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J Schneiderman

Publications and source records attributed to J Schneiderman.

At least 19 recordsLinked to original sources
PubMed2006

Effects of fibulin-5 on attachment, adhesion, and proliferation of primary human endothelial cells.

BACKGROUND: Fibulin-5 is a novel extracellular protein that is thought to act as a bridging peptide between elastin fibers and cell surface integrins in blood vessel wall. Fibulin-5 binding to endothelial cell (EC) surface integrins may effect cell proliferation and cell attachment to extracellular matrix (ECM) or to artificial surfaces. In this paper, we describe the effects of fibulin-5 on attachment, adhesion, and proliferation of primary human EC. After demonstrating that fibulin-5 over-expression inhibited EC proliferation, we tested the hypothesis that co-expression of fibulin-5 and VEGF165 will lead to unique EC phenotype that will exhibit increased adherence properties and retain its proliferation capacity. METHODS AND RESULTS: Fibulin-5 and VEGF165 gene transfer to primary human saphenous vein endothelial cells was accomplished using retroviral vectors encoding the two genes. Transgene expression was verified using immunohistochemistry, Western blotting, and ELISA. Fibulin 5 over-expression tended to improve immediate EC attachment (30 min after seeding) and improved significantly adhesion (>40%) under shear stress tested 24h after EC seeding. The effects of fibulin-5 and VEGF165 on EC proliferation in the presence or absence of basic FGF were also tested. EC expressing fibulin-5 had reduced proliferation while VEGF165 co-expression ameliorated this effect. CONCLUSION: Fibulin-5 improved EC attachment to artificial surfaces. Dual transfer of fibulin-5 and VEGF165 resulted in EC phenotype with increased adhesion and improved proliferation. This unique EC phenotype can be useful for tissue engineering on endovascular prostheses.

Cell Adhesion↗
PubMed2004

Sequential therapy with activated prothrombin complex concentrate and recombinant factor VIIa in patients with severe haemophilia and inhibitors.

Patients with haemophilia and inhibitors have bleeding episodes that can be refractory to home therapy with either activated prothrombin complex concentrate (APCC) or recombinant factor VIIa (rFVIIa). Sequential therapy with these products has not been widely used because of concern regarding the possibility of thrombosis. This report describes the results of a retrospective chart review of five hospitalized children with severe haemophilia and inhibitors who have been treated with sequential doses of APCC and rFVIIa for refractory bleeding. These patients all had failed home therapy with APCC and rFVIIa alone. A total of 20 admissions were documented covering 170 hospital days, including 91 days of combination therapy. While being closely monitored in the hospital, they received alternating doses of APCC and rFVIIa every 6 h. Anywhere from one to three doses of rFVIIa were given every 2 h between APCC doses. Doses of APCC ranged from 35 to 80 U kg(-1) dose(-1), and doses of rFVIIa ranged from 80 to 225 mcg kg(-1) dose(-1). There was no clinical or laboratory evidence of thrombosis, thrombocytopenia, or disseminated intravascular coagulation (DIC). We found the combination of these factors to be safe and effective for patients with refractory bleeds. However, we recommend this aggressive therapy only in the inpatient setting with careful monitoring of the physical examination and frequent laboratory screening to assess for thrombosis and DIC, and without the concurrent use of antifibrinolytic medications.

Adolescent↗
PubMed2000

Thromboangiitis obliterans: an old disease in need of a new look.

Almost a century after Buerger's original description of thromboangiitis obliterans, there is still no consensus about diagnostic criteria. The lack of a universally accepted method of diagnosis causes confusion, and mars research efforts. Some authors quote 'hematological disease' as one of the exclusion criteria. But in most recent reports, suspected Buerger patients did not undergo hematological tests to diagnose or rule out any primary or secondary hypercoagulable states. However, immunogenetic studies of Buerger's disease have led to a revived interest in the role of blood coagulation in the pathogenesis of thromboangiitis obliterans. Some association has been suggested between Buerger's disease and the antiphospholipid syndrome, as well as hyperhomocysteinemia. Other thrombophilic conditions have been described anecdotally in patients with Buerger's disease. In view of this developing line of investigation, there is a clear need to redefine the diagnostic algorithm and the criteria for diagnosing Buerger's disease.

Antiphospholipid Syndrome↗
PubMed2000

Aortic aneurysm and dissection are not associated with an increased risk for giant cell arteritis/ polymyalgia rheumatica.

It has recently been claimed that giant cell arteritis (GCA) is associated with a markedly increased risk of aortic aneurysm formation or rupture. In the present study, the opposite approach was taken, by looking for the incidence of GCA and polymyalgia rheumatica (PMR) in patients with aortic aneurysm, aortic dissection, or both (AA/D). The records of 315 consecutive patients admitted with the diagnosis of AA/D were reviewed. In addition, follow up information was obtained in 82 patients by examination in the outpatient clinic. After careful examination and assessment of clinical and laboratory data, it was found that none of the 82 patients who survived hospitalisation and were available for examination had GCA or PMR. Moreover, review of the retrospective data available from hospital records of the total consecutive 315 patients with AA/D failed to find any patient with a diagnosis of GCA/PMR. In conclusion, the present study did not find an increased prevalence of GCA/PMR among a cohort of Israeli patients with AA/D. Therefore, it is suggested that a thorough investigation aiming to diagnose GCA/PMR is not cost effective in most of the elderly patients presenting with AA/D.

Aortic Dissection↗
PubMed2000

Abciximab in carotid stenting for postsurgical carotid restenosis: intermediate results.

PURPOSE: To report intermediate results of a pilot study in which the glycoprotein IIb/IIIa receptor antagonist abciximab was given to patients during percutaneous carotid stenting for recurrent internal carotid artery (ICA) stenosis. The objective was to prevent procedure-related cerebral embolic events and decrease the incidence of recurrent stenosis. METHODS: Sixteen patients (9 women; mean age 66.5 years, range 39-78) with severe ICA recurrent stenosis (>80%) underwent balloon angioplasty and stenting. Before the procedure, abciximab was administered intravenously as a bolus (0.25 mg/kg) followed by a 12-hour continuous infusion (10 microg/min). RESULTS: Fifteen patients received stents (14 Wallstent and 1 Strecker); 1 vessel was dilated with only 50% improvement in luminal diameter. Two stented arteries had residual stenosis (<30%) but satisfactory luminal diameter was achieved in the remaining 13 (81%) arteries. There were no neurological ischemic events during or following the procedure, nor were there any bleeding or peripheral vascular complications. Duplex surveillance studies up to 12 months revealed no significant recurrent stenosis in the treated vessels. CONCLUSIONS: The administration of abciximab in conjunction with percutaneous revascularization procedures for postsurgical carotid artery stenosis may reduce cerebral ischemic episodes. It may also attenuate restenosis in the treated artery.

Abciximab↗
PubMed1999

Immunolocalization of beta2-glycoprotein I (apolipoprotein H) to human atherosclerotic plaques: potential implications for lesion progression.

BACKGROUND: beta2-Glycoprotein I (beta2GPI) is a major antigenic target of antiphospholipid antibodies, which possesses natural anticoagulant properties. The aim of the present study was to determine its presence and localization within human atherosclerotic plaques and to study its association with endothelial cells and monocyte macrophages in vitro. METHODS AND RESULTS: Human atherosclerotic lesions were obtained after carotid endarterectomies and studied immunohistochemically with anti-beta2GPI as well as antibodies to CD4/CD8, macrophages, and adhesion molecules. In vitro, human umbilical vein endothelial cells (HUVECs) and U937 (myelomonocytic cell line) cells were investigated for their ability to associate with radiolabeled beta2GPI. We found beta2GPI to be abundantly expressed within the subendothelial regions and intimal-medial borders of human atherosclerotic plaques and to colocalize with CD4-positive lymphocytes. This observation was confirmed by Western blot applied on homogenates of atherosclerotic lesions with anti-beta2GPI antibodies. Both HUVECs and U937 cells bound labeled beta2GPI, and the process was inhibited by oxidized LDL and not by native LDL. CONCLUSIONS: The abundant presence of human beta2GPI within the lesions, its association with endothelial cells and macrophages, and its colocalization with CD4-positive lymphocytes suggests that it may serve as a target for an immune-mediated reaction that can influence lesion progression.

Animals↗
PubMed1998

Disrupted mobile aortic plaques are a major risk factor for systemic embolism in the elderly.

Protruding aortic plaques--especially those with mobile properties--on transesophageal echocardiography (TEE) are a potential source of stroke and systemic embolism in the elderly. Whether the various morphologies of atheromas with mobile components represent potential differences in the risk for embolic events has not been thoroughly elucidated. The goal of the present study was to determine the association between embolic events and the various types of mobile lesions in the thoracic aorta. Our population consisted of 569 consecutive patients (age 18-83 years) referred for TEE over 27 months; 108 (19%) of them were referred to evaluate recent embolism (cerebral in 97 and peripheral or both in 11; group I) and the remaining 461 were admitted for reasons unrelated to embolism (group II). In group I, 35 patients (32%) exhibited protruding plaques; those were fixed in 10 (9%) and with a mobile component in 25 (23%). In group II, plaques were found in only 13 patients (3%); fixed in 9 (2%) and mobile in 4 (1 %). Twenty-four patients with mobile lesions in group I were > 50 years old, and 21 of them (88%) were > 60 years old. While the presence of fixed plaques was associated with a moderate increase in the risk for systemic embolism (adjusted odds ratio 4.1; 95% confidence interval 1.3-56.4), mobile lesions were linked to a striking augmentation of this risk (odds ratio 30.1; 95% confidence interval 7.8-132.6). The majority of mobile lesions (76%) in group I represented disrupted atheromas with characteristic ulcerations or echolucency within the plaque suggestive of intraatheroma hemorrhage, whereas these TEE features were not observed in 89% of the mobile lesions in group II (p = 0.0003). We conclude that among the various types of mobile aortic lesions, the disrupted protruding plaques are a major risk factor for stroke and embolic events in the elderly.

Adolescent↗
PubMed1998

Patterns of expression of fibrinolytic genes and matrix metalloproteinase-9 in dissecting aortic aneurysms.

Although extensive tissue remodeling occurs during the various phases of aortic dissection, the underlying proteinases remain to be identified. Matrix metalloproteinase-9 (MMP-9) and components of the fibrinolytic system have been implicated in numerous tissue remodeling events and were therefore analyzed in surgical specimens of acute (n = 9), subacute (n = 4), and chronic (n = 7) aortic dissection by in situ hybridization. In the acute phase, intense plasminogen activator inhibitor 1 (PAI-1) gene expression was apparent in areas interfacing the dissecting hematoma, but no tissue-type PA (t-PA), urokinase-type PA (u-PA), or MMP-9 mRNAs were detected. Although PAI-1 mRNA was still present in the subacute phase, t-PA, u-PA, and MMP-9 mRNAs were now obvious, with PA gene expression co-localizing with areas of PAI-1 gene expression. In the chronic phase, PAI-1 mRNA was demonstrated around erythrocyte extravasations and surrounding bands of medial degeneration. However, there was little expression of PAs in these areas, and no MMP-9 was detected. Thus, fibrinolytic genes and MMP-9 are differentially expressed during the progression of aortic dissections. The kinetics of expression are consistent with acute fibrinolytic shutdown in response to the initial injury, a secondary subacute phase with active proteolysis, and finally, a chronic hypofibrinolytic state. Extensive neovascularization in the chronic phase may further reduce the physical stability of the dissected wall.

Acute Disease↗
PubMed1997

Expression of fibrinolytic genes in tissues from human atherosclerotic aneurysms and from obese mice.

The disturbances in the balance of pro- and antifibrinolytic activity, as observed in AAA and obesity, respectively, have considerable potential for influencing both intra- and extravascular fibrinolytic events and may be causally related to the development of vascular disease. For example, the wall of the aortic atherosclerotic aneurysm seems to host an uneven distribution and imbalanced expression of the various components of the fibrinolytic system. The sites of increased proteolytic activity may contribute to localized neovascularization and promote the rapid breakdown of ECM components, which result in mural weakening and eventual rupture of untreated aortic aneurysms. On the other hand, the disturbance of the normal hemostatic balance observed in obesity appears to result from the elevated expression of PAI-1 by the adipose tissue. Our data strongly suggest that the adipocyte is one of the primary cells in the adipose tissue capable of expressing PAI-1 both in obesity, and in response to cytokines and hormones like TNF-alpha and insulin. Since both TNF-alpha and insulin are known to increase in obesity, the elevated levels of PAI-1 observed in the plasma of obese individuals may result from TNF-alpha and/or insulin induction of PAI-1 in the adipose tissue itself.

Aneurysm↗
PubMed1997

The effect of an angiotensin converting enzyme inhibitor on skin microvascular hyperaemia in microalbuminuric insulin-dependent diabetes mellitus.

Patients with longstanding insulin-dependent (Type 1) diabetes mellitus (IDDM) are reported to have microvascular complications in most capillary beds. The microvascular hyperaemia of the skin in normoalbuminuric and microalbuminuric IDDM patients and healthy volunteers was measured with laser Doppler flowmetry. The effect of 3 and 9 months of treatment with captopril, an angiotensin converting enzyme inhibitor, on hyperaemia in the microalbuminuric patients was studied. Mean (+/- SD) pretreatment duration of skin postocclusive reactive hyperaemia was longer in microalbuminuric than in both normoalbuminuric patients and healthy volunteers (118.2 +/- 34.4 vs 57.8 +/- 16.0 vs 63.3 +/- 18.3 sec, respectively, p < 0.00001). After 3 and 9 months of captopril treatment the prolonged hyperaemia was shortened to 78.6 +/- 45.6 s (p < 0.01) and 62.3 +/- 55.6 s (p < 0.03), respectively. Urinary albumin excretion decreased from 63.9 +/- 43.5 to 33.4 +/- 28.1 mg 24 h-1 at 3 months treatment (p < 0.002) and 43.1 +/- 38.5 mg 24 h-1 at the end of the study period (p < 0.02). A positive correlation between changes in urinary albumin excretion and the shortening of the skin postocculsive reactive hyperaemia was found. Blood pressure remained in the same range throughout. These results show that captopril affects skin blood flow, independent of its hypotensive effect. This action may reflect the influence of angiotensin converting enzyme inhibitor on vascular beds other than those of the kidneys.

Adolescent↗
PubMed1996

Impairment of the postural venoarteriolar response in young type 1 diabetic patients. A study by laser doppler flowmetry.

The skin blood flow and venoarteriolar response (VAR) in the feet of the young type 1 diabetic patients were studied with laser Doppler flowmetery. The findings were correlated with diabetic microangiopathy in 24 young patients without neuropathy--14 with diabetic microangiopathy, 10 without--and 10 healthy controls. In type 1 diabetic patients and skin blood flow, after lowering of the leg, was significantly higher in the microangiopathic patients than in the healthy controls, 5.3 +/- 1.4 vs 3 +/- 1.5, (P < 0.01). The VAR index was significantly lower in both groups of diabetics as compared with controls. In conclusions laser Doppler flowmetry is an easy and reliable noninvasive technique to evaluate skin blood flow abnormalities in the the feet of young type 1 diabetic patients, including those without neuropathy. The VAR has been found abnormal in the feet of young diabetic patients with and without microangiopathy, regardless of the presence of peripheral neuropathy.

Adolescent↗
PubMed1995

Expression of fibrinolytic genes in atherosclerotic abdominal aortic aneurysm wall. A possible mechanism for aneurysm expansion.

Expansion of atherosclerotic abdominal aortic aneurysm (AAA) has been attributed to remodeling of the extracellular matrix by active proteolysis. We used in situ hybridization to analyze the expression of fibrinolytic genes in aneurysm wall from eight AAA patients. All specimens exhibited specific areas of inflammatory infiltrates with macrophage-like cells expressing urokinase-type plasminogen activator (u-PA) and tissue-type PA (t-PA) mRNA. Type 1 PA inhibitor (PAI-1) mRNA was expressed at the base of the necrotic atheroma of all specimens and also within some of the inflammatory infiltrates where it frequently colocalized in regions containing u-PA and t-PA mRNA expressing cells. However, in these areas, the cellular distribution of the transcripts for t-PA and u-PA extended far beyond the areas of PAI-1 expression. These observations suggest a local ongoing proteolytic process, one which is only partially counteracted by the more restricted expression of PAI-1 mRNA. An abundance of capillaries was also obvious in all inflammatory infiltrates and may reflect local angiogenesis in response to active pericellular fibrinolysis. The increased fibrinolytic capacity in AAA wall may promote angiogenesis and contribute to local proteolytic degradation of the aortic wall leading to physical weakening and active expansion of the aneurysm.

Adult↗
PubMed1994

Modulation of the fibrinolytic system by major peripheral ischemia.

PURPOSE: A rat model was developed to investigate the effects of acute peripheral ischemia on the components of the fibrinolytic system. METHODS: Laparotomy was performed and ischemia was introduced by total aortic clamping at a subrenal position. Control animals underwent sham laparotomy alone. Plasma and tissue samples were collected for analysis at 30, 60, 90, and 120 minutes after operation. RESULTS: Functional assays of rat plasma revealed a dramatic and transient increase in tissue-type plasminogen activator (tPA) activity within 30 minutes of the onset of ischemia. A simultaneous decline in plasminogen activator inhibitor activity was observed. Immunohistochemical analysis suggested this initial increase in tPA activity resulted primarily from the release of stored tPA from ischemic vascular tissues. Northern blot analysis revealed that both tPA and plasminogen activator inhibitor-1 messenger RNA levels were elevated at 60 to 120 minutes in well-perfused tissues distant from the ischemic insult. CONCLUSIONS: Collectively, these data demonstrate that acute peripheral ischemia results in a rapid and transient increase in plasma fibrinolytic activity, concomitant with the early release of stored tPA from ischemic vascular tissues. In addition, peripheral ischemia appears to stimulate both tPA and plasminogen activator inhibitor-1 gene expression in well-perfused tissues at later time points, consistent with the existence of humoral mediators.

Adipose Tissue↗
PubMed1993

Intra-arterial thrombolytic therapy: a combined approach with angioplasty and/or minor surgery.

Low-dose intra-arterial treatment was performed in 124 patients who underwent a total of 142 procedures. The series included 87 occluded arteries and 55 occluded grafts. In only 29 instances (21%) was thrombolysis alone sufficient. In another 77 procedures (54%) the thrombolysis was followed by either angioplasty or minor surgery. In the remaining 36 treatments (25%) lysis of the occlusion failed. A successful end result of combined treatment was achieved in 67 of 77 (87%) procedures. Including the 29 patients in whom thrombolysis alone sufficed, a total of 96 of the 142 procedures (67%) were successful, with the overall success rate being better in grafts (78%) than in arteries (61%). The suprainguinal lesions had a significantly better response compared to the infra-inguinal ones. The evaluation of all procedures was done at the time of discharge from hospital. Complications were related either to local or systemic hemorrhage or distal embolization. Death related to treatment occurred in three patients.

Adult↗