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Contractile proteins in myocardial cells are regulated by factor(s) released by blood vessels.

The importance of perfusion of the coronary vasculature in the regulation of ATPase activity of myosin in rat myocardial cells has been studied. Quantitative histochemistry was used to determine the activity of the enzyme among cells in tissues that had been either perfused through the coronary system or superfused over the surface of the tissue. Enzymatic activity was measured in cryostatic sections from three different preparations: 1) hearts frozen immediately after removal from the animal; 2) isolated hearts frozen after they had been perfused through the coronary circulation; and 3) isolated papillary muscles or trabeculae that had been superfused after dissection and then frozen. ATPase activity was measured in the isolated tissues at different times after dissection. Both calcium- and actin-activated myosin ATPase activities were uniform among cells in both the ventricles of the hearts frozen immediately after dissection and those that had been perfused through the coronary system. In the superfused tissues, although calcium-activated myosin ATPase activity was uniform, actin-activated ATPase activity was not uniform for about 90 minutes after the dissection, the period required for stabilization of the contraction. The pattern of nonuniformity was complex. In all bundles the lowest enzymatic activity was found in the most superficial cells. In very thin bundles, the cells in the center had the highest activity. In the medium and thicker bundles, there were three concentric zones of actin-activated ATPase activity, the superficial zone with the lowest activity, an intermediate zone with high activity, and a central zone with lower activity. Within each zone, the activity was often greatest in myocardial cells immediately next to blood vessels even though the blood vessels had not been perfused. The transverse distribution of ATPase activity of myosin could be explained by a mechanism in which cells in blood vessels (presumably endothelium) release a substance that upregulates myosin ATPase activity, with the rate of release being related to the local oxygen tension. A downregulating substance may also be produced. The period of stabilization of the contraction coincides with the time during which the pattern of actomyosin ATPase activity is nonuniform. These data suggest that the contractile proteins are regulated by a substance produced by blood vessels in proportion to the local PO2, and possibly in relation to shear force on the vascular endothelium.

Adenosine Triphosphatases↗

Plug effect of erythrocytes in capillary blood vessels.

As an idealized problem of the motion of blood in small capillary blood vessels, the low Reynolds number flow of plasma (a newtonian fluid) in a circular cylindrical tube involving a series of circular disks is studied. It is assumed in this study that the suspended disks are equally spaced along the axis of the tube, and that their centers remain on the axis of the tube and that their faces are perpendicular to the tube axis. The inertial force of the fluid due to the convective acceleration is neglected on the basis of the smallness of the Reynolds number. The solution of the problem is derived for a quasi-steady flow involving infinitesimally thin disks. The numerical calculation is carried out for a set of different combinations of the interdisk distance and the ratio of the disk radius to the tube radius. The ratio of the velocity of the disk to the average velocity of the fluid is calculated. The different rates of transport of red blood cells and of plasma in capillary blood vessels are discussed. The average pressure gradient along the axis of the tube is computed, and the dependence of the effective viscosity of the blood on the hematocrit and the diameter of the capillary vessel is discussed.

Blood Flow Velocity↗

A quantitative investigation of immunocytochemically stained blood vessels in normal, benign, premalignant and malignant human oral cheek epithelium.

The present study was designed to determine whether increased vascularity occurs during malignant transformation of human oral cheek epithelium. Nine normal (N) samples were taken from the resection margins of benign lesions; the pathological lesions were classified as chronic inflammation (CI; n = 11), fibrous hyperplasia (FH; n = 12), lichen planus (LIP; n = 8), dysplasia (DYS; n = 5), squamous cell carcinoma (SCC; n = 25; well differentiated [SCCWD]; n = 10; moderately to poorly differentiated [SCCMPD]; n = 15) and epithelium adjacent to carcinomas (EAC; n = 6). Sections were stained with monoclonal antibody (mAb) against vimentin using an ABC immunoperoxidase technique. All blood vessels present within a depth of 0.9 mm of lamina propria were quantified irrespective of their morphology. The blood vessel parameters quantified were volume density (VVBV, CT), number per unit area (NABV, CT), length per unit volume (LVBV, CT) and mean transverse sectional area (ABV). VVBV, CT increased significantly between normal and all pathological groups. Amongst the pathological groups, statistical differences were detected between CI and SCC, CI and EAC, FH and SCCWD, FH and EAC, LIP and SCC, LIP and EAC, DYS and SCCWD and DYS and EAC. The EAC group had the highest VVBV, CT and the values of NABV, CT and LVBV, CT were significantly higher in all the pathological groups when compared with the normal group. No significant differences were detected between any of the pathological group. The parameter ABV increased significantly between normal and DYS, FH, SCC, EAC, FH and EAC, FH and SCC, CI and EAC, CI and SCC, LIP and EAC and LIP and SCC. Spearman rank correlations detected a positive correlation between the severity of oral lesions and all of the blood vessel parameters. We conclude that a mAb against vimentin improved the identification of smaller blood vessels and the blood vessel data suggest that angiogenesis occurs in premalignant and malignant lesions of human oral cheek epithelium. Angiogenesis seems to play an essential role in sustaining the actively growing and transforming cells.

Adolescent↗

Degree of differentiation and blood vessel proximity in B16 melanoma.

Corded structures consisting of rows of viable tumour cells around a central blood vessel are present in a number of transplantable mouse tumours, including transplantable B16 melanomas. These tumours were used to assess, by stereological means at the EM level, the range of differentiation of the melanoma cells, according to their position in relation to the central blood vessel. The mitotic index was also determined for perivascular and peripheral tumour cells separately. Furthermore, the transition of peripherally located cells into necrotic tumour cells is described at the EM level. Results shown an important increase in differentiation in peripheral tumour cells, whereas the mitotic index is highest in perivascular cells. Necrotic peripheral cells show features of apoptotic necrosis, together with necrosis of the ischaemic type. Results indicate that both proliferation and differentiation of melanoma cells are related to their position around a central blood vessel, and that peripheral necrosis is not exclusively due to lack of oxygen.

Animals↗

Assembly of trunk and limb blood vessels involves extensive migration and vasculogenesis of somite-derived angioblasts.

Vascular development requires the assembly of precursor cells into blood vessels, but how embryonic vessels are assembled is not well understood. To determine how vascular cells migrate and assemble into vessels of the trunk and limb, marked somite-derived angioblasts were followed in developing embryos. Injection of avian somites with the cell-tracker DiI showed that somite-derived angioblasts in unperturbed embryos migrated extensively and contributed to trunk and limb vessels. Mouse-avian chimeras with mouse presomitic mesoderm grafts had graft-derived endothelial cells in blood vessels at significant distances from the graft, indicating that mouse angioblasts migrated extensively in avian hosts. Mouse graft-derived endothelial cells were consistently found in trunk vessels, such as the perineural vascular plexus, the cardinal vein, and presumptive intersomitic vessels, as well as in vessels of the limb and kidney rudiment. This reproducible pattern of graft colonization suggests that avian vascular patterning cues for trunk and limb vessels are recognized by mammalian somitic angioblasts. Mouse-quail chimeras stained with both the quail vascular marker QH1 and the mouse vascular marker PECAM-1 had finely chimeric vessels, with graft-derived mouse cells interdigitated with quail vascular cells in most vascular beds colonized by graft cells. Thus, diverse trunk and limb blood vessels have endothelial cells that developed from migratory somitic angioblasts, and assembly of these vessels is likely to have a large vasculogenic component.

Animals↗

The distribution of the anticancer drug Doxorubicin in relation to blood vessels in solid tumors.

PURPOSE: Anticancer drugs gain access to solid tumors via the circulatory system and must penetrate the tissue to kill cancer cells. Here, we study the distribution of doxorubicin in relation to blood vessels and regions of hypoxia in solid tumors of mice. EXPERIMENTAL DESIGN: The distribution of doxorubicin was quantified by immunofluorescence in relation to blood vessels (recognized by CD31) of murine 16C and EMT6 tumors and human prostate cancer PC-3 xenografts. Hypoxic regions were identified by injection of EF5. RESULTS: The concentration of doxorubicin decreases exponentially with distance from tumor blood vessels, decreasing to half its perivascular concentration at a distance of about 40 to 50 mum, The mean distance from blood vessels to regions of hypoxia is 90 to 140 microm in these tumors. Many viable tumor cells are not exposed to detectable concentrations of drug following a single injection. CONCLUSIONS: Limited distribution of doxorubicin in solid tumors is an important and neglected cause of clinical resistance that is amenable to modification. The technique described here can be adapted to studying the distribution of other drugs within solid tumors and the effect of strategies to modify their distribution.

Animals↗

On the adaptive detection of blood vessels in retinal images.

This paper proposes an automated blood vessel detection scheme based on adaptive contrast enhancement, feature extraction, and tracing. Feature extraction of small blood vessels is performed by using the standard deviation of Gabor filter responses. Tracing of vessels is done via forward detection, bifurcation identification, and backward verification. Tests over twenty images show that for normal images, the true positive rate (TPR) ranges from 80% to 91%, and their corresponding false positive rates (FPR) range from 2.8% to 5.5%. For abnormal images, the TPR ranges from 73.8% to 86.5% and the FPR ranges from 2.1% to 5.3%, respectively. In comparison with two published solution schemes that were also based on the STARE database, our scheme has lower FPR for the reported TPR measure.

Algorithms↗

Effect of thrombin on isolated canine blood vessels.

The aim of the present study was to assess whether or not thrombin affects vascular smooth muscle activity by a direct action on the blood vessel wall. In isolated saphenous veins and femoral and pulmonary arteries thrombin did not affect basal tension, but in pulmonary and portal mesenteric veins it caused contraction. In saphenous and femoral veins and in femoral and pulmonary arteries the enzyme depressed contractions evoked by alpha-adrenergic stimulation. In the saphenous vein thrombin also depressed contractions induced with acetylcholine or potassium ions. In this blood vessel the relaxation caused by thrombin was abolished by antithrombin III and the tripeptide D-phenylalanine-proline-arginine-CH2Cl, a specific inhibitor of the enzyme center of thrombin. In pulmonary and portal mesenteric veins, thrombin potentiated the contractile response to norepinephrine. These contractile effects of thrombin were also abolished by D-phenylalanine-proline-arginine-CH2Cl. Thus, thrombin causes relaxation or contraction of blood vessels through a direct action on the blood vessel wall. These effects are due to its proteolytic activity.

Acetylcholine↗

Mast cell population density, blood vessel density and histamine content in normal human skin.

Mast cell population density was determined in normal skin from two regions of the arm of several healthy men and compared with blood vessel density and histamine concentration in the same sites. Mast cell and blood vessel counts were made in 1--1.5 micrometer thick plastic sections, by light microscopy and tissue-histamine concentrations were determined by automated fluorimetric analysis. Statistically significant correlations were found between mast cell counts, blood vessel counts and histamine content in skin from the upper arm but no similar correlations were obtained in the forearm. Anatomical differences between the two sites may have been the cause of this discrepancy. Wide variations in mast cell counts and blood vessel density were found in different sections from the same biopsy samples which confirms the notion that dermal mast cells are unevenly distributed. Analysis of variance of the mast cell counts showed that the variance between sections from different blocks from the same biopsy samples was greater than the variance between adjacent biopsies. There was also a marked variation in the histamine content between biopsy samples from sites only 2 cm apart in the same subject.

Adult↗

Blood flow rate and total blood flow related to length density and total length of blood vessels in mini-pig urinary bladder after chronic outflow obstruction and after recovery from obstruction.

Chronic partial bladder outlet obstruction was created in mini-pigs by implanting a 6-7 mm ring around the proximal urethra. After a median obstruction period of 63 days the ring was removed, and after a median recovery period of 60 days the animals were sacrificed. At each study occasion the blood flow rate (ml per 100 g per min) was measured by washout of locally injected 133Xe in the bladder wall and the washout curves analyzed by the corrected initial slope method. Stereological estimation of length density and total length of blood vessels in the bladder were performed. The results can be summarized as follows: (1) no differences in the blood flow rate at the time of ring implantation, obstruction, or recovery, (2) no decrease in the blood flow rate in normal bladders after bladder distension, (3) a significant decrease in blood flow rate in obstructed bladders after distension, (4) a 6-fold increase in total bladder blood flow after obstruction, (5) an unchanged blood flow per length of blood vessels per min during the study, (6) no changes in length densities of blood vessels during the study, and (7) a 7-fold increase in total length of blood vessels after obstruction and reversion to control level after recovery. The unchanged blood flow per length of vessels implies that capillary proliferation matched the increased bladder mass during the study.

Animals↗

Intraepithelial blood vessels in the vomeronasal neuroepithelium of the rat. A light and electron microscopic study.

Epithelial-vascular relationships are established during the development of the vomeronasal neuroepithelium of the rat. Special attention is given to the fine structure of the endothelial wall of intra-epithelial vessels, to ultrastructural aspects of the neuronal-vascular relationships, and to the appearance of inclusion bodies in the neuronal cells adjacent to these vessels. The neuronal perikarya surrounding the blood vessels are filled with highly developed smooth endoplasmic reticulum. Possible functional implications of the vascularization of the neuroepithelium of the vomeronasal organ in mediating olfacto-endocrine relationship are discussed. It is suggested that the intra-epithelial blood vessels are at least supportive and nutritive in nature, while their implication in an olfacto-endocrine connection remains obscure.

Animals↗

Responses of bone and joint blood vessels in cats and rabbits to electrical stimulation of nerves supplying the knee.

1. Experiments were performed to assess the extent to which knee joint blood flow in cats and rabbits is affected by electrical stimulation of the nerve supply to the knee. 2. Absolute changes in blood flow were measured using the radiolabelled microsphere (approximately 15 microns) technique whilst relative changes in blood flow were assessed using laser Doppler flowmetry. 3. Despite deep general anaesthesia, sympathetic nerve fibres innervating cat knee joint blood vessels showed marked 'tone'. 4. Blood flow to the joint capsule (synovium and overlying fibrous and areolar tissues) was substantially reduced (by approximately 90% in the cat and approximately 45% in the rabbit) during electrical stimulation of the articular nerve supply. 5. The percentage change in the laser Doppler flowmeter signal did not differ significantly from the percentage change in blood flow measured by microsphere technique. 6. Blood vessels in the cancellous bone of the distal femur (condyles) and proximal tibia (plateau) appear to be innervated by vasoconstrictor fibres which reach their effectors via the articular nerves. However, the cortical bone and red marrow of the diaphysis of the femur do not receive such innervation. 7. The potency of the vasoconstrictor influences acting on joint blood vessels could be of relevance in the pathogenesis of inflammatory joint diseases.

Anesthesia, General↗

[Pathological changes of the blood vessels in rabbit femoral head with glucocorticoid-induced necrosis].

OBJECTIVE: To observe the pathological changes in the blood vessels in rabbit femoral head with glucocorticoid-induced necrosis and investigate the pathogenesis of glucocorticoid-induced osteonecrosis. METHODS: Twenty New Zealand white rabbits were randomly divided into two groups, namely group A. which was injected with horse serum and prednisone and group B as the control group. Chinese ink was injected into the femoral cavity of the rabbits to observe the blood vessels in the femoral head under optical microscope and the femoral head was examined histopathologically. RESULTS: Compared with the normal control group, the rabbits in group A had significantly decreased number of perfused vessels, which was featured by defective perfusion, osteocytie pyknosis or necrosis, increase of empty ostoocyte lacunae and fat cells, decrease of hematopoietic tissue, and blood vessel occlusion. CONCLUSION: Vascular occlusion and vasculitis due to glucocorticoid treatment may cause avascular necrosis of the femoral head.

Animals↗

Selective photothermolysis of blood vessels following flashlamp-pumped pulsed dye laser irradiation: in vivo results and mathematical modelling are in agreement.

Laser therapy using the pulsed dye laser is the standard treatment for port-wine stains (PWS). But the mechanism of action has not been elucidated completely, yet. The dorsal skin-fold chamber model in hamsters was used to investigate the effects of laser treatment (lambda(em)=585 nm; pulse duration: 0.45 ms; fluence: 6 J per cm2) on blood vessels. Vessels (n=3394) were marked with FITC dextran (MW 150 kDa) and diameters (2-186 microm) were measured using intravital fluorescence microscopy up to 24 h following irradiation. Histology (H&E, TUNEL, CD31) was taken 1 or 24 h after irradiation. The experimental results were compared with the predictions of a mathematical model based on the finite-element method. Following irradiation treatment the number of unperfused vessels decreases with decreasing vessel diameter in vivo. Histology indicated a restriction of tissue injury to the irradiated area after 1 h. Blood vessels contained aggregated red blood cells. After 24 h tissue damage occurred also outside the irradiated area and thrombus formation was visible. These results were in agreement with the mathematical calculations. In addition to initial physical effects after pulsed dye laser treatment delayed biological processes contribute significantly to the reduction of perfused blood vessels. Because of incomplete photocoagulation of smaller blood vessels (diameter 2-16 microm) a complete bleaching of PWS seems to be unlikely.

Animals↗

Histochemical study on the activity of some oxidative and hydrolytic enzymes in the normal human endometrium blood vessels and at various intervals after applying the intra uterine contraceptive device.

The paper intends to study the cytoenzymological modifications of the human endometrium blood vessels after applying the intrauterine contraceptive device for a long period of time. The results were different according to the: type of the enzyme-ATP-ase, Lactatdehydrogenase, Leucineaminopeptidase, NADH2-citochrome-c-reductase, the components of the blood vessel wall (intima, media, adventitia), the blood vessel diameter, the hormonal cyclic stage.

Adenosine Triphosphatases↗

Heterogeneous distribution of [3H]alpha,beta-methylene ATP binding sites in blood vessels.

A radioligand binding assay and autoradiographic localisation of P2X-purinoceptors were carried out in several different blood vessels from rat, guinea-pig and rabbit by using [3H]alpha,beta-methylene ATP ([3H]alpha,beta-MeATP) as the radioligand. The radioligand binding assay on rabbit ear artery showed that the binding process was saturable, and a high density of P2X-purinoceptors was observed. Autoradiographic localisation showed that the specific [3H]alpha,beta-MeATP binding sites were only associated with the smooth muscle of the blood vessels. Semi-quantitation of the autoradiographs revealed significant differences in the densities of P2X-purinoceptors amongst the vessels studied. Generally the medium- and small-sized arteries had higher densities of P2X-purinoceptor than the elastic and large muscular arteries. In some large muscular arteries, such as the rabbit carotid, renal, hepatic and mesenteric, the outer region of vessel had a higher density of receptors than the inner region. The veins in this study were sparsely labelled, except portal veins where the longitudinal and circular layers of muscles were found to have different densities of P2X-purinoceptors. The results from this study provide direct evidence for the existence of P2X-purinoceptors in blood vessels; furthermore, the distribution of the P2X-purinoceptors is consistent with known pharmacological responses elicited by ATP in these vessels.

Adenosine Triphosphate↗

Assembly and processing of procollagen type III in chick embryo blood vessels.

The processing of [3H]proline-labeled procollagen III in excised chick embryo blood vessels was found to differ significantly from that of procollagen I in the same tissue. While first the amino propeptides and then the carboxyl propeptides were fairly rapidly cleaved from procollagen I, only the carboxyl propeptides were split off procollagen III, leaving pN-collagen III. This intermediate, which is only slowly converted to collagen III by loss of amino propeptides, was characterized by its sedimentation properties, isolation of the amino propeptide, and reaction with purified antibodies that are specific against bovine amino propeptide III. It is interchain disulfide-linked, both through the amino propeptide and the carboxyl ends of the collagen chains. The conversion of procollagen III to pN-collagen III either in blood vessels, or after isolation by a carboxyl procollagen peptidase obtained from chick tendon fibroblast cultures, is inhibited by 50 mM arginine. Underhydroxylated procollagen III was isolated from blood vessels treated with alpha, alpha'-dipyridyl. Its amino propeptides reacted with the above antibodies but were not linked to each other. In contrast, its carboxyl propeptides were interchain disulfide-bridged, supporting previous suggestions that the carboxyl propeptides play a role in the assembly of procollagen trimer.

Animals↗

Endothelial cell origin and migration in embryonic heart and cranial blood vessel development.

Using the QH-1 monoclonal antibody as a marker for quail endothelium, blockage and transplant experiments were carried out to construct fate maps for the embryonic endocardium, to determine whether preendocardial angioblasts are migratory, and, if these cells are migratory, to outline the pathways that they use for directed migration in embryonic blood vessel development. Recent descriptive studies using QH-1 to make immunofluorescent whole mounts have described a sequence of events leading to the establishment of the embryonic heart tube. These reports suggest that the pattern for the endocardium and cranial vasculature is established by migrating angioblasts that form vascular cords which mature into blood vessels. Blockage experiments showed that the ventrolateral edge of the anterior intestinal portal serves as a substrate for the directed migration of pre-endocardial angioblasts and that the pattern of the cranioventral vasculature forms independent of the source of angioblasts. Transplant experiments showed that the origin for endocardial angioblasts lies in mesodermal tissue just anterior to Henson's node, that these cells undergo directed migration to the pericardial area, and that angioblasts are pluripotent with the ability to form different blood vessels. The transplant studies also showed that the embryonic mesoderm may contribute to extraembryonic blood vessels on the embryonic yolksac. These results support the hypothesis that embryonic blood vessels may develop by either the vasculogenesis or by the angiogenesis mechanism, and show that the endocardium of the primitive heart tube forms by vasculogenesis.

Animals↗