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Additional Approach (additional + approach)
Selected AbstractsEngineering therapeutic monoclonal antibodiesIMMUNOLOGICAL REVIEWS, Issue 1 2008Xiao-yun Liu Summary: During last two decades, the chimerization and humanization of monoclonal antibodies (mAbs) have led to the approval of several for the treatment of cancer, autoimmune diseases, and transplant rejection. Additional approaches have been used to further improve their in vivo activity. These include combining them with other modalities such as chemotherapy and redesigning them for improved pharmacokinetics, effector function, and signaling activity. The latter has taken advantage of new insights emerging from an increased understanding of the cellular and molecular mechanisms that are involved in the interaction of immunoglobulin G with Fc receptors and complement as well as the negative signaling resulting from the hypercrosslinking of their target antigens. Hence, mAbs have been redesigned to include mutations in their Fc portions, thereby endowing them with enhanced or decreased effector functions and more desirable pharmacokinetic properties. Their valency has been increased to decrease their dissociation rate from cells and enhance their ability to induce apoptosis and cell cycle arrest. In this review we discuss these redesigned mAbs and current data concerning their evaluation both in vitro and in vivo. [source] Origin and phylogeny of Guyniidae (Scleractinia) in the light of microstructural dataLETHAIA, Issue 1 2000Jaros, aw Stolarski The set of skeletal characters of the Recent azooxanthellate coral Guynia annulata Duncan, 1872 is unique among extant scleractinians and encompasses: (a) undifferentiated septal calcification centers (in most extant scleractinians calcification centers are clearly separated); (b) completely smooth septal faces (septa of almost all extant scleractinians bear granular ornamentation); (c) deeply recessed septa in respect to the epithecal rim in the adult coralla (in adults of the majority of extant scleractinians the relationships between septa and wall are the reverse); and (d) an aseptal part of the initial ontogenetic stage, just above the basal plate (almost all known scleractinians have a septate initial coralla). Skeletal features of five other extant traditional guyniids are typical of other caryophylliines (and of Scleractinia). However, the wall types present in different species of traditional guyniids exceed limits traditionally attributed to one caryophylliine family: i.e., Stenocyathus and Truncatoguynia have a marginothecal wall like the Flabellidae, whereas Schizocyathus and Temnotrochus usually have an entirely epithecal wall, as in Gardineriidae (Volzeioidea). Moreover, Pourtalocyathus and Schizocyathus show intraspecific variation in distribution of septal calcification centers (separated vs. non-separated) and in wall types (epithecal vs. consisting of large spherulite-like bodies). These major differences in skeletal architecture form the basis for a new, threefold taxonomical subdivision of the traditional guyniids: (1) Guyniidae Hickson, 1910, containing only monospecific Guynia with an epithecal wall, and septa with non-separated calcification centers; (2) Schizocyathidae fam.n., groups Microsmilia Schizocyathus, Pourtalocyathus, Temnotrochus, which have an epithecal wall and septa with usually well-separated calcification centers; and (3) Stenocyathidae fam.n. with Stenocyathus and Truncatoguynia which have a marginothecal wall and septa with well-separated calcification centers. Despite differences in the basic architecture of the skeleton, all taxa attributed to these families have ,thecal pores' formed by selective dissolution of the skeleton. I propose two hypotheses for evolutionary relationships among Guyniidae, Schizocyathidae, and Stenocyathidae: (1) Hypothesis A: the three families are not phylogenetically related and ,pores' originated independently in different scleractinian lineages: e.g., Guyniidae may represent distant zardinophyllid or gigantostyliid descendants, Schizocyathidae may be a volzeioid offshoot, whereas Stenocyathidae may be a flabellid descendant; (2) Hypothesis B: the three families are phylogenetically related and ,thecal pores' are synapomorphic for the clade (superfamily Guynioidea). Additional approaches, such as anatomical observations, molecular studies on guyniid DNA sequences, and in-depth studies on scleractinian biomineralization will be necessary to test these hypotheses. [source] MOLECULAR AND PHYLOGENETIC CHARACTERIZATION OF PHORMIDIUM SPECIES (CYANOPROKARYOTA) USING THE CPCB-IGS-CPCA LOCUS,JOURNAL OF PHYCOLOGY, Issue 1 2005Ivanka Teneva The accurate determination of species of Cyanoprokaryota/Cyanophyceae has many important applications. These include the assessment of risk with regard to blooms in water reservoirs as well as the identification of species capable of producing valuable bioactive compounds. Commonly, Cyanoprokaryota are classified based on their morphology. However, morphological criteria are not always reliable because they may change, for example, due to environmental factors. Thus, genetic and molecular analyses are a promising additional approach, but their application has so far been limited to relatively few genera. In light of this, we present here the first characterization of species and strains of the genus Phormidium Kütz. based on the cpcB-IGS-cpcA locus of the phycocyanin operon. In phylogenetic analyses using deduced amino acid sequences of the cpcB-cpcA regions, Phormidium was found to be polyphyletic. This analysis appeared to be dominated by the cpcB region, which is characterized by a relatively high percentage of informative substitutions. The percentage of variable positions within the cpcB-IGS-cpcA locus overall was 16.5%, thereby indicating a level of divergence remarkably higher than that reported for Nodularia and Arthrospira in previous studies relying on cpcB-IGS-cpcA. Further, alignment of informative nucleotide substitutions in the cpcB-IGS-cpcA sequences revealed a mosaic distribution, which may be indicative of genetic recombination events. Finally, the length and sequences of the IGS region alone proved useful as markers to differentiate the cyanobacterial genus Phormidium. However, whether the IGS region per se is sufficiently discriminatory to differentiate between Phormidium species or even strains requires further investigation using newly identified Phormidium sequence data. [source] Automutanolysin disrupts clinical isolates of cariogenic streptococci in biofilms and planktonic cellsMOLECULAR ORAL MICROBIOLOGY, Issue 6 2009P. Thanyasrisung Introduction:, Dental caries remains one of the most common chronic infectious diseases throughout the world. The formation of dental plaque is one of the caries risk factors. As a consequence, the removal of plaque may reduce the incidence of caries development. We identified an autolysin produced by Streptococcus mutans named auto-mutanolysin (Aml). Aml selectively lyses S. mutans and Streptococcus sobrinus. The specificity towards these cariogenic bacteria suggests that Aml may be used to prevent dental caries. Here, with the aim towards therapeutic application, we investigated the lytic activity of Aml against clinical isolates of S. mutans and S. sobrinus using planktonic cells and biofilms. Methods:, Planktonic cell suspensions and biofilms of clinically isolated streptococci were treated with Aml in the absence or the presence of Triton X-100. The lytic activity of Aml was monitored as the change in turbidity. The disruption of biofilms was evaluated by detecting the released DNA by polymerase chain reaction and observing the alteration of optical density of treated biofilms. Results:, Triton X-100 enhances the lytic ability of Aml. Using planktonic cells, Aml had various lysis levels against clinical strains. Repeated Aml treatment showed disruption of the biofilm using the representative clinical strains. Conclusion:, Our study demonstrates that Aml has an ability to lyse planktonic and biofilm cells of clinically isolated mutans streptococci in the presence of Triton X-100. These results suggest the possibility of using Aml as an alternative or additional approach for caries prevention. [source] CAN WE DIFFERENTIATE BETWEEN AIRWAY AND VASCULAR SMOOTH MUSCLE?CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 11 2004Darren J Fernandes SUMMARY 1.,Airway smooth muscle (ASM) has recently been termed the ,frustrated' cell of the lung given that contraction of ASM has no proven useful physiological function in adults and yet is indelibly associated with pathological conditions by virtue of its unwanted airflow-limiting actions in asthma. In contrast, pulmonary vascular smooth muscle contraction plays an essential role in the control of blood flow through the lung. 2.,Little is known of the differences in phenotype between human ASM and pulmonary vascular smooth muscle (VSM) tissues, but differences in contractile protein and transcription factor expression and regulation of contractile protein promoter activity have been documented. Similarly, the embryological signals in mice required for differentiation of ASM versus pulmonary VSM are distinct. 3.,Bronchoconstriction in asthma is currently treated with ,2 -adrenoceptor agonists, which relax contracted ASM cells. An additional approach may be to use gene therapy to render ASM unable to contract (via disruption of their contractile apparatus organization). 4.,Application of ASM-specific gene therapies would rely on minimal actions on other lung smooth muscle tissues, including pulmonary and bronchial vascular smooth muscle. The combination of mRNA analysis of laser-captured microdissected tissue with in situ immunohistochemical staining for protein should be very useful in terms of being able to characterize definitively the differences in mRNA and protein expression between the smooth muscle species of the lung. Any discovery of an ASM-selective target could provide a novel lead for ASM-directed anti-asthma therapy. [source] Working at the interface of phylogenetics and population genetics: a biogeographical analysis of Triaenops spp. (Chiroptera: Hipposideridae)MOLECULAR ECOLOGY, Issue 4 2007A. L. RUSSELL Abstract New applications of genetic data to questions of historical biogeography have revolutionized our understanding of how organisms have come to occupy their present distributions. Phylogenetic methods in combination with divergence time estimation can reveal biogeographical centres of origin, differentiate between hypotheses of vicariance and dispersal, and reveal the directionality of dispersal events. Despite their power, however, phylogenetic methods can sometimes yield patterns that are compatible with multiple, equally well-supported biogeographical hypotheses. In such cases, additional approaches must be integrated to differentiate among conflicting dispersal hypotheses. Here, we use a synthetic approach that draws upon the analytical strengths of coalescent and population genetic methods to augment phylogenetic analyses in order to assess the biogeographical history of Madagascar's Triaenops bats (Chiroptera: Hipposideridae). Phylogenetic analyses of mitochondrial DNA sequence data for Malagasy and east African Triaenops reveal a pattern that equally supports two competing hypotheses. While the phylogeny cannot determine whether Africa or Madagascar was the centre of origin for the species investigated, it serves as the essential backbone for the application of coalescent and population genetic methods. From the application of these methods, we conclude that a hypothesis of two independent but unidirectional dispersal events from Africa to Madagascar is best supported by the data. [source] Emerging trends in the treatment of rapid cycling bipolar disorder: a selected reviewBIPOLAR DISORDERS, Issue 4 2000Robert M Post Recent evidence suggests that lithium therapy (even as supplemented by antidepressants and neuroleptics) is inadequate for the majority of patients with bipolar illness, and particularly those with rapid cycling. Valproate and carbamazepine have emerged as adjuncts and alternatives, but they, too, often require additional approaches with lithium, thyroid hormones, and other putative mood stabilizers, including nimodipine (and related dihydropyridine calcium channel blockers), lamotrigine, gabapentin, topiramate, and the atypical neuroleptics. Evaluating how these agents and the unimodal antidepressants are optimally applied and sequenced in the treatment of bipolar illness with its multiple subtypes, patterns and comorbidities will require much future investigation and the development of new methodological clinical trial approaches. [source] A Multidimensional Meta-Analysis of Psychotherapy for Bulimia NervosaCLINICAL PSYCHOLOGY: SCIENCE AND PRACTICE, Issue 3 2003Heather Thompson-Brenner We report a multidimensional meta-analysis of psychotherapy trials for bulimia nervosa published between 1980 and 2000, including multiple variables in addition to effect size such as inclusion and exclusion, recovery, and sustained recovery rates. The data point to four conclusions. First, psychotherapy leads to large improvements from baseline. Approximately 40% of patients who complete treatment recover completely, although 60% maintain clinically significant posttreatment symptoms. Second, individual therapy shows substantially better effects than group therapy for the therapies tested. Third, additional approaches or treatment parameters (e.g., number of sessions) need to be tested for the substantial number of patients who enter treatment and do not recover. Finally, the utility of meta-analyses can be augmented by including a wider range of outcome metrics, such as recovery rates and posttreatment symptom levels. [source] | |||||||||||||