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M Symons

Publications and source records attributed to M Symons.

51 records · Page 3Linked to original sources

Activation of rat liver phospholipase D by the small GTP-binding protein RhoA.

Stimulation of phospholipase D by guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) in rat liver plasma membranes indicates the involvement of GTP-binding proteins. We used RhoGDI, an inhibitor of GDP dissociation from small GTP-binding proteins of the Rho family, to determine the involvement of these proteins. Incubation, and subsequent washing, of plasma membranes with RhoGDI dose-dependently diminished GTP gamma S-stimulated phospholipase D activity, as determined by accumulation of phosphatidylethanol in the presence of ethanol. Incubation with RhoGDI also caused a rapid and dose-dependent appearance of RhoA in the wash, which was associated with the inhibition of phospholipase D. RhoGDI also rapidly extracted Cdc42 from membranes, but Rac1 was not extracted. Full reconstitution of GTP gamma S-stimulated phospholipase D in RhoGDI-washed membranes was achieved with recombinant RhoA. There was partial reconstitution with Rac1 and no enhancement with Cdc42 or ADP-ribosylation factor. The response to RhoA was dose-dependent (EC50 = 0.5 microM). ADP-ribosylation of RhoA by Clostridium botulinum C3 exoenzyme did not affect its ability to recover GTP gamma S-stimulated phospholipase D activity in RhoGDI-washed membranes. These findings support a role for GTP-binding proteins of the Rho family in the activation of membrane-associated phospholipase D and implicate RhoA as the major protein involved.

Adenosine Diphosphate Ribose↗

A multileaf collimator field prescription preparation system for conventional radiotherapy.

PURPOSE: The purpose of this work is to develop a prescription preparation system for efficient field shaping using a multileaf collimator that can be used in community settings as well as research institutions. The efficiency advantage of the computer-controlled multileaf collimator, over cerrobend blocks, to shape radiation fields has been shown in conformal treatments, which typically require complete volumetric computerized tomographic data for three-dimensional radiation treatment planning--a utility not readily available to the general community. As a result, most patients today are treated with conventional radiation therapy. Therefore, we believe that it is very important to fully use the same efficiency advantage of multileaf collimator as a block replacement in conventional practice. METHODS AND MATERIAL: The multileaf collimator prescription preparation systems developed by us acquires prescription images from different sources, including film scanner, and radiation treatment planning systems. The multileaf collimator angle and leaf positions are set from the desired field contour defined on the prescription image, by minimizing the area discrepancies. Interactive graphical tools include manual adjustment of collimator angle and leaf positions, and definition of portions of the field edges that require maximal conformation. Data files of the final leaf positions are transferred to the multileaf collimator controller via a dedicated communication link. RESULTS: We have implemented the field prescription preparation system and a network model for integrating the multileaf collimator and other radiotherapy modalities for routine treatments. For routine plan evaluation, isodose contours measured with film in solid water phantom at prescription depth are overlaid on the prescription image. Preliminary study indicates that the efficiency advantage of the MLC over cerrobend blocks in conformal therapy also holds true for conventional treatments. CONCLUSION: Our model of computer-controlled prescription, evaluation, and treatment using multileaf collimators can be effectively implemented in both community settings and research institutions. The resultant increase in treatment efficiency and accuracy is now available for conventional radiotherapy.

Humans↗

Binding of 14-3-3 proteins to the protein kinase Raf and effects on its activation.

To identify proteins that may participate in the activation of the protein kinase Raf, proteins that interact with Raf were selected in a two-hybrid screen. Two members of the 14-3-3 protein family were isolated that interacted with both the amino terminal regulatory regions of Raf and the kinase domain of Raf, but did not compete with the guanine nucleotide-binding protein Ras for binding to Raf. 14-3-3 proteins associated with Raf in mammalian cells and accompanied Raf to the membrane in the presence of activated Ras. In yeast cells expressing Raf and MEK, mammalian 14-3-3 beta or 14-3-3 zeta activated Raf to a similar extent as did expression of Ras. Therefore, 14-3-3 proteins may participate in or be required for the regulation of Raf function. These findings suggest a role for 14-3-3 proteins in Raf-mediated signal transduction.

14-3-3 Proteins↗

Activation of Raf as a result of recruitment to the plasma membrane.

The small guanine nucleotide binding protein Ras participates in a growth promoting signal transduction pathway. The mechanism by which interaction of Ras with the protein kinase Raf leads to activation of Raf was studied. Raf was targeted to the plasma membrane by addition of the COOH-terminal localization signals of K-ras. This modified form of Raf (RafCAAX) was activated to the same extent as Raf coexpressed with oncogenic mutant Ras. Plasma membrane localization rather than farnesylation or the presence of the additional COOH-terminal sequence accounted for the activation of RafCAAX. The activation of RafCAAX was completely independent of Ras; it was neither potentiated by oncogenic mutant Ras nor abrogated by dominant negative Ras. Raf, once recruited to the plasma membrane, was not anchored there by Ras; most activated Raf in cells was associated with plasma membrane cytoskeletal elements, not the lipid bilayer. Thus, Ras functions in the activation of Raf by recruiting Raf to the plasma membrane where a separate, Ras-independent, activation of Raf occurs.

Amino Acid Sequence↗

Canine plasma alkaline phosphatase polymorphism and its relationship with the canine Tr blood group system.

A canine blood group antigen, QN, which was detected by a naturally occurring alloantibody in the antiglobulin test, was shown to be antigenically related to the human A and cattle J antigens by absorption experiments. Family studies supported a dominant mode of inheritance with the gene controlling the production of QN being dominant to the gene responsible for its absence. Frequencies of the QN and Tr antigens and serological data strongly suggested that the two antigens are identical. Two canine plasma alkaline phosphatase variants, F and S, were detected by starch gel electrophoresis, pH 8.65. Assuming genetic control of two codominant alleles, ALPF and ALPS, the distributions of types in families differed significantly from expectation. A relationship between the ALP and Tr(QN) systems was demonstrated with Tr-positive animals having a significant deficiency of S alkaline phosphatase types.

Alkaline Phosphatase↗

Canine blood groups: description of 20 specificities.

Twenty blood typing reagents, four agglutinins and 16 operable in the antiglobulin test, were prepared from 54 antisera which were produced in 24 dogs. Two of the reagents were identified as anti-B and Nf6. Two of the antigens were shown by absorption and family studies to be linear subtypes. In most cases, detailed family studies demonstrated a Mendelian dominant inheritance for the genes controlling the canine red cell antigens. Gene frequencies were determined in various breeds of dogs and in the dingo.

Agglutinins↗

Expansion of the canine A blood group system.

A detailed study of the canine A blood group system was undertaken, resulting in the expansion of this system into a three-factor, four-allelic one with the recognition of an additional subtype, a3. The serological and extensive family data supported the proposed genetic theory of four alleles with dominance with the order being Aa1, Aa2, Aa3 and A-. Gene frequencies of the alleles were determined in various breeds of dogs with frequencies in the general Brisbane population being 0.244 (Aa1), 0.042 (Aa2), 0.045 (Aa3) and 0.669 (A-).

Alleles↗

Lentinginous dysplastic naevi in the elderly: a potential precursor for malignant melanoma.

Seventy-seven skin biopsies diagnosed histologically as lentiginous junctional naevi from individuals aged over 60 years were reviewed. Seventy-three specimens showed a primarily nested pattern with disordered arthitecture concentrated within the rete ridges conforming to the pathology of a lentiginous dysplastic naevus. In 28 biopsies this was combined with a melanoma in situ. The latter was reflected by a focal loss of the rete ridge system, confluent melanocytic hyperplasia and single cell invasion of the epidermis by atypical malanocytes. Four biopsies showed lentiginous junctional naevi with only isolated naevus cell nests without a disordered architecture or cellular atypia. Thirty-seven of the 57 naevi in men were located on the back in contrast to 5 of the 20 women. In women the lower limb was the most frequent site with 8 of the 20 lesions originating at this site in contrast to 1 of the 57 men. The pathological diagnosis of dysplastic lentiginous naevi in the elderly needs to be recognised as having a high association of melanoma-in-situ changes.

Aged↗

The light-induced carotenoid absorbance changes in Rhodopseudomonas sphaeroides: an analysis and interpretation of the band shifts.

An analysis has been made of the spectrum of the carotenoid absorption band shift generated by continuous illumination of chromatophores of the GlC-mutant of Rhodopseudomonas sphaeroides at room temperature by means of three computer programs. There appears to be at least two pools of the same carotenoid, only one of which, comprising about 20% of the total carotenoid content, is responsible for the light-induced absorbance changes. The 'remaining' pool absorbs at wavelengths which were about 5 nm lower than those at which the 'changing' pool absorbs. This difference in absorption wavelength could indicate that the two pools are influenced differently by permanent local electric fields. The electrochromic origin of the absorbance changes has been demonstrated directly; the isosbestic points of the absorption difference spectrum move to shorter wavelengths upon lowering of the light-induced electric field. Band shifts up to 1.7 nm were observed. A comparison of the light-induced absorbance changes with a KCl-valinomycin-induced diffusion potential has been used to calibrate the electrochromic shifts. The calibration value appeared to be 137 +/- 6 mV per nm shift.

Bacterial Chromatophores↗

Chronic diseases in the rubber industry.

An overview is presented of epidemiologic studies of chronic diseases in the rubber industry. Analyses of the mortality experience during the period 1964-1972 of workers age 40-64 and retirees age 65-84 of two large rubber and tire manufacturing companies consistently disclosed excesses of deaths attributed to leukemia and lymphosarcoma, and for cancers of the stomach, large intestine, and prostate. The relation of site-specific malignancies to work histories and grouped occupational titles as surrogate measures of work-related exposures to possible carcinogens is described. There was no evidence of company-wide, sizable, consistent excess for the other major chronic diseases causes of death. Although a total cohort deficit in the mortality rate for lung cancer was found, there was a history of increased frequency of exposure to certain work areas among lung cancer decedents. Morbidity studies, including analysis of disability retirements, and ad hoc questionnaire and health testing surveys, disclosed excesses of chronic pulmonary diseases. There was evidence of an interactive effect in the association of work and smoking histories with pulmonary disability retirement.

Adult↗

Stages of change and psychosocial correlates of fruit and vegetable consumption among rural African-American church members.

PURPOSE: This study examined the relationship between stages of change, other psychosocial factors, and fruit and vegetable (F&V) consumption among rural African-Americans participating in a 5 a Day study. DESIGN: The cross-sectional design assessed associations between F&V intake, stage of change, self-efficacy, beliefs, barriers, and social support. SETTING: Participants were surveyed by telephone. SUBJECTS: Subjects were 3557 adult church members (response rate, 79.1%), aged 18 and over from 10 North Carolina counties. MEASURES: A seven-item food frequency measured F&V intake. Stage of change was measured using four items; other psychosocial variables were measured using Likert scales. Chi-square tests and analysis of variance were used in statistical analyses. RESULTS: The majority of participants (65%) were in the preparation stage of change. Individuals in action/maintenance consumed an average of 6.5 daily F&V servings compared to 3.3 to 3.5 servings for those in precontemplation, contemplation, and preparation. Self-efficacy, social support, and belief about how many daily F&V servings are needed, were positively associated with stage. Barriers were most prevalent among precontemplators. CONCLUSIONS: The findings support the applicability of the stages-of-change model to dietary change among rural African-Americans. The relationship between stage, self-efficacy, social support, and barriers supports using a multicomponent intervention strategy.

Adult↗

High spirits.

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Charities↗