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Travel patterns and risk behavior in solid organ transplant recipients.

BACKGROUND: International travel is associated with an increased risk of enteric, vector-borne and bloodborne infections. The risk of acquiring travel-related illness is higher in those who are immunocompromised. However, little is known about travel practices and risk behaviors in transplant recipients who travel. We herein profile transplant recipients who travel, and characterize their pre-travel precautions, travel activities, burden of illness, and exposure history. METHODS: With the use of a standardized and validated questionnaire, patients attending a transplant clinic were surveyed regarding recent travel and risk behaviors. RESULTS: Of 267 transplant recipients who participated, 95 (36%) indicated that they had recently traveled outside Canada and the USA. Their mean age was 49.9 years, 54% were male, and 54% were born outside Canada. Eighty-six percent of travelers were receiving at least two immunosuppressive drugs at the time of their trip. Sixty-six percent of travelers sought pre-travel advice, primarily from their transplant physician. Sixty-three percent traveled to areas where hepatitis A is endemic, but only 5% had received hepatitis A immunization. Fifty percent traveled to dengue- and malaria-endemic areas, but,25% adhered to mosquito prevention measures. Ten percent reported behaviors that exposed them to blood or body fluids, including injections, body piercing, and casual sexual activity. CONCLUSIONS: Solid organ transplant recipients represent a unique group of compromised travelers; however, few were adequately protected against travel-associated enteric, vector-borne and bloodborne pathogens.

Adolescent↗

Effects of experimentally induced ametropia on the morphology and optical quality of the avian crystalline lens.

PURPOSE: To examine the effects of refractive error on avian lens morphology and optical quality. METHODS: Hatchling white leghorn chicks were unilaterally goggled for 7 days with either a form-deprivation goggle (n = 12), a -10 D defocus goggle (n = 12), or a +10 D defocus goggle (n = 12) to induce myopia and hyperopia. Optical quality of lenses (focal length and focal length variability) from treated and contralateral control eyes was assessed using a scanning laser apparatus. Lens morphology was examined by light and electron microscopy. RESULTS: Although the induction of refractive errors did not significantly alter lens size, shape, paraxial focal length, or average focal length, average focal length variability increased. Lenses from eyes goggled with form-deprivation and +10 D defocus goggles demonstrated a twofold increase in average focal length variability, when compared with their contralateral controls. The morphology of the lens is not altered by these experimental manipulations. CONCLUSIONS: This study provides evidence that the refractive development of the chick lens is not independent of the refractive development of the ocular globe and that chick lenticular development is influenced by both genetics and visual experience.

Animals↗

An acute and coincident increase in FABP expression and lymphatic lipid and drug transport occurs during intestinal infusion of lipid-based drug formulations to rats.

PURPOSE: To determine a) whether administration of lipid-based formulations can acutely up-regulate the intestinal expression of I-FABP and L-FABP and b) whether this occurs coincidentally with an increase in intestinal lymphatic lipid and drug transport. METHODS: The expression of I-FABP and L-FABP mRNA (using q-PCR) and protein (using immunohistochemistry and Western blotting) in enterocytes was compared with data describing transport of lipid and drug into intestinal lymph following infusion of a set of lipid-based formulations. RESULTS: Administration of relatively small amounts of oleic acid (5-20 mg/h) over a 5 h period to rats acutely up-regulated the expression, and altered the intracellular distribution of, I-FABP and L-FABP in the enterocytes of the small intestinal epithelia. The increase in expression of I-FABP and L-FABP correlated well with previous data describing the transport of lipid and drug into intestinal lymph following infusion of the same formulations. CONCLUSION: The expression and intracellular distribution of I-FABP and L-FABP are acutely influenced by lipid infusion over a time period relevant to feeding or the administration of pharmaceutical lipidic formulations, and these changes occur coincidentally with increased drug transport into the lymphatics.

Animals↗

Acute hemodynamic effects of pacing in patients with Fontan physiology: a prospective study.

OBJECTIVES: The purpose of this research was to assess the hemodynamic response to atrial, ventricular, and dual-chamber pacing in patients with Fontan physiology. BACKGROUND: Bradycardia, due to sinus node dysfunction or atrioventricular (AV) block, with need for pacing, is common after the Fontan operation. The optimal pacing mode for Fontan patients is unknown, but is critical, as hemodynamic aberrancies may cause severe clinical deterioration. We hypothesized that AV synchrony is vital for maximizing Fontan hemodynamics. METHODS: A cross-over trial was conducted with 21 patients (age 2 to 18 years, median 4 years; male patients = 13) in the intensive care unit after a Fontan operation. Hemodynamic parameters, including mean left atrial pressure (LAP, in mm Hg), mean pulmonary artery pressure (PAP, in mm Hg), mean arterial blood pressure (MAP, in mm Hg), and indexed cardiac output via Fick (Qs, in l/min/m2) were measured with atrial, ventricular, and dual-chamber pacing. Measurements were made after pacing for 10 min in each mode, and a 10-min rest was given between each pacing maneuver. RESULTS: Asynchronous ventricular (VOO) pacing resulted in significantly worse hemodynamics when compared to dual-chamber (DOO) and atrial (AOO) pacing with a higher LAP (9.4 VOO; 6.8 DOO; 5.4 AOO) and PAP (15.2 VOO; 13.5 DOO; 12.7 AOO) and lower Qs (3.0 VOO; 3.5 DOO; 3.9 AOO) and MAP (60.1 VOO; 66.5 DOO; 67.2 AOO). CONCLUSIONS: Asynchronous ventricular pacing, after the Fontan procedure, has acute, adverse hemodynamic consequences (elevated LAP and PAP and decreased Qs and MAP).

Adolescent↗

Controlled perfusion decreases reperfusion injury after high-flow reperfusion.

INTRODUCTION: Some investigators have suggested that high pulmonary artery flow rates increase the risk of severe reperfusion injury after lung transplantation. We hypothesized that controlling the initial flow rate and pulmonary artery pressure would decrease the severity of lung dysfunction in the setting of high-flow reperfusion. METHODS: Using our isolated, ventilated, blood-perfused rabbit lung model, all groups underwent lung harvest, 4-hour storage (4 degrees C), and blood reperfusion. We measured pulmonary artery pressure, peak inspiratory pressure, arterial oxygenation, and wet-to-dry weight ratio. Group 1 (control, n = 8) underwent reperfusion at 60 ml/min for 30 minutes. Group 2 (high flow, n = 8) underwent reperfusion at 120 ml/min for 30 minutes. Group 3 (controlled flow, n = 8) underwent initial reperfusion at 60 ml/min for 5 minutes, followed by reperfusion at 120 ml/min for 25 minutes. RESULTS: Group 1 had significantly improved pulmonary artery pressure, peak inspiratory pressure, arterial oxygenation, and wet-to-dry weight ratio measurements compared with groups 2 and 3 after 30 minutes of reperfusion. However, Group 3 had improved pulmonary artery pressure, peak inspiratory pressure, arterial oxygenation, and wet-to-dry weight ratio measurements compared with Group 2. CONCLUSIONS: High-flow reperfusion results in severe reperfusion injury after lung transplantation. Controlled reperfusion using a low initial flow rate decreases the severity of reperfusion injury associated with high-flow rates.

Animals↗

Determinants of carotid microembolization.

PURPOSE: Earlier studies have highlighted risk factors for perioperative stroke after carotid endarterectomy, such as female sex, preoperative symptoms, and cerebral infarction. In this study, we investigated the relationship between these factors and perioperative microembolization. METHODS: A total of 235 patients were entered in the study at two centers. Transcranial Doppler ultrasound scanning was possible in 190 patients (81%) and was performed for 1 hour preoperatively and continuously intraoperatively as a means of detecting microemboli and monitoring mean middle cerebral artery velocity. The findings of transcranial Doppler ultrasound scanning were related to perioperative risk factors by means of univariate analysis. RESULTS: Microemboli were detected in 28 (15%), 79 (42%), and 98 (52%) patients preoperatively, during carotid artery dissection, and after closure of the artery, respectively. Having 10 or more emboli after carotid artery closure was more common in women (P = .04) and in patients with symptomatic carotid artery disease (P = .04) and was demonstrated in three of the six patients who had a perioperative stroke. These three patients also had preoperative evidence of cerebral infarction and an intraoperative middle cerebral artery velocity less than 40 cm/s. CONCLUSION: In this study, perioperative microembolization was more common in women and patients with symptomatic carotid artery disease. These findings may explain the increased risk of carotid surgery in these patients.

Adult↗

Serum anti-Mullerian hormone levels during controlled ovarian hyperstimulation in women with polycystic ovaries with and without hyperandrogenism.

BACKGROUND: Anti-Mullerian hormone (AMH) is expressed in pre- and small-antral follicles. High serum levels are found in women with polycystic ovaries (PCO), accordant with their increased content of small follicles. To evaluate the relationship between AMH, folliculogenesis and hyperandrogenism, we compared serum AMH levels between women with PCO with and without hyperandrogenism and normal controls during controlled ovarian hyperstimulation (COH). METHODS: Nineteen women with PCO and hyperandrogenism (group A), 10 women with PCO but no hyperandrogenism (group B) and 23 ovulatory women with normal ovarian morphology (group C, controls) underwent COH with the long protocol. Serum levels of AMH, estradiol, androstenedione and follicular tracking were determined before gonadotropins treatment (day 0) and every 2-4 days up to the day of HCG administration. RESULTS: AMH levels declined gradually throughout COH in the three groups, but remained higher in groups A and B compared with the controls. Significantly higher levels were found in group A compared with group B, despite comparable numbers of small follicles. Multiple regression analysis revealed that both the number of small follicles and serum androgens were correlated to AMH. CONCLUSIONS: Women with PCO have higher serum AMH levels during COH than controls. Hyperandrogenism is associated with an additional increase in AMH. It is conceivable that hyperandrogenism may reflect more severe disruption of folliculogenesis in women with PCO or may affect AMH secretion.

Adult↗

Immune activation and induction of HIV-1 replication within CD14 macrophages during acute Plasmodium falciparum malaria coinfection.

OBJECTIVES: To determine the impact of Plasmodium falciparum malaria coinfection and its treatment on cellular reservoirs of viral replication in HIV-1-infected persons and to relate this to changes in systemic immune activation. METHODS: Plasma samples were obtained from HIV-1-infected individuals (n = 10) at diagnosis of acute malaria, 4 weeks after parasite clearance and from HIV-infected aparasitemic controls (n = 10). Immunomagnetic HIV-1 capture analysis was used to determine the cellular origin of cell-free virus particles present in all 30 plasma samples and indices of immune activation were measured using enzyme-linked immunosorbent assays. RESULTS: Compared with controls, the detectable proportion of HIV-1 particles derived from CD14 macrophages and CD26 lymphocytes was increased in persons with acute malaria coinfection and correlated with markedly increased plasma concentrations of both proinflammatory cytokines and soluble markers of macrophage and lymphocyte activation. Parasite clearance following treatment with antimalarial drugs resulted in decreased detection of HIV-1 particles derived from the CD14 macrophage cell subset and correlated with a marked diminution in systemic immune activation. CONCLUSIONS: Acute P. falciparum malaria coinfection impacts virus-host dynamics in HIV-1-infected persons at the cellular level, notably showing a reversible induction of HIV-1 replication in CD14 macrophages that is associated with changes in immune activation.

Animals↗

The role of alternative splicing of the adhesion molecule, CD44, in lymphoid malignancy.

AIM: To investigate the expression of CD44 isoforms containing variant exon 6 (v6) in a well characterised cohort of patients with non-Hodgkin's lymphoma (NHL) and chronic lymphocytic leukaemia (CLL), and to correlate this with phenotype and disease course. METHODS: Cryostat sections of OCT embedded diagnostic nodal material from NHL patients and cryopreserved mononuclear preparations from CLL patients were used as sources of RNA. After reverse transcription, PCR was carried out with amplimers positioned at either side of the variant exon insertion site to amplify all possible CD44 isoforms. Those isoforms containing v6 were identified after Southern blotting and hybridisation with a radiolabelled oligonucleotide. RESULTS: Of 32 NHL samples analysed, 16 did not express CD44 isoforms containing v6, six expressed an isoform containing exon v6 alone, and 10 expressed v6 long isoforms which contained exon v6 in addition to other variant exons. These data did not correlate with lymphoma classification, disease staging, or the presence or absence of extranodal disease. However, those patients expressing v6 long CD44 isoforms had a worse overall survival than those that did not. The plateau of the survival curves was 50% compared with 82%. No v6 long isoforms were detected in the 21 CLL samples investigated. CONCLUSIONS: The expression of v6 long CD44 isoforms is associated with aggressive disease in NHL, independent of grade, stage, or presence of extranodal disease.

Alternative Splicing↗

Effect of benzodiazepines on structural and conceptual/lexical priming.

RATIONALE: Impaired perceptual priming, as assessed by naming reaction times and accuracy, for briefly presented contour-deleted pictures under lorazepam has been documented in several studies but whether the nature of this impairment is visual versus conceptual/lexical is not clear. We used a previously developed paradigm to examine whether lorazepam affects visual processes involved in the coding of contour information or conceptual/lexical representations. METHOD: Three groups were tested (lorazepam, diazepam and placebo). In the study phase, participants named line drawings, presented for 500 ms, in which 50% of the contour was deleted by removing every other line and vertex from each part. In the test phase, participants saw the identical picture, its complement (the other 50% of the contour), or a samename/different-shape picture, each presented for 200 ms. RESULTS: For all three groups, the magnitude of priming, as assessed by naming RTs and error rates, was equivalent in the identical and in the complementary conditions and the amount of facilitation was reduced in the same-name condition. Perceptual priming occurred both in the lorazepam and in the diazepam groups, though reduced, compared to placebo, for RTs. No conceptual priming (i.e. facilitated performance in the same-name condition) was observed in the benzodiazepine groups. CONCLUSION: Equivalent priming for identical and complementary pictures in the three groups suggests that benzodiazepines do not affect the activation of the geon structural description. The lack of priming for same-name pictures suggests that benzodiazepines affect access, retrieval or selection of conceptual/lexical information.

Adolescent↗

Distribution of the matrix metalloproteinases stromelysin, gelatinases A and B, and collagenase in Crohn's disease and normal intestine.

AIMS: To investigate the role of the matrix metalloproteinases (MMPs) in the connective tissue changes seen in the intestine in Crohn's disease. METHODS: Indirect immunofluorescence microscopy using specific antibodies to the MMPs (collagenase, gelatinase A and B, and stromelysin) were used to assess the distribution of these enzymes in normal and diseased intestine. RESULTS: In normal intestine the matrix metalloproteinases were confined to a few isolated inflammatory cells, but in Crohn's disease, the inflammatory infiltrate was associated with increased numbers of polymorphonuclear leucocytes which stained positive for gelatinase B. Stromelysin was also detected extracellularly on the connective tissue matrix in regions of smooth muscle cell proliferation and mucosal degradation. Interestingly, in ulcerative colitis, another inflammatory bowel disease, stromelysin was localised in the lamina propria in regions of mucosal loss. CONCLUSIONS: The increased numbers of inflammatory cells containing gelatinase B, and the localisation of extracellular stromelysin in regions of fibrosis and mucosal degradation, suggest that these enzymes have a role in the pathological changes seen in Crohn's disease. In cases of ulcerative colitis stromelysin was also detected on the lamina propria in regions of mucosal loss, and seems to be associated with the connective tissue changes that precede mucosal loss.

Colitis, Ulcerative↗

Determination of the plasma levels of metyrapone and its enantiomeric metyrapol metabolites by direct plasma injection and multidimensional achiral-chiral chromatography.

The development and validation of a direct injection high-performance liquid chromatographic (HPLC) method, with column switching, for the determination of metyrapol enantiomers and metyrapone in human plasma is described. The system used in this work was composed of a restricted access media (RAM) bovine serum albumin (BSA) octyl column coupled to an amylose tris(3,5-dimethoxyphenylcarbamate) chiral column. Water was used as eluent for the first 5 min at a flow rate of 1.0 ml/min for the elution of the plasma proteins and then acetonitrile-water (30:70 v/v) for the transfer and analysis of metyrapol enantiomers and metyrapone, which were detected by UV at lambda = 260 nm. The total analysis time was about 32 min. The calibration curves for each enantiomer and for the metyrapone were linear in the ranges 0.075-0.75 microg/ml and 0.150-1.50 microg/ml, respectively. Recoveries, intra- and interday precision and accuracy were determined using three quality controls, one low (0.18 microg/ml), one medium (0.75 microg/ml), and one high (1.35 microg/ml) plasma concentration. Quantitative recoveries and good precision and accuracy were obtained. The limit of quantitation were 0.045 microg/ml for both enantiomers and for the metyrapone.

Calibration↗

Effect of lateral sphincterotomy on internal anal sphincter function. A computerized vector manometry study.

PURPOSE: This study was designed to investigate the effect of lateral sphincterotomy on internal anal sphincter function in patients with chronic anal fissure. METHODS: Using an eight-channel perfusion catheter and computerized data analysis, a prospective manometric study was performed on patients with chronic anal fissure undergoing lateral sphincterotomy (LS). RESULTS: Mean resting pressure (MRP) in patients with anal fissure (85.1 mmHg) was significantly higher (P = 0.012) than control subjects (63.3 mmHg). One week following LS there was a significant reduction in MRP (50.0 mmHg; P = 0.0014), and this was maintained when reassessed five weeks later (MRP = 56.4 mmHg; P = 0.0019). There was no significant difference in coefficient of variation (a measure of the degree of manometric asymmetry of the anal canal) in the control group (mean, 8.9 percent) and in patients with anal fissure (mean, 7.7 percent; P = 0.43). LS created a significant increase in anal canal resting manometric asymmetry when assessed at one (mean, 17.3 percent; P = 0.0013) and six weeks (mean, 11.7 percent; P = 0.027) after the procedure. CONCLUSION: LS produces a global and symmetric decrease in anal canal resting pressure. In addition, it produces a significant increase in manometric asymmetry of the resting anal canal by creating a detectable segmental defect.

Adult↗

Endoscopic direct cholangioscopy by using an ultra-slim upper endoscope: a feasibility study.

BACKGROUND: The search for an easier and less cumbersome technique to perform direct visual examination of the biliary tree is still underway. OBJECTIVE: To assess the feasibility of performing endoscopic direct cholangioscopy utilizing an ultra-slim upper endoscope designed for pediatric patients. DESIGN: Prospective, observational, pilot study. SETTING: Tertiary referral center. PATIENTS: Three patients who underwent endoscopic retrograde cholangiography for evaluation and treatment of choledocholithiasis. METHODS: Following the completion of the endoscopic retrograde cholangiography, a 0.035-inch diameter super-stiff Jagwire (Boston Scientific Corp, Natick, Mass) was placed in the common bile duct. Using the wire to maintain access, we removed the duodenoscope and backloaded the wire onto an ultra-slim upper endoscope (GIF-XP 160, Olympus America Inc, Melville, NY), which was advanced over the guidewire under fluoroscopic and endoscopic control into the duodenum and then across the ampulla of Vater into the common bile duct and upstream. RESULTS: Endoscopic direct cholangioscopy was attempted and successfully completed in all 3 patients. One patient was found to have persistent large amount of sludge and stones, and was referred for surgery. In the other two patients, endoscopic direct cholangioscopy demonstrated complete duct clearance, obviating the need for stent placement and repeat endoscopic retrograde cholangiography procedures. LIMITATIONS: Small sample size, pilot study. CONCLUSIONS: Endoscopic direct cholangioscopy with an ultra-slim upper endoscope originally designed for pediatric use is feasible. Future advances in endoscope development, as well as specifically designed accessories, could lead to the next generation of intraductal diagnosis and therapy.

Aged↗

Differential distribution of HLA-DQ beta/DR beta epitopes in the two forms of Guillain-Barré syndrome, acute motor axonal neuropathy and acute inflammatory demyelinating polyneuropathy (AIDP): identification of DQ beta epitopes associated with susceptibility to and protection from AIDP.

Guillain-Barré syndrome (GBS), an acute, immune-mediated paralytic disorder affecting the peripheral nervous system, is the most common cause of acute flaccid paralysis in the post-polio era. GBS is classified into several subtypes based on clinical and pathologic criteria, with acute inflammatory demyelinating polyneuropathy (AIDP) and acute motor axonal neuropathy (AMAN) being the most common forms observed. To better understand the pathogenesis of GBS and host susceptibility to developing the disease, the distribution of HLA class II Ags along with the seroreactivity to Campylobacter jejuni were investigated in a population of GBS patients from northern China. Using DNA-based typing methods, 47 patients with AMAN, 25 patients with AIDP, and 97 healthy controls were studied for the distribution of class II alleles. We found that the DQ beta RLD(55-57)/ED(70-71) and DR beta E(9)V(11)H(13) epitopes were associated with susceptibility to AIDP (p = 0.009 and p = 0.004, respectively), and the DQ beta RPD(55-57) epitope was associated with protection (p = 0.05) from AIDP. These DQ beta/DR beta positional residues are a part of pockets 4 (DQ beta 70, 71, DR beta 13), 6 (DR beta 11), and 9 (DQ beta 56, 57, DR beta 9); have been demonstrated to be important in peptide binding and T cell recognition; and are associated with other diseases that have a pathoimmunological basis. Class II HLA associations were not identified with AMAN, suggesting a different immunological mechanism of disease induction in the two forms of GBS. These findings provide immunogenetic evidence for differentiating the two disease entities (AMAN and AIDP) and focuses our attention on particular DR beta/DQ beta residues that may be instrumental in understanding the pathophysiology of AIDP.

Acute Disease↗

Motor vehicle occupant injuries in New Zealand children, 1981-90.

AIM: To determine the incidence of motor vehicle occupant injuries in New Zealand children and to consider future directions for prevention. METHODS: The Ministry of Health's national mortality and morbidity files for the years 1981-1990 were examined to identify all deaths and hospital discharges for motor vehicle occupant injuries in children between the ages of 0-14 years. RESULTS: Over the 10 year period, there was an average of 26 deaths and 433 hospitalisations annually. Fatality rates were highest for the age group 0-2 years, whereas hospitalisation rates were highest for those aged 3-4 years. Although mortality rates were similar for Maori and nonMaori children, the hospitalisation rate for Maori children was more than three times that for nonMaori children. No significant trends in either fatality or hospitalisation rates were evident. DISCUSSION: Motor vehicle occupant injury is an important public health problem in New Zealand children. Reductions in the numbers of motor vehicle occupant deaths and hospitalisations will require not only legislative changes aimed at increasing restraint use, but also the development of strategies to ensure compliance with the legislation. The identification of barriers to the use of child restraints is likely to facilitate the development of effective strategies aimed at increasing occupant restraint use.

Accidents, Traffic↗

Apolipoprotein E-epsilon 4 protects against severe liver disease caused by hepatitis C virus.

The outcome of infection with hepatitis C virus (HCV) varies greatly. The virus associates with serum lipoproteins, including those containing apolipoprotein E (apoE) and apolipoprotein B (apoB), and may enter cells via the low-density lipoprotein receptor (LDLR). ApoE genotypes can affect the extent of damage in diseases caused by 2 other viruses--herpes simplex virus type 1 (HSV1; in Alzheimer's disease and herpes labialis) and human immunodeficiency virus (HIV). We therefore investigated whether specific apoE and apoB alleles were associated with different outcomes of HCV infection. A total of 156 anti-HCV-positive patients and 104 non-HCV-infected patients were studied. Liver biopsy specimens from patients with chronic HCV infection (n = 111) were assessed for disease severity by the Knodell system. ApoE and apoB genotypes were determined by standard polymerase chain reaction (PCR) methods. There was no significant difference among the apoE genotypes of HCV-infected subjects compared with previously published population data, or between HCV-RNA positive or negative patients. However, chronically HCV-infected subjects with mild liver disease (n = 65) had a significantly higher apoE-epsilon 4 allele frequency (20.0%) than those (n = 46) with severe disease (6.5%). ApoB alleles alone or in combination with apoE were not associated with mild or severe disease. The overall apoE allele frequencies of patients with liver disease not caused by HCV were similar to those of the total HCV group and in contrast to the HCV patients, the apoE allele frequencies were similar in those patients with no or mild fibrosis as compared with those with bridging fibrosis or cirrhosis. In conclusion, carriage of an apoE-epsilon 4 allele may be protective against liver damage caused by HCV, but not against damage due to various nonviral causes. This is yet another case in which apoE may determine the severity of a viral disease.

Adult↗

Incorporation of naive bone marrow derived cells into the vascular architecture of brain tumor.

OBJECTIVE: Neovascularization is essential for tumor growth and invasion. Mounting evidence suggests that tumor cells recruit circulating endothelial progenitor cells to promote vasculogenesis to compliment tumor angiogenesis. This study examines the constitutive role of bone marrow-derived cells in this process. METHODS: Rat glioma cells were implanted into brains of T-cell-depleted knockout mice. At various timepoints after tumor implantation, naïve bone marrow cells from ubiquitous transgenic mice expressing green fluorescent protein (GFP) were infused into these animals. The incorporation of GFP-positive cells into the vascular architecture was visualized by fluorescence confocal microscopy in conjunction with the transcription profiles of vascular endothelial growth factor (VEGF) and angiopoietin-1 and -2 (Ang-1 and Ang-2). RESULTS: Of the cells infused, 8 days after tumor implantation, 0.49% were found exclusively sequestered in the vicinity of tumor vessels. This coincided with a decline in the expression of Ang-1 and a rise in the expression of VEGF and Ang-2. A few of these cells (0.66 of the 0.49%) localized onto the vascular wall. They resembled endothelial cells and expressed vWF. CONCLUSION: The incorporation of bone marrow-derived unpurified endothelial cells into the tumor vascular bed is both time-limited and infrequent. These cells may play a supportive rather than a constitutive role in tumor neovascularization.

Angiogenic Proteins↗