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An endothelial cell adhesion protein for monocytes recognized by monoclonal antibody IG9. Expression in vivo in inflamed human vessels and atherosclerotic human and Watanabe rabbit vessels.

BACKGROUND: Monocyte adhesion to the vascular endothelium, an important component of an inflammatory response, is one of the earliest detected events in the pathogenesis of atherosclerosis. We have identified a monocyte adhesion molecule, recognized by monoclonal antibody (mAb) IG9, on the cell surface of human umbilical vein endothelial cells (HUVEC) treated with tumor necrosis factor-alpha (TNF-alpha), interleukin-1, or lipopolysaccharide. Endothelial cell expression in vitro and in vivo of the protein recognized by mAb IG9 (IG9 protein) was further characterized. EXPERIMENTAL DESIGN: The kinetics of cytokine-induced IG9 protein expression on HUVEC were evaluated by enzyme-linked immunosorbent assay. TNF-alpha-treated HUVEC surface proteins, labeled with [125I]Na, were solubilized in NP-40 detergent and immunoprecipitated with mAb IG9 to determine the molecular weight of the IG9 protein. The functional role of the IG9 protein in monocyte binding in vitro to cytokine-activated endothelial cells was established in adhesion assays utilizing U937 cells (human promyelomonocytic cell line) and human peripheral blood monocytes. Minimally oxidized or modified low density lipoproteins (MM-LDL) have previously been shown to induce monocyte adhesion to endothelial cells for up to 48 hours after exposure. In order to characterize the adhesion molecule(s) contributing to this increase in monocyte binding, MM-LDL-treated HUVEC and human aortic endothelial cells were assayed for monocyte adhesion molecule expression by enzyme-linked immunosorbent assay. In addition, mAb IG9-mediated alterations in MM-LDL-induced monocyte binding were studied in endothelial-monocyte adhesion assays. To assess IG9 protein expression in vivo, formalin-fixed, paraffin-embedded sections of inflamed human tissues obtained from lung and healing myocardial infarctions, in addition to sections of human atherosclerotic coronary arteries, were analyzed by immunohistochemistry. Tissue sections from atherosclerotic Watanabe heritable hyperlipidemic rabbit aortas were also included in these studies. RESULTS: The IG9 protein, undetected on untreated HUVEC, was expressed on their cell surface within 3 hours of treatment with TNF-alpha, peaked at 4 to 9 hours, and persisted for up to 48 hours as determined by enzyme-linked immunosorbent assay. A similar kinetic profile was elicited by interleukin-1 and lipopolysaccharide, whereas interferon-gamma (IFN-gamma) had minimal effect on IG9 expression. The IG9 protein has a molecular weight of 105,000 as determined by immunoprecipitation studies with TNF-alpha-treated HUVEC protein lysates. mAb IG9 significantly inhibited the binding of U937 cells and human peripheral blood monocytes to TNF-alpha-treated HUVEC and had no effect on peripheral blood lymphocyte or granulocyte adhesion. Treatment of human aortic endothelial cells or HUVEC with MM-LDL for 24 hours induced IG9 protein expression 3-fold above background with no concomitant increase in binding of antibodies to intercellular adhesion molecule-1 (ICAM-1), E-selectin, or vascular cell adhesion molecule-1 (VCAM-1), endothelial cell adhesion proteins involved in monocyte binding. mAb IG9 F(ab')2 inhibited MM-LDL-induced monocyte adhesion to HAEC by 23%. Immunohistochemical analysis demonstrated that the endothelial cell lining of vessels in human lung and heart with evidence of inflammation characterized by an extensive mononuclear cell infiltration exhibited reactivity with mAb IG9, whereas vessels with no evidence of inflammation in the same sections as well as in sections from normal lung and heart were nonreactive.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Extramural vessel wall hematoma causing a reduced vessel diameter after coronary stenting: diagnosis by intravascular ultrasound and treatment by stent implantation.

An extramural vessel wall hematoma occurred immediately after implanting a coronary stent in an in-stent-restenosis of the intermedius branch. Angiography showed a significant luminal reduction distal to the intervention site. Intravascular ultrasound revealed an extramural echolucent zone compressing the vessel lumen. Stent implantation compressed the hematoma and allowed adequate myocardial perfusion. This demonstrates the value of intravascular ultrasound (IVUS) in cases of unusual angiographic results which can help to manage complications after coronary intervention.

Coronary Angiography↗

Surface view of strial vessel, prominence vessel, and external sulcus cells as revealed by scanning electron microscopy.

The stria vascularis and the spiral prominence in the lateral cochlear wall were observed with scanning electron microscopy (SEM) after dissolving out the epithelial layer and the basement membrane by tryptic digestion and HCl hydrolysis. The external sulcus cells have regularly arranged pegs and a fine basal interdigitation on the cell surface. The strial vessel and the spiral prominence vessel could be visualized well and the characteristic surface view of their periendothelial cells presented. The former has cytoplasmic processes with a fine branching appearance similar to red coral and the latter has bulged popcorn like processes. Their functional significance is discussed.

Animals↗

[The so-called recanalisation of cotyledonary vessels with endangitis obliterans of placenta vessels (author's transl)].

With a graphic reconstruction on serial sections, performed with placentas which altogether showed so-called recanalisation, it is possible to work out the fact, that the recanalisation is an effect of the paravascular capillary network and with it to clarify the problem of the so-called recanalisation. It is proved, that the paravascular capillaries undertake compensatory hemodynamic functions and this undertaking of function prevents a complete occlusion of the cotyledonary vessels, so that you have to speak of restlumen and restflow but not of recanalisation. The endangitis obliterans of cotyledonary vessels is again unequivocally pointed out by this phenomenon as a intravital process.

Capillaries↗

A case of vessel perforation during interventional neuroradiological procedure. Operative findings of the perforated vessel.

A case of vessel perforation by a guide wire during an interventional neuroradiological procedure is reported. The patient was a 59-year-old woman with a left frontal basal arteriovenous malformation (AVM) fed by the left anterior cerebral artery. Transarterial embolization of the AVM was attempted. During the procedure, vessel perforation by the guide wire occurred at the left A1-A2 junction and resulted in subarachnoid hemorrhage, which stopped spontaneously. The patient developed progressive obstructive hydrocephalus, and surgical treatment was performed. The AVM was totally removed after ventricular drainage, and the arterial perforation site was explored. When clot around the left A1-A2 junction was removed, hemorrhage recurred. This hemorrhage was similar to what has been observed when a small perforating artery was avulsed. The hemorrhage site was coagulated under temporary occlusion of both A1 segments. Surgical intervention was probably not necessary for this type of bleeding if it had stopped spontaneously, because the rebleeding from the small pinhole would be unlikely, and the operation was more hazardous than the usual aneurysmal surgery.

Cerebral Arteries↗

LDL phenotype B and other lipid abnormalities in patients with large vessel disease and small vessel disease.

BACKGROUND AND PURPOSE: Controversies concerning the significance of lipid abnormalities in stroke come mostly from the researches that studied lipid profile without considering stroke aetiologies. We investigated the prevalence of LDL phenotype B and other lipid abnormalities in stroke survivors with large vessel disease (LVD) or small vessel disease (SVD) (TOAST criteria) and in control subjects (CS). METHODS: We studied 30 patients with LVD and 41 patients with SVD screened out of 585 stroke patients and 30 CS who fulfilled the following exclusion criteria: cardiac disorders, renal or hepatic failure, diabetes mellitus, or treatment with lipid-lowering agents. At least 3 months after stroke, the concentrations of total cholesterol (TC), HDL cholesterol (HDL-C), LDL cholesterol (LDL-C), triglycerides (TGs), apolipoprotein E (apoE), and lipoprotein (a) [lp(a)] were measured and LDL phenotypes and apoE isoforms were identified. RESULTS: Patients with LVD had significantly higher concentrations of LDL-C than CS (p<0.05). They had higher concentrations of TGs and lower concentrations of HDL-C than patients with SVD and CS (p<0.05). LDL phenotype B was more frequent in patients with LVD (63.3%) than in patients with SVD (39.0%) or in CS (16.7%) (p<0.05). The concentration of apoE was higher in patients with LVD than in patients with SVD or in CS (p<0.05). The percentage of patients with increased level of lp(a) (i.e., >30 mg/ml) was greater in patients with LVD (36.7%) than in CS (10%) (p<0.05). CONCLUSIONS: Patients with stroke due to LVD, but not SVD, have high prevalence of atherogenic lipid abnormalities, including increased frequency of LDL phenotype B and higher percentage of increased lp(a) level, like patients with other atherogenic diseases.

Aged↗

Cerebral revascularization by omental free flap using contralateral superficial temporal vessels as recipient vessels: case report.

BACKGROUND: Although the most common technique of cerebral revascularization is superficial temporal artery to middle cerebral artery bypass, we occasionally encounter a situation in which the ipsilateral superficial temporal artery is not available. Treatment may require several techniques including long vein graft bypass. METHODS: A 54-year-old man experienced transient ischemic attacks, and cerebral angiography revealed occlusion of the right common carotid artery. Cerebral blood flow study revealed reduced perfusion reserve capacity of the right cerebral hemisphere. We applied an omental free flap to the brain surface using the contralateral superficial temporal vessels as recipient vessels. RESULTS: Cerebral blood flow study revealed improvement of perfusion reserve capacity. Cerebral angiography revealed good collateral circulation from the omentum to the brain. The patient has not experienced a transient ischemic attack, following additional ligation of the occipital artery 13 months after the first operation. CONCLUSIONS: Because an omental flap has a long pedicle and its circulation can be monitored easily, this method is safe and as effective as a long bypass graft in a patient such as ours in whom the ipsilateral superficial temporal artery is not available for anastomoses.

Anastomosis, Surgical↗

Rodent models of global cerebral ischemia: a comparison of two-vessel occlusion and four-vessel occlusion.

1. Human stroke is a complex and heterogeneous phenomenon that may defy attempts to develop a unitary animal model with which to address all of the relevant issues. 2. Focal models are regarded by many to be the approach of choice, but both global and focal models of cerebral ischemia can be sources of useful and complementary insight. 3. Of the global models, four-vessel occlusion requires a preparatory operative procedure that may increase the risk of extraneous factors confounding the response to the ischemic insult itself. The procedures are only partly reversible, with the vertebral arteries remaining permanently occluded. 4. The two-vessel occlusion model is easier to perform in a single procedure, and the less-intrusive surgical intervention allows greater scope for recovery experiments. The occlusion is fully reversible. 5. Many classes of compounds with therapeutic potential have been identified in the laboratory, often on the basis of success in one class of animal model, but translating these successes into a clinical context has proved singularly difficult. If, in future, compounds of interest are tested across a range of the available models, the likelihood of subsequent clinical success may be enhanced.

Animals↗

Alanine uptake by the endothelium of canine blood vessels and by the vessels of human umbilical cord.

In order to determine whether the endothelium of vascular wall fragments possesses an active uptake mechanism for alanine identical to the one present in endothelial cells in tissue culture samples of canine aorta, carotid artery and vena cava, human umbilical cord vessels, were incubated in vitro in the presence of labelled alanine. In a series of experiments, it was observed that all the tissues investigated accumulated a significant amount of this substrate against a concentration gradient, and that the accumulation was saturable in the presence of sodium. This uptake was sodium-dependent, was significantly inhibited by ouabain and was greatly reduced under anoxic conditions. Finally, the uptake was completely abolished by prior mechanical or osmotic destruction of the intima. In conclusion, the very reproducible measurement of active alanine uptake in fragments of blood vessels may be a valuable method of evaluating the integrity of the endothelium.

Alanine↗

Vessel sizing wire: accurate vessel measurement using digital subtraction arteriography.

A simple method of measuring vessel diameters using intraarterial digital subtraction angiography has been designed. With a catheter in place within the vessel of interest, a segmented guide wire with known dimensions is advanced into the catheter in the area to be measured. We have used the method successfully for balloon angioplasty as well as balloon embolization.

Angiography↗

[Comparison of plasma concentrations of fibrinogen in patients with ischemic stroke due to large vessel disease and small vessel disease].

BACKGROUND AND PURPOSE: Hyperfibrinogenemia is a known cardiovascular risk factor, but its role as a risk factor for ischemic stroke remains controversial. Most studies on this topic did not consider the different etiologies of ischemic stroke. We designed this study to compare plasma fibrinogen concentrations in patients with acute ischemic stroke due to large vessel disease (LVD) or small vessel disease (SVD). MATERIAL AND METHODS: We studied 203 patients with acute ischemic stroke, including 107 patients with SVD and 96 subjects with LVD. Etiology of stroke was established according to the TOAST criteria, using computed tomography, ultrasonography of the carotid and vertebral arteries as well as echocardiography. The plasma concentration of fibrinogen was measured in venous blood samples drawn within 48 hours from the onset of stroke. RESULTS: Patients with LVD were more likely to be men and more likely to have ischemic heart disease. The median plasma concentration of fibrinogen was higher in patients with LVD [3.7 g/l (2.9-4.9 g/l)] than in patients with SVD [3.2 g/l (2.6-3.8 g/l); p=0.0001]. Hyperfibrinogenemia (i.e. plasma fibrinogen concentration >3.5 g/l) occurred more frequently in patients with LVD (54.2%) than in patients with SVD (35.5%; p=0.008). CONCLUSIONS: Patients with ischemic stroke due to LVD have a higher concentration of plasma fibrinogen than patients with SVD, they also present more frequently with hyperfibrinogenemia. Further studies of risk factors for stroke should take into account various etiologies of ischemic stroke.

Age Factors↗

Differential endothelial injury caused by vascular clamps and vessel loops. I. Normal vessels.

Silicone rubber looped tourniquets were compared with standard crossmembered metallic peripheral vascular occlusive clamps in a canine aorto-iliac vessel model to compare the degree and severity of endothelial injury as demonstrated by scanning electron microscopy. The moderate-to-severe injury incurred by the standard clamps was not seen whatsoever with the looped tourniquets. Selective and preferential use of silastic rubber vessel tourniquet loops for vascular occlusion and control is thus advocated.

Animals↗

[Morphological study on innervation of the cerebrospinal blood vessels. II. Spinal blood vessels].

The distribution patterns of aminergic and cholinergic nerve fibers in the feline spinal blood vessels were studied by means of amine histofluorescence and acetylcholinesterase (AChE) staining. The anterior spinal artery had a dense network of aminergic and AChE-positive (probably cholinergic) nerve fibers. The posterior spinal vein, in contrast, had only aminergic nerve fibers. Intraparenchymal small blood vessels in the spinal cord also had strongly fluorescent (probably peripheral) aminergic nerve fibers. This was quite a characteristic feature in the spinal cord. The distribution pattern and the density of these two sorts of nerve fibers widely varied with the individual segment of the spinal cord. The thoracic spinal cord had the lowest number of these nerve fibers throughout the spinal cord. This fact may give a clue to explain why the thoracic spinal cord is most susceptible to ischemic change.

Acetylcholinesterase↗

[Current applications of numeric angiography in the study of cervico-cerebral vessels, the aorta, pulmonary vessels and following vascular surgery].

Numeric angiography is an examination of choice for studying the thoraco-abdominal aorta, whatever the underlying pathological condition, and is often the only angiographic investigation useful and necessary for deciding on therapy in cases of aneurysm. In contrast, results are unsuccessful in approximately 15% of cases when neck vessels are studied. Significant lesions nearly always produce sufficient information for the decision as to therapy to be made. Vascular surgery follow up is an excellent indication for numeric angiography, whatever the surgical technique used or the anatomic site involved. Reliable data can be obtained from pulmonary vessels by the use of this method in patients with pulmonary embolism, arteriovenous malformations, and abnormal venous return.

Angiography↗

[Results of surgical treatment of various vessel diseases. 1. Great vessel diseases (author's transl)].

Three hundred and three cases of great vessel diseases have been experienced during the last 18 years at the Second Department of Surgery, Hokkaido University Hospital. Those cases consisted of 36 congenital anomalies of the aorta, 41 aortitis syndromes, 145 aneurysms of the thoracic and abdominal aorta, 20 obstructions of the aorta, 10 arterio-venous fistulas, and 51 obstructions of the great vein. The results of surgical treatment of those cases were reviewed. Although the results have progressively improved, special problembs to be solved are remained in treatment of complexed aortic coarctation, aortitis syndrome, aneurysm of the thoracic aorta, dissecting aneurysm, and obstruction of the great vessels.

Aorta↗

Internal mammary vessels as recipient vessels to the free TRAM flap.

For the reconstruction of the breast after mastectomy, it is possible to use the internal mammary artery and vein as recipient vessels. The authors consider their experience and some new knowledge gained on the basis of 53 cases. They try to promote the indisputable advantages of the use of the mentioned recipient vessels.

Female↗

[Pseudo-stenosis caused by vessel wall invagination during interventional treatment of 2 coronary vessels in a patient].

We report on a 59-year-old man who underwent a combined procedure of directional coronary atherectomy (DCA) and PTCA of significant lesions of the right coronary artery (RCA) and the left circumflex artery (LCX). Already after positioning of a standard guide wire in the right coronary artery a new excentric "pseudo-stenosis" was observed in the proximal part of the right coronary artery. Since the patient remained symptom free, a 7F DCA catheter was introduced to the stenotic area in the mid RCA, which led to an extension of the narrowing, involving the total segment proximal to the DCA catheter. Directional coronary atherectomy was performed without complications. Removal of the catheter, after successful DCA, and administration of intracoronary nitroglycerin did not relieve the proximal narrowing, which disappeared spontaneously after the guide wire was pulled out. During PTCA of the left circumflex using a standard guide wire and a 3.0 mm Monorail balloon catheter, a similar tight narrowing of the origin of the LCX was observed, which could also not be influenced by vasodilator drugs, but relieved after wire removal. Until now, this phenomenon has only been described for the right coronary artery. The reason underlying intimal folding is a shifting of the intimal layer against the medial layer of the vessel wall. Our observation firstly describes this phenomenon of "pseudo narrowing" in two different vessels in one patient. We, like other authors before, recommend that interventional therapy of these pseudo-lesions should be avoided.

Angioplasty, Balloon, Coronary↗

Effects of photodynamic therapy using mono-L-aspartyl chlorin e6 on vessel constriction, vessel leakage, and tumor response.

The effect of photodynamic therapy using mono-L-aspartyl chlorin e6 (NPe6) on both direct cytotoxicity and vascular damage was examined. Sprague-Dawley rats bearing chondrosarcoma tumor were given i.v. injections of 5 or 10 mg/kg NPe6 and exposed to 135-J/cm2 664-nm laser light either 4 or 24h after NPe6 injection. The percentage of viable tumor cells was estimated either immediately after the completion of light treatment or 24 h after treatment using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Measurements of arteriole constriction and venule leakage in normal cremaster tissues were made during and 1 h after the light treatment. Tumor response was evaluated for the 4 different NPe6 dose and time combinations. Both direct tumor cytotoxicity and vascular stasis were observed during light treatment. Vessel leakage did not occur. Blood flow stasis was a result of platelet aggregation and the mechanical obstruction of flow rather than vessel constriction. The magnitude of direct cytotoxicity and vascular response was dependent on both the amount of NPe6 delivered and the delay between injection and light treatment. Tumor cure was found in animals either when given high NPe6 doses or when treated early after NPe6 injection. Treatment regimens which maximized the effect of both vascular stasis and direct tumor cytotoxicity were found to produce the best tumor response. Dose combinations which produced vascular stasis with minimal early cytotoxicity did not result in cure. The combined mechanisms of damage after photodynamic therapy using NPe6 suggests that this photosensitizer may have specific advantages for clinical use and provides a benchmark for the development of new photosensitizers.

Animals↗