose diameter is less than 5 mm, being similar to ephelides (freckles). The other type is a large macular type, characterized by a few round to oval, brown macules whose diameter is beyond 1 cm. Some of their surface are hyperkeratotic and become elevated to produce seborrheic keratosis. Again, the early sign of photoaging in Japanese is pigmentated spots and these pigmentation disorders increase with age. Among the pigmentary changes, nevus of Ota, acquired dermal melanocytosis, melasma and large macular type of solar lentigo are characteristic skin changes found in the Japanese in addition to ephelides and small macular type of solar lentigo. Seasonal changes of the various functional properties of the skin including skin color assessed by non-invasive bioengineering techniques [4]. When we consider skin tone, color and melanogenesis, UV light from the sunlight is the most potent environmental stress, although we cannot forget also the important influence of environmental relative humidity affects our skin functions as well as its appearance. We investigated seasonal influences on the various properties of the skin in 39 healthy Japanese females consisting of different age groups. Their skin is thought to be affected by the UV light in summer, and by the exposure to the dry and cold air in winter. Materials and methods Biophysical, non-invasive measurements, including transepidermal water loss (TEWL) as a parameter for the barrier function of the stratum corneum (SC), high frequency conductance as a parameter for the hydration state of the SC, skin color and casual surface lipid levels, were conducted during late summer and winter months. Skin color was determined with a chromameter according to the L*a*b* CIE 1976 system, where L* is an attribute on the luminance scale, a* that on the red versus green scale and b* that on the yellow versus blue scale. All the measurements were conducted in an environment controlled-chamber (21 ± 1 °C room temperature, and 50 ± 3% relative humidity). Results The barrier function of the SC was found to be significantly impaired in winter on the cheek as compared with that measured in summer, whereas no such seasonal change was apparent both in the hydration state of the SC and sebum levels on the cheek. In the assessment of the skin color on the cheek, a significant increase in a* (redness) and a decrease in b* (yellowness) were observed in winter. In contrast, on the flexor forearm, the values of L* (luminescence) increased in winter, but no seasonal change was noted in the values of a* and b*. In this study, skin changes with aging were also found by the non-invasive bioengineering methods. The value of TEWL on the cheek tended to increase with age, whereas no significant change was observed in the value of TEWL on the forearm. In the assessment of skin color, b* value on the cheek significantly increased with age whereas a* and L* values on the cheek did not show any significant change with age. Summary of this study We think that such an increase in yellowness with aging of the cheek skin is a phenomenon unique to the Japanese (Asians) since an increase in b* value was not observed in Caucasians [2]. The facial skin that is always exposed shows barrier impairment in a dry and cold winter environment and demonstrates increased yellowness in skin color because of a prolonged exposure to the UV light from the sun in the summer season. The non-invasive bioengineering methods are useful to demonstrate even invisible seasonal changes occurring in the same individuals and changes with age occurring in the skin. References 1.,Goh, S.H. The treatment of visible signs of senescence: the Asian experience. Br. J. Dermatol.122, 105,109 (1990). 2.,LeFur, I., Numagami, K., Guinot, C. et al. Age-related reference values of skin color in Caucasian and Japanese healthy women according to skin site. Pigment Cell Res. 7, 67 (1999). 3.,Chung, J.H., Lee, S.H., Youn, C.S. et al. Cutaneous photodamage in Koreans: influence of sex, sun exposure, smoking, and skin color. Arch. Dermatol. 137, 1043,1051 (2001). 4.,Kikuchi, K., Kobayashi, H., Le Fur, I. et al. Winter season affects more severely the facial skin than the forearm skin: comparative biophysical studies conducted in the same Japanese females in later summer and winter. Exog. Dermatol. 1, 32,38 (2002). [source] Pharmacokinetics and tolerability of modafinil tablets in Chinese subjectsJOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 4 2008P. Xu PhD Summary Objective:, To investigate the pharmacokinetics and tolerability of modafinil in Chinese subjects. Methods:, Twelve healthy volunteers were given an escalating single dose of modafinil (100, 200 and 400 mg) in a three-period study (study 1). Another 12 volunteers received 100 mg twice daily for 7 days in multiple-dose study (study 2). Blood samples were taken from 0 to 60 h for study 1. And samples for study 2 were collected before administration on three consecutive morning and then from 0 to 60 h after the last dose. Pharmacokinetic parameters were calculated and compared with results from published data. Results:, In study 1, Cmax and area under the concentration,time curve of modafinil and modafinil acid were increased proportionally with dose levels; t1/2 was independent on the dose levels. In study 2, the steady state was reached on day 4, and mean trough plasma concentration of modafinil was 1·36 ± 0·34 ,g/mL. Apparent plasma clearance and apparent volume of distribution were lower in 100 mg twice-daily group than those in 100 mg single group. The adverse events were mild and moderate in study 1 and 2. Conclusions:, In this pharmacokinetic study, modafinil was safe and well tolerated by young healthy Chinese subjects. The major pharmacokinetic parameters of modafinil in Chinese subjects are similar to those reported in Caucasians although the half-life seems to be longer in the former than in the latter. This apparent difference requires investigation. [source] Ages and inferred causes of Late Pleistocene glaciations on Mauna Kea, Hawai'i,JOURNAL OF QUATERNARY SCIENCE, Issue 6-7 2008Jeffrey S. Pigati Abstract Glacial landforms on Mauna Kea, Hawai'i, show that the summit area of the volcano was covered intermittently by ice caps during the Late Pleistocene. Cosmogenic 36Cl dating of terminal moraines and other glacial landforms indicates that the last two ice caps, called Older Makanaka and Younger Makanaka, retreated from their maximum positions approximately 23,ka and 13,ka, respectively. The margins and equilibrium line altitudes of these ice caps on the remote, tropical Pacific island were nearly identical, which would seem to imply the same mechanism for ice growth. But modelling of glacier mass balance, combined with palaeotemperature proxy data from the subtropical North Pacific, suggests that the causes of the two glacial expansions may have been different. Older Makanaka air atop Mauna Kea was likely wetter than today and cold, whereas Younger Makanaka times were slightly warmer but significantly wetter than the previous glaciation. The modelled increase in precipitation rates atop Mauna Kea during the Late Pleistocene is consistent with that near sea level inferred from pollen data, which suggests that the additional precipitation was due to more frequent and/or intense tropical storms associated with eastward-moving cold fronts. These conditions were similar to modern La Niña (weak ENSO) conditions, but persisted for millennia rather than years. Increased precipitation rates and the resulting steeper temperature lapse rates created glacial conditions atop Mauna Kea in the absence of sufficient cooling at sea level, suggesting that if similar correlations existed elsewhere in the tropics, the precipitation-dependent lapse rates could reconcile the apparent difference between glacial-time cooling of the tropics at low and high altitudes. Copyright © 2008 John Wiley & Sons, Ltd. [source] Habitat-dependent foraging in a classic predator,prey system: a fable from snowshoe haresOIKOS, Issue 2 2005Douglas W. Morris Current research contrasting prey habitat use has documented, with virtual unanimity, habitat differences in predation risk. Relatively few studies have considered, either in theory or in practice, simultaneous patterns in prey density. Linear predator,prey models predict that prey habitat preferences should switch toward the safer habitat with increasing prey and predator densities. The density-dependent preference can be revealed by regression of prey density in safe habitat versus that in the riskier one (the isodar). But at this scale, the predation risk can be revealed only with simultaneous estimates of the number of predators, or with their experimental removal. Theories of optimal foraging demonstrate that we can measure predation risk by giving-up densities of resource in foraging patches. The foraging theory cannot yet predict the expected pattern as predator and prey populations covary. Both problems are solved by measuring isodars and giving-up densities in the same predator,prey system. I applied the two approaches to the classic predator,prey dynamics of snowshoe hares in northwestern Ontario, Canada. Hares occupied regenerating cutovers and adjacent mature-forest habitat equally, and in a manner consistent with density-dependent habitat selection. Independent measures of predation risk based on experimental, as well as natural, giving-up densities agreed generally with the equal preference between habitats revealed by the isodar. There was no apparent difference in predation risk between habitats despite obvious differences in physical structure. Complementary studies contrasting a pair of habitats with more extreme differences confirmed that hares do alter their giving-up densities when one habitat is clearly superior to another. The results are thereby consistent with theories of adaptive behaviour. But the results also demonstrate, when evaluating differences in habitat, that it is crucial to let the organisms we study define their own habitat preference. [source] Cryptic self-incompatibility and distyly in Hedyotis acutangula Champ. (Rubiaceae)PLANT BIOLOGY, Issue 3 2010X. Wu Abstract Distyly, floral polymorphism frequently associated with reciprocal herkogamy, self- and intramorph incompatibility and secondary dimorphism, constitutes an important sexual system in the Rubiaceae. Here we report an unusual kind of distyly associated with self- and/or intramorph compatibility in a perennial herb, Hedyotis acutangula. Floral morphology, ancillary dimorphisms and compatibility of the two morphs were studied. H. acutangula did not exhibit precise reciprocal herkogamy, but this did not affect the equality of floral morphs in the population, as usually found in distylous plants. Both pin and thrum pollen retained relatively high viability for 8 h. The pollen to ovule ratio was 72.5 in pin flowers and 54.4 in thrum flowers. Pistils of pin flowers remained receptive for longer than those of thrum flowers. No apparent difference in the germination rate of pin and thrum pollen grains was observed when cultured in vitro, although growth of thrum pollen tubes was much faster than that of pin pollen tubes. Artificial pollination revealed that pollen tube growth in legitimate intermorph crosses was faster than in either intramorph crosses or self-pollination, suggesting the occurrence of cryptic self-incompatibility in this species. Cryptic self-incompatibility functioned differently in the two morphs, with pollen tube growth rates after legitimate and illegitimate pollination much more highly differentiated in pin flowers than in thrum flowers. No fruit was produced in emasculated netted flowers, suggesting the absence of apomixis. Our results indicate that H. acutangula is distylous, with a cryptic self-incompatibility breeding system. [source] Gender-specific molecular heterosis of dopamine D2 receptor gene (DRD2) for smoking in schizophreniaAMERICAN JOURNAL OF MEDICAL GENETICS, Issue 6 2002Hong-Seock Lee Abstract We examined the genetic effect of DRD2 A1 allele in 167 Korean schizophrenics in relation to their smoking habit. Although there was no apparent difference in the genotype distributions of DRD2 gene among the female schizophrenics (n,=,66), the male counterpart (n,=,101) showed significant differences in their genotype distributions. The comparison between male smoking and non-smoking patients showed the difference in genotype distribution (P,=,0.010) with a higher prevalence of A1 allele (P,=,0.020) and frequency of heterozygotes (P,=,0.005), but not frequency of the A1 allele. The A1A2 heterozygotes male showed significantly higher smoking rate compared to the A1A1 or A2A2 homozygotes male, and non-smokers were deficient in heterozygotes. By contrast, among female schizophrenics, the heterozygotes showed a lower smoking rate than homozygotes and there were more heterozygotes in non-smokers. The deviation from Hardy-Weinberg expectations was observed in male and female non-smokers showing quite opposite profiles. Highly significant differences were seen between male and female non-smokers in A1 prevalence (P,=,0.001), genotype distribution (P,=,0.00011), and frequency of heterozygotes (P,=,0.00003), but not in A1 frequency. The analyses from both male and female as one group showing no significant difference in the genotype distributions between smokers and non-smokers could be explained by the gender difference in the genetic effect of DRD2 A1 allele. Our findings present the gender-specific molecular heterosis of DRD2 gene in relation specifically to the smoking status of schizophrenic patients. They indicate the importance of heterosis and gender effects that should be taken into consideration for the association studies. © 2002 Wiley-Liss, Inc. [source] Zinc ions in ,-cells of obese, insulin-resistant, and type 2 diabetic rats traced by autometallographyAPMIS, Issue 12 2003L. G. SØNDERGAARD Zinc ions in the secretory granules of ,-cells are known to glue insulin molecules, creating osmotically stable hexamers. When the secretory granules open to the surface, the zinc ion pressure decreases rapidly and pH levels change from acid to physiological, which results in free insulin monomers and zinc ions. The released zinc ions have been suggested to be involved in a paracrine regulation of ,- and ,-cells. Since zinc is intimately involved in insulin metabolism and because zinc homeostasis is known to be disturbed in type 2 diabetes, we decided to study the ultrastructural localisation of zinc ions in insulin-resistant and type 2 diabetic rats as compared to controls. By means of autometallography, the only method available for demonstrating zinc ions at ultrastructural levels, we found zinc ions in the secretory granules and adjacent to the plasma membrane. The membrane-related staining outside the plasma membrane reflects release of zinc ions during exocytosis. No apparent difference was found in the ultrastructural localisation of zinc ions when we compared the obese Zucker (fa/fa) rats, representing the insulin resistance syndrome, and the GK rats, representing type 2 diabetes, with controls. This suggests that the ultrastructural localisation of zinc ions is unaffected by the development of type 2 diabetes in rats in a steady state of glycaemia. [source] L6-S1 spinal nerve stimulation reduces micturition frequency in anaesthetized rats with cyclophosphamide-induced cystitisBJU INTERNATIONAL, Issue 2 2006FRANÇOIS A. GIULIANO OBJECTIVE To further investigate the rationale for using spinal nerve stimulation (SNS) for treating bladder overactivity associated with cystitis in a rat model of cyclophosphamide-induced cystitis, as several studies suggested that symptoms associated with chronic cystitis could be treated using stimulation of sacral spinal nerves, but the mechanisms by which it works are unknown. MATERIALS AND METHODS Cystitis was induced by i.p. injection of cyclophosphamide 48 h before the experiments in anaesthetized male rats. Neurograms were taken by placing a recording electrode onto the pelvic nerve and a stimulating electrode on either the L6 or S1 ipsilateral spinal nerves. Two selected intensities were then evaluated for SNS in control and cyclophosphamide-treated rats during cystometry. RESULTS Cyclophosphamide resulted in significant bladder overactivity. There was no apparent difference in the neurograms generated in response to SNS of the S1 and L6 spinal nerves, and between cyclophosphamide and control rats. Intensities of 200 µA (A,-fibre-specific) and 2 mA (A,+ C-fibres) were chosen for SNS. Continuous SNS at 200 µA significantly reduced the frequency of voiding and non-voiding contractions in cyclophosphamide-treated rats. SNS at 2 mA resulted in the abolition of voiding contractions, accompanied by continuous leakage of urine. CONCLUSION SNS recruiting only A,-fibre produced fewer voiding contractions in cyclophosphamide-treated rats, to a level similar to that from the control rats. These results support the ability of SNS to decrease bladder overactivity in a pathophysiological model of chemical irritation of the bladder. [source] Expression patterns of the ATM gene in mammary tissues and their associations with breast cancer survivalCANCER, Issue 9 2007Chuanzhong Ye MD Abstract BACKGROUND. The ataxia-telangiectasia mutated (ATM) gene plays a critical role in cell-cycle arrest, apoptosis, and DNA repair. However, to date, no study has directly investigated the association between ATM gene expression and breast cancer survival. METHODS. ATM gene expression levels were evaluated in tumor and adjacent normal tissue from patients diagnosed with primary breast cancer or BBD using quantitative real-time reverse transcription polymerase chain reaction (RT-PCR) assays. Cox regression models were used to evaluate the association of ATM gene expression and survival in a cohort of 471 breast cancer patients. RESULTS. In breast cancer cases, ATM expression in cancer tissues was decreased by approximately 50% compared with adjacent normal tissues from the same patients. In BBD cases, the expression level of the ATM gene was similar in benign tumor tissue and adjacent normal tissues. No apparent difference was found in ATM gene expression levels in adjacent normal tissues obtained from cancer patients or BBD controls. Compared with patients with the lowest tertile of the ATM mRNA, patients in the upper 2 tertiles had more favorable disease-free survival (hazard ratio [HR] = 0.46, 95% confidence interval [CI]: 0.30,0.73 and HR = 0.52, 95% CI: 0.33,0.81, respectively) and overall survival (HR = 0.56, 95% CI: 0.35,0.92 and HR = 0.70, 95% CI: 0.43,1.13, respectively). CONCLUSIONS. The ATM gene expression was down-regulated in breast cancer tissues and a high ATM gene expression level in breast cancer tissue was associated with a favorable prognosis. Cancer 2007. © 2007 American Cancer Society. [source] Examining rival theories of demographic influences on political support: The power of regional, ethnic, and linguistic divisions in UkraineEUROPEAN JOURNAL OF POLITICAL RESEARCH, Issue 4 2002Lowell W. Barrington What effects do regional, linguistic, and ethnic divisions have on support for the government and political system? What is the effect of each when the others are controlled for? Are apparent differences in support across regions simply compositional effects of ethno-linguistic patterns in those regions? This article provides answers to these questions, through the analysis of late 1998 mass survey data from Ukraine. The results indicate that region of residence strongly shapes support for the government and regime. Ethnicity and language, on the other hand, have weaker effects than scholars would expect, once region is controlled for. Thus, regional differences are not simply reflecting ethno-linguistic patterns in Ukraine, as scholars have often implied. These findings shed light on rival theoretical approaches to understanding regional, ethnic and linguistic sources of identity. They also highlight the necessity for scholars who have emphasized ethnic and linguistic cleavages in other countries to consider controlling for region of residence before jumping to conclusions about effects on political attitudes. Finally, the findings have narrower, but important, implications for the study of Ukraine and for its stability. [source] Statistical theory of weak field thermoremanent magnetization in multidomain particle ensemblesGEOPHYSICAL JOURNAL INTERNATIONAL, Issue 2 2003Karl Fabian SUMMARY A non-equilibrium statistical theory of multidomain thermoremanent magnetization (TRM) is developed, which describes thermal magnetization changes as continuous inhomogeneous Markov processes. The proposed theory relies on three very general physical properties of TRM: (a) The probability that a magnetization state Sj is transformed during an infinitesimal temperature change into state Si depends only on external conditions and on Sj, but not on previously assumed states. (b) Due to time inversion symmetry of the Maxwell equations, the magnetic energies are invariant with respect to inversion of all spins in zero field. (c) The probability that an energy barrier between two magnetization states is overcome during a thermal process is governed by Boltzmann statistics. From these properties, the linearity of TRM with field is derived for generic multidomain particle ensembles. The general validity of Thellier's law of additivity of partial TRM's in weak fields is established and a method for proving a large class of similar additivity laws is developed. The theory allows consistent treatment of blocking and unblocking of remanence in multidomain particle ensembles and naturally explains apparent differences between blocking and unblocking temperatures. [source] Mineral absorption in tapirs (Tapirus spp.) as compared to the domestic horseJOURNAL OF ANIMAL PHYSIOLOGY AND NUTRITION, Issue 6 2009M. Clauss Summary To test whether mineral recommendations for horses are likely to guarantee adequate mineral provision for tapirs (Tapirus spp.), we investigated the apparent absorption (aA) of macro and micro-minerals in 18 tapirs from five zoological institutions in a total of 24 feeding trials with total faecal collection. Samples of feeds and faeces were analysed for Ca, P, Mg, Na, K, Fe, Cu and Zn. The resulting aA coefficients and the linear relationships of apparently absorbable dietary mineral content to total dietary mineral content (per 100 g dry matter) were compared with data for domestic horses. While there were no apparent differences in the absorption patterns for P, K, Na, Fe, Cu or Zn, the absorption of both Ca and Mg was distinctively higher in tapirs than in horses. Tapirs are browsers that are adapted to a diet of higher Ca content and higher Ca:P ratio than equids, and high absorptive efficiency for Ca might have evolved to ensure that high dietary Ca concentrations do not lead to the binding of dietary P in the intestine, making it unavailable for hindgut microbes. Similar to other hindgut fermenters, in tapirs, absorption coefficients for Ca increased with dietary Ca:P ratio, and urinary Ca:creatinine ratios increased with dietary Ca. Several zoo diets used were deficient in one or more minerals. When compared with faeces of free-ranging animals, faeces of zoo animals had higher concentrations of most minerals, probably indicating a lesser diluting effect of indigestible fibre in zoo animals. [source] Induced changes in total serum IgE concentration in the Brown Norway rat: potential for identification of chemical respiratory allergensJOURNAL OF APPLIED TOXICOLOGY, Issue 1 2002E. V. Warbrick Abstract A variety of chemicals can cause sensitization of the respiratory tract and occupational asthma that may be associated with IgE antibody production. Topical exposure to chemical respiratory allergens such as trimellitic anhydride (TMA) has been shown previously to induce increases in the total serum concentration of IgE in BALB/c strain mice. Contact allergens such as 2,4-dinitrochlorobenzene (DNCB), which apparently lack respiratory sensitizing potential, fail to provoke similar changes. However, it became apparent with time that there was some inter-animal variation in constitutive and inducible IgE levels. We have now examined the influence of topical exposure to TMA and DNCB on serum IgE levels in the Brown Norway (BN) rat. Such animals can be bled serially and thus it is possible to perform longitudinal analyses of changes in serum IgE concentration. The kinetics of IgE responses therefore can be followed on an individual animal basis, allowing discrimination between transient and sustained increases in serum IgE concentration. Rats (n = 5) were exposed on shaved flanks to 50% TMA, to 1% DNCB (concentrations that elicit comparable immune activation with respect to draining lymph node cellularity and proliferation) or to vehicle alone. Total IgE was measured by enzyme-linked immunosorbent assay in serum samples taken prior to and 14,42 days following initial exposure. Those animals having high pre-existing IgE levels (>1.0 µg ml,1) were excluded from subsequent analyses. The levels of serum IgE in the majority of rats exposed to DNCB or vehicle alone remained relatively stable throughout the duration of all the experiments conducted, although some animals displayed transient increases in serum IgE. Only TMA treatment was associated with a significant and sustained increase in the level of serum IgE in the majority of experiments. The elevated concentrations of IgE induced by topical exposure to TMA are persistent, the results reported here demonstrating that induced changes in IgE are maximal or near maximal at approximately 35 days, with a significant increase in IgE demonstrable for at least 42 days following the initiation of exposure. Interestingly, although TMA and DNCB at the test concentrations used were found to be of comparable overall immunogenicity with regard to lymph node activation and the induction of lymph node cell proliferation, there were apparent differences in humoral immune responses. Thus, not only did exposure to TMA stimulate increases in total serum IgE concentration and the production of specific IgE antibody, but also a more vigorous IgG antibody response was provoked by TMA compared with DNCB. These data suggest that the measurement of induced changes in serum IgE concentration in the BN strain of rat is able to differentiate between different classes of chemical allergen. Given the inter-animal variation in IgE production, it would be prudent to incorporate a concurrent assessment of responses induced by treatment with TMA as a positive control against which to assess the activity of other test materials. Copyright © 2002 John Wiley & Sons, Ltd. [source] Long-term immunogenicity of preservative-free hepatitis B vaccine formulations in adults,JOURNAL OF MEDICAL VIROLOGY, Issue 10 2009Pierre Van Damme Abstract Vaccination with recombinant hepatitis B vaccines is highly effective in preventing hepatitis B infection. Recently, a preservative-free (PF) formulation of hepatitis B vaccine [GlaxoSmithKline (GSK) Biologicals, Rixensart, Belgium] has been licensed. The immunogenicity of the PF hepatitis B vaccine and antibody persistence 6 years later was assessed in this study. This formulation was compared with the preservative- containing (PC) formulation of the vaccine and a low-preservative (LP) content formulation. Five hundred forty-one healthy adult subjects were evaluated in the primary study. Over 94% of the subjects in the three study groups had seroprotective anti-HBs antibody concentrations (,10,mIU/ml) 1 month after completing primary vaccination. Antibody measurements in 242 healthy adults who returned for the follow-up study and who had received primary vaccination 6 years earlier showed that over 81% of subjects in the three study groups still had anti-HBs antibody concentrations ,10,mIU/ml. No apparent differences in antibody decline or distribution between the study groups were observed. These results indicate that the removal of preservatives from the hepatitis B vaccine does not affect adversely its immunogenicity both in the short and in the longer term. J. Med. Virol. 81:1710,1715, 2009. © 2009 Wiley-Liss, Inc. [source] Effects of ketamine on formalin-induced activity in the spinal dorsal horn of spinal cord-transected cats: differences in response to intravenous ketamine administered before and after formalinACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 8 2000H. Nagasaka Background: Although formalin has been widely used as an algesic substance in rodent studies, the unique biphasic effect seen in rats is not present in humans. Humans, like cats, have a monophasic behavioral response to formalin injection. Electrophysiologically, spinal dorsal horn neurons in cats also have what could be considered a monophasic response after the initial burst of activity following formalin injection. Although several studies of the effects of ketamine on formalin responses have been carried out in rodents, we are unaware of similar studies in cats. We hypothesize that such species differences may explain observed differences in preemptive analgesic effects. Therefore, we examined the effects of ketamine on activity of spinal wide dynamic range (WDR) neurons evoked by formalin injection in cats. Methods: We investigated in cats the effect of ketamine on the activity of WDR neurons in the spinal dorsal horn that was evoked by formalin. In addition, we studied the effects of pre- and post-administration of ketamine on the maintained phase of the formalin response. Each dose was a subanesthetic, anesthetic or high anesthetic dose (3.0 mg · kg,1, 10 mg · kg,1, and 30 mg · kg,1). Results: Intravenously administered ketamine produced a dose-dependent depression of evoked activity that was significantly greater when the drug was administered before formalin. Conclusions: In spite of the species differences in responses to formalin, there still appears to be a clear preemptive effect of ketamine in the cat. Species differences may not explain apparent differences between human and animal preemptive analgesia. [source] The immunology of susceptibility and resistance to scabiesPARASITE IMMUNOLOGY, Issue 8 2010S. F. WALTON Summary The transmission of scabies occurs with the burrowing of Sarcoptes scabiei var. hominis mites into the skin. Infestation invariably leads to the development of localized cutaneous inflammation, pruritis and skin lesions. Classical transmission studies document an initial increase in S. scabiei numbers subsequent to primary infestation with a gradual reduction as host immunity develops. However, certain individuals fail to control infection and develop severe crusting of the skin, accompanied with extremely high mite burdens, elevated antibody levels and eosinophilia. These individuals have the nonhealing form of the human disease known as crusted scabies. The genetic predisposition for susceptibility or resistance to S. scabiei infection in humans is hypothesized to correlate with the dominance of an IgE-driven Th2 response in severe disease or an interferon-,-dominated Th1 response that promotes parasite control. However, recent data reveals complexities in cytokine regulation in the skin and the mechanisms of acquired resistance and immune escape. In this review, we consider the recent immunological and biomolecular advances in understanding the human host immune response to S. scabiei infestations in the context of earlier studies and attempt to reconcile apparent differences and emphasize those aspects of the Th1/Th2 model that are supported or refined. [source] A trial of two trouts: comparing the impacts of rainbow and brown trout on a native galaxiidANIMAL CONSERVATION, Issue 4 2010K. A. Young Abstract Rainbow trout Oncorhynchus mykiss and brown trout Salmo trutta are the world's two most widespread exotic fishes, dominate the fish communities of most cold-temperate waters in the southern hemisphere and are implicated in the decline and extirpation of native fish species. Here, we provide the first direct comparison of the impacts of rainbow and brown trout on populations of a native fish by quantifying three components of exotic species impact: range, abundance and effect. We surveyed 54 small streams on the island of Chiloé in Chilean Patagonia and found that the rainbow trout has colonized significantly more streams and has a wider geographic range than brown trout. The two species had similar post-yearling abundances in allopatry and sympatry, and their abundances depended similarly on reach-level variation in the physical habitat. The species appeared to have dramatically different effects on native drift-feeding Aplochiton spp., which were virtually absent from streams invaded by brown trout but shared a broad sympatric range with rainbow trout. Within this range, the species' post-yearling abundances varied independently before and after controlling for variation in the physical habitat. In the north of the island, Aplochiton spp. inhabited streams uninvaded by exotic trouts. Our results provide a context for investigating the mechanisms responsible for apparent differences in rainbow and brown trout invasion biology and can help inform conservation strategies for native fishes in Chiloé and elsewhere. [source] Subgroup Hypotheses: Clinician's Friend or Researcher's Fiction?ACADEMIC EMERGENCY MEDICINE, Issue 8 2009Peter C. Wyer MD Abstract Researchers and clinicians may be tempted to consider apparent differences in effects of interventions in subgroups of study populations for the purposes of individualizing care or directing subsequent focused research efforts. Such "subgroup hypotheses" have a high propensity of being artifacts of chance and are rarely supported when stringent criteria are applied. Subgroup hypotheses emerging from single trials should rarely if ever be considered for application. This article describes published criteria for evaluating the believability of a subgroup hypothesis and presents a conceptual framework for understanding the principles underlying those criteria. Examples of both failed and validated subgroup hypotheses drawn from emergency medicine research are given. [source] Diagnosis and classification of periodontal diseaseAUSTRALIAN DENTAL JOURNAL, Issue 2009J Highfield Abstract Periodontal diseases have been recognized and treated for at least 5000 years. Clinicians have recognized for many years that there are apparent differences in the presentation of periodontal diseases and have attempted to classify these diseases. Systems of classifications of disease have arisen allowing clinicians to develop structures which can be used to identify diseases in relation to aetiology, pathogenesis and treatment. It allows us to organize effective treatment of our patients' diseases. Once a disease has been diagnosed and classified, the aetiology of the condition and appropriate evidence-based treatment is suggested to the clinician. Common systems of classification also allow effective communication between health care professionals using a common language. Early attempts at classification were made on the basis of the clinical characteristics of the diseases or on theories of their aetiology. These attempts were unsupported by any evidence base. As scientific knowledge expanded, conventional pathology formed the basis of classification. More recently, this has been followed by systems of classification based upon our knowledge of the various periodontal infections and the host response to them. Classification of periodontal diseases has, however, proved problematic. Over much of the last century clinicians and researchers have grappled with the problem and have assembled periodically to review or develop the classification of the various forms of periodontal disease as research has expanded our knowledge of these diseases. This has resulted in frequent revisions and changes. A classification, however, should not be regarded as a permanent structure. It must be adaptable to change and evolve with the development of new knowledge. It is expected that systems of classification will change over time. This review examines the past and present classifications of the periodontal diseases. [source] Effect of omeprazole on the pharmacokinetics of paricalcitol in healthy subjectsBIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 2 2007Rameshraja Palaparthy Abstract Paricalcitol capsules are indicated for the prevention and treatment of secondary hyperparathyroidism in chronic kidney disease (CKD). Proton pump inhibitors are prescribed to CKD patients to treat gastroesophageal reflux. This was a single dose, crossover study evaluating the effect of omeprazole, change in gastric pH as a result thereof, on the pharmacokinetics (PK) of paricalcitol. Twenty-six healthy subjects were administered paricalcitol capsules (16 µg) alone (regimen A), and following a single dose of OMP (40 mg) (regimen B), with a washout of at least 7 days. Plasma samples for paricalcitol concentrations were collected for 48 h post-paricalcitol dose. The plasma paricalcitol concentrations were measured using an LC,MS/MS assay (LOQ=0.02 ng/ml) and paricalcitol pharmacokinetic parameters were estimated using non-compartmental methods. The point estimates and the corresponding 90% confidence intervals for Cmax and AUC0-, to evaluate paricalcitol,omeprazole interaction were 1.032 [0.920,1.158] and 1.041 [0.951,1.139], respectively. No significant differences in Tmax (regimen A: 2.9 h vs regimen B: 2.6 h) or t1/2 (6.83 h vs 6.6 h) between the regimens were observed. Hence, the co-administration of omeprazole does not affect the PK of paricalcitol. Both regimens were well tolerated and no apparent differences among the regimens with respect to safety were observed. Copyright © 2007 John Wiley & Sons, Ltd. [source] Cloning and Characterization of Long-Chain Fatty Alcohol Oxidase LjFAO1 in Lotus japonicusBIOTECHNOLOGY PROGRESS, Issue 3 2008Shilan Zhao The Lotus japonicus EST database was searched against Arabidopsis thalianaAtFAO3, a full-length cDNA that encodes a membrane-bound, flavin-containing, hydrogen peroxide generating, long-chain fatty alcohol oxidase. One EST fragment was detected, and the corresponding full-length cDNA was obtained by screening a cDNA library of L. japonicus. The LjFAO1 genomic DNA was amplified by PCR, to give a product 3.6 kb in length. Comparison between the LjFAO1 cDNA and genomic DNA revealed that the LjFAO1 contains 3 exons and 2 introns. RT-PCR analysis showed that the LjFAO1 was expressed in the whole plant, with the highest expression level in the apex and the lowest expression level in the siliques. The LjFAO1 gene was down-regulated by cold stress in both the apex and the cotelydon of the 8-day old seedlings, the first time that a long-chain alcohol oxidase has been shown to respond directly to stress. The full length cDNA and a C-terminal truncated version were overexpressed in Escherichia coli. The full length version of LjFAO1 exhibited long-chain fatty alcohol oxidase activity and was subsequently purified by Ni-NTA chromatography. The active LjFAO1 protein showed substrate specificities toward 1-dodecanol, 1-hexadecanol, and 1,16-hexadecanediol with Km values 59.6 ± 14.8 (,M), 40.9 ± 8.2 (,M) and 19.4 ± 1.5 (,M), respectively, suggesting apparent differences in substrate preferences with AtFAO3. [source] A mouse model of pemphigus vulgaris by adoptive transfer of naive splenocytes from desmoglein 3 knockout miceBRITISH JOURNAL OF DERMATOLOGY, Issue 2 2004M. Aoki-Ota Summary Background, Pemphigus vulgaris (PV) is an autoimmune blistering disease caused by antidesmoglein3 (anti-Dsg3) IgG autoantibodies. Recently, we developed a PV mouse model by adoptive transfer of splenocytes from recombinant Dsg3-immunized Dsg3,/, mice to Rag2,/, immunodeficient mice that expressed Dsg3. Objectives, We determined whether the adoptive transfer of naive splenocytes from nonimmunized Dsg3,/, mice induces the anti-Dsg3 IgG production and the PV phenoytpe in recipient mice. Methods, We adoptively transferred naive Dsg3,/, splenocytes into Rag2,/, mice and compared their PV phenoytpe with those mice receiving immunized Dsg3,/, splenocytes. The numbers of splenocytes and their subpopulations required for anti-Dsg3 IgG production were examined. Results, Mice that received naive Dsg3,/, splenocytes produced anti-Dsg3 IgG, which bound to keratinocyte cell surfaces in vivo, and developed the PV phenotype, including oral erosions with suprabasilar acantholysis. Antibody production and the appearance of the PV phenotype were delayed by approximately 2 weeks in mice that received naive splenocytes compared with mice that received immunized splenocytes. However, once the PV phenotypes developed, there were no apparent differences in disease severity between the two models. Interestingly, the anti-Dsg3 IgG titres were significantly lower in mice that received naive splenocytes than in mice that received immunized splenocytes, suggesting that the former antibodies were more potent than the latter. The frequency of anti-Dsg3 IgG production depended on the number of transferred naive splenocytes. Both CD4+ T cells and B220+ B cells from naive Dsg3,/, mice were essential for the production of anti-Dsg3 IgG antibodies. Conclusions, Dsg3-specific naive lymphocytes in Dsg3,/, mice can be primed and activated by the endogenous Dsg3 in recipient mice to produce pathogenic anti-Dsg3 IgG without active immunization. This approach using naive lymphocytes provides a unique model to dissect immunological mechanisms of tolerance against peripheral autoimmune targets. [source] Tax credits, insurance, and the use of medical careCANADIAN JOURNAL OF ECONOMICS, Issue 2 2005Michael Smart Little is known about the effects of such tax measures on individual behaviour, in contrast to the extensive research on the tax exemption for employer-provided health insurance. In this paper, we exploit variation in the after-tax cost of health expenditures under the tax law to estimate the tax price elasticity of demand for prescription drugs, health insurance, and other eligible expenditures. We find evidence of moderate to large tax price elasticities, compared with traditional point-of-service price elasticity estimates , despite the apparent differences in the way tax subsidies are experienced by consumers. In contrast, we find no evidence the tax subsidy affects demand for health insurance on the intensive margin, which we show is consistent with the theory of optimal self-insurance. We discuss the implications of our results for recent proposals to reform public and private health insurance systems. JEL classification: I1, H2 Crédits d'impôt, assurance et l'utilisation des soins médicaux., Les systèmes d'impôt sur le revenu des particuliers au Canada, aux Etats-Unis et ailleurs permettent des déductions ou crédits d'impôt pour les dépenses directes en soins de santé assumées par les particuliers ou pour les primes d'assurance privée. On connaît mal les effets de ces mesures fiscales sur le comportement des personnes par comparaison avec les résultats extensifs de la recherche sur les effets des exemptions fiscales pour l'assurance santé fournie par les employeurs. Dans ce texte, on utilise la variation dans le fardeau des dépenses pour la santé après impôt selon les diverses juridictions pour évaluer l'élasticité de la demande de médicaments d'ordonnance, de l'assurance santé, et d'autres dépenses éligibles en réponse à des différences de prix fiscaux. On découvre que l'ordre de grandeur des élasticité se situe entre modérée et grande quand on les compare aux évaluations des élasticités traditionnelles de la demande aux points de service par rapport aux prix , et ce malgré les différences apparentes dans les expériences de ces subventions fiscales pour les consommateurs. D'autre part, on ne trouve pas de support pour l'hypothèse que les subventions fiscales affectent la demande d'assurance santéà la marge intensive , ce qui concorde bien avec ce que nous enseigne la théorie de l'auto-assurance optimale. On discute les implications de ces résultats pour certaines réformes récentes proposées aux systèmes d'assurance santé privés et publics. [source] Delayed neovascularization in inflammation-induced corneal neovascularization in interleukin-10-deficient miceACTA OPHTHALMOLOGICA, Issue 2 2010Branka Samolov Abstract. Purpose:, To investigate the potential modulatory role of interleukin-10 (IL-10) in the suture model for corneal neovascularization. Methods:, Neovascularized areas were measured on corneal flat-mounts in IL-10,/, and wild-type C57BL6 mice. The inflammatory cellular response was characterized with immunohistochemistry. Gene expression was measured by real-time polymerase chain reaction. Results:, IL-10,/, mice showed a delayed neovascular response compared to wild-type animals at day 6 after suture, when approximately half of the cornea was neovascularized. No apparent differences in inflammatory responses or in messenger RNA (mRNA) expression for proangiogenic factors were detected in IL-10,/, versus wild-type mice. Conclusion:, IL-10 appears to have a proangiogenic effect in the suture model for corneal neovascularization that cannot be explained by either IL-10's anti-inflammatory effect or apparent cross-talk with the angiogenic factors vascular endothelial growth factor (VEGF)-A, metalloproteinase (MMP)-2 and MMP-9, angiopoietin (Ang)-1 and Ang-2. [source] Percutaneous permeation of enantiomers and racemates of chiral drugs and prediction of their flux ratios using thermal data: A pharmaceutical perspectiveCHIRALITY, Issue 5 2003Mohsen I. Afouna Abstract Albeit pharmacological, pharmacokinetic, and toxicological differences between enantiomeric pairs or between the pure enantiomers and racemate of chiral drugs are known to exist for decades, we are just beginning to realize that there are apparent differences between these species with respect to their percutaneous permeation as well. Such differences in permeation are likely to be enhanced when chiral drugs are formulated with chiral excipients, necessitating a careful assessment of the effect of formulation excipients on the permeation as well as the overall therapeutic outcomes. The in vitro transport data from the preclinical investigations, using laboratory animal models and/or in vitro cell culture systems, must be carefully validated in vivo as there are differences between these models and the human skin. Mathematical models such as MTMT that utilize the interdependence of certain physicochemical characteristics and percutaneous permeability have a predictive value in assessing the flux behavior of enantiomers and racemates. Chirality 15:456,465, 2003. © 2003 Wiley-Liss, Inc. [source] |