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MAL
Selected AbstractsIdentification of some human genes oppositely regulated during esophageal squamous cell carcinoma formation and human embryonic esophagus developmentDISEASES OF THE ESOPHAGUS, Issue 3 2010M. V. Zinovyeva SUMMARY Here we directly compared gene expression profiles in human esophageal squamous cell carcinomas and in human fetal esophagus development. We used the suppression subtractive hybridization technique to subtract cDNAs prepared from tumor and normal human esophageal samples. cDNA sequencing and reverse transcription polymerase chain reaction (RT-PCR) analysis of RNAs from human tumor and the normal esophagus revealed 10 differentially transcribed genes: CSTA, CRNN, CEACAM1, MAL, EMP1, ECRG2, and SPRR downregulated, and PLAUR, SFRP4, and secreted protein that is acidic and rich in cysteine upregulated in tumor tissue as compared with surrounding normal tissue. In turn, genes up- and downregulated in tumor tissue were down- and upregulated, respectively, during development from the fetal to adult esophagus. Thus, we demonstrated that, as reported for other tumors, gene transcriptional activation and/or suppression events in esophageal tumor progression were opposite to those observed during development from the fetal to adult esophagus. This tumor ,embryonization' supports the idea that stem or progenitor cells are implicated in esophageal cancer emergence. [source] A folding variant of human ,-lactalbumin induces mitochondrial permeability transition in isolated mitochondriaFEBS JOURNAL, Issue 1 2001Camilla Köhler A human milk fraction containing multimeric ,-lactalbumin (MAL) is able to kill cells via apoptosis. MAL is a protein complex of a folding variant of ,-lactalbumin and lipids. Previous results have shown that upon treatment of transformed cells, MAL localizes to the mitochondria and cytochrome c is released into the cytosol. This is followed by activation of the caspase cascade. In this study, we further investigated the involvement of mitochondria in apoptosis induced by the folding variant of ,-lactalbumin. Addition of MAL to isolated rat liver mitochondria induced a loss of the mitochondrial membrane potential (,,m), mitochondrial swelling and the release of cytochrome c. These changes were Ca2+ -dependent and were prevented by cyclosporin A, an inhibitor of mitochondrial permeability transition. MAL also increased the rate of state 4 respiration in isolated mitochondria by exerting an uncoupling effect. This effect was due to the presence of fatty acids in the MAL complex because it was abolished completely by BSA. BSA delayed, but failed to prevent, mitochondrial swelling as well as dissipation of ,,m, indicating that the fatty acid content of MAL facilitated, rather than caused, these effects. Similar results were obtained with HAMLET (human ,-lactalbumin made lethal to tumour cells), which is native ,-lactalbumin converted in vitro to the apoptosis-inducing folding variant of the protein in complex with oleic acid. Our findings demonstrate that a folding variant of ,-lactalbumin induces mitochondrial permeability transition with subsequent cytochrome c release, which in transformed cells may lead to activation of the caspase cascade and apoptotic death. [source] Attenuation of proliferation in oligodendrocyte precursor cells by activated microgliaJOURNAL OF NEUROSCIENCE RESEARCH, Issue 8 2010Deanna L. Taylor Abstract Activated microglia can influence the survival of neural cells through the release of cytotoxic factors. Here, we investigated the interaction between Toll-like receptor 4 (TLR4)-activated microglia and oligodendrocytes or their precursor cells (OPC). Primary rat or N9 microglial cells were activated by exposure to TLR4-specifc lipopolysaccharide (LPS), resulting in mitogen-activated protein kinase activation, increased CD68 and inducible nitric oxide synthase expression, and release of the proinflammatory cytokines tumor necrosis factor (TNF) and interleukin-6 (IL-6). Microglial conditioned medium (MGCM) from LPS-activated microglia attenuated primary OPC proliferation without inducing cell death. The microglial-induced inhibition of OPC proliferation was reversed by stimulating group III metabotropic glutamate receptors in microglia with the agonist L-AP4. In contrast to OPC, LPS-activated MGCM enhanced the survival of mature oligodendrocytes. Further investigation suggested that TNF and IL-6 released from TLR4-activated microglia might contribute to the effect of MGCM on OPC proliferation, insofar as TNF depletion of LPS-activated MGCM reduced the inhibition of OPC proliferation, and direct addition of TNF or IL-6 attenuated or increased proliferation, respectively. OPC themselves were also found to express proteins involved in TLR4 signalling, including TLR4, MyD88, and MAL. Although LPS stimulation of OPC did not induce proinflammatory cytokine release or affect their survival, it did trigger JNK phosphorylation, suggesting that TLR4 signalling in these cells is active. These findings suggest that OPC survival may be influenced not only by factors released from endotoxin-activated microglia but also through a direct response to endotoxins. This may have consequences for myelination under conditions in which microglial activation and cerebral infection are both implicated. © 2010 Wiley-Liss, Inc. [source] Down-regulation of members of glycolipid-enriched membrane raft gene family, MAL and BENE, in cervical squamous cell cancersJOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH (ELECTRONIC), Issue 1 2004Mitsuko Hatta Abstract Persistent human papillomavirus infections cause infected epithelial cells to lose cellular polarity leading to cell transformation. Glycolipid-enriched membrane (GEM) rafts are implicated in polarized sorting of apical membrane proteins in epithelial cells and even in signal transduction. The MAL and BENE are essential component of the GEM raft's machinery for apical sorting of membrane proteins. In this study we demonstrated down-regulation of MAL and BENE mRNA in over two-thirds of primary cervical squamous cell cancers (14 and 15 of 20 cases, for MAL and BENE, respectively) when compared to corresponding non-cancerous uterine squamous cells. Allelic loss or hyper-methylation was not accompanied by MAL or BENE mRNA down-expression in human primary cervical cancers in microsatellite allelic analysis and HpaII-PCR-based methylation analysis of the MAL and BENE genomic region. In addition, we note down-regulation of these genes in established cervical cancer cell lines. These results suggest that down-regulation of MAL and BENE genes, which are essential components of the cellular polarized sorting system, play an important role in human cervical squamous cell cancer development. [source] A review of photodynamic therapy in cutaneous leishmaniasisJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 8 2008EM Van Der Snoek Summary We present a review of six clinical studies investigating the use of photodynamic therapy (PDT) using porphyrin precursors for the treatment of Old World cutaneous leishmaniasis (CL). Thirty-nine patients with a total of 77 lesions received PDT using a range of treatment schedules following topical application of aminolevulinic acid (ALA) or methyl-aminolevulinate (MAL). The tissue response to PDT is accompanied by a mild burning sensation, erythema and reversible hypo- and hyperpigmentation. Few mechanistic studies have addressed the principles underlying the use of PDT for CL. All six reviewed papers suggest that PDT with porphyrin precursors is relatively effective in treating CL. Data are still limited, and PDT cannot at this point be recommended in routine clinical practice. The mechanism of action of this promising therapeutic modality needs to investigated further and additional controlled trials need to be performed. [source] Evidence-based review of lasers, light sources and photodynamic therapy in the treatment of acne vulgarisJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 3 2008M Hædersdal Abstract Background, There is a considerable need for effective and safe treatment for acne vulgaris. Objective, In a systematic review with an evidence-based approach to assess the effects of optical treatments for acne vulgaris. Methods, Original publications of controlled clinical trials were identified through searches in PubMed and the Cochrane Library. Results, A total of 16 randomized controlled trials (RCT) and 3 controlled trials (CT) were identified, involving a total of 587 patients. Interventions included photodynamic therapy (PDT; 5 RCTs), infrared lasers (4 RCTs), broad-spectrum light sources (3 RCTs, 1 CT), pulsed dye lasers (PDL; 2 RCTs, 1 CT), intense pulsed light (IPL; 1 RCTs, 2 CTs), and potassium titanyl phosphate laser (1 RCT). The randomization method was mentioned in 6 of 16 RCTs, and one trial described adequate allocation concealment. Most trials were intraindividual trials (12 of 19), which applied blinded response evaluations (12 of 19) and assessed a short-term efficacy up to 12 weeks after treatment (17 of 19). Based on the present best available evidence, we conclude that optical treatments possess the potential to improve inflammatory acne on a short-term basis with the most consistent outcomes for PDT [up to 68% improvement, aminolevulinic acid (ALA), methyl-aminolevulinic acid (MAL) and red light]. IPL-assisted PDT seems to be superior to IPL alone. Only two trials compare optical vs. conventional treatments, and further studies are needed. Side-effects from optical treatments included pain, erythema, oedema, crusting, hyperpigmentation, pustular eruptions and were more intense for treatments combined with ALA or MAL. Conclusion, Evidence from controlled clinical trials indicates a short-term efficacy from optical treatments for acne vulgaris with the most consistent outcomes for PDT. We recommend that patients are preoperatively informed of the existing evidence, which indicates that optical treatments today are not included among first line treatments. [source] Photodynamic therapy: update 2006 Part 2: Clinical resultsJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 4 2007PG Calzavara-Pinton Abstract In several randomized, controlled studies, the application of a standard preparation containing methyl-aminolevulinate (MAL; Metvix®, Galderma, F), followed by red light irradiation proved effective and well tolerated in the treatment of actinic keratosis and basal cell carcinoma, and has now been approved for clinical use in European countries. A brand name aminolevulinic acid (ALA) solution (Levulan Kerastick®, Dusa Pharmaceuticals Inc., Wilmington, MA) plus blue light exposure has been approved for the treatment of actinic keratosis in the USA. Randomized and controlled studies have shown that MAL as well as ALA are also effective in the treatment of Bowen's disease. In addition, a large and growing number of open studies or case reports have evaluated its use in the treatment of a broad range of other neoplastic, inflammatory and infectious skin diseases. However, efficacy and definite advantages over standard therapies remain to be clarified because the experimental design of these studies was often poor, the number of enrolled patients was generally low, and the follow-up was shorter than 12 months. However, these studies have suggested a few possible clinical applications worthy of further investigation. A growing number of laboratory and clinical findings suggest that several new synthetic sensitizers, besides ALA and MAL, may be helpful in the treatment of non-melanoma skin cancers, melanoma metastasis, and selected inflammatory and infective skin diseases. These compounds are deliverable intravenously, have short half-lives both in the blood and skin, and are highly efficient. However, they are as of yet not approved for clinical use. [source] Photodynamic therapy: update 2006 Part 1: Photochemistry and photobiologyJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 3 2007PG Calzavara-Pinton Abstract Photodynamic therapy (PDT) is a two-step therapeutic technique in which the topical or systemic delivery of photosensitizing drugs is followed by irradiation with visible light. Activated photosensitizers transfer energy to molecular oxygen, generating reactive oxygen species (ROS). The subsequent oxidation of lipids, amino acids and proteins induces cell necrosis and apoptosis. In addition, ROS indirectly stimulate the transcription and release of inflammatory mediators. The photosensitizers are selective, in that they penetrate and accumulate in tumour cells or in the endothelium of newly formed vessels while generally avoiding the surrounding healthy tissue. The mechanisms of penetration through the cell membrane and the pattern of subcellular localization strongly influence the type of cellular effect. The photobiology and photoimmunology of the haematoporphyrin (Hp) derivative and its purified, lyophilized and concentrated form porfimer sodium have been investigated over the past 30 years. However, interest in PDT in dermatology was not raised until the 1990s with the availability of a simple and effective technique, the topical application of aminolaevulinic acid (ALA) and its methyl ester (methyl aminolaevulinate, MAL) followed by irradiation with broadband red light. At the same time, several new ,second-generation' synthetic sensitizers (e.g. benzoporphyrin derivatives, phthalocyanines, chlorins and porphycenes) became available. These compounds are chemically pure, highly efficient, selective and safe, while offering the advantage that the generalized skin photosensitivity they produce lasts for only a short time. They are currently under clinical evaluation but have not yet been approved for clinical use. This paper provides an overview of the chemistry of the photosensitizers, the photobiology and photoimmunology of the photodynamic reaction as well as the photophysical characteristics of the light sources available for PDT. [source] Sex-dimorphic effects of progesterone and its reduced metabolites on gene expression of myelin proteins by rat Schwann cellsJOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 2 2006Valerio Magnaghi Abstract Data obtained in our and other laboratories have indicated that progesterone (P) and its derivatives, dihydroprogesterone (DHP) and tetrahydroprogesterone (THP), stimulate the expression of two myelin proteins of the peripheral nervous system (PNS) [i.e., glycoprotein zero (P0) and peripheral myelin protein 22 (PMP22)]. We have now considered the effects of P and its derivatives on these and other myelin proteins [i.e., myelin-associated glycoprotein (MAG) and myelin and lymphocyte protein (MAL)] in sex-specific cultures of rat Schwann cells. Gene expression of myelin proteins was assessed by RNase protection assay. Treatment with P or DHP induced a stimulatory effect on P0 mRNA levels in male but not in female Schwann cells. In contrast, treatment with THP increased gene expression of P0 exclusively in female Schwann cells. A similar sex-difference was also evident for other myelin proteins. Indeed, PMP22 expression was stimulated by treatment with P in male cultures, whereas THP induced an increase of mRNA levels in female cultures. Moreover, MAG was stimulated by THP treatment in male cultures only, whereas MAL expression was unaffected by neuroactive steroid treatment in both male and female cultures. In conclusion, the present observations indicate that the effects of neuroactive steroids on myelin proteins are sexually dimorphic. This finding might represent an important background for sex-specific therapies of acquired and inherited peripheral neuropathies. [source] 5-Aminolevulinic Acid Derivatives in Photomedicine: Characteristics, Application and PerspectivesPHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 4 2006Nicolas Fotinos ABSTRACT The introduction of lipophilic derivatives of the naturally occurring heme precursor 5-aminolevulinic acid (5-ALA) into photomedicine has led to a true revival of this research area. 5-ALA-mediated photodynamic therapy (PDT) and fluorescence photodetection (FD) of neoplastic disease is probably one of the most selective cancer treatments currently known in oncology. To date, this method has been assessed experimentally for the treatment of various medical indications. However, the limited local bioavailability of 5-ALA has widely prevented its use in daily clinical practice. Although researchers were already aware of this drawback early during the development of 5-ALA-mediated PDT, only recently have well-established concepts in pharmaceutical science been adapted to investigate ways to overcome this drawback. Recently, two derivatives of 5-ALA, methylaminolevulinate (MAL) and hexylaminolevulinate (HAL), gained marketing authorization from the regulatory offices in Europe and Australia. MAL is marketed under the trade name Metvix for the treatment of actinic keratosis and difficult-to-treat basal cell carcinoma. HAL has recently been launched under the trade name Hexvix to improve the detection of superficial bladder cancer in Europe. This review will first present the fundamental concepts underlying the use of 5-ALA derivatives in PDT and FD from a chemical, biochemical and pharmaceutical point of view. Experimental evidences from preclinical data on the improvements and limits observed with 5-ALA derivatives will then be introduced. The state-of-the-art from clinical studies with 5-ALA esters will be discussed, with special emphasis placed on the process that led to the development of MAL in dermatology and to HAL in urology. Finally, we will discuss promising medical fields in which use of 5-ALA derivatives might potentially lead to further use of this methodology in photomedicine. [source] Photodynamic therapy for the treatment of a giant superficial basal cell carcinomaPHOTODERMATOLOGY, PHOTOIMMUNOLOGY & PHOTOMEDICINE, Issue 1 2009Donato Calista Summary A 74-year-old man was referred to our department for the treatment of a 15 × 15 cm superficial basal cell carcinoma (BCC) on his lumbar region. As surgical excision was considered too destructive, photodynamic therapy (PDT) was proposed. Methyl 5-aminolevulinate (MAL) cream was applied under occlusion for 3 h before illumination with a light-emitting diode lamp with an emission peak of 632 nm, a fluence rate of 83.3 mW/cm, and a light dose of 37 J/cm. A second MAL-PDT session was repeated 1 week later. The neoplastic area healed in 30 days. No recurrence has occurred after a 40-month follow-up period, but clinical observation continues. Although surgery still remains the treatment of choice for giant BCC, for which the local invasiveness and metastatic potential are well known, we offered our patient the option of PDT because we believed that classical surgery could hardly provide the same satisfactory outcome. As far as we know, this is the first case of giant BCC treated with PDT. [source] Homoeological relationships between the f chromosome of Brassica rapa and the e chromosome of Brassica oleraceaPLANT BREEDING, Issue 2 2002Y. Kaneko Abstract Eight plants of the putative double monosomic addition line (DMAL, 2n= 20) were developed by crossing a monosomic chromosome addition line of radish [f(A)-type monosomic addition line (MAL) (2n= 19)] carrying the f chromosome of Brassica rapa (2n= 20, AA) with another [e(C)-type MAL (2n= 19)] having the echromosome of Brassica oleracea (2n= 18, CC). The homoeological relationships between the two alien chromosomes were investigated by morphological, cytogenetic and random amplified polymorphic DNA (RAPD) analysis. Seventeen morphological traits that were not present in the radish cv. ,Shogoin' were observed in both MALs and these traits were substantially exhibited in DMAL plants. At the first metaphase of pollen mother cells (PMCs), the two parental MALs showed a chromosome configuration of 9II +1I, demonstrating impossibility of recombination between the R and the added chromosomes. The DMALs formed 10II in approximately 73% of PMCs, with one bivalent showing loose pairing between two chromosomes differing in size. In an attempt to identify the two MALs by RAPD-specific markers using 26 selected random primers, 13 and 20 bands were specific for the f(A)-type and the e(C)-type MALs, respectively; 12 bands were common to both MALs (26.7%). In conclusion, the f chromosome of B. rapa is homoeologous to the e chromosome of B. oleracea. The genetic domain (genes) for 17 morphological traits are linked to each homoeologous chromosome bearing 27% of the corresponding RAPD markers. [source] Photodynamic therapy of multiple actinic keratoses: reduced pain through use of visible light plus water-filtered infrared A compared with light from light-emitting diodesBRITISH JOURNAL OF DERMATOLOGY, Issue 3 2010V. Von Felbert Summary Background, Photodynamic therapy (PDT) with methyl aminolaevulinate (MAL) is an effective treatment for multiple actinic keratoses (AKs). Pain, however, is a major side-effect. Objectives, To compare pain intensity, efficacy, safety and cosmetic outcome of MAL PDT with two different light sources in an investigator-initiated, randomized, double-blind study. Methods, Eighty patients with multiple AKs grade I,II were assigned to two groups: group 1, MAL PDT with visible light and water-filtered infrared A (VIS + wIRA); group 2, MAL PDT with light from light-emitting diodes (LEDs), with a further division into two subgroups: A, no spray cooling; B, spray cooling on demand. MAL was applied 3 h before light treatment. Pain was assessed before, during and after PDT. Efficacy, side-effects, cosmetic outcome and patient satisfaction were documented after 2 weeks and 3, 6 and 12 months. Where necessary, treatment was repeated after 3 months. Results, Seventy-six of the 80 patients receiving MAL PDT completed the study. Patient assessment showed high efficacy, very good cosmetic outcome and high patient satisfaction. The efficacy of treatment was better in the group of patients without spray cooling (P = 0·00022 at 3 months, P = 0·0068 at 6 months) and showed no significant differences between VIS + wIRA and LED. VIS + wIRA was significantly less painful than LED: the median of maximum pain was lower in the VIS + wIRA group than in the LED group for PDT without spray cooling. Pain duration and severity assessed retrospectively were less with VIS + wIRA than with LED, irrespective of cooling. Conclusions, All treatments showed high efficacy with good cosmetic outcome and high patient satisfaction. Efficacy of treatment was better without spray cooling. VIS + wIRA PDT was less painful than LED PDT for PDT without spray cooling. [source] Topical aminolaevulinic acid- and aminolaevulinic acid methyl ester-based photodynamic therapy with red and violet light: influence of wavelength on pain and erythemaBRITISH JOURNAL OF DERMATOLOGY, Issue 5 2009P. Mikolajewska Summary Background, Photodynamic therapy (PDT) is based on the combination of an exogenously administered precursor of photosensitizer [protoporphyrin IX (PpIX)] synthesis and exposure to light. Choosing the optimal wavelength is important. Red light penetrates deeper into tissue, while violet light is more efficient in activating PpIX but does not penetrate so deeply. Objectives, We studied PpIX formation and the PDT effect after application to human skin of creams containing aminolaevulinic acid (ALA) and aminolaevulinic acid methyl ester (MAL). The aim of the study was to investigate whether the wavelength of the light used has an influence on pain sensations during topical PDT with the different prodrugs. Methods, ALA cream (10%) and MAL cream (10%) were topically applied on the skin of 10 healthy volunteers. After 24 h the application site was exposed to 8 mW cm,2 violet laser or to 100 mW cm,2 red laser light. The erythema index was monitored up to 24 h after light exposure. For the first time the pain during topical ALA- and MAL-PDT was assessed by measuring the time taken for pain to occur. Also, for the first time, the intensities of the light sources were calibrated so as to have the same relative quantum efficiency. Results, The pain sensation during ALA-PDT with red light came 22 s sooner than during ALA-PDT with violet light, which is statistically significant (P < 0·05). Moreover, ALA-PDT with red light gave stronger and more persistent erythema than ALA-PDT with violet light. ALA induced about three times more PpIX than MAL. No statistically significant differences were found for erythema, or for the time for pain to occur, in the case of MAL-PDT with red vs. violet light. Conclusions, Topical ALA-PDT with violet light allows longer exposure times before pain is induced and gives less erythema as compared with topical ALA-PDT with red light. [source] Calcitriol treatment improves methyl aminolaevulinate-based photodynamic therapy in human squamous cell carcinoma A431 cellsBRITISH JOURNAL OF DERMATOLOGY, Issue 2 2009E. Cicarma Summary Background, Photodynamic therapy (PDT) using methyl aminolaevulinate (MAL) provides a new, approved method for treatment of skin cancer and its precursors. However, MAL-based PDT is not very efficient for poorly differentiated skin carcinoma. Thus, novel strategies to enhance the PDT effect are needed. Objectives, In order to improve the efficacy of MAL-based PDT, we investigated the effect of adding calcitriol, a prodifferentiation hormone, to human squamous cell carcinoma A431 cells in vitro. Methods, A short course (24 h) of calcitriol pretreatment was applied in A431 cells, and, subsequently, MAL-induced protoporphyrin IX (PpIX) was measured. Results, Calcitriol pretreatment of the cells elevated their PpIX levels. Furthermore, the cell damage after exposure to blue light was significantly higher in calcitriol-treated cells. Increased photoinactivation correlated with higher levels of PpIX in the calcitriol-pretreated cells. Conclusions, Calcitriol enhances MAL-based PDT in A431 cells. [source] Alteration of the Diastereoselectivity of 3-Methylaspartate Ammonia Lyase by Using Structure-Based MutagenesisCHEMBIOCHEM, Issue 13 2009Hans Raj Abstract 3-Methylaspartate ammonia-lyase (MAL) catalyzes the reversible amination of mesaconate to give both (2S,3S)-3-methylaspartic acid and (2S,3R)-3-methylaspartic acid as products. The deamination mechanism of MAL is likely to involve general base catalysis, in which a catalytic base abstracts the C3 proton of the respective stereoisomer to generate an enolate anion intermediate that is stabilized by coordination to the essential active-site MgII ion. The crystal structure of MAL in complex with (2S,3S)-3-methylaspartic acid suggests that Lys331 is the only candidate in the vicinity that can function as a general base catalyst. The structure of the complex further suggests that two other residues, His194 and Gln329, are responsible for binding the C4 carboxylate group of (2S,3S)-3-methylaspartic acid, and hence are likely candidates to assist the MgII ion in stabilizing the enolate anion intermediate. In this study, the importance of Lys331, His194, and Gln329 for the activity and stereoselectivity of MAL was investigated by site-directed mutagenesis. His194 and Gln329 were replaced with either an alanine or arginine, whereas Lys331 was mutated to a glycine, alanine, glutamine, arginine, or histidine. The properties of the mutant proteins were investigated by circular dichroism (CD) spectroscopy, kinetic analysis, and 1H NMR spectroscopy. The CD spectra of all mutants were comparable to that of wild-type MAL, and this indicates that these mutations did not result in any major conformational changes. Kinetic studies demonstrated that the mutations have a profound effect on the values of kcat and kcat/KM; this implicates Lys331, His194 and Gln329 as mechanistically important. The 1H NMR spectra of the amination and deamination reactions catalyzed by the mutant enzymes K331A, H194A, and Q329A showed that these mutants have strongly enhanced diastereoselectivities. In the amination direction, they catalyze the conversion of mesaconate to yield only (2S,3S)-3-methylaspartic acid, with no detectable formation of (2S,3R)-3-methylaspartic acid. The results are discussed in terms of a mechanism in which Lys331, His194, and Gln329 are involved in positioning the substrate and in formation and stabilization of the enolate anion intermediate. [source] Microbiological effect of photodynamic therapy (PDT) in healthy volunteers: a comparative study using methyl aminolaevulinate and hexyl aminolaevulinate creamCLINICAL & EXPERIMENTAL DERMATOLOGY, Issue 6 2007A. Yung Summary Background., Acne vulgaris is a common skin problem that affects up to 90% of adolescents. Colonization of the duct with Propionibacterium species is one of the factors implicated in the development of acne. Owing to the increasing incidence of antibiotic resistance, there has been an greater interest in the development of new methods to treat acne. Early studies have shown that photodynamic therapy (PDT) with aminolaevulinic acid (ALA) can lead to prolonged improvement in acne. Newer derivatives of ALA such as methyl aminolaevulinate hydrochloride (MAL) and hexyl aminolaevulinate hydrochloride (HAL) have been developed for use in PDT, with the potential benefits of higher lipophilicity and penetration potential. Objectives., To determine the microbiological effect and tolerability of a single application of HAL-PDT and to compare it with MAL-PDT in healthy volunteers. Methods., This was a randomised double-blind study to examine the microbiological effects and safety of a single application of MAL-PDT and HAL-PDT on normal skin in 18 healthy volunteers. Bacterial skin samples for Propionibacterium spp. and Micrococceae were obtained at baseline and 2, 4, 7 and 14 days. Results., Following PDT with MAL and HAL, a statistically significant transient reduction in mean density of Propionibacterium spp. 2 days after treatment using each agent (P < 0.05 for both) was found. There were no significant changes in mean number of Micrococceae for the duration of the study period. Treatment with HAL-PDT and MAL-PDT was well tolerated. Overall, HAL-PDT was associated with fewer side-effects compared with MAL-PDT (P < 0.01) over the 14 day study period. Conclusion., HAL-PDT and MAL-PDT transiently reduce density of Propionibacterium spp. density to a similar degree in normal healthy individuals. The transient reduction in Propionibacterium spp. suggests that the prolonged antiacne effect of PDT relies on factors independent of bacterial density. HAL-PDT appears to be better tolerated than MAL-PDT. [source] DNA damage in peripheral blood leukocytes of physically active individuals as measured by the alkaline single cell gel electrophoresis assayENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 4 2009Gursatej Gandhi Abstract DNA damage induced by physical activity and/or exercise has been reported under different conditions but not for individuals maintaining physical fitness by regular strenuous exercise. Therefore, we compared levels of DNA damage in blood leukocytes of 40 healthy individuals (35 males, 5 females) who regularly exercised in gymnasiums/health clubs and 15 healthy sedentary controls who had never exercised. The former group was selected (after informed consent) on the basis of how long they had been exercising on a regular basis as well as their exercise schedule and regimen. The length of time since starting a regular exercise regimen ranged from 2 months to 9 years, whereas the daily exercise duration ranged from 40 min to 3 hrs and warm-up sessions ranged from none to 90 min. The length of DNA migration (44.66 ± 2.68 ,m in males, 29.62 ± 1.69 ,m in females) and the percentage of cells with tails (79.86 ±1.27% in males, 67.20 ± 0.96% in females) in peripheral blood leukocytes of physically active individuals were increased significantly (P < 0.001) with respect to corresponding values in control males and females (18.85 ± 1.79 ,m, 23.37 ± 3.94 ,m; 24.50 ± 1.98%, 33.00 ± 4.44%, respectively). Highly significant differences for DNA damage were also observed between physically active males and females. These observations, in the absence of any other exposures, indicate a correlation between strenuous exercise to keep fit and increased levels of DNA damage. This finding may have relevance in terms of the ageing process, with diseases associated with aging, and with carcinogenesis. Environ. Mal. Mutagen. 2009. © 2009 Wiley-Liss, Inc. [source] Chenopodium probstii and Chenopodium missouriense: two North American plant species in the Czech Republic, Slovak Republic and neighbouring countriesFEDDES REPERTORIUM, Issue 5-6 2004J. Dostálek Ing. This paper presents the results of a floristic-taxonomic survey of two North American invasive species, Chenopodium probstiiAellen and Ch. missourienseAellen, in the Czech Republic, Slovak Republic and neighbouring countries. It is based mainly on the results of a re-analysis of the authors' herbarium material collected from 1957 to 2003, deposited mainly in the PRA Herbarium (herbarium of the Institute of Botany of the Academy of Sciences of the Czech Republic in Pr,honice near Prague). Also, the chorology and ecology of both species in Czechian and Slovakian are discussed. In addition, a summary of data on the occurrence of both species throughout their distribution is presented, with emphasis on European records. On the basis of this analysis, the hypothetical origin of Ch. probstii in North America is confirmed. First-time records of this species are presented for Egypt, North Korea, Poland, Slovenia, Croatia and Romania. The second species, Ch. missouriense, is reported for the first time from Slovakia and Austria. Sources of further dissemination of both species in their secondary European area of distribution are described. In Europe, both these invasive species are in the pro- cess of naturalisation (ephemerophyte , epoecophyte), approximately in the resting-phase lag; significant range expansion can be expected in the near future, especially for Ch. probstii. Chenopodium probstii und Chenopodium missouriense, zwei nordamerikanische Arten in der Tschechischen Republik, der Slowakischen Republik und benachbarten Ländern Diese Arbeit präsentiert Ergebnisse einer floristisch-taxonomischen Untersuchung von zwei nordamerikanischen Invasionsarten, und zwar Chenopodium probstiiAellen und Ch. missourienseAellen in der Tschechischen Republik, in der Slowakischen Republik und in benachbarten Ländern. Sie stützt sich vorwiegend auf Resultate des eigenen Herbarmaterials der Jahre 1957,2003, das vorwiegend im Herbarium PRA (= Herbarsammlung des Botanischen Instituts der Akademie der Wissenschaften der Tschechischen Republik in Pr,honice bei Praha) deponiert ist. Auch wurden Chorologie und Ökologie beider Arten in Tschechien und in der Slowakei analysiert. Gleichzeitig wurden die Angaben über das Vorkommen beider Arten im gesamten Areal unter besonderer Berücksichtigung der Geschichte ihrer Ausbreitung im sekundären Teil ihrer Areale, vor allem in Europa zusammengefasst. Durch diese Analyse wurde der Ursprung von Ch. probstii in Nordamerika bestätigt. Chenopodium probstii wurde als neue adventive Art auch in Ägypten und Nordkorea, in Europa zum ersten Mal in Polen, Slowenien, Kroatien und Rumänien beobachtet. Eine weitere Art, Ch. missouriense, wurde zum ersten Mal in der Slowakei und in Österreich erwähnt. Diasporenquellen beider Arten im sekundären europäischen Areal werden ebenfalls angeführt. In Europa sind beide invasive Arten im Prozess der Einbürgerung (Ephemerophyt , Epoökophyt), die vermutlich in der Ruhephase abläuft. Eine expansive Ausbreitung können wir in der nächsten Zeit vor allem von Ch. probstii erwarten. Bisher gehören beide Arten zu den potentiellen Unkräutern. [source] Signal transduction by the lipopolysaccharide receptor, Toll-like receptor-4IMMUNOLOGY, Issue 2 2004Eva M. Pålsson-McDermott Summary An understanding of lipopolysaccharide (LPS) signal transduction is a key goal in the effort to provide a molecular basis for the lethal effect of LPS during septic shock and point the way to novel therapies. Rapid progress in this field during the last 6 years has resulted in the discovery of not only the receptor for LPS , Toll-like receptor 4 (TLR4) , but also in a better appreciation of the complexity of the signalling pathways activated by LPS. Soon after the discovery of TLR4, the formation of a receptor complex in response to LPS, consisting of dimerized TLR4 and MD-2, was described. Intracellular events following the formation of this receptor complex depend on different sets of adapters. An early response, which is dependent on MyD88 and MyD88-like adapter (Mal), leads to the activation of nuclear factor-,B (NF-,B). A later response to LPS makes use of TIR-domain-containing adapter-inducing interferon-, (TRIF) and TRIF-related adapter molecule (TRAM), and leads to the late activation of NF-,B and IRF3, and to the induction of cytokines, chemokines, and other transcription factors. As LPS signal transduction is an area of intense research and rapid progress, this review is intended to sum up our present understanding of the events following LPS binding to TLR4, and we also attempt to create a model of the signalling pathways activated by LPS. [source] HUI M,lama O Ke Kai: a positive prevention-based youth development program based on native hawaiian values and activities,JOURNAL OF COMMUNITY PSYCHOLOGY, Issue 8 2009Earl S. Hishinuma Evaluation of after-school programs that are culturally and place-based and promote positive youth development among minority and indigenous youths has not been widely published. The present evaluation is the first of its kind of an after-school, youth-risk prevention program called Hui Mal,ma O Ke Kai (HMK), that emphasizes Native Hawaiian values and activities to promote positive youth development for fifth and sixth graders (N=110) in a rural Native Hawaiian community. Results indicated positive gains on youth self-reports in Native Hawaiian values, self-esteem, antidrug use, violence prevention strategies, and healthy lifestyle in Year 1, and in family cohesion, school success, and violence prevention strategies in Year 2. Parent reports of their children indicated positive gains in selected domains. Implications include the support for a promising culturally appropriate program, expansion to middle-school-aged youths, and parent involvement. © 2009 Wiley Periodicals, Inc. [source] Design, synthesis, characterization and in-vivo activity of a novel salmon calcitonin conjugate containing a novel PEG-lipid moietyJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 3 2010Weiqiang Cheng Abstract Objectives The aim of the study was to explore (1) the synthesis of a novel poly(ethylene glycol) modified lipid (PEG-lipid, PL) containing a chemically active tri-block linker, ,-maleimido lysine (Mal), and its conjugation with salmon calcitonin (sCT), and (2) the biophysical properties and activity of the resulting conjugate, Mal-PL-sCT, relative to the control, 2PEG-Mal-sCT, which comprises sCT conjugated with ,-palmitoyl- N -,-maleimido- l -lysine at cysteine 1 and cysteine 7, and PEG moieties at lysine 11 and lysine 18 via a conventional stepwise method. Methods The PEG-lipid was obtained by condensing palmitic acid derivative of ,-maleimido lysine with methoxy poly(ethylene glycol) amine. Under reductive conditions, the PEG-lipid readily reacted with sCT to yield the resultant compound, Mal-PL-sCT. Key findings Dynamic light scattering analyses suggested that Mal-PL-sCT and 2PEG-Mal-sCT exhibited robust helical structures with a high tendency to aggregate in water. Both compounds were more stable against intestinal degradation than sCT, although Mal-PL-sCT was less stable than 2PEG-Mal-sCT. However, 2PEG-Mal-sCT did not possess hypocalcaemic activity while Mal-PL-sCT retained the hypocalcaemic activity of sCT when it was subcutaneously injected in the rat model. Multiple functional groups may be conjugated to a peptide via a tri-block linker without the risk of obliterating the intrinsic bioactivity of the peptide. Conclusions The resultant novel PEG-lipid has a potential role to optimize protein and peptide delivery. [source] Development and validation of the maximal electro-shock seizure model in dogsJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 6 2007P. R. TERRITO The development and validation of the maximal electro-shock (MES) model using phenobarbital (Pb) as the positive control is described. This approach builds on previous work in rodent model systems, and has been adapted to dogs as a tool for pharmaceutical dose selection. Dogs, like rodents, exhibit generalized convulsions which manifest as progressive clinical signs in a dose (electrical current) dependent fashion. At the limit (300 mA, 200 msec) animals underwent clonic-tonic convulsions consistent with complete generalized (Grand Mal) seizures with a grade 3 clinical score (CS) and a menace response time of 98.5 ± 24.4 sec (n = 8). Pretreatment of animals with Pb at 3, 10, and 30 mg/kg, in a 4-by-4 complete block crossover design (Latin-Square), resulted in a dose-dependant reduction in CS and menace response time. Estimates of plasma Pb concentration taken prior to MES induction showed a similar dose-dependent reduction in CS and menace response time with concentration. Using a cumulative logistic regression model, a predicted 50% probability of a CS = 1 was approximately 11.4 mg/kg. In addition, plasma Pb concentrations predicted a 50% probability of a CS = 1 occurs at plasma Pb concentration of approximately 16.0 ,g/mL. Combined these data suggest that MES is a useful model for evaluating generalized convulsions in canines and may provide a tool for dose selection of novel pharmaceutical compounds. [source] Titelbild: Beton- und Stahlbetonbau 3/2008BETON- UND STAHLBETONBAU, Issue 3 2008Article first published online: 22 FEB 200 Die Rheinbrücke Wesel hat eine Gesamtlänge von ca. 773 m sowie eine maximale Spannweite von 335 m und wird nach ihrer Fertigstellung die drittgrößte Schrägseilbrücke Deutschlands sein. Nach der 2. Strelasundquerung werden hier zum zweiten Mal in Deutschland die von der DYWIDAG entwickelten Parallellitzenbündel eingesetzt. Sie bestehen in der freien Seillänge aus einzeln korrosionsgeschützten, zueinander parallel in einem Hüllrohr geführten Schrägseillitzen. Die DYNA Grip®-Verankerung bietet die Möglichkeit, einzelne Litzen eines Seiles auszuwechseln und zu inspizieren. (Foto: Donges Stahlbau GmbH) [source] Die Chemie des Katers: Alkohol und seine FolgenCHEMIE IN UNSERER ZEIT (CHIUZ), Issue 1 2007Klaus Roth Prof. Das Überfluten jeder einzelnen Zelle unseres Körpers mit einer großen Menge Ethanol führt zu Störungen im Stoffwechsel aller Organe. Dies erklärt die große Variationsbreite der Symptome nach zu großer Ethanolaufnahme. Gegen den Kater gibt es keine echte Heilung. "Chemie in unserer Zeit" empfiehlt: Viel reines Wasser gegen den Wasserverlust, eine Aspirin oder Ibuprofen gegen die pochenden Kopfschmerzen, Fruchtsaft gegen den Glucosemangel, Muttis kräftige Hühnerbrühe gegen den Elektrolytverlust, eine Vitamintablette wegen ihres sehr wirksamen Placebo-Effekts, Zuspruch und Mitleidsbekundungen der Lieben und dann , wenn der Kreislauf und die Kontrolle der unteren Extremitäten den aufrechten Gang es zulassen, einen Spaziergang an der frischen Luft. Dabei sollte man intensiv über die Sinnlosigkeit übermäßigen Trinkens nachdenken. Das hilft, und am nächsten Tag ist alles vorbei , zumindest bis zum nächsten Mal. Na dann: Helau und Alaaf! Flooding of every cell in our body with a huge amount of ethanol affects the entire metabolism of all organs. This explains the broad variation of symptoms after drinking to much. There is no real cure für hangover. "Chemie in unserer Zeit" recommends much pure water against the dehydration, aspirin or ibuprofen against the throbbing headaches, fruit juice against hypoglycemia, Mom's powerful chicken soup to compensate for electrolyte losses, a vitamine pill because of its powerful placebo-effect, compassion and words of comfort of the loved ones and finally , if blood circulation and control of the lower extremities admit an upright walk , a long stroll in fresh air. Meanwhile one should think deeply about the pointlessness of excessive drinking. This all helps and on the next day it will all be over , at least until next time. Well then: Cheers and Bottoms up! [source] Photosensitivity in Relation to Epileptic Syndromes: A Survey from an Epilepsy Center in JapanEPILEPSIA, Issue 3 2001Hideaki Shiraishi Summary: ,Purpose: We examined the incidence and distribution of photosensitivity among the different age groups and different types of epilepsies and epileptic syndromes. Furthermore, we considered the influence of ethnic and geographic factors on the incidence of photoparoxysmal response (PPR) in epilepsy patients. Methods: We analyzed the responses to intermittent photic stimulation (IPS) by using a Grass PS22 or PS33 photic stimulator for in 2,187 unselected patients with epilepsy who were treated in our center. Results: The classic PPR was elicited in 37 (1.7%) patients. The mean age of these 37 patients was 17.0 years. The subpopulation of patients having PPR included 2.0% of all patients with symptomatic generalized epilepsy, 5.6% (p < 0.01) of those with idiopathic generalized epilepsy, 0.7% of those with symptomatic localization-related epilepsy, and 2.9% of those with undetermined epilepsy. PPR accounted for 17.4 % (p < 0.01) of the patients with juvenile myoclonic epilepsy, 7.6% (p < 0.01) of those with grand mal on awakening, and 6.1% (p < 0.01) of those with symptomatic occipital lobe epilepsy. The incidence of PPR increased in patients up to age 15 years, and suddenly decreased after age 20 years. Conclusion: The present study presents the first report from eastern Asia, analyzing the incidence of PPR with a restricted definition comparable to the other studies, and the rate of PPR was relatively low compared with the studies performed in the European countries. We could confirm the clear relation between age and positive PPR. [source] Syntheses, Crystal Structures and Magnetic Properties of Carboxylato-Bridged Polymeric Networks of MnIIEUROPEAN JOURNAL OF INORGANIC CHEMISTRY, Issue 2 2006Subal Chandra Manna Abstract Three new carboxylato-bridged polymeric networks of MnII having,molecular formula [Mn(ox)(dpyo)]n (1), {[Mn2(mal)2(bpee)(H2O)2]·0.5(bpee)·0.5(CH3OH)}n (2) and {[Mn3(btc)2(2,2,-bipy)2(H2O)6]·4H2O}n (3) [dpyo, 4,4,-bipyridine N,N,-dioxide; bpee, trans -1,2 bis(4-pyridyl)ethylene; 2,2,-bipy, 2,2,-bipyridine; ox = oxalate dianion; mal = malonate dianion; btc = 1,3,5-benzenetricarboxylate trianion] have been synthesized and characterized by single-crystal X-ray diffraction studies and low temperature magnetic measurements. Structure determination of complex 1 reveals a covalent bonded 2D network containing bischelating oxalate and bridging dpyo; complex 2 is a covalent bonded 3D polymeric architecture, formed by bridging malonate and bpee ligands, resulting in an open framework with channels filled by uncoordinated disordered bpee and methanol molecules. Whereas complex 3, comprising btc anions bound to three metal centers, is a 1D chain which further extends its dimensionality to 3D via - and H-bonding interactions. Low temperature magnetic measurements reveal the existence of weak antiferromagnetic interaction in all these complexes. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006) [source] A new species of Anthurium (Araceae) from Espírito Santo State, eastern BrazilFEDDES REPERTORIUM, Issue 1-2 2005E. G. Gonçalves Dr. A new species of Anthurium (A. viridispathum E.G.Gonç., sp. nova) is described and illustrated. It occurs in rocky outcrops in Espírito Santo state, eastern Brazil. It seems to be closer to AnthuriumvalidinerviumEngl., but differs in the primary lateral veins departing from the midrib in a more obtuse angle (45,55° not 30°), much wider spathe (2,2.3 times longer than broad, not 5,6) and inflorescenes longer than leaves (much shorter in A. validinervium). Anthurium viridispathum is tentavely placed in the section UrospadixEngl. subsection ObscureviridiaEngl. (© 2005 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) Eine neue Art der Gattung Anthurium (Araceae) aus dem Staat Espírito Santo, Ostbrasilien Eine neue Art der Gattung Anthurium (A. viridispathum E.G.Gonç., sp. nova) wird beschrieben und abgebildet. Sie findet sich in felsigen Aufschlüssen im Bundesstaat Espírito Santo, Ostbrasilien. Sie ist eng verwandt mit Anthurium validinerviumEngl., untercheidet sich aber durch primäre Seitenadern, die von der Mittelrippe in einem größeren Winkel (45,55°, nicht 30°) abgehen, einer viel breiteren Spatha (2,2,3 mal länger als breit, nicht 5,6 mal) und Blütenständen länger als die Blätter (wesentlich kürzer in A. viridinervium). Anthuriumviridispathum wird unter Vorbehalt in die sect. UrospadixEngl. subsect. ObscureviridiaEngl. gestellt. [source] Records of Bursaphelenchus spp. intercepted in imported packaging wood at Ningbo, ChinaFOREST PATHOLOGY, Issue 5 2006J. Gu Summary From January 2003 to June 2005, samples from 3416 batches of wooden packaging material were inspected for the presence of nematodes in the Ningbo Entry,Exit Inspection and Quarantine Bureau, China. Bursaphelenchus spp. were detected in 202 batches from 25 different countries. The following species were identified on the basis of their morphology and their intergenic transcribed spacer-restriction fragment length polymorphism (ITS-RFLP) patterns: B. xylophilus, B. fungivorus, B. rainulfi, B. hylobianum, B. thailandae, B. mucronatus, B. aberrans, B. lini, B. singaporensis, B. doui, B. conicaudatus, B. vallesianus, B. pinasteri, B. hofmanni and B. arthuri. The most frequently found species were B. mucronatus (57 batches), B. xylophilus (40 batches), B. fungivorus (21 batches), B. rainulfi (19 batches) and B. thailandae (nine batches). The pine wood nematode B. xylophilus was not only found in packaging wood imported from areas where it is known to occur (i.e. The United States of America, Japan, Korea, Hong Kong and Taiwan), but also from countries considered to be free of this dangerous pest (i.e. Brazil, Thailand, Belgium, The Netherlands, Italy and Spain). The occurrence of B. xylophilus in packaging wood from countries regarded as being free of the nematode can most likely be explained by the global circulation of wooden packaging material among infested and non-infested countries. Our findings emphasize the need to fully implement international standards on phytosanitary treatment of packaging wood, in order to prevent further spread of the pine wood nematode, and the need for careful re-examination of the current heat treatment measures. Résumé De Janvier 2003 à Juin 2005, des échantillons de 3416 lots de matériel d'emballage en bois ont été inspectés pour rechercher la présence de nématodes au bureau de quarantaine de Ningbo, en Chine. Des Bursaphelenchus spp. ont été détectés dans 202 lots en provenance de 25 pays différents. Les espèces suivantes ont été identifiées sur la base de leur morphologie et des profils de restriction de l'ITS: B. xylophilus, B. fungivorus, B. rainulfi, B. hylobianum, B. thailandae, B. mucronatus, B. aberrans, B. lini, B. singaporensis, B. doui, B. conicaudatus, B. vallesianus, B. pinasteri, B. hofmanni, et B. arthuri. Les espèces les plus fréquemment trouvées sont B. mucronatus (57 lots), B. xylophilus (40 lots), B. fungivorus (21 lots), B. rainulfi (19 lots) et B. thailandae (9 lots). Le nématode du pin, B. xylophilus, a été trouvé dans du bois d'emballage en provenance non seulement de zones où sa présence est connue (Etats-Unis, Japon, République de Corée, Hongkong et Taïwan) mais aussi de pays considérés comme indemnes de ce redoutable pathogène (Brésil, Thaïlande, Belgique, Pays-Bas, Italie et Espagne). La présence de B. xylophilus dans du bois d'emballage de pays considérés comme indemnes s'explique probablement par la circulation généralisée de matériel d'emballage en bois entre pays infestés ou non. Nos résultats soulignent la nécessité d'appliquer pleinement les normes de traitement phytosanitaire du bois d'emballage, afin d'éviter une plus grande dissémination du nématode du pin, et de réexaminer de façon approfondie les mesures actuelles de traitement thermique. Zusammenfassung Von Januar 2003 bis Juni 2005 wurde im Quarantäne-Inspektionsbüro in Ningbo, China, das Verpackungsholz von 3416 Sendungen nematologisch untersucht. Bursaphelenchus spp. wurden in 202 Sendungen aus 25 verschiedenen Ländern festgestellt. Folgende Arten wurden morphologisch und mit Hilfe der ITS-RFLP-Methode identifiziert: B. xylophilus, B. fungivorus, B. rainulfi, B. hylobianum, B. thailandae, B. mucronatus, B. aberrans, B. lini, B. singaporensis, B. doui, B. conicaudatus, B. vallesianus, B. pinasteri, B. hofmanni, und B. arthuri. Die am häufigsten gefundenen Arten waren B. mucronatus (57 mal), B. xylophilus (40), B. fungivorus (21), B. rainulfi (19) and B. thailandae (9). Der Quarantäneschädling B. xylophilus wurde nicht nur in Verpackungsholz aus Gebieten mit bekannter Verbreitung des Nematoden (USA, Japan, Republik Korea, Hongkong, Taiwan) gefunden, sondern auch aus Ländern, die als frei vom Kiefernholznematoden gelten (Brasilien, Belgien, Niederlande, Italien, Spanien). Die Feststellung von B. xylophilus in Verpackungsholz aus Nichtbefallsländern kann nur durch Zirkulation des Verpackungsholzes zwischen Befalls- und Nichtbefallsländern erklärt werden. Der mittlere prozentuale Anteil der jegliche Nematoden enthaltenden Packholzproben lag im Zeitraum von Januar 2000 bis August 2005 bei 21,3 %; eine klare Tendenz zur Zu- oder Abnahme war während dieser Jahre nicht erkennbar. Die Befunde unterstreichen die Notwendigkeit der strikten Anwendung international erarbeiteter Standards der phytosanitären Behandlung von Verpackungsholz zur Verhinderung der Verschleppung des Kiefernholznematoden und der Überprüfung der Wirksamkeit der zur Zeit angewandten Maßnahmen. [source] Update on peptidylarginine deiminases and deimination in skin physiology and severe human diseasesINTERNATIONAL JOURNAL OF COSMETIC SCIENCE, Issue 3 2007M.-C. Méchin Synopsis Deimination (or citrullination) is a recently described post-translational modification, but its consequences are not yet well understood. It is catalysed by peptidylarginine deiminases (PADs). These enzymes transform arginyl residues involved in a peptidyl link into citrullyl residues in a calcium-dependent manner. Several PAD substrates have already been identified like filaggrin and keratins K1 and K10 in the epidermis, trichohyalin in hair follicles, but also ubiquitous proteins like histones. PADs act in a large panel of physiological functions as cellular differentiation or gene regulation. It has been suggested that deimination plays a role in many major diseases such as rheumatoid arthritis, multiple sclerosis, Alzheimer's disease and psoriasis. Five human genes (PADIs), encoding five highly conserved paralogous enzymes (PAD1-4 and 6), have been characterized. These genes are clustered in a single locus, at 1p35-36 in man. Only PAD1-3 are expressed in human epidermis. PADs seem to be controlled at transcriptional, translational and activity levels and they present particular substrate specificities. In this review, we shall discuss these main biochemical, genetic and functional aspects of PADs together with their pathophysiological implications. Résumé La désimination (ou citrullination) est une modification post-traductionnelle catalysée par les peptidyl-arginine désiminases (PADs), décrite depuis peu et dont les conséquences sont encore mal comprises. Ces enzymes transforment, de façon dépendante du calcium, les résidus arginyl engagés dans un lien peptidique en résidus citrullyl. Plusieurs substrats ont été identifiés: la filaggrine et les cytokératines K1 et K10 de l'épiderme, la trichohyaline dans le follicule pileux mais aussi des protéines ubiquistes comme les histones. Les PADs interviennent dans de nombreuses fonctions physiologiques telles que la différenciation cellulaire ou la régulation génique. La désimination pourrait jouer un rôle dans plusieurs maladies sévères et fréquentes comme la polyarthrite rhumatoïde, la sclérose en plaque, la maladie d'Alzheimer ou encore le psoriasis. Cinq gènes humains (PADIs) codant pour 5 enzymes paralogues conservées (PAD1-4 et 6) ont été caractérisés. Ils sont regroupés en un seul locus, en 1p35-36 chez l'homme. Seules les PAD1-3 sont exprimées dans l'épiderme humain. Les PADs semblent contrôlées aux niveaux transcriptionnel et traductionnel, ainsi qu'au niveau de leur activité. Elles présentent chacune leurs spécificités de substrats. Ces principaux aspects biochimiques, génétiques et fonctionnels des PADs tout comme leurs implications physiopathologiques seront discutés dans cette revue. [source] | ||||||||||||||||||||||||||||||||||