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Lymphatic vessels in inflamed human dental pulp.

Investigation has been performed on both the light and electron microscopic characteristics of the lymphatic vessels present in the dental pulp of human teeth which have been affected by serious carious lesions. These conditions provoke a severe inflammatory response resulting in structural and functional modifications of the tissue; increase of the tissue pressure is followed by the need for a more intensive lymphatic drainage. In the inflamed pulps, dilated lymphatic vessels with distended walls and "open junctions" between endothelial cells are detectable. On the other hand they lack certain endothelial structures which characterize the morphology of these vessels under normal conditions. In the pulpal regions affected by fibrotic proliferation shrunken vessels with irregular profiles are present. From these observations it is possible to obtain other information on the mechanisms regulating the lymphatic drainage in different structural and functional conditions of the interstitium.

Dental Pulp↗

The role of alpha- and beta-adrenoceptors in the response to noradrenaline of lymphatic vessels isolated from the bovine mesentery.

The role of postsynaptic adrenoceptors in the spontaneous activity of isolated bovine mesenteric lymphatic vessels was characterized. Low concentrations of noradrenaline (less than 10(-6) M) increased the amplitude and the frequency of the spontaneous contractions whereas high concentrations (less than 10(-6) M) depressed the activity. beta-Adrenoceptor blockade with propranolol enhanced the stimulation by noradrenaline and suppressed the inhibition. alpha 1-Blockade by prazosin or alpha 2-blockade by idazoxan antagonized the stimulation by noradrenaline and potentiated the inhibition. Activation of alpha 1-adrenoceptors by methoxamine, or of alpha 2-adrenoceptors by clonidine, stimulated lymphatic activity. The increases in the amplitude and frequency of the spontaneous contractions produced by each agonist were competitively antagonized by prazosin and idazoxan, respectively. Our results confirm the presence of postjunctional beta-, alpha 1-and alpha 2-adrenoceptors in lymphatic vessels and show that each of these receptors plays an important role in the adrenergic regulation of the spontaneous activity, with beta-adrenoceptors mediating inhibition, and alpha 1- and alpha 2-adrenoceptors mediating stimulation.

Animals↗

Independent prognostic impact of lymphatic vessel density and presence of low-grade lymphangiogenesis in cutaneous melanoma.

The aim of this study was to determine lymphatic vessel density (LVD) in a series of nodular melanoma and correlate the findings with the expression of several angiogenic factors, including vascular endothelial growth factor-C, basic fibroblast growth factor (bFGF), patient survival, and clinico-pathologic data. Patients with nodular melanoma and complete follow-up information were included. Lymphatic vessels were immunostained with the LYVE-1 and Podoplanin antibodies, and LVD was evaluated in both intra- and peri-tumoral (LVDpt) areas. Median LVD was 6.3 and 12.5 vessels/mm(2) in intra- and peri-tumoral areas, and coexpression of LYVE-1 and Ki-67/MIB-1 in lymphatic endothelial cells within the tumor was demonstrated, indicating active but low-grade lymphangiogenesis. Increased LVDpt was significantly associated with localization on the extremities (P = 0.005), decreased tumor thickness (P = 0.036), absence of vascular invasion (P = 0.004), brisk lymphocytic infiltration (P = 0.018), low proliferative rate by Ki-67 (P = 0.011), increased bFGF expression in tumor cells (P = 0.01) as well as in endothelial cells (P = 0.008), and decreased tumor cell expression of Ephrin-A1 (P = 0.009). Decreased LVD in intra-tumoral areas and LVDpt both predicted improved survival rates in multivariate analyses (for LVDpt, Hazard ratio: 2.1, P = 0.009). We found that decreased LVD was present in thicker and more proliferative tumors (Ki-67) and that increased LVD was significantly associated with improved patient survival in multivariate analysis. In addition, our data suggest the presence of low-grade intra-tumoral lymphangiogenesis in melanoma and a stimulating role of bFGF in lymphangiogenesis.

Cell Division↗

The lymphatic vessels and their relationship to lymph formation in the human urinary bladder.

After endoscopic transurethral biopsies of normal human urinary bladder, an extensive network of small initial lymphatic vessels was depicted by means of light and electron microscopy. Using light microscopy, lymphatic vessels were seen in the mucosa and submucosa and formed a complex network in the detrusor muscular coat. These lymphatics were characterized by an irregular and attenuated wall and increased in number and size from the superficial to the deeper region of the bladder. Ultrastructurally, the lymphatic wall was characterized by endothelial cells joined together end-to-end or by complicated interdigitations. Often intercellular channels and gaps between two contiguous endothelial cells were present. A broad network of elastic and collagen fibers joined the lymphatic endothelial wall to the neighboring connective tissue. Nevertheless, as far as the fibrillar component was concerned, the vesical intramuscular lymphatic endothelial wall lacked elastic fibers. These anatomic variations were examined in reference to lymph formation in an organ (the urinary bladder) which undergoes continual changes in volume and pressure.

Adult↗

Ultrasonographic evidence of abnormal lymphatic vessels in young men with adult Wuchereria bancrofti infection in the scrotal area.

PURPOSE: We determined the prevalence and magnitude of dilatation of the lymphatic vessels of the spermatic cord in men infected with Wuchereria bancrofti, which is known major cause of hydrocele in the tropics. MATERIALS AND METHODS: Scrotal ultrasound was performed with a 7.5 MHz, transducer in 78 men from Recife, Brazil (endemic for filariasis) and in 15 from a nonendemic area. RESULTS: Among men from Recife the lymphatic vessels were dilated (1.3 to 15.0 mm., mean 3.8) at the location of the adult worm. Vessel diameter was not associated with hydrocele. CONCLUSIONS: Lymphatic dilation was observed in all men with ultrasonographically detectable W. bancrofti infection, even those who were asymptomatic.

Adolescent↗

[The TEM investigations of lymphatic vessels in the acute inflamed dental pulps].

OBJECTIVE: The purpose of this study was to investigate the possible ultrastructural modifications of the lymphatic capillaries in the acute inflamed dental pulps. METHODS: The ultrastructural features of the lymphatic vessels endothelial wall in the human normal and acute inflamed dental pulps were investigated by TEM using conventional methods. RESULTS: The lymphatic capillaries in normal dental pulp were characterized by a thin wall with an irregular profile. The endothelial cells were joined one another by specialized junctional complexes, such as end-to-end contacts, overlapping and more complex interdigitation. Opening junctions were never present in these vessels. The cytoplasm of the endothelial cells was rich in micropinocytotic vesicles. In the acute inflamed pulpal tissue, the lymphatic vessels were dilated and the intercellular adjoining structure were less intricate, end-to-end contacts and overlaping were most frequent ones. Opening junctions were frequently detectable. In particular, the micropinocytotic vesicles were almost absent. CONCLUSION: In the acute inflamed pulpal tissue, the modification occurs in the diameter of lymphatic capillaries, intercellular adjoining structures and the amounts of micropinocytotic vesicles, so we thought that a network of lymphatic vessels drained the dental pulp.

English Abstract↗

[Saccular initial segments of the lymphatic vessel system].

It is commonly said that the lymphatic system begins "blindly" as saccular outpocketings. In order to examine these saccular outpocketings, 120 injections into the conjunctival lymphatics of 60 bovine postmortem eyes were carried out, measuring the level of injection pressure and simultaneously documenting the various filling stages photographically. 20 trials were selected for further analysis. We recorded low initial pressures when the tip of the needle was situated close to a larger lymphatic vessel and the coloured solution (1% aqueous Berliner Blue) as possibly applied intravascularly. Higher initial pressures were seen on positioning inside fine networks of vessels. Extremely high initial pressures without any visible filling of vessels but in the presence of simultaneously increasing depots of dye were probably caused by absent or insufficient connection between the tip of the needle and a vessel. During lymphography numerous coarser and finer, tube-like projections (saccular outpocketings) filled, from which further progression of the coloured solution could only be observed when higher injection pressures were applied. We were able to prove that such segments had connections to neighbouring vessels as well as forming plexus of their own. Based on our findings we have reason to doubt the existence of tube-like initial segments in the lymphatic system. Rather in the conjunctiva of the bovine eye this system has the structure of a fine network where tube-like segments can be demonstrated as temporary filling stages.

Animals↗

Onset of abnormal blood and lymphatic vessel function and interstitial hypertension in early stages of carcinogenesis.

Recent improvements in diagnostic methods have opened avenues for detection and treatment of (pre)malignant lesions at early stages. However, due to the lack of spontaneous tumor models that both mimic human carcinogenesis and allow direct optical imaging of the vasculature, little is known about the function of blood and lymphatic vessels during the early stages of cancer development. Here, we used a spontaneous carcinogenesis model in the skin of DNA polymerase eta-deficient mice and found that interstitial fluid pressure was already elevated in the hyperplastic/dysplastic stage. This was accompanied by angiogenic blood vasculature that exhibited altered permeability, vessel compression, and decreased alpha-smooth muscle actin-positive perivascular cell coverage. In addition, the lymphatic vessels in hyperplastic/dysplastic lesions were partly compressed and nonfunctional. These novel insights may aid early detection and treatment strategies for cancer.

Animals↗

Lymphatic vessel density in vocal cord carcinomas assessed with LYVE-1 receptor expression.

BACKGROUND AND PURPOSE: Early stage vocal cord carcinomas are usually cured by radiation therapy despite the use of portals that exclude the cervical lymph nodes. We investigated whether the lymphatic vessel density (LVD) of vocal cord carcinomas differs from that of other head and neck carcinomas. PATIENTS AND METHODS: Deparaffinized tissue from tumors of 60 patients diagnosed with head and neck squamous cell carcinoma (HNSCC) were immunostained for LYVE-1, a novel lymphatic vessel marker. Twenty-two had vocal cord carcinoma. Tumor blood vessel density (BVD) was assessed using immunostaining for CD31. RESULTS: Tumor overall LVD, including both intra- and peritumoral lymph vessels, was 10-fold lower than the BVD (5 counts/mm2 vs. 52 mm(-2), respectively). A high LVD was associated with a high BVD (P = .002), but neither was associated with the tumor size. Both tumor LVD and BVD were lower in vocal cord carcinomas than in HNSCCs arising at other sites (median, 0 vs. 7 mm(-2), P=.016; and median, 36 vs. 52 mm(-2), P = .006, respectively). Only one vocal cord carcinoma was associated with a regional metastasis at the time of the diagnosis. Among the rest of the cases tumor size was a better predictor for the presence of regional metastases than tumor BVD or LVD in a logistic regression model (odds ratio 2.2, 95% CI 1.1-4.5). CONCLUSION: Vocal cord carcinomas have a low lymph vessel density as compared with HNSCCs arising at other sites.

Adult↗

High LYVE-1-positive lymphatic vessel numbers are associated with poor outcome in breast cancer.

PURPOSE: The clinical significance of intratumoral or peritumoral lymph vessel density is not known. LYVE-1, a lymphatic endothelium-specific hyaluronan receptor, is a novel lymphatic vessel marker that is expressed on lymph vessel endothelial cells of both normal and neoplastic tissues. EXPERIMENTAL DESIGN: We investigated expression of LYVE-1 by immunohistochemistry in 180 unilateral, invasive ductal breast carcinomas and assessed the presence and density of lymph vessels within the tumor and at the tumor periphery. RESULTS: A minority (12%) of breast carcinomas had intratumoral lymph vessels, whereas peritumoral lymph vessels were identified in almost all cases (94%). No substantial association was found between the number of LYVE-1-positive vessels and the number of CD31 or vascular endothelial growth factor receptor-3-positive vessels, or vascular endothelial growth factor-C expression. The number of metastatic axillary lymph nodes increased in parallel with increasing lymph vessel counts (P = 0.033). A higher than the median lymph vessel count at the tumor periphery was significantly associated with unfavorable distant disease-free survival and overall survival. Women with high peritumoral lymph vessel density had only 58% (95% confidence interval, 46-70%) 5-year distant disease-free survival as compared with 74% (66-83%) among those with a low peritumoral lymph vessel density (P = 0.0088). In contrast, the presence of intratumoral lymph vessels was associated with neither axillary nodal status nor survival. Lymph vessel density was not an independent prognostic factor in a multivariate survival analysis. CONCLUSIONS: A high peritumoral lymph vessel density is associated with a poor outcome in ductal breast cancer.

Adult↗

5-HT decreases contractile and electrical activities in lymphatic vessels of the guinea-pig mesentery: role of 5-HT 7-receptors.

1 Constriction measurements and intracellular microelectrode recordings were performed in vitro on lymphatic vessels isolated from the guinea-pig mesentery to investigate whether 5-hydroxytryptamine (5-HT) affected lymphatic pumping and smooth muscle membrane potential. 2 5-HT decreased in a concentration-dependent manner the frequency of constrictions induced by intraluminal vessel perfusion. In nonperfused vessels, 5-HT hyperpolarized the lymphatic smooth muscle membrane potential and decreased the frequency and amplitude of spontaneous transient depolarizations (STDs). 3 The actions of 5-HT were significantly reversed by the 5-HT(7) receptor antagonist (2R)-1-[(3-hydroxyphenyl)sulfonyl]-2-[2-(4-methyl-1-piperidinyl)ethyl]pyrrolidine (SB269970, 0.5 micro M) and by the 5-HT(1/2/5/7) receptor antagonists methysergide (0.5 micro M), and were mimicked by the 5-HT(1/7)-receptor agonist, 5-CT. 4 The 5-HT(4)-receptor antagonists 1-methyl-1H-indole-3-carboxylic acid [1-2-[(methyl sulfonyl) amino] ethyl-4-piperidinyl] methyl ester (GR113808, 1 micro M) and (1-piperidinyl) ethyl 1H-indole 3-carboxylate (SB203186, 1 micro M) did not significantly affect the 5-HT-induced responses. The 5-HT(4)-receptor agonist 1-(4-amino-5-chloro-2-methoxy-phenyl)-3-[1-(2-methylsulfonylamino) ethyl-4-piperidinyl]-1-propanone hydrochloride (RS67506) decreased the constriction frequency, albeit only at 50 micro M and without affecting the smooth muscle membrane potential. 5 Responses to 5-HT were attenuated by the nitric oxide synthase inhibitor N(G)-nitro L-arginine (100 micro M), whereas indomethacin (10 micro M) and tetrodotoxin (1 micro M) were without effects. 6 5-HT-induced responses were inhibited by the ATP-sensitive K(+) channel blocker, glibenclamide (10 micro M) and the cAMP-dependent protein kinase inhibitor N-[2-(p-bromociannamylamino)-ethyl]-5-isoquinolinesulfonamide-dichloride (H89, 10 micro M) blocked the hyperpolarization. 7 These results suggest that 5-HT modulates the rate of lymphatic vessel pumping by eliciting K(ATP) channel-mediated smooth muscle hyperpolarization and decrease in STD activity, which appear to be mediated by activation of 5-HT(7) receptors coupled to cAMP production.

Animals↗

Lymphatic vessel density as a prognostic indicator for patients with stage I cervical carcinoma.

Lymphatic vessel density (LVD) was recently considered important for spread of several malignant tumors. However, there are no reports describing the situation in cervical carcinoma. The purpose of this study was to investigate whether LVD could serve as a risk factor for nodal metastasis and recurrence of cervical carcinoma in 147 cases of stage I patients. Other questions were if depth of invasion, proliferation rate, and tumor size could be used as predictive markers for Chinese patients with cervical carcinoma. The lymphatics were determined by immunohistochemistry with the antibody to LYVE-1, a specific lymphatic endothelium marker, and average LVD was calculated. Double immunohistochemistry and double immunofluorescence staining for LYVE-1/CD34 were used to distinguish between lymphatic and blood vessels. The results showed that average LVD in cervical carcinoma was statistically associated with inflammatory cell infiltration of carcinoma tissues, but not associated with other pathological parameters. Average LVD of the cases with nodal metastasis or recurrence was significantly higher than the cases without metastasis and recurrence in both stage IA and stage IB cervical carcinomas. The correlation between both depth of invasion and tumor size with nodal metastasis and recurrence of cervical carcinoma was also statistically significant. Ki-67 labeling index was found to be correlated with the recurrence of disease, but not to be correlated with nodal metastasis. We concluded that for the patients with stage I cervical carcinoma, increased LVD could serve as a high-risk factor for nodal metastasis and recurrence. Depth of invasion and tumor size could also be useful indicators.

Biomarkers, Tumor↗

[Individual and age-related differences in the anatomy of the main deferent lymphatic vessels of the human heart and their applied significance].

One hundred human hearts of various age have been investigated. Structure, size of their main deferent lymphatic vessels are defined by the organ's form, sex and age of the persons. According to the position signs, extreme forms of their topography have been revealed. In the left--the course in the adventitia of the anterior wall of the pulmonary trunk and of the ascending aorta. In the left--the course in the adventitia of the right lateral wall of the ascending aorta and of the pulmonary trunk. The number of the extraorganic vessels, that bring lymph out of the heart, is from 1 up to 3. The anastomoses made between certain parts of the lymph nodes and the extraorganic lymphatic vessels in the transplanted and removed hearts are more economic.

Adolescent↗

[The myocytes of the lymphatic vessels].

Histo- and ultrastructure of myocytes of the lymphatic vessels has been studied in some farm animals. Architectonics, amount and interconnection of myocytes in the lymphangion wall have been investigated. Communicational and gap myo-myocytic contacts revealed give a possibility to suppose that there exists a direct connection between myocytes. This is important for conducting electrical stimulation from one cell to another. For the myocytes abundance of myofilaments, and in some--an essential accumulation of mitochondria are specific; they are morphological manifestation of contractile function of myocytes.

Animals↗

[Ultrastructure of the lymphatic vessels of the urinary bladder].

The fine structure and morphological aspects of superficial and deep lymphatic vessels of Chiroptera' bladder (Vesperugo savi and Rinolophus f.e.) have been studied, under seasonal, physiological conditions of different lymphatic flux (winter lethargic state and summertime). The endothelial walls of subepithelial, intramuscular and subserosal-peritoneal, lymphatic networks show an uninterrupted course together with both simple and complex intercellular contacts, constantly jointed by specialized junctional complexes, such as zonulae adhaerentes and occludentes. The abluminal surface is often almost entirely encircled by a thick layer of fibrillary connective tissue. Seasonal cytological modifications of possible importance and morphological aspects typical of the each individual network have not been detected in the lymphatic endothelium. On the other hand the abundance distribution of clear intracytoplasmic vesicles and the frequent occurrence of micropinocytotic vesicles in the luminal and abluminal membrane surface have been shown. Canalicular structures have also been demonstrated, even if quantitatively less numerous with respect to those seen in the chiliferous vessels of the same species of Chiroptera. The Authors believe that most of the transendothelial transport in the above mentioned lymphatic vessels occur through the micropinocytotic vesicles and also through the intra-endothelial channels made up by the vessel wall, without any intervention of intercellular contacts or specialized junctions. The possible role of substances within the interstitium in inducing the appearance of canaliculi in the endothelial wall is discussed.

Animals↗

Characterization of beta-adrenoceptor subtypes and indications for two cell populations in isolated bovine mesenteric lymphatic vessels.

The pharmacological characterization of beta-adrenoceptor subtypes and the identification of two cell populations were investigated in isolated bovine mesenteric lymphatic vessels. The beta-adrenoceptor agonists isoprenaline, dobutamine and salbutamol concentration dependently decreased the amplitude and the frequency of spontaneous contractions and the amplitude of electrically induced contractions. The order of potency was isoprenaline greater than salbutamol greater than dobutamine. These effects were competitively antagonized by atenolol with pA2 values close to 7 with isoprenaline and dobutamine as agonists, and near 5.5 with salbutamol as the agonist. Noradrenaline concentration dependently reduced electrically induced contractions, an effect which was reversed to a slight enhancement after blockade of beta-adrenoceptors with propranolol (10(-6) M). These results confirmed the presence of postjunctional beta 1- and beta 2-adrenoceptor subtypes in lymphatic vessels and provide the first indication of the existence of two pharmacologically and functionally distinct cell populations, one of which exhibits pacemaker activity.

Adrenergic beta-Agonists↗

Endothelin-mediated constriction of prenodal lymphatic vessels in the canine forelimb.

Endothelin is a 21 amino acid peptide which is produced by the vascular endothelium and is believed to be the mediator of endothelium-dependent vasoconstriction. In the current study we assessed the ability of synthetic human endothelin-1 to affect prenodal lymphatic vessel contractility in the canine forelimb. Intralymphatic infusion of endothelin at 1.09 x 10(-9), 1.09 x 10(-8) and 1.09 x 10(-7) M significantly constricted lymphatic vessels as evidenced by dose-dependent increases in lymphatic perfusion pressure. The increase in lymphatic perfusion pressure seen during intralymphatic infusion of endothelin at 1.09 x 10(-8) M during the intra-arterial infusion of phentolamine was not significantly different from that seen prior to phentolamine, indicating that endothelin-mediated lymphatic constriction is not alpha-receptor mediated. Intra-arterial infusion of endothelin at three infusion rates significantly increased forelimb arterial, systemic and lymphatic perfusion pressures. The constriction seen when endothelin (1.09 x 10(-8) M) was infused intralymphatically in the intact lymphatic system was not significantly different from that observed when only the prenodal lymph vessel was perfused. This indicated that the lymph nodes and efferent lymph vessels do not contribute significantly to the lymphatic constriction produced by endothelin. These data are consistent with the hypothesis that endothelin may modulate lymphatic function under either normal or pathophysiological conditions.

Animals↗

VEGF121 induces proliferation of vascular endothelial cells and expression of flk-1 without affecting lymphatic vessels of chorioallantoic membrane.

We have studied the effect of VEGF(121) homodimer and VEGF(121/165) heterodimer on the chorioallantoic membrane (CAM) of 13-day-old chick embryos. The factors were applied in doses of 2-4 micrograms and the effects were evaluated macroscopically after 2 and 3 days. Histological studies were performed on semi- and ultrathin sections. Proliferation was studied according to the BrdU-anti-BrdU method on whole mounts and sections. The labeling density was quantified in whole mounts. The fractal dimension, D, of the vascular tree was assessed as a value for vascular bifurcation density. Both forms of VEGF induce brush-like vessel formation in the precapillary region. New capillaries are found in the stroma of the CAM, which normally does not contain capillaries. Our results show that VEGF(121) is a specific endothelial cell mitogen. A fourfold increase of BrdU-labeled endothelial cells is found after VEGF(121) application. The fractal dimension of the vascular tree increases from 1.26 in the controls to 1.44 (VEGF(121)) and 1.41 (VEGF(121/165)). The endothelial cells of the newly formed capillaries possess many mitochondria and micropinocytotic vesicles, but no fenestrations. These capillaries are obviously formed by intussusceptive microvascular growth. Signs of sprouting are almost absent. An effect on the lymphatic vessels of the CAM is not detectable. Compared to VEGF(165) and VEGF(121/165), VEGF(121) diffuses over a slightly greater distance. Using in situ hybridization, VEGF receptor-2 (flk-1/Quek1) and the homologous flt-4 (Quek2) receptor were studied in the CAM of normal quail embryos and after VEGF(121) application on the CAM of 11-day-old quail embryos. During normal development, flk-1 expression becomes restricted to vascular endothelial cells of large vessels in the stroma of the CAM. VEGF(121) application induces expression of flk-1 in capillaries that normally do not express the receptor. In the normal development of the CAM, flt-4 becomes restricted to endothelial cells of vessels that appear to be lymphatic vessels. Application of VEGF(121) does not alter flt-4 expression.

Allantois↗