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Selected AbstractsAre CB1 receptor antagonists nootropic or cognitive impairing agents?DRUG DEVELOPMENT RESEARCH, Issue 8 2009Stephen A. Varvel Abstract For more than a decade, a considerable amount of research has examined the effects of rimonabant (SR 141716) and other CB1 receptor antagonists in both in vivo and in vitro models of learning and memory. In addition to its utility in determining whether the effects of drugs are mediated though a CB1 receptor mechanism of action, these antagonists are useful in providing insight into the physiological function of the endogenous cannabinoid system. Several groups have reported that CB1 receptor antagonists enhance memory duration in a variety of spatial and operant paradigms, but not in all paradigms. Conversely, disruption of CB1 receptor signaling also impairs extinction learning in which the animal actively suppresses a learned response when reinforcement has been withheld. These extinction deficits occur in aversively motivated tasks, such as in fear conditioning or escape behavior in the Morris water maze task, but not in appetitively motivated tasks. Similarly, in electrophysiological models, CB1 receptor antagonists elicit a variety of effects, including enhancement of long-term potentiation (LTP), while disrupting long-term depression (LTD) and interfering with transient forms of plasticity, including depolarization-induced suppression of inhibition (DSI) and depolarization-induced suppression of excitation (DSE). The collective results of the in vivo and in vitro studies employing CB1 receptor antagonists, demonstrate that these receptors play integral roles in different components of cognitive processing. Functionally, pharmacological blockade of CB1 receptors may strengthen memory duration, but interferes with extinction of learned behaviors that are associated with traumatic or aversive memories. Drug Dev Res 70:555,565, 2009. © 2009 Wiley-Liss, Inc. [source] Long-lasting hippocampal potentiation and contextual memory consolidationEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 12 2001Benedetto Sacchetti Abstract In order to ascertain whether there are hippocampal electrophysiological modifications specifically related to memory, exploratory activity and emotional stress, extracellular electrical activity was recorded in hippocampal slices prepared from the brains of male adult rats. Several groups of animals were employed: (i) rats which had freely explored the experimental apparatus (8 min exposure); (ii) rats which had been subjected, in the same apparatus, to a fear conditioning paradigm training entailing the administration of aversive electrical footshocks (8 min exposure); (iii) rats to which the same number of aversive shocks had been administered in the same apparatus, but temporally compressed so as to make difficult the association between painful stimuli and the apparatus (30 s exposure); (iv) naïve rats never placed in the apparatus. Half of the rats from each treatment group were used for retrieval testing and the other half for hippocampal excitability testing. The conditioned freezing response was exhibited for no less than 4 weeks. Hippocampal excitability was measured by means of input,output curves (IOC) and paired-pulse facilitation curves (PPF). Retrieval testing or brain slices preparation were performed at increasing delays after the training sessions: immediately afterwards or after 1, 7 or 28 days. Only the rats subjected to the fear conditioning training exhibited freezing when placed again in the apparatus (retrieval testing). It was found that IOCs, with respect to naïve rats, increased in the conditioned animals up to the 7-day delay. In free exploration animals the IOCs increased only immediately after the training session. In all other rats no modification of the curves was observed. IOC increases do not appear to imply presynaptic transmitter release modifications, because they were not accompanied by PPF modifications. In conclusion, a clear-cut correlation was found between the increase in excitability of the Schaffer collateral,CA1 dendrite synapses and freezing response consolidation. [source] Changes in microbial diversity in industrial wastewater evaporation ponds following artificial salinationFEMS MICROBIOLOGY ECOLOGY, Issue 2 2008Eitan Ben-Dov Abstract The salinity of industrial wastewater evaporation ponds was artificially increased from 3,7% to 12,16% (w/v), in an attempt to reduce the activity of sulfate-reducing bacteria (SRB) and subsequent emission of H2S. To investigate the changes in bacterial diversity in general, and SRB in particular, following this salination, two sets of universal primers targeting the 16S rRNA gene and the functional apsA [adenosine-5,-phosphosulfate (APS) reductase ,-subunit] gene of SRB were used. Phylogenetic analysis indicated that Proteobacteria was the most dominant phylum both before and after salination (with 52% and 68%, respectively), whereas Firmicutes was the second most dominant phylum before (39%) and after (19%) salination. Sequences belonging to Bacteroidetes, Spirochaetes and Actinobacteria were also found. Several groups of SRB from Proteobacteria and Firmicutes were also found to inhabit this saline environment. Comparison of bacterial diversity before and after salination of the ponds revealed both a shift in community composition and an increase in microbial diversity following salination. The share of SRB in the 16S rRNA gene was reduced following salination, consistent with the reduction of H2S emissions. However, the community composition, as shown by apsA gene analysis, was not markedly affected. [source] The biology of lantibiotics from the lacticin 481 group is coming of ageFEMS MICROBIOLOGY REVIEWS, Issue 2 2007Alain Dufour Abstract Lantibiotics are antimicrobial peptides from the bacteriocin family, secreted by Gram-positive bacteria. These peptides differ from other bacteriocins by the presence of (methyl)lanthionine residues, which result from enzymatic modification of precursor peptides encoded by structural genes. Several groups of lantibiotics have been distinguished, the largest of which is the lacticin 481 group. This group consists of at least 16 members, including lacticin 481, streptococcin A-FF22, mutacin II, nukacin ISK-1, and salivaricins. We present the first review devoted to this lantibiotic group, knowledge of which has increased significantly within the last few years. After updating the group composition and defining the common properties of these lantibiotics, we highlight the most recent developments. The latter concern: transcriptional regulation of the lantibiotic genes; understanding the biosynthetic machinery, in particular the ability to perform in vitro prepeptide maturation; characterization of a novel type of immunity protein; and broad application possibilities. This group differs in many aspects from the best known lantibiotic group (nisin group), but shares properties with less-studied groups such as the mersacidin, cytolysin and lactocin S groups. [source] Ethnic skin types: are there differences in skin structure and function?,INTERNATIONAL JOURNAL OF COSMETIC SCIENCE, Issue 2 2006A. V. Rawlings Synopsis People of skin of colour comprise the majority of the world's population and Asian subjects comprise more than half of the total population of the earth. Even so, the literature on the characteristics of the subjects with skin of colour is limited. Several groups over the past decades have attempted to decipher the underlying differences in skin structure and function in different ethnic skin types. However, most of these studies have been of small scale and in some studies interindividual differences in skin quality overwhelm any racial differences. There has been a recent call for more studies to address genetic together with phenotypic differences among different racial groups and in this respect several large-scale studies have been conducted recently. The most obvious ethnic skin difference relates to skin colour which is dominated by the presence of melanin. The photoprotection derived from this polymer influences the rate of the skin aging changes between the different racial groups. However, all racial groups are eventually subjected to the photoaging process. Generally Caucasians have an earlier onset and greater skin wrinkling and sagging signs than other skin types and in general increased pigmentary problems are seen in skin of colour although one large study reported that East Asians living in the U.S.A. had the least pigment spots. Induction of a hyperpigmentary response is thought to be through signaling by the protease-activated receptor-2 which together with its activating protease is increased in the epidermis of subjects with skin of colour. Changes in skin biophysical properties with age demonstrate that the more darkly pigmented subjects retaining younger skin properties compared with the more lightly pigmented groups. However, despite having a more compact stratum corneum (SC) there are conflicting reports on barrier function in these subjects. Nevertheless, upon a chemical or mechanical challenge the SC barrier function is reported to be stronger in subjects with darker skin despite having the reported lowest ceramide levels. One has to remember that barrier function relates to the total architecture of the SC and not just its lipid levels. Asian skin is reported to possess a similar basal transepidermal water loss (TEWL) to Caucasian skin and similar ceramide levels but upon mechanical challenge it has the weakest barrier function. Differences in intercellular cohesion are obviously apparent. In contrast reduced SC natural moisturizing factor levels have been reported compared with Caucasian and African American skin. These differences will contribute to differences in desquamation but few data are available. One recent study has shown reduced epidermal Cathepsin L2 levels in darker skin types which if also occurs in the SC could contribute to the known skin ashing problems these subjects experience. In very general terms as the desquamatory enzymes are extruded with the lamellar granules subjects with lowered SC lipid levels are expected to have lowered desquamatory enzyme levels. Increased pores size, sebum secretion and skin surface microflora occur in Negroid subjects. Equally increased mast cell granule size occurs in these subjects. The frequency of skin sensitivity is quite similar across different racial groups but the stimuli for its induction shows subtle differences. Nevertheless, several studies indicate that Asian skin maybe more sensitive to exogenous chemicals probably due to a thinner SC and higher eccrine gland density. In conclusion, we know more of the biophysical and somatosensory characteristics of ethnic skin types but clearly, there is still more to learn and especially about the inherent underlying biological differences in ethnic skin types. Résumé, Les gens qui ont une peau de couleur représentent la majorité de la population mondiale et les sujets asiatiques en représentent plus de la moitié. Pourtant la littérature consacrée aux caractéristiques de ces sujets est limitée. Plusieurs groupes de travail ont essayé au cours des dernières années de comprendre les différences sous-jacentes de la structure et de la fonction de la peau de différentes ethnies. Maisla plupart de ces études ont été réalisées à petite échelle et dans certains cas les différences observées entre les individus au niveau de la qualité de la peau ne font pas ressortir de différence entre races. Récemment, un besoin d'études reliant les diffèrences génétiques et phénotypiques entre différents groupes raciaux s'est fait sentir et de ce fait beaucoup d'études à grande èchelle ont été entreprises. La différence la plus évidente, entre les peaux ethniques, est leur couleur liée à la présence de la mélanine. La photoprotection induite par ce polymère influence le taux de vieillissement de la peau entre les différents groupes raciaux qui finalement sont tous sujets au processus de photovieillissement. Généralement, les caucasiens ont des signes plus précoces et plus importants de formation de rides et de relâchement de la peau; en général, les problèmes d'augmentation de la pigmentation sont observés sur les peaux de couleur, bien qu'une grande étude ait rapporté que des sujets originaires de l'Asie de l'Est vivant aux U.S.A. avaient le moins de taches pigmentaires. On pense que la réponse d'une induction hyperpigmentaire est due à un signal envoyé par le récepteur 2 activé par une protéase. Le récepteur 2 augmente en même temps que la protéase activatrice dans l'épiderme des sujets ayant une peau de couleur. Les changements dans les propriètés biophysiques de la peau en fonction de l'âge montrent que les sujets qui ont la pigmentation la plus sombre gardent une peau plus jeune par comparaison aux groupes qui possèdent une pigmentation moins forte. Toutefois, bien qu'ayant un stratum corneum plus compact, il existe des rapports divergents sur la fonction barrière de ces sujets. Dans le cas d'agression chimique ou mécanique, la fonction barrière du stratum corneum est considérée plus forte chez les sujets à peau plus foncée, malgré leurs taux plus faibles encéramide. On doit garder à l'esprit que la fonction barrière du stratum corneum dépend de toute son architecture et pas seulement de sa teneur en lipides. On considère que la peau asiatique à unePIE (TEWL) basale similaire à la peau caucasienne, ainsi que des taux en céramides comparables, mais on constate que dans le cas d'agression mécanique, elle possède un effet barrière le plus faible. Des différences dans la cohésion intercellulaire sont évidentes. A contrario, on a mis en évidence des taux d'hydratation (NMF) plus faibles dans son stratum corneum, comparativement à la peau caucasienne et afro-américaine. Ces différences expliquent les variations au niveau de la desquamation, mais on a très peu de données sur ce sujet. Une étude récente a mis en évidence des taux réduits de Cathepsin L2 dans l'épiderme des types de peau plus sombre, ce qui, si cela se produisait dans le stratum corneum, expliquerait les problèmes biens connus de cendrage de la peau que ces sujets connaissent. En terme très gènéral, étant donné que les enzymes liées à la desquamation sont libérées avec les granules lamellaires, on s'attend à ce que les sujets ayant des taux de lipides faibles dans le stratum corneum aient des taux d'enzymes liés à la desquamation faibles. On constate chez les sujets noirs une augmentation de la taille des pores, de la sécrétion du sébum et de la microflore cutanée. On observe également chez ces sujets une augmentation de la taille des granules mastocellulaires. Le phénomène de peau sensible se retrouve à une fréquence similaire dans les différents groupes raciaux, mais il existe des différences subtiles dans lesstimuli nécessaires pour l'induire. En tout cas, plusieurs études montrent que la peau asiatique est peut-être plus sensible aux produits chimiques exogènes, ce qui probablement est dûà un stratum corneum plus mince et à une densité de glandes eccrines plus élevées. En conclusion, c'est sur les caractéristiques biophysiques et somato-sensorielles des différents types de peaux ethniques que nous en savons plus, mais il est clair qu'il nous reste à comprendre encore beaucoup de choses principalement sur leurs différences biologiques. [source] Two cases of reactive perforating collagenosis arising at the site of healed herpes zosterINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 3 2001Hye Nam Lee MD Case 1 A 67-year-old South Korean woman presented with a painful eruption on the left trunk. Several groups of vesicles with an erythematous and edematous base were situated unilaterally within the distribution of the left T9 dermatome; they had been present for 7 days. A diagnosis of herpes zoster was made, and treatment with acyclovir, analgesics, tranquilizers, and wet dressings produced a moderate response. Two weeks after onset, the lesions appeared to have healed with a scar. Four months later, however, the patient noticed another eruption of papules in the postherpetic area (Fig. 1A,B). Figure 1. Case 1. (A) Multiple erythematous papules on the left trunk along the T9 dermatome. (B) Multiple erythematous papules with a keratotic central plug The biopsy specimen showed a cup-shaped epidermal invagination filled with a keratotic plug containing basophilic debris and collagen, with perforation of the epidermis. Masson's trichrome stain identified refractile fibers within the epidermis as hyalinized and degenerating collagen. Van Gieson staining for elastic fibers was negative in the epidermis and in the crater. These findings are consistent with reactive perforating collagenosis (RPC). Case 2 A 66-year-old South Korean woman developed herpes zoster of the left neck and shoulder, which resolved after an uncomplicated course. Two months later, a zosteriform, pink, papular eruption developed at the site of the resolved herpes zoster. Examination revealed multiple, erythematous papules with a central umbilication containing a firmly adherent keratotic plug on the left shoulder and neck (Fig. 2A). Figure 2. Case 2. (A) Multiple erythematous papules on the left neck and shoulder along the C4 dermatome. (B) Cup-shaped epidermal invagination filled with keratotic plug containing basophilic debris and degenerated collagen, with perforation of the epidermis (hematoxylin and eosin stain, ×,100) The biopsy specimen showed a dome-shaped lesion with a central crater that extended from the epidermis to the papillary dermis and contained degenerated collagen in vertical strands (Fig. 2B). [source] Molluscicides from some common medicinal plants of eastern Uttar Pradesh, IndiaJOURNAL OF APPLIED TOXICOLOGY, Issue 1 2010Sunil Kumar Singh Abstract Many aquatic snails act as intermediate hosts for the larvae of trematodes, Fasciola hepatica and Fasciola gigantica, which cause the diseases fascioliasis and schistosomiasis. The WHO has tested several thousands of synthetic compounds for the control of the snail host. Although effective, these molluscicides have so far not proved themselves to be entirely satisfactory. With a growing awareness of environmental pollution, efforts are being made to discover molluscicidal products of plant origin. Being products of biosynthesis, these are potentially biodegradable in nature. Several groups of compounds present in various plants have been found to be toxic to target organisms at acceptable doses ranging from <1 to 100,ppm. Common medicinal plants, i.e. Thevetia peruviana, Alstonia scholaris (Family; Apocynaceae), Euphorbia pulcherima and Euphorbia hirta (Family; Euphorbiaceae), have potent molluscicidal activity against freshwater snails. The toxicological actions of Thevetia peruviana may be due to the presence of apigenin-5-methyl ether (flavonoid) and triterpenoid glycosides, while a number of alkaloids (pseudo-akuammigine in addition to betulin, ursolic acid and ,-sitosterol), steroids and triterpenoids are present in Alstonia scholaris and the diterpenoids, pulcherrol, ,-sitosterol, hentriacontane, ellagic acid and ,-amyrin are present in Euphorbia hirta and in Euphorbia pulcherima. Although, at present very little literature is available on the control of vector snails through plant origin pesticides, an attempt has been made in this review to assemble all the known information on molluscicidal properties of common medicinal plants of eastern Uttar Pradesh, India, which might be useful for the control of harmful snails. Copyright © 2009 John Wiley & Sons, Ltd. [source] Treatment of alcoholic hepatitisJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 4 2002Jacquelyn J Maher Abstract, Alcoholic hepatitis is a common disease with an overall 1-year mortality of 20%. Although the classical treatment for alcoholic hepatitis is abstinence, in some individuals abstinence alone is inadequate to promote survival and recovery. This is particularly true of patients with severe alcoholic hepatitis, who are identified by jaundice, coagulopathy and neutrophilia. Within the last two decades, several agents have been examined as treatments for alcoholic hepatitis and cirrhosis. They have targeted several key processes in the pathophysiology of alcoholic liver disease, including hypermetabolism, inflammation, cytokine dysregulation and oxidant stress. The compounds that offer the greatest survival benefit to patients with severe alcoholic hepatitis are corticosteroids. Several groups have reported excellent results with corticosteroids, but positive results are not uniform, and there remains some controversy over their efficacy. Even if corticosteroids are beneficial for alcoholic hepatitis, they are not recommended for all patients at risk. Consequently, other agents are being tested that have broader applicability to individuals with contraindications to steroids. In this regard, pentoxifylline shows some promise, as does enteral feeding with medium chain triglycerides. Independent efforts are also being directed toward treatment of chronic alcoholic liver disease and alcoholic cirrhosis. Anti-oxidants have received the greatest attention; drugs such as S -adenosyl-methionine may be of benefit. This and others are under active study. © 2002 Blackwell Publishing Asia Pty Ltd [source] Allelic diversity associated with aridity gradient in wild emmer wheat populationsPLANT CELL & ENVIRONMENT, Issue 1 2008ZVI PELEG ABSTRACT The association between allelic diversity and ecogeographical variables was studied in natural populations of wild emmer wheat [Triticum turgidum ssp. dicoccoides (Körn.) Thell.], the tetraploid progenitor of cultivated wheat. Patterns of allelic diversity in 54 microsatellite loci were analyzed in a collection of 145 wild emmer wheat accessions representing 25 populations that were sampled across naturally occurring aridity gradient in Israel and surrounding regions. The obtained results revealed that 56% of the genetic variation resided among accessions within populations, while only 44% of the variation resided between populations. An unweighted pair-group method analysis (UPGMA) tree constructed based on the microsatellite allelic diversity divided the 25 populations into six major groups. Several groups were comprised of populations that were collected in ecologically similar but geographically remote habitats. Furthermore, genetic differentiation between populations was independent of the geographical distances. An interesting evolutionary phenomenon is highlighted by the unimodal relationship between allelic diversity and annual rainfall (r = 0.74, P < 0.0002), indicating higher allelic diversity in populations originated from habitats with intermediate environmental stress (i.e. rainfall 350,550 mm year,1). These results show for the first time that the ,intermediate-disturbance hypothesis', explaining biological diversity at the ecosystem level, also dominates the genetic diversity within a single species, the lowest hierarchical element of the biological diversity. [source] Optimization of an siRNA-expression system with an improved hairpin and its significant suppressive effects in mammalian cellsTHE JOURNAL OF GENE MEDICINE, Issue 7 2004Makoto Miyagishi Abstract Background RNA interference (RNAi) is a phenomenon in which expression of an individual gene can be specifically silenced by introducing a double-stranded RNA, one complementary to the gene, into cells. This phenomenon can be observed in mammalian cells when small interfering RNAs (siRNAs) are used, and is receiving attention as the most powerful tool for reverse genetics in the post genome era. Several groups have developed vector-based siRNA-expression systems that can induce RNAi in living cells. Methods We describe here a comparative analysis of various siRNA-expression systems, in which we examined the effects of stem length, loop sequence and insertion of mutation(s) and/or bulges in the stem sequence on silencing effects and on the stability of the vectors. Results As a result of the comparative analysis, we determined the following optimized siRNA-expression system: U6 promoter-driven hairpin-type dsRNA with 21-nt stem length, three to four mutations in the sense strand only, and the optimized 9-nt loop sequence, derived from microRNA. Moreover, we demonstrate that the siRNA-expression system with a tetracycline-regulated U6 promoter(s) could have the potential to control RNAi in cells, and that the HIV vector-mediated transfer of an siRNA-expression cassette into cells resulted in efficient silencing of a target gene at a multiplicity of infection as low as five. Conclusion The mutated hairpin siRNAs and their genetically stable coding vectors could be very useful for gene knockdown experiments, and could further benefit gene therapy using RNAi. Copyright © 2004 John Wiley & Sons, Ltd. [source] Identification and characterization of a new conserved motif within the presequence of proteins targeted into complex diatom plastidsTHE PLANT JOURNAL, Issue 2 2005Oliver Kilian Summary Several groups of algae evolved by secondary endocytobiosis, which is defined as the uptake of a eukaryotic alga into a eukaryotic host cell and the subsequent transformation of the endosymbiont into an organelle. Due to this explicit evolutionary history such algae possess plastids that are surrounded by either three or four membranes. Protein targeting into plastids of these organisms depends on N-terminal bipartite presequences consisting of a signal and a transit peptide domain. This suggests that different protein targeting systems may have been combined during establishment of secondary endocytobiosis to enable the transport of proteins into the plastids. Here we demonstrate the presence of an apparently new type of transport into diatom plastids. We analyzed protein targeting into the plastids of diatoms and identified a conserved amino acid sequence motif within plastid preprotein targeting sequences. We expressed several diatom plastid presequence:GFP fusion proteins with or without modifications within that motif in the diatom Phaeodactylum tricornutum and found that a single conserved phenylalanine is crucial for protein transport into the diatom plastids in vivo, thus indicating the presence of a so far unknown new type of targeting signal. We also provide experimental data about the minimal requirements of a diatom plastid targeting presequence and demonstrate that the signal peptides of plastid preproteins and of endoplasmic reticulum-targeted preproteins in diatoms are functionally equivalent. Furthermore we show that treatment of the cells with Brefeldin A arrests protein transport into the diatom plastids suggesting that a vesicular transport step within the plastid membranes may occur. [source] Development of Mechanical Circulatory Support Devices in ChinaARTIFICIAL ORGANS, Issue 11 2009Wei Wang Abstract Myocardial dysfunction leading to low cardiac output syndrome is a common clinical pathophysiological state. Currently, the use of mechanical circulatory support (MCS) is an essential aspect of the treatment of patients with cardiac failure. Several groups in China are engaged in the design and development of MCS devices. These devices can be classified as pulsatile, rotary, and total artificial heart (TAH). There are two types of pulsatile pump, which are driven by air (pneumatic). One of these pumps, the Luo-Ye pump, has been used clinically for short-term support since 1998. The other is a push-plate left ventricular device, which has a variable rate mode. Various rotary devices are classified into axial and centrifugal pumps, depending on the impeller geometry. Most rotary pumps are based on the maglev principle, and some types have been used clinically. Others are still being studied in the laboratory or in animal experiments. Furthermore, certain types of total implantable pump, such as the UJS-III axial pump and the UJS-IV aortic valvo-pump, have been developed. Only one type of TAH has been developed in China. The main constituents of this artificial heart are two axial pumps, two reservoir tanks mimicking the right and left atria, flow meters, two pressure gauges, and a resistance adaptor. Although the development of mechanical assist devices in China is still in a nascent stage, a number of different types of MCS devices are currently being studied. [source] Immunohistochemical expression of vascular endothelial growth factor, matrix metalloproteinase 2, and matrix metalloproteinase 9 in cutaneous melanocytic lesionsCANCER, Issue 9 2002M.D., Oriana Simonetti Ph.D. Abstract BACKGROUND Vascular endothelial growth factor (VEGF), an endothelial cell mitogen, plays a hierarchical role in regulating physiologic and pathologic angiogenesis. Moreover, the transformation from noninvasive to invasive carcinomas is accompanied by focal disruption and discontinuity of the basement membrane. Several groups of proteases have been implicated in tumor cell invasion, including the 72-kDa gelatinase A/Type IV collagenase (matrix metalloproteinase 2 [MMP-2]) and the 92-kDa gelatinase B/Type IV collagenase (MMP-9). METHODS The authors assessed the immunohistochemical expression of VEGF and metalloproteinases MMP-2 and MMP-9 in paraffin embedded biopsy specimens of malignant melanomas (18 invasive melanomas and 10 in situ melanomas); dysplastic nevi with architectural disorder and cytologic atypia of melanocytes; Spitz nevi; and compound or predominantly intradermal, ordinary, benign melanocytic nevi. RESULTS Strong cytoplasmic staining for VEGF was observed in melanoma cells in as many as 77% of primary invasive melanomas, whereas only 25% of the in situ melanomas exhibited a detectable immunoreactivity for VEGF. It is interesting to note that no immunoreactivity was shown by any nevi; Spitz nevi, in particular, showed negative immunoreactivity to VEGF. Invasive melanomas and in situ melanomas displayed coexpression of MMP-2 and MMP-9, although to a variable extent. In particular, high MMP-2 staining was observed in 14 of 18 invasive melanomas; moreover, strong MMP-2 expression also was observed in 60% of in situ melanomas, whereas the residual 40% of those melanomas showed a moderate level of positivity. CONCLUSIONS On the basis of the current data showing that malignant melanocytic tumors displayed strong VEGF expression, whereas benign melanocytic proliferations showed no immunoreactivity for VEGF, VEGF also may be used as a discriminating factor to distinguish malignant melanoma from lesions of uncertain histology. Cancer 2002;95:1963,70. © 2002 American Cancer Society. DOI 10.1002/cncr.10888 [source] Haplotypes of the interleukin-4 receptor , chain gene associate with susceptibility to and severity of atopic asthmaCLINICAL & EXPERIMENTAL ALLERGY, Issue 10 2004A.-M. Hytönen Summary Background Development of asthma is likely to depend on a complex interaction between environmental and genetic factors. Several groups have suggested the gene of the IL-4 receptor , chain (IL4R) as a candidate gene for the development of asthma, although association with single polymorphisms has shown contradicting results. Objective We chose to analyse IL4R gene haplotypes and assess their possible relevance in susceptibility to asthma and to certain clinical phenotypes. Methods IL4R gene haplotypes were analysed, based on the three markers C-3223T, Q551R and I50V, using the expectation,maximization algorithm, in 170 atopic asthma patients and 350 controls, all adult Swedish Caucasians. Results Our data showed significantly higher levels of soluble IL-4R (sIL-4R) in asthma patients compared with controls (P<0.0001). Furthermore, we showed a significant association between the IL4R haplotype containing the alleles T-3223, V50 and R551 (TVR) of the IL4R gene, and susceptibility to atopic asthma, with a frequency of 6.5% in the patients compared with 1% in the controls (P<0.0005). A subgroup of patients with heterozygous or homozygous state for the T-3223, V50 and R551 alleles, also had lower levels of sIL-4R in their circulation compared with patients with homozygous state in the C-3223, I50 and Q551 alleles (P<0.05) and showed less severe asthma according to lung function test (P<0.05). Analysis of single markers showed the T-3223 IL4R allele to associate with lower serum levels of sIL-4 receptor (P<0.0001) and patients carrying the T allele also had more symptoms of active asthma (wheezing, P<0.01; coughing, P<0.05 and breathing difficulties, P<0.01). Conclusion Our data suggest that asthmatic patients with low levels of sIL-4 receptor may represent a genetically distinct subgroup of atopic asthma. TVR haplotype analyses confirm the importance of IL4R as a candidate gene for susceptibility to asthma. This finding may have implications for the understanding of the pathogenesis of asthma and possibly for the development of more specific therapies. [source] Nucleic acid sensing receptors in systemic lupus erythematosus: development of novel DNA- and/or RNA-like analogues for treating lupusCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 2 2010P. Lenert Summary Double-stranded (ds) DNA, DNA- or RNA-associated nucleoproteins are the primary autoimmune targets in SLE, yet their relative inability to trigger similar autoimmune responses in experimental animals has fascinated scientists for decades. While many cellular proteins bind non-specifically negatively charged nucleic acids, it was discovered only recently that several intracellular proteins are involved directly in innate recognition of exogenous DNA or RNA, or cytosol-residing DNA or RNA viruses. Thus, endosomal Toll-like receptors (TLR) mediate responses to double-stranded RNA (TLR-3), single-stranded RNA (TLR-7/8) or unmethylated bacterial cytosine (phosphodiester) guanine (CpG)-DNA (TLR-9), while DNA-dependent activator of IRFs/Z-DNA binding protein 1 (DAI/ZBP1), haematopoietic IFN-inducible nuclear protein-200 (p202), absent in melanoma 2 (AIM2), RNA polymerase III, retinoic acid-inducible gene-I (RIG-I) and melanoma differentiation-associated gene 5 (MDA5) mediate responses to cytosolic dsDNA or dsRNA, respectively. TLR-induced responses are more robust than those induced by cytosolic DNA- or RNA- sensors, the later usually being limited to interferon regulatory factor 3 (IRF3)-dependent type I interferon (IFN) induction and nuclear factor (NF)-,B activation. Interestingly, AIM2 is not capable of inducing type I IFN, but rather plays a role in caspase I activation. DNA- or RNA-like synthetic inhibitory oligonucleotides (INH-ODN) have been developed that antagonize TLR-7- and/or TLR-9-induced activation in autoimmune B cells and in type I IFN-producing dendritic cells at low nanomolar concentrations. It is not known whether these INH-ODNs have any agonistic or antagonistic effects on cytosolic DNA or RNA sensors. While this remains to be determined in the future, in vivo studies have already shown their potential for preventing spontaneous lupus in various animal models of lupus. Several groups are exploring the possibility of translating these INH-ODNs into human therapeutics for treating SLE and bacterial DNA-induced sepsis. [source] Trade-Offs between Species Conservation and the Size of Marine Protected AreasCONSERVATION BIOLOGY, Issue 1 2010P. M. CHITTARO áreas marinas protegidas; conservación de la biodiversidad; relaciones especies,área Abstract:,Moving from single-species- to ecosystem-based management requires an understanding of how community-level attributes such as diversity change with area. We used survey data from bottom trawls to examine spatial patterns of species richness in U.S. Pacific coastal fishes. Specifically, we generated and compared species,area relationships (SARs) for species classified into several groups on the basis of maximum body size, trophic level, diet, maximum depth, geographic affinity, and taxonomic order. Because SARs among groups were not parallel and z values varied significantly for several groups, groups of species were under- or overrepresented (depending on the size of the area) relative to their proportions in the entire community (i.e., entire U.S. Pacific coast). In this way, differences in SARs help demonstrate trade-offs between species representation and coastal area and suggest strategies (such as targeting the protection of habitats and locations where a particular species or groups of species are maximized) that may minimize the size of marine protected areas (MPAs) but protect diversity at the level of the community and functional group. Resumen:,El traslado del manejo de una sola especie al manejo basado en ecosistemas requiere del entendimiento de los cambios en atributos de la comunidad como el cambio de diversidad con el área. Utilizamos datos de muestreo de redes de arrastre para examinar patrones espaciales de la riqueza de especies en peces costeros del Pacífico en E. U. A. Específicamente, generamos y comparamos relaciones especies,área (REAs) para especies clasificadas en varios grupos con base en la talla máxima, nivel trófico, profundidad máxima, afinidad geográfica y orden taxonómico. Debido a que las REAs entre grupos no fueron paralelas y que los valores de z variaron significativamente para varios grupos, los grupos de especies estuvieron sub- o sobre- representados (dependiendo del tamaño del área) en relación con sus proporciones en toda la comunidad (i.e., toda la costa del Pacífico en E. U. A.). De esta manera, las diferencias en REAs ayudan a demostrar el balance entre la representación de especies y el área costera y sugieren estrategias (como la protección de hábitats y localidades donde se maximiza una especie o grupo de especies) que pueden minimizar el tamaño de áreas marinas protegidas pero proteger la diversidad al nivel de la comunidad y grupo funcional. [source] Arnold Heller and the lymph pumpACTA PHYSIOLOGICA, Issue 3 2005K. Aukland Abstract This article reviews studies on lymph propulsion in the lymph vessels by active contraction of the vessels, first described by Arnold Heller in 1869 in German language, and here translated into English. His observations were first confirmed by Beatrice Carrier (1926) and Howard Flory et al. (1927), and several groups were active up to World war II. Few publications appeared in the period 1940--1960, followed by increasing activity and development of new experimental techniques for use both in various experimental animals and in humans. Recently it has been shown that passive lymph flow may add to active propulsion. Both mechanisms depend on lymph formation, i.e. the uptake of interstitial fluid by the initial lymph vessels which is still not well understood. [source] Novel genes involved in Ciona intestinalis embryogenesis: Characterization of gene knockdown embryosDEVELOPMENTAL DYNAMICS, Issue 7 2007Mayuko Hamada Abstract The sequenced genome of the urochordate ascidian Ciona intestinalis contains nearly 2,500 genes that have vertebrate homologues, but their functions are as yet unknown. To identify novel genes involved in early chordates embryogenesis, we previously screened 200 Ciona genes by knockdown experiments using specific morpholino oligonucleotides and found that suppression of the translation of 40 genes caused embryonic defects (Yamada et al. [2003] Development 130:6485,6495). We have since examined an additional 304 genes, that is, screening 504 genes overall, and a total of 111 genes showed morphological defects when gene function was suppressed. We further examined the role of these genes in the differentiation of six major tissues of the embryo: endoderm, muscle, epidermis, neural tissue, mesenchyme, and notochord. Based on the similarity of phenotypes of gene knockdown embryos, genes were categorized into several groups, with the suggestion that the genes within a given group are involved in similar developmental processes. For example, five were shown to be novel genes that are likely involved in ,-catenin,mediated endoderm formation. The type of large-scale screening used is, therefore, a powerful approach to identify novel genes with significant developmental functions, the details of which will be determined in future studies. Developmental Dynamics 236:1820,1831, 2007. © 2007 Wiley-Liss, Inc. [source] Ecological control analysis: being(s) in control of mass flux and metabolite concentrations in anaerobic degradation processesENVIRONMENTAL MICROBIOLOGY, Issue 2 2007Wilfred F. M. Röling Summary Identification of the functional groups of microorganisms that are predominantly in control of fluxes through, and concentrations in, microbial networks would benefit microbial ecology and environmental biotechnology: the properties of those controlling microorganisms could be studied or monitored specifically or their activity could be modulated in attempts to manipulate the behaviour of such networks. Herein we present ecological control analysis (ECA) as a versatile mathematical framework that allows for the quantification of the control of each functional group in a microbial network on its process rates and concentrations of intermediates. In contrast to current views, we show that rates of flow of matter are not always limited by a single functional group; rather flux control can be distributed over several groups. Also, control over intermediate concentrations is always shared. Because of indirect interactions, through other functional groups, the concentration of an intermediate can also be controlled by functional groups not producing or consuming it. Ecological control analysis is illustrated by a case study on the anaerobic degradation of organic matter, using experimental data obtained from the literature. During anaerobic degradation, fermenting microorganisms interact with terminal electron-accepting microorganisms (e.g. halorespirers, methanogens). The analysis indicates that flux control mainly resides with fermenting microorganisms, but can shift to the terminal electron-accepting microorganisms under less favourable redox conditions. Paradoxically, halorespiring microorganisms do not control the rate of perchloroethylene and trichloroethylene degradation even though they catalyse those processes themselves. [source] ENVIRONMENTAL NICHE EQUIVALENCY VERSUS CONSERVATISM: QUANTITATIVE APPROACHES TO NICHE EVOLUTIONEVOLUTION, Issue 11 2008Dan L. Warren Environmental niche models, which are generated by combining species occurrence data with environmental GIS data layers, are increasingly used to answer fundamental questions about niche evolution, speciation, and the accumulation of ecological diversity within clades. The question of whether environmental niches are conserved over evolutionary time scales has attracted considerable attention, but often produced conflicting conclusions. This conflict, however, may result from differences in how niche similarity is measured and the specific null hypothesis being tested. We develop new methods for quantifying niche overlap that rely on a traditional ecological measure and a metric from mathematical statistics. We reexamine a classic study of niche conservatism between sister species in several groups of Mexican animals, and, for the first time, address alternative definitions of "niche conservatism" within a single framework using consistent methods. As expected, we find that environmental niches of sister species are more similar than expected under three distinct null hypotheses, but that they are rarely identical. We demonstrate how our measures can be used in phylogenetic comparative analyses by reexamining niche divergence in an adaptive radiation of Cuban anoles. Our results show that environmental niche overlap is closely tied to geographic overlap, but not to phylogenetic distances, suggesting that niche conservatism has not constrained local communities in this group to consist of closely related species. We suggest various randomization tests that may prove useful in other areas of ecology and evolutionary biology. [source] Miniaturization of Fluorescence Microscopes Using Fibre OpticsEXPERIMENTAL PHYSIOLOGY, Issue 6 2002Fritjof Helmchen In both medical research and diagnostics characterization of biological tissue on the cellular level relies on high-resolution optical microscopy. In most cases, however, tissue is excised for microscopic investigation, in part because conventional microscopes are bulky instruments. Imaging of cells in the intact living organism has been difficult. Over the last decade several groups have developed miniature confocal microscopes that use fibre optics to deliver light to the specimen and to measure either reflected or excited fluorescence light. In addition, two-photon excitation recently has been employed in a small portable ,fibrescope'. A potential clinical application of these microscope probes is their endoscopic use for optical biopsy of inner organs or guidance of conventional biopsy. As a mobile research tool they may permit imaging of neuronal activity in the brain of awake, behaving animals. Here, we review technological approaches to build miniaturized fluorescence microscopes and discuss their potential applications. [source] Deconstructing language by comparative gene expression: from neurobiology to microarrayGENES, BRAIN AND BEHAVIOR, Issue S1 2006M. C. Oldham Language is a defining characteristic of our species that has emerged quite recently on an evolutionary timescale. Understanding the neurobiological substrates and genetic underpinnings of language constitutes a basic challenge for both neuroscience and genetics. The functional localization of language in the brain has been progressively refined over the last century through studies of aphasics and more recently through neuroimaging. Concurrently, structural specializations in these brain regions have been identified by virtue of their lateralization in humans and also through comparisons with homologous brain regions in non-human primate species. Comparative genomics has revealed the genome of our closest living relative, the chimpanzee, to be astonishingly similar to our own. To explore the role that changes in the regulation of gene expression have had in recent human evolution, several groups have used microarrays to compare expression levels for thousands of genes in the brain between humans and chimpanzees. By applying this approach to the increasingly refined peri-sylvian network of brain regions involved in language, it may be possible to discern functionally significant changes in gene expression that are universal among humans but unique to our species, thus casting light on the molecular basis of language in the brain. [source] Threshold Voltage Shifts in Organic Thin-Film Transistors Due to Self-Assembled Monolayers at the Dielectric SurfaceADVANCED FUNCTIONAL MATERIALS, Issue 6 2009Stefan K. Possanner Abstract Recently, it has been shown by several groups that the electrical characteristics of organic thin-film transistors (OTFTs) can be significantly influenced by depositing self-assembled monolayers (SAMs) at the organic semiconductor/dielectric interface. In this work, the effect of such SAMs on the transfer characteristics and especially on the threshold voltage of OTFTs is investigated by means of two-dimensional drift-diffusion simulations. The impact of the SAM is modeled either by a permanent space charge layer that can result from chemical reactions with the active material, or by a dipole layer representing an array of ordered dipolar molecules. It is demonstrated that, in both model cases, the presence of the SAM significantly changes the transfer characteristics. In particular, it gives rise to a modified, effective gate voltage Veff that results in a rigid shift of the threshold voltage, ,Vth, relative to a SAM-free OTFT. The achievable amount of threshold voltage shift, however, strongly depends on the actual role of the SAM. While for the investigated device dimensions, an organic SAM acting as a dipole layer can realistically shift the threshold voltage only by a few volts, the changes in the threshold voltage can be more than an order of magnitude larger when the SAM leads to charges at the interface. Based on the analysis of the different cases, a route to experimentally discriminate between SAM-induced space charges and interface dipoles is proposed. The developed model allows for qualitative description of the behavior of organic transistors containing reactive interfacial layers; when incorporating rechargeable carrier trap states and a carrier density-dependent mobility, even a quantitative agreement between theory and recent experiments can be achieved. [source] IBD international genetics consortium: International cooperation making sense of complex diseaseINFLAMMATORY BOWEL DISEASES, Issue 3 2003Juleen A. Cavanaugh Ph.D. Abstract The Inflammatory Bowel Disease International Genetic Consortium was formed in Oxford in 1997. Since then it has grown to include twelve groups from around the world that are each actively involved in identifying the genes that are involved in susceptibility to IBD. The approach of the IBDIGC is to attempt to overcome one of the major issues in complex disease analysis,that of obtaining sufficient power to analyze successfully the inheritance of IBD,by collaboratively studying large numbers of well documented families with multiple affected individuals. This strategy has been marked by considerable success with the publication of a paper authored by the IBDIGC substantiating the localization of IBD1 to chromosome 16. This publication served to encourage researchers and eventually resulted in the identification by several groups simultaneously of risk alleles in the NOD2 gene that cosegregate with disease. The IBDIGC provides a model for studies in complex disease genetics, showing that research groups both large and small can participate equally in complex disease gene identification through the formation of large international consortia. [source] Deep into the Shinnyo Spiritual WorldINTERNATIONAL JOURNAL OF JAPANESE SOCIOLOGY, Issue 1 2001Akira Kawabata "Shinnyo-en" (Garden of the Truth) is one of the most famous religious groups in Japan today. But outside Shinnyo-en it is difficult to understand Shinnyo teaching. By focusing on the words from interviews, this article depicts its spiritual world and analyzes the function of its spiritual power on interviewees. The believers' narrative is interpreted from a sociological perspective using computer-aided qualitative data analysis and a life history approach. The computer-aided coding method is found to be an effectual means to discover significant factors in Shinnyo teachings. This method has four steps: (1) interview transcripts are input in ASCII format in several groups according to the time we interviewed; (2) KT2 system, a set of programs for computerized content analysis, disaggregates the transcripts into words to which I assign codes; (3) the codes are integrated into several meaningful categories for a cross-tabular examination of two variables, times and categories; (4) a contour map made from the cross-table helps to grasp the significance of the categories and their relations in a life history. This procedure enables us to understand the significance of the "self", and the transformation of the "self" according to the time flows. The contour map of the belief commands a panoramic view of Shinnyo teaching. From this point of view we can scrutinize the interview data and describe the Shinnyo spiritual world as it is understood. [source] Theory of chemical bonds in metalloenzymes XIII: Singlet and triplet diradical mechanisms of hydroxylations with iron-oxo species and P450 are revisitedINTERNATIONAL JOURNAL OF QUANTUM CHEMISTRY, Issue 15 2009Kizashi Yamaguchi Abstract Electronic structures of the Compound I (CpdI) in P450 are investigated on the basis of spin coupling forms of iron-oxo (Fe(IV)O) cores and radical ligand (,L) groups to generalize previous singlet and triplet diradical (TD) mechanisms for oxygenations of alkanes with Fe( IV)O. Orbital interaction schemes for four lower-lying spin configurations of CpdI with HC bond of substrate are examined to elucidate how magnetic coupling modes correlate with radical reaction pathways for hydroxylation reactions on the basis of the broken symmetry (BS) molecular orbital (MO) model. The configuration correlation diagrams for the four configurations model are depicted on the basis of the isoelectronic analogy among O, O2, and Fe( IV)O, in addition to Coulomb exchange energy on the iron site, which determines its local spin configuration. Important role of ligand spin (,L) of CpdI for regulation of hydroxylation mechanisms is clarified with the aid of the spin coupling forms. Transition states for one quartet and three doublet configurations under the BS MO approximation are examined on the basis of potential curve crossings along reaction pathways. The four transition structures and corresponding radical intermediates for methane and trimethyl methane with CpI are located by the BS hybrid Kohn,Sham density functional theory (DFT) (B3LYP) method to confirm the orbital interaction schemes. Spin density populations obtained by the BS B3LYP calculations are found to be consistent with the theoretical predictions based on the four configurations model. The configuration and state correlation diagrams by BS B3LYP before and after spin projection are also consistent with the BS MO interaction schemes, which provide local SD and TD mechanisms of hydroxylation with CpdI. The present BS MO-theoretical framework is useful for systematic understanding of a lot of recent BS hybrid DFT computational results for hydroxylation reactions with CpdI and configuration correlation diagrams reported by several groups. Implications of the present theoretical and computational results are discussed in relation to several experimental characteristics of hydroxylation reactions with iron-oxo species and P450. © 2009 Wiley Periodicals, Inc. Int J Quantum Chem, 2009 [source] Does Unrealistic Optimism Change Following a Negative Experience?,JOURNAL OF APPLIED SOCIAL PSYCHOLOGY, Issue 6 2001Frank P. Mkenna One important counteracting force that may decrease the effects of unrealistic optimism is personal experience with threat. To examine this hypothesis, several groups were examined who had been exposed to varying degrees of threat. It was found that only those who had been exposed to the most severe threat (being hospitalized after a road accident) showed differential comparative risk estimates from those who had experienced no threat. Differences between these two groups were also found for their self-reported risk behavior. The generality of the debiasing effect was assessed by examining risk perceptions in other domains. It was found that the effect was domain specific. [source] The classic receptor for 1,,25-dihydroxy vitamin D3 is required for non-genomic actions of 1,,25-dihydroxy vitamin D3 in osteosarcoma cellsJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 4 2006Soraya Bravo Abstract 1,,25-dihydroxy vitamin D3 has a major role in the regulation of the bone metabolism as it promotes the expression of key bone-related proteins in osteoblastic cells. In recent years it has become increasingly evident that in addition to its well-established genomic actions, 1,,25-dihydroxy vitamin D3 induces non-genomic responses by acting through a specific plasma membrane-associated receptor. Results from several groups suggest that the classical nuclear 1,,25-dihydroxy vitamin D3 receptor (VDR) is also responsible for these non-genomic actions of 1,,25-dihydroxy vitamin D3. Here, we have used siRNA to suppress the expression of VDR in osteoblastic cells and assessed the role of VDR in the non-genomic response to 1,,25-dihydroxy vitamin D3. We report that expression of the classic VDR in osteoblasts is required to generate a rapid 1,,25-dihydroxy vitamin D3-mediated increase in the intracellular Ca2+ concentration, a hallmark of the non-genomic actions of 1,,25-dihydroxy vitamin D3 in these cells. J. Cell. Biochem. 99: 995,1000, 2006. © 2006 Wiley-Liss, Inc. [source] Personal imports of drugs to Japan in 2005 , an analysis of import certificatesJOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 5 2008K. Tsuji MS Summary Background:, Personal imports of unapproved drugs are made by physicians and patients in Japan. Such imports require submission of a request for an import certificate from the Regional Bureau of Health and Welfare (RBHW). So far, there have been few reports on personal imports of drugs in Japan. Objective:, To assess the extent and nature of personal imports of drugs in Japan. Methods:, The date, product name and amount of drug imported were provided by RBHW for each personal import made by physicians in 2005. All imports were classified into several groups including whether they were for ,prescription drugs for non-cosmetic use (PDNC)' or ,prescription drugs for cosmetic use (PDC)'. Identification of PDNC was made by International Non-proprietary Name (INN). All drugs were classified under therapeutic groups. For the most frequently imported unapproved drugs, the approval year in the US/EU and development status in Japan were recorded. Results:, A total of 12 196 personal imports were initiated by physicians in 2005. 5428 were for PDNCs corresponding to 242 drugs by INN. 55 PDNCs were each the subject of 10 or more imports. 11 drugs (252 imports) out of the top 55 PDNCs were available on the Japanese market during 2005 and 44 (4713 imports) were not approved. Of the 44 unapproved drugs, 11 (1019 imports) had been approved and 10 (2785 imports) were in the pre-registration phase as of December 31, 2006. Of the 44 unapproved drugs, 12 (1213 imports) were approved during 2000,2004, and 17 (3138 imports), during 1995,1999 in the US or EU. While the majority of imported drugs were antineoplastic drugs, drugs for various kinds of non-serious diseases were also imported. Conclusions:, A substantial number of unapproved drugs were being imported to Japan. A formal system for monitoring the use of those drugs should be established. [source] Psychotherapeutic case conceptualization using plan analysis for bipolar affective disorder,JOURNAL OF CLINICAL PSYCHOLOGY, Issue 4 2009Ueli Kramer Abstract Valid individualized case conceptualization methodologies, such as plan analysis, are rarely used for the psychotherapeutic treatment conceptualization and planning of bipolar affective disorder (BD), even if data do exist showing that psychotherapy interventions might be enhanced by applying such analyses for treatment planning for several groups of patients. We applied plan analysis as a research tool (Caspar, 1995) to N=30 inpatients presenting BD, who were interviewed twice. Our study aimed at producing a prototypical plan structure encompassing the most relevant data from the 30 individual case conceptualizations. Special focus was given to links with emotions and coping plans. Inter-rater reliability of these plan analyses was considered sufficient. Results suggest the presence of two subtypes based on plananalytic principles: emotion control and relationship control, along with a mixed form. These subtypes are discussed with regard to inherent plananalytic conflicts, specific emotions and coping plans, as well as symptom level and type. Finally, conclusions are drawn for enhancing psychotherapeutic practice with BD patients, based on the motive-oriented therapeutic relationship. © 2009 Wiley Periodicals, Inc. J Clin Psychol 65: 1,16, 2009. [source] | |||||||||||||||||||||||||||||||||||||||||||