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L Phillips

Publications and source records attributed to L Phillips.

At least 37 records · Page 2Linked to original sources
PubMed1988

Structure and function of contractile proteins in muscle fibres.

The structural unit of muscle has long been defined as the myofibril, a supramolecular assembly of a dozen or more proteins of which two, actin and myosin, comprise more than 75%. In the past 40 years since Albert Szent-Gyorgyi first described the contractile response from the complex of actin and myosin, knowledge of the structure and function of these contractile proteins has been substantially refined. This paper describes these new discoveries and identifies the problems which remain to be elucidated.

Actins↗
PubMed1987

Interaction of phalloidin with chemically modified actin.

Modification of Tyr-69 with tetranitromethane impairs the polymerizability of actin in accordance with the previous report [Lehrer, S. S. and Elzinga, M. (1972) Fed. Proc. 31, 502]. Phalloidin induces this chemically modified actin to form the same characteristic helical thread-like structure as normal F-actin. The filaments bind myosin heads and activate the myosin ATPase activity as effectively as normal F-actin. When a dansyl group is introduced at the same point [Chantler, P. D. and Gratzer, W. B. (1975) Eur. J. Biochem. 60, 67-72], phalloidin still induces the polymerization. The filaments bind myosin heads and activate the myosin ATPase activity. These results indicate that Tyr-69 is not directly involved in either an actin-actin binding site or the myosin binding site on actin. Moreover, the results suggest that phalloidin binds to actin monomer in the presence of salt and its binding induces a conformational change in actin which is essential for polymerization, or that actin monomer fluctuates between in unpolymerizable and polymerizable form while phalloidin binds to actin only in the polymerizable form and its binding locks the conformation which causes the irreversible polymerization of actin. Modification of Tyr-53 with 5-diazonium-(1H)tetrazole blocks actin polymerization [Bender, N., Fasold, H., Kenmoku, A., Middelhoff, G. and Volk, K. E. (1976) Eur. J. Biochem. 64, 215-218]. Phalloidin is unable to induce the polymerization of this modified actin nor does it bind to it. Phalloidin does not induce the polymerization of the trypsin-digested actin core. These results indicate that the site at which phalloidin binds is involved in polymerization and the probable conformational change involved in polymerization may be modulated through this site.

Actins↗
PubMed1987

Dissociation between global and regional systolic and diastolic ventricular function during coronary occlusion and reperfusion.

Indexes of global ventricular function such as the ejection fraction (EF) and the peak diastolic filling rate (PDFR) are often used to assess the effects of coronary recanalization in patients with myocardial infarction. In this investigation we assessed the relationship between these global indexes and directly measured indexes of regional function during 15 minutes of coronary occlusion followed by 120 minutes of reperfusion in 22 open-chest dogs. A computerized nuclear cardiac probe was used to assess EF and PDFR. Indexes of regional function were measured by Doppler ultrasonic wall-thickening probes. During coronary occlusion, paradoxical systolic thinning occurred and the EF and PDFR decreased an average of 31.6% and 24.4%, respectively. During reperfusion the EF and PDFR improved rapidly and at 60 minutes were similar to baseline. Systolic wall thickening improved more gradually and remained abnormal throughout reperfusion. Likewise, indexes of diastolic function (mean rate to half end-diastolic thinning and late diastolic thinning fraction) recovered slowly and remained abnormal throughout reperfusion (78% and 69.7%, respectively). The correlation between the rate of change of global and regional function was poor during both coronary occlusion and reperfusion. Thus, during coronary occlusion the global and regional indexes of ventricular function undergo directionally similar changes. However, during coronary reperfusion the global indexes do not reflect the slow recovery of the stunned myocardium.

Animals↗
PubMed1987

Lymphocyte proliferation to antigen E: demonstration of the restriction of antigen E-specific T cells to ragweed-allergic donors.

Allergic sensitivity to ragweed is common among atopic individuals in North America and can be associated with symptoms of seasonal hay fever and increased airway reactivity in asthma. This sensitivity is mediated by IgE antibody to ragweed antigens that in turn is presumed to be the product of B-lymphocytes regulated by various T cell subsets. Proliferation in vitro by lymphocytes obtained from individuals allergic to ragweed and cultured in the presence of ragweed antigen E (AgE) has been repeatedly described, but a comprehensive study of this proliferation has questioned the specificity of this response. We have examined this question and found that in the first week of culture, the specific lymphocyte proliferation to AgE may be obscured by high background and mitogen-like proliferation. However, by carrying the cells for a longer period of time in culture and providing a second in vitro boost with AgE, specific proliferation could be clearly documented. Lymphocytes from atopic ragweed-allergic donors proliferated at levels 20 to 50 times beyond background in the presence of AgE. Cells from nonragweed-allergic donors (either nonatopic or atopic) did not do so. The AgE-responsive cells could be expanded in culture and demonstrated to be T cells. Moreover, AgE-responsive T cells could only be cloned from AgE-allergic donors and, after expansion and subcloning, demonstrated to respond to AgE but not partially purified dust mite antigen. In contrast, a clone of T cells from a dust mite-sensitive individual proliferated in response to the dust mite antigen but not AgE.

Allergens↗
PubMed1986

Aridicins, novel glycopeptide antibiotics. III. Preparation, characterization, and biological activities of aglycone derivatives.

The aglycone and two pseudoaglycones of aridicin A were prepared by selective hydrolysis and characterized, chemically and biologically. These new analogs demonstrate improved activities in vitro over the parent antibiotics against methicillin sensitive and resistant staphylococci. The major determinant of activity is the mannose substituent, the presence of which results in less potent compounds. The analogs have potent activity against enterococci.

Animals↗
PubMed1986

Comparative laboratory studies on alpha-methoxyimino furyl- and phenylacetamido cephalosporins: structure-activity relationships.

Eleven new cephalosporins (three phenylacetamido and eight furylacetamido) containing a methoxyimino group on the 7 beta-acyl side chain and having various substituents at their 3-positions, exhibited similar qualitative, but differing quantitative in vitro antibacterial spectra compared to that of cefuroxime, the first therapeutically used alpha-methoxyimino cephalosporin. The syn-isomers and the alpha-acyl substituted compounds are more active than either the anti-isomer or the beta-acyl substituted compounds. Compounds containing substituted tetrazole rings at the 3-position are likewise more active than those containing other types of substituents in this position. In vivo (mouse) the heterocyclic furylacetamido compounds are more efficacious (protective) than the aromatic phenylacetamido compounds. The furylacetamido alpha-methoxyimino cephalosporins containing at the 3-position the tetrazole group carrying an acidic function possess favorable pharmacokinetic properties, i.e., higher serum levels and prolonged biological half-lives in mouse and squirrel monkey and extensive binding to serum proteins.

Animals↗
PubMed1985

Gallium-67 scintigraphy in well-differentiated lymphocytic lymphoma of the skin.

Skin lymphomas are now divided into "T" or thymic cell lymphomas (mycosis fungoides being the principal type) and "B" cell lymphomas after the bursa of Fabricius. The "T" cell lymphomas all are identified by the thymic or cerebriform cell. Those lymphomas of the skin which do not contain these characteristic cells are derived from the bursa cells and are termed "B" cell lymphomas. A large percentage of these non "T" cell lymphomas have been histologically diagnosed as lymphocytic lymphoma of the skin (1). The authors had an opportunity to scan a patient with histologically proven lymphocytic lymphoma of the skin with Ga-67 and obtained on excellent correlation between gallium accumulation in the skin lesions and histologic confirmation of lymphocytic lymphoma.

Gallium Radioisotopes↗
PubMed1985

Antimicrobial activity of aridicins, novel glycopeptide antibiotics with high and prolonged levels in blood.

Three new glycopeptide antibiotics, aridicins A, B, and C, produced by Kibdelosporangium aridum have a spectrum of antimicrobial activity in vitro which is similar to that of vancomycin. The antimicrobial activities of these glycopeptides against clinical bacterial isolates were compared with those of vancomycin and other related glycopeptide antibiotics in vitro by agar dilution and microtiter broth dilution tests and in vivo in mouse protection studies. In vitro they were somewhat less effective than vancomycin against strains of Staphylococcus aureus and less active against coagulase-negative Staphylococcus spp. However, they were more active than vancomycin against strains of Streptococcus faecalis and markedly superior to vancomycin and other glycopeptide antibiotics against strains of Clostridium difficile. In experimental infections, aridicin A was effective against strains of S. aureus, S. epidermidis, Streptococcus faecalis, and Streptococcus pyogenes, although its 50% effective doses were higher than those of vancomycin when administered after infection. After subcutaneous administration, aridicin A had a higher peak level in serum and a longer half-life than vancomycin or teicoplanin. The aridicins were markedly superior to vancomycin when administered prior to infection in mouse protection tests, indicating long-acting potential.

Animals↗
PubMed1985

Staphylococcus aureus Tour, a selectively mouse-pathogenic strain for experimental chemotherapeutic study (a note).

Staphylococcus aureus Tour is a unique strain. It is highly pathogenic to mice but not to other laboratory animals and primates. This selective pathogenicity makes it useful for experimental chemotherapeutic studies. Since it is highly specialized for mice, it imitates the natural course of infection and produces death after intraperitoneal infection of a relatively few cells even when suspended in isotonic saline. This strain has been found to be very sensitive (MIC's) to various beta-lactams and gentamicin as well as useful for infection-protection studies in mice (ED50's) with a series of cephalosporins.

Cephalosporins↗
PubMed1985

Validation of left ventricular volume measurements by radionuclide angiography.

A nongeometric, attenuation-corrected technique to quantitate left ventricular volumes using equilibrium radionuclide angiography was validated in vitro and in vivo. In vitro experiments were performed to derive a linear attenuation coefficient, which was then employed in the volume determinations using balloons in a water bath. Good in vitro correlation was found between radionuclide and actual volumes (r = 0.99, p less than 0.0001), over a wide range (5 to 400 ml). In vivo validation was done by comparing the nuclear technique to contrast angiography in 29 patients: Good correlations were found for end-diastolic volume (r = 0.98), end-systolic volume (r = 0.95), stroke volume (r = 0.96), and ejection fraction (r = 0.85). When the conventional linear attenuation coefficient was used, the radionuclide technique consistently overestimated volumes in vitro and in vivo. Although high intraobserver and interobserver correlation coefficients were found (r from 0.88 to 0.93), significant individual variability existed, particularly in the interobserver data. Our data provide unique validation of radionuclide volume determinations, using an experimentally determined attenuation coefficient, which results in improved accuracy.

Adult↗
PubMed1984

Monoclonal antibodies to the Ca2+ + Mg2+-dependent ATPase of sarcoplasmic reticulum identify polymorphic forms of the enzyme and indicate the presence in the enzyme of a classical high-affinity Ca2+ binding site.

In order to determine whether polymorphic forms of the Ca2+ + Mg2+-dependent ATPase exist, we have examined the cross-reactivity of five monoclonal antibodies prepared against the rabbit skeletal muscle sarcoplasmic reticulum enzyme with proteins from microsomal fractions isolated from a variety of muscle and nonmuscle tissues. All of the monoclonal antibodies cross-reacted in immunoblots against rat skeletal muscle Ca2+ + Mg2+-dependent ATPase but they cross-reacted differentially with the enzyme from chicken skeletal muscle. No cross-reactivity was observed with the Ca2+ + Mg2+-dependent ATPase of lobster skeletal muscle. The pattern of antibody cross-reactivity with a 100,000 dalton protein from sarcoplasmic reticulum and microsomes isolated from various muscle and nonmuscle tissues of rabbit demonstrated the presence of common epitopes in multiple polymorphic forms of the Ca2+ + Mg2+-dependent ATPase. One of the monoclonal antibodies prepared against the purified Ca2+ + Mg2+-dependent ATPase of rabbit skeletal muscle sarcoplasmic reticulum was found to cross-react with calsequestrin and with a series of other Ca2+-binding proteins and their proteolytic fragments. Its cross-reactivity was enhanced in the presence of EGTA and diminished in the presence of Ca2+. Its lack of cross-reactivity with proteins that do not bind Ca2+ suggests that it has specificity for antigenic determinants that make up the Ca2+-binding sites in several Ca2+-binding proteins including the Ca2+ + Mg2+-dependent ATPase.

Animals↗