Search PubMed⌕ Search

Biomedical subjects

M Simons

Publications and source records attributed to M Simons.

At least 55 records · Page 3Linked to original sources
PubMed1999

Interventional radiology and the use of metal stents in nonvascular clinical practice: a systematic overview.

PURPOSE: The intent of this systematic overview was to describe the clinical role of metal stents in nonvascular health care interventions and the level of evidence supporting their use. MATERIALS AND METHODS: Structured searches of Medline were conducted and limited to original peer-reviewed articles published in English. RESULTS: Clinical practice involving metal stents was reported in more than 109 clinical series involving 4,753 patients. Stents were placed mainly for palliation of malignant biliary, esophageal, and airway obstruction in patients who were untreatable or had surgically unresectable lesions. Assessment of these interventions has so far centered on safety and technical success. Efficacy, quality of life, and costing factors were not routinely reported. Randomized trial evidence was available but limited; six randomized trials involving metal stents have been reported. Three trials involved biliary malignant obstruction, and all three reported metal stent (132 patients) palliation to be superior to plastic stent palliation (136 patients) based on longer patency and lower reintervention costs. Safety and complication differences between stents, however, were inconsistent across trials. In three trials involving esophageal malignant obstruction, metal stent (82 patients) palliation was reported to be superior to plastic stent (41 patients), based on lower complication and reintervention rates, and superior to laser therapy (18 patients), based on better dysphagia relief. CONCLUSION: Use of metal stents has been reported for obstructed ducts and passageways of most body systems. There is, however, limited controlled trial evidence confirming the advantages of their use over plastic stents or other forms of treatment.

Cholestasis↗
PubMed1999

Tomato seed and root exudate sugars: composition, utilization by Pseudomonas biocontrol strains and role in rhizosphere colonization.

The role of tomato seed and root exudate sugars as nutrients for Pseudomonas biocontrol bacteria was studied. To this end, the major exudate sugars of tomato seeds, seedlings and roots were identified and quantified using high-performance liquid chromatographic (HPLC) analysis. Glucose, fructose and maltose were present in all studied growth stages of the plant, but the ratios of these sugars were strongly dependent on the developmental stage. In order to study the putative role of exudate sugar utilization in rhizosphere colonization, two approaches were adopted. First, after co-inoculation on germinated tomato seeds, the root-colonizing ability of the efficient root-colonizing P. fluorescens strain WCS365 in a gnotobiotic quartz sand-plant nutrient solution system was compared with that of other Pseudomonas biocontrol strains. No correlation was observed between the colonizing ability of a strain and its ability to use the major exudate sugars as the only carbon and energy source. Secondly, a Tn5lacZ mutant of P. fluorescens strain WCS365, strain PCL1083, was isolated, which is impaired in its ability to grow on simple sugars, including those found in exudate. The mutation appeared to reside in zwf, which encodes glucose-6-phosphate dehydrogenase. The mutant grows as well as the parental strain on other media, including tomato root exudate. After inoculation of germinated sterile tomato seeds, the mutant cells reached the same population levels at the root tip as the wild-type strain, both alone and in competition, indicating that the ability to use exudate sugars does not play a major role in tomato root colonization, despite the fact that sugars have often been reported to represent the major exudate carbon source. This conclusion is supported by the observation that the growth of mutant PCL1083 in vitro is inhibited by glucose, a major exudate sugar, at a concentration of 0.001%, which indicates that the glucose concentration in the tomato rhizosphere is very low.

Carbohydrate Metabolism↗
PubMed1999

Adenovirus-mediated gene transfer of inhibitors of apoptosis protein delays apoptosis in cerebellar granule neurons.

The inhibitor of apoptosis (IAP) family of antiapoptotic genes, originally discovered in baculovirus, exists in animals ranging from insects to humans. Here, we investigated the ability of IAPs to suppress cell death in both a neuronal model of apoptosis and excitotoxicity. Cerebellar granule neurons undergo apoptosis when switched from 25 to 5 mM potassium, and excitotoxic cell death in response to glutamate. We examined the endogenous expression of four members of the IAP family, X chromosome-linked IAP (XIAP), rat IAP1 (RIAP1), RIAP2, and neuronal apoptosis inhibitory protein (NAIP), by semiquantitative reverse PCR and immunoblot analysis in cultured cerebellar granule neurons. Cerebellar granule neurons express significant levels of RIAP2 mRNA and protein, but expression of RIAP1, NAIP, and XIAP was not detected. RIAP2 mRNA content and protein levels did not change when cells were switched from 25 to 5 mM potassium. To determine whether ectopic expression of IAP influenced neuronal survival after potassium withdrawal or glutamate exposure, we used recombinant adenoviral vectors to target XIAP, human IAP1 (HIAP1), HIAP2, and NAIP into cerebellar granule neurons. We demonstrate that forced expression of IAPs efficiently blocked potassium withdrawal-induced N-acetyl-Asp-Glu-Val-Asp-specific caspase activity and reduced DNA fragmentation. However, neurons were only protected from apoptosis up to 24 h after potassium withdrawal, but not at later time points, suggesting that IAPs delay but do not block apoptosis in cerebellar granule neurons. In contrast, treatment with 100 microM or 1 mM glutamate did not induce caspase activity and adenoviral-mediated expression of IAPs had no influence on subsequent excitotoxic cell death.

Adenoviridae↗
PubMed1999

Exogenous administration of gangliosides displaces GPI-anchored proteins from lipid microdomains in living cells.

Exogenous application of gangliosides to cells affects many cellular functions. We asked whether these effects could be attributed to the influence of gangliosides on the properties of sphingolipid-cholesterol microdomains on the plasma membrane, also termed rafts. The latter are envisaged as lateral assemblies of sphingolipids (including gangliosides), cholesterol, and a specific set of proteins. Rafts have been implicated in processes such as membrane trafficking, signal transduction, and cell adhesion. Recently, using a chemical cross-linking approach with Madin-Darby canine kidney (MDCK) cells permanently expressing a GPI-anchored form of growth hormone decay accelerating factor (GH-DAF) as a model system, we could show that GPI-anchored proteins are clustered in rafts in living cells. Moreover, this clustering was dependent on the level of cholesterol in the cell. Here we show that incubation of MDCK cells with gangliosides abolished subsequent chemical cross-linking of GH-DAF. Furthermore, insertion of gangliosides into the plasma membrane of MDCK GH-DAF cells renders GH-DAF soluble when subjected to extraction with Triton X-114 at 4 degrees C. Our data suggest that exogenous application of gangliosides displaces GPI-anchored proteins from sphingolipid-cholesterol microdomains in living cells.

Animals↗
PubMed1999

Attenuation of endothelium-dependent dilation of pig pulmonary arterioles after cardiopulmonary bypass is prevented by monoclonal antibody to complement C5a.

UNLABELLED: We examined whether pulmonary endothelial dysfunction associated with cardiopulmonary bypass (CPB) may be mediated by complement C5a in pigs. Pigs were placed on normothermic CPB for 1 h with or without a previous administration of 1.6 mg/kg anti-C5a monoclonal antibody (MAb), then reperfused for 2 h. Pulmonary tissue myeloperoxidase activity was measured. Expression of nitric oxide synthase (NOS) was measured by reverse transcriptase polymerase chain reaction and Western blotting. Pulmonary arterioles approximately 100 microm in diameter were preconstricted with the thromboxane analog U46619 1 microM, and relaxation responses to adenosine diphosphate 10(-9)-10(-4) M, substance P 10(-12)-10(-6) M, and sodium nitroprusside 10(-9)-10(-4) M were examined in vitro by videomicroscopy. Relaxation to the endothelium-dependent dilators adenosine diphosphate and substance P was attenuated after CPB; this attenuation was prevented by the previous administration of MAb. Relaxation to sodium nitroprusside was not affected by CPB. Neutrophil sequestration, as measured by MPO activity, increased after CPB, either with or without MAb. Transcription of NOS was unchanged by CPB, but translation of constitutive NOS was decreased after CPB, and this decrease was prevented by a previous administration of MAb. We conclude that pig pulmonary endothelial dysfunction associated with CPB may be mediated by C5a. The mechanism may involve changes in NOS translation. IMPLICATIONS: In pigs, pulmonary endothelial dysfunction may occur after cardiopulmonary bypass due to product(s) of complement activation.

Animals↗
PubMed1999

Directed membrane transport is involved in process formation in cultured podocytes.

Mature glomerular visceral epithelial cells, or podocytes, are unique cells with a complex cell architecture. Characteristically, they possess a highly branched array of major processes and foot processes, which are essential for glomerular filtration in the kidney. A podocyte cell line with the potential to exhibit many features of differentiated podocytes, particularly the formation of cell processes, was recently established. In this study, it is shown that directed membrane transport is involved in process formation in cultured podocytes. The well-characterized vesicular stomatitis virus G was used as a marker protein for the biosynthetic pathway in these cells. It seems that newly synthesized vesicular stomatitis virus G is preferentially delivered into the cell processes of the podocytes, where it is colocalized with known regulators of vesicular transport from the Golgi apparatus to the plasma membrane, such as the small GTPase rab8 and the sec6/sec8 complex. To determine the role of vesicular transport in process formation, cells were treated with brefeldin A, a drug that disrupts the trafficking of post-Golgi transport vesicles. As a result, the podocytes reversibly lost their ability to form processes. These findings suggest that podocytes are dependent on a constant fresh source of lipids and proteins to form their processes.

Animals↗
PubMed1999

Angiogenesis in cardiovascular disease: current status and therapeutic potential.

Therapeutic angiogenesis, in the form of growth factor protein administration or gene therapy, has emerged as a new method of treatment for patients with severe, inoperable coronary artery disease. Improved myocardial perfusion and function after the administration of angiogenic growth factors has been demonstrated in animal models of chronic myocardial ischaemia. Recently, preliminary clinical trials using growth factor proteins or genes encoding these angiogenic factors have demonstrated clinical and other objective evidence of relevant angiogenesis. Thus, therapeutic angiogenesis has the potential to extend treatment options to patients who are not optimal candidates for conventional methods of myocardial revascularisation.

Angiogenesis Inducing Agents↗
PubMed1999

Intracoronary and intravenous administration of basic fibroblast growth factor: myocardial and tissue distribution.

Therapeutic angiogenesis using various heparin-binding growth factors is a promising treatment for ischemic heart disease. Single dose intracoronary (IC) or i.v. delivery are most practical for clinical use. This study was designed to investigate the myocardial and tissue deposition of basic fibroblast growth factor (bFGF) after IC and i.v. administration in normal and chronically ischemic animals. Twenty-four Yorkshire pigs were used (12 normal and 12 ischemic animals) with IC and i.v. administration of 125I-bFGF (25 microCi) combined with cold bFGF (30 microg) and heparin (3 mg). Tissue and myocardial distribution was determined at 1 and 24 h by measuring 125I-bFGF specific activity and by organ and light level autoradiography. The liver accounted for the majority of 125I-bFGF activity at 1 h (37.6 +/- 17.1% for IC and 42.1 +/- 17.7% for i.v. delivery), with a reduction to 2.8 +/- 1.5% for IC and 1.5 +/- 0.9% for i.v. delivery by 24 h. Total cardiac specific activity at 1 h was 0.88 +/- 0.89% for IC and 0.26 +/- 0.08% for i.v. administration (p =.12) and decreased to 0.05 +/- 0.04% (p =.05, versus 1 h) and 0. 04 +/- 0.01% (p <.001, versus 1 h) at 24 h, respectively. IC but not i.v. delivery resulted in higher deposition in ischemic than normal myocardium. IC delivery resulted in enhanced bFGF deposition only in myocardial territories subtended by the infused artery. Intravenous delivery compares favorably with IC delivery with a 3- to 4-fold reduction in myocardial deposition at 1 h and with similar solid organ deposition. The less invasive nature of i.v. delivery, its potential for repeat administration, and its applicability to a larger population may offset its resultant reduced myocardial deposition. Efficacy studies are ongoing.

Animals↗
PubMed1999

Therapeutic Angiogenesis Using Endocardial Approach to Administration: Techniques and Results.

The availability of various angiogenic growth factors and gene therapy vectors, and the demonstration of their angiogenic potential in animal models of chronic myocardial ischemia, has propelled their investigation in clinical trials of therapeutic angiogenesis in patients with ischemic heart disease. Although most preclinical studies have employed methods of prolonged drug delivery and local therapy, the need for repeated administration and invasive access has limited the clinical usefulness of these delivery strategies. Intracoronary and intravenous delivery, with their potential widespread applicability, has fueled their use in most clinical trials of therapeutic angiogenesis; however, the significant systemic recirculation, limited myocardial retention, and potential for serious systemic adverse events are major limitations to their clinical use. Epicardial delivery using surgical access has been used in several clinical studies, but the need for surgical access and general anesthesia may limit the usefulness of this technique. The development of percutaneous endocardial delivery catheters using fluoroscopic guidance or Biosense NOGA (Biosense Laboratories, Haifa, Israel) electromagnetic three- dimensional navigation system has generated significant interest in the use of this delivery strategy in therapeutic myocardial angiogenesis studies. These strategies are being intensively investigated in preclinical studies with clinical studies soon to follow. We describe the limited experience with these drug delivery devices.

Journal Article↗
PubMed1999

Therapeutic Angiogenesis Using Basic Fibroblast Growth Factor and Vascular Endothelial Growth Factor Using Various Delivery Strategies.

Therapeutic angiogenesis is a novel technique that may provide a treatment strategy for ischemic heart diseasepatients who are not candidates for standard revascularization procedures. It works by promoting the growth of blood vessels provide new venues for blood flow. Basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) are the most widely studied angiogenic agents. They have been shown to induce functionally significant angiogenesis in various animal models of chronic myocardial ischemia using various delivery strategies. Preclinical and clinical studies using these growth factors are reviewed with an emphasis on the different delivery strategies,including intracoronary and intravenous delivery; left atrial injections; intrapericardial administration; local intravascular and perivascular delivery; and intramyocardial delivery using single bolus delivery, repeated administration, gene therapy, and sustained delivery. Although intracoronary and intravenous delivery may be preferred for their ease of use and their applicability to a large patient population, systemic recirculation and lack of sustained tissue exposure to these therapeutic agents may limit the usefulness of this approach. Intrapericardial and intramyocardial administration, sustained local delivery, and second-generation gene therapy vectors may allow a safer and more sustained administration and may be preferable for clinical use. However, only well-designed randomized, double-blind placebo-controlled trials using outcome measures tailored to myocardial angiogenesis will determine the feasibility and effectiveness of this treatment modality.

Journal Article↗
PubMed1998

Effects of ischemic preconditioning on myocardial perfusion, function, and microvascular regulation.

BACKGROUND: Ischemic preconditioning (PC) has been advocated as a method to preserve myocardial function and perfusion during minimally invasive direct coronary bypass (MIDCAB). We examined the effects of PC on indexes of myocardial function, perfusion, and endothelial and beta-adrenergic coronary regulation after 30 minutes of ischemia and 60 minutes of reperfusion (IR). METHODS AND RESULTS: Five groups of pigs were studied: (1) PC-IR: PC by 3 cycles of 5-minute left anterior descending coronary artery occlusion (CO) and 5-minute reperfusion (Rep) + 30 minutes of CO + 60 minutes of Rep; (2) IR alone: 30 minutes of CO + 60 minutes of Rep; (3) PC alone; (4) PC-IR-glibenclamide (GLIB): PC-IR + infusion of GLIB; (5) control: noninstrumented. Reactivity (in vitro) of coronary arterioles (70 to 150 microns) from the myocardial area at risk was examined with video microscopy. beta-Adrenergic microvascular relaxations to isoproterenol, forskolin, and 8-bromo-cAMP were significantly reduced after IR alone (P < 0.05 versus control, 2-way ANOVA). PC before IR restored these responses to normal (P < 0.05 PC-IR versus IR alone), and GLIB abolished this effect of PC. Subepicardial endothelium-dependent microvascular relaxation to ADP was significantly reduced after IR alone (P < 0.01 versus control) but was preserved in both the PC-IR and PC-IR-GLIB groups (P < 0.05 versus IR alone). The response of vessels to ADP from the subendocardium was significantly reduced in all groups compared with the control response (all P < 0.05 versus control). Nitroprusside elicited a similar response in vessels from all groups. PC before IR did not affect the reduced myocardial percent segmental shortening or left ventricular maximal dP/dt, did not affect myocardial perfusion in the subepicardium or subendocardium, and did not change expression of the inducible or the constitutively expressed isoforms of nitric oxide synthase. CONCLUSIONS: PC before IR preserves beta-adrenergic signal transduction in coronary smooth muscle through a KATP channel mechanism, whereas PC preserves endothelium-dependent relaxation in the subepicardium through a mechanism not related to KATP channels or the enhanced expression of nitric oxide synthase. Nevertheless, PC does not improve short-term myocardial function or baseline myocardial perfusion after IR. Thus, the short-term beneficial role of PC in myocardial protection during MIDCAB may be limited.

Adrenergic beta-Agonists↗
PubMed1998

Myocardial VEGF expression after cardiopulmonary bypass and cardioplegia.

BACKGROUND: Vascular endothelial growth factor (VEGF) is a heparin-binding glycoprotein that plays a critical role in angiogenesis, vascular remodeling, and regulation of vascular tone and permeability. Because myocardial and peripheral edema and systemic hypotension occur frequently after cardiac operations, we examined the effects of cardiopulmonary bypass (CPB) and cardioplegia on gene expressions of VEGF protein and the VEGF tyrosine kinase receptor flk-1 and coronary vascular responses to VEGF. METHODS AND RESULTS: Pigs (n = 6) were placed on normothermic CPB and hearts were arrested for 1 hour with a hyperkalemic, cold blood cardioplegic solution. Pigs were then separated from CPB and perfused off CPB for an additional 2 hours. Myocardial and skeletal muscle specimens were obtained for Northern analysis of VEGF protein, flk-1 receptor, and basic fibroblast growth factor (bFGF) mRNA before CPB and after 2 hours of reperfusion. Isolated, precontracted coronary arterioles in pre-CPB dilated potently to exogenous VEGF (dilation = 26 +/- 4% of precontraction at 10(-12) mol/L VEGF). Cardioplegia-reperfusion was associated with a 4 +/- 2-fold (P < 0.05 vs pre-CPB) increase in myocardial VEGF protein mRNA, whereas no similar increase was observed in the skeletal muscle. Flk-1 mRNA was increased 6 +/- 3-fold (P < 0.05 vs pre-CPB) after reperfusion, whereas it was unchanged in the skeletal muscle. Relaxations of precontracted coronary arterioles to VEGF were significantly increased (40 +/- 6% at 10(-12) mol/L, P < 0.05 vs pre-CPB) after 2 hours of reperfusion, but those to the endothelium-dependent vasodilator ADP and the endothelium-independent vasodilator nitroprusside were not changed, suggesting that the VEGF receptors remain intact and function is selectively upregulated. In contrast, relaxation responses of microvessels to bFGF were not altered after cardioplegia-reperfusion, and there was no increase in bFGF mRNA in either myocardium or skeletal muscle. CONCLUSIONS: This study shows that VEGF protein and its flk-1 receptor gene expressions are selectively increased and the potent VEGF-induced vascular responses are enhanced in the coronary microcirculation after blood cardioplegia. The respective parameters are unchanged in the skeletal muscle after normothermic CPB. These findings may have important implications regarding postoperative coronary blood flow regulation, increases in myocardial edema, and vascular remodeling after cardioplegia-reperfusion.

Animals↗
PubMed1998

Phosphorylation of the cytoplasmic tail of syndecan-4 regulates activation of protein kinase Calpha.

Syndecans are transmembrane proteoglycans capable of carrying both heparan and chondroitin sulfate chains. The cytoplasmic tail of syndecan-4 was recently reported to undergo in vivo phosphorylation on Ser183 in the membrane-proximal part of the tail (Horowitz, A., and Simons, M. (1998) J. Biol. Chem. 273, 10914-10918). However, the functional consequences of this event remain unknown. The cytoplasmic tail of syndecan-4 is known to undergo multimerization and to activate protein kinase Calpha (PKCalpha), with both events depending on the presence of the commonly occurring phospholipid phosphatidylinositol 4,5-bisphosphate (PIP2). In the present investigation we found that phosphorylation of Ser183 produced a 10-fold reduction in the ability of syndecan-4 to activate PKCalpha, without affecting its ability to bind the PKC. Because Ser183 is adjacent to positively charged lysine groups that resemble PIP2-binding regions in several other proteins, phosphorylation of this serine may affect the binding affinity of the syndecan-4 cytoplasmic tail to PIP2. We found that the Ser183-phosphorylated cytoplasmic tail of syndecan-4 has indeed a significantly lower affinity to PIP2 compared with the nonphosphorylated tail. Furthermore, Ser183 phosphorylation abolished PIP2-dependent oligomerization of syndecan-4 cytoplasmic tails. We conclude that Ser183 phosphorylation regulates syndecan-4-dependent activation of PKCalpha by reducing the affinity to PIP2 and inhibiting the oligomerization of syndecan-4 cytoplasmic tails. These results further support the role of syndecan-4 in signal transduction in endothelial cells.

Animals↗
PubMed1998

Myb-dependent regulation of thrombospondin 2 expression. Role of mRNA stability.

The nuclear transcription factor c-Myb, which is highly expressed in hematopoietic cells, has been shown to be functional in NIH 3T3 cells: cells that do not possess detectable levels of c-Myb. To identify endogenous target genes of c-Myb in fibroblasts, RNA isolated from NIH 3T3 cells stably transfected with a full-length or a dominant negative c-myb construct (GREMyb and GREMEn, respectively) was subjected to differential display analysis. 5'-Rapid amplification of cDNA ends of a selected band, sequencing, and a nucleotide homology search led to the identification of thrombospondin 2 (TSP 2) as the gene product repressed in GREMyb and induced in GREMEn cells. The pattern of TSP 2 expression during the cell cycle was consistent with c-myb-dependent regulation. The possibility that the identified transcript was TSP 1, a homologous product known to be repressed by v-Src, c-Jun, and v-Myc, was ruled out by using a TSP 2-specific DNA probe and by showing a distinct pattern of regulation of TSP 1 and TSP 2 expression. Nuclear run-on and TSP 2 promoter-reporter (chloramphenicol acetyltransferase) assays showed similar transcriptional levels in GREMyb and NIH 3T3 cells. However, mRNA stability studies showed a much shorter TSP 2 mRNA half-life in GREMyb compared with wild type NIH 3T3 cells, suggesting that c-myb affects TSP 2 expression via a post-transcriptional mechanism. The implications of a protooncogene-mediated suppression of TSP expression are discussed.

3T3 Cells↗
PubMed1998

Cholesterol depletion inhibits the generation of beta-amyloid in hippocampal neurons.

The amyloid precursor protein (APP) plays a crucial role in the pathogenesis of Alzheimer's disease. During intracellular transport APP undergoes a series of proteolytic cleavages that lead to the release either of an amyloidogenic fragment called beta-amyloid (Abeta) or of a nonamyloidogenic secreted form consisting of the ectodomain of APP (APPsec). It is Abeta that accumulates in the brain lesions that are thought to cause the disease. By reducing the cellular cholesterol level of living hippocampal neurons by 70% with lovastatin and methyl-beta-cyclodextrin, we show that the formation of Abeta is completely inhibited while the generation of APPsec is unperturbed. This inhibition of Abeta formation is accompanied by increased solubility in the detergent Triton X-100 and is fully reversible by the readdition of cholesterol to previously depleted cells. Our results show that cholesterol is required for Abeta formation to occur and imply a link between cholesterol, Abeta, and Alzheimer's disease.

Alzheimer Disease↗
PubMed1998

Regulation of syndecan-4 phosphorylation in vivo.

Recent studies suggest that some of the heparan sulfate-carrying proteoglycans may directly participate in signaling via their cytoplasmic tail. The present investigation addresses the potential involvement of syndecan-4, a widely expressed transmembrane proteoglycan, in this process. We found that the cytoplasmic tail of syndecan-4 is phosphorylated on a single serine residue (Ser183) in growth-arrested NIH 3T3 fibroblasts, with a stoichiometry of 0.3 mol Pi/mol syndecan-4. Treatment of the cells with a protein kinase C (PKC)-activating phorbol ester lead to a 2.5-fold increase in Ser183 phosphorylation. This increase was inhibited by a generic PKC inhibitor but not by an inhibitor specific to the calcium-dependent conventional PKCs, suggesting that the cytoplasmic tail of syndecan-4 is phosphorylated by a calcium-independent novel PKC isozyme. Application of 10-30 ng/ml basic fibroblast growth factor (bFGF) produced a 2-3-fold reduction in the phosphorylation of syndecan-4. Because treatment with the phosphatase inhibitor calyculin prevented the bFGF-induced decrease in syndecan-4 phosphorylation, the effect of bFGF appears to be mediated by a protein serine/threonine phosphatase type 1 or 2A. We conclude that the cytoplasmic tail of syndecan-4 is subject to in vivo phosphorylation on Ser183, which is regulated by the activities of a novel PKC isozyme and a bFGF-dependent serine/threonine phosphatase.

3T3 Cells↗
PubMed1998

Activity of iodine-123 metaiodobenzylguanidine in childhood neuroblastoma: lack of relation to tumour differentiation in vivo.

Neuroblastoma (NB) tumour cells have a remarkable tendency to differentiate spontaneously or under the influence of certain drugs. It is not clear whether metaiodobenzylguanidine (MIBG) uptake correlates with differentiation of NB cells. In 28 tumours of 26 patients, iodine-123 MIBG uptake in primary NBs was studied in relation to tumour differentiation, tumour size, cell density and degree of necrosis in subsequently resected specimens. Genetic features such as the presence of chromosomal aberrations (1p-deletion and MYCN amplification) and/or P-glycoprotein (mdr-1 gene product) were also evaluated in relation to MIBG uptake. A highly variable and unpredictable intensity of MIBG uptake was observed in primary as well as secondary resected tumours. This intensity did not relate to any of the above-mentioned factors except that there was a trend towards more intense uptake with increasing size of the tumour. We conclude from our observations that, in contrast to commonly held opinion, well-differentiated tumours do not a priori show a lower MIBG uptake in vivo, even when there are a low number of viable cells and a high degree of necrosis. The degree of differentiation or tumour viability and necrosis following longstanding chemotherapeutic treatment cannot be predicted by the MIBG scan findings. The observed MIBG uptake may be importantly influenced by factors other than those associated with cellular differentiation.

3-Iodobenzylguanidine↗