Search PubMed⌕ Search

Biomedical subjects

T Hunter

Publications and source records attributed to T Hunter.

At least 289 records · Page 16Linked to original sources
PubMed1986

Phosphorylation of the transforming protein of Rous sarcoma virus: direct demonstration of phosphorylation of serine 17 and identification of an additional site of tyrosine phosphorylation in p60v-src of Prague Rous sarcoma virus.

We provide direct evidence that serine 17 is the major site of serine phosphorylation in p60v-src, the transforming protein of Rous sarcoma virus, and in its cellular homolog, p60c-src. The amino acid composition of the tryptic peptide containing the major site of serine phosphorylation in p60v-src was deduced by peptide map analysis of the protein labeled biosynthetically with a variety of radioactive amino acids. Manual Edman degradation revealed that the phosphorylated serine in this peptide was the amino terminal residue. These data are consistent only with the phosphorylation of serine 17. The major site of serine phosphorylation in chicken p60c-src, the cellular homolog of p60v-src, is contained in a tryptic peptide identical to that containing serine 17 in p60v-src of Schmidt Ruppin Rous sarcoma virus of subgroup A. Serine 17 is therefore also phosphorylated in p60c-src. The p60v-src protein encoded by Prague Rous sarcoma virus was found to contain two sites of tyrosine phosphorylation. The previously unrecognized site of tyrosine phosphorylation may be tyrosine 205 or possibly tyrosine 208. Treatment of Prague Rous sarcoma virus-infected cells with vanadyl ions stimulated the protein kinase activity of p60v-src and increased the phosphorylation of tyrosine 416 but not the phosphorylation of the additional site of tyrosine phosphorylation.

Amino Acid Sequence↗
PubMed1986

Altered sites of tyrosine phosphorylation in pp60c-src associated with polyomavirus middle tumor antigen.

We characterized the tyrosine phosphorylation sites of free pp60c-src and of pp60c-src associated with the polyomavirus middle tumor antigen (mT) in transformed avian and rodent cells. The sites of tyrosine phosphorylation in the two populations of pp60c-src were different, both in vitro and in vivo. Free pp60c-src was phosphorylated in vitro at a single site, tyrosine 416. pp60c-src associated with mT was phosphorylated in vitro on tyrosine 416 and on one or more additional tyrosine residues located in the amino-terminal region of the molecule. Free pp60c-src in polyomavirus mT-transformed cells was phosphorylated in vivo on tyrosine 527. In contrast, pp60c-src associated with mT was phosphorylated in vivo on tyrosine 416 and not detectably on tyrosine 527. Thus, the in vivo phosphorylation sites of pp60c-src associated with mT in transformed cells are identical to those of pp60v-src, the Rous sarcoma virus transforming protein. The results suggest that altered phosphorylation of pp60c-src associated with mT may play a role in the enhancement of the pp60c-src protein kinase activity and in cell transformation by polyomavirus.

Amino Acids↗
PubMed1986

The protein-tyrosine kinase substrate p36 is also a substrate for protein kinase C in vitro and in vivo.

p36, a major in vivo substrate of protein-tyrosine kinases, is shown to be phosphorylated at serine 25, a site very close to the major site of tyrosine phosphorylation by pp60v-src, tyrosine 23 (J. R. Glenney, Jr., and B. F. Tack, Proc. Natl. Acad. Sci. USA 82:7884-7888, 1985). We present evidence suggesting that protein kinase C mediates phosphorylation of serine 25.

Amino Acid Sequence↗
PubMed1986

From c-src to v-src, or the case of the missing C terminus.

The acutely-transforming avian virus, Rous sarcoma virus, arose as the result of the transduction of the c-src gene of the chicken by a relatively benign avian leucosis virus. In the viral genome, the src gene is expressed in the form of a 60 kDa phosphoprotein, pp60v-src, which is a protein-tyrosine kinase. Cellular transformation results from the excessive or chronic phosphorylation of cellular proteins by pp60v-src. The c-src gene has been present in the genome of eukaryotes, at least since the evolutionary emergence of Drosophila. Like its viral descendant, it encodes a 60 kDa protein-tyrosine kinase, termed pp60c-src. Both pp60v-src and pp60c-src are bound to membranes. pp60c-src is expressed at low levels in most cell types but it is found in high amounts in neural tissues and in platelets. pp60c-src might therefore participate in vesicle-mediated secretion. pp60c-src is less active as a protein-tyrosine kinase then pp60v-src and does not induce cellular transformation, even when expressed at levels comparable to those of pp60v-src. The potency of pp60v-src apparently results from the fact that the region of the c-src gene encoding the C terminus of pp60c-src was lost during the genesis of the v-src gene. This region of pp60c-src contains a site of tyrosine phosphorylation whose occupancy apparently leads to diminished enzymatic activity. The deletion of this site may abolish the normal regulation of the protein kinase activity. If so, transformation could simply be the consequence of the inability of the cell to regulate the activity of pp60v-src.

Animals↗
PubMed1986

Delayed evoked potentials in patients with ankylosing spondylitis.

Visual, brainstem auditory and somatosensory evoked potentials were studied in 30 patients with ankylosing spondylitis (AS). Twenty-four patients were male and 6 were female. The mean age was 44 years and the mean duration of AS was 16 years (range 1-34 years). Evoked potential abnormalities affecting the visual pathways were recorded in 18 (60%) patients. Somatosensory evoked potentials were abnormal in 19 (63%) patients, and 9 patients had impaired function on brainstem auditory evoked potentials. The pathophysiology of these abnormalities is unknown. We recommend that caution be exercised in interpreting delayed evoked potentials if multiple sclerosis is suspected in a patient with AS.

Adult↗
PubMed1985

Protein phosphorylation and growth control.

Many growth factor receptors and retroviral transforming proteins share the property of phosphorylating proteins on tyrosine. Several substrates for both types of protein-tyrosine kinase have been identified. Treatment of quiescent cells with growth factors such as EGF and PDGF, whose receptors have ligand-stimulated protein-tyrosine kinase activities, induces tyrosine phosphorylation of three proteins, p45, p42 and p41. Two phosphorylated forms of p42 are found, the more basic of which is present in some but not all cells transformed by viral protein-tyrosine kinases. p42 is rapidly (as early as 1 min) but transiently (decreased to baseline by 2h) phosphorylated following PGDF or EGF treatment of quiescent fibroblasts. At saturating levels of mitogen the stoichiometry of p42 phosphorylation is greater than 50%. p42 is a highly conserved, rare (0.002% of total cell protein), soluble cytoplasmic protein. IGF I and insulin, whose receptors also have ligand-stimulated protein-tyrosine kinase activity, induce p42 phosphorylation in appropriate cells. In the case of insulin this effect has been observed in cells with large numbers of insulin receptors. p42 is also phosphorylated in response to mitogens whose receptors lack protein-tyrosine kinase activity, for example 12-O-tetradecanoylphorbol-13-acetate (TPA) and thrombin. For TPA there is evidence that this is an indirect effect due to the activation of a protein-serine/threonine kinase. On the basis of the highly conserved nature of this response and its generality, it seems likely that tyrosine phosphorylation of p42 is important for at least early responses to mitogens.

Animals↗
PubMed1985

Development of a prosthetic venous valve.

The pathology of thrombophlebitis primarily results from the obliteration of venous valves in the lower extremities. The objective of this study was to develop a prosthetic venous valve that could be implanted in the human femoral system to ameliorate the deleterious effects of thrombophlebitis. Prosthetic venous valves were produced from two materials: Pellethane valves were fabricated from a dip-casting process; umbilical vein valves were produced by a fixation process. The valves were evaluated as implants within the external jugular veins of 10 research dogs. Each animal was implanted with one Pellethane valve in one external jugular vein and one umbilical vein venous valve in the contralateral jugular vein. Each valve was positioned over a stainless-steel cylinder that had been implanted into the jugular veins in such a manner that there existed no blood-cylinder interaction. Patency of the valves was determined by X-ray venography at 24, 48, and 72 h and at 5 and 8 days postoperatively. All of the umbilical vein venous valves were occluded by the end of 48 h, whereas two of the Pellethane venous valves remained patent for at least 5 days but were occluded at 8 days. The results of this study suggest the possibility of success of Pellethane valve implants in the venous circulation and indicate future directions for study.

Animals↗
PubMed1985

Geometry and motion of the knee for implant and orthotic design.

By analysing sections of distal femurs in the computer, and by making direct measurements, the posterior femoral condyles were shown to closely fit spherical surfaces. The center of the spheres were then used as reference points and used to define reference axes in a motion study. In flexing from 0 to 120 degrees the medial femoral condyle moved little, the lateral moved posteriorly by 17 mm, and there was an axial rotation of 20 degrees. The data were applied to implant and orthotic design and evaluation.

Computers↗
PubMed1985

Protein kinase C phosphorylates pp60src at a novel site.

The transforming protein of Rous sarcoma virus (pp60v-src) and its normal cellular homolog (pp60c-src) are demonstrated to be phosphorylated at serine 12 in vivo under certain conditions. We propose that protein kinase C is responsible for this modification based on the following evidence. First, the tumor promoters, 12-O-tetradecanoylphorbol-13-acetate and teleocidin, and synthetic diacylglycerol, known activators of protein kinase C in vivo, cause nearly complete phosphorylation of pp60src at serine 12. Second, among five purified serine/threonine-specific protein kinases tested, only protein kinase C phosphorylates pp60c-src and pp60v-src in vitro at serine 12. Third, purified protein kinase C phosphorylates a synthetic peptide corresponding to the N-terminal 20 amino acids of pp60c-src at serine 12. The physiological significance of this novel phosphorylation is discussed.

Amino Acid Sequence↗
PubMed1985

Effects of age and disease on the pharmacokinetics and pharmacodynamics of sulindac.

The disposition and effect on hemostasis of a single 150 mg dose of sulindac was studied in young healthy subjects and in older patients with arthritis. Older patients were restudied after 2 weeks of sulindac, 150 mg b.i.d. The only difference in disposition of the first dose was a reduced plasma sulfone metabolite concentration in the elderly patients with arthritis. Chronic sulindac dosing resulted in accumulation of the drug and its sulfone and sulfide metabolites in plasma to a greater extent than previously reported for young subjects. No differences in renal clearance of sulindac and its sulfone metabolite related to age or chronic drug dosing were observed. No renal excretion of the active sulfide metabolite was detected. Bleeding time in the elderly patients was shorter than in the young healthy subjects before sulindac dosing, but was prolonged in the elderly patients after 2 weeks of dosing to values similar to control data from the young healthy subjects. This change correlated weakly with plasma sulfide metabolite concentrations. Differences in bleeding time were not reflected in changes in platelet aggregation induced by adenosine diphosphate either with respect to age or chronic drug dosing. Our data provide no justification for lowering the recommended dose of sulindac for patients older than 65 years of age.

Adult↗
PubMed1985

Restriction of the in vitro and in vivo tyrosine protein kinase activities of pp60c-src relative to pp60v-src.

The tyrosine protein kinase activities of pp60c-src and pp60v-src were compared. The activities were qualitatively similar in vitro when the src proteins were bound in an immune complex with monoclonal antibody; both proteins utilized either ATP or GTP as phosphate donors, preferred Mn2+ to Mg2+, and had similar exogenous substrate specificities. The specific activity of pp60c-src was about 10-fold lower than that of pp60v-src for exogenous substrate phosphorylation but was only 1.1- to 2-fold lower than that of pp60v-src for autophosphorylation. Six glycolytic enzymes, including three not previously identified as substrates for pp60src phosphorylation, were phosphorylated by both pp60c-src and pp60v-src. Levels of pp60c-src fourfold higher than the amount of pp60v-src in src-plasmid-transformed cells did not detectably alter the level of phosphotyrosine in cellular proteins, but increasing the expression of pp60c-src another twofold (which induces cells to form foci in monolayer culture (P.J. Johnson, P.M. Coussens, A.V. Danko, and D. Shalloway, Mol. Cell. Biol. 5:1073-1083, 1985) resulted in a threefold increase in the level of cellular protein phosphotyrosine. Immunoprecipitation and analysis of the alkali-stable phosphoproteins by two-dimensional electrophoresis showed that, in contrast to pp60v-src-transformed cells, pp36 and enolase are only weakly phosphorylated in these high-level pp60c-src overexpresser cells. Even allowing for the in vitro differences in specific activities of phosphorylation, these results suggest that the pp60c-src tyrosine protein phosphorylating activity may be restricted relative to that of pp60v-src by additional in vivo mechanisms.

Adenosine Triphosphate↗
PubMed1985

Sulfasalazine in severe rheumatoid arthritis: a study to assess potential correlates of efficacy and toxicity.

Thirty-one patients with chronic active rheumatoid arthritis (RA) resistant to gold and/or penicillamine therapy, were treated with sulfasalazine, 2-3 g daily, in a 12-week open study. Nineteen patients completed the study, and of these, 13 showed clinical improvement. Twelve patients were withdrawn from the study because of nausea (8), mouth ulcers (1), disease flare (1) and noncompliance (2). There was no significant difference in serum sulfasalazine concentrations among responders, nonresponders and patients who were withdrawn. Our data suggest that sulfasalazine may be of benefit in the treatment of RA. Further studies are necessary to determine if toxicity and/or efficacy might be related to serum concentrations of sulfasalazine metabolites.

Adult↗
PubMed1985

Measurements of maximum respiratory pressures in polymyositis and dermatomyositis.

Measurements of maximum respiratory pressures and routine pulmonary function tests were performed in 8 patients with polymyositis (PM) and 2 patients with dermatomyositis (DM). Serial measurements of routine pulmonary function tests in 8 patients remained unchanged. Maximum respiratory pressures were decreased initially in 7 patients with proximal muscle weakness and clinically active muscle disease and improved with corticosteroid therapy in the 5 patients who were followed serially. In 3 patients with clinically stable disease the maximum respiratory muscle power was normal. Serial measurements of maximum respiratory pressures have been of value in monitoring patients with PM and DM.

Adult↗
PubMed1985

Plasma and synovial fluid concentrations of salicylic acid and its metabolites in patients with joint effusions.

Equilibration of salicylic, salicyluric and gentisic acids between plasma and synovial fluid (SF) was measured in 36 patients receiving chronic salicylate therapy and from whom SF was required for diagnostic purposes. Gentisic and salicyluric acids equilibrated completely, while SF salicylic acid concentration was less than that in plasma. The presence of significant gentisic acid concentrations in SF could contribute to the therapeutic response to chronic salicylate therapy, since its antiinflammatory effect is even greater than that of acetylsalicylic acid.

Adult↗