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E D Reis

Publications and source records attributed to E D Reis.

At least 19 recordsLinked to original sources
PubMed2003

Encapsulation of packaging cell line results in successful retroviral-mediated transfer of a suicide gene in vivo in an experimental model of glioblastoma.

AIMS: Retroviral-mediated gene therapy has been proposed as a primary or adjuvant treatment for advanced cancer, because retroviruses selectively infect dividing cells. Efficacy of retroviral-mediated gene transfer, however, is limited in vivo. Although packaging cell lines can produce viral vectors continuously, such allo- or xenogeneic cells are normally rejected when used in vivo. Encapsulation using microporous membranes can protect the packaging cells from rejection. In this study, we used an encapsulated murine packaging cell line to test the effects of in situ delivery of a retrovirus bearing the herpes simplex virus thymidine kinase suicide gene in a rat model of orthotopic glioblastoma. MATERIALS AND METHODS: To test gene transfer in vitro, encapsulated murine psi2-VIK packaging cells were co-cultured with baby hamster kidney (BHK) cells, and the percentage of transfected BHK cells was determined. For in vivo experiments, orthotopic C6 glioblastomas were established in Wistar rats. Capsules containing psi2-VIK cells were stereotaxically implanted into these tumours and the animals were treated with ganciclovir (GCV). Tumours were harvested 14 days after initiation of GCV therapy for morphometric analysis. RESULTS: Encapsulation of psi2-VIK cells increased transfection rates of BHK target cells significantly in vitro compared to psi2-VIK conditioned medium (3 x 10(6) vs 2.3 x 10(4) cells; P<0.001). In vivo treatment with encapsulated packaging cells resulted in 3% to 5% of C6 tumour cells transduced and 45% of tumour volume replaced by necrosis after GCV (P<0.01 compared to controls). CONCLUSION: In this experimental model of glioblastoma, encapsulation of a xenogeneic packaging cell line increased half-life and transduction efficacy of retrovirus-mediated gene transfer and caused significant tumour necrosis.

Animals↗
PubMed2003

[Microvascular denudation of the femoral artery of the mouse as a model for restenosis].

OBJECTIVE: To present technique and results of a microvascular denudation of the common femoral artery of the mouse as a model for inducing intimal hyperplasia in interventional radiology. MATERIALS AND METHODS: Under general anesthesia introduced by intraperitoneal injection, 14 B6129F1 hybrid mice (7 females and 7 males) at a mean age of 12.1 +/- 1.8 weeks and a mean weight of 28 +/- 2.8 grams had a groin incision of the vascular bundle directly distal to the inguinal ligament in preparation of placing a vascular clamp. Thereafter, the femoral artery was dissected distal to the origin of the epigastric artery and a loop prepared for a ligation proximal to the planned arteriotomy. Through an arteriotomy performed free-hand with a pair of micro scissors, a 0.010" (= 0.25 mm) guidewire was introduced into the vessel and advanced to the aortic bifurcation. The guide-wire was moved back and forth three times. The same procedure was performed on the other side as sham-operation, i.e., without introduction and passage of a guidewire. The resulting changes of the vessel wall were evaluated by histology and morphometry. RESULTS: Four weeks after intervention, the mean intima-to-media-ratio (IMR) was 1.80 +/- 0.28. A significant difference was observed between the sexes, with an IMR of 1.41 +/- 0.29 in females and an IMR of 2.24 +/- 0.45 in males (p = 0.0173). The neointima led to an overall luminal loss of 50.2% +/- 8.3% without significant sex difference (p = 0.09), but the average luminal loss was still more severe in females, amounting to 43.9% in comparison to 56.1% in males. This technique induces a significant neointima formation in a reproducible manner. The internal elastic membrane was preserved in all vessels. CONCLUSION: This technique is an excellent model to examine the differences between genetically modified mice to clarify the role of putative key molecules in the pathophysiology of restenosis.

Angioplasty, Balloon↗
PubMed2001

Elevating high-density lipoprotein cholesterol in apolipoprotein E-deficient mice remodels advanced atherosclerotic lesions by decreasing macrophage and increasing smooth muscle cell content.

BACKGROUND: HDL cholesterol levels are inversely correlated with coronary heart disease risk in humans, and in animal studies, HDL elevation decreases formation and progression of foam-cell lesions. The potential for HDL to affect preexisting advanced atherosclerotic lesions is not known. To approach this issue, we used a novel mouse aortic transplantation model. METHODS AND RESULTS: ApoE-deficient (EKO) mice were fed a Western-type diet for 6 months, and thoracic aortic segments containing advanced lesions replaced segments of the abdominal aorta of 4-month-old EKO syngeneic mice not expressing (plasma HDL cholesterol approximately 26 mg/dL) or expressing (HDL approximately 64 mg/dL) a human apoAI (hAI) transgene. Both types of recipients had comparable non-HDL cholesterol levels. Five months after transplantation, mice were killed and grafts analyzed. Compared with lesion area in pretransplant mice (0.14+/-0.04 mm(2), mean+/-SEM), there was progression in the EKO recipients (0.39+/-0.06 mm(2), P<0.01). Compared with EKO recipients, hAI/EKO recipients had retarded progression (0.24+/-0.04 mm(2), P<0.05). Immunostaining for CD68 and other macrophage-associated proteins, monocyte chemoattractant protein-1, acyl coenzyme A:cholesterol acyltransferase, and tissue factor, in lesions of pretransplant and EKO recipient mice showed abundant macrophages. In contrast, compared with any other group, lesional macrophage area in hAI/EKO mice decreased >80% (P<0.003), and smooth muscle cell content (alpha-actin staining) increased >300% (P<0.006). The decrease in macrophages and increase in smooth muscle cells was primarily in the superficial subendothelial layer. CONCLUSIONS: Increasing HDL cholesterol levels in EKO mice retards progression of advanced atherosclerotic lesions and remodels them to a more stable-appearing phenotype.

Actins↗
PubMed2001

Variable protection of beta 3-integrin--deficient mice from thrombosis initiated by different mechanisms.

Platelet integrin alpha IIb beta 3 (GPIIb/IIIa) plays a central role in the initiation of arterial thrombosis, but its contribution to disseminated microvascular thrombosis is less well defined. Therefore, wild-type mice (beta 3(+/+)), beta 3-integrin-deficient mice (beta 3(-/-)), and wild-type mice treated with a hamster monoclonal antibody (1B5) that blocks murine alpha IIb beta 3 function were tested in models of large-vessel and microvascular thrombosis. In the large-vessel model, ferric chloride was used to injure the carotid artery, and the time to thrombosis was measured. In beta 3(+/+) mice, the median time to occlusion was 6.7 minutes, whereas occlusion did not occur in any of the beta 3(-/-) mice tested (P <.001). Fab and F(ab')(2) fragments of 1B5 increased the median time to occlusion. To initiate systemic intravascular thrombosis, prothrombotic agents were administered intravenously, and platelet thrombus formation was monitored by the decrease in circulating platelet count. Three minutes after the injection of adenosine diphosphate (ADP), collagen + epinephrine, or tissue factor, the platelet counts in beta 3(+/+) mice decreased by 289, 424, and 429 x 10(3)/microL, respectively. beta 3(-/-) mice and wild-type mice pretreated with 1B5 Fab (1 mg/kg, IP) were nearly completely protected from the effects of ADP. In contrast, beta 3(-/-) mice were only partially protected from the effects of collagen + epinephrine and minimally protected from the effects of tissue factor. In all cases, less fibrin became deposited in the lungs of beta 3(-/-) mice than in wild-type mice. These results suggest that though alpha IIb beta 3 plays a dominant role in large-vessel thrombosis, it plays a variable role in systemic intravascular thrombosis. (Blood. 2001;98:1055-1062)

Animals↗
PubMed2001

Beta(3)-integrin-deficient mice but not P-selectin-deficient mice develop intimal hyperplasia after vascular injury: correlation with leukocyte recruitment to adherent platelets 1 hour after injury.

BACKGROUND: Intimal hyperplasia contributes to restenosis after percutaneous vascular interventions. Both beta(3)-integrins, alpha(V)beta(3) and alpha(IIb)beta(3) (glycoprotein IIb/IIIa), and leukocytes have been implicated in neointimal formation, based in part on the results obtained using antagonists to 1 or both receptors in animal models. METHODS AND RESULTS: The responses in wild-type mice, beta(3)-integrin-deficient mice, and P-selectin-deficient mice were studied in a model of transluminal endothelial injury of the femoral artery. At 4 weeks, beta(3)-integrin-deficient mice were not protected from developing intimal hyperplasia, whereas P-selectin-deficient mice were protected. Within 1 hour of injury, several layers of platelets deposited on the arteries of wild-type mice and a single layer of platelets deposited on the vessels of beta(3)-integrin-deficient mice; in both cases, leukocytes were recruited to the platelet layer. In P-selectin-deficient mice, the platelet layer was less compact and extended further into the lumen but did not recruit leukocytes. CONCLUSIONS: In a model of transluminal arterial injury, absence of early leukocyte recruitment and not deficiency of beta(3)-integrins correlated with a reduction in neointimal formation. Blockade of P-selectins may be an effective therapeutic strategy to decrease restenosis after percutaneous vascular interventions.

Animals↗
PubMed2001

Esophageal cancer as second primary tumor after breast cancer radiotherapy.

BACKGROUND: An increased risk of esophageal cancer has been reported in survivors of breast cancer treated with radiotherapy. This study further characterizes this association. METHODS: Through hospital databases, 118 patients (109 men, 9 women) treated for esophageal cancer between 1985 and 1993 were identified, of whom 37 had 60 synchronous or metachronous cancers. 5 women had primary esophageal cancer after having breast cancer, and are the subjects of this case-control study. RESULTS: All 5 women had been treated with radical mastectomy and adjuvant radiotherapy; none received chemotherapy. Their ages at the time of breast cancer ranged from 36 to 82 years; at esophageal cancer, 61 to 95 years. Time between radiotherapy and esophageal cancer varied from 13 to 31 years. All esophageal cancers were squamous cell carcinomas. Mean survival after esophageal cancer was 14.2 months. CONCLUSIONS: Radio-induced esophageal cancer can occur as a second primary cancer in women who survive at least 1 decade after mastectomy and adjuvant radiotherapy.

Adult↗
PubMed2001

Current controversies in shock and resuscitation.

Many controversies and uncertainties surround resuscitation of hemorrhagic shock caused by vascular trauma. Whereas the basic pathophysiology is better understood, much remains to be learned about the many immunologic cascades that lead to problems beyond those of initial fluid resuscitation or operative hemostasis. Fluid therapy is on the verge of significant advances with substitute oxygen carriers, yet surgeons are still beset with questions of how much and what type of initial fluid to provide. Finally, the parameters chosen to guide therapy and the methods used to monitor patients present other interesting issues.

Biological Transport↗
PubMed2001

Effect of p27 deficiency and rapamycin on intimal hyperplasia: in vivo and in vitro studies using a p27 knockout mouse model.

SUMMARY: Rapamycin, an immunosuppressant and antiproliferative agent, reduces intimal hyperplasia after arterial injury in animal models and in a preliminary study in humans. Rapamycin treatment reportedly increases expression of p27, a cyclin-dependent kinase inhibitor. This mechanism was tested using a p27-deficient (p27 -/-) murine model. Aortic smooth muscle cells from wild-type (WT) and p27 -/- mice were isolated and cultured. Cell proliferation, assessed by cell count and (3)H-thymidine incorporation, was inhibited significantly by rapamycin in WT and p27 -/- cells at concentrations of 1 ng/ml, 10 ng/ml, and 100 ng/ml (p < 0.05, versus control). The in vivo effect on intimal hyperplasia was studied in p27 -/- and WT mice after femoral artery transluminal injury. Rapamycin treatment was started 2 days before injury and maintained for 2 weeks (1 mg/kg per 48 hours, ip). No significant differences in intima-to-media ratio were found between WT (1.1 +/- 0.1) and p27 -/- mice (1.0 +/- 0.1) 4 weeks after injury. Rapamycin significantly (p < 0.05) reduced intima-to-media ratios in both WT (0.7 +/- 0.1) and p27 -/- mice (0.5 +/- 0.1), compared with untreated mice. p27 deficiency did not alter the arterial wall proliferative response to injury. The inhibitory effect of rapamycin on intimal hyperplasia occurred via a p27-independent mechanism. The in vitro data showed that this effect was mediated through decreased proliferation and enhanced apoptosis.

Animals↗
PubMed2001

Dramatic remodeling of advanced atherosclerotic plaques of the apolipoprotein E-deficient mouse in a novel transplantation model.

OBJECTIVE: Regression of atherosclerotic lesions is an important goal. No extensive experimental evidence shows that it can be achieved for advanced lesions. To study this, we developed a model to maintain a long-term change in the plasma lipoprotein environment of advanced arterial lesions of hyperlipidemic (apolipoprotein E [apoE]-deficient) mice. METHODS: The apoE-deficient mice (plasma total cholesterol of 1334 +/- 219 [+/- SEM] mg/dL) on a typical Western diet for 38 weeks had advanced atherosclerotic lesions (ie, beyond the macrophage foam cell stage) throughout the arterial tree. Lesion-containing thoracic aortas were transplanted (replacing a segment of abdominal aorta) into either apoE-deficient or wild-type (WT) (total cholesterol of 86 +/- 10 mg/dL) recipients. Grafts were harvested after 9 weeks. RESULTS: Compared with pretransplant lesions (area = 0.0892 +/- 0.0179 mm(2)), lesion size tended to increase in apoE-deficient to apoE-deficient grafts (0.2411 +/- 0.0636 mm(2); P =.06), whereas a significant reduction was seen in apoE-deficient to WT grafts (0.0214 +/- 0.0049 mm(2); P <.001). Also, foam cells were absent in apoE-deficient to WT grafts, but abundant in pretransplant lesions and apoE-deficient to apoE-deficient grafts. Grafts were evaluated noninvasively in vivo with magnetic resonance imaging, and wall thickening was detected in the apoE-deficient to apoE-deficient group. CONCLUSIONS: Nearly complete regression of advanced atherosclerotic lesions can be achieved with sustained normalization of the plasma lipoprotein profile. Syngeneic arterial transplantation in mice is a novel and valuable model system for atherosclerosis research; and magnetic resonance imaging can detect differences in characteristics in lesions undergoing regression.

Animals↗
PubMed2001

Peripheral arterial disease. Medical management in primary care practice.

Peripheral arterial disease (PAD) is caused by atherosclerosis, the leading cause of death and disability in patients age 50 and older. PAD progresses gradually and silently over many years, occluding the lumen of arteries that supply blood to the extremities. Symptoms of peripheral arterial insufficiency include intermittent claudication, rest pain, and impotence. Nonoperative management--including the control of risk factors such as hypertension, diabetes, hyperlipidemia, and smoking--is the most effective method to lower the risk of morbidity from PAD. Diagnostic technologies such as color duplex imaging, MRI, and MRA complement the clinical assessment of PAD and provide a stronger foundation for treatment decisions in the primary care setting.

Aged↗
PubMed2001

Visceral artery aneurysms: experience in a tertiary-care center.

Visceral artery aneurysms (VAAs) often rupture and cause serious morbidity or death. The purpose of this study was to identify conditions associated with VAA in a series of 30 patients treated at our institution from 1988 through 1998. Demographics, types of aneurysms, associated conditions, diagnoses, treatments, and outcomes were recorded and analyzed. Thirty patients (16 men and 14 women) with VAA were identified. The arteries involved were splenic (eight), renal (ten), hepatic (nine), hypogastric (one), celiac (one), and pancreaticoduodenal (one). Five of eight (63%) splenic artery aneurysms occurred in women; however, gender was not a factor in other aneurysmal groups. Splenic artery aneurysm also was associated with cirrhosis in four of the eight (50%) patients. Five of the nine (56%) hepatic artery aneurysms were associated with cirrhosis; two of these were pseudoaneurysms that occurred after liver transplantation. Five of ten (50%) renal artery aneurysms were associated with juxtarenal abdominal aortic aneurysms. Celiac and pancreaticoduodenal aneurysms were associated with gastrointestinal bleeding. Treatments included surgery (19), embolization (eight), and observation alone (three). These data demonstrate that association with other conditions varies according to subgroups of VAA. Despite advances in diagnosis and therapy the heterogeneity of VAA suggests that management must remain individualized.

Adult↗
PubMed2000

Sulindac inhibits neointimal formation after arterial injury in wild-type and apolipoprotein E-deficient mice.

Neointimal hyperplasia is a critical component of restenosis, a major complication of angioplasty and related therapeutic procedures. We studied the effects of hyperlipidemia and the nonsteroidal anti-inflammatory drugs, aspirin (acetyl-salicylic acid; ASA), and sulindac, on neointimal formation in a mouse femoral arterial injury model. At 2 months of age, normolipidemic, wild-type (WT), and hyperlipidemic, apolipoprotein E-deficient (apoE-/-) mice were divided into three treatment groups: Western-type diet (WD), WD + ASA (200 mg/kg food), and WD + sulindac (300 mg/kg food). After 1 week, mice underwent arterial injury and treatments were maintained for 4 weeks. Histomorphometry of the injured arteries showed striking effects of plasma cholesterol levels and drug treatment on neointimal hyperplasia. In the WD or WD + ASA groups, apoE-/- mice had twice the neointimal area than WT mice ( approximately 30,000 vs. 13,000 microm(2) per section; P < 0.0001). Compared with ASA or WD alone, sulindac treatment resulted in approximately 70% (P = 0.0001) and 50% (P = 0.01) reductions in the neointimal area in apoE-/- and WT mice, respectively. ASA, at a dose sufficient to inhibit platelet aggregation, did not affect neointimal formation in mice of either genotype. Evidence of macrophages was noted in the lesions of apoE-/- mice in the WD and WD + ASA groups, but remarkably, none was detectable with sulindac treatment, despite hyperlipidemia, suggesting early steps in the response to injury were abrogated. These results demonstrate sulindac reduces neointimal formation in both normolipidemic and hyperlipidemic settings and raise the possibility that similar benefits may be obtained in patients undergoing angioplasty and related procedures.

Animals↗
PubMed2000

Comparative study of antithrombotic effect of a low molecular weight heparin and unfractionated heparin in an ex vivo model of deep arterial injury.

Thrombosis after plaque rupture triggers the onset of acute coronary events. The treatment of choice for patients with acute coronary syndromes is conventional unfractionated heparin. Low molecular weight heparin has recently been reported to be as effective and even safer than unfractionated heparin. In this study, the effects of the low molecular weight heparin reviparin and unfractionated heparin on thrombus formation were examined under dynamic conditions using an extracorporeal perfusion chamber in a porcine model. Thrombus formation was assessed by the deposition of porcine 123I-fibrin(ogen) and autologous 111In-platelets on porcine tunica media at high and low shear rates. Reviparin reduced the fibrinogen molecules deposited on injured vessels at high shear rates (252+/-80 molecules x 10(12)/cm2 for reviparine (200 U/kg/hour) vs. 624+/-70 x 10(12)/cm for unfractionated heparin (200 U/kg/hour) (p<0.05). At low shear rates, fibrinogen deposition was also significantly reduced by reviparin (130+/-15 molecules x 10(12)/cm2) compared to unfractionated heparin (192+/-40 x 10(12)/cm2 at 200 U/kg/hour; p<0.05). No change in platelet deposition was detected after heparin administration in either treatment group. In conclusion, the low molecular weight heparin reviparin has a higher antithrombotic potential than unfractionated heparin. Reviparin may have advantages over unfractionated heparin in treatment and prevention of acute coronary syndromes.

Adenosine Diphosphate↗
PubMed2000

Isolated granulomatous phlebitis: rare cause of ischemic necrosis of the colon: report of a case.

Isolated phlebitis of the gastrointestinal tract is rare and potentially life threatening. We report on a patient who developed peritonitis, requiring emergency laparotomy, total colectomy, and ileostomy because of colon necrosis. The specimen displayed multiple ulcerations and erosions. Histology showed a predominantly lymphocytic infiltrate of small-sized and middle-sized veins in the submucosa and subserosa, associated with granulomas and foci of vein wall necrosis. Arteries were spared. No local recurrence or systemic vasculitis developed during a follow-up period of two years. Isolated granulomatous phlebitis seems to be self-limited, and its cause is unknown. Surgical resection of the diseased intestine is usually curative.

Colectomy↗
PubMed2000

Splenic artery aneurysm in the 1990s.

Splenic artery aneurysms (SAA), although rare, are the most common visceral artery aneurysms and are known for their potential for rupture. Pregnancy and portal hypertension have been known as major risk factors. With improved methods of diagnosis and minimally invasive therapy, management and outcome of SAA may change significantly. The purpose of this study was to analyze our institutional experience with SAA during the past decade. Charts of all patients (six women, three men; mean age, 60.5 [range: 31 to 81] years) with diagnoses of SAA from 1988 to 1999 were reviewed. Associated conditions included essential hypertension (6), portal hypertension (3), diabetes (1), intracranial aneurysm (1), and polyarteritis nodosa (1). Six patients were asymptomatic, and three had ruptured SAA. Diagnosis was made by angiography (2), computed tomography (3), ultrasonography (3), and exploratory laparotomy (1). Six patients underwent surgery (five required splenectomy), one had embolization, and two had no intervention. Three postoperative deaths occurred-two (intracranial aneurysm, myocardial infarction) in the first month, one (sepsis) in the ninth month. An association of liver disease with SAA was confirmed; however, no association with pregnancy was noted. Surgical treatment followed traditional methods, and mortality correlated with presence of severe comorbidity.

Adult↗