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Biomedical subjects

J S Yu

Publications and source records attributed to J S Yu.

At least 109 records · Page 6Linked to original sources
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↗
PubMed1994

Meniscal ossicle: MR imaging appearance in three patients.

Meniscal ossicles are rare. Radiographically, these ossicles often are mistaken for intra-articular bodies. We evaluated the application of magnetic resonance imaging to determine whether this technique is efficacious in differentiating meniscal ossicles from intra-articular bodies.

Humans↗
PubMed1994

Protein kinase FA/glycogen synthase kinase-3 predominantly phosphorylates the in vivo site Thr97-Pro in brain myelin basic protein: evidence for Thr-Pro and Ser-Arg-X-X-Ser as consensus sequence motifs.

In a previous study, protein kinase FA/glycogen synthase kinase-3 (FA/GSK-3) was identified as a myelin basic protein (MBP) kinase associated with intact brain myelin. In this report, the phosphorylation sites of MBP by kinase FA/GSK-3 were further determined by two-dimensional electrophoresis/TLC, phosphoamino acid analysis, tryptic peptide mapping, Edman degradation, and direct sequencing. Kinase FA/GSK-3 phosphorylates MBP on both threonine and serine residues. Three tryptic phosphopeptide peaks were resolved by C18 reverse-phase HPLC. Sequential manual Edman degradation together with direct sequence analysis revealed that T(p)PPPSQGK is the phosphorylation site sequence for the first major phosphopeptide peak. When mapping with the bovine brain MBP sequence, we finally demonstrate Thr97-Pro, one of the in vivo phosphorylation sites in MBP, as the major site phosphorylated by kinase FA/GSK-3, implicating a physiologically relevant role of FA/GSK-3 in the regulation of brain myelin function. By using the same approach, we also identified NIVT94(p)PR as the phosphorylation site sequence in the second major tryptic phosphopeptide derived from [32P]MBP phosphorylated by kinase FA/GSK-3, further indicating that kinase FA/GSK-3 represents a Thr-Pro motif-directed MBP kinase involved in the phosphorylation of brain myelin.

Amino Acid Sequence↗
PubMed1994

Protein kinase FA/glycogen synthase kinase-3 alpha after heparin potentiation phosphorylates tau on sites abnormally phosphorylated in Alzheimer's disease brain.

Previously, we identified protein kinase FA/glycogen synthase kinase-3 alpha (GSK-3 alpha) as a brain microtubule-associated tau kinase that phosphorylates Ser235 and Ser404 of tau and causes its electrophoretic mobility shift in gels, a unique property characteristic of paired helical filament-associated pathological tau (PHF-tau) in Alzheimer's disease brains. In this study, we found that the activity of kinase FA/GSK-3 alpha towards phosphorylation of brain tau could be stimulated approximately fourfold by heparin. The phosphorylation molar ratio was increased simultaneously up to 9 mol of phosphates/mol of tau, resulting in a reduced mobility of tau with an apparent molecular mass shift to approximately 68 kDa in sodium dodecyl sulfate gels, which is very similar to that observed in Alzheimer-tau. Tryptic digestion of 32P-labelled tau, followed by HPLC and two-dimensional separation on TLC cellulose plates, revealed eight major phosphopeptides. Phosphoamino acid analysis together with sequential manual Edman degradation and protein sequence analysis further revealed that, in addition to Ser235 and Ser404, heparin generated Thr212, Thr231, Ser262, Ser324, and Ser356, the five extra phosphorylation sites in tau. As Ser235, Ser262, Ser324, Ser356, and Ser404 (particularly the site of Ser262) have been identified as five of the most potent sites in tau responsible for reducing microtubule binding possibly involved in neuronal degeneration, and Thr231, Ser235, Ser262, and Ser404 are four of the most well documented sites abnormally phosphorylated in Alzheimer-tau, the results provide initial evidence that protein kinase FA/GSK-3 alpha after heparin potentiation may represent one of the most potent systems possibly involved in the abnormal phosphorylation of PHF-tau in Alzheimer's disease brains.

Alzheimer Disease↗
PubMed1994

Central (interior) osteophytes of the distal femur. Imaging and pathologic findings.

RATIONALE AND OBJECTIVES: To characterize central osteophytes (COs) of the distal femur, imaging features that enable their differentiation from intra-articular bodies were identified, and the frequency of overlying articular cartilage abnormalities was determined. METHODS: The authors inspected 133 distal femoral specimens and retrospectively reviewed knee radiographs of 48 symptomatic patients and magnetic resonance images of 60 symptomatic patients for presence of COs. The location and imaging features of COs, and their association with marginal osteophytes (MOs), were recorded. Articular cartilage abnormalities, if any, were documented in patients who underwent magnetic resonance imaging. RESULTS: Specimen analysis showed a 41% prevalence of COs, 95% association of COs with MOs, and predominance of large COs in the medial femoral condyle (81%). Radiographic analysis revealed a 9.8% prevalence of COs in the distal femur. Magnetic resonance images demonstrated a 14.3% prevalence of COs, with the majority (73%) accompanied by an overlying cartilage that had abnormal signal intensity or morphology, or both. CONCLUSIONS: Central osteophytes are a common finding in the distal femur. Based on their location and cortical continuity with the underlying bone, most COs can be differentiated from intra-articular bodies.

Adult↗
PubMed1994

MR imaging of injuries of the extensor mechanism of the knee.

Rupture of the extensor mechanism of the knee must be diagnosed early in order to be successfully treated. However, the clinical signs of this condition may be concealed by hematoma or hemarthrosis. The noninvasiveness and accuracy of magnetic resonance (MR) imaging make it useful in detection of such ruptures. Normal quadriceps tendons have a laminated appearance on MR images. The normal patella has signal intensity similar to that of bone marrow and cortex, while normal patellar tendons have homogeneous low signal intensity with all sequences. Patellar fractures, bone bruises, and avulsion of the tibial tubercle manifest as changes in marrow signal intensity. The laminated configuration of the quadriceps tendon allows distinction between partial and complete tears; both may be accompanied by edema and hemorrhage, which manifest as increased signal intensity on T2-weighted images. Ruptures of the patellar tendon also manifest as increased signal intensity on T2-weighted images.

Humans↗
PubMed1994

Intramedullary hemorrhage in spinal cord hemangioblastoma. Report of two cases.

The authors describe two cases of intramedullary hemorrhage caused by thoracic hemangioblastoma. Both patients presented with acute paraplegia. The lesion in the first case was diagnosed by myelography and in the second by magnetic resonance imaging. Emergency surgical evacuation of the intramedullary hematoma and tumor was performed in these patients. Hemangioblastoma was confirmed by histopathological examination in both cases. Both patients remain paraplegic after 7 and 1 years, respectively. Intramedullary hemorrhage is a rare and devastating effect of spinal hemangioblastoma.

Adult↗
PubMed1994

Relation of cyst counts with numbers of total nuclei of Pneumocystis carinii in rats.

Wistar rats were induced of Pneumocystis carinii infection by injection with methyl-prednisolone to correlate the cyst counts and numbers of nuclei. Seven sections of the lungs were examined by impression smears and also whole lung homogenates were screened for nucleus counting for each rat. At the first week of the experiment, all of the impression smears except one were cyst negative but trophic forms were counted around 10(6). At the third week, the cysts appeared one per 20 immersion oil lens fields. The nuclei were on the order of 10(7) at this period, and this amount of Pc is regarded as the limit of cyst detection on impression smears. When the nuclei were over 10(9) in the lungs, the cysts were counted about 50 in 20 microscopic fields. The organisms were distributed in the lungs without any predilection focus. The present data suggest that the trophic forms, proliferate first and the cysts appear later in the lungs.

Animals↗
PubMed1994

Magnetic resonance imaging of the wrist.

As improvements in surface coil technology and imaging sequences continue, increased applicability of MRI to small yet complex structures such as the wrist is assured. Almost certainly, the full potential of MRI in the wrist has yet to be realized, and its versatility is perhaps limited only by the radiologist's experience. As we become more adept at this modality, it will become an increasingly important component in the radiology armamentarium.

Adult↗
PubMed1993

Synergistic control mechanism for abnormal site phosphorylation of Alzheimer's diseased brain tau by kinase FA/GSK-3 alpha.

When a synthetic peptide fragment (VAVVRTPPKSPSSAK) which corresponds to amino acid residues 226-240 from brain microtubule-associated protein tau was used as a testing substrate, we found that protein kinase FA/GSK-3 alpha was almost inactive towards this substrate. In sharp contrast, when Ser-10 of this peptide was replaced by a phosphoserine, the phosphopeptide fragment (VAVVRTPPKS(p)PSSAK) became an excellent substrate for kinase FA/GSK-3 alpha. Sequential manual Edman degradation together with phosphoamino acid analysis and protein sequencing further revealed that Thr-6 of the peptide fragment which corresponds to an important abnormal phosphorylation site Thr-231 in Alzheimer's diseased brain tau was the only site that was greatly phosphorylated, demonstrating that a pre-phosphorylation becomes a prerequisite and is essential for promoting phosphorylation of Thr-231. Taken together, the results provide initial evidence that kinase FA/GSK-3 alpha mediates a synergistic phosphorylation control mechanism involved in the abnormal site phosphorylation of Alzheimer's diseased brain tau.

Alzheimer Disease↗
PubMed1993

Treatment of glioma by engineered interleukin 4-secreting cells.

The ability of interleukin-4 (IL-4) to mediate an antitumor response to human gliomas was studied in vivo in nude mice. To allow the effect of IL-4 to be exerted over a relatively short distance and at an optimal concentration, a transfected tumor cell line expressing a high level of IL-4 was used in mixed tumor transplantation assays. There was a significant inhibition of growth of the U87 human glioma line when the IL-4-secreting cell line, LT-1, was implanted s.c. with the glioma in 5 nude mice when compared to contralateral control tumors consisting of the U87 glioma and IL-4-negative control cells. In addition, there was a prolongation of survival when U87 along with IL-4-secreting cells were implanted intracerebrally in 12 nude mice compared to 12 control nude mice implanted with U87 and IL-4-negative control cells and 11 control animals receiving U87 alone. Histological analysis 4 days after i.c. inoculation revealed the presence of a dramatic eosinophil infiltrate and tumor necrosis. The absence of viable glioma cells as well as resolution of inflammation 19 days after treatment suggests the potential for complete tumor regression without ongoing inflammatory sequelae resulting from cytokine treatment.

Adjuvants, Immunologic↗
PubMed1993

Immunological and biochemical study on tissue and subcellular distributions of protein kinase FA (an activating factor of ATP.Mg-dependent protein phosphatase): a simplified and efficient procedure for high quantity purification from brain.

Although protein kinase FA/GSK-3 alpha (an activating factor of ATP.Mg-dependent protein phosphatase) has been established as a cytosolic enzyme in mammalian nonnervous tissues involved in the metabolic regulation, immunological and biochemical studies on tissue and subcellular distributions demonstrate that kinase FA/GSK-3 alpha is in fact a membrane-associated enzyme and most abundantly exists in brain particulate membrane fractions depending on the tissue homogenization conditions. For instance, when brain was homogenized in Polytron without 0.32 M sucrose, approximately 40% of the total FA/GSK-3 alpha was found in the cytosol. However, when brain was homogenized in buffer containing 0.32 M sucrose and in a glass homogenizer with Teflon pestle, more than 80% of the total FA/GSK-3 alpha was found associated with the particulate membrane fractions. By manipulating these findings, we have developed a simplified procedure for purification of homogeneous kinase FA/GSK-3 alpha in high recovery and in a substantial amount from brain tissue. The data explain why kinase FA/GSK-3 alpha cannot be isolated in a reasonable amount from most mammalian tissues for the past years. The specific pure antibody that can specifically recognize kinase FA/GSK-3 alpha from crude tissue extracts together with the high quantity purification of the enzyme as presented in this report provides an initial key step for studies on the role of kinase FA/GSK-3 alpha in the regulation of brain functions especially in the brain particulate membrane fractions.

Amino Acid Sequence↗
PubMed1993

Protein kinase FA/GSK-3 phosphorylates tau on Ser235-Pro and Ser404-Pro that are abnormally phosphorylated in Alzheimer's disease brain.

Previously, we identified protein kinase FA/glycogen synthase kinase-3 (GSK-3) as a microtubule-associated protein tau kinase that can incorporate 4 mol of phosphates into 1 mol of tau protein and cause its electrophoretic mobility shift in sodium dodecyl sulfate gels, a unique property characteristic of paired helical filament-associated pathological tau (PHF-tau) in Alzheimer's disease brains. In this report, we identified TPPKS(p)PSAAK and SPVVSGDTS(p)PR as two phosphorylation site sequences phosphorylated by kinase FA/GSK-3 in tau using peptide sequence analysis and sequential manual Edman degradation for radiosequencing. When mapping with human brain tau sequence, we further identified Ser235-Pro and Ser404-Pro as the two major phosphorylation sites according to the numbering of the longest tau isoform. Ser235 and Ser404 have been reported as two of the major abnormal phosphorylation sites in PHF-tau. Taken together, the results provide initial evidence that protein kinase FA/GSK-3 may represent one of the Ser-Pro motif-directed tau kinases involved in the abnormal phosphorylation of pathological PHF-tau in Alzheimer's disease brain.

Alzheimer Disease↗
PubMed1993

Identification and characterization of protein kinase FA/glycogen synthase kinase 3 in clathrin-coated brain vesicles.

Mg-ATP-dependent protein phosphatase activating factor [kinase FA/glycogen synthase kinase 3 (GSK-3)] has been identified in highly purified clathrin-coated vesicles (CCVs) isolated from pig brain. Kinase FA was found to exist in an inactive state but can be activated by 1% Triton X-100 or 1 M Tris-HCl extraction in brain CCVs. Activation of kinase FA in CCVs is due to disassociation of the kinase from CCVs as demonstrated on sucrose density-gradient ultracentrifugation and Sepharose CL-4B gel filtration. Using purified brain CCVs as substrates, kinase FA enhanced the endogenous phosphorylation of assembly protein complexes in the molecular weight range of 100,000-130,000 severalfold, as demonstrated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by autoradiography. Comparisons with well-defined brain CCV-associated endogenous protein kinases such as pp50 kinase/AP50 and casein kinase 2 provide evidence that kinase FA/GSK-3 represents a third potent and unique CCV-associated protein kinase distinctly different from the previously described CCV protein kinases, suggesting the possible involvement of kinase FA in the regulation of CCV functions in the brain. The results also support the notion that protein kinase FA is involved in cell surface signal transduction in the CNS.

Animals↗
PubMed1992

The mechanism of activation of protein kinase FA (the activator of type-1 protein phosphatase) in brain synaptosomes.

The ATP.Mg-dependent type-1 protein phosphatase and its activating factor (protein kinase FA) were identified to exist in brain synaptosome. The inactive protein phosphatase was found to exist in the synaptosomal cytosol whereas its activating factor (protein kinase FA) was present in the synaptosomal membrane, indicating that the inactive protein phosphatase and its activating factor FA are localized in two separate subcellular compartments. The membrane-bound FA was found to exist in two forms; approximately 75% of FA is inactive and trypsin-resistant, whereas 25% of FA is active and trypsin-labile. When membranes were incubated with exogenous phospholipase C, the inactive/trypsin-resistant FA could be activated and sequestered to become the active/trypsin-labile FA in a time- and dose-dependent manner. Taken together, the results provide initial evidence that the activation-sequestration of membrane-bound protein kinase FA may represent one mode of control modulating the activity of protein kinase FA and thereby to activate protein phosphatase in brain synaptosome, representing an efficient regulatory mechanism for regulating neurotransmission in the central nervous system.

Adenosine Triphosphate↗
PubMed1992

Reversible hyperphosphorylation and reorganization of vimentin intermediate filaments by okadaic acid in 9L rat brain tumor cells.

Okadaic acid (OA), a protein phosphatase inhibitor, was found to induce hyperphosphorylation and reorganization of vimentin intermediate filaments in 9L rat brain tumor cells. The process was dose dependent. Vimentin phosphorylation was initially enhanced by 400 nM OA in 30 min and reached maximal level (about 26-fold) when cells were treated with 400 nM OA for 90 min. Upon removal of OA, dephosphorylation of the hyperphosphorylated vimentin was observed and the levels of phosphorylation returned to that of the controls after the cells recovered under normal growing conditions for 11 h. The phosphorylation and dephosphorylation of vimentin induced by OA concomitantly resulted in reversible reorganization of vimentin filaments and alteration of cell morphology. Cells rounded up as they were entering mitosis in the presence of OA and returned to normal appearance after 11 h of recovery. Immuno-staining with anti-vimentin antibody revealed that vimentin filaments were disassembled and clustered around the nucleus when the cells were treated with OA but subsequently returned to the filamentous states when OA was removed. Two-dimensional electrophoresis analysis further revealed that hyperphosphorylation of vimentin generated at least seven isoforms having different isoelectric points. Furthermore, the enhanced vimentin phosphorylation was accompanied by changes in the detergent-solubility of the protein. In untreated cells, the detergent-soluble and -insoluble vimentins were of equal amounts but the solubility could be increased when vimentins were hyperphosphorylated in the presence of OA. Taken together, the results indicated that OA could be involved in reversible hyperphosphorylation and reorganization of vimentin intermediate filaments, which may play an important role in the structure-function regulation of cytoskeleton in the cell.

Animals↗