Biomedical subjects

J S Yu

Publications and source records attributed to J S Yu.

At least 91 records · Page 5Linked to original sources

PubMed1995

Dysfunction of protein kinase FA/GSK-3 alpha in lymphocytes of patients with schizophrenic disorder.

As compared to normal people, the lymphocytes of patients with schizophrenia were found to have an impairment of ATP.Mg-dependent protein phosphatase activation. More importantly, the impaired protein phosphatase activation in the lymphocytes of schizophrenic patients could be consistently and completely restored to normal by exogenous pure protein kinase FA/glycogen synthase kinase-3 alpha (kinase FA/GSK-3 alpha) (the activating factor of ATP.Mg-dependent protein phosphatase), indicating that the molecular mechanism for the impaired protein phosphatase activation in schizophrenic patients may be due to a functional loss of kinase FA/GSK-3 alpha. Immunoblotting and kinase activity analysis in an anti-kinase FA/GSK-3 alpha immunoprecipitate further demonstrate that both cellular activities and protein levels of kinase FA/GSK-3 alpha in the lymphocytes of schizophrenic patients were greatly impared as compared to normal controls. Statistical analysis revealed that the lymphocytes isolated from 37 normal people contain kinase FA/GSK-3 alpha activity in the high levels of 14.8 +/- 2.4 units/mg of cell protein, whereas the lymphocytes of 48 patients with schizophrenic disorder contain kinase FA/GSK-3 alpha activity in the low levels of 2.8 +/- 1.6 units/mg, indicating that the different levels of kinase FA/GSK-3 alpha activity between schizophrenic patients and normal people are statistically significant. Taken together, the results provide initial evidence that patients with schizophrenic disorder may have a common impairment in the protein levels and cellular activities of kinase FA/GSK-3 alpha, a multisubstrate protein kinase and a multisubstrate protein phosphatase activator in their lymphocytes.

Amino Acid Sequence↗

PubMed1995

Association of protein kinase FA/GSK-3alpha (a proline-directed kinase and a regulator of protooncogenes) with human cervical carcinoma dedifferentiation/progression.

Computer analysis of protein phosphorylation-sites sequence revealed that most transcriptional factors and viral oncoproteins are prime targets for regulation of proline-directed protein phosphorylation, suggesting an association of proline-directed protein kinase (PDPK) family with neoplastic transformation and tumorigenesis. In this report, an immunoprecipitate activity assay of protein kinase FA/glycogen synthase kinase-3alpha (kinase FA/GSK-3alpha) (a particular member of PDPK family) has been optimized for human cervical tissue and used to demonstrate for the first time significantly increased (P < 0.001) activity in poorly differentiated cervical carcinoma (82.8 +/- 6.6 U/mg of protein), moderately differentiated carcinoma (36.2 +/- 3.4 U/mg of protein), and well-differentiated carcinoma (18.3 +/- 2.4 U/mg of protein) from 36 human cervical carcinoma samples when compared to 12 normal controls (4.9 +/- 0.6 U/mg of protein). Immunoblotting analysis further revealed that increased activity of kinase FA/GSK-3alpha in cervical carcinoma is due to overexpression of protein synthesis of the kinase. Taken together, the results provide initial evidence that overexpression of protein synthesis and cellular activity of kinase FA/GSK-3alpha may be involved in human cervical carcinoma dedifferentiation/progression, supporting an association of proline-directed protein kinase with neoplastic transformation and tumorigenesis. Since protein kinase FA/GSK-3alpha may function as a possible regulator of transcription factors/proto-oncogenes, the results further suggest that kinase FA/GSK-3alpha may play a potential role in human cervical carcinogenesis, especially in its dedifferentiation and progression.

Amino Acid Sequence↗

PubMed1995

Melorheostosis with an ossified soft tissue mass: MR features.

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Femur↗

PubMed1995

Desmoplastic fibroma of the calcaneus.

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Adult↗

PubMed1995

Effect of Mg2+ concentrations on phosphorylation/activation of phosphorylase b kinase by cAMP/Ca(2+)-independent, autophosphorylation-dependent protein kinase.

In a previous report [Yu and Yang, Biochem. Biophys. Res. Commun. 207, 140-147 (1995)], phosphorylase b kinase from rabbit skeletal muscle was found to be phosphorylated and activated by a cyclic nucleotide- and Ca(2+)-independent protein kinase previously identified as an autophosphorylation-dependent multifunctional protein kinase (autokinase) from brain and liver [Yang et al., J. Biol. Chem. 262, 7034-7040, 9421-9427 (1987)]. In this report, the effect of Mg2+ ion concentration on the auto-kinase-catalyzed activation of phosphorylase b kinase is investigated. The levels of phosphorylation and activation of phosphorylase b kinase catalyzed by auto-kinase are found to be dependent on the concentration of Mg2+ ion used. Phosphorylation of phosphorylase b kinase at high Mg2+ ion (> 9 mM) is 2-3 times higher than that observed at low Mg2+ ion (1 mM) and this results in a further 2- to 3-fold activation of the enzyme activity at high Mg2+ ion. Analysis of the phosphorylation stoichiometry of alpha and beta subunits of phosphorylase b kinase at different Mg2+ ion concentrations further reveals that the phosphorylation level of the beta subunit remains almost unchanged, whereas the phosphorylation level of the alpha subunit increases dramatically and correlates with the increased enzyme activity. In similarity with the beta subunit, phosphorylations of myelin basic protein and histone 2A by auto-kinase are also unaffected by Mg2+ ion. Taken together, the results provide initial evidence that Mg2+ ion may specifically render the alpha subunit a better substrate for auto-kinase to cause further phosphorylation/activation of phosphorylase b kinase, representing a new mode of control mechanism for the regulation of auto-kinase involved in the phosphorylation and concurrent activation of phosphorylase b kinase.

Adenosine Triphosphate↗

PubMed1995

Gene therapy for brain tumors.

Gene therapy has opened new doors for treatment of neoplastic diseases. This new approach seems very attractive, especially for glioblastomas, since treatment of these brain tumors has failed using conventional therapy regimens. Many different modes of gene therapy for brain tumors have been tested in culture and in vivo. Many of these approaches are based on previously established anti-neoplastic principles, like prodrug activating enzymes, inhibition of tumor neovascularization, and enhancement of the normally weak anti-tumor immune response. Delivery of genes to tumor cells has been mediated by a number of viral and synthetic vectors. The most widely used paradigm is based on the activation of ganciclovir to a cytotoxic compound by a viral enzyme, thymidine kinase, which is expressed by tumor cells, after the gene has been introduced by a retroviral vector. This paradigm has proven to be a potent therapy with minimal side effects in several rodent brain tumor models, and has proceeded to phase 1 clinical trials. In this review, current gene therapy strategies and vector systems for treatment of brain tumors will be described and discussed in light of further developments needed to make this new treatment modality clinically efficacious.

Antibody Formation↗

PubMed1995

Plantar compartments of the foot: MR appearance in cadavers and diabetic patients.

PURPOSE: To demonstrate the plantar compartments of the foot on magnetic resonance (MR) images. MATERIALS AND METHODS: The plantar compartments of four cadaveric feet underwent MR imaging and were sectioned. Fifteen MR studies in 11 patients with compartmental fluid were evaluated. The epicenter of infection was determined from review of the history, radiographs, and MR images. RESULTS: In the cadaveric feet, distribution of contrast material conformed to the compartmental anatomic features. MR findings in the specimen correlated exactly with gross findings. All seven feet with infection centered at the second through fourth metatarsal heads demonstrated only central compartment fluid. In seven of eight feet with a more medial or lateral epicenter of infection, fluid was seen in the lateral or medial compartment and in the central compartment. In one foot with a lateral epicenter of infection, fluid was confined to the lateral compartment. CONCLUSION: MR imaging accurately depicts the compartmental anatomic features of the foot.

Cadaver↗

PubMed1995

Complete dislocation of the knee: spectrum of associated soft-tissue injuries depicted by MR imaging.

OBJECTIVE: Complete knee dislocation is a rare injury. The purpose of this study was to evaluate the spectrum of injuries that are depicted by MR imaging in patients with a dislocation of the knee and to determine if there is any predictive factor that might indicate those patients who may be at risk for popliteal nerve injury. MATERIALS AND METHODS: A retrospective search for patients sustaining traumatic knee dislocations who had radiographs and an MR imaging examination of the knee as part of their initial evaluation was done at three level I trauma centers for the period between 1989 and 1993. Each MR examination was independently reviewed by three osteoradiologists for ligamentous, tendinous, meniscal, and osseous injuries. Equivocal diagnoses were decided by consensus. Only patients who underwent surgery were selected. MR imaging findings were confirmed at the time of surgery. Seventeen patients (15 men, two women; age range, 14-62 years; mean age, 29 years) were studied. Motor vehicle accident, fall from a height, a vehicle striking a pedestrian, and football injury were common mechanisms of injury. Posterior dislocation (seven patients) and anterior dislocation (five patients) were the most common injuries. RESULTS: At the time of surgery, all patients had complete tears of the anterior cruciate ligament, 15 had complete tears of the posterior cruciate ligament, nine had complete tears of the medial collateral ligament, and 12 had tears of the fibular collateral ligament (nine tore both the fibular collateral ligament and the biceps femoris tendon). Popliteal tendon tears occurred in eight patients (six complete, two partial). Of the six patients with complete tears of the popliteal tendon, five occurred at the musculotendinous junction; all were the result of either posterior or posterolateral dislocations. Four patients had injuries to the peroneal nerve; three of the four also had tears of the popliteal tendon. On MR imaging, the integrity of the anterior cruciate and lateral collateral ligaments was correctly depicted in all 17 patients; evaluation of the posterior cruciate ligament resulted in one false-positive and one false-negative diagnosis of a tear; evaluation of the medial collateral ligament resulted in one false-positive diagnosis of a tear; and one false-positive diagnosis of a tear occurred with evaluation of the popliteal tendon. CONCLUSION: Knee dislocations cause extensive disruption of the ligaments that stabilize the knee and the surrounding soft-tissue structures, including the popliteal artery. Nearly all will result in disruption of the cruciate ligments and, often, injury of the collateral ligaments. An injury to the popliteal tendon denotes a more severe injury. The mechanism of injury that results in a popliteal tendon tear may also increase the possibility of a peroneal nerve injury. Recognition of this pattern of injuries on MR imaging enables precautionary observation for ischemic changes of the foot to be instituted in patients that otherwise may not be considered at risk for acute vascular compromise.

Adolescent↗

PubMed1995

Correlation of MR imaging and pathologic findings in athletes undergoing surgery for chronic patellar tendinitis.

OBJECTIVE: Jumper's knee, or chronic patellar tendinitis, can be a source of considerable pain in athletes. The changes that occur with shearing of the tendinous fibers from repeated microtrauma can progress to significant degeneration and increase the risk of tendon rupture. In order to better understand this phenomenon, a correlative study relating the MR imaging and pathologic findings was performed. SUBJECTS AND METHODS: Nine high-performance athletes 18-22 years old (mean age, 20 years) underwent operation of 11 knees for long-standing jumper's knee. The average period of symptoms was 3 years (range, 2 to 6 years). MR knee examinations were performed before surgery in all athletes. The symptoms, MR findings, and pathological findings were correlated. RESULTS: There was focal thickening in the proximal one third of the patellar tendon (range, 9-16 mm; mean, 12 mm) in all 11 knees, involving the medial portion of the tendon in 10 and the center in one. On proton-density-weighted MR images, all knees demonstrated a focus of abnormal signal intensity in the proximal one third of the patellar tendon. On T2-weighted MR images, 10 knees demonstrated abnormal signal intensity; eight were isointense to that seen on proton-density-weighted images, and two were relatively hyperintense. Ten tendons demonstrated a poorly defined posterior margin. Pathologically, the areas of abnormal signal intensity corresponded to tissue containing tenocyte hyperplasia, prominent angiogenesis with endothelial hyperplasia, loss of longitudinal collagenous architecture, and microtears with collagen fiber separation. Hyaline degeneration was present in specimens from every patient. CONCLUSION: In athletes with chronic patellar tendinitis, areas of abnormal signal intensity on MR imaging corresponded to degenerative pathologic changes consistent with angiofibroblastic tendinosis. In nearly all patients, the tendon thickening occurred eccentrically. Disproportionate medial tendon thickening may be related to unequal tensile forces across the knee joint, resulting in greater stress on the medial portion of the extensor mechanism of the knee.

Adolescent↗

PubMed1995

Assessment of articular cartilage thickness of the humeral head: MR-anatomic correlation in cadavers.

OBJECTIVE: The purpose of our study was to evaluate several commonly used MR sequences to determine how accurately each demonstrates the thickness of the articular cartilage of the humeral head. MATERIALS AND METHODS: Ten cadaveric shoulders (age at death, 58-92 years; mean, 79 years) were imaged with fat-suppressed transaxial T1-weighted spin-echo three-dimensional gradient-recalled sequences, both before and after injection of 12 ml of diluted gadopentetate dimeglumine. Articular cartilage was measured to the nearest 10th of a millimeter on the MR images and corresponding anatomic sections. RESULTS: Cartilage could not be differentiated from surrounding structures in 14 of 112 locations (13%) on the spin-echo images obtained without contrast material, in 4 of 112 locations (4%) on the spin-echo images obtained with contrast material, in 4 of 112 locations (4%) on the gradient-echo images obtained without contrast material, and in 6 of 112 locations (5%) on the gradient-echo images obtained with contrast material. Mean true cartilage thickness was 1.23 mm (SD, 0.52 mm). The mean MR-anatomic differences (absolute values) were 0.38 mm for the spin-echo images obtained without contrast material, 0.42 mm for the spin-echo images obtained with contrast material, 0.49 mm for the gradient-echo images obtained without contrast material, and 0.37 mm for the gradient-echo images obtained with contrast material. There was a tendency to overestimate thin cartilage and to underestimate thick cartilage. CONCLUSION: Several of the routinely used MR sequences, with and without intraarticular contrast medium, may cause errors in the assessment of the articular cartilage of the humeral head. Some of these errors result from either insufficient contrast between cartilage and surrounding structures or inadequately concentrated contrast medium.

Aged↗

PubMed1995

MR arthrography of the hip: improved imaging of the acetabular labrum with histologic correlation in cadavers.

OBJECTIVE: The objective of this study was to correlate findings on conventional MR imaging and MR arthrography of the hip with pathologic findings in cadavers with abnormal labra to determine (1) the efficacy of MR imaging in assessing labral degeneration, (2) whether delineation of the labrum from the joint capsule is possible, and (3) if the conspicuity of surface abnormalities of the labrum is improved by administering intraarticular contrast material. MATERIALS AND METHODS: Twelve cadaveric hip joints were obtained from elderly cadavers. Each hip was examined using fat-suppressed three-dimensional spoiled GRASS (gradient-recalled acquisition in the steady state) (SPGR) imaging and T1-weighted spin-echo imaging before and after intraarticular injection of contrast material. Thirty-six labral sections (three from each hip joint) were evaluated histologically to determine the labral-capsular relationship, the presence of degeneration, and the configuration of the labral base. These findings were correlated with the results of a blinded MR evaluation of these sections. RESULTS: Delineation of the labrum from the adjacent joint capsule was possible on SPGR and T1-weighted MR arthrographic images (34 of 36 and 33 of 36 specimens, respectively), but was not consistently possible on standard SPGR and T1-weighted MR images (7 of 36 and 4 of 36 specimens, respectively). The sensitivities and specificities of the various MR sequences in evaluating labral degeneration varied from 50% to 67%, and from 25% to 94%. Increased signal at the base was common in both the normal (n = 12) and the abnormal (n = 24) labrum. CONCLUSION: Conspicuity of the acetabular labral complex is enhanced with the intraarticular administration of contrast material. Although MR arthrography did not improve our specificity for diagnosing labral degeneration, the detection of surface abnormalities, particularly those near the base, was significantly improved.

Acetabulum↗

PubMed1995

MR imaging versus alternative imaging techniques.

MR imaging is the method of choice in evaluating a large number of soft-tissue abnormalities; however, it has certain draw-backs, some of which may make other imaging methods more suitable. MR imaging is more expensive than alternative imaging methods; it may not be affordable for screening purposes and for diagnoses obtainable by less expensive imaging methods. In addition, immediate scheduling is not always possible for MR imaging, and an MR scanner may not be available close to the patient's home, which may be important for imaging follow-up. These factors support the use of other imaging modalities, with sonography frequently being the appropriate choice. In some situations, mainly in the presence of certain biomedical implants and devices, MR imaging is contraindicated. Additionally, under some circumstances patient access may be difficult during MR imaging; sonography and CT therefore are preferable (as for imaging guided biopsy). Moreover, some artifacts, such as motion artifacts, may have less relevance in other imaging methods (such as sonography), which may be important in noncooperative patients and children. MR imaging may not be specific in tumors and infection; this deficiency is shared with most alternative imaging methods, with the exception of scintigraphy in selected indications. Lastly, standard radiography and CT commonly are superior to MR imaging in diagnosing calcification and abnormalities of cortical bone. Consequently, in selected cases and for screening purposes, methods other than MR imaging should be considered for depicting soft-tissue structures.

Artifacts↗

PubMed1994

Okadaic acid, a serine/threonine phosphatase inhibitor, induces tyrosine dephosphorylation/inactivation of protein kinase FA/GSK-3 alpha in A431 cells.

Alkaloids↗

PubMed1994

Tyrosine dephosphorylation and concurrent inactivation of protein kinase FA/GSK-3 alpha by genistein in A431 cells.

Modulation of protein kinase FA/GSK-3 alpha by tyrosine phosphorylation in A431 cells was investigated. Kinase FA/GSK-3 alpha was found to exist in a highly tyrosine-phosphorylated/activated state in resting cells but could become tyrosine-dephosphorylated and inactivated down to less than 30% of control values in a concentration-dependent manner by 50-400 microM genistein (a specific tyrosine kinase inhibitor), as demonstrated by metabolic 32P-labeling of the cells followed by immunoprecipitation and two-dimensional phosphoamino acid analysis and by immunodetection in an antikinase FA/GSK-3 alpha immunoprecipitate kinase assay. Taken together, the results provide evidence that kinase FA/GSK-3 alpha may exist in a highly tyrosine-phosphorylated/activated state in resting cells which can be tyrosine-dephosphorylated and inactivated by extracellular stimulus and that tyrosine kinase(s) and/or tyrosine phosphatase(s) may play a role in the modulation of kinase FA/GSK-3 alpha activity in cells.

Amino Acid Sequence↗

PubMed1994

Tumor promoter phorbol ester reversibly modulates tyrosine dephosphorylation/inactivation of protein kinase FA/GSK-3 alpha in A431 cells.

The signal transduction mechanism of protein kinase FA/GSK-3 alpha by tyrosine phosphorylation in A431 cells was investigated. Kinase FA/GSK-3 alpha was found to exist in a highly tyrosine-phosphorylated/activated state in resting cells but could be tyrosine-dephosphorylated and inactivated to approximately 60% of the control level when cells were acutely treated with 1 microM tumor promoter phorbol ester (TPA) at 37 degrees C for 30 min, as demonstrated by metabolic 32P-labeling the cells, followed by immunoprecipitation and two-dimensional phosphoamino acid analysis and by immunodetection in an antikinase FA/GSK-3 alpha immunoprecipitate kinase assay. Conversely, when cells were chronically treated with 1 microM TPA at 37 degrees C for 24 h and processed under identical conditions, kinase FA/GSK-3 alpha was found to be rephosphorylated on tyrosine residue and reactivated to approximately 130% of the original control level. Taken together, the results provide initial evidence that the phosphotyrosine content and cellular activity of kinase FA/GSK-3 alpha can be modulated in a reversible manner by short-term and long-term exposure of A431 cells to TPA. Since acute exposure of cells to TPA causes up-regulation of cellular protein kinase C (PKC) activity and prolonged exposure to TPA causes down-regulation of PKC, the results further suggest that the TPA-mediated modulation of PKC may play a role in the regulation of tyrosine phosphorylation and concurrent activation of kinase FA/GSK-3 alpha in cells, representing a new mode of signal transduction pathway for the regulation of this multisubstrate/multifunctional protein kinase in cells.

Amino Acid Sequence↗

PubMed1994

MR imaging of the accessory soleus muscle appearance in six patients and a review of the literature.

We examined seven ankles with an accessory soleus muscle to determine if the magnetic resonance (MR) imaging features were sufficient to allow accurate diagnosis of this anomalous muscle. We believe that the diagnosis of an accessory soleus muscle is unequivocal with MR imaging on the basis of morphology and signal intensity. Therefore, we suggest that this imaging method should be utilized in patients suspected of having a mass or with persistent swelling in the region of the ankle with or without pain, for the noninvasive diagnosis of this muscle and to better define the regional anatomy presperatively if surgery is being considered for relief of symptoms.

Adolescent↗

PubMed1994

Ossification of the Achilles tendon: imaging abnormalities in 12 patients.

Ossification of the Achilles tendon is a rare clinical entity that is characterized by the presence of an ossific mass contained within the fibrocartilaginous substance of the tendon. Because the radiographic features of this condition have not been documented entirely and the magnetic resonance (MR) imaging findings have not been determined, a review of 16 affected tendons in 12 patients was performed in an attempt to characterize the imaging abnormalities associated with this process. MR imaging was performed in three Achilles tendons which demonstrated thickening of the tendons at the level of the ossifications and a lack of intratendinous signal abnormalities compatible with acute tendinitis. Signal intensity similar to that of bone marrow was present in the ossifications.

Achilles Tendon↗

PubMed1994

Autophosphorylation-dependent protein kinase phosphorylates Ser25, Ser38, Ser65, Ser71, and Ser411 in vimentin and thereby inhibits cytoskeletal intermediate filament assembly.

The autophosphorylation-dependent protein kinase has been identified as a potent vimentin kinase that incorporates 2 mol of phosphates per mol of protein and generates five major phosphorylation sites in vimentin. Tryptic phosphopeptide mapping by high-performance liquid chromatography followed by sequential manual Edman degradation and direct peptide sequence analysis revealed that Ser-25, Ser-38, Ser-65, and Ser-71 in the amino-terminal domain and Ser-411 in the carboxyl-terminal domain are the phosphorylation sites in vimentin phosphorylated by this kinase, indicating that autophosphorylation-dependent protein kinase is a potent and unique vimentin kinase. Functional study further revealed that phosphorylation of vimentin by autophosphorylation-dependent protein kinase can completely inhibit polymerization and assembly of the cytoskeletal intermediate filament as demonstrated by electron microscopic analysis. Taken together, the results provide initial evidence that the autophosphorylation-dependent protein kinase may function as a vimentin kinase involved in the structure-function regulation of the cytoskeletal system. The results also support the notion that this cyclic nucleotide- and calcium-independent protein kinase may function as a multisubstrate/multifunctional protein kinase involved in the regulation of diverse cell functions.

Amino Acid Sequence↗