Are we teaching phototherapy? Results of an informal survey of phototherapy education.
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Curriculum↗
Biomedical subjects
L J Green
Publications and source records attributed to L J Green.
LY303366 exhibits rapid and potent fungicidal activity in flow cytometric assays of yeast viability.
LY303366 is a semisynthetic analog of the antifungal lipopeptide echinocandin B that inhibits (1,3)-beta-D-glucan synthase and exhibits efficacy in animal models of human fungal infections. In this study, we utilized flow cytometric analysis of propidium iodide uptake, single-cell sorting, and standard microbiological plating methods to study the antifungal effect of LY303366 on Saccharomyces cerevisiae and Candida albicans. Our data indicate that an initial 5-min pulse treatment with LY303366 caused yeasts to take up propidium iodide and lose their ability to grow. Amphotericin B and cilofungin required longer exposure periods (30 and 180 min, respectively) and higher concentrations to elicit these fungicidal effects. These two measurements of fungicidal activity by LY303366 were highly correlated (r > 0.99) in concentration response and time course experiments. As further validation, LY303366-treated yeasts that stained with propidium iodide were unable to grow in single-cell-sorted cultures. Our data indicate that LY303366 is potent and rapidly fungicidal for actively growing yeasts. The potency and rapid action of this new fungicidal compound suggest that LY303366 may be useful for antifungal therapy.
Anidulafungin↗
The integrin beta subunit.
The integrin family of cell adhesion receptors plays a fundamental role in the processes involved in cell division, differentiation and movement. The extracellular domains of integrin alpha/beta heterodimers mediate cell-matrix and cell-cell contacts while their cytoplasmic tails associate with the cytoskeleton. Integrins are capable of transducing information in a bidirectional manner and the beta subunit is now recognised to play an important role in this process. Recent studies have led to the identification of a ligand-binding region on the beta subunit similar to that already characterised on some alpha subunits, and sequences in the cytoplasmic tails of the beta subunits that interact with cytoskeletal and signalling components. Adhesive events can also play a role in the progression of all four major classes of human disease--neoplastic, inflammatory, traumatic and infectious--and the specific nature of integrin adhesion mechanisms make them an attractive target for therapy.
CD18 Antigens↗
Quantitative detection of platelet GPIIb-IIIa receptor antagonist activity using a flow cytometric method.
Platelet-membrane surface receptors are important targets for pharmacologic intervention in cardiovascular disease. Among these, glycoprotein (GP) IIb-IIIa is dominant and integrally involved in platelet aggregation and thrombus formation. When activated, GPIIb-IIIa binds soluble fibrinogen (Fb) in a key, early step of this process. New drugs are under development that block Fb binding to GPIIb-IIIa and inhibit platelet aggregation. A thorough understanding of the relationship between circulating drug levels and the extent of GPIIb-IIIa receptor occupancy in humans is crucial for safe and efficacious use of these agents. Described here is the development of a new technique for measurement of GPIIb-IIIa receptor occupancy. In this assay, activated human platelets are incubated with biotinylated fibrinogen (Fb-biotin) followed by antibiotin-FITC.The extent of Fb binding is determined using flow cytometric analysis. Our results indicate that Fb-biotin binds rapidly to activated platelets and its detection is dependent on incubation temperature. Platelets that were pre-incubated with the GPIIb-IIIa antagonist echistatin were inhibited from binding Fb-biotin in a concentration-dependent manner. The fluorescence of processed samples was stable for two weeks in the cold. The assay described here is simple, cost effective, and can be adapted for use in clinical evaluations of these new drugs.
Biotin↗
An RGD to LDV motif conversion within the disintegrin kistrin generates an integrin antagonist that retains potency but exhibits altered receptor specificity. Evidence for a functional equivalence of acidic integrin-binding motifs.
Integrin ligands almost invariably employ a variant of either the RGD or LDV motif as a key element of their receptor recognition site. These short acidic peptide sequences collaborate with specific nonhomologous flanking residues and spatially separate "synergy" sequences to determine receptor binding specificity. Although the consensus sequences for RGD and LDV motifs are quite different, their common use suggests that they might share a critical role in receptor-ligand engagement. To date, the effects of interconversion of the two motifs within a natural protein framework have not been tested; however, in this study, we have converted the natural RGD site found in the snake venom disintegrin kistrin into an LDV motif and examined the effects of the change on the specificity of integrin recognition and on disintegrin potency. While an assessment of receptor binding using cell adhesion and purified integrin solid-phase assays demonstrated recognition of recombinant RGD kistrin by alphaVbeta3 and alpha5beta1, a series of LDV kistrin chimeras did not bind to these integrins, but instead were recognized specifically by alpha4beta1. The minimal change to elicit this distinct switch in receptor specificity was found to involve alteration of only three residues within kistrin. Alanine scanning mutagenesis was used to provide further information on the functional contribution of the three residues. More important, the LDV kistrin chimeras also retained much of the characteristic potency of RGD kistrin, indicating that the kistrin scaffold is optimized for presentation of both RGD and LDV sequences. These findings provide evidence for similarities in motif pharmacophore and reinforce the hypothesis that RGD and LDV sites have an equivalent functional role in receptor binding. They also demonstrate the potential for other disintegrin-containing proteins, perhaps from the ADAM family, to employ LDV sequences for integrin binding.
Amino Acid Sequence↗
Neurocutaneous melanosis and Dandy-Walker syndrome in an infant.
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Abnormalities, Multiple↗
Inhibition of integrin-ligand binding by recombinant kistrins.
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Amino Acid Sequence↗
Integrin alpha 2 I-domain is a binding site for collagens.
Integrins alpha 1 beta 1 and alpha 2 beta 1 are major cellular receptors for collagens. The alpha 1 and alpha 2 subunits contain a approximately 200 amino acid inserted domain (I-domain) in their N-terminal region and, because of the homology between the I-domains and the collagen-binding A-domains of von Willebrand factor, it has been suggested that the I-domains might mediate the collagen-binding functions of alpha 1 beta 1 and alpha 2 beta 1. In order to fully investigate this hypothesis, we have generated recombinant human alpha 2 I-domain (r alpha 2I) by reverse transcriptase-polymerase chain reaction/bacterial expression and tested its ability to mediate the collagen-binding functions of alpha 2 beta 1. R alpha 2 I binds specifically to type I collagen in a concentration-dependent manner: binding is cation dependent and, like the complete receptor, is supported by magnesium and manganese ions but not by calcium ions. R alpha 2I is recognised by anti-functional anti-alpha 2 monoclonal antibodies 6F1, 5E8 and P1E6 in capture ELISAs, and anti-functional antibodies inhibited r alpha 2I-collagen binding. In addition, r alpha 2I inhibits cell spreading on collagen. R alpha 2I is therefore a collagen-binding domain and can account for many of the collagen-binding functions of integrin alpha 2 beta 1. We have also determined the collagen specificity of r alpha 2I and found that it binds types I, II and XI collagen.
Animals↗
Competitive binding of vascular cell adhesion molecule-1 and the HepII/IIICS domain of fibronectin to the integrin alpha 4 beta 1.
The integrin receptor alpha 4 beta 1 binds to two different ligands, the extracellular matrix glycoprotein fibronectin and the endothelial cell surface protein vascular cell adhesion molecule-1 (VCAM-1). Using probes derived from each ligand and a variety of cell adhesion and ligand-receptor binding assays, we have investigated the relationship between the mechanisms of fibronectin and VCAM-1 interaction with alpha 4 beta 1. CS1 peptide, which represents the dominant active site from the HepII/IIICS recognition domain in fibronectin, was found to inhibit VCAM-1-dependent adhesion in three different assays: MOLT-4 T lymphoblastic leukaemia cell attachment to immobilized recombinant soluble VCAM-1 (rsVCAM-1), MOLT-4 cell attachment to monolayers of VCAM-1-transfected COS-1 cells, and A375-SM melanoma cell spreading on immobilized rs VCAM-1. Half-maximal inhibition required CS1 concentrations of 1.7-3.0 mg/ml, some 3-7-fold higher than that needed to autoinhibit adhesion to CS1-IgG conjugate. Using a more sensitive solid-phase receptor-ligand binding assay, CS1 was found to be a potent inhibitor of the binding of rsVCAM-1 to alpha 4 beta 1 (half-maximal inhibition at 13 micrograms/ml). In agreement with cell-based assays, severalfold lower concentrations of CS1 were required to inhibit binding of recombinant HepII/IIICS region of fibronectin (half-maximal inhibition at 3 micrograms/ml). VCAM-1-alpha 4 beta 1 binding was blocked not only by CS1 peptide but also by the recombinant HepII/IIICS region of fibronectin. Kinetic analysis of CS1 inhibition of VCAM-1 binding revealed that it was directly competitive in nature, indicating that VCAM-1 and fibronectin recognize either identical or spatially overlapping binding sites on alpha 4 beta 1. The implications of these results for the future design of VCAM-1 antagonists are discussed.
Amino Acid Sequence↗
Photoaging and the skin. The effects of tretinoin.
The appearance of photoaged skin is cosmetically unacceptable to many in our society. Ostensibly, avoidance of ultraviolet light and sunlight from early childhood is most desirable but not likely to happen in our culture. Tretinoin is the only pharmacologic compound shown to partially reverse some signs of photoaging. Improvement with tretinoin therapy has been quantified clinically and histologically. A major degree of improvement occurs in 6 to 12 months, and maintenance treatment one to three times per week may continue this response. Tretinoin therapy should optimally be used with daily moisturizer and sunscreen applications. Psychosocial benefits of tretinoin therapy, use of tretinoin for intrinsically aged or non-Caucasian skin, and higher-strength tretinoin therapy for severely photoaged skin need to be further explored. It is possible that some subsets of patients with photoaged skin may respond better than others.
Animals↗
The minimal essential sequence for a major cell type-specific adhesion site (CS1) within the alternatively spliced type III connecting segment domain of fibronectin is leucine-aspartic acid-valine.
Fibronectin contains at least two major domains that support cell adhesion. One is the central cell-binding domain that is recognized by a variety of cell types via the integrin alpha 5 beta 1. The second, originally identified by its ability to support melanoma cell adhesion, is located in the alternatively spliced type III connecting segment (IIICS). A dominant cell type-specific adhesion site within the IIICS has been localized to a peptide designated as CS1 comprising its amino-terminal 25 residues. The receptor for CS1 is the integrin alpha 4 beta 1. We have synthesized a variety of peptides with overlapping sequences in order to identify the minimum active amino acid sequence of this major cell adhesion site. A peptide comprising the carboxyl-terminal 8 amino acids of CS1, EILDVPST, was found to support melanoma cell spreading, while all peptides without this sequence had little or no activity. Two smaller overlapping pentapeptides, EILDV and LDVPS, were also active, whereas EILEV, containing a conservative substitution of Glu for Asp, was inactive. These data suggested that the minimum sequence for cell adhesion activity is Leu-Asp-Val, the tripeptide sequence common to both active peptides. This prediction was confirmed by the observed ability of the Leu-Asp-Val peptide itself to block spreading on fibronectin, whereas Leu-Glu-Val was inactive. Interspecies amino acid sequence comparison also supports the importance of the LDV sequence, since it is completely conserved in the IIICS regions of human, rat, bovine, and avian fibronectins.
Amino Acid Sequence↗
Physical and mechanical properties of elastomers in orthodontic positioners.
Elastomers for conventional Kesling-type tooth positioners are relatively inelastic and are primarily indicated as finishing devices. However, new materials, first described in the Japanese literature, with claims of a greater range of tooth movement warrant a comparison with conventional materials. Physical and mechanical property testing of positioner elastomers has not been reported in the orthodontic literature. This investigation compared properties of a high temperature vulcanizing (HTV) Japanese silicone (Orthocon) to three traditional polyurethane and vinyl-based polymers and five experimental silicone elastomers. Fourier transform infrared spectroscopy established the definitive chemical composition of the urethane and vinyl materials obtained from a commercial positioner laboratory. Tear strength, tensile strength, tensile stress at selected elongations, and ultimate elongation of all materials were evaluated at 37 degrees C in an aqueous environment. Hardness and water sorption values also were determined and an in vitro force measurement apparatus was fabricated to determine force levels exerted by positioner materials at low displacements. Orthocon was statistically different (Duncan's multiple range test, p less than 0.05) from the traditional commercial urethane and vinyl materials. Orthocon had lower tear strength than the traditional materials. It also demonstrated lower stress values below 100% elongation. The parameters of tensile stress at 50% elongation and ultimate elongation were statistically identical for Orthocon and one experimental silicone material.
Absorption↗
Immunological abnormalities in autoimmune chronic active hepatitis.
Autoimmune chronic active hepatitis is often associated with clinical and laboratory features that resemble those observed in systemic lupus erythematosus (SLE). We describe a 24-year-old woman with autoimmune chronic active hepatitis who was studied for serologic markers of autoimmunity and for immune clearance in terms of in vivo Fc receptor function. A markedly depressed immune clearance and splenic uptake of radiolabelled and IgG coated autologous erythrocytes was observed. The magnitude of this defect equaled or exceeded the most severe defects seen in a group of patients with SLE. This phenomenon was associated with markedly depressed serum C4 levels, a variably positive Sm antibody, and normal circulating immune complex concentrations. In addition, many clinical extrahepatic manifestations meeting criteria for classifying SLE were present. These findings further support the concept of autoimmune chronic active hepatitis and SLE being part of spectrum of overlapping autoimmune diseases.
Adult↗
Root resorption in maxillary central incisors following active orthodontic treatment.
The purpose of this study was to determine if apical root resorption associated with orthodontic treatment continues after the termination of active treatment (that is, the removal of fixed appliances). A sample of 45 subjects who had experienced root resorption during treatment was selected from the orthodontic clinic at the State University of New York at Buffalo. The length of the maxillary central incisors was measured from lateral cephalometric radiograms taken before treatment, after active treatment, and after retention. From these data, the resorption occurring during and after active treatment was calculated. The mean amount of root resorption during active treatment was 2.93 mm. The mean amount of root resorption during the posttreatment period was 0.1 mm. There was a statistical difference between these two means using the Student's t test at the 0.05 level of significance. The reliability coefficient comparing the first tracings and measurements in the 19 cases that were retraced and remeasured was r = 0.993. The data from this radiographic study support the hypothesis that root resorption associated with orthodontic treatment ceases with the termination of active treatment. There was also evidence to suggest that when posttreatment root resorption does occur, it is not necessarily associated with large amounts of root resorption during the active treatment period. It is more likely associated with other factors, such as traumatic occlusion and active force-delivering retainers.
Adolescent↗
An increase in plasminogen activator mRNA occurs at an early stage in ethylnitrosourea-induced transformation of rat brain cells.
Brain tumor cells cultured after transplacental induction by the nitrosamide, N-ethyl-N-nitrosourea had a higher level of plasminogen activator activity than control cells from adult rat brain. Cultures (BE10) derived 2 days after exposure to the carcinogen showed a rise in this proteolytic activity at the 17th passage but were not able to form colonies in agar or tumours in syngeneic rats until passages 44/45. Cultures (BE11) derived 2 days after exposure to buffer did not show a rise in this enzyme activity nor were they able to grow in agar or animals at comparable passages. Zymography and inhibition studies showed that the enzyme produced by the tumour cells was related to human tissue-type plasminogen activator rather than to urokinase. Northern blot analysis showed a higher level of tissue plasminogen activator related mRNA in tumour cells than control cells. There was an increase in mRNA level during passaging of the carcinogen-exposed culture, BE10, which correlated with the increased enzyme activity. There was no rise in the barely detectable mRNA levels of the comparable buffer-exposed culture, BE11. The results suggest that alteration in the transcriptional control of this proteolytic enzyme occurs at an early stage in the transformation process.
Animals↗
Bivariate path analysis of twin children for stature and biiliac diameter: estimation of genetic variation and co-variation.
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Adolescent↗
A dental-facial attractiveness scale. Part I. Reliability and validity.
Since the decision to seek orthodontic treatment is frequently the result of concerns about appearance, assessment of need for treatment should include an impartial evaluation of dental-facial appearance. While some of the standardized techniques for assessing malocclusion have included a consideration of esthetic impairment, they tend to confound this with functional impairment. The purpose of this study was to develop a valid and reliable index that provides relatively objective judgments of dental-facial attractiveness. The subjects in this study were eighth- and ninth-grade children seeking orthodontic treatment and their siblings, and eighth- and ninth-grade children not seeking treatment and their siblings. Photographs of the children were rated for dental-facial attractiveness by lay and dental judges. Children were also assessed for severity of malocclusion by means of the Treatment Priority index. Children seeking treatment were perceived as significantly less attractive than children not seeking treatment. Dental judges rated children seeking treatment as more attractive than did nondental judges. Intraclass reliability coefficients were moderate to high.
Adolescent↗
Development and validation of a measure of attitudes toward malocclusion.
The Orthodontic Attitude Survey was designed to assess children's and their parents' attitudes toward malocclusion and orthodontic treatment. Five consistent clusters of attitudes had discriminant validity, and were significantly related to plans for orthodontic treatment and to objective and subjective indicators of the child's occlusal status and appearance.
Adolescent↗