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Biomedical subjects

G L Johnson

Publications and source records attributed to G L Johnson.

At least 73 records · Page 4Linked to original sources
PubMed1997

Single therapeutic catheterization to treat coexisting coarctation of the aorta and patent ductus arteriosus.

A case of a pediatric patient found to have coexisting coarctation of the aorta and patent ductus arteriosus who underwent balloon dilation of the coarctation and coil occlusion of the ductus in a single cardiac catheterization is presented. Review of the English literature revealed no previous reports of this combination of transcatheter interventions during a single catheterization procedure.

Aortic Coarctation↗
PubMed1997

Rapamycin potentiates dexamethasone-induced apoptosis and inhibits JNK activity in lymphoblastoid cells.

The immunosuppressant rapamycin (RAP) potentiated apoptosis of the murine T lymphoblastoid cell line S49 induced by dexamethasone (DEX), while RAP by itself did not induce apoptosis of the cells. FK506, in contrast, had no effect on DEX-induced apoptosis; moreover, an excess of FK506 reversed the potentiation of apoptosis by RAP, indicating that RAP exerts its effects through binding to FKBP. Both RAP and FK506 enhanced the MMTV promoter activity by dexamethasone, suggesting that the potentiation of apoptosis is not likely explained by the selective enhancement of transcriptional activity of the glucocorticoid receptor. Of interest, the basal activity of c-Jun kinase (JNK), whose activation has been recently suggested to be involved in cell survival signals in lymphocytes, was reduced by RAP in S49 cells. The reduction of JNK activity by RAP was reversed by the addition of an excess of FK506. In summary, we demonstrate for the first time that RAP has the ability to inhibit JNK activity in lymphocytes where the drug enhances apoptosis.

3T3 Cells↗
PubMed1997

Infantile myofibromatosis.

Infantile myofibromatosis is a mesenchymal tumor most commonly seen in infancy. The tumors have a variable appearance on CT/MR and often simulate a more aggressive neoplasm. This report describes CT/MR findings in cases of infantile myofibromatosis with pathologic correlation. Discussion into the success of imaging in suggesting the correct diagnosis is also addressed.

Buttocks↗
PubMed1997

MEKKs, GCKs, MLKs, PAKs, TAKs, and tpls: upstream regulators of the c-Jun amino-terminal kinases?

Regulation of the mitogen-activated protein kinase (MAPK) family members - which include the extracellular response kinases (ERKs), p38/HOG1, and the c-Jun amino-terminal kinases (JNKs) - plays a central role in mediating the effects of diverse stimuli encompassing cytokines, hormones, growth factors and stresses such as osmotic imbalance, heat shock, inhibition of protein synthesis and irradiation. A rapidly increasing number of kinases that activate the JNK pathways has been described recently, including the MAPK/ERK kinase kinases, p21-activated kinases, germinal center kinase, mixed lineage kinases, tumor progression locus 2, and TGF-beta-activated kinase. Thus, regulation of the JNK pathway provides an interesting example of how many different stimuli can converge into regulating pathways critical for the determination of cell fate.

Animals↗
PubMed1997

Analysis of mutant platelet-derived growth factor receptors expressed in PC12 cells identifies signals governing sodium channel induction during neuronal differentiation.

The mechanisms governing neuronal differentiation, including the signals underlying the induction of voltage-dependent sodium (Na+) channel expression by neurotrophic factors, which occurs independent of Ras activity, are not well understood. Therefore, Na+ channel induction was analyzed in sublines of PC12 cells stably expressing platelet-derived growth factor (PDGF) beta receptors with mutations that eliminate activation of specific signalling molecules. Mutations eliminating activation of phosphatidylinositol 3-kinase (PI3K), phospholipase C gamma (PLC gamma), the GTPase-activating protein (GAP), and Syp phosphatase failed to diminish the induction of type II Na+ channel alpha-subunit mRNA and functional Na+ channel expression by PDGF, as determined by RNase protection assays and whole-cell patch clamp recording. However, mutation of juxtamembrane tyrosines that bind members of the Src family of kinases upon receptor activation inhibited the induction of functional Na+ channels while leaving the induction of type II alpha-subunit mRNA intact. Mutation of juxtamembrane tyrosines in combination with mutations eliminating activation of PI3K, PLC gamma, GAP, and Syp abolished the induction of type II alpha-subunit mRNA, suggesting that at least partially redundant signaling mechanisms mediate this induction. The differential effects of the receptor mutations on Na+ channel expression did not reflect global changes in receptor signaling capabilities, as in all of the mutant receptors analyzed, the induction of c-fos and transin mRNAs still occurred. The results reveal an important role for the Src family in the induction of Na+ channel expression and highlight the multiplicity and combinatorial nature of the signaling mechanisms governing neuronal differentiation.

Animals↗
PubMed1997

Primary adrenal ganglioneuroma: CT findings in four patients.

OBJECTIVE: The purpose of this study was to characterize the appearance of adrenal ganglioneuroma on CT scans and to define the specific imaging features of the tumor. CONCLUSION: Adrenal ganglioneuroma is an uncommon benign tumor that is revealed as a solid adrenal mass on CT scans. Specific CT features such as calcification and lesion enhancement may simulate a primary adrenal carcinoma. However, in our four patients, no signs of local invasion or vascular extension were noted. The specific diagnosis of adrenal ganglioneuroma requires either biopsy or surgical removal for documentation.

Adrenal Gland Neoplasms↗
PubMed1997

Regulation of uterine immune function during the estrous cycle and in response to infectious bacteria in sheep.

Uterine infections are a major reproductive problem in livestock. We conducted two experiments to investigate factors that may modulate uterine responses to infectious bacteria. In Exp. 1, ewes received intrauterine inoculations of either saline or bacteria (75 x 10(7) cfu of Actinomyces pyogenes and 35 x 10(7) cfu of Escherichia coli) on either d 0 or 7 of the estrous cycle. Vena caval samples containing uteroovarian blood were collected twice daily from 12 h before until 6 d after inoculation. Only ewes inoculated with bacteria on d 7 developed infections. Basal (4.8 vs .4 pmol), lipopolysaccharide-stimulated (14.2 vs 6.1 pmol), and concanavalin A-stimulated (65.8 vs 21.6 pmol) blastogenesis (i.e., [3H]thymidine incorporation) of vena caval lymphocytes was greater (P < or = .002) for ewes inoculated with bacteria or saline on d 0 rather than on d 7. The number (per 100 white blood cells) of lymphocytes was greater (41.3 vs 30.8, P < .001) and that of neutrophils was less (42.5 vs 51.6, P < .001) in ewes inoculated on d 0 rather than d 7. Bacteria increased (P < .05) vena caval PGF(2 alpha) but not PGE2 concentrations. In Exp. 2, two protein fractions (molecular weights of > or = 100 kDa and approximately 12.7 kDa) from chromatography of uterine flushings collected on d 0 or 7, or 18 d after ovariectomy on d 0 or 7, modulated phytohemagglutinin-stimulated blastogenesis; the heavier fraction from d 0 had a stimulatory component, but the major effects of the fractions were inhibitory. The differences in immune function and regulation between d 0 and 7 probably explain how the uterus of follicular phase ewes was able to prevent the development of an infection.

Actinomyces↗
PubMed1996

Activation of MEKK by formyl-methionyl-leucyl-phenylalanine in human neutrophils. Mapping pathways for mitogen-activated protein kinase activation.

Mechanisms of neutrophil activation in response to chemoattractants remain incompletely understood. We have recently reported a Ras-mediated c-Raf pathway leading to the activation of mitogen-activated protein (MAP) kinase in human neutrophils stimulated with the chemoattractant formyl-Met-Leu-Phe (FMLP). However, concern that Raf activation may not fully account for the early FMLP-mediated human neutrophil responses prompted us to investigate the activation of MAP kinase/ERK kinase (MEK) by MEK kinase (MEKK). In cell lysates we identified protein species at 180, 160, 110, 72, and 54 kDa with a monoclonal antibody to MEKK. Activation of MEKK was determined on immunoprecipitates from FMLP-stimulated neutrophils by in vitro kinase assay, which utilized both MEK1 and MEK2 as substrates. It was rapid, detectable at 30 s and reaching a plateau at 5 min, and it was inhibited in a dose-dependent fashion by a specific phosphatidylinositol 3-kinase inhibitor, wortmannin. Partial inhibition by pertussis toxin was observed. We were unable to show inhibition of the MEKK response by GF 109203X, a protein kinase C-specific inhibitor. These data indicate that in neutrophils activation of MEKK in addition to Raf may underlie stimulation of MAP kinase and other MAP kinase homologues by FMLP.

Androstadienes↗
PubMed1996

Influence of age on the effect of bidirectional cavopulmonary anastomosis on left ventricular volume, mass and ejection fraction.

OBJECTIVES: We sought to identify age-related differences in the ventricular response of patients after bidirectional cavopulmonary anastomosis (CPA) and to compare changes in the ventricular response among children < 3 years of age who underwent CPA with that of age-matched control subjects who had a systemic to pulmonary artery shunt alone. BACKGROUND: Pre-Fontan CPA has been advocated over a systemic to pulmonary artery shunt alone in patients with a single ventricle to facilitate ventricular volume unloading and minimize risk of the Fontan operation. METHODS: Our study evaluated 23 patients who initially received a systemic to pulmonary artery shunt as an initial procedure before subsequent Fontan palliation. In eight of these patients (group I), bidirectional CPA was performed before age 3 years, and in four (group II), it was performed after age 10 years. The remaining 11 patients (group III, age and weight control group for group I) were maintained with their initial shunt until they underwent Fontan palliation. Serial echocardiographic analysis was used retrospectively to evaluate left ventricular volume and mass and systolic pump function (ejection fraction) before and after bidirectional CPA. RESULTS: Through 10 months of follow-up, group I patients showed significant decreases in indexed end-diastolic volume both after CPA (120 ml/m1.5 body surface area vs. 78 ml/m1.5, p = 0.001) and in comparison with values in patients in group II and III, who showed no changes in end-diastolic volume (p < 0.001). Indexed ventricular mass decreased moderately after bidirectional CPA in group I (from 228 g/m1.5 body surface area to 148 g/m1.5) but remained unchanged in groups II and III. The differences in trends between groups I and III were significant (p = 0.03). Ejection fraction decreased significantly in group II versus group I patients (0.48 to 0.27 vs. 0.51 to 0.52, p < 0.05) after CPA. Oxygen saturation measurements before and after bidirectional CPA revealed a significant increase in group I (73% to 86%, p < 0.001) and a decrease in group II (82% to 73%, p < 0.01). CONCLUSIONS: Bidirectional CPA facilitates ventricular volume unloading and promotes regression of left ventricular mass in younger children (< 3 years) in preparation for a Fontan operation. In contrast, bidirectional CPA is of questionable value in older children as a staging procedure for Fontan palliation.

Aging↗
PubMed1996

Repression of adipogenesis by adenylyl cyclase stimulatory G-protein alpha subunit is expressed within region 146-220.

The heterotrimeric G-protein alpha subunit stimulatory with respect to adenylyl cyclase (Gsalpha) represses adipogenesis of 3T3-L1 mouse embryonic fibroblasts. Derepression occurs in response to inducers, to oligodeoxynucleotides antisense to Gsalpha, and to overexpression of heterotrimeric G-protein alpha subunit 2, inhibitory with respect to adenylyl cyclase (Gialpha2). Constitutive expression of Gsalpha blocks adipogenesis and was exploited as an assay, in which chimeras of Gialpha2 and Gsalpha were expressed stably in 3T3-L1 cells to define the region controlling adipogenesis. N-terminal analysis revealed region 146-220 of Gsalpha as a repressor of adipogenesis; substitution of Gialpha2 abolished the ability of the chimera to repress adipogenesis in response to inducers. Expression of a chimera in which the 146-235 region of Gsalpha was embedded in Gialpha2 fully repressed adipogenesis in response to the inducers. C-terminal analysis revealed no loss of function for truncated Gsalpha, lacking the terminal 38 residues. The repressor domain for adipogenesis maps to a region that includes switch domains I and II and is spatially distinct from the regions mapped for control of adenylyl cyclase.

1-Methyl-3-isobutylxanthine↗
PubMed1996

The kinase-inactive PDGF beta-receptor mediates activation of the MAP kinase cascade via the endogenous PDGF alpha-receptor in HepG2 cells.

The PDGF beta-receptor in which the active-site lysine in the kinase domain has been mutated to arginine (K634R) tacks intrinsic kinase activity. When expressed in HepG2 cells, the kinase-inactive PDGF beta-receptor was tyrosine phosphorylated in response to PDGF-BB. Previously, HepG2 cells were thought to be devoid of PDGF alpha-receptor primarily due to lack of specific antibody which precluded detection of the PDGF alpha-receptor. In fact, these cells express low levels of PDGF alpha-receptor. In HepG2 cells that express the kinase-inactive PDGF beta-receptor, PDGF-BB activates the PDGF alpha-receptors to trans phosphorylate the kinase-inactive PDGF beta-receptor in an intermolecular fashion. As a result, stimulation of HepG2 cells that express the kinase-inactive receptor leads to activation of serine/threonine kinases of the MAP kinase cascade which include RAF-1, MEK-1 and p42 MAP kinase. In contrast, the kinase-inactive receptor does not activate any signaling pathways when it is expressed in PC12 cells which do not express the endogenous PDGF alpha-receptor. Thus, the kinase-inactive K634R PDGF beta-receptor is able to enhance PDGF-BB signaling in HepG2 cells that express the PDGF alpha-receptor.

3T3 Cells↗
PubMed1996

Activation of a p38 mitogen-activated protein kinase in human neutrophils by lipopolysaccharide.

Stimulation of human neutrophils by LPS is central to the pathogenesis of sepsis and the adult respiratory distress syndrome. The intracellular signaling pathway that results in cellular responses following LPS stimulation in neutrophils is unknown. We report that exposure of neutrophils to LPS results in the phosphorylation and activation of a p38 mitogen-activated protein (MAP) kinase, occurring in a concentration-dependent manner, with maximum response at 20 to 25 min. Partial purification of a p38 MAP kinase by ion exchange chromatography established it as distinct from the p42/p44 (extracellular signal-regulated kinases (ERK-1 and ERK-2) MAP kinases). Activation of the p38 MAP kinase by LPS in human neutrophils occurs via CD14, a proposed LPS receptor, and requires the presence of plasma containing the LPS-binding protein. This intracellular signaling pathway is independent of protein kinase C and does not involve Raf, MAP/ERK kinase kinase-1, MAP/ERK kinase-1, or MAP/ERK kinase-2 and does not result in the activation of the p42/p44 ERK MAP kinases or the c-jun N-terminal kinases.

Adult↗
PubMed1996

Fibroblast growth factor-2 suppression of tumor necrosis factor alpha-mediated apoptosis requires Ras and the activation of mitogen-activated protein kinase.

Treatment of L929 cells with tumor necrosis factor alpha (TNFalpha) activates a programmed cell death pathway resulting in apoptosis. We investigated the intracellular signaling pathways activated in L929 cells by TNFalpha. TNFalpha robustly activates Jun kinase (JNK), a member of the mitogen-activated protein kinase (MAPK) family. In addition, p42(MAPK) is activated, but a 10-fold greater concentration of TNFalpha was required for substantial MAPK activation than was needed for maximal JNK stimulation. Simultaneous treatment of L929 cells with fibroblast growth factor (FGF-2) significantly reduced the apoptotic response to TNFalpha. FGF-2 substantially activated the Raf/MEK/MAPK (where MEK is mitogen-activated protein kinase kinase) pathway but did not affect TNFalpha activation of JNK. These results indicate that although JNK may play an important role in transmitting the TNFalpha signal from the cell surface to the nucleus, activation of the JNK pathway is not sufficient to induce apoptosis. Expression of dominant-negative Asn-17 Ras in L929 cells diminished the FGF-2 stimulation of p42(MAPK) and eliminated the protective effect of FGF-2. Asn-17 Ras expression did not affect JNK activity and had no effect on TNFalpha activation of JNK. Pharmacological inhibition of MEK-1 activity by incubation of cells with the compound PD 098059 blocked p42(MAPK) activation and FGF-2 protection against apoptosis. Interestingly, activated Val-12 Ras expression substantially enhanced TNFalpha-mediated apoptosis in L929 cells, but Val-12 Ras did not constitutively activate MAPK in L929 cells and FGF-2 partially protected Val-12 Ras-expressing cells from TNFalpha-mediated apoptosis. Our data indicate that activation of the MAPK pathway mediates an FGF-2 protective effect against apoptosis and highlights the important role that integration of multiple intracellular signaling pathways plays in the regulation of cell growth and death.

Animals↗
PubMed1996

Aggregation of the FcepsilonRI on mast cells stimulates c-Jun amino-terminal kinase activity. A response inhibited by wortmannin.

Aggregation of the high-affinity Fc receptors for immunoglobulin E (IgE) (FcepsilonRI) on the surface of mast cells initiates intracellular signal transduction pathways including the tyrosine phosphorylation of cellular proteins, phosphoinositide hydrolysis, an increase in intracellular calcium, and protein kinase C activation. These signals are believed to be involved in the exocytic release of inflammatory mediators such as vasoactive amines, cytokines, and lipid metabolites. However, the downstream consequences of these early activation events are not well defined. One exception is the activation of the extracellular signal-regulated kinases/mitogen-activated protein kinases. One member of the mitogen-activated protein kinase superfamily, designated c-Jun amino-terminal kinase (JNK), has been recently identified. JNK is activated following dual phosphorylation at a Thr-Pro-Tyr motif in response to diverse stimuli including tumor necrosis factor-alpha, heat shock, or ultraviolet irradiation. We found that JNK was strongly activated by antigen cross-linking in a mouse mast cell line passively sensitized with ovalbumin-specific IgE. Anti-mouse IgE antibody also activated JNK. MEK kinase 1 (MEKK1) which activates the JNK activator, JNK kinase (JNKK), was similarly activated by antigen stimulation. JNK but not p42(erk2) activation induced by antigen was significantly inhibited in the presence of wortmannin, a known inhibitor of phosphatidylinositol 3-kinase. These results indicate that in response to the aggregation of FcepsilonRI on mast cells, phosphatidylinositol 3-kinase activation is involved in the stimulation of the MEKK1, JNKK, JNK pathway.

Amino Acid Sequence↗