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Selected AbstractsDissociation of function between the dorsal and the ventral hippocampus in spatial learning abilities of the rat: a within-subject, within-task comparison of reference and working spatial memoryEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 3 2004Helen H. J. Pothuizen Abstract Lesions restricted to the dorsal, but not the ventral, hippocampus severely impair the formation of spatial memory. This dissociation was first demonstrated using the water maze task. The present study investigated whether the dorsal and the ventral hippocampus are involved differentially in spatial reference and spatial working memory using a four-baited/four-unbaited version of the eight-arm radial maze task. This test allows the concurrent evaluation of reference and working memory with respect to the same set of spatial cues, and thereby enables a within-subjects within-task comparison between the two forms of memory functions. Rats with N -methyl- d -aspartic acid-induced excitotoxic lesions of the dorsal hippocampus, ventral hippocampus or both were compared with sham and unoperated controls. We showed that dorsal lesions were as effective as complete lesions in severely disrupting both reference and working spatial memory, whereas rats with ventral lesions performed at a level comparable with controls. These results lend further support to the existence of a functional dissociation between the dorsal and the ventral hippocampus, with the former being preferentially involved in spatial learning. [source] Human lactoferrin activates NF-,B through the Toll-like receptor 4 pathway while it interferes with the lipopolysaccharide-stimulated TLR4 signalingFEBS JOURNAL, Issue 9 2010Ken Ando Lactoferrin (LF) has been implicated in innate immunity. Here we reveal the signal transduction pathway responsible for human LF (hLF)-triggered nuclear factor-,B (NF-,B) activation. Endotoxin-depleted hLF induces NF-,B activation at physiologically relevant concentrations in the human monocytic leukemia cell line, THP-1, and in mouse embryonic fibroblasts (MEFs). In MEFs, in which both tumor necrosis factor receptor-associated factor 2 (TRAF2) and TRAF5 are deficient, hLF causes NF-,B activation at a level comparable to that seen in wild-type MEFs, whereas TRAF6-deficient MEFs show significantly impaired NF-,B activation in response to hLF. TRAF6 is known to be indispensable in leading to NF-,B activation in myeloid differentiating factor 88 (MyD88)-dependent signaling pathways, while the role of TRAF6 in the MyD88-independent signaling pathway has not been clarified extensively. When we examined the hLF-dependent NF-,B activation in MyD88-deficient MEFs, delayed, but remarkable, NF-,B activation occurred as a result of the treatment of cells with hLF, indicating that both MyD88-dependent and MyD88-independent pathways are involved. Indeed, hLF fails to activate NF-,B in MEFs lacking Toll-like receptor 4 (TLR4), a unique TLR group member that triggers both MyD88-depependent and MyD88-independent signalings. Importantly, the carbohydrate chains from hLF are shown to be responsible for TLR4 activation. Furthermore, we show that lipopolysaccharide-induced cytokine and chemokine production is attenuated by intact hLF but not by the carbohydrate chains from hLF. Thus, we present a novel model concerning the biological function of hLF: hLF induces moderate activation of TLR4-mediated innate immunity through its carbohydrate chains; however, hLF suppresses endotoxemia by interfering with lipopolysaccharide-dependent TLR4 activation, probably through its polypeptide moiety. [source] Favorable effect of adefovir on the number and functionality of myeloid dendritic cells of patients with chronic HBV,HEPATOLOGY, Issue 4 2006Renate G. van der Molen In patients with chronic hepatitis B virus (HBV), 2 predominant precursor dendritic cell (DC) subtypes, the myeloid dendritic cell (mDC) and the plasmacytoid dendritic cell (pDC), were recently found to be functionally impaired. HBV DNA was found to be present in the DC subtypes, but no viral replication could be detected. The question remains whether simply the presence of the virus and viral proteins causes this dysfunction of DCs. To address this issue, the effect of viral load reduction resulting from treatment with the nucleotide analogue adefovir dipivoxil on the number and functionality of circulating DCs was studied during 6 months of treatment. Treatment resulted in a mean 5 log10 decrease in the viral load and normalization of alanine aminotransferase within 3 months. The number of mDCs, but not of pDCs, increased significantly over 6 months of treatment to a level comparable to that of uninfected healthy controls. The allostimulatory capacity of isolated and in vitro matured mDCs increased significantly after 3 months of treatment. Accordingly, mDCs exhibited an increased capacity to produce tumor necrosis factor alpha and interleukin-12 after 3-6 months of treatment. There was no change in interferon alpha production by pDCs during treatment. In conclusion, adefovir treatment results in an improvement in the number and functionality of mDCs, but not of pDCs. Our findings provide clues for the reasons why current antiviral therapy does not lead to consistently sustained viral eradication. (HEPATOLOGY 2006;44:907,914.) [source] Effect of a transient perturbation on marine bacterial communities with contrasting historyJOURNAL OF APPLIED MICROBIOLOGY, Issue 3 2010O. Zemb Abstract Aims:, To evaluate the importance of the bacterial composition on the resilience of the organic matter assimilation in the sea. Methods and Results:, Chemostats were inoculated with coastal and offshore bacterial communities. Bacterial density and protein synthesis increased before stabilizing, and this response to confinement was more marked in the offshore chemostats. Before the toluene perturbation the community structure in the coastal chemostats remained complex whereas the offshore chemostats became dominated by Alteromonas sp. After the perturbation, bacterial protein synthesis was inhibited before peaking briefly at a level fivefold to that observed before the perturbation and then stabilizing at a level comparable to that before the perturbation. Alteromonas dominated both the coastal and the offshore communities immediately after the perturbation and the coastal communities did not recover their initial complexity. Conclusions:, Cell lysis induced by the toluene perturbation favoured the growth of Alteromonas which could initiate growth rapidly in response to the nutrient pulse. Despite their different community structure in situ, the resilience of protein synthesis of coastal and offshore bacterial communities was dependent on Alteromonas, which dominated in the chemostats. Significance and Impact of the Study:, Here we show that although Alteromonas sp. dominated in artificial offshore and coastal communities in chemostats, their response time to the shock was different. This suggests that future perturbation studies on resilience in the marine environment should take account of ecosystem history. [source] Familial Hypocalciuric Hypercalcemia Caused by an R648stop Mutation in the Calcium-Sensing Receptor Gene ,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 12 2002Mika Yamauchi Abstract In this study, we report an 84-year-old female proband in a Japanese family with familial hypocalciuric hypercalcemia (FHH) caused by an R648stop mutation in the extracellular calcium-sensing receptor (CaR) gene. At the age of 71 years, she presented with hypercalcemia (11.4 mg/dl), hypocalciuria (Cca/Ccr = 0.003), hypermagnesemia (2.9 mg/dl), and a high-serum parathyroid hormone (PTH) level (midregion PTH, 3225 [160,520] pg/ml). At the age of 74 years, a family screening was carried out and revealed a total of 9 hypercalcemic individuals (all intact PTH values <62 pg/dl) among 17 family members tested, thus, being diagnosed as FHH. Two and one-half of three clearly enlarged parathyroid glands were resected, because persistently high PTH levels (intact PTH, 292 pg/ml; midregion PTH, 5225 pg/ml) and the presence of a markedly enlarged parathyroid gland by several imaging modalities (ultrasonography, computed tomography [CT], magnetic resonance imaging [MRI], and subtraction scintigraphy) suggested coexistent primary hyperparathyroidism (pHPT); however, hypercalcemia persisted postoperatively. Histological and immunohistochemical examination revealed that the resected parathyroid glands showed lipohyperplasia as well as normally expressed Ki67, vitamin D receptor (VDR), and the CaR. Sequence analysis disclosed that the proband and all affected family members had a heterozygous nonsense (R648stop) mutation in the CaR gene. This mutation is located in the first intracellular loop; thus, it would be predicted to produce a truncated CaR having only one transmembrane domain (TMD) and lacking its remaining TMDs, intracellular loops, and C-terminal tail. Western analysis of biotinylated HEK293 cells transiently transfected with this mutant receptor showed cell surface expression of the truncated protein at a level comparable with that of the wild-type CaR. The mutant receptor, however, exhibited no increase in intracellular free calcium concentration (Ca2+i) when exposed to high extracellular calcium concentrations (Ca2+o). The proband's clinical course was complicated because of associated renal tubular acidosis (RTA) and nephrotic syndrome. However, it was unclear whether their association affected the development of elevated serum PTH and parathyroid gland enlargement. This report is the first to show that an R648stop CaR mutation yields a truncated receptor that is expressed on the cell surface but is devoid of biological activity, resulting in FHH. [source] Reduction in glutamate uptake is associated with extrasynaptic NMDA and metabotropic glutamate receptor activation at the hippocampal CA1 synapse of aged ratsAGING CELL, Issue 5 2010Brigitte Potier Summary This study aims to determine whether the regulation of extracellular glutamate is altered during aging and its possible consequences on synaptic transmission and plasticity. A decrease in the expression of the glial glutamate transporters GLAST and GLT-1 and reduced glutamate uptake occur in the aged (24,27 months) Sprague,Dawley rat hippocampus. Glutamatergic excitatory postsynaptic potentials recorded extracellularly in ex vivo hippocampal slices from adult (3,5 months) and aged rats are depressed by DL-TBOA, an inhibitor of glutamate transporter activity, in an N -Methyl- d- Aspartate (NMDA)-receptor-dependent manner. In aged but not in young rats, part of the depressing effect of DL-TBOA also involves metabotropic glutamate receptor (mGluRs) activation as it is significantly reduced by the specific mGluR antagonist d-methyl-4-carboxy-phenylglycine (MCPG). The paired-pulse facilitation ratio, a functional index of glutamate release, is reduced by MCPG in aged slices to a level comparable to that in young rats both under control conditions and after being enhanced by DL-TBOA. These results suggest that the age-associated glutamate uptake deficiency favors presynaptic mGluR activation that lowers glutamate release. In parallel, 2 Hz-induced long-term depression is significantly decreased in aged animals and is fully restored by MCPG. All these data indicate a facilitated activation of extrasynaptic NMDAR and mGluRs in aged rats, possibly because of an altered distribution of glutamate in the extrasynaptic space. This in turn affects synaptic transmission and plasticity within the aged hippocampal CA1 network. [source] The Impact of the Big 8 Mergers on Market Power: Evidence from the Hong Kong MarketJOURNAL OF INTERNATIONAL FINANCIAL MANAGEMENT & ACCOUNTING, Issue 1 2005Dominica Suk-yee Lee This study examines the impact of the Big 8 mergers on market power in an audit market where the merging firms have little presence. Audit fee changes for each merger participating firm are identified and fee changes for several post-merger years are examined. The pre-merger differential market power between the merging and non-merging long-established Big 8 firms (Price Waterhouse and KPMG Peat Marwick) in Hong Kong provides a unique opportunity to examine whether the mergers could help the merging firms to increase their market power. The results are consistent with the hypotheses that the audit fees of the merging firms were significantly lower than that of the non-merging, long-established Big 8 firms before the mergers, but the audit fees of the merged firms increased significantly to a level comparable with that of the latter group after the mergers. In addition, the market share of the merged firms increased significantly after the mergers. However, no association is found between market concentration and market power. Overall, the results show that the Big 8 mergers have helped the merged firms increase their market power and market share in the Hong Kong audit market where they had little presence. [source] Patterns of performance degradation and restoration during sleep restriction and subsequent recovery: a sleep dose-response studyJOURNAL OF SLEEP RESEARCH, Issue 1 2003Gregory Belenky SUMMARY Daytime performance changes were examined during chronic sleep restriction or augmentation and following subsequent recovery sleep. Sixty-six normal volunteers spent either 3 (n = 18), 5 (n= 16), 7 (n = 16), or 9 h (n = 16) daily time in bed (TIB) for 7 days (restriction/augmentation) followed by 3 days with 8 h daily TIB (recovery). In the 3-h group, speed (mean and fastest 10% of responses) on the psychomotor vigilance task (PVT) declined, and PVT lapses (reaction times greater than 500 ms) increased steadily across the 7 days of sleep restriction. In the 7- and 5-h groups speed initially declined, then appeared to stabilize at a reduced level; lapses were increased only in the 5-h group. In the 9-h group, speed and lapses remained at baseline levels. During recovery, PVT speed in the 7- and 5-h groups (and lapses in the 5-h group) remained at the stable, but reduced levels seen during the last days of the experimental phase, with no evidence of recovery. Speed and lapses in the 3-h group recovered rapidly following the first night of recovery sleep; however, recovery was incomplete with speed and lapses stabilizing at a level comparable with the 7- and 5-h groups. Performance in the 9-h group remained at baseline levels during the recovery phase. These results suggest that the brain adapts to chronic sleep restriction. In mild to moderate sleep restriction this adaptation is sufficient to stabilize performance, although at a reduced level. These adaptive changes are hypothesized to restrict brain operational capacity and to persist for several days after normal sleep duration is restored, delaying recovery. [source] Outbreak of Neurologic Disease Caused by Equine Herpesvirus-1 at a University Equestrian CenterJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 1 2007Rick W. Henninger Background: Equine herpesvirus type 1 (EHV-1) infection causes neurologic disease in horses. However, risk factors for the disease and long-term prognosis are poorly characterized. Hypothesis: There are identifiable risk factors for equine herpes-1 myeloencephalopathy. Animals: The entire population of 135 horses housed within the equestrian facility. Methods: A descriptive study investigated the clinical, serologic, virologic, and management aspects of an outbreak of EHV-1 myeloencephalopathy. Results: Out of 135 horses at the facility, 117 displayed signs of EHV-1 infection. Forty-six horses developed neurologic deficits characterized by symmetrical hind limb ataxia and weakness. Twelve horses that developed neurologic deficits became recumbent and did not survive. The development of severe neurologic deficits during the outbreak was associated with the presence of residual deficits at the 6-month examination. Within 1 year of the outbreak onset, all horses that survived had returned to an exercise level comparable to that experienced before the outbreak. Factors associated with the development of neurologic disease included age of > 5 years, location in the south or arena stall areas, and highest rectal temperature on day 3 or later of the febrile period. Conclusions and clinical importance: Being > 5 years of age, having had a rectal temperature of > 103.5°F, and highest rectal temperature occurring on or after the 3rd day of the febrile period were the factors most predictive of the development of neurologic disease and death. Data obtained during this outbreak substantiate previous findings relating to clinical aspects and diagnosis of EHV-1 myeloencephalopathy. The prophylactic and therapeutic use of acyclovir during this outbreak is described. [source] Origin of the Vertebrate Visual Cycle: III.PHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 6 2006-Monooxygenase Homologues in Ciona intestinalis, -carotene 1, Distinct Distribution of RPE6 We previously identified three genes that encode putative visual cycle proteins that are homologues of retinal G-protein coupled receptor (Ci-opsin3), cellular retinaldehyde-binding protein (Ci-CRALBP) and ,-carotene 15,15,-monooxygenase (Ci-BCO) in the ascidian Ciona intestinalis. Ci-opsin3 and Ci-CRALBP are localized in both ocellus photoreceptor cells and surrounding non-photoreceptor cells in the brain vesicle of the larva. In the present study, we investigated the possible role and evolutionary origin of the BCO/RPE65 family in the visual cycle by analyzing Ci-BCO localization by immunohistochemistry and by identifying a novel gene that encodes a homologue of retinal pigment epithelium,specific 65 kDa protein (Ci-RPE65) in C. intestinalis. In situ hybridization and expressed sequence tag (EST) profiles consistently suggest that Ci-RPE65 is not significantly expressed in the ocellus and brain vesicle of the larva. Ci-RPE65 is expressed in the neural complex, a photoreceptor organ of the adult ascidian, at a level comparable to that of Ci-opsin3 and Ci-CRALBP. Ci-RPE65 is also expressed in various adult tissues, including the gill, body wall and intestine, suggesting that Ci-RPE65 plays a role in addition to that in the visual cycle. In contrast, Ci-BCO is predominantly localized in ocellus photoreceptor cells of the larva. The larval visual cycle seems to use Ci-opsin3 as a photoisomerase. Our results also suggest that the RPE65-dependent visual cycle is used in the adult photoreceptors of a primitive chordate. [source] Overexpression of the acidic dehydrin WCOR410 improves freezing tolerance in transgenic strawberry leavesPLANT BIOTECHNOLOGY JOURNAL, Issue 5 2004Mario Houde Summary Progress in freezing tolerance (FT) improvement through plant breeding approaches has met with little success in the last 50 years. Engineering plants for greater FT through plant transformation is one possible way to reduce the damage caused by freezing. Here, we report an improvement of the selection procedure and the transfer of the wheat Wcor410a acidic dehydrin gene in strawberry. The encoded protein has previously been shown to be associated with the plasma membrane, and its level of accumulation has been correlated with the degree of FT in different wheat genotypes. The WCOR410 protein was expressed in transgenic strawberry at a level comparable with that in cold-acclimated wheat. Freezing tests showed that cold-acclimated transgenic strawberry leaves had a 5 °C improvement of FT over wild-type or transformed leaves not expressing the WCOR410 protein. However, no difference in FT was found between the different plants under non-acclimated conditions, suggesting that the WCOR410 protein needs to be activated by another factor induced during cold acclimation. These data demonstrate that the WCOR410 protein prevents membrane injury and greatly improves FT in leaves of transgenic strawberry. A better understanding of the limiting factors allowing its activation may open up the way for engineering FT in different plant organs, and may find applications for the cryopreservation of human tissues and organs. [source] Activation of human T lymphocytes under conditions similar to those that occur during exposure to microgravity: A proteomics studyPROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 7 2005Angela Risso Abstract A number of experiments, conducted under microgravity conditions, i.e. in space shuttle biolaboratories or in ground based systems simulating the conditions occurring in microgravity, show that in hypogravity, in vitro human lymphocyte activation is severely impaired. However, very early stimulation steps of T lymphocytes are not compromised, since CD69 receptor, the earliest membrane activation marker, is expressed by T cells at a level comparable to that observed on 1 g activated lymphocytes. Since CD69 engagement, together with submitogenic doses of phorbol esters, transduces an activation signal to T lymphocytes, we undertook a comparative study on the stimulation mediated through this receptor on human CD3+ cells cultured under conditions similar to those which occur during exposure to microgravity, i.e. in clinorotation, or at 1 g. During the early hours of activation, increased levels of intracellular calcium and increased mitochondrial membrane potential were detectable in clinorotating as well as in 1 g cells. However, after 48 hours clinorotation, interleukin 2 production by T lymphocytes was significantly reduced and cell proliferation was greatly decreased. By means of a differential proteomics approach on T cells activated in clinorotation or at 1 g for 48 hours, we were able to detect statistically significant quantitative protein alterations. Seven proteins with modified expression values were identified; they are involved in nucleic acids processing, proteasome regulation and cytoskeleton structure. [source] Brief communication: Rethinking the impact of the 1918 influenza pandemic on sex differentials in mortalityAMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY, Issue 4 2009L.A. Sawchuk Abstract This study will assess the general impact of the 1918 influenza on overall mortality and its impact on mortality attributable to pulmonary tuberculosis in a small-scale population. Using life table and decomposition methodologies, changes in mortality in Gibraltar used a scheme that identified a pre-epidemic period (1904,1917), the epidemic year (1918), and the post-epidemic period (1919,1927). Overall health in both sexes fell significantly in 1918 with a drop in life expectancy at birth, however, health quickly rebounded in the post-epidemic period. In the case of women, there was a significant increase in life expectancy at birth after the epidemic. The impact of influenza on the magnitude of sex differentials in the life expectancy at birth fell during epidemic year but returned to a level comparable to that of the pre-epidemic period. With respect to respiratory tuberculosis deaths, the immediate impact of influenza was restricted to only a significant increase in the rate among women (aged 15,54). In the post-epidemic period, tuberculosis mortality rates returned to the pre-epidemic state in both sexes. The findings from Gibraltar stand in contrast opposition to results reported for experience in the United States during the 1918 flu. Am J Phys Anthropol, 2009. © 2009 Wiley-Liss, Inc. [source] ORIGINAL ARTICLE: Differences in the Soluble HLA-G Blood Serum Concentration Levels in Patients with Ovarian Cancer and Ovarian and Deep EndometriosisAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 5 2010Pawel Mach Citation Mach P, Blecharz P, Basta P, Marianowski P, Skret-Magierlo J, Kojs Z, Grabiec M, Wicherek L. Differences in the soluble HLA-G blood serum concentration levels in patients with ovarian cancer and ovarian and deep endometriosis. Am J Reprod Immunol 2010 Problem, The relationship between endometriosis and cancer has been widely discussed in the literature but is still not well clarified. Perhaps significantly, soluble human leukocyte antigen-G (sHLA-G) has been identified in the microenvironment of both ovarian cancer and endometrioma. The aim of this study has been to evaluate the sHLA-G levels in the blood sera of women with deep endometriosis and ovarian endometrioma over the course of the menstrual cycle and to compare to the levels of sHLA-G in the blood sera of women with ovarian cancer. Method of study, In our study, we examined the blood sera obtained from 123 patients operated on because of ovarian cancer (65 cases), ovarian endometrioma (30 cases), and deep endometriosis (28 cases). We decided to compare the levels of sHLA-G in patients with endometriosis to those found in patients with ovarian cancer with respect to the menstrual cycle phases. The sHLA-G concentration level was measured by enzyme-linked immunosorbent assay kit. Results, The level of sHLA-G concentration in the blood serum of patients with deep endometriosis fluctuates over the course of the menstrual cycle, and during the proliferative and secretory phases, it remains at a high level comparable to that found in patients with ovarian cancer. By contrast, the level of sHLA-G concentration in the blood serum of patients with ovarian endometrioma fluctuates minimally over the course of the different menstrual cycle phases and, as in patients with ovarian cancer, it remains at high level during the proliferative phase. Conclusion, sHLA-G blood serum concentration levels would seem to provide important information regarding the degree of immune system regulation disturbance in both ectopic endometrial cells and the cancer cell suppressive microenvironment. [source] Decrease in carotid intima-media thickness in hypothyroid patients after normalization of thyroid functionCLINICAL ENDOCRINOLOGY, Issue 5 2003Toshiki Nagasaki Summary objective, This case,control study was carried out to assess whether levothyroxine (L-T4) replacement might cause regression of the enhanced atherosclerosis seen in hypothyroid patients. patients and methods, Intima-media thickness (IMT) in the common carotid artery (CCA) was measured from digitalized still images taken during scanning by high-resolution ultrasonography as an indicator of early atherosclerosis. Thirty-five hypothyroid patients were examined for their CCA IMT before and 1 year after normalization of thyroid function by L-T4 replacement. As control, 35 healthy subjects were enrolled from among the participants in a local health-check programme conducted at the Osaka City University Hospital. results, Basal CCA IMT was significantly higher in hypothyroid patients [0·635 ± 0·018 (mean ± SE) mm] than in control subjects (0·559 ± 0·021 mm, P < 0·005). After 1 year of euthyroidism, 34 out of 35 patients showed a significant decrease of CCA IMT, to 0·552 ± 0·015 mm (P < 0·0001), a level comparable to normal controls. CCA IMT change was closely associated with basal levels of total cholesterol (r = ,0·472, P= 0·0031), low-density lipoprotein (LDL) cholesterol (r = ,0·441, P= 0·0076) and the total/HDL cholesterol ratio (r =,0·435, P= 0·0057), but not with any of the other variables measured except for age (r = ,0·353, P= 0·0296). conclusions, This study demonstrated that L-T4 treatment might have the potential to reverse the progression of atherosclerosis in hypothyroid patients. Furthermore, it suggests that increased levels of LDL cholesterol and the total/HDL cholesterol ratio have an important role in the increased common carotid intima-media thickness in hypothyroid patients. [source] The effects of acute exercise and high lactate levels on 35% CO2 challenge in healthy volunteersACTA PSYCHIATRICA SCANDINAVICA, Issue 5 2002G. Esquivel Objective:, To test the possible antipanic effects of acute exercise in healthy volunteers exposed to an inhalation of 35% CO2 challenge. Method:, Twenty healthy subjects in a randomized separate group design, performed exercise in a bicycle ergometer reaching >6 mm of blood lactate and a control condition of minimal activity in the same fashion with no lactate elevation. Immediately afterwards an inhalation of a vital capacity using a mixture of 35% CO2/65% O2 through a mask was given on both conditions. Results:, Subjects under the exercise condition reported less panic symptoms than controls after a CO2 challenge on the diagnostic statistical manual-IV (DSM-IV) Panic Symptom List but no difference on the Visual Analogue Anxiety Scale. Conclusion:, Subjects under the exertion condition had lactate levels comparable with those of lactate infusions but an inhibitory rather than accumulative effect was seen when combined with a CO2 challenge. [source] Kava in Arnhem Land: a review of consumption and its social correlatesDRUG AND ALCOHOL REVIEW, Issue 3 2000Alan R. Clough Abstract The debate about the effects and public health importance of the way Aboriginal people drink kava has been confounded by claims, based on anecdote, of imputed health effects. Anecdote and comment have promoted the perception that dosage levels among Aboriginal people are much greater than in Pacific island societies. In this paper we review published data about kava consumption, and evaluate it with respect to information collected from observation of one Aboriginal community in Arnhem Land (Northern Territory) where people tend to consume kavaat a steady tempo; 37g of kava powder containing around 3800mg of kava lactones in 670ml of water in an hour. The highest levels of consumption in Arnhem Land have been reported to be up to 900g/week of kava powder with heavy consumers drinking at least 610g/week, levels comparable to estimates for Pacific-island societies. The significance of a steady drinking tempo means that an individual's weekly kava consumption relates directly to the amount of time spent drinking which, in turn, is correlated with categories of social setting of drinking (p < 0.0002). Lone drinkers appear to be the heaviest users while lowest consumption takes place in private domestic situations, where people enjoy kava as part of family group activities. Surrogates of consumption levels may be found in local socio-economic circumstances. This approach may be useful when more direct measurement of consumption is difficult or impossible. [source] Polybrominated diphenyl ethers, toxaphenes, and other halogenated organic pollutants in great blue heron eggsENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 2 2010Louise Champoux Abstract The great blue heron (Ardea herodias) has been used as a bioindicator of the state of the St. Lawrence River (Québec, Canada) since 1996. At 5-year intervals, selected breeding colonies along the River and its estuary are visited to estimate reproductive success and determine levels of contamination. Brominated flame retardants are found in many ecosystems and are increasing in concentration in the Great Lakes, which is the source of much of the water for the St. Lawrence River. In 2001 and 2002, in addition to polychlorinated biphenyls (PCBs) and chlorinated pesticides, the levels of polybrominated diphenyl ethers (PBDEs), polychlorinated bornanes (toxaphene) congeners and non- ortho -substituted PCBs were measured for the first time in pools of great blue heron eggs. The PBDE levels in great blue heron eggs (70,1,377,ng/g wet wt) were comparable to those measured in herring gull (Larus argentatus) eggs from the Great Lakes. Toxaphene was detected in great blue heron eggs at levels comparable to those of other major chlorinated pesticides. Major toxaphene congeners were octachlorobornane P44 and the nonachlorobornane P50. Environ. Toxicol. Chem. 2010;29:243,249. © 2009 SETAC [source] Mercury-induced reproductive impairment in fish,,ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 5 2009Kate L. Crump Abstract Mercury is a potent neurotoxin, and increasing levels have led to concern for human and wildlife health in many regions of the world. During the past three decades, studies in fish have examined the effects of sublethal mercury exposure on a range of endpoints within the reproductive axis. Mercury studies have varied from highly concentrated aqueous exposures to ecologically relevant dietary exposures using levels comparable to those currently found in the environment. This review summarizes data from both laboratory and field studies supporting the hypothesis that mercury in the aquatic environment impacts the reproductive health of fish. The evidence presented suggests that the inhibitory effects of mercury on reproduction occur at multiple sites within the reproductive axis, including the hypothalamus, pituitary, and gonads. Accumulation of mercury in the fish brain has resulted in reduced neurosecretory material, hypothalamic neuron degeneration, and alterations in parameters of monoaminergic neurotransmission. At the level of the pituitary, mercury exposure has reduced and/or inactivated gonadotropin-secreting cells. Finally, studies have examined the effects of mercury on the reproductive organs and demonstrated a range of effects, including reductions in gonad size, circulating reproductive steroids, gamete production, and spawning success. Despite some variation between studies, there appears to be sufficient evidence from laboratory studies to link exposure to mercury with reproductive impairment in many fish species. Currently, the mechanisms underlying these effects are unknown; however, several physiological and cellular mechanisms are proposed within this review. [source] Health-related Quality of Life of People with Epilepsy Compared with a General Reference Population: A Tunisian StudyEPILEPSIA, Issue 7 2004Hela Mrabet Summary:,Purpose: The goal of the study was to assess the health-related quality of life (HRQOL) of persons with epilepsy (PWE) by using the short form survey 36 (SF-36), to compare it with that of a control group and to detect factors influencing it. Methods: We collected clinical and demographic data and information on health status by using the Arabic translation of the SF-36 questionnaire from two groups: (a) 120 PWE consulting our outpatient clinic during a period of 4 months, and (b) 110 Tunisian citizens, representative of the Tunisian general population, as a control group. Results: The mean age of PWE group was 32.74 years, and 45.5% were men. Idiopathic generalized epilepsies were observed in 44.5% of cases, and symptomatic partial epilepsies, in 30%. The most commonly prescribed drug was sodium valproate (VPA). For the SF-36, PWE had lower scores than the control group for only three subscales: general health perception, mental health, and social functioning. Seizure frequency, time since last seizure, and the antiepileptic drug (AED) side effects were the most important variables influencing the HRQOL among PWE. Seizure-free adults have HRQOL levels comparable to those of the control group. Sociodemographic variables had no influence on the SF-36 subscales. Conclusions: HRQOL is impaired in Tunisian PWE. The influencing factors identified in this study differ from the previously published data. Several possible reasons such as family support and cultural and religious beliefs are proposed to explain these cross-cultural differences. A larger study should be conducted to verify such findings. [source] Nramp1 -functionality increases iNOS expression via repression of IL-10 formationEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 11 2008Gernot Fritsche Abstract In mice, resistance to certain intracellular microbes depends on the expression of a late phagosomal protein termed natural-resistance associated macrophage protein 1 (Nramp1, Slc11a1). Nramp1- functionality is associated with alterations of cellular iron homeostasis and a sustained pro-inflammatory immune response, including the formation of the antimicrobial effector molecule NO. To investigate the underlying mechanism we used RAW-264.7 murine macrophage cells stably transfected with a functional Nramp1 allele (RAW-37) or Nramp1 non-functional controls (RAW-21). We found that the production of and signalling by the anti-inflammatory cytokine IL-10 was significantly enhanced in macrophages lacking functional Nramp1. Upon infection of macrophages with Salmonella typhimurium pathogen survival was significantly better in RAW-21 than in RAW-37, which inversely correlated to NO and TNF-, formation. Addition of a neutralising anti-IL-10 antibody to RAW-21 cells led to a significantly reduced survival of S. typhimurium within these cells and enhanced formation of NO and TNF-, reaching levels comparable to that observed in cells bearing functional Nramp1. Oppositely, supplementation of iron to RAW-21 cells further increased IL-10 formation. Thus, Nramp1 mediates effective host defence in part via suppression of excessive IL-10 production which may relate to Nramp1- mediated reduction of cellular iron pools, thus strengthening antimicrobial effector mechanisms. [source] Brain mitochondrial aldehyde dehydrogenase: relation to acetaldehyde aversion in low-alcohol-drinking (UChA) and high-alcohol-drinking (UChB) ratsADDICTION BIOLOGY, Issue 4 2003María elena Quintanilla Previous reports indicate that the low-drinker (UChA) rats, when compared to high-drinker (UChB) rats, display lower mitochondrial aldehyde dehydrogenase (ALDH2) activity due to a mutation of the Aldh2 gene. Because a later study found line differences in sensitivity to the aversive effects of acetaldehyde (AcH) administered intraperitoneally (i.p.), which were not associated with the line difference detected in blood AcH levels, the present study examined the contribution of brain ALDH2 activity to AcH aversion in UChA and UChB rats. In experiment 1, we established the dose-response curves for AcH aversion (25, 50 or 100 mg/kg i.p.) in rats of both lines by using a conditioned taste aversion (CTA) paradigm. The results confirm our previous finding that UChA and UChB rats presented marked differences in their AcH aversion thresholds, which were not associated with the line differences detected in blood AcH levels. In experiment 2, the possibility that the inhibition of the brain ALDH2 would lower the AcH aversion threshold in both lines was studied by determining the effect of cyanamide (10 mg/kg i.p.) pretreatment, an inhibitor of ALDH, on AcH aversion, blood AcH levels and brain ALDH2 activity. The finding that blocking the brain ALDH2 (52%) by cyanamide can make a non-aversive dose of AcH (25 mg/kg) aversive to UChA and UChB rats at blood AcH levels comparable to those induced by a non-aversive dose of AcH (100 mg/kg) in control UChB rats indicates that the line difference in AcH aversion is associated more with brain ALDH2 activity than with liver ALDH2 activity. [source] Localization of nAChR subunit mRNAs in the brain of Macaca mulattaEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 10 2000Zhi-Yan Han Abstract We present here a systematic mapping of nAChR subunit mRNAs in Macaca mulatta brain. A fragment, from the transmembrane segments MIII to MIV of Macaca neuronal nAChR subunits was cloned, and shown to exhibit high identity (around 95%) to the corresponding human subunits. Then, specific oligodeoxynucleotides were synthesized for in situ hybridization experiments. Both ,4 and ,2 mRNA signals were widely distributed in the brain, being stronger in the thalamus and in the dopaminergic cells of the mesencephalon. Most brain nuclei displayed both ,4 and ,2 signals with the exception of some basal ganglia regions and the reticular thalamic nucleus which were devoid of ,4 signal. ,6 and ,3 mRNA signals were selectively concentrated in the substantia nigra and the medial habenula. The strongest signals for ,3 or ,4 mRNAs were found in the epithalamus (medial habenula and pineal gland), whereas there were no specific ,3 or ,4 signals in mesencephalic dopaminergic nuclei. ,5 and ,7 mRNA signals were found in several brain areas, including cerebral cortex, thalamus and substantia nigra, although at a lower level than ,4 and ,2. The distribution of ,3, ,4, ,5, ,6, ,7, ,2, ,3 and ,4 subunit mRNAs in the monkey is substantially similar to that observed in rodent brain. Surprisingly, ,2 mRNA signal was largely distributed in the Macaca brain, at levels comparable with those of ,4 and ,2. This observation represents the main difference between rodent and Macaca subunit mRNA distribution and suggests that, besides ,4,2*, ,2,2* nAChRs constitute a main nAChR isoform in primate brain. [source] Role of insulin, insulin-like growth factor-1, hyperglycaemic food and milk consumption in the pathogenesis of acne vulgarisEXPERIMENTAL DERMATOLOGY, Issue 10 2009Bodo C. Melnik Abstract:, It is the purpose of this viewpoint article to delineate the regulatory network of growth hormone (GH), insulin, and insulin-like growth factor-1 (IGF-1) signalling during puberty, associated hormonal changes in adrenal and gonadal androgen metabolism, and the impact of dietary factors and smoking involved in the pathogenesis of acne. The key regulator IGF-1 rises during puberty by the action of increased GH secretion and correlates well with the clinical course of acne. In acne patients, associations between serum levels of IGF-1, dehydroepiandrosterone sulphate, dihydrotestosterone, acne lesion counts and facial sebum secretion rate have been reported. IGF-1 stimulates 5,-reductase, adrenal and gonadal androgen synthesis, androgen receptor signal transduction, sebocyte proliferation and lipogenesis. Milk consumption results in a significant increase in insulin and IGF-1 serum levels comparable with high glycaemic food. Insulin induces hepatic IGF-1 secretion, and both hormones amplify the stimulatory effect of GH on sebocytes and augment mitogenic downstream signalling pathways of insulin receptors, IGF-1 receptor and fibroblast growth factor receptor-2b. Acne is proposed to be an IGF-1-mediated disease, modified by diets and smoking increasing insulin/IGF1-signalling. Metformin treatment, and diets low in milk protein content and glycaemic index reduce increased IGF-1 signalling. Persistent acne in adulthood with high IGF-1 levels may be considered as an indicator for increased risk of cancer, which may require appropriate dietary intervention as well as treatment with insulin-sensitizing agents. [source] Naturally occurring dominant resistance mutations to hepatitis C virus protease and polymerase inhibitors in treatment-naïve patients,,§HEPATOLOGY, Issue 6 2008Thomas Kuntzen Resistance mutations to hepatitis C virus (HCV) nonstructural protein 3 (NS3) protease inhibitors in <1% of the viral quasispecies may still allow >1000-fold viral load reductions upon treatment, consistent with their reported reduced replicative fitness in vitro. Recently, however, an R155K protease mutation was reported as the dominant quasispecies in a treatment-naïve individual, raising concerns about possible full drug resistance. To investigate the prevalence of dominant resistance mutations against specifically targeted antiviral therapy for HCV (STAT-C) in the population, we analyzed HCV genome sequences from 507 treatment-naïve patients infected with HCV genotype 1 from the United States, Germany, and Switzerland. Phylogenetic sequence analysis and viral load data were used to identify the possible spread of replication-competent, drug-resistant viral strains in the population and to infer the consequences of these mutations upon viral replication in vivo. Mutations described to confer resistance to the protease inhibitors Telaprevir, BILN2061, ITMN-191, SCH6 and Boceprevir; the NS5B polymerase inhibitor AG-021541; and to the NS4A antagonist ACH-806 were observed mostly as sporadic, unrelated cases, at frequencies between 0.3% and 2.8% in the population, including two patients with possible multidrug resistance. Collectively, however, 8.6% of the patients infected with genotype 1a and 1.4% of those infected with genotype 1b carried at least one dominant resistance mutation. Viral loads were high in the majority of these patients, suggesting that drug-resistant viral strains might achieve replication levels comparable to nonresistant viruses in vivo. Conclusion: Naturally occurring dominant STAT-C resistance mutations are common in treatment-naïve patients infected with HCV genotype 1. Their influence on treatment outcome should further be characterized to evaluate possible benefits of drug resistance testing for individual tailoring of drug combinations when treatment options are limited due to previous nonresponse to peginterferon and ribavirin. (HEPATOLOGY 2008;48:1769,1778.) [source] A role for asymmetric dimethylarginine in the pathophysiology of portal hypertension in rats with biliary cirrhosis,,HEPATOLOGY, Issue 6 2005Wim Laleman Reduced intrahepatic endothelial nitric oxide synthase (eNOS) activity contributes to the pathogenesis of portal hypertension (PHT) associated with cirrhosis. We evaluated whether asymmetric dimethylarginine (ADMA), a putative endogenous NOS inhibitor, may be involved in PHT associated with cirrhosis. Two rat models of cirrhosis (thioacetamide [TAA]-induced and bile duct excision [BDE]-induced, n = 10 each), one rat model of PHT without cirrhosis (partial portal vein,ligated [PPVL], n = 10), and sham-operated control rats (n = 10) were studied. We assessed hepatic NOS activity, eNOS protein expression, plasma ADMA levels, and intrahepatic endothelial function. To evaluate intrahepatic endothelial function, concentration,effect curves of acetylcholine were determined in situ in perfused normal rat livers and livers of rats with TAA- or BDE-induced cirrhosis (n = 10) that had been preincubated with either vehicle or ADMA; in addition, measurements of nitrite/nitrate (NOx) and ADMA were made in perfusates. Both models of cirrhosis exhibited decreased hepatic NOS activity. In rats with TAA-induced cirrhosis, this decrease was associated with reduced hepatic eNOS protein levels and immunoreactivity. Rats with BDE-induced cirrhosis had eNOS protein levels comparable to those in control rats but exhibited significantly higher plasma ADMA levels than those in all other groups. In normal perfused liver, ADMA induced impaired endothelium-dependent vasorelaxation and reduced NOx perfusate levels, phenomena that were mimicked by NG -nitro- L -arginine-methyl ester. In contrast to perfused livers with cirrhosis induced by TAA, impaired endothelial cell-mediated relaxation in perfused livers with cirrhosis induced by BDE was exacerbated by ADMA and was associated with a decreased rate of removal of ADMA (34.3% ± 6.0% vs. 70.9% ± 3.2%). In conclusion, in rats with TAA-induced cirrhosis, decreased eNOS enzyme levels seem to be responsible for impaired NOS activity; in rats with biliary cirrhosis, an endogenous NOS inhibitor, ADMA, may mediate decreased NOS activity. (HEPATOLOGY 2005;42:1382,1390.) [source] Ischemic preconditioning affects interleukin release in fatty livers of rats undergoing ischemia/reperfusionHEPATOLOGY, Issue 3 2004Anna Serafín The present study evaluates the effect of ischemic preconditioning on interleukin-1 (IL-1) and interleukin-10 (IL-10) generation following hepatic ischemia/reperfusion (I/R) in normal and steatotic livers as well as the role of nitric oxide (NO) in this process. Increased IL-1, and IL-10 levels were observed in normal livers after I/R. Steatotic livers showed higher IL-1, levels than normal livers, and IL-10 at control levels. The injurious role of IL-1, and the benefits of IL-10 on hepatic I/R injury was shown with the use of IL-1 receptor antagonist (IL-1ra), anti-IL-10 polyclonal antibody against IL-10 (anti-IL-10) and exogenous IL-10. The effective dose of these treatments was different in both types of livers. Preconditioning prevented IL-1, release and increased IL-10 generation after I/R in normal and steatotic livers. IL-1, or anti-IL-10 pretreatments reversed the benefits of preconditioning. IL-1, action inhibition in a preconditioned group that was pretreated with anti-IL-10 did not modify the benefits of preconditioning. In addition, anti-IL-10 pretreatment in the preconditioned group resulted in IL-1, levels comparable to those observed after I/R. NO inhibition eliminated the benefits of preconditioning on IL-10 release, IL-1, levels, and hepatic injury. In conclusion, preconditioning, through IL-10 overproduction, inhibits IL-1, release and the ensuing hepatic I/R injury in normal and steatotic livers. IL-10 generation induced by preconditioning could be mediated by NO. (HEPATOLOGY 2004;39:688,698.) [source] Combinatorial Modification of Degradable Polymers Enables Transfection of Human Cells Comparable to Adenovirus,ADVANCED MATERIALS, Issue 19 2007J. Green End-modified poly(,-amino ester)s, easy-to-synthesize degradable polymers, are able to deliver DNA to primary human cells at levels comparable to adenovirus and two orders of magnitude better than the commonly used non-viral vector, polyethylenimine. Small structural changes are found to affect multiple steps of gene delivery including the DNA binding affinity, nanoparticle size, intracellular DNA uptake, and final protein expression. In vivo, these polymer modifications enhance DNA delivery to ovarian tumors. [source] God's will, God's punishment, or God's limitations?JOURNAL OF CLINICAL PSYCHOLOGY, Issue 6 2007Religious coping strategies reported by young adults living with serious mental illness Qualitative research has demonstrated that religious meaning-making coping, defined as attributions of a stressful life event that involve the sacred, is particularly relevant to persons with serious mental illness. However, recent research advances in the study of religious coping have yet to be employed in clinical samples. This longitudinal study examines religious meaning-making coping in a sample of 48 young adults diagnosed with schizophrenia or bipolar disorder over a one-year period. Young adults with mental illness generally reported using religious meaning-making coping in levels comparable to nonpsychiatric samples. Reports of benevolent religious reappraisals were associated with perceptions of positive mental health, whereas punishing God reappraisals and reappraisals of God's power were associated with self-reported distress and personal loss. Religious coping variables accounted for variation in adults' reports of psychiatric symptoms and personal loss one year later over and above demographic and global religious variables. Implications of findings for clinical practice are discussed. © 2007 Wiley Periodicals, Inc. J Clin Psychol. [source] Detection of infectious haematopoietic necrosis virus and infectious salmon anaemia virus by molecular padlock amplificationJOURNAL OF FISH DISEASES, Issue 4 2006P J Millard Abstract A new method for the molecular detection of the fish pathogens, infectious haematopoietic necrosis virus (IHNV) and infectious salmon anaemia virus (ISAV), is described. By employing molecular padlock probe (MPP) technology combined with rolling circle amplification (RCA) and hyperbranching (Hbr), it is possible to detect RNA target sequence from these viruses at levels comparable with those detected by the polymerase chain reaction (PCR), but without prior reverse transcription. The use of MPP technology combined with RCA and Hbr for the detection of IHNV and ISAV in fish exhibited selectivity comparable with that of PCR while potentially reducing the time and cost required for analysis. The method described was used to detect as few as 104 DNA oligonucleotide targets and was sequence-specific at the single base level. Viral RNA could be detected directly, either alone or in the presence of non-viral RNA from fish tissue. This technology is applicable for detecting a variety of microbes, in addition to IHNV and ISAV, and is ideal for further integration into a biosensor platform for on-site diagnosis of pathogen infection in fish. [source] | ||||||||||||||||||||||||||||||||||