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Biomedical subjects

M J Lee

Publications and source records attributed to M J Lee.

At least 19 recordsLinked to original sources
PubMed2003

The role of the interventional radiologist in enteral alimentation.

The provision of enteral nutrition through the placement of gastrostomy/gastrojejunostomy tubes is a well-established procedure. Traditionally, these catheters have been placed either surgically or endoscopically; however, over the past two decades interventional radiologists have increasingly performed these procedures successfully. The perceived advantages of this route lie in the reported lower morbidity and mortality rates. In addition, percutaneous radiologically guided (PRG) catheters may be placed in certain subgroups of patients in whom it would be technically difficult or impossible by other routes, e.g., patients with head and neck or oesophageal tumours. The aim of this review is to describe the techniques of radiologically placed gastrostomy/gastrojejunostomy, discuss its indications and contraindications, describe any associated potential complications and compare PRG results with the more established techniques of open surgical and endoscopic placement. We also describe some recent procedural and catheter modifications.

Enteral Nutrition↗
PubMed2003

Ultrasound-guided endocavitary drainage of pelvic abscesses: technique, results and complications.

AIM: To evaluate the experience in our institution with ultrasound-guided transrectal and transvaginal (endocavitary) drainage of pelvic abscesses. MATERIALS AND METHODS: Eighteen patients (four male, 14 female; mean age 55 years, range 30-78 years) presenting with pelvic abscesses were referred to our institution for therapeutic drainage over a 4 year period. Patients received broad-spectrum antibiotics prior to drainage, which was performed by either the transvaginal or transrectal route under ultrasound guidance. Patients were given sedo-analgesia in the form of midazolam and fentanyl and local anaesthesia was also employed. Eight French catheters were inserted into the abscess cavities, and patients were subsequently monitored on a daily basis by a member of the interventional radiology team until such time as it was deemed appropriate to remove the catheter. RESULTS: Eighteen catheters were placed in 17 patients, and transvaginal aspiration alone was performed in one patient. Drainage was successful in 16 of 17 patients, but a transgluteal approach was ultimately required in the remaining patient to enable passage of a larger catheter into an infected haematoma. The mean duration of drainage was 5 days, mean time to defervesce 2 days. Spontaneous catheter dislodgement occurred in four patients associated with straining, but this did not have any adverse effect in three of the four patients. CONCLUSION: Endocavitary drainage is an effective method of treatment for pelvic abscesses. Spontaneous catheter dislodgement does not affect patient outcome.

Abscess↗
PubMed2002

Value of MR pancreatography in the evaluation of patients with chronic pancreatitis.

AIM: To determine the diagnostic accuracy of magnetic resonance (MR) pancreatography and to define its role in the imaging work-up of patients with severe chronic pancreatitis. MATERIAL AND METHODS: Thirty-two patients (13 men and 19 women; 15-84 years old; mean age, 48 years) with severe chronic pancreatitis diagnosed using cross-sectional imaging, examination using contrast medium (endoscopic retrograde cholangiopancreatography, pseudocyst injection) and/or surgical findings underwent MR pancreatography performed using a two-dimensional multi-slice fast spin echo technique. All patients underwent transabdominal pancreatic sonography and computed tomography (CT) was performed in 12 patients. Two observers independently assessed the MR pancreatograms for pancreatic duct dilatation and pancreatic duct abnormalities. Compared to the final diagnosis, the accuracy of MR pancreatography in revealing complications of chronic pancreatitis was calculated and its role in the radiological work-up of patients with chronic pancreatitis evaluated. RESULTS: When compared to the final diagnosis, MR pancreatography showed the following sensitivity, specificity and diagnostic accuracy: for filling defects in pancreatic duct, 56-78%, 100% and 87-94%, respectively; for strictures, 75-88%, 92-96% and 88-94%, respectively; and for pseudocysts 100%, 100% and 100%, respectively. Filling defects were correctly diagnosed in all patients when MR pancreatography was interpreted in combination with cross-sectional imaging. Contrast pancreatography was required for the complete evaluation of strictures and communication with pseudocysts. CONCLUSION: MR pancreatography is poorly sensitive but specific in revealing pancreatic duct filling defects and strictures. However, when MR pancreatography is interpreted in combination with sonography and CT, it provides sufficient information to plan therapy in the majority of patients.

Adolescent↗
PubMed2002

Prospective comparison of MRA with catheter angiography in the assessment of patients with aortoiliac occlusion before surgery or endovascular therapy.

AIM: The purpose of this study was to evaluate the usefulness of gadolinium enhanced 3D magnetic resonance (MR) angiography (CE MRA) as an alternative to translumbar or brachial angiography in the pre-operative work-up of patients with aortoiliac occlusion. MATERIALS AND METHODS: Nineteen patients (14 men and five women; age range 45-77 years; mean 62 years), not suitable for perfemoral angiography (aortoiliac occlusion, n = 18; infected femoro-femoral graft with femoral artery pseudoaneurysm, n = 1), underwent pre-operative CE MRA and catheter angiography (translumbar, n = 5; brachial, n = 14). CE MRA was performed using a 3D fast spoiled gradient-recalled pulse sequence during the intravenous injection of 40 ml of gadolinium DTPA and a 32-s breath-hold. All patients subsequently underwent surgical (n = 13) or percutaneous transluminal (n = 6) treatment for their vascular disease. The accuracy of CE MRA was determined compared with the findings at catheter angiography taken as the gold standard. RESULTS: CE MRA gave accurate information about the occlusion, inflow and distal run-off in the majority of patients. CE MRA revealed occlusions with an accuracy of 94.7% in the aortic segment, 98.7% in the iliac segment, and 100% in the common femoral segment. The arterial segments distal to the common femoral artery were not completely visualized in four patients but CE MRA provided sufficient information to plan either surgical or percutaneous transluminal therapy in all but one patient. CONCLUSION: CE MRA is highly accurate in showing the presence and extent of aortoiliac occlusions. In our study group, CE MRA gave sufficient information in the pre-operative evaluation of aortoiliac occlusion.

Aged↗
PubMed2002

Hepatic metastases from an unknown primary neoplasm (UPN): survival, prognostic indicators and value of extensive investigations.

AIM: The objectives of this study were to identify prognostic features for patients with hepatic metastases and unknown primary neoplasms (UPN), determine the common primary tumours, assess the value of diagnostic tests in finding these tumours, and evaluate the impact of therapy and knowledge of the primary tumour on patient survival. MATERIALS AND METHODS: Eighty-eight patients with UPN and liver biopsy proven hepatic metastases over a 10-year period were reviewed (M:F, 58:30; age range 27-91 years, median 64.5 years). Histopathology, diagnostic investigations and success at identifying the primary neoplasm were recorded. In addition, in 70 patients with adenocarcinoma histology (M:F, 48:22; age range 27-91 years, median 65 years), treatment and survival data from the date of biopsy were recorded. RESULTS: The histological spectrum included adenocarcinoma in 70, neuroendocrine in four, squamous cell carcinoma in four, small cell carcinoma in four, carcinoid in two, hepatoma in one and three others. Extensive investigation identified a primary neoplasm in 16/88 patients (18%) including colorectal in six, gastric in two, lung in four, oesophageal in two, prostate in one and carcinoid in one. In the adenocarcinoma group survival data were available for 62/70 patients. Sixteen of 62 patients received active treatment with either surgery, chemotherapy, radiotherapy or a combination protocol. Forty-six of 62 patients received palliative care alone. Median survival for the adenocarcinoma group overall was 49 days. The median survival for treated patients (49 days) versus untreated patients (52 days) was not significantly different (P=0.128). Patients <65 years were more likely to receive active treatment than those >65 years (P=0.006). Age with a hazard ratio (HR) of 1.01 (P=0.178), active treatment (HR=0.65;P=0.194), knowledge of the primary neoplasm (HR=0.60;P=0.213) and male gender (HR=0.88;P=0.642) had no significant effect on survival. CONCLUSION: Although hepatic metastases are associated with poor prognosis, it is essential that a liver biopsy be performed to obtain a histological diagnosis. Adenocarcinoma metastases carry a dismal prognosis, and no prognostic factors, including knowledge of the primary tumour, are significant for patient survival. Extensive investigation is not warranted in patients with adenocarcinoma liver metastases.

Adenocarcinoma↗
PubMed2002

Displacement of occluded plastic endoprostheses into the duodenum during percutaneous biliary drainage: description of an under-reported technique.

AIM: Percutaneous transhepatic biliary drainage (PTBD) is occasionally requested in patients with an occluded plastic stent in situ. We describe a technique for dislodging the stent into the duodenum during PTBD. MATERIALS AND METHODS: Twelve patients (M:F, 9:3 mean age 70 years) with plastic stents in the common bile duct (CBD) underwent PTBD. Eleven patients had malignant obstruction and one patient had Mirizzi's syndrome and a large duodenal diverticulum. PTBD was performed using right lobe access in nine patients and a left hepatic access in three patients. The level of biliary obstruction was at the lower CBD in five patients, mid-CBD in four patients and upper CBD in three patients. After standard percutaneous biliary access was established, an 8mm by 4 cm balloon catheter was gently inflated alongside the upper end of the plastic stent and advanced over a stiff guidewire, towards the duodenum, to dislodge the plastic stent. RESULTS: Plastic stents were successfully dislodged in all 11 patients with malignancy and metallic stents were deployed for palliation. In nine of 11 patients with malignant lesions the PTBD dislodgement of the plastic stent and insertion of a metallic stent was carried out as a single-step procedure. In two patients with biliary sepsis, a two-step procedure was necessary. In the patient with Mirizzi's syndrome the plastic stent could not be dislodged. No complications were observed. CONCLUSION: Plastic stents, inserted at ERCP, can be dislodged in the majority of cases at PTBD using a balloon catheter inserted alongside the failed stent without complication.

Aged↗
PubMed2002

Glutathione peroxidase levels throughout normal pregnancy and in pre-eclampsia.

OBJECTIVE: Evidence suggests that hemoglobin, in addition to its function as a carrier of oxygen, also serves to transport nitric oxide, as S-nitroso cysteine, from the lungs to the peripheral circulation, where it can be released. Glutathione peroxidase, besides being an important antioxidant, is known to catalyze the release of nitric oxide from smaller carrier molecules, and may play a role in the distribution of nitric oxide throughout the body. In light of these findings, we sought to determine whether glutathione peroxidase levels differed throughout gestation, and specifically between pre-eclamptic and normal women. METHODS: A nested case-control study of women receiving routine prenatal care was conducted. Pre-eclampsia was defined by a blood pressure of at least 140 mmHg systolic and/or 90 mmHg diastolic as well as proteinuria > 300 mg/24 h or > 2+ by dipstick, both occurring on two occasions at least 6 h apart. Blood was collected in heparinized tubes and was then centrifuged in a clinical centrifuge for 10 min. Plasma was frozen promptly at -80 degrees C for later enzyme-linked immunosorbent assay (ELISA), with which plasma glutathione peroxidase was determined. RESULTS: The maternal demographics of the pre-eclamptic and non-pre-eclamptic study groups did not significantly vary with respect to mean maternal age, gravidity, parity and gestational age at the time of delivery. The median maternal ages were 33 and 34 years, and the median gestational ages at the time of birth were 37.5 and 38.1 weeks, respectively. In evaluating the glutathione peroxidase levels of all patients across the three trimesters, we found that there was essentially no difference in mean levels (83.7, 81.0 and 89.5 ng/ml, respectively). There was no difference between the pre-eclamptic and non-pre-eclamptic patients, again stratified by trimester. A linear regression analysis indicated that the plasma glutathione peroxidase concentration did not correlate with gestational age or the presence of pre-eclampsia. CONCLUSIONS: Plasma glutathione peroxidase expression is similar across all trimesters. There is no change in the glutathione peroxidase levels in pre-eclamptic patients.

Adult↗
PubMed2001

Lysophospholipids--receptor revelations.

Upon cell activation, membrane phospholipids are metabolized into potent lysophospholipid (LP) mediators, such as sphingosine 1-phosphate and lysophosphatidic acid. LPs fulfill signaling roles in organisms as diverse as yeast and humans. The recent discovery of G protein-coupled receptors for LPs in higher eukaryotes, and their involvement in regulating diverse processes such as angiogenesis, cardiac development, neuronal survival, and immunity, has stimulated growing interest in these lipid mediators. LP receptor biology has generated insights into fundamental cellular mechanisms and may provide therapeutic targets for drug development.

Animals↗
PubMed2001

Inhibition of ALDH3A1-catalyzed oxidation by chlorpropamide analogues.

In our efforts to identify agents that would specifically inhibit ALDH3A1, we had previously studied extensively the effect of an N(1)-alkyl, an N(1)-methoxy, and several N(1)-hydroxy-substituted ester derivatives of chlorpropamide on the catalytic activities of ALDH3A1s derived from human normal stomach mucosa (nALDH3A1) and human tumor cells (tALDH3A1), and of two recombinant aldehyde dehydrogenases, viz. human rALDH1A1 and rALDH2. The N(1)-methoxy analogue of chlorpropamide, viz. 4-chloro-N-methoxy-N-[(propylamino)carbonyl]benzenesulfonamide (API-2), was found to be a relatively selective and potent inhibitor of tALDH3A1-catalyzed oxidation as compared to its ability to inhibit nALDH3A-catalyzed oxidation, but even more potently inhibited ALDH2-catalyzed oxidation, whereas an ester analogue, viz. (acetyloxy)[(4-chlorophenyl)sulfonyl]carbamic acid 1,1-dimethylethyl ester (NPI-2), selectively inhibited tALDH3A1-catalyzed oxidation as compared to its ability to inhibit nALDH3A1-, ALDH1A1- and ALDH2-catalyzed oxidations, and this inhibition was apparently irreversible. Three additional chlorpropamide analogues, viz. 4-chloro-N,O-bis(ethoxycarbonyl)-N-hydroxybenzenesulfonamide (NPI-4), N,O-bis(carbomethoxy)methanesulfohydroxamic acid (NPI-5), and 2-[(ethoxycarbonyl)oxy]-1,2-benzisothiazol-3(2H)-one 1,1-dioxide (NPI-6), were evaluated in the present investigation. Quantified were NAD-linked oxidation of benzaldehyde catalyzed by nALDH3A1 and tALDH3A1, and NAD-linked oxidation of acetaldehyde catalyzed by rALDH1A1 and rALDH2, all at 37 degrees C and pH 8.1, and in the presence and absence of inhibitor. NPI-4, NPI-5 and NPI-6 were not substrates for the oxidative reactions catalyzed by any of the ALDHs studied. Oxidative reactions catalyzed by the ALDH3A1s, rALDH1A1 and rALDH2 were each inhibited by NPI-4 and NPI-5. NPI-6 was a poor inhibitor of nALDH3A1- and tALDH3A1-catalyzed oxidations, but was a relatively potent inhibitor of rALDH1A1- and rALDH2-catalyzed oxidations. In all cases, inhibition of ALDH-catalyzed oxidation was directly related to the product of inhibitor concentration and preincubation (enzyme+inhibitor) time. As judged by the product values (microM x min) required to effect 50% inhibition (IC(50)): (1) nALDH3A1 and tALDH3A1 were essentially equisensitive to inhibition by NPI-4 and NPI-5, and both enzymes were poorly inhibited by NPI-6; (2) rALDH1A1 was, relative to the ALDH3A1s, slightly more sensitive to inhibition by NPI-4 and NPI-5, and far more sensitive to inhibition by NPI-6; and (3) rALDH1A1 was, relative to rALDH2, essentially equisensitive to inhibition by NPI-5, whereas, it was slightly more sensitive to inhibition by NPI-4 and NPI-6.

Aldehyde Dehydrogenase↗
PubMed2001

Enhancement of phospholipase D activity by overexpression of amyloid precursor protein in P19 mouse embryonic carcinoma cells.

It has been shown that phospholipase D (PLD) activity is stimulated by the beta-amyloid protein in neuronal cells. The aim of this study was to determine whether overexpression of the amyloid precursor protein (APP) affects the activity and the level of PLD expression in P19 embryonic carcinoma cells. We observed that the unstimulated basal PLD activity was higher in wild-type APP(695)-transfected cells than in non-transfected control cells. The protein kinase C (PKC) activator, phorbol 12-myristate 13-acetate (PMA), has been shown to activate PLD. PMA-stimulated PLD activity was 3-fold higher in the APP overexpressing cells than in the control cells. P19 cells express two distinct PLD isozymes, PLD1 and PLD2. The level of PLD2 expression was increased by APP overexpression. Although the PKC inhibitor, GF109203X, inhibited PMA-stimulated PLD activity, it did not affect the high basal PLD activity induced by APP overexpression. Neuronal differentiation of the P19 cells by retinoic acid did not affect the basal or PMA stimulated-PLD activity. Interestingly, APP overexpression in the differentiated P19 cells also led to an increase in PLD activity. The PLD activity of the P19 cells is apparently regulated by amyloid protein through both PKC-dependent and -independent mechanisms.

Amyloid beta-Protein Precursor↗
PubMed2001

Determination of 2-amino-1-methyl-6-phenylimidazo[4,5- b]pyridine (PhIP) and its metabolite 2-hydroxyamino-PhIP by liquid chromatography/electrospray ionization-ion trap mass spectrometry.

2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is the most abundant heterocyclic aromatic amine found in cooked meat. It is metabolically activated by the human cytochrome P450 enzymes to form the carcinogenic metabolite N2-OH-PhIP. PhIP has been found to induce tumors in rats and is a suspected human carcinogen. In the present work, we have developed and validated a liquid chromatography-electrospray ionization/ion trap mass spectrometry (LC-ESI/ITMS) method for the determination of PhIP and N2-OH-PhIP. PhIP was incubated with microsomes prepared from the human liver; the PhIP and N2-OH-PhIP formed were isolated from the biomatrices by solid-phase extraction using C18 cartridges, with recoveries greater than 86%. Subsequently, the products were separated on a microbore reversed-phase C18 liquid chromatograph coupled to an ESI-ITMS. The ESI interface and the ITMS were tuned for various parameters, and data acquisition was performed in selective ion monitoring mode. The detection limit of PhIP and N2-OH-PhIP was 1 and 10 pg, respectively. The method is highly sensitive and selective, has simple sample preparation protocols, and should be applicable to the study of the metabolic activation of PhIP in various human tissues.

Chromatography, Liquid↗
PubMed2001

Molecular identification of IgE-dependent histamine-releasing factor as a B cell growth factor.

The culture supernatants of LK1 cells, murine erythroleukemia cells, showed B cell-stimulating activity. Purification and NH(2)-terminal sequence analysis revealed that one of the candidates was murine IgE-dependent histamine-releasing factor (IgE-HRF), which is known to induce histamine from basophils. Recombinant IgE-HRF (rHRF) obtained from Escherichia coli- or 293-transformed embryonal kidney cells was tested for B cell-stimulating activity. Both rHRFs stimulated B cell proliferation in a dose-dependent manner. However, boiling or anti-HRF Ab abolished the B cell stimulatory effects of rHRF. Recombinant HRF showed strong synergistic effects with IL-2, IL-4, and IL-5 for B cell activation, with maximal activity in the presence of anti-CD40 AB: Recombinant HRF increased MHC class II expression of B cells. It also increased Ig production from B cells. Treatment with polymyxin B, a neutralizing peptide antibiotic of LPS, did not reduce the activity of rHRF. In addition, FACS analysis using PE-conjugated rHRF showed that HRF bound to B cells. Recombinant HRF up-regulated the expression of IL-1 and IL-6 in B cells. In vivo administration of rHRF or the cDNA for rHRF increased total and Ag-specific Ig synthesis. Taken together, these results indicate that HRF stimulates B cell activation and function.

Animals↗
PubMed2001

Intracardiac echocardiographic guidance and monitoring during percutaneous endomyocardial gene injection in porcine heart.

In an effort to develop a guiding and monitoring tool for transmyocardial gene transfer, we have evaluated the feasibility of intracardiac echocardiography (ICE) to guide percutaneous endomyocardial gene transfer (PEGT), and monitor complications, in a pig model. ICE (5.5-10 MHz), complemented by fluoroscopy, was utilized to guide a needle injection into the heart in 19 normal pigs. Using this system, we injected Evans blue dye into eight pigs (group I), a mixture of pCK-CAT plasmid and India ink into seven pigs (group II), and pCK-LacZ plasmid into four pigs (group III). In all pigs, ICE contributed to the injection procedure by guiding the catheter to anatomically distinct sites, and by assisting stabilization of the catheter-endocardial contact. ICE predicted the injection sites correctly in 56 of 64 sites (87.5%) in group I, and in 42 of 42 sites (100%) in group II. Leakage of injectate into the left ventricular cavity could be detected by the microbubbles generated. The sites of injections appeared as foci of bright myocardial echodensity, which persisted until the end of the procedure. The procedures were not associated with significant morbidity or mortality. The expression of the chloramphenicol acetyltransferase (CAT) gene was identified in 40 sites from 42 injections (95.2%) in group II. In group III, histology showed positive beta-galactosidase staining of myocytes limited around the needle track with low transfection efficiency (<1%). These results suggest that real-time ICE monitoring proves safe and useful during PEGT for guiding needle injection, monitoring leakage, ensuring delivery of injectate into the myocardium, and instantly diagnosing cardiac complications, resulting in successful gene transfer.

Animals↗
PubMed2001

Preconditioning with fetal cord blood facilitates engraftment of primary childhood T-cell acute lymphoblastic leukemia in immunodeficient mice.

Childhood T-cell acute lymphoblastic leukemia (T-ALL) is one of the most common childhood cancers. It is reported that preconditioning sublethally irradiated immunodeficient NOD/SCID (nonobese diabetic/X-linked severe combined immunodeficient) mice with human cord blood mononuclear cells facilitates the engraftment, expansion, and dissemination in these mice of primary T-ALL cells obtained from patients at the time of diagnosis. Cells recovered from mouse bone marrow or spleen resembled the original leukemia cells from patients with respect to surface lineage markers and T-cell receptor Vbeta gene rearrangements. Moreover, the pattern of leukemia dissemination in mouse tissues, resulting in universally fatal leukemia, is reminiscent of the human clinical disease. In addition, the fidelity of the model to the human disease is documented with regard to the presence of morphologically identifiable human leukemia cells in mouse bone marrow and blood and the maintenance of leukemia-initiating capacity within the leukemia-engrafted mouse. Therefore, several lines of independent approaches are used to suggest that the engrafted cells are of human leukemia origin and are not derived from cord blood. The in vivo model described here should enable the study of the growth properties of primary T-ALL cells obtained from patients and should prove useful in evaluating the potential efficacy of therapeutic strategies directed toward T-ALL.

Adolescent↗
PubMed2001

Endogenous production of nitric oxide by vascular endothelial growth factor down-regulates proliferation of choriocarcinoma cells.

The trophoblast-like choriocarcinoma cell line BeWo expresses a receptor for vascular endothelial growth factor (VEGF) and proliferates in response to VEGF. Nitric oxide (NO) seems to play a key role in the VEGF-induced proliferation of endothelial cells but the NO mechanistic regulation of VEGF-stimulated trophoblast proliferation is presently unclear. We assessed the effect of exogenous VEGF on BeWo cell proliferation by [3H]thymidine incorporation. The VEGF-induced proliferation of BeWo cells was significantly increased by the NO synthase (NOS) inhibitor, N(omega)-nitro-l-arginine methyl ester (L-NAME), but was inhibited by the NO donor, sodium nitroprusside. Treatment of the cells with 10 ng/ml of VEGF increased not only eNOS expression but also NO production. The extracellular signal-regulated kinase (Erk) of the mitogen-activated protein kinase (MAPK) family was activated by VEGF as demonstrated by the phosphorylation of Erk in Western blots. The effects of VEGF on NO production and the expression of endothelial NOS (eNOS) were attenuated by treating BeWo cells with the selective inhibitor of MAPK kinase, PD98059. VEGF-stimulated proliferation of BeWo cells was inhibited by the tyrosine kinase inhibitor genistein but increased by PD98059. Other kinase inhibitors, including LY294002 (phosphoinositide 3-kinase inhibitor) and SB203580 (P38 MAPK inhibitor), had no effect on the proliferation of the cells and NO production. These results indicate that endogenous NO production down-regulates the VEGF-stimulated proliferation of BeWo cells and that the activation of Erk plays an important role in this mechanism.

Animals↗
PubMed2001

Sphingosine 1-phosphate activates Akt, nitric oxide production, and chemotaxis through a Gi protein/phosphoinositide 3-kinase pathway in endothelial cells.

Sphingosine 1-phosphate (SPP) binds to members of the endothelial differentiation gene family (EDG) of receptors and leads to diverse signaling events including cell survival, growth, migration and differentiation. However, the mechanisms of how SPP activates these proangiogenic pathways are poorly understood. Here we show that SPP signals through the EDG-1 receptor to the heterotrimeric G protein G(i), leading to activation of the serine/threonine kinase Akt and phosphorylation of the Akt substrate, endothelial nitric-oxide synthase (eNOS). Inhibition of G(i) signaling, and phosphoinositide 3-kinase (PI 3-kinase) activity resulted in a decrease in SPP-induced endothelial cell chemotaxis. SPP also stimulates eNOS phosphorylation and NO release and these effects are also attenuated by inhibition of G(i) signaling, PI 3-kinase, and Akt. However, inhibition of NO production did not influence SPP-induced chemotaxis but effectively blocked the chemotactic actions of vascular endothelial growth factor. Thus, SPP signals through G(i) and PI 3-kinase leading to Akt activation and eNOS phosphorylation.

Animals↗