Biomedical subjects

C E Brewster

Publications and source records attributed to C E Brewster.

12 recordsLinked to original sources

PubMed1999

Association between src-kinases and the polyoma virus oncogene middle T-antigen requires PP2A and a specific sequence motif.

Polymoma virus encodes a potent oncogene, the middle T-antigen (MT), that induces cell transformation by copying the actions of tyrosine kinase associated growth factor receptors. A crucial component of MT transformation is its ability to bind and stimulate the activity of src-family kinases. However, the mechanism by which this is achieved remains unclear. Tyrosine phosphorylation of MT by src-kinases then provides binding sites for SH2 and PTB domain containing molecules in a paradigm of receptor action. We present evidence here that the MT/src complex contains equi-molar amounts of PP2A, and that phosphatase activity may be required for the interaction of MT with both PP2A and the src-family. PP2A, then, is a necessary component of the MT-src complex. We also show that two motifs in the 185 to 210 region of MT, each consisting of a basic area followed by a serine or threonine, are essential for interaction with src-kinases, but not PP2A. The spacing between the serine or threonine and the basic sequence also appears to be important. Substituting a cysteine residue in place of Thr203 in MT has no affect on the binding of pp60c-src, showing that these sites interact with src-kinases by a novel mechanism that does not require phosphorylation.

Amino Acid Sequence↗

PubMed1997

pp60c-src binding to polyomavirus middle T-antigen (MT) requires residues 185 to 210 of the MT sequence.

Interaction with the src family of tyrosine kinases is crucial to the transforming action of polyomavirus middle T-antigen (MT). Association with MT activates the tyrosine kinase activity of pp60(c-src) and, through subsequent MT phosphorylation, creates binding sites for signalling molecules whose stimulation culminates in cell transformation. Despite this importance, and many studies, little is known of the mechanisms by which pp60(c-src) binds to MT. We report here isolation of the first MT mutants that disrupt pp60(c-src) binding without affecting the interaction between MT and protein phosphatase 2A (PP2A). Through deletion analysis we established that interaction with pp60(c-src) requires the sequences between amino acids 185 and 210 of MT, but these residues have no effect on PP2A binding. Cells expressing these mutants showed few altered properties, indicating that the PP2A-MT interaction alone has little influence on cell phenotype. Subcellular location of these mutant MT molecules was indistinguishable by immunofluorescence analysis from that of wild-type MT but was altered markedly on loss of PP2A binding. This suggests a possible role for PP2A in specifying subcellular distribution.

Amino Acid Sequence↗

PubMed1994

Transformation by polyoma virus middle T-antigen involves the binding and tyrosine phosphorylation of Shc.

Polyoma virus middle T-antigen converts normal fibroblasts to a fully transformed, tumorigenic phenotype. It achieves this, at least in part, by binding and activating one of the non-receptor tyrosine kinases, pp60c-src, pp62c-yes or pp59c-fyn (reviewed in refs 2 and 3). As a result, middle T-antigen itself is phosphorylated on tyrosine residues, one of which (Tyr 315) acts as a binding site for the SH2 domains of phosphatidylinositol-3'OH kinase 85K subunit. Here we show that another tyrosine phosphorylation site in middle T-antigen (Tyr 250; refs 4, 5) acts as a binding region for the SH2 domain of the transforming protein Shc. This results in Shc also becoming tyrosine-phosphorylated and binding to the SH2 domain of Grb2 (ref. 10). This probably stimulates p21ras activity through the mammalian homologue of the Drosophila guanine-nucleotide-exchange factor Sos (reviewed in ref. 11). We suggest that middle T-antigen transforms cells by acting as a functional homologue of an activated tyrosine kinase-associated growth-factor receptor.

Adaptor Proteins, Signal Transducing↗

PubMed1994

Treatment approaches following foot and ankle injury.

A complete and effective rehabilitation program begins with a thorough subjective and objective evaluation of the problem and injury presented. Biomechanical changes, whether they are anatomically induced or as a result of a form of compensation, must be identified and properly addressed. During the initial phase of rehabilitation, the issues of pain and swelling often must be resolved before full range of motion and return to normal strength can be achieved successfully during the more advanced stages. It is important to incorporate the entire lower quadrant in exercises that are designed to improve proprioception and function, using both in open and closed kinetic chain exercises. Finally, the demands to which the patient is returning to must be recognized to successfully complete the recovery phase.

Ankle Injuries↗

PubMed1991

Musculoskeletal conditioning of the older athlete.

A musculoskeletal conditioning program has been shown to result in physical benefits for older individuals. Exercise may influence the rate of bone loss, muscular strength and mass, flexibility, and endurance levels. In turn, these factors may influence the potential for possible future injury. Special precautions should be taken for the older population with emphasis on environmental factors, hydration, and underlying health issues such as cardiorespiratory and orthopedic problems. These concerns may require modifications of the exercise program.

Aged↗

PubMed1990

Myofibroblasts and subepithelial fibrosis in bronchial asthma.

A thickened bronchial epithelial basement membrane has long been regarded as a histopathologic characteristic of bronchial asthma. As we had previously demonstrated that this phenomenon is due to the deposition of interstitial collagens and fibronectin, we have now sought to determine the nature of the cell responsible for this process by studying endobronchial biopsies from eight normal and seven asthmatic volunteers by immunohistochemistry and electron microscopy. Biopsies were stained with PR 2D3, a monoclonal antibody to myofibroblasts of the pericrypt sheath of the colon and a monoclonal antibody to alpha-smooth muscle actin. The thickness of the subepithelial collagen and the organelle content of the cells therein were determined by electron microscopy. The subepithelial collagen thickness in the normal subjects ranged from 2.16 to 6.26 microns, while that in the asthmatic subjects ranged from 3.75 to 11.1 microns (Mann-Whitney test; P = 0.05). Elongated cells in the collagen layer were identified by staining with PR 2D3. As this antibody also stains smooth muscle, consecutive frozen sections were stained for alpha-smooth muscle actin and the number of positive cells per millimeter of basement membrane was subtracted from the count for PR 2D3. This yielded a count of 4.9 to 9.4 cells/mm in the normal subjects and 11.9 to 20.6 cells/mm in the asthmatics (P = 0.001). There was a highly significant correlation between the depth of subepithelial collagen and the number of PR 2D3-positive, alpha-smooth muscle actin-positive cells (Spearman rank correlation; r = 0.764 and P = 0.006). Electron microscopy confirmed the myofibroblastic nature of these cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Actins↗

PubMed1988

Rehabilitation of the nonreconstructed anterior cruciate ligament-deficient knee.

Management of the patient with an ACL-deficient knee continues to be controversial. In the patient with an acute ligament disruption, arthroscopic examination if employed should be followed by a physical therapy program that restores not only range of motion and strength, but also prepares the athlete for the return to his sport. Patients with chronic ACL-insufficiency must be evaluated meticulously with regard to pain and instability with functional activities followed by a vigorous attempt at conservative care including bracing.

Athletic Injuries↗

PubMed1987

Development of a clinical physical therapy research program.

Clinical physical therapy research is important for the continued growth of the physical therapy profession. Such research results in improved patient care and heightens the professional standing of the physical therapy field. One of the major barriers to clinical physical therapy research is unfamiliarity with the research process by practicing physical therapists. The purpose of this article is to present a model for developing a clinical physical therapy research program that may assist novice investigators interested in initiating clinical physical therapy research at their facility.

Models, Theoretical↗

PubMed1987

Rehabilitation of shoulder joint instabilities.

The overall goal of the rehabilitation period is a return to full range of motion and a strengthening of the muscles that have a role in protecting the shoulder from injury. Rehabilitation is accomplished gradually and is performed initially in a limited range that excludes the terminal 30 degrees at either end. Two key muscle groups are to be strengthened. One group is for the glenohumeral joint: the deltoid, latissimus dorsi, pectoralis major, and the rotator cuff muscles--especially the subscapularis muscle for internal rotation and the infraspinatus and the teres minor muscles for external rotation. The second group, the trapezius, rhomboids, and serratus anterior muscles, is strengthened for scapular control. Finally, general conditioning and trunk flexibility exercises are critical for a return to former competitive levels.

Exercise Therapy↗

PubMed1986

Modification of quadriceps femoris muscle exercises during knee rehabilitation.

Rehabilitation of the quadriceps femoris muscle is the cornerstone of full recovery after inactivity, immobilization, or surgery of the knee. Muscle strengthening programs often are interrupted by patients' complaints of pain experienced during exercise, which frequently prolong the patients' convalescence period. Specific modifications of standard quadriceps femoris muscle exercises often allow completely pain-free exercise, thus providing a faster progression of treatment and a subsequently shorter rehabilitation period. The purposes of this article are to review briefly patellofemoral biomechanics as it relates to quadriceps muscle rehabilitation and to summarize several modifications that in our clinical experience repeatedly have reduced pain during exercise.

Ankle Joint↗

PubMedDate not supplied

The effects of electrical stimulation on the quadriceps during postoperative knee immobilization.

Immobilization of the knee after anterior cruciate ligament (ACL) reconstruction results in marked thigh atrophy and decrease in quadriceps strength that may prolong the rehabilitation program of the injured athlete. Fifteen male volunteers undergoing ACL reconstruction were divided into two groups, stimulation (during immobilization) and nonstimulation. Measurements of thigh circumference and isometric quadriceps strength were tested preoperatively, immediately after cessation of cast immobilization (6 weeks), and at 9 and 12 weeks postoperatively. The changes in circumference and strength between the first preoperative test and all subsequent tests were compared for statistical significance (Student's t-test, P less than 0.5) between the two groups. The decrease in quadriceps strength of the stimulation group during immobilization was significantly less than that of the nonstimulation group, although later differences between the two groups were not significant. There were no significant differences in thigh atrophy between the two groups. In conclusion, isometric quadriceps torque decreases resulting from immobilization can be significantly lessened by application of electrical stimulation during immobilization. Electrical stimulation to the quadriceps does not significantly alter thigh circumference changes that occur during immobilization.

Adolescent↗

PubMedDate not supplied

Acute tears of the medial head of the gastrocnemius.

Twenty-five patients with acute tears of the medial head of the gastrocnemius were evaluated in follow-up from 1 to 3 years after injury. The patients were treated with a heel lift, calf sleeve, and physical therapy. The majority of the patients were men who injured their dominant lower extremity in one explosive episode. Cybex II testing revealed no significant difference in the plantarflexion strength of the noninjured and injured extremity after healing. All patients returned to their previous level of athletic activity.

Adult↗