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Biomedical subjects

L Phillips

Publications and source records attributed to L Phillips.

At least 145 records · Page 8Linked to original sources
PubMed1990

Characterization of the specificity of peptide binding to four DR haplotypes.

This study describes the establishment of a peptide-binding assay for purified, detergent-solubilized DR molecules. For each of the DR specificities and peptides studied, a unique pattern of interaction was observed. Excellent correlation was detected between the DR1-, 2-, 5-, and 52a-binding capacities and the known DR restrictions of a panel of synthetic peptides. This supports the immunologic relevance of the binding assay, and emphasizes the importance of determinant selection in defining the immune response of individuals. We have also examined the capacity of a panel of DR-restricted peptides to compete with one another for binding to DR1. The results obtained are compatible with a single peptide-binding site on DR molecules. The peptide-binding capacity of the four different DR types (DR1, DR2, DR5, and DR52a) has been further examined by testing a collection of 133 different peptides. This collection is unbiased with respect to previously known DR binding and restrictions, and includes peptides of eukaryotic, bacterial, and viral origins. It was found that: 1) approximately 15 to 35% of the peptides tested bound any given DR type; 2) DR-binding capacities appeared to correlate with each other, suggesting that different alleles of the DR isotype may recognize related structures on an Ag molecule; and 3) despite the statistical correlation between binding capacity of different DR types, approximately 50% of the peptides that were positive binders still were specific in that they could bind only one of the four DR molecules tested. Degenerate binding (i.e., binding to most or all the DR molecules tested) was detected in only a minority of the cases analyzed (approximately 25%).

Amino Acid Sequence↗
PubMed1990

19F NMR study of the myosin and tropomyosin binding sites on actin.

Actin was labeled with pentafluorophenyl isothiocyanate at Lys-61. The label was sufficiently small not to affect the rate or extent of actin polymerization unlike the much larger fluorescein 5-isothiocyanate which completely inhibits actin polymerization [Burtnick, L. D. (1984) Biochim. Biophys. Acta 791, 57-62]. Furthermore, the label resonances in the 376.3-MHz 19F NMR spectrum were unaffected by actin polymerization. However, the binding of the relaxing protein tropomyosin resulted in the fluorinated Lys-61 resonances broadening out beyond detection due to a substantial increase in the effective correlation time of the label. Similarly, the binding of myosin subfragment 1 to F-actin resulted in the dramatic broadening of the labeled Lys-61 resonances. Thus, Lys-61 on actin appears to be closely associated with the binding sites for both tropomyosin and myosin, suggesting that both these proteins can compete for the same site on actin. The other region of actin known to be involved in myosin binding, Cys-10, was found to be more remote from the actin-actin interfaces than Lys-61. Labels on Cys-10 exhibited substantially greater mobility than fluorescein 5-isothiocyanate attached to Lys-61 which appeared to be held down on the surface of the actin monomer. This may sterically hinder the actin-actin interaction about 1 nm from the tropomyosin/myosin binding site.

Actins↗
PubMed1990

Comparison of three related methods to select T cell-presented sequences of protein antigens.

A comparison of three methods to predict T cell-presented sequences within antigenic proteins led to the view that recurrent hydrophobic residues might nucleate excised peptides as alpha-helices against hydrophobic surfaces. Such helices could be protease-protected structures on their way to desetope binding. The compared methods were: the amphipathicity algorithm of DeLisi and Berzofsky [Proc. natn. Acad. Sci. U.S.A. 82, 7048-7052. (1985)] as modified by Margalit et al. [J. Immun. 138, 2213-2229. (1987)] the strip of-helix hydrophobicity algorithm (SOHHA) of Stille et al. [Molec. Immun. 24, 1021-1027. (1987)] and the motifs algorithm of Rothbard and Taylor [EMBO J. 7, 93-100. (1988)]. Correct prediction was defined at two levels of stringency: (1) the predicted sequence overlapped the experimentally reported sequence when the ratio of the intersection of both to the union of both greater than or equal to 0.5 or (2) the sequences touched when there was a non-empty intersection of both sequences. We determined the sensitivity (correct predictions/number of reported T cell-presented sequences) and efficiency (correct predictions/number of predictions) at each level of stringency. In terms of overlap, the SOHHA was more sensitive (0.43) than the amphipathicity (0.29) (not significant) and motifs (0.0, 0.0) (p less than 0.05) predictions and more efficient (0.35) than the amphipathicity (0.14) and motifs (0.0, 0.0) predictions. At the less stringent criterion touching, the amphipathicity method (0.71) was as sensitive as motif Rothbard-4 (0.79) and more sensitive than SOHHA (0.57) and motif Rothbard-5 (0.43). At that criterion, the SOHHA was more efficient (0.47) than the amphipathicity (0.36) and motifs (0.25, 0.40) methods. We hypothesize that the comparability of these approaches reflected the common, predominant influence of recurrent hydrophobicity in their predictions.

Algorithms↗
PubMed1990

Inhibition of collagen II-induced arthritis in mice--a comparison of the effects of Sch 24937, immunosuppressants and nonsteroidal antiinflammatory drugs on the clinical expression of disease.

Previous studies from this laboratory have described Sch 24937 as a potent immunosuppressive agent that is particularly effective in suppressing humoral immune responses in mice. These findings prompted an evaluation of the effects of Sch 24937 in type II collagen-induced arthritis in mice where disease manifestations include the development of a strong humoral response to the collagen antigen. Sch 24937 reduced the incidence and severity of arthritis in collagen sensitized mice which appeared to be directly related to the immunosuppressive properties of the drug. However in contrast to the steroid betamethasone which also exhibited immunosuppressive activity, Sch 24937 did not prevent the changes occurring in the lymphocyte population of the draining lymph nodes of mice immunized with type II collagen. While the exact mechanism of the immunosuppressive activity of Sch 24937 remains to be elucidated, its mode of action in suppressing arthritis differs at least to some extent from that of a steroid.

Animals↗
PubMed1990

Ethical reasoning associated with the feeding of terminally ill elderly cancer patients. An international perspective.

An international nursing research study examined the ethical decision-making of "good and experienced" registered nurses in eight countries. The subjects were asked about their decision to feed or not to feed a hypothetical terminally ill, mentally alert, elderly cancer patient who refuses to eat. Cultural variations were demonstrated in the decisions as well as differences in ethical justification. The majority of nurses who would not feed appeared to use the principle of autonomy, whereas nurses who would feed the patient used beneficence as justification. Conditions under which nurses would change their decision to either feed or not feed the patient against her will included doctor's orders and lack of peer support for the decision. The majority of nurses clearly experienced a dilemma.

Adult↗
PubMed1989

Surgical correction of concomitant cranioventral abdominal wall, caudal sternal, diaphragmatic, and pericardial defects in young dogs.

Seven puppies with concomitant congenital cranioventral abdominal wall, caudal sternal, diaphragmatic, and pericardial defects were treated surgically when they were between 10 and 12 weeks old. Three pups had ventricular septal defects that were not corrected. Diaphragmatic herniorrhaphy without extension of the diaphragmatic defect was performed in 6 pups. In one pup, paracostal extension of the diaphragmatic defect was necessary to decrease tension on the diaphragmatic closure. All pups were healthy at 6-month follow-up examinations, but 2 of 3 pups with ventricular septal defects had moderate generalized cardiomegaly evident on thoracic radiography. Early surgical correction of the congenital defects in these pups was usually simple because there were few or no thoracic adhesions, the dogs were small, the defects were small in 6 of 7 dogs, and the costal arch was pliable in each dog.

Abdominal Muscles↗
PubMed1989

Prediction of protein helices with a derivative of the strip-of-helix hydrophobicity algorithm.

The strip-of-helix hydrophobicity algorithm was devised to identify protein sequences which, when coiled as alpha or 3(10) helices, had one axial, hydrophobic strip and otherwise variably hydrophilic residues. The strip-of-helix hydrophobicity algorithm also ranked such sequences according to an index, the mean hydrophobicity of amino acids in the axial strip. This algorithm well predicted T cell-presented fragments of antigenic proteins. A derivative of this algorithm (the structural helices algorithm (SHA] was tested for the prediction of helices in crystallographically defined proteins. For the SHA, eight amino acid sequences, 2 cycles plus one amino acid in an alpha helix, with strip-of-helix hydrophobicity indices greater than 2.5, were selected with overlapping segments joined. These selections were terminated according to simple "capping rules," which took into account the roles of N-terminal Asn or Pro and C-terminal Gly in the stability of helices. In analyses of 35 crystallographically defined proteins with known alpha and 3(10) helices, the predictions with the SHA overlapped (had overlap indices x greater than or equal to 0.5) with 34% of known helices, touched (had overlap indices 0.5 greater than x greater than 0) or overlapped with 66% of known helices, or were neighboring (came within 6 residues) or touched or overlapped with 82% of known helices. At each level of judging the quality of prediction, the SHA was usually less sensitive (correct predictions/total number of known helices) and more efficient (correct predictions/total number of predictions) than the Chou-Fasman and Garnier-Robson methods. It was simpler in design and calculation. The chemical mechanisms underlying these algorithms appear to apply both to protein folding and to selection of T cell-presented antigenic sequences.

Algorithms↗
PubMed1988

Idiopathic pleural effusion in a dog.

Idiopathic pleural effusion was diagnosed in a 4-year-old female Poodle. Treatment included giving low doses of furosemide for 5 months and giving low doses of prednisone that eventually were given on alternate days and discontinued 16 months after initial evaluation. Idiopathic pleural effusion in this dog was eosinophilic. The clinical importance and diagnostic value of this finding were not determined. In man, idiopathic pleural effusions have a high correlation with eosinophilic pleural effusions.

Animals↗
PubMed1988

Growth allometry of craniomandibular muscles, tendons, and bones in the laboratory rat (Rattus norvegicus): relationships to oromotor maturation and biomechanics of feeding.

This study addressed the problem of how growth of craniomandibular muscles, tendons, and bones influences the acquisition of oromotor skills and biomechanics of feeding in the laboratory rat (Rattus norvegicus). Rats representing a 6.6-fold size range were dissected, and muscles, tendons, and mandibles were weighed. Cross-sectional areas of tendons and bones providing attachment surfaces for muscles were estimated. Ontogenetic scaling of craniomandibular muscles, tendons, and bones was described by using linear regression models, and departures from size-required compensations were used to characterize changes in oromotor function. A two-dimensional model was developed which permitted calculation of mechanical advantages of four masticatory muscles; the model was used to show how mandibular growth and tooth eruption influence the biomechanics of rat feeding. Relative to mandible weight, most jaw muscles scaled either isometrically or positively, tendon cross-sectional areas scaled isometrically or negatively, and bone surfaces scaled negatively. With the exception of the superficial masseter and internal pterygoid muscles, mechanical advantages did not change significantly during mandible growth. Growth patterns of craniomandibular muscles, tendons, and bones contribute significantly to changes in morphology and oromotor function.

Animals↗
PubMed1988

The immunohistochemical demonstration of early perineurial change in the development of localized hypertrophic neuropathy.

A case of localized hypertrophic mononeuropathy was studied by electron microscopy and immunohistochemistry for S100 protein, epitopes recognized by the Leu-7 monoclonal antibody, 200 kD neurofilament polypeptide, and the epithelial membrane antigen (EMA). The primary role of perineurial cell proliferation without the participation of Schwann cells in this process was directly demonstrated by EMA immunohistochemistry. Focal delamination of the EMA-positive perineurium, increased fibrosis between its layers, and compartmentalization of the fascicles by EMA-positive septae were the first recognizable changes. In practice, recognition of these early changes by EMA immunocytochemistry may be important for the clear definition of functionally unimpaired segmental margins for excision and graft implantation, and also for the future study of the process responsible for aberrant perineurial proliferation.

Adolescent↗
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↗