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Histological characteristics of tumors in blood vessels play an important role in tumor progression of invasive ductal carcinoma of the breast.

Whether the characteristics of tumor cells in blood vessels play an important role in the tumor progression of invasive ductal carcinoma (IDC) of the breast is not known. The purpose of this study was to investigate the significance of the characteristics of tumor cells in blood vessels in relation to tumor progression in 247 IDC patients with blood vessel invasion, in comparison with well-known histological parameters. Blood vessel tumor embolus dimensions were measured. Nuclear atypia, numbers of mitotic and apoptotic figures, and fibrosis grade of tumor cells in blood vessels were assessed. Cox proportional hazard multivariate analyses showed that >2 mitotic figures in blood vessel tumors significantly increased the hazard rates (HRs) of disease-free survival (P=0.002) and initial distant organ metastasis-free survival (IDOMS) in node-negative IDCs (P=0.005), and the HRs of disease-free survival (DFS, P=0.007) and IDOMS (P=0.015) in node-positive IDCs. Apoptotic figures >2 in blood vessel tumor emboli significantly increased the HR of overall survival (P=0.007) in node-positive IDCs. The present study showed the number of mitotic and apoptotic figures in tumor cells in the blood vessels to play a very important role in the tumor progression of IDCs.

Adult↗

Origins of the neurovascular bundle: interactions between developing nerves and blood vessels in embryonic chick skin.

Growth cones of nerves and endothelial cells of blood vessels are closely analogous in their migratory behavior, and they are both set a similar task during the early development of a limb. Both must invade the mesenchyme to form ramifying networks of large nerves and vessels. Both systems must densely pervade certain regions of the developing limb, such as muscle rudiments, and both form dense cutaneous plexuses at precisely the same depth beneath the epidermis. Moreover, adult tissues show many examples of neurovascular bundles in which nerves and blood vessels run closely parallel and branch in a correlated fashion, suggesting some interdependence during development. We have examined the interrelationship between developing nerves and blood vessels in chick wing skin because it allows a particularly convenient two-dimensional analysis of the two systems which can be revealed simultaneously in the same preparation by injection of Indian ink combined with silver-staining. We show that nerves do not use blood vessels as pathways along which to crawl, but that there are two other ways in which neurovascular associations arise: in some situations nerves and blood vessels follow the same route because they are responding independently to the same mesenchymal cues; and in some situations nerves induce blood vessels to remodel around them.

Animals↗

[A study of the influence scan timing and depiction of blood vessel diameter in CE-3DMRA: simulation by pulsatile flow].

In imaging using contrast-enhanced three-dimensional magnetic resonance angiography (CE-3DMRA), optimizing the delay time from the start of intravenous injection of contrast medium to the start of scanning has generally been an important concern when obtaining blood vessel images of good contrast. Recent methods of mechanically assessing the attainment of contrast medium injection include Smart-Prep and others. Another method is the Test Bolus, in which a small amount of contrast medium determines the timing of scan start, in quest of the time intensity curve. Because these methods are not necessarily satisfactory, the corrected method is used in clinical cases. In terms of how scan timing affects blood vessel depiction, no study has examined pulsatile flow, which is carried out by simulation. On the other hand, there are reports on data filling of k-space using imitation blood vessels on a computer and simple experimental equipment. This research examined experimentally blood vessel depiction according to scan timing and the diameter of blood vessels by using a systemic circulation simulator that incorporated hemodynamic circulation in which pulsatile flow is the same as that of a human body, using an artificial heart developed especially for MRI. It is thought that scan timing in CE-3DMRA affects the depiction of blood vessels for which the diameter of the blood vessel differs from the experimental result. Phase-encoding k-space data filling is the contrast-to-noise ratio (CNR) of each blood vessel irrespective of sequential and centric k-space ordering. The timing shift phenomenon, in which a blood vessel is so thin that the scan timing is overdue and shows a relatively high value, can occur. Moreover, that scan timing affects not only the diameter of a blood vessel but also depiction of the narrowing of a stenotic blood vessel or a branch blood vessel was demonstrated clinically and experimentally. Therefore, blood vessel depiction changes with scan timing, and it is clinically important to determine the time of arrival of contrast medium and the duration of the enhancement effect in quest of the time intensity curve by test bolus when clearly describing the target blood vessel.

Blood Vessels↗

Minimum blood vessel diameter measured by magnification angiography.

Visibility of small blood vessels was improved by magnification angiography of biologic specimens. Blood vessel diameter was determined for increasing magnifications by various screen-film combination. Significantly smaller vessels were recognized with the magnification technique in all screen combinations. Noisy screen-film combinations with better square wave transfer functions did not allow visualization of blood vessels as small as those screen-film combinations with poorer square wave transfer functions but less noise.

Angiography↗

Increased nerve and blood vessel ingrowth associated with proteoglycan depletion in an ovine anular lesion model of experimental disc degeneration.

STUDY DESIGN: Nerves and blood vessel distribution in discs were localized immunohistochemically and correlated with the proteoglycan contents of normal and degenerate disc tissues. OBJECTIVE: The aim of the present study was to systematically evaluate whether nerve and blood vessel ingrowth was associated with depletion of disc proteoglycans and degenerative changes in an established experimental model of disc degeneration. SUMMARY OF BACKGROUND DATA: Animal models of disc degeneration, allowing longitudinal study of pathogenic mechanisms, are limited. The ovine model enables systematic monitoring of blood vessel and nerve ingrowth during the development of disc degeneration after injury to the anulus fibrosus. METHODS: Merino sheep received a controlled left anterolateral surgical defect in the outer anulus fibrosus of the L1-L2 and L3-L4 discs (lesion group); sham-operated controls received the retroperitoneal anterolateral approach only. Animals were killed 3, 6, 12, and 26 months postoperation, and the discs were collected for histology and compositional and morphologic analyses. Sagittal tissue sections were stained with toluidine blue and hematoxylin and eosin; Type IV collagen immunolocalization visualized blood vessel ingrowth, and nerves were immunolocalized using monoclonal antibodies to growth-associated protein (GAP-43), protein gene product 9.5, and glial fibrillary acidic protein. RESULTS: Compositional and histologic results demonstrated early focal depletion 3-12 months postoperation of glycosaminoglycan associated with lesion development, increased blood vessel and nerve ingrowth, and infiltration of cells from the outer anulus fibrosus along the plane of the original defect. Blood vessel numbers in the outer to mid third of the anulus fibrosus were elevated in the lesion discs 3-6 months postoperation reaching a maximum at 12 months postoperation; nerves immunoreactive with protein gene product 9.5 (also maximal at 12 months postoperation) were often found associated (but not exclusively) with blood vessels, and some nerves were also reactive with GAP-43 and glial fibrillary acidic protein, but only at 12 months postoperation. CONCLUSIONS: Nerve and blood vessel ingrowth into the anulus fibrosis were strongly associated with proteoglycan depletion. The ovine anular lesion model of disc degeneration is a useful experimental model for the systematic evaluation of nerve and blood vessel development after anular injury.

Animals↗

[Improvement in the mechanical properties of artificial blood vessel suitable for the extracranial cerebral artery].

Saphenous vein interposition grafts have been commonly used for the reconstruction of occlusive lesions in the extracranial cerebral vessels, such as carotid or vertebral arteries. In contrast, cerebral revascularization using an artificial blood vessel has not been so common. This is due to the fact that conventional artificial blood vessels have been too firm or too rigid for use in the neurosurgery. Another reason is that the long term patency rate of small caliber artificial blood vessels has usually been inferior to that found in autologous vein grafts. The purpose of this study was to develop a soft and compliant artificial blood vessel suitable for cerebrovascular surgery. This new artificial blood vessel is made of polyurethane, porous in structure (porous polyurethane). Thus, multiple small-sized pores exist both in the inner and outer surfaces, and in the wall of the porous polyurethane graft. To test its mechanical properties, we evaluated stress-strain curves and compliance. In comparison to expanded polytetrafluoroethylene graft (Goretex), which has been one of the most commonly used artificial blood vessels in the cardiovascular surgery, the mechanical properties of the porous polyurethane graft more closely resembled those of the common carotid artery in dogs. Thus, porous polyurethane graft was shown to be a soft and compliant new artificial blood vessel. This means not only that it can be maneuvered with technical ease for anastomosis but also that there is a reduction of compliance-mismatch between the host vessel and the artificial vessel. Compliance mismatch has been documented as a major factor in the inducement of intimal hyperplasia, which causes a delayed occlusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Matrix metalloproteinases in blood vessel development in human fetal skin and in cutaneous tumors.

In vitro angiogenesis models suggest that new blood vessel formation requires the induction and secretion by endothelial cells of matrix metalloproteinases. These enzymes assist in the controlled proteolytic degradation of the surrounding extracellular matrix during blood vessel formation. The results of in vitro studies cannot be extrapolated directly to the process of in vivo angiogenesis because the type of matrix employed and the repertoire of enzymes secreted by cells in vivo differ dramatically from in vivo conditions. To investigate the in vivo role of matrix metalloproteinases in blood vessel development, we looked for the presence of these proteinases in endothelial cells involved in fetal angiogenesis and in neovascularization of certain invasive skin tumors using immunofluorescent staining. In fetal tissue, interstitial collagenase was present in both early microvessels developing from undifferentiated mesoderm and in microvessels involved in elongation and sprout formation from preexisting blood vessels. In aggressive skin tumors, i.e., morpheaform and recurrent basal cell carcinomas and squamous cell carcinomas, there was a marked increase in the number of collagenase-containing blood vessels, often extending into the tumor nests. Immunofluorescent staining failed to detect stromelysin, matrilysin, or gelatinase A and B (72- and 92-kDa type IV collagenases, respectively) in fetal or tumor blood vessels. These findings are consistent with the hypothesis that proteolytic degradation of the extracellular matrix is required for the formation of new blood vessels. Interstitial collagenase appears to play an important role in this process.

Adult↗

Selective ablation of immature blood vessels in established human tumors follows vascular endothelial growth factor withdrawal.

Features that distinguish tumor vasculatures from normal blood vessels are sought to enable the destruction of preformed tumor vessels. We show that blood vessels in both a xenografted tumor and primary human tumors contain a sizable fraction of immature blood vessels that have not yet recruited periendothelial cells. These immature vessels are selectively obliterated as a consequence of vascular endothelial growth factor (VEGF) withdrawal. In a xenografted glioma, the selective vulnerability of immature vessels to VEGF loss was demonstrated by downregulating VEGF transgene expression using a tetracycline-regulated expression system. In human prostate cancer, the constitutive production of VEGF by the glandular epithelium was suppressed as a consequence of androgen-ablation therapy. VEGF loss led, in turn, to selective apoptosis of endothelial cells in vessels devoid of periendothelial cells. These results suggest that the unique dependence on VEGF of blood vessels lacking periendothelial cells can be exploited to reduce an existing tumor vasculature.

Androgens↗

The histology of lumbar intervertebral disc herniation. The significance of small blood vessels in the extruded tissue.

Six hundred surgical cases of lumbar intervertebral disc herniation were evaluated histologically for the presence of blood vessels. These patients ranged in age from 12 to 77 years. Blood vessels were observed in 57 of 101 cases of complete prolapse type of herniated disc (56.4%), 12 of 32 cases of incomplete prolapse type of herniated disc (37.5%), and 53 of 467 cases of protrusion type of intervertebral disc herniation (11.3%). The presence of blood vessels in intervertebral discs was also investigated in postmortem specimens. Blood vessels were observed in 293 of 616 intervertebral discs (T10-L5), in individuals older than 40 years of age from 100 postmortem spines. The specimen age range was 16-89 years. Most of the blood vessels seen in the extruded tissue, exposed to the epidural space in cases of complete and incomplete prolapse type of herniation, are thought to have been newly formed after herniation occurred. As invasion of the intervertebral disc by blood vessels was found to occur with the advance of age, it is possible that such blood vessels become extruded with the intervertebral disc tissue. The intervertebral disc may herniate posteriorly in three basic patterns. The first pattern is "protrusion type of herniated disc." In protrusion hernia type there is abnormal posterior bulging of the anulus fibrosus. The disc pathology is predominantly nucleus pulposus, and the peripheral layer of the anulus fibrosus remains attached to the vertebral body bony rim, however.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

How a highly complex three-dimensional network of blood vessels regresses: the gill blood vascular system of tadpoles of Xenopus during metamorphosis. A SEM study on microvascular corrosion casts.

The morphology and vasculature of filter plates and filter rows of tadpoles of Xenopus laevis Daudin were studied from prometamorphosis (stage 56) to metamorphic climax (stage 62) by scanning electron microscopy (SEM) of (i) critical point-dried specimens and (ii) microvascular corrosion casts. The number and frequencies of the highest branching orders of venous filter row vessels, which reach their maximum (6) in stage 58, as well as vessel diameters, interbranching distances, and branching angles were measured. Branching orders continuously decrease until stage 62, so that only two are left. Vessel (luminal) diameters increased from 16.9 +/- 0.65 microm (SEM) (stage 56) to 19.3 +/- 0.61 microm (stage 58) (branching order 0) and then decreased to 16.7 +/- 0.91 microm (stage 62). Interbranching distances were largest in stage 59 (57.5 +/- 2.07 microm (branching order 0). Branching angles were highest in stage 62 (91.4 degrees +/- 8.82 degrees; branching order 2) and lowest in stage 56 (76.0 degrees +/- 4.64 degrees; branching order 4). From the morphology of cast vessels we conclude that vascular regression is organized by progressive "fusion" of opposite vessels in the highest branching orders ("miniaturization") until only a single capillary loop connects the terminal arteriole and the main filter fold venule. With obliteration of the single capillary loop, the regression of the gill vasculature is terminated. It is noted that the "fusion" of gill vessels is reminiscent of "reversed" intussusceptive microvascular growth.

Animals↗

Association between hemosiderin deposition and blood vessel regression during involution of foreign-body granuloma. Histochemical and ultrastructural study.

We have characterized the sequence of events resulting in vessel occlusion and stasis of blood flow during involution of a foreign-body granuloma using histochemistry and electron microscopy. In the microvascular bed of the granulation tissue accompanying the progressive resorption of an implanted collagen sponge, endothelial cells protruded into the vascular lumen, resulting in the occlusion of the lumens of venules and capillaries. Examination of sections stained by the TUNEL method showed brown-yellow stained structures in the vascular lumen during regression of blood vessels. However, the ultrastructural profiles of endothelial cells effectively involved in the vessel occlusion showed none of the cardinal morphological features of apoptosis. These endothelial cells which displayed remarkable indentations of their nuclei in the form of nuclear pinches and/or deep pockets bulged conspicuously into the lumen. Such endothelial cells served as effective valves by protruding into the lumens of small blood vessels, and eventually the vessels were completely plugged by red blood cells. However, protruding endothelial cells subsequently shed into the vascular lumen by deviating themselves from the constitution of the vessel wall. The endothelial cells undergoing apoptosis were removed by intraluminal macrophages. Between the 130 and 140 day, the occurrence of small vessels tightly packed with erythrocytes reached a peak value in the granulation tissue and was accompanied by hemosiderin deposits. The plugged vessels were frequently associated with erythrocyte extravasation, leading to openings between degenerated endothelial cells due to the disappearance of endothelial cytoplasmic projections. Extravasated erythrocytes were rapidly eliminated by phagocytic cells such as mononuclear macrophages and multinucleated giant cells, and ended as hemosiderin deposits in granulation and/or scar tissue at the end of the experimental period (130-140 days). The morphological analysis of this regression sequence suggests that the protrusion of endothelial cells with the nuclear deformation is a mechanism contributing to the occlusion of blood vessels and consequently leads to erythrocyte extravasation.

Animals↗

Engineering of fibrin-based functional and implantable small-diameter blood vessels.

We engineered implantable small-diameter blood vessels based on ovine smooth muscle and endothelial cells embedded in fibrin gels. Cylindrical tissue constructs remodeled the fibrin matrix and exhibited considerable reactivity in response to receptor- and nonreceptor-mediated vasoconstrictors and dilators. Aprotinin, a protease inhibitor of fibrinolysis, was added at varying concentrations and affected the development and functionality of tissue-engineered blood vessels (TEVs) in a concentration-dependent manner. Interestingly, at moderate concentrations, aprotinin increased mechanical strength but decreased vascular reactivity, indicating a possible relationship between matrix degradation/remodeling, vasoreactivity, and mechanical properties. TEVs developed considerable mechanical strength to withstand interpositional implantation in jugular veins of lambs. Implanted TEVs integrated well with the native vessel and demonstrated patency and similar blood flow rates as the native vessels. At 15 wk postimplantation, TEVs exhibited remarkable matrix remodeling with production of collagen and elastin fibers and orientation of smooth muscle cells perpendicular to the direction of blood flow. Implanted vessels gained significant mechanical strength and reactivity that were comparable to those of native veins. Our work demonstrates that fibrin-based TEVs hold significant promise for treatment of vascular disease and as a biological model for studying vascular development and pathophysiology.

Animals↗

Bronchial blood vessel dimensions in asthma.

The extent to which the bronchial vasculature contributes to airway wall thickening in large and small airways in patients with asthma is unknown. The aim of this study was to quantify the number and the area occupied by blood vessels in the airway submucosa of patients with and without asthma. We used the monoclonal antibody Factor VIII to measure the blood vessels between the airway basement membrane and the outer border of the smooth muscle. In large cartilaginous airways in patients with fatal asthma, the number and area of large blood vessels were increased and the number and area of small blood vessels were decreased, compared with that in patients with nonfatal asthma and control subjects. However, the total number of blood vessels and the total area occupied by blood vessels per square millimeter in the airway submucosa were similar in patients with fatal asthma or nonfatal asthma and in control subjects in all airway size groups. Blood vessels were distended to a mean value of 80% of their estimated maximal area. The increased number of larger vessels in patients with fatal asthma raises the possibility that vascular congestion associated with an acute severe asthma attack may distend blood vessels. The finding of similar numbers of blood vessels per square millimeter of submucosa in control subjects and in patients with asthma suggests that blood vessels increase in number in patients with asthma only in proportion to increased airway wall area. It is unlikely that submucosal vessels could act as capacitance vessels and significantly alter inner airway wall thickness.

Adult↗

Laser fluence for permanent damage of cutaneous blood vessels.

Treatment of vascular disorders may be improved by a more thorough understanding of laser-blood vessel interaction. In this study, the probability of permanent damage to a given type and size of blood vessel was determined as a function of fluence at the top (superficial edge) of the vessel lumen. A 532 nm wavelength, 10 ms pulse duration, 3 mm spot size laser was used to perform approximately 250 irradiations of subdermal blood vessels in the hamster dorsal skin flap preparation. The radiant exposure required for a 50% probability of permanent damage was calculated using a probit analysis of experimental results. Threshold radiant exposure increased with larger blood vessel diameters and was greater for arterioles than venules. Monte Carlo modeling of a typical blood vessel geometry revealed that fluence at the top of the blood vessel lumen was amplified by a factor of approximately 2.4 over tissue surface radiant exposure, due to light scattering in the tissue and internal reflection at the skin-air interfaces.

Animals↗

Florence Sabin and the mechanism of blood vessel lumenization during vasculogenesis.

The notion that blood vessel lumina and primordial blood plasma are linked by a single mechanism, intracellular vacuolation of angioblasts, has, for the most part, been overlooked since it was first described in the early decades of the last century. That vacuolation may play a major role in blood vessel formation during vasculogenesis is revisited from the perspective of Florence Sabin's seminal studies in the nascent mesoderm of living chick blastoderms.

Animals↗

An immunohistochemical study of the blood vessels within primary hepatocellular tumours.

We studied the blood vessels in routinely formalin-fixed and paraffin-processed tissue from 18 hepatocellular carcinomas, three "small" hepatocellular carcinomas, and 15 benign nodular lesions representing a spectrum of conditions with which liver cell carcinomas may be confused. These were stained for a basement membrane component (collagen IV) and endothelial markers (Factor VIII-related antigen, Ulex europaeus lectin binding, and QBEnd10). The staining pattern of normal and cirrhotic liver was also examined in tissue removed with these tumours. There was an increased expression by small blood vessels for collagen IV in carcinomas and benign lesions compared with cirrhotic nodules. All endothelial markers (Factor VIII-related antigen, QBEnd10, and Ulex europaeus binding) were best expressed in liver cell carcinomas. These differences were of degree and pattern, and no single marker distinguished benign from malignant lesions. The differences in staining pattern taken together with other clinical and pathological information should be useful in diagnosis particularly of small liver cell carcinoma. The differences between benign and malignant lesions support the idea that malignant neoplastic blood vessels in the liver are of a different basic biological type from normal hepatic sinusoids, and this difference could be exploited further in future therapy.

Binding Sites↗

Prognostic significance of blood vessel invasion in carcinoma of the breast in women.

Prognostic significance of blood vessel invasion in carcinoma of the female breast has been evaluated by study of 242 cases of radical mastectomy done at the Tata Memorial Hospital. The significance of axillary node involvement with the disease has been simultaneously evaluated. In the absence of blood vessel invasion and lymph node metastasis the 5 year survival rate was 98%. Compared with this, 5 year survival rate was reduced to 59% when the blood vessel invasion was present but no lymph node metastasis. Only 12% survived for 5 years when both blood vessels and lymph nodes were involved with the disease. The study indicated that blood vessel invasion in the primary breast carcinoma is more significant than lymph node metastasis.

Adult↗

Theoretical foundation on a noninvasive estimation for viscoelastic mechanical property of blood vessels by ultrasonic Doppler effect.

The method used in this paper is developed to estimate the degree of viscoelasticity of the blood vessel wall in a noninvasive mechanical method. In this proposed method, we can obtain an output waveform connected with mechanical behavior of blood vessels by using Ultrasonic Doppler Effect Sensory (UDES). Characterizing parameters on this waveform are established to estimate the mechanical properties of blood vessels. By analyzing the characteristics of these parameters, we attempt to estimate the viscoelastic property of blood vessels. Previously, it was found that these parameters are related to viscoelastic mechanical properties of materials. In this paper, we carried out computer analysis on the mechanical viscoelastic model and compared the theoretical behavior of blood vessels with the experimental output waveform by UDES. From these results, it was proved that values of these parameters connect with the change of the viscoelastic mechanical property of blood vessels. Therefore, the characterizing parameters of experimental output waveforms can be used to estimate the viscoelastic property of blood vessels in a noninvasive method.

Animals↗