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Blood vessel invasion and axillary lymph node involvement as prognostic indicators for human breast cancer.

Blood vessel invasion and axillary lymph node involvement were examined in 175 breast cancer patients. The incidence of blood vessel invasion was 35%. The presence of blood vessel invasion was highly associated with early disease recurrence. The association of poor prognosis with blood vessel invasion was independent of clinical stage, menopausal status, node status, tumor size, or postsurgical treatment. Those patients with blood vessel invasion and two or more positive nodes were at extremely high risk for early recurrence (70% recurrence by two years compared with 15% recurrence in the remainder of the patients). Thus, blood vessel invasion is a useful indicator of early recurrence in patients with primary breast cancer and, in combination with node status, is a prognostic indicator with high discriminatory power.

Axilla↗

Blood vessel formation in the avian limb bud involves angioblastic and angiotrophic growth.

The vasculature of the avian limb bud takes its origin from the intersomitic vessels as can be shown by ink perfusion of the embryo. While the primitive vessels form a central network in the early limb bud, an area of about 100 microns in width from the ectoderm inward remains free from lumenized vessels. However, this subectodermal avascular zone contains isolated angioblasts, which can be demonstrated by confocal laser scanning microscopy in connection with QH-1-staining. QH-1-positive cells from the avascular zone are capable of giving rise to endothelial cells when grafted ectopically into a "permissive" environment such as the dorso-lateral paraxial mesoderm. Several grafting sites are compared regarding their permissiveness for capillary formation. In order to investigate the origin of the QH-1-positive angioblasts we carried out injections of DiI-Ac-LDL, which is specifically taken up by endothelial cells and macrophages, and found the lumenized vessels and a few isolated cells in the peripheral limb mesoderm stained. In double-labelling studies combining DiI-Ac-LDL and QH-1, it can be shown that there exists a pool of isolated angioblasts that are only QH-1-positive, but have not incorporated DiI-Ac-LDL. In contrast to the lumenized vessels in the core of the limb bud, we found that angioblasts in the avascular zone do not proliferate, as shown by proliferation studies applying the BrdU-method to semithin sections in connection with QH-1-labelled parallel sections. We conclude that the vascularization of the avian limb bud is achieved by a combination of angiotrophic growth (sprouting of vessels) and angioblastic growth (recruitment of angioblasts from the limb mesoderm.

Animals↗

Novel threadlike structures (Bonghan ducts) inside lymphatic vessels of rabbits visualized with a Janus Green B staining method.

A staining method has been developed for in situ and in vivo observation of a threadlike tissue afloat inside the lymphatic vessels of rabbits without adherence to the vessel wall. The existence of this novel structure was not noticed previously because it is extremely difficult to detect it by microscopic inspection of lymphatic vessels. We have found a method that utilizes Janus Green B (JGB), which stained heavily the novel structure. The tissue was studied by confocal laser scanning microscopy (CLSM), light microscopy, and cryoscanning electron microscopy (cryo-SEM). The CLSM image obtained by acridine orange staining of the novel tissue revealed its characteristic nuclei distribution: rod-shaped nuclei of 10-20 microm length aligned in a broken-line/striped fashion. Hematoxylin and eosin staining revealed the threadlike structure passing through a lymphatic valve as histologically distinct from lymphatic vessels and valves. The cryo-SEM image showed the threadlike structure inside a collapsed lymphatic vessel. There were spherical globular structures observable inside sinuses in a rapidly frozen sample, which suggests liquid flowing through the longitudinal ductules in the threadlike structure. The specific staining of the JGB suggests that these threadlike structures inside lymphatic vessels have a high density of mitochondria in their cells and/or nerve-like properties, either of which may provide important clues to their physiological function.

Animals↗

Prognosis of culprit lesion PTCA in acute myocardial infarction for multi versus single vessel disease.

UNLABELLED: We studied 417 patients undergoing single vessel culprit lesion percutaneous transluminal coronary angioplasty (PTCA) for acute myocardial infarction to determine the impact of disease in other vessels. Group A (189 patients, 45%) had coronary artery disease (greater than or equal to 70% stenosis) in at least 1 additional vessel while Group B (228 patients, 55%) did not. The groups were similar in sex distribution (A = 75% male, B = 76%), number of lesions in the single culprit vessel dilated (1 lesion in 83% A, 80% B), and PTCA success (A = 92%, B-94%) (all p = NS). Group A patients were older (63 +/- 10 vs. 56 +/- 11 years) and had more prior myocardial infarctions (27% vs. 7%), and more prior coronary artery bypass grafting (15% vs. 0.4%) (all p less than .01). Group A patients were more likely to have repeat catheterization (48% vs. 32%, p less than .005) although restenosis of the infarct-related vessel was similar (A = 24%, B = 16%) (p = NS). Group A was more likely to need angioplasty in a 2nd vessel (23% vs. 8%) and to need coronary artery bypass grafting (20% vs. 8%) (both p less than .001). Cumulative mortality was higher in Group A at 1 month (10% vs. 5%), 1 year (11% vs. 6%), and long-term (13% vs. 7%). This difference appeared to be due to the impact of lower mean ejection fraction in Group A. CONCLUSION: Treatment of acute myocardial infarction by direct PTCA of the culprit lesion can be performed with a high likelihood of success in patients with or without multivessel coronary artery disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Alterations in reference vessel diameter following intracoronary stent implantation: important consequences for restenosis based on percent diameter stenosis.

The scaffolding effect of stent implantation has the potential to alter vascular geometry and dimensions. The objective of this study was to determine the impact of intracoronary stent implantation on the reference vessel diameter and the consequences of this on the frequency of restenosis applying the binary definitions of restenosis based on percent diameter stenosis. Routine angiographic follow-up was performed in 79/80 consecutive patients who had a single elective Palmaz-Schatz stent implanted in denovo lesions in native coronary arteries 6.5 +/- 3.4 mo after the index procedure. Complete quantitative angiographic follow-up was available in 78 (98%). The mean reference vessel diameter was 2.9 +/- 0.6 mm preprocedure, increased to 3.1 +/- 0.5 mm immediately poststent implantation and was 2.6 +/- 0.6 mm at follow-up (F = 6.45, P = 0.0001, ANOVA for repeated measures). In view of the varying reference vessel diameter, percent diameter stenosis postangioplasty and at follow-up was determined by two methods: (1) automatically by the quantitative coronary angiographic analysis system and (2) by expressing the minimal luminal diameter postangioplasty and at follow-up as a function of the original preprocedural reference vessel diameter. The restenosis rate was significantly greater for all definitions of restenosis when the minimal luminal diameter was determined as a function of the original preprocedure reference vessel diameter (e.g., 34% vs. 18% for the > or = 50% criterion, P = 0.018). Stent implantation results in alterations in reference vessel diameter, which have important consequences for the frequency of restenosis presented as a binary variable based on percent diameter stenosis.

Aged↗

Expression of VEGFR-3 and 5'-nase in regenerating lymphatic vessels of the cutaneous wound healing.

The vascular endothelial growth factor-C (VEGF-C), a specific lymphangiogenic growth factor, raises new questions and perspectives in studying lymphatic development and regeneration. Wound healing skins in mice were processed for 5'-nucleotidase (5'-Nase) and VEGFR-3 (the receptor of VEGF-C) histochemical staining to distinguish lymphatics from blood capillaries and to analyze lymphangiogenesis. In the wounds of 3-5 days after injury, anti-VEGFR-3 immunopositive signals unevenly appeared in 5'-Nase-positive lymphatic vessels in the subcutaneous tissue. A few small circular and irregular lymphatic-like structures with VEGFR-3 expression scattered in the dermal and subcutaneous tissues. Between days 7 and 15 of the wounds, numerous accumulated vasculatures were stained for 5'-Nase and PECAM-1, extending irregularly along the wound edge. Von Willebrand factor was expressed in the endothelial cells of blood vessels and lymphatics in the subcutaneous tissue. Ultrastructural changes of lymphatic vessels developed at different stages, from lymphatic-like structures to newly formed lymphatic vessels with an extremely thin and indented wall. Endothelial cells of the lymphatic vessel were eventually featured by typical intercellular junctions, which deposited with reaction products of VEGFR-3 and 5'-Nase-cerium but lacked VEGF-C expression. The present findings indicate that VEGF-C-induced lymphangiogenesis occurs from the subcutaneous to the dermis along the wound healing edge, especially in the dermal-subcutaneous transitional area, favorable to growth of regenerating lymphatic vessels.

5'-Nucleotidase↗

The influence of mechanical forces and flow mechanisms on vessel occlusion.

The exact mechanism of irradiation-induced occlusion of normal or abnormal retinal vessels is still to a large extent obscure. Blood flow acts as a powerful heat dissipation mechanism. Therefore, a procedure which reduces flow velocity as rapidly as possible after the beginning of irradiation may work with higher efficiency. A theory based on a simplified assumption states that vessel narrowing techniques, which involve only a short length of the vessel to be occluded by a small focus diameter irradiation beam, are less efficient in bringing blood velocity down than a procedure which narrows the vessel over a greater length by a larger focus diameter irradiation beam. The thrombus building up over a greater length of the affected part of the vessel may also better resist the pressure head building up after thrombogenesis is complete because friction between thrombus and vessel wall is larger, and occlusion may, therefore, be more durable. One has to assess, therefore, whether a small-spot technique, which is presumed to be less efficient and may need repetitions, is in fact less innocuous for the surrounding retina--as is generally assumed--than a technique using a larger beam diameter, which, because it is more efficient, may need fewer or even no repetitions.

Blood Flow Velocity↗

Retinal and choroidal vessel closure using phthalocyanine photodynamic therapy.

Chloro-aluminum sulfonated phthalocyanine (CASPc) is a photoactive dye capable of generating photochemical reactions when excited with 675 nm light. We used CASPc to produce photochemical closure of retinal medullary ray vessels and choroidal vessels in normal rabbits. Irradiation prior to CASPc injection produced no photographic, angiographic, or histologic lesions in any eyes. Identical irradiation of medullary ray and choroidal vessels after CASPc injection produced complete vessel closure in all eyes. Histopathologic examination showed marked thrombosis of medullary ray and choroidal vessels, with minimal damage to contiguous tissues including the neurosensory retina. We conclude that CASPc can produce profound closure of normal retinal and choroidal vessels with minimal deleterious effect on surrounding tissues.

Aluminum↗

New vascular tissue rapidly replaces neural parenchyma and vessels destroyed by a contusion injury to the rat spinal cord.

Blood vessels identified by laminin staining were studied in uninjured spinal cord and at 2, 4, 7, and 14 days following a moderate contusion (weight drop) injury. At 2 days after injury most blood vessels had been destroyed in the lesion epicenter; neurons and astrocytes were also absent, and few ED1+ cells were seen infiltrating the lesion center. By 4 days, laminin associated with vessel staining was increased and ED1+ cells appeared to be more numerous in the lesion. By 7 days after injury, the new vessels formed a continuous cordon oriented longitudinally through the lesion center. ED1+ cells were abundant at this time point and were found in the same area as the newly formed vessels. Astrocyte migration from the margins of the lesion into the new cordon was apparent. By 14 days, a decrease in the number of vessels in the lesion center was observed; in contrast, astrocytes were more prominent in those areas. In addition to providing a blood supply to the lesion site, protecting the demise of the newly formed vascular bridge might provide an early scaffold to hasten axonal regeneration across the injury site.

Animals↗

Interaction of activated natural killer cells with normal and tumor vessels in cranial windows in mice.

A mammary carcinoma, MCa IV, was grown in syngeneic C3H mice in a cranial window preparation which permitted the in vivo observation of the growth and microcirculation of the tumors. Fluorescently labeled activated natural killer (A-NK) cells were injected into the external carotid artery and their interactions with normal and tumor vessels were quantified by video microscopy. Cells which entered the tumor vessels adhered heterogeneously to these vessels, regardless of vessel size or blood flow rates and bound with an efficiency ranging from 0 to 82% of the incoming cell flux. Normal brain tissue showed significantly fewer binding cells per microscopic field (9 +/- 5 vs 85 +/- 27 cells/1.3 mm2) and the few cells which were retained by the normal tissue were highly deformed, suggesting mechanical rather than adhesive entrapment. These studies indicate that A-NK cells bind in high numbers to segments of the vessels of mammary tumors growing in an intracranial site when administered through an arterial route; however, some tumor vessels may escape recognition by these cells. These findings suggest that A-NK cells may be used as carriers of genes for anti-cancer agents.

Animals↗

Ultrastructure of the endometrial blood vessels during implantation of the rat blastocyst.

The ultrastructure of the blood vessels of the endometrium was analysed during implantation of the blastocyst in rats, at the time of appearance of the Pontamine Blue Reaction. Vessels from implantation sites and from interimplantation sites were compared. In vessels from implantation sites the endothelial cells showed fenestrations covered by diaphragms. In addition, small interruptions (gaps) between the endothelial cells were observed. These features were present in vessels larger than 5 micrometers in diameter and more than 100 micrometers away from the uterine epithelium, both in the mesometrial and antimesometrial wall of the endometrium. Vessels from interimplantation sites displayed neither fenestrations nor interruptions. The endothelial cells of the implantation sites displayed morphological signs of metabolic activation. These consisted of increased numbers of polyribosomes, well developed Golgi complexes and prominent nucleoli. The fenestrations and gaps in the vessel wall were interpreted as constituting the morphological basis for the increase in vascular permeability and the consequent edema which characterize the Pontamine Blue Reaction.

Animals↗

The basement membrane of the persisting maternal blood vessels in the placenta of Callithrix jacchus.

Formation and morphology of the thickened basement membrane-like layer around the persisting maternal vessels of the Callithrix jacchus placenta were investigated from day 45 until term (day 142) using light, electron and immunofluorescence microscopy. Thickening occurs with the establishment of contacts between the vessels and the syncytiotrophoblast (day 48). Final thickness is reached at about day 100. The course of the vessels shows wide gaps where the maternal blood flows freely into the intertrabecular spaces. As revealed by electron microscopy, the extracellular sheath around the maternal vessels consists of an inner subendothelial basement membrane (3-6 microns) and an outer fibril-containing layer (2-4 microns). Cell debris is seen between the two layers and in the basement membrane. Plaques of granular and fine-filamentous material are incorporated into the fibril-containing layer. The synthesis of the basement membrane material is localized in the endothelial cells. Immunofluorescence microscopy reveals collagen types IV and V, laminin and heparan sulfate proteoglycan (BM-1) in the sheath around the persisting vessels. Fibronectin occurs only in certain areas or in the form of dots. Collagen types I and III are not seen in the region of the vascular wall. It can, therefore, be assumed that the subendothelial layer represents a genuine basement membrane; the fibrils consist of collagen type V and the plaques contain fibronectin. The existence of the thick perivascular sheath is attributed to the persistence and stability of the maternal vessels.

Animals↗

The architecture of the most peripheral retinal vessels.

The vascular bed of the extreme periphery of the human retina is characterized by the occurrence of relatively wide arcades and bridging vessels connecting the peripheral portions of arteries and veins. These vessels differ from the more posterior capillaries not only by their larger diameter but also by the presence of a perivascular halo, which consists of an electron-translucent ground substance containing fine collagen fibrils, basement membrane material, dense bodies, vesicles, and portions of macrophages. The appearance of the external portion of the halo and the relationship of its collagen fibrils to the basement membrane of the surrounding Müller cells is indistinguishable from that of the cortical vitreous and the inner limiting membrane located at the vitreoretinal interface. Toward the periphery the thickness of the halo increases from vessel to vessel. As a rule, one or more of the vessel loops closet to the ora serrata are occluded. The structure of these occluded vessels is identical with the structure of the halo.

Animals↗

Coronary vessel-wall and lumen imaging using radial k-space acquisition with MRI at 3 Tesla.

This study investigates the feasibility of imaging the coronary lumen and vessel-wall, using MRI with a radial k-space trajectory at 3 T. Such radial trajectories offer the advantage of greater vessel sharpness than traditional Cartesian trajectories. This field strength offers an increased signal-to-noise ratio (SNR) compared with 1.5 T, which compensates for the slight SNR reduction due to the radial sequence. Images of the coronary lumen were acquired for seven healthy volunteers. In ten volunteers the vessel wall was scanned, with blood suppression using oblique-slab adiabatic re-inversion. Scans were performed during free breathing, using prospective respiratory navigator-gating. Coronary lumen scans had SNR of 16.0+/-1.9 and contrast-to-noise ratio (CNR) of 10.3+/-2.1, showing acceptable image quality. Vessel wall images showed good image quality, with mean SNR of 16.6+/-2.0/5.8+/-2.8/10.1+/-2.2 for vessel wall/lumen/epicardial fat. The wall-blood CNR was 10.7+/-2.7, and wall-fat CNR was 6.5+/-2.5. It is concluded that radial gradient-echo imaging at 3 T is a promising method for coronary vessel-wall imaging, and is also feasible for imaging the coronary lumen.

Adipose Tissue↗

MR imaging of the vessel wall.

Since the risks for thrombosis are more dependent on plaque composition than on the degree of luminal narrowing, the radiological assessment of atherosclerosis should extend beyond mere depiction of the arterial lumen. High-resolution MRI of the vessel wall can provide important information about the individual makeup of atherosclerotic plaques, potentially enabling early detection and characterization of lesions before narrowing of the vessel lumen occurs. The MR-based assessment of the vessel wall with sufficient spatial resolution and image contrast, however, remains challenging. Requirements include high signal-to-noise ratio, high contrast-to-noise ratio, good signal penetration depth and homogeneous signal throughout the vessel under investigation, as well as imaging protocols encompassing various contrast weightings. Numerous dedicated radiofrequency (RF) coils have been developed to achieve these goals employing either external surface phased-array coils, or alternatively, utilizing intravascular coils to image the vessel wall from inside the vessel and thus being invasive. For the non-invasive approach of imaging with surface coils, the carotid and the right coronary arteries have been favoured since they are of critical importance and since they are relatively superficial structures, accessible from the outside. To detect the early development of plaque and visualize it globally rather than locally, intravascular contrast agents on the basis of ultrasmall particles of iron oxide can be used as a marker of macrophage activity within the plaque. In the long run, it appears likely that the combination of luminal MR angiography with the administration of susceptibility-based contrast agents and subsequent high-resolution MR of detected atherosclerotic lesions with dedicated RF coils could evolve as the diagnostic concept of choice for the assessment of atherosclerotic disease.

Arteriosclerosis↗

[The optics of retinal blood vessels and their significance for scanning laser Doppler flowmetry].

Recently, the scanning laser Doppler flowmetry (SLDF) has been developed as a standard method for the quantification of retinal blood flow. However, the measured quantities flow, volume, and velocity depend on the angle between the direction of the blood flow and of the light. The underlying theory assumes isotropic illumination of the vessel. This assumption, however, is not valid for light back-scattered from retinal vessels. This paper investigates the contribution of different pathways of the light to the SLDF signal by a Monte Carlo simulation. It is shown that the light measured on a vessel having a thickness of 50 microns is predominantly back-scattered from the blood inside the vessel, whereas the measurement on vessels 20 microns in diameter or less also includes light transmitted through the vessel.

Blood Flow Velocity↗

Coronary artery distensibility and compensatory vessel enlargement--a novel parameter influencing vascular remodeling?

Vascular remodeling implies the concept of compensatory vessel enlargement to preserve luminal dimensions during atheromatous plaque development. However, negative remodeling, i.e. vessel shrinkage in response to plaque accumulation has also been described. So far, the factors influencing positive or negative remodeling are uncertain. We hypothesized that vascular distensibility, a measure of vessel compliance, is related to compensatory enlargement. In 58 patients undergoing intravascular ultrasound interrogation of a de novo lesion prior to coronary intervention, the cross-sectional vessel area (VA), lumen area (LA) and plaque area (PA = VA minus LA) were measured at end diastole and end systole at the lesion site and at the proximal and distal reference segments. Positive remodeling was defined to be present when the VA at the lesion was > 1.05 times larger than that at the proximal reference (group A), negative remodeling when the VA at the lesion was < 0.95 of the reference site (group C) and in-between was considered to be intermediate (group B). Vessel compliance was measured by calculating vascular distensibility. Results showed a similar LA at the lesion site in all groups (4.18+/-2.18 vs. 4.36+/-1.19 vs. 3.74+/-1.81 mm2, NS) while VA and PA were significantly larger in group A (17.19+/-5.08 vs. 14.22+/-3.66 and 12.45+/-4.82 mm2, p = 0.005 and 13+/-4.55 vs. 9.95+/-3.58 and 8.7+/-3.83, p = 0.003, respectively). Vascular distensibility at the proximal reference segment was significantly greater in group A (3.55+/-2.67 vs. 1.25+/-1.03 and 0.85+/-0.73 mmHg(-1), p < 0.001) with a positive correlation between remodeling and distensibility (R = 0.52, p < 0.001). In a multiple regression model including clinical and lesional factors, distensibility was the only predictor of remodeling. In conclusion, these results suggest that compensatory vessel enlargement occurs to a greater degree in patients with increased coronary artery distensibility, which appears to be a predictor for positive remodeling.

Adaptation, Physiological↗

A new biomechanical perfusion system for ex vivo study of small biological intact vessels.

The vascular endothelium transduces physical stimuli within the circulation into physiological responses, which influence vascular remodelling and tissue homeostasis. Therefore, a new computerized biomechanical ex vivo perfusion system was developed, in which small intact vessels can be perfused under well-defined biomechanical forces. The system enables monitoring and regulation of vessel lumen diameter, shear stress, mean pressure, variable pulsatile pressure and flow profile, and diastolic reversal flow. Vessel lumen measuring technique is based on detection of the amount of flourescein over a vessel segment. A combination of flow resistances, on/off switches, and capacitances creates a wide range of pulsatile pressures and flow profiles. Accuracy of the diameter measurement was evaluated. The diameters of umbilical arteries were measured and compared with direct ultrasonographic measurement of the vessel diameter. As part of the validation the pulsatile pressure waveform was altered, e.g., in terms of pulse pressure, frequency, diastolic shape, and diastolic reversal flow. In a series of simulation experiments, the hemodynamic homeostasis functions of the system were successfully challenged by generating a wide range of vascular diameters in artificial and intact human vessels. We conclude that the system presented may serve as a methodological and technical platform when performing advanced hemodynamic stimulation protocols.

Animals↗