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At least 559 records · Page 31Linked to original sources
PubMed2002

Significance of blood vessel leakiness in cancer.

Despite major advances in the field of tumor angiogenesis, relatively little attention has been paid to the permeability of blood vessels in tumors. The leakiness of tumor vessels is well documented in experimental tumor models and in human cancer, but the mechanism is poorly understood, as are the implications to the rate of cancer growth, predisposition to metastasis, and delivery of macromolecular therapeutics to tumor cells. Sixteen experts in the fields of cancer biology and vascular biology gathered at the William Guy Forbeck "Focus on the Future" Conference to discuss this topic. The meeting was the first of its kind focused on the significance of blood vessel leakiness in tumors. The participants discussed the cellular basis of tumor vessel leakiness, endothelial barrier function of blood vessels, monitoring tumor vessel leakiness, mediators of endothelial leakiness, consequences of tumor vessel leakiness, genomic analysis of vascular targets, targeting drugs to tumor vessels, and therapeutic manipulation of tumor vessels. The group concluded that a more complete understanding of the basic biology of tumor vessels will be necessary to fully appreciate the consequences of vessel leakiness in cancer. New research tools such as intravital measurements of tumor blood flow and vessel leakiness, in vivo phage display, magnetic resonance imaging, and use of selective angiogenesis inhibitors will contribute to this understanding.

Animals↗
PubMed2001

Vascular morphogenesis and remodeling in a human tumor xenograft: blood vessel formation and growth after ovariectomy and tumor implantation.

To determine mechanisms of blood vessel formation and growth in solid tumors, we used a model in which LS174T human colon adenocarcinomas are grown in the isolated ovarian pedicle of nude mice. Reconstruction of 3500 histological serial sections demonstrated that a new vascular network composed of venous-venous loops of varying sizes grows inside the tumor from the wall of the adjacent main vein. Loops elongate and remodel to establish complex loop systems. The mechanisms of loop formation and remodeling correspond to intussusceptive microvascular growth (IMG). In the tissue surrounding the tumor segmentation, another mechanism of IMG is prevalent in venous vessels. Comparison to vascular morphogenesis in the ovariectomized pedicle not only confirms the existence of corresponding mechanisms in both systems, but also reveals numerous sprouts that are superimposed onto loop systems and pathological deviations of loop formation, remodeling, and segmentation in the tumor. These pathological mechanisms interfere with vessel patency that likely cause heterogenous perfusion and hypoxia thus perpetuating angiogenesis. Blood vessel formation based on IMG was also detected in a large thrombus that completely occluded a part of an ovarian artery branch.

Adenocarcinoma↗
PubMed1984

Fluorescence microscopic morphometry of functioning blood vessels and adrenergic nerves in myocardium.

The purpose of this study was to quantify the percent volume of actively functioning blood vessels in five dogs subjected to ligation of the left anterior descending artery and to localize catecholamine-containing nerve terminals in the same tissue blocks. Radioactive microspheres were injected to determine the extent of flow reduction in the ischemic zone. After 1 or 3 hr of occlusion, thioflavin-S (0.125 ml/Kg of a 4% solution) was injected intravenously 15 sec prior to removal of the heart. Tissue samples were reacted with paraformaldehyde to visualize catecholamine-containing nerve terminals prior to embedding in paraffin. The percent volume of blood vessels labeled with thioflavin-S was quantitated in tissue sections using a point-counting technique in which a small dot from a video screen was projected through an image-projecting tube and moved by computer control over the image of the fluorescent tissue. In the nonischemic zone, the mean blood flow determined by the microsphere technique was 1.29 ml/min/g +/- 0.48 (SD), and the mean volume percent of thioflavin-labeled vessels was 12.67 +/- 3.30. In the ischemic and border zone areas, there was wide range of flow reduction, and there was a significant correlation between the blood flow measured with microspheres and the percent volume of thioflavin-labeled blood vessels (R = 0.80, P less than 0.001). In the nonischemic zone, both blood vessels and catecholamine-containing nerve terminals were visible; however, in the ischemic zone, few labeled vessels were seen, although nerve terminals were often present.(ABSTRACT TRUNCATED AT 250 WORDS)

Anatomy↗
PubMed1988

The changes of enzymatic activity in blood vessel walls of rat brain during extrauterine development. Histophotometric studies.

The investigations of acylohydrolase acylocholine (cholinesterase) enzymatic activity in the brain vessels walls were performed during extrauterine ontogenic development on 3rd, 7th, 14th, 21st, 28th, 40th and 60th days of life and in the 18 months old rats using Koelle method. Objective evaluation of histoenzymatic reaction intensity is rather difficult because of subjective factors and technical problems. Therefore, our estimations were performed by the use of microscopic unit "Morphoquant" produced by CARL ZEISS Jena factory and coupled with a KSR 4100 ROBOTRON computer. The measurements on 50 fields from parietal cortex or callosal corpus were executed using white light. The area of a single measuring field was 4,200 micron2. The results of measurements were expressed as the percentage of the measured field area occupated by blood vessels with positive ChE reaction in their walls. The results indicate that the amount of blood vessels with positive ChE reaction during the whole postnatal development is increasing. In particular, a very intense increase in the amount of vessels with ChE reaction take place between 7th to 14th days of extrauterine life. In the white matter of callosal corpus a very strong increase in the blood vessels amount with positive ChE reaction is visible between 21st and 28th days of life. In the brains of 18 months old rats a decrease in the positive blood vessels amount was noted. When compared to the parietal cortex, this decrease was higher in corpus callosum. From 40th day of life the amount of blood vessels with positive histoenzymatic reaction for ChE was higher in the grey matter than in the white matter.

Animals↗
PubMed1999

Relationship between nicotinamide adenine dinucleotide phosphate-diaphorase-reactive neurons and blood vessels in basal ganglia.

The relationship between nicotinamide adenine dinucleotide phosphate-diaphorase-positive neurons and blood vessels was investigated within the rat basal ganglia. Nicotinamide adenine dinucleotide phosphate-diaphorase-positive cell bodies, dendrites or axon-like processes surrounding many but not all blood vessels were observed in the caudate-putamen, ventral pallidum, medial part of the globus pallidus, substantia nigra and subthalamic nucleus. It is concluded that this close relationship contributes to the local vasodilator effect of nitric oxide in the regulation of blood flow in cerebral blood vessels.

Animals↗
PubMed2004

[Blood vessel imaging before creation of dialysis fistula].

THE AIM: Of the study was to present own experience in imaging forearm blood vessels before creating hemodialysis access. MATERIAL AND METHODS: The studied group consisted of 45 hemodialysed patients. Colour duplex sonography (US) was performed in 17 patients before creating the first hemodialysis fistula and phlebography in 27 patients before creating next fistula. In the first group diameter and blood flow parameters in the arteries and deep veins of the upper limb were evaluated. In the second group diameter of patients' veins was assessed. In patients before creating the first fistula the US examination in 4/17 cases showed blood vessels, which were insufficient to create fistula. Among 27 patients who underwent phlebography in 13 cases a stenosis or occlusion was demonstrated and in 6 lack of appropriate superficial veins. CONCLUSIONS: Colour duplex sonography and phlebography are useful in evaluation of blood vessels before creating a vascular access. Phlebography is a method of choice in imaging subclavian and brachiocephalic vein.

Adult↗
PubMed1995

Blood vessel morphometry in human colorectal lesions.

Neovascularisation in tumours of different cell origins has been well documented qualitatively. In this report, we have assessed vascular architecture in different pathological lesions of the colorectum by quantifying blood vessel parameters in order to detect subtle morphological changes using objective methods. Colorectal tissue samples were obtained from resected large bowels containing malignant tumours. Biopsies were taken from defined sites in the resected specimen and were classified as normal (N), potentially premalignant mucosa (PPM), adenomatous polyp (P) and adenocarcinoma (ADCA). All tissues were fixed in modified Karnovsky's fixative for 4 hrs and postfixed in 1% OsO4 for 1 hr. Samples were processed for EM under standardized procedures and embedded in Epon. 0.5 microns semithin sections from five patients per group were stained with toluidine blue. A multistage systematic sampling procedure was adopted. The inner outlines of all blood vessels in the lamina propria (LP) were digitised using a Zeiss VIDAS Image Analyzer at a final magnification of x1,050. The area of the reference (LP) was also measured. No attempt was made to distinguish between the different types of vessel. The morphometric blood vessels parameters quantified were volume density (Vv), numerical density (NA), length density (LV) and mean transverse sectional area (A). Statistically significant differences in Vv and A were detected between all groups except between N and PPM and between P and ADCA. No significant differences in NA and LV were present in any group comparisons. The mean values of all parameters were the highest in ADCA.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗
PubMed2005

Prognostic value of lymphatic and blood vessel invasion in neuroendocrine tumors of the lung.

Few data on the influence of vessel invasion on the progression of neuroendocrine lung tumors are available. Because of the lack of specific markers, previous studies could not reliably discriminate lymphatic and blood vessels. By immunostaining for podoplanin, specific for lymphatic endothelium, and CD34 antigen, we assessed lymphatic and blood vessel invasion in 120 tissue specimens of patients with neuroendocrine lung tumors. Lymphovascular invasion was correlated with clinicopathologic parameters, and its prognostic relevance was evaluated. Lymphatic vessels were identified exclusively at the tumor invasion front, whereas blood capillaries were also seen within tumors. Lymphatic vessel as well as lymphatic and blood vessel invasion was prevalent in patients with high-grade neuroendocrine tumors and advanced tumor stages, closely associated with lymph node metastases (P < 0.0001). In univariate analysis, these two invasion types correlated with decreased disease-free survival (both P < 0.0001), whereas blood vessel invasion alone did not. In multivariate analysis, only tumor grade and lymph node status remained statistically significant factors for prognosis (P = 0.016 and P < 0.0001). Our results suggest that evaluation of lymphatic vessel invasion is important in neuroendocrine lung tumors serving as a prognostic parameter for disease-free survival.

Adolescent↗
PubMed2000

[Experimental study on the extent of injured blood vessels in an avulsion amputation model].

OBJECTIVE: To measure the length and extent of the injured blood vessels in an avulsion amputation model. METHODS: Twenty rabbits were randomly divided into 2 groups. Group A was a sharp amputation group, and group B was an avulsion amputation group. The length and extent of the injured blood vessel was observed with naked eye, operation microscope and electron microscope, and the limbs were replanted. Group A and B were explored at three days and ten days after the replantation respectively. The patency rate and healing process were compared. RESULTS: All the severed ends of vessels in group A were neat with almost the same injured range in the three layers of the vessel wall about 1 mm away from the severed end. The vessels of group B were damaged seriously, the endothelial cells were deleted. The "jumping-like" damage could be observed in the elastic fibers. The injury of 2 to 3 mm away from the normal vessel wall could be observed by operation microscope. CONCLUSION: The damage of avulsion amputation vessels was irregular, 2 to 3 mm or more tissues should be excised under the microscope in the process of operation in order to ensure the healthy intact blood vessel walls.

Amputation, Traumatic↗
PubMed2006

Dysferlin is a new marker for leaky brain blood vessels in multiple sclerosis.

Dysferlin is a muscle protein involved in cell membrane repair and its deficiency is associated with muscular dystrophy. We describe that dysferlin is also expressed in leaky endothelial cells. In the normal central nervous system (CNS), dysferlin is only present in endothelial cells of circumventricular organs. In the inflamed CNS of patients with multiple sclerosis (MS) or in animals with experimental autoimmune encephalomyelitis, dysferlin reactivity is induced in endothelial cells and the expression is associated with vascular leakage of serum proteins. In MS, dysferlin expression in endothelial cells is not restricted to vessels with inflammatory cuffs but is also present in noninflamed vessels. In addition, many blood vessels with perivascular inflammatory infiltrates lack dysferlin expression in inactive lesions or in the normal-appearing white matter. In vitro, dysferlin can be induced in endothelial cells by stimulation with tumor necrosis factor-alpha. Hence, dysferlin is not only a marker for leaky brain vessels, but also reveals dissociation of perivascular inflammatory infiltrates and blood-brain barrier disturbance in multiple sclerosis.

Animals↗
PubMed2001

[A research on the quantification of retinal blood vessels in cases of arteriovenous crossing pressure syndrome caused by hypertension].

The method for quantification of retinal blood vessels in cases of arteriovenous crossing pressure syndrome caused by hypertension was studied. The matched filtering pre-processing of image enhancement for local retinal blood vessels and closing of mathematical morphology for image smoothing, and the method of scale-up lineation for contour determination of retinal blood vessels and optimal seeking algorithm with reversible quantification were used to measure the pathological deformation of vessel, thus providing a computer method for auxiliary diagnosis of relative diseases.

Algorithms↗
PubMed2002

In-vivo non-invasive study of the thermoregulatory function of the blood vessels in the rat tail using magnetic resonance angiography.

In rats, a significant portion of total body heat loss occurs through sympathetically mediated changes in tail blood flow, making the rat tail a convenient model to study vasomotor activity during thermoregulation. Our aim was to perform a non-invasive study of the mechanisms of blood vessel control in the rat tail upon increasing body temperature. In anaesthetized rats, blood vessel temperature was monitored using non-invasive thermistors positioned on the skin surface, covering the ventral artery (Ta) and lateral vein (Tv), and changes in blood vessel size were measured using in-vivo magnetic resonance angiography (MRA). Two important regions of the tail (base and middle) were studied during a gradual rise of rectal temperature (Tr) from 37 to 40 degrees C. MRA data show that increasing Tr causes increased diameter of both arteries and veins of the tail, that venous diameter changes are greater than arterial diameter changes, and that diameter changes of both types of vessel are greater at the base of the tail than in the middle. Temperature data allowed calculation of (Ta - Tv), which we used as an index of flow through arteriovenous anastomoses (AVAs). The data suggest that AVAs near the base of the tail are important in heat exchange, and that they remain open only for Tr values between 38 and 39 degrees C.

Animals↗
PubMed2006

Localization and quantification of platelet-rich thrombi in large blood vessels with near-infrared fluorescence imaging.

BACKGROUND: Imaging of thrombus formation in vivo has been limited by the inability to directly visualize and measure thrombi in large blood vessels in real time. Near-infrared light, with its superior tissue penetration and reduced scatter, could potentially solve this problem. METHODS AND RESULTS: Platelets were labeled with the near-infrared fluorophore IR-786. Optimal total fluorescence yield occurred at 6 attomoles of IR-786 per platelet. IR-786-labeled platelets were tested for their ability to detect thrombus formation in large animal model systems relevant to common human vascular procedures. Invisible near-infrared light did not distort the surgical field in any way, and even after optimization of per-platelet fluorescent yield, platelets remained fully functional. Intravenous infusion of just 3.6x10(10) labeled platelets into a 35-kg Yorkshire pig permitted thrombus visualization, with a signal-to-background ratio > or = 2, for at least 2 hours in coronary, carotid, and femoral vessels. Platelet-rich, actively growing clots were monitored in real time and quantified with respect to size and kinetics after injury to vessels, cutaneous incisions, intravascular stent insertion, or introduction of embolic coils. Similarly, formed clots were monitored in real time during thrombolysis with streptokinase and heparin. Vessel patency was assessed independently with a second near-infrared fluorescent blood pool agent. CONCLUSIONS: IR-786-labeled platelets provide sensitive, specific, and real-time visualization of thrombi in thick-walled blood vessels. In addition to immediate application in cardiac, transplant, and vascular surgery, the mechanisms that underlie thrombus formation in large blood vessels can now be investigated.

Animals↗
PubMed1991

Effect of refraction on optical microscopic measurement of internal blood-vessel diameter and its correction.

In optical microscopic measurement of internal blood-vessel diameters, the effect of refraction must be taken into account to ensure accuracy of the result. This effect is discussed and an analytical correction formula derived. Phantom blood vessels with known internal and external diameters were used to test the validity of the correction formula. The errors obtained prior to correction were reduced significantly after correction.

Blood Vessels↗
PubMed1993

[In vivo and in vitro study of experimental occlusion of choroidal and retinal blood vessels in the miniature pig].

Experimental occlusion of ocular blood vessels was performed in 25 eyes of 20 adult miniature pigs. The hyperacute, acute, subacute and chronic effects of these occlusions were studied by photography and fluorescein angiography of the ocular fundus in the living animals, and post-mortem by microscopic examination of histologic sections and stereomicroscopic study of vascular corrosion casts. Transection of the lateral posterior ciliary arteries was performed in eleven eyes and resulted in manifest chorioretinal ischaemic atrophy in confined areas of the ocular fundus. One month and longer after arterial transection, revascularization was found in the areas in which hypoperfusion had been induced, but no indications of neovascularization were observed. In one eye the lateral vortex veins were occluded by ligation. The subsequent fluorescein angiograms demonstrated only an insignificant local retardation of the choroidal filling. Filling defects of the choroidal vasculature and chorioretinal ischaemic lesions were not observed in the living animal nor in the vascular corrosion cast. Transection of the lateral posterior ciliary arteries was combined with ligation of the lateral vortex veins in seven eyes. These experiments resulted in lesions which were less severe than the sequels caused by transection of the lateral posterior ciliary arteries only. This observation was explained by the retrograde flow of venous blood which is rich in oxygen from the medial to the lateral choroidal quadrants. Consequently, ligation of the lateral vortex veins has a protective influence on the acute ischaemic lesions provoked by transection of the lateral posterior ciliary arteries. Simultaneous transection of the lateral posterior ciliary arteries and lateral chorioretinal arteries was performed in eight eyes. In the subacute and chronic stages, 1 and 4 months respectively after the vascular transection, proliferation of the retinal pigment epithelium and intraretinal neovascularization were observed in three out of five eyes examined. A fibrogliotic tissue mass containing newly formed blood vessels was found in between the reduplicated retinal pigment epithelium and the external layers of the sensory retina. The miniature pig offers an interesting ophthalmologic model because the ischaemic chorioretinal lesions and intraretinal gliovascular membranes which can be induced experimentally in this species present numerous similarities with the sequels of chorioretinal vascular occlusions in man.

Angiography↗
PubMed1984

Perivascular serotoninergic neurons: somatodendritic contacts and axonic innervation of blood vessels.

As shown by histofluorescence studies, a number of brain stem serotoninergic neurons have their cell bodies and dendrites in intimate contact with parenchymal blood vessels, including arterioles (perivascular serotoninergic neurons). Another, apparently distinct, phenomenon which was evidenced is the existence of a diffuse innervation by long serotoninergic axons of intrinsic blood vessels. These axons seem to be continuous with an adventitial nerve fiber network surrounding extrinsic blood vessels. A novel significant finding was that some of the perivascular neurons themselves can project an axonic process into the wall of the same vessel they embrace with their cell body and dendrites (a receptive as well as a vasomotor function?).

Animals↗
PubMed2006

Alteration in alpha- and beta- adrenoceptor profile of rabbit-knee-joint blood vessels due to chronic inflammation.

Experiments were performed to investigate the nature of alpha- and beta-adrenoceptors in blood vessels supplying the posterior capsule of the chronically inflamed rabbit knee joint, and results were compared to the finding from previous experiments on the normal and acutely inflamed joint to assess any alteration which may occur in the adrenoceptor profile due to the chronic inflammation process. Electrical stimulation of the posterior articular nerve resulted in vasoconstriction that was completely blocked by phentolamine. This constrictor response was almost equally inhibited by prazosin and yohimbine. The dose-response curves to close intraarterial injection of alpha-adrenoceptor agonists showed a rank-order potency of adrenaline = clonidine = phenylephrine. The adrenaline dose-response curve was shifted to the right by administration of alpha-antagonists with a rank-order potency of phentolamine = prazosin = yohimbine. At this stage of experiments, there was an equal response of alpha(1)- and alpha(2)- adrenoceptors in blood vessels of the chronically inflamed rabbit knee joint. In another group of animals, the neurally mediated vasodilatation, which appeared after administration of phentolamine, was completely blocked by propranolol and was reduced significantly by ICI118551, but the effect of atenolol was not significant. The dose-response curve to close intraarterial injection of beta-adrenoceptor agonists showed a rank-order potency of: isoprenaline > salbutamol > dobutamine. The isoprenaline dose-response curve was shifted to the right by administration of beta-antagonists with rank-order potency of propranolol > ICI118551 > atenolol. These experiments showed a greater beta(2)-adrenoceptor response than beta(1)-adrenoceptor response in chronically inflamed rabbit-knee-joint blood vessels. Overall, compared to previous experiments on normal joint in which alpha(2)- and beta(1)-adrenoceptor responses predominated, and in acutely inflamed joint in which an equal alpha(1)/alpha(2) and beta(1)/beta(2) response was shown, in chronically inflamed joint the sympathetic constriction response was returned toward normal. No more alpha-adrenoceptor shift had happened, and the shift of beta(1) to beta(2) response continued.

Animals↗