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Selected AbstractsA 6-month follow-up study of 1048 patients diagnosed with an occupational skin diseaseCONTACT DERMATITIS, Issue 5 2009Tarja Mälkönen Background: Occupational skin diseases (OSDs) often have considerable medical and occupational consequences. Previous data on prognostic factors have been derived from studies with fairly small sample sizes. Objectives: To determine the medical and occupational outcome in 1048 patients diagnosed with OSD at the Finnish Institute of Occupational Health and to identify the prognostic risk factors for the continuation of OSD. Methods: Patients examined in 1994,2001 filled out a follow-up questionnaire 6 months after the diagnosis. Data on atopy, contact allergies, and occupation were analysed. Results: Six months after the diagnosis the skin disease had healed in 27% of the patients. The OSD had cleared up in 17% of those with no changes at work, and in 34% of those who had changed their job/occupation. The best clearing had occurred in the patients with contact urticaria (35%), whereas the healing of allergic (27%) and irritant (23%) contact dermatitis was similar. The risk factors for continuing occupational contact dermatitis (OCD) were no changes in work, age > 45 years, food-related occupations, respiratory atopy, and male sex. Conclusions: The healing of OSD was associated with discontinuation of the causative exposure. A change in work and the presence of easily avoidable work-related allergies were associated with a good prognosis. [source] Autologous Cultured Fibroblast Injection for Facial Contour Deformities: A Prospective, Placebo-Controlled, Phase III Clinical TrialDERMATOLOGIC SURGERY, Issue 3 2007ROBERT A. WEISS MD BACKGROUND Previous data indicate that injections of autologous fibroblasts increase collagen formation, accompanied by a concomitant increase in thickness and density of dermal collagen. OBJECTIVE The purpose of this study was to determine efficacy and side effects of autologous living fibroblast injections versus placebo in a randomized Phase III trial for the treatment of various facial contour defects. METHODS This was a double-blind, randomized comparison of injectable living autologous fibroblast cells and placebo for the treatment of facial contour defects (N=215). Live fibroblasts (20 million/mL) or placebo (the transport medium without living cells) were given as three doses administered at 1- to 2-week intervals. Efficacy evaluations were performed 1, 2, 4, 6, 9, and 12 months after the first injection. RESULTS Living fibroblasts produced statistically significantly greater improvements in dermal deformities and acne scars than did placebo. The difference between live fibroblast injections and placebo achieved statistical significance at 6 months (p<.0001). At 9- and 12-month follow-up, live fibroblast,treated patients continued to demonstrate benefit from treatment with response rates of 75.0 and 81.6%, respectively. No serious treatment-related adverse events were reported. CONCLUSIONS Our results indicate that autologous fibroblast injections can safely and effectively produce improvements in rhytids, acne scars, and other dermal defects continuing for at least 12 months after injection. [source] Comparing hormonal and symptomatic responses to experimental hypoglycaemia in insulin- and sulphonylurea-treated Type 2 diabetesDIABETIC MEDICINE, Issue 7 2009P. Choudhary Abstract Aims, Patients with diabetes rely on symptoms to identify hypoglycaemia. Previous data suggest patients with Type 2 diabetes develop greater symptomatic and hormonal responses to hypoglycaemia at higher glucose concentrations than non-diabetic controls and these responses are lowered by insulin treatment. It is unclear if this is as a result of insulin therapy itself or improved glucose control. We compared physiological responses to hypoglycaemia in patients with Type 2 diabetes patients treated with sulphonylureas (SUs) or insulin (INS) with non-diabetic controls (CON). Methods, Stepped hyperinsulinaemic hypoglycaemic clamps were performed on 20 subjects with Type 2 diabetes, 10 SU-treated and 10 treated with twice-daily premixed insulin, and 10 age- and weight-matched non-diabetic controls. Diabetic subjects were matched for diabetes duration, glycated haemoglobin (HbA1c) and hypoglycaemia experience. We measured symptoms, counterregulatory hormones and cognitive function at glucose plateaux of 5, 4, 3.5, 3 and 2.5 mmol/l. Results, Symptomatic responses to hypoglycaemia occurred at higher blood glucose concentrations in SU-treated than INS-treated patients [3.5 (0.4) vs. 2.6 (0.5) mmol/l SU vs. INS; P = 0.001] or controls [SU vs. CON 3.5 (0.4) vs. 3.0 (0.6) mmol/l; P = 0.05]. They also had a greater increase in symptom scores at hypoglycaemia [13.6 (11.3) vs. 3.6 (6.1) vs. 5.1 (4.3) SU vs. INS vs. CON; P = 0.017]. There were no significant differences in counterregulatory hormone responses or impairment of cognitive function among groups. Conclusions, Sulphonylurea-treated subjects are more symptomatic of hypoglycaemia at a higher glucose level than insulin-treated subjects. This may protect them from severe hypoglycaemia but hinder attainment of glycaemic goals. [source] Heat Shock Protein Expression is Increased in Cardiac and Skeletal Muscles of Fischer 344 Rats After Endurance TrainingEXPERIMENTAL PHYSIOLOGY, Issue 1 2000T. R. Samelman Heat shock proteins (HSPs) are expressed when cells are exposed to various types of stress and they may provide protection against cellular insult. Previous data have shown increases in HSP expression following acute exhaustive exercise in rats (Locke et al. 1990, 1995; Salo et al. 1991) and humans (Liu et al. 1999); however, it is not known if chronic exercise will increase resting levels of HSPs. The purpose of this study was to determine if basal protein levels of HSP 72/73 and HSP 60 are increased in cardiac and skeletal muscle of endurance trained Fischer 344 rats. Heart, soleus (SOL) and lateral gastrocnemius (LG) muscles were removed and hearts were sectioned into left ventricle (LV), right ventricle (RV) and atria (AT). Endurance training improved myocardial citrate synthase activity by 88, 90 and 77% and cytochrome c oxidase activity by 58, 51 and 89% in LV, RV and AT, respectively. LV and RV oxidative enzyme activities were greater when compared to AT for both trained and untrained rats (P < 0.05). HSP 72/73 expression was significantly greater (P < 0.05) in LV, RV and SOL from endurance trained versus from control rats (26, 45 and 67%, respectively). HSP 60 was also increased (P < 0.05) in LV, RV and SOL in trained relative to untrained rats. HSP 72/73 and HSP 60 were unchanged in AT and LG after training. These results indicate that endurance training increases the basal expression of stress proteins and this observation is consistent with the hypothesis that endurance training may activate a protective mechanism to stress. [source] Effects of interval between diagnosis and time of survey upon preferred information format for prostate cancer patientsJOURNAL OF MEDICAL IMAGING AND RADIATION ONCOLOGY, Issue 2 2009CF Sharpley Summary Previous data indicate that receiving adequate information about their cancer can assist patients to cope with treatment and comply with treatment regimes. The aim of the present study was to determine whether time since diagnosis affected patients' evaluations of the information they had received at the time of their diagnosis. Two hundred and thirty-seven patients who had received a diagnosis and treatment for prostate cancer 4 months earlier completed a questionnaire about their ratings of, and preferences for, various types of information, their anxiety and depression levels and some background data. The most common and preferred form of information that the patients in the current study received was verbal information during an interview with their oncologist. Demographic factors and levels of anxiety and depression did not influence patient information preferences. Time since diagnosis was associated with elevated anxiety and depression, and consequent lower recall of having received information, but also with positive inflation of the value of the material that they did recall having received. Patients may not recall information given to them early after diagnosis and may make unreliable evaluations of its value to them due to psychological state. [source] Synthesis and receptor binding of IgG1 peptides derived from the IgG Fc regionJOURNAL OF MOLECULAR RECOGNITION, Issue 2 2004Katalin Uray Abstract The IgG binding Fc, receptors (Fc,Rs) play a key role in defence against pathogens by linking humoral and cell-mediated immune responses. Impaired expression and/or function of Fc,R may result in the development of pathological autoimmunity. Considering the functions of Fc,Rs, they are potential target molecules for drug design to aim at developing novel anti-inflammatory and immunomodulatory therapies. Previous data mostly obtained by X-ray analysis of ligand,receptor complexes indicate the profound role of the CH2 domain in binding to various Fc,Rs. Our aim was to localize linear segments, which are able to bind and also to modulate the function of the low affinity Fc,Rs, like Fc,RIIb and Fc,RIIIa. To this end a set of overlapping octapeptides was prepared corresponding to the 231,298 sequence of IgG1 CH2 domain and tested for binding to human recombinant soluble Fc,RIIb. Based on these results, a second group of peptides was synthesized and their binding properties to recombinant soluble Fc,RIIb, as well as to Fc,Rs expressed on the cell surface, was investigated. Here we report that peptide representing the Arg255,Ser267 sequence of IgG1 is implicated in the binding to Fc,RIIb. In addition we found that peptides corresponding to the Arg255,Ser267, Lys288,Ser298 or Pro230,Val240 when presented in a multimeric form conjugated to branched chain polypeptide in uniformly oriented copies induced the release of TNF,, a pro-inflammatory cytokine from MonoMac monocyte cell line. These findings indicate that these conjugated peptides are able to cluster the activating Fc,Rs, and mediate Fc,R dependent function. Peptide Arg255,Ser267 can also be considered as a lead for further functional studies. Copyright © 2004 John Wiley & Sons, Ltd. [source] Preconditioning with thrombin can be protective or worsen damage after endothelin-1-induced focal ischemia in ratsJOURNAL OF NEUROSCIENCE RESEARCH, Issue 3 2006Petra Henrich-Noack Abstract The serine protease thrombin has shown direct neuroprotective and neurotoxic effects on brain tissue in cerebral ischemia. Previous data suggested that thrombin-induced protection in vivo can be achieved by preconditioning rather than by acute treatment. In the current work, we used a model of mild ischemia to investigate the effects of preischemic intracerebral thrombin injection on neural damage. By intracerebral injection of endothelin-1 in freely moving animals, we achieved middle cerebral artery occlusion (MCAO), and 7 days postischemia we performed histological quantification of the infarct areas. Thrombin was injected as a preconditioning stimulus intracerebrally 7 days or 2 and 3 days before ischemia. For acute treatment, thrombin was injected 20 min before MCAO. Thrombin induced significant neuroprotection when given 7 days before endothelin-1-induced MCAO but was deleterious when given 2 and 3 days before the insult. The deleterious effect was not seen when thrombin was given acutely before ischemia. Our data demonstrate that preconditioning with thrombin can protect against damage or worsen ischemic damage. Its effect depended on the time interval between thrombin injection and insult. A low dose of thrombin did not induce a major deleterious effect in the acute phase of the infarct development after mild transient ischemia. © 2006 Wiley-Liss, Inc. [source] Impact of progestagens on activated protein C (APC) resistance among users of oral contraceptivesJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 9 2004M. Alhenc-Gelas Summary., Oral contraceptive (OC) use is associated with an increased risk of venous thromboembolism. Previous data reported higher thrombotic risk in women using third-generation combined OC than in those using second generation OC. The difference could be explained by differential effects of progestagens on plasma sensitivity to activated protein C (APC). The main purpose of this cross-sectional study was to assess the influence of a progestagen-only OC (chlormadinone acetate) as well as the effect of several combined OC with different progestagen components on APC resistance. The effect of APC on endogenous thrombin potential (ETP) was investigated in the plasma of healthy women using either combined OC (n = 82) or progestagen-only OC (n = 28), and in non-users (n = 64). Carriers of factor V Leiden were excluded. Compared with non-users, there was no significant change in APC resistance in women using progestagen-only OC. Women who used combined OC were less sensitive to APC than non-users (P < 0.001) and the difference was significantly more pronounced in women using third-generation OC (n = 41) than in those who used second-generation OC containing levonorgestrel (n = 22) (P < 0.05). Compared with OC containing levonorgestrel, use of norethisterone-containing OC (n = 9) was associated with an increased resistance to APC (P < 0.05). Women who used cyproterone-containing OC (n = 10) were less sensitive to APC than those using third-generation OC (P < 0.05) or second-generation OC containing levonorgestrel (P < 0.05). Protein S, factor II and FVIII levels explained in part the OC-related changes in APC sensitivity variations. ETP-based APC resistance may contribute to explain why different brands of OC can be associated with different levels of thrombogenicity. [source] Role of gender and race mismatch and graft failure in patients undergoing liver transplantationLIVER TRANSPLANTATION, Issue 6 2002Vinod K. Rustgi MD Previous data have suggested an increased risk of graft failure in male recipients of female livers, and in nonwhite recipients of orthotopic liver transplantation. United Network for Organ Sharing records of liver transplantations from 1992 through 2000 with at least one follow-up visit were reviewed. Analysis of these data was performed with proportional hazards regression, controlling for follow-up time, age, gender, ethnicity, number of comorbidities, functional status at time of transplant, and status 1 designation. Separate analyses comparing transplants among whites and blacks only and matched versus mismatched transplants for male and female recipients were performed. The results revealed that gender-mismatched patients (n = 13,992) had a higher likelihood of graft failure when compared with gender matched transplants (n = 18,522) (12.2% versus 11.3% respectively, P = .013). After controlling for the above potential confounders, gender-mismatched patients were found to have a 6.9% increase in likelihood of graft failure, (P = .042). Female recipients receiving male organs had no significant change in the risk of graft failure (11.5%; P = .368). A worse outcome was found in male recipients receiving female organs (12.9%; P = .0003). Graft failure rate among patients with donors matched by race (white to white or nonwhite to nonwhite; n = 21,818) was 11.6% versus 11.9%, and among unmatched patients (n = 10,697), the difference was not significant (P = .33). Multivariate regression analysis controlling for potential confounders confirmed that this difference was not significant (P = .21). Mismatch between black donors and white recipients was found to increase the risk of liver graft failure (27.4%, P = < .0001), independently of gender, number of comorbidities, and functional status at time of transplant. [source] Osteoporosis in inflammatory bowel disease: effect of calcium and vitamin D with or without fluorideALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2002V. Abitbol Background: Previous data have indicated low bone formation as a mechanism of osteoporosis in inflammatory bowel disease. Fluoride can stimulate bone formation. Aim: To assess the effect of fluoride supplementation on lumbar spine bone mineral density in osteoporotic patients with inflammatory bowel disease treated in parallel with calcium and vitamin D. Methods: In this prospective, randomized, double-blind, parallel and placebo-controlled study, 94 patients with inflammatory bowel disease (lumbar spine T score below , 2 standard deviations, normal serum 25OH vitamin D), with a median age of 35 years, were included. Bone mineral density was measured by dual-energy X-ray absorptiometry. Patients were randomized to receive daily either sodium monofluorophosphate (150 mg, n=45) or placebo (n=49) for 1 year, and all received calcium (1 g) and vitamin D (800 IU). The relative change in bone mineral density from 0 to 12 months was tested in each group (fluoride or placebo) and compared between the groups. Results: Lumbar spine bone mineral density increased significantly in both groups after 1 year: 4.8 ± 5.6% (n=29) and 3.2 ± 3.8% (n=31) in the calcium,vitamin D,fluoride and calcium,vitamin D,placebo groups, respectively (P < 0.001 for each group). There was no difference between the groups (P=0.403). Similar results were observed according to corticosteroid intake or disease activity. Conclusions: Calcium and vitamin D seem to increase lumbar spine density in osteoporotic patients with inflammatory bowel disease; fluoride does not provide further benefit. [source] Changes in diets of individual Baltic ringed seals (Phoca hispida botnica) during their breeding season inferred from stable isotope analysis of multiple tissuesMARINE MAMMAL SCIENCE, Issue 1 2008Tuula Sinisalo Abstract The stable isotope ratios (,13C and ,15N) of three tissues with different metabolic rates (plasma, liver, and muscle) were used to investigate temporal variation in diet among nine individual Baltic ringed seals (Phoca hispida botnica Gmelin) from the Bothnian Bay, northeast Baltic Sea. The isotope values from plasma should reflect the most recent diet, values from liver the diet of the past weeks prior to sampling, and values from muscle should integrate diet over almost the entire breeding season of the ringed seals. In general, ,13C values of liver were more enriched in 13C than were those of either muscle or plasma, suggesting that the diet of the seals may have included a higher proportion of 13C-enriched benthic prey in April. Females showed more variable ,13C values than males, suggesting possible gender differences in diet or in foraging locations. The differences that were apparent between females possibly reflect individual variation in the onset and duration of parturition and lactation, both of which likely restrict female foraging. Previous data from parasite infections and from alimentary tract contents of the same seals were linked to the isotope data to assist in drawing inferences about changes in the diets of individual seals. [source] Dynamin 2 associates with complexins and is found in the acrosomal region of mammalian spermMOLECULAR REPRODUCTION & DEVELOPMENT, Issue 6 2007Longmei Zhao Abstract Previous data showed that complexin I, a SNARE regulatory protein, is localized in and/or around the acrosome and is necessary for the acrosome reaction in sperm. To understand how complexin I regulates the acrosome reaction, we used complexin-GST pulldown assays to identify interacting proteins. We showed that both complexins I and II bound mouse sperm dynamin 2. Dynamin 2 is a 100 kDa GTPase essential to many aspects of endocytosis but its potential role in exocytosis is unknown. Dynamin 2 is expressed in rat testis and widely expressed in other tissues; however, the function of dynamin 2 in germ cells is uncertain. Dynamin 2 protein was detected in mouse testis and was most abundant in or around the developing acrosome of spermatids. In addition, dynamin 2 was co-localized with complexin I in the acrosomal region of mammalian sperm. Its co-localization and interaction with complexin I suggest that dynamin 2 may play a role during acrosome formation and/or acrosomal exocytosis. Mol. Reprod. Dev. 74: 750,757, 2007. © 2006 Wiley-Liss, Inc. [source] Expression of p27BBP/eIF6 is highly modulated during Xenopus laevis embryogenesisMOLECULAR REPRODUCTION & DEVELOPMENT, Issue 4 2006Maria Carmela Vaccaro Abstract Protein p27BBP/eIF6 is necessary for ribosomal function of all cells. Previous data showed that from mammals to yeast p27BBP/eIF6 is involved in the biogenesis of ribosomal subunit 60S and its association with the 60S prevents premature 80S formation regulated by PKC signaling, indicating that phosphorylation of p27BBP/eIF6 is needed for translation to occur. While in vitro p27BBP/eIF6 is constitutively expressed, and it has a high level of expression in cycling cells, in vivo its expression varies according to tissues and appears regulated by factors up to now unknown. p27BBP/eIF6 has never been investigated in developing organisms where its upregulation can be correlated with tissue growth and differentiation. In this study we have sequenced p27BBP/eIF6 cDNA and studied its expression during development of Xenopus laevis, as the first step for studying its regulation. The amino acid sequence is highly conserved with two putative PKC phosphorylation sites in serine, one site being typical of Xenopus. At the end of gastrulation, the p27BBP/eIF6 riboprobe localizes in the neural plate and in the paraxial mesoderm. In particular, from stage 24, a clear-cut localization occurs in the perspective head. In embryos exposed to teratogens, the localization of p27BBP/eIF6 riboprobe varies according to the change of head size caused by the treatment. p27BBP/eIF6 expression is particularly evident in differentiating olfactory pits, the lens, otic vesicles, and in branchial arches. Features of particular interest are p27BBP/eIF6 high level of expression in the eye field, and in the mid-hindbrain-boundary, two regions with high proliferative activity. Altogether, data indicate that a modulated expression of p27BBP/eIF6 occurs in developing anlagens in addition to a basal level of expression, and may suggest a correlation between p27BBP/eIF6 and proliferative activity. Moreover, the X. laevis cDNA isolation and characterization offer new hints for further studies in relation to potential p27BBP/eIF6 phosphorylation. Mol. Reprod. Dev. © 2006 Wiley-Liss, Inc. [source] The Surgical Anatomy of Lumbar Medial Branch Neurotomy (Facet Denervation)PAIN MEDICINE, Issue 3 2004Peter Lau FRACR ABSTRACT Objective., To demonstrate the validity of placing electrodes parallel to the target nerve in lumbar radiofrequency neurotomy. DESIGN., Previous data on the anatomy of the lumbar dorsal rami were reviewed and a demonstration cadaver was prepared. Under direct vision, electrodes were placed on, and parallel to, the L4 medial branch and the L5 dorsal ramus. Photographs were taken to record the placement, and radiographs were taken to illustrate the orientation and location of the electrode in relation to bony landmarks. Results., In order to lie in contact with, and parallel to, the target nerve, electrodes need to be inserted obliquely from below, so that their active tip crosses the neck of the superior articular process. At typical lumbar levels, the tip should lie opposite the middle two quarters of the superior articular process. At the L5 level, it should lie opposite the middle and posterior thirds of the S1 superior articular process. Conclusion., If electrodes are placed parallel to the target nerve, the lesions made can be expected to encompass the target nerves. If electrodes are placed perpendicular to the nerve, the nerve may escape coagulation, or be only partially coagulated. Placing the electrode parallel to the nerve has a demonstrated anatomical basis, and has been vindicated clinically. Other techniques lack such a basis, and have not been vindicated clinically. Suboptimal techniques may underlie suboptimal outcomes from lumbar medial branch neurotomy. [source] In vitro antigen presenting cell-derived IL-10 and IL-6 correlate with Trichuris muris isolate-specific survivalPARASITE IMMUNOLOGY, Issue 3 2009R. D'ELIA SUMMARY Trichuris muris, the mouse whipworm, is used as a laboratory model of the human parasite T. trichiura. Three laboratory isolates of T. muris exist , the E, J and S isolates. Previous data have shown that the S isolate survives to chronicity in C57BL/6 mice unlike the E and J isolates, which are expelled. The ability of the S isolate to persist is thought to be due to it secreting unique excretory/secretory antigens, which interact with APCs such that protective T cell responses do not develop. To determine whether APCs respond differently to E/S antigens from the three isolates we cultured isolate-specific E/S with bone marrow-derived macrophages (BMM,) and dendritic cells (BMDCs) in vitro. Markers of co-stimulation and levels of MHC-II were analysed by FACS and cytokine levels in supernatants quantified. E/S antigens from the S isolate consistently stimulated significantly higher levels of IL-10 and IL-6 from both macrophages (F4/80+CD11b+CD11c,) and dendritic cells (CD11c+CD11b+F4/80,) compared to J and E isolate E/S. If these in vitro differences in APC-derived cytokines, particularly IL-10, are biologically significant in vivo, they may contribute to the S isolate survival, by creating a regulatory cytokine environment in which protective immune responses are less effective. [source] Twinning on the brain: The effect on neurodevelopmental outcomes,AMERICAN JOURNAL OF MEDICAL GENETICS, Issue 2 2009Thuy Mai Luu Abstract Twinning is currently considered a complex multifactorial trait. Few studies have explored how the unique genetic and environmental influences that create twinning affect phenotypes and outcomes. Previous data has shown that twins account for a significant proportion of preterm and low-birth-weight infants, who are at risk for long-term neurodevelopmental disabilities such as cerebral palsy and cognitive impairment. More recently, it has been postulated that even without these co-morbidities, twinning in and of itself may incur a neurodevelopmental disadvantage even among term newborns. The purpose of this review is to report primarily on neuromotor outcomes of twins compared to singletons. In addition, we describe specific environmental risk factors among twins which are associated with poorer outcomes. Several putative neurodevelopmental modulators are explored, including death of a co-twin, chorionicity, birth weight discordance, and twin-twin transfusion. By teasing out environmental influences that potentially influence neurocognitive outcomes, families can receive more specific counseling and developmental services can be provided to those twins at especially high risk. © 2009 Wiley-Liss, Inc. [source] The Causal Element for the Lactase Persistence/ non-persistence Polymorphism is Located in a 1 Mb Region of Linkage Disequilibrium in EuropeansANNALS OF HUMAN GENETICS, Issue 4 2003M. Poulter Summary Expression of lactase in the intestine persists into adult life in some people and not others, and this is due to a cis -acting regulatory polymorphism. Previous data indicated that a mutation leading to lactase persistence had occurred on the background of a 60 kb 11-site LCT haplotype known as A (Hollox et al. 2001). Recent studies reported a 100% correlation of lactase persistence with the presence of the T allele at a CT SNP at ,14 kb from LCT, in individuals of Finnish origin, suggesting that this SNP may be causal of the lactase persistence polymorphism, and also reported a very tight association with a second SNP (GA ,22 kb) (Enattah et al. 2002). Here we report the existence of a one megabase stretch of linkage disequilibrium in the region of LCT and show that the ,14 kb T allele and the ,22 kb A allele both occur on the background of a very extended A haplotype. In a series of Finnish individuals we found a strong correlation (40/41 people) with lactose digestion and the presence of the T allele. The T allele was present in all 36 lactase persistent individuals from the UK (phenotyped by enzyme assay) studied, 31/36 of whom were of Northern European ancestry, but not in 11 non-persistent individuals who were mainly of non-UK ancestry. However, the CT heterozygotes did not show intermediate lactase enzyme activity, unlike those previously phenotyped by determining allelic transcript expression. Furthermore the one lactase persistent homozygote identified by having equally high expression of A and B haplotype transcripts, was heterozygous for CT at the ,14 kb site. SNP analysis across the 1 megabase region in this person showed no evidence of recombination on either chromosome between the ,14 kb SNP and LCT. The combined data shows that although the ,14 kb CT SNP is an excellent candidate for the cause of the lactase persistence polymorphism, linkage disequilibrium extends far beyond the region searched so far. In addition, the CT SNP does not, on its own, explain all the variation in expression of LCT, suggesting the possibility of genetic heterogeneity. [source] Collar-induced elevation of mRNA and functional activity of 5-HT1B receptor in the rabbit carotid arteryBRITISH JOURNAL OF PHARMACOLOGY, Issue 8 2000Inge S Geerts Hypersensitivity to serotonin (5-HT) develops in rabbit collared carotid arteries. Previous data demonstrated the involvement of 5-HT1 -like receptors which are not active in normal carotid arteries. This study investigated the interaction in the rabbit carotid artery between 5-HT and a moderate tone as this can uncover functional 5-HT1 -like receptors. Furthermore, the expression of messenger RNA (mRNA) and protein of 5-HT1B, 5-HT1D and 5-HT2A receptors was addressed. Silicone collars were placed around the carotid arteries of male New Zealand White rabbits for 1 week. Rings from inside (=collar) and outside (=sham) the collar were either mounted in isolated organ baths for isometric force measurements or frozen in liquid nitrogen to isolate total RNA or proteins which were subsequently analysed by respectively reverse transcriptase-polymerase chain reaction and Western blot analysis. In sham and collared rings concentration-response curves (CRC's) to 5-HT were monophasic. Only in collared segments the presence of a 5-HT2A antagonist (spiperone or ketanserin, 0.1 ,M) revealed a biphasic CRC which was even more pronounced when a moderate tone was induced by KCl pointing to functional 5-HT1 -like receptors. The rabbit carotid artery constitutively expressed 5-HT1B and 5-HT2A mRNA, not 5-HT1D mRNA. Manipulation of the carotid artery increased the 5-HT1B mRNA level. Collar placement raised it even further. The 5-HT2A mRNA level remained unchanged. All the anti-5-HT receptor antibodies tested resulted in variable, non specific patterns with multiple bands. In conclusion, collar placement elevates mRNA expression and activity of the 5-HT1B receptor in the rabbit carotid artery. British Journal of Pharmacology (2000) 131, 1723,1731; doi:10.1038/sj.bjp.0703732 [source] Arabidopsis thaliana protein, ATK1, is a minus-end directed kinesin that exhibits non-processive movementCYTOSKELETON, Issue 3 2002Adam I. Marcus Abstract The microtubule cytoskeleton forms the scaffolding of the meiotic spindle. Kinesins, which bind to microtubules and generate force via ATP hydrolysis, are also thought to play a critical role in spindle assembly, maintenance, and function. The A. thaliana protein, ATK1 (formerly known as KATA), is a member of the kinesin family based on sequence similarity and is implicated in spindle assembly and/or maintenance. Thus, we want to determine if ATK1 behaves as a kinesin in vitro, and if so, determine the directionality of the motor activity and processivity character (the relationship between molecular "steps" and microtubule association). The results show that ATK1 supports microtubule movement in an ATP-dependent manner and has a minus-end directed polarity. Furthermore, ATK1 exhibits non-processive movement along the microtubule and likely requires at least four ATK1 motors bound to the microtubule to support movement. Based on these results and previous data, we conclude that ATK1 is a non-processive, minus-end directed kinesin that likely plays a role in generating forces in the spindle during meiosis. Cell Motil. Cytoskeleton 52:144,150, 2002. © 2002 Wiley-Liss, Inc. [source] Expression of the NET family member Zfp503 is regulated by hedgehog and BMP signaling in the limbDEVELOPMENTAL DYNAMICS, Issue 4 2008Edwina McGlinn Abstract The NET/Nlz family of zinc finger transcription factors contribute to aspects of developmental growth and patterning across evolutionarily diverse species. To date, however, these molecules remain largely uncharacterized in mouse and chick. We previously reported that limb bud expression of Zfp503, the mouse orthologue of zebrafish nlz2/znf503, is dependent on Gli3. Here, we show that Zfp503/Znf503 is expressed in a restricted pattern during mouse and chick embryogenesis, with particularly dynamic expression in the developing limbs, face, somites, and brain. We also add to our previous data on Gli3 regulation by showing that the anterior domain of Zfp503 expression in the mouse limb is responsive to genetic and nongenetic manipulation of hedgehog signaling. Finally, we demonstrate that posterior expression of Znf503 in the chick limb is responsive to bone morphogenetic protein (BMP) signaling, indicating that Zfp503/Znf503 may act at the nexus of multiple signaling pathways in development. Developmental Dynamics 237:1172,1182, 2008. © 2008 Wiley-Liss, Inc. [source] Particle path length distributions in meandering gravel-bed streams: results from physical modelsEARTH SURFACE PROCESSES AND LANDFORMS, Issue 9 2003Richard S. Pyrce Abstract In gravel-bed rivers with well-de,ned pool,bar morphology, the path length of transported bed particles must be, at least during ,channel-forming' ,ows, equal to the length scale of the morphology. This is the basis for some methods for estimating bed material transport rates. However, previous data, especially from ,eld tests, are often strongly positively skewed with mean much shorter than the pool,bar spacing. One possible explanation is that positively skewed distributions occur only in channels lacking distinct pool,bar topography or only at lower discharges in pool,bar channels. A series of ,ume experiments using ,uorescent tracers was used to measure path length distributions in low-sinuosity meandering channels to assess the relation with channel morphology and ,ow conditions. At channel-forming ,ows, 55 to 75 per cent of the tracer grains were deposited on the ,rst point bar downstream of the point of tracer input, with 15 per cent passing beyond the ,rst bar. Path length distributions are symmetrical with mean equal to the pool,bar spacing and can be described with a Cauchy distribution. In some cases there was a secondary mode close to the point of tracer introduction; this bimodal distribution ,ts a combined gamma,Cauchy distribution. Only when discharge was reduced below the channel-forming ,ow were frequency distributions unimodal and positively skewed with no relation to the pool,bar spacing. Thus, path length distributions become more symmetrical, and mean path length increases to coincide with pool,bar spacing, as ,ow approaches channel-forming conditions. This is a substantial modi,cation of existing models of particle transfer in gravel-bed rivers. Copyright © 2003 John Wiley & Sons, Ltd. [source] Sociocultural Variation in Mothers' Control over Children's BehaviorETHOS, Issue 1 2004Associate Professor Tiia Tulviste Prior findings of strict control of middle-class Estonian mothers have not been consistent with middle-class parent,child interaction patterns reported in other studies. The current study sought to find out to what degree the tendency to be more controlling toward children can be explained by the Estonian mothers' own experience of growing up in a totalitarian society. With this aim, measures of maternal controlling attitudes and actual verbal control of children were employed in a second country with a similar history of Soviet occupation,Latvia, and compared with previous data on Estonian, Finnish, and Swedish mono- and bicultural mothers. The questionnaire data revealed that Estonian (including Swedish,Estonian) and Latvian mothers placed higher emphasis on controlling children than did Finnish and Swedish mothers. At the same time, in their real-life interactions, only Estonian mothers living in Estonia exhibited a highly directive conversational style. Finally, the discussion focuses on possible reasons for cultural variability in maternal controlling attitudes and actual control of children. [source] Functional segregation of plural regions representing cardinal contours in cat primary visual cortexEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 7 2004Gang Wang Abstract Our previous data based on an imaging study suggested that, in cat area 17, the representations of cardinal orientations overlap less than the representation of their nearby angles. The purpose of this study was to further investigate the underlying single-cell properties. Optical imaging was performed first to map the cortical regions corresponding to the four principal contours, the two cardinals and the two obliques. The cortical region activated by a principal orientation but not by the +10° or ,10° neighbouring angles, namely the area with optically relative independent orientation selectivity (RIOS), was mapped together with the regions that overlapped with the +10° and/or ,10° neighbouring angles (non-RIOS). Electrode penetrations were targeted to the RIOS and non-RIOS regions in each of the four orientations. A comparison between the RIOS and the non-RIOS regions documented a significantly higher percentage of cells with the orientation preference of the cardinal orientations in the cardinal RIOS region than that seen in the other regions. Additionally, the difference in the tuning width of cells between the RIOS and non-RIOS in the cardinal region was significantly larger than the difference between the RIOS and non-RIOS in the oblique region. The cells in the cardinal RIOS region were tuned more sharply and the cells in cardinal non-RIOS region more broadly than the oblique RIOS and/or the non-RIOS region, which showed no significant difference. These data strongly suggest the existence of functional segregation in the region corresponding to the cardinal contours. [source] Prevalence of the MspI and Ile462Val SNPs of Cytochrome P-450 1A1 in Hidradenitis SuppurativaEXPERIMENTAL DERMATOLOGY, Issue 6 2010Ansgar Lukowsky Please cite this paper as: Prevalence of the MspI and Ile462Val SNPs of Cytochrome P-450 1A1 in Hidradenitis Suppurativa. Experimental Dermatology 2010; 19: 541,542. Abstract:, Hidradenitis Suppurativa (HS) is a chronic inflammatory skin disease that affects the hair follicles in the axillary, perianal and inguinal area. Its cause and pathogenesis are unknown, but cigarette smoking increases the risk of developing HS conceivably by accumulating toxic metabolites in sweat. The xenobiotic compounds from tobacco are metabolized by the cytochromes P-450. The cytochrome P-450 1A1 (CYP1A1), one of the most active isoenzymes, harbours several polymorphisms. Two of them, MspI and Ile462Val single nucleotide polymorphism (SNP), are associated with enhanced activity and inducibility. Performing direct DNA sequencing, we investigated the frequencies of these SNP in 51 patients with HS, 45 of these were smokers. We found similar overall SNP rates in our patients in comparison with previous data for Caucasian or German controls. Obviously, there is no relation between the occurrence of these SNPs and the risk of developing HS. [source] New data for sandwich panels on the correlation between the SBI test method and the room corner reference scenarioFIRE AND MATERIALS, Issue 1 2005Jesper Axelsson Abstract Assessment of the fire behaviour of sandwich panels is continuously under discussion. The fire behaviour of these panels is a combination of material characteristics such as the core material and mechanical behaviour of the panels such as joints, dilations etc. The use of small or intermediate scale tests can be questioned for such types of products. Within the proposed European product standard for sandwich panels (prEN 14509) the intermediate scale test method SBI (EN 13823) has been suggested as the fire test method to certify panels. The standard does, however, use quite an artificial mounting procedure, which does not fully reflect the end-use conditions of the panels. In a previous research project conducted by Nordtest it was shown that the correlation between the SBI test method and both the ISO 9705 and ISO 13784 part 1 was insufficient. The test data produced for the SBI test method, however, did not use the above mentioned mounting technique. In this article new data for a number of products are added to the database using the mounting procedure of the product standard. The data are compared with the previous data and show that the mounting method of the product standard results in slightly more severe conditions but that there are still discrepancies with the full-scale test results. The data also show an unacceptable level of repeatability due to the fact that small dilations result in a wide variation of classification result. The new data together with the old data show once more that it is dangerous to make a fire safety assessment of a sandwich panel based on small or intermediate scale tests. Copyright © 2004 John Wiley & Sons, Ltd. [source] A tumour-associated DEAD-box protein, rck/p54 exhibits RNA unwinding activity toward c-myc RNAs in vitroGENES TO CELLS, Issue 8 2003Yukihiro Akao Background:, The rck/p54 protein of 473 amino acids belongs to the family of DEAD-box/putative RNA helicase proteins. DEAD-box proteins have been implicated in a wide variety of cellular processes ranging from the initiation of protein synthesis and ribosome biosynthesis to premRNA splicing by means of modifying the RNA structure. Our previous data suggested that rck/p54 positively affected the translation initiation of c-myc mRNA. Results:, The data obtained from morphological studies and surface plasmon resonance assays clearly indicated that the protein specifically bound to c-myc RNA transcripts (RNAs) and exhibited RNA unwinding activity toward c-myc RNAs in the presence of ATP in vitro. Experiments using a deletion mutant of rck/p54 retaining only its N-terminal 289 amino acids demonstrated that the deleted C-terminal 184 amino acid domain is involved in the RNA unwinding activity. Conclusion:, These findings strongly suggest that rck/p54 may play an important role in translation initiation by restructuring mRNAs even in the cell and contribute to carcinogenesis. [source] The interaction between ,S, the stationary phase , factor, and the core enzyme of Escherichia coli RNA polymeraseGENES TO CELLS, Issue 3 2002Frédéric Colland Background: The RNA polymerase holoenzyme of Escherichia coli is composed of a core enzyme (subunit structure ,2,,,) associated with one of the , subunits, required for promoter recognition. Different , factors compete for core binding. Among the seven , factors present in E. coli, ,70 controls gene transcription during the exponential phase, whereas ,S regulates the transcription of genes in the stationary phase or in response to different stresses. Using labelled ,S and ,70, we compared the affinities of both , factors for core binding and investigated the structural changes in the different subunits involved in the formation of the holoenzymes. Results: Using native polyacrylamide gel electrophoresis, we demonstrate that ,S binds to the core enzyme with fivefold reduced affinity compared to ,70. Using iron chelate protein footprinting, we show that the core enzyme significantly reduces polypeptide backbone solvent accessibility in regions 1.1, 2.5, 3.1 and 3.2 of ,S, while increasing the accessibility in region 4.1 of ,S. We have also analysed the positioning of ,S on the holoenzyme by the proximity-dependent protein cleavage method using ,S derivatives in which FeBABE was tethered to single cysteine residues at nine different positions. Protein cutting patterns are observed on the , and ,, subunits, but not ,. Regions 2.5, 3.1 and 3.2 of ,S are close to both , and ,, subunits, in agreement with iron chelate protein footprinting data. Conclusions: A comparison between these results using ,S and previous data from ,70 indicates similar contact patterns on the core subunits and similar characteristic changes associated with holoenzyme formation, despite striking differences in the accessibility of regions 4.1 and 4.2. [source] Sensitivity to the locomotor-stimulant effects of ethanol and allopregnanolone: a quantitative trait locus study of common genetic influenceGENES, BRAIN AND BEHAVIOR, Issue 7 2006A. A. Palmer Previous studies have suggested that common genetic mechanisms influence sensitivity to the locomotor-stimulant effects of ethanol and allopregnanolone. We conducted two quantitative trait locus (QTL) studies to identify chromosomal regions that harbor genes that influence locomotor response to ethanol (2 g/kg) and allopregnanolone (17 mg/kg) using F2 crosses between C57BL/6J and DBA/2J mice. Because our previous data from the BXD recombinant inbred strains had indicated that chromosome 2 contained QTL for sensitivity to the locomotor-stimulant effects of both ethanol and allopregnanolone, we also tested reciprocal chromosome 2 congenic strains for sensitivity to the locomotor-stimulant effects of both drugs. The F2 analysis for ethanol sensitivity identified significant QTL on chromosomes 1 and 2 and suggestive QTL on chromosomes 5 and 9. The analysis of the allopregnanolone F2 study identified suggestive QTL on chromosomes 3, 5 and 12. Suggestive evidence for a female-specific QTL on chromosome 2 was also found. The studies of congenic mouse strains indicated that both the congenic strains captured one or more QTL for sensitivity to the locomotor-stimulant effects of both ethanol (2 g/kg) and allopregnanolone (17 mg/kg). When Fisher's method was used to combine the P values for the RI, F2 and congenic studies of the chromosome 2 QTL, cumulative probability scores of 9.6 × 10,15 for ethanol and 7.7 × 10,7 for allopregnanolone were obtained. These results confirm the presence of QTL for ethanol and allopregnanolone sensitivity in a common region of chromosome 2 and suggest possible pleiotropic genetic influence on sensitivity to these drugs. [source] Developmental impact on trans -acting dosage effects in maize aneuploidsGENESIS: THE JOURNAL OF GENETICS AND DEVELOPMENT, Issue 2 2001Jennifer L. Cooper Abstract Summary: The reduction in vigor or viability caused by aneuploidy may be the result of trans -acting dosage effects that reduce gene expression. To investigate the molecular and developmental parameters of aneuploid syndromes, the expression of sucrose synthase1 (sus1) and shrunken1 (sh1) was studied in 2-week-old plants. Expression of sus1 and sh1 was first investigated in euploids, where it was found that both transcripts varied in a diurnal fashion. Chromosome arm number can be varied in a series from one to three doses in maize. In the 14 aneuploid dosage series examined, most caused changes in sus1 and sh1 RNA levels that were both gene and tissue specific. Results were compared to previous data from embryo and endosperm tissue. More dosage effects were detected and the magnitude of RNA level modulation was greater in 2-week-old plant tissue. These findings suggest that the molecular consequences of aneuploidy might become more severe as development progresses. genesis 31:64,71, 2001. © 2001 Wiley-Liss, Inc. [source] Synergistic induction of cyclin D1 in oligodendrocyte progenitor cells by IGF-I and FGF-2 requires differential stimulation of multiple signaling pathwaysGLIA, Issue 10 2007Terra J. Frederick Abstract D-type cyclins are direct targets of extracellular signals and critical regulators of G1 progression. Our previous data demonstrated that IGF-I and FGF-2 synergize to enhance cyclin D1 expression, cyclin E/cdk2 complex activation, and S-phase entry in OP cells. Here, we provide a mechanistic explanation for how two growth factor signaling pathways converge on a major cell cycle regulator. IGF-I and FGF-2 differentially activate signaling pathways to coordinately promote cyclin D1 expression. We show that the p44/p42 MAPK signaling pathway is essential for FGF-2 induction of cyclin D1 mRNA. In contrast, blocking the PI3-Kinase pathway results in loss of IGF-I/FGF-2 synergistic induction of cyclin D1 protein levels. Moreover, the presence of IGF-I significantly enhances nuclear localization of cyclin D1, which also requires PI3K signaling. GSK-3,, a downstream target of the PI3K/Akt pathway, is phosphorylated in the presence of IGF-I in OPs. Consistent with a known role for GSK-3, in cyclin D1 degradation, we show that proteasome inhibition in OPs exposed to FGF-2 increased cyclin D1 levels, equivalent to levels seen in IGF-I/FGF-2 treated cells. Thus, we provide a model for cyclin D1 coordinate regulation where FGF-2 stimulation of the MAPK pathway promotes cyclin D1 mRNA expression while IGF-I activation of the PI3K pathway inhibits proteasome degradation of cyclin D1 and enhances nuclear localization of cyclin D1. © 2007 Wiley-Liss, Inc. 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