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PubMed2005

Lymphatic vessel contractile activity and intestinal inflammation.

Edema is a consistent observation in inflammatory bowel disease (IBD), and immune responses are inevitable in inflammation. Because the lymphatic system is an integral part of both tissue fluid homeostasis and immune reactions, it is likely that lymphatics play a role in the complex etiology of IBD. Despite the consistent findings that the lymphatic system is altered during gastrointestinal inflammation, the majority of studies conducted on the disease only mention the lymphatic system in passing. The effects of inflammatory mediators on lymphatic vessel function also remain poorly defined, despite its essential role in immunity and prevention of tissue edema. Processes allowing effective lymph transport are altered during inflammation, however, the mode of alteration and reason why lymphatics are ineffective in inflammatory reactions need to be further investigated. In addition, these processes have not yet been examined in an appropriate animal model and little has been done using in vivo methods of investigation in any model of gastrointestinal inflammation. This paper reviews the role of the lymphatic system in intestinal inflammation, as well as the role of the inflammatory products in mediating lymphatic contractile function.

Animals↗
PubMed1994

Lymphatic drainage system after left radical neck dissection.

The thoracic duct is the main lymphatic vessel that drains most of the body's lymph and all of the intestinal chyle into the venous system. The thoracic duct may be ligated during left radical neck dissection (RND) without any significant sequelae. The lymphatic system must, therefore, have collateral channels. The present study shows an increased incidence of pleural effusion after left RND when compared to right RND. We suggest that this represents the inability of the collateral system to immediately accommodate the increased volume of chyle.

Carcinoma, Squamous Cell↗
PubMedDate not supplied

Osmotically absorbed water preferentially enters the cutaneous capillaries of the pelvic patch in the toad Bufo marinus.

Cutaneously absorbed water in anurans has two potential routes of movement from the skin interstitium into the body fluids, via the cutaneous capillaries and/or the lymphatic system. We investigated the lymphatic route at the pelvic patch skin under the influence of isoproterenol and arginine vasotocin in Bufo marinus by continuously aspirating lymph from the lymph sacs draining the pelvic patch while the animals absorbed water. Changes in body mass, lymph mass, and lymph osmolality were measured. If absorbed water entered the lymph space directly, we expected, relative to controls, (1) no difference in change in body mass, (2) lymph mass to be greater, and (3) lymph osmolality to be lower. None of these predictions were confirmed. We also tested the possibility that absorbed water was stored in the skin interstitium by measuring the surface density of pelvic skin immediately after it absorbed water. If water was stored, we expected the surface density of this skin to be greater than that of control skin. No difference in surface density was found. These results provide strong evidence that absorbed water does not directly enter the lymphatic system and is not stored in the skin. Consequently, osmotically absorbed water must enter via a transcapillary route.

Animals↗
PubMed1999

Transmission routes of HIV-1 gp120 from brain to lymphoid tissues.

The blood-brain barrier (BBB) restricts the entry of antiviral agents into the CNS thereby facilitating the creation of a reservoir of HIV that could potentially reinfect peripheral tissues. We characterized the efflux from brain of radioactively labeled viral coat HIV-1 gp120 (I-gp120) after intracerebroventricular (i.c.v.) injection. The half-time disappearance rate of I-gp120 from brain was 12.6 min, which was faster than could be explained by the reabsorption of cerebrospinal fluid into blood but could not be explained by a saturable transporter. After i.c.v. injection, I-gp120 appeared in the serum and was sequestered by spleen and the cervical nodes, demonstrating a potential for virus within the CNS to reinfect peripheral tissues. However, the amount of I-gp120 appearing in serum was less than that expected based on the efflux rate, whereas uptake by the cervical nodes was much greater after i. c.v. than after i.v. injection of I-gp120. These findings were explained by drainage from the brain directly to the cervical lymph nodes through the brain's primitive lymphatic system. These lymphatics potentially provide a pathway through which CNS reservoirs of HIV-1 could directly reinfect lymphoid tissue without being exposed to circulating antiviral agents.

Acids↗
PubMed1997

[Radiologic appearance of primary anomalies of the lymphatic vessel system of the lung. Review and personal results].

Congenital disorders of the lymphatics of the lung are rare. On the basis of a literature review and our own experiences the disorders are divided into four groups and their radiographic findings are described. Pulmonary lymphangiectasia shows not typical signs. As an expression of the underlying pathophysiologic processes CT shows thickening of interlobular septs, interstitial edema and pleural effusions. Neither architectural distraction nor thickening of intralobular septs was seen. Lymphangioleiomyomatosis shows rather typical findings with multiple thin-walled bullae. In contrast to the opinion that architectural distraction is not seen in LAM we sometimes found signs of fibrosis. Disseminated pulmonary lymphangioma is characterised by proliferation of lymph vessels. CT-findings of this disorder have not been described before. CT shows multiple disseminated nodules of up to 2.5 cm accompanied by multiple bullae of similar distribution and size.

Humans↗
PubMed2003

The second valve system in lymphatics.

The mechanism for interstitial fluid uptake into the lymphatics of the microcirculation remains speculative and uncertain. There exists a system of intralymphatic valves that prevent reflow along the length of the lymphatic channels, but these valves are insufficient to provide unidirectional flow at the level of the initial lymphatics. We propose that initial lymphatics have a two-valve system: a (primary) valve system at the level of the endothelium in addition to the classical (secondary) intralymphatic valves. The primary valves, in conjunction with the secondary valves, provide a mechanism that facilitates the unidirectional flow during periodic compression and expansion of initial lymphatics.

Animals↗
PubMed1998

Lymphedema management training for physical therapy students in the United States.

BACKGROUND: The objective of this study was to determine to what extent accredited physical therapy programs in the United States were presenting the principles of lymphedema management and whether regional differences existed. METHODS: States were grouped into four geographic regions: Northeast, South, Midwest, and West. From mid-June to mid-July, 1997, 63 of 148 (42.6%) accredited physical therapy (PT) programs in the United States completed and returned the questionnaires. Participants received a cover letter, consent form, and lymphedema survey by e-mail, facsimile, or regular post. The lymphedema survey covered a wide variety of issues relating to five areas: 1) general and 2) specific anatomy and physiology of the lymphatic system, 3) pathogenesis of lymphedema, 4) traditional (compression pumps/garments), and 5) innovative (European/Australian) treatment techniques for lymphedema. "Yes" responses indicated that specific information was included in the curriculum. Frequency of yes responses for each of the five areas were counted and converted into percentages. Regional responses were compared with the total combined responses with a modified binomial technique. RESULTS: PT programs in the United States were providing 89% of our designated content in the general anatomy and physiology of the lymphatic system, 73% in the pathogenesis of lymphedema, 65% in traditional treatment techniques, 48% in innovative treatment techniques, and 42% in the specific anatomy and physiology of the lymphatic system. No individual region differed significantly (P > 0.05) from the combined results. CONCLUSIONS: The participating PT programs appeared to be providing instruction in general anatomy and physiology of the lymphatic system, pathogenesis of lymphedema, and traditional treatment techniques. However, far less instruction on the specific anatomy and physiology of the lymphatic system and innovative treatment techniques is offered. We believe that PT students would benefit with more curricular content in these latter two categories in order to acquire the knowledge and skills to combat the devastating effects of lymphedema.

Breast Neoplasms↗
PubMed1995

[The laryngeal lymph vessel system of the human. A morphologic and lymphography study with clinical viewpoints].

Laryngeal carcinomas have different metastatic characteristics depending on their locations. Although these changes could be explained by differences in density of the lymphatic system, studies of the laryngeal lymphatic system have been controversial. To clarify these differences the lymphatic systems of 184 organ specimens were investigated with light and electron microscopy, histochemistry and injection techniques. Three types of lymphatic vessels were found in the larynx: lymph sinuses, precollectors and collectors. The highest density of lymphatics was found in the supraglottic larynx. From this region, lymph drained via 3-6 collectors to a hypopharyngeal collector. The subglottic lymph mainly drained via 2-4 collectors to paratracheal and mediastinal lymph nodes. The lymph system of the vocal folds was sparse but drained mainly to the supraglottic larynx. No lymph collector was found in the mucosa of the vocal fold. According to these results, the incidence of lymphatic spread correlated first with the density of the initial lymphatics in the various laryngeal regions and secondly (and probably of greater significance) with nearness of tumor to the laryngeal collectors.

Endothelium, Lymphatic↗
PubMed1984

[Clinical and surgical anatomy of the lymphatic circulation of pancreas].

Data was collected from results of injection and dissection of 100 autopsy specimens; the examination of 34 case-reports of cancer patients; the injection of lymphatics in 14 live dogs; and the reconstruction of the mesodorsal region of the pancreas from a 30 mm embryo using Born's technique. Anatomy of the pancreas and lymph vessels shows that the "primary mesodorsal region" of the pancreas is two-fold; a right part for the right side of pancreas: the retroportal process (RPP); a left part for the left side of pancreas, a formation not previously described: the left lateroportal process (LLPP). Whereas lymphatic drainage visible on the anterior surface of the pancreas is apparently as described, posterior drainage, which collects lymph from posterior and anterior vessels, is quite atypical. The right portion drains into the RPP and the left into the LLPP. Terminal collecting vessels of pancreatic lymphatics have only a short distance to travel before emptying into the thoracic duct. The study of lymph node metastases from pancreatic cancer appears to confirm these cadaver anatomic results but the series is too small for valid exploitation. The very rapid passage into the thoracic duct probably greatly diminishes the value of widely extended surgery, justification for the latter being exclusively to remove lymph nodes insofar as adjuvant therapy has currently failed to demonstrate absolute efficacy. Precise knowledge of the anatomy of the pancreatic lymphatics should allow development of experimental models to study lymph circulation changes during acute pancreatitis. Pancreatic edema, an enzyme-rich fluid, is an essentially "lymphatic" edema. The interstitial and lymphatic shunt pathways due to increased duct pressure were evident during the dog study. The lymphatic system acts as a "buffer system" or "safety valve" against progression to necrosis. Ligature of very proximal pancreatic lymphatic efferents (included in the bands) was followed by a fatal necrotic pancreatitis on both occasions when this was performed. Development and study of a lymphagogue drug for the treatment of acute pancreatitis is a justifiable project. A protocol is proposed which combines lymphagogue treatment with anti-enzymes, the former assists use of the enzymes by the lymphatic system. The anti-proteases prevent the onset of fatal shock caused by the outpouring of enzymes into the lymphatic system and the general circulation.

Adult↗
PubMed1980

A model for cardiopathy induced by Trypanosoma brucei brucei in mice. A histologic and immunopathologic study.

The successful induction of pancarditis in mice by the use of Trypanosoma brucei brucei is reported. The sequential analysis of whole-organ sections demonstrated the presence of trypanosomes in the cardiac structures from the fourth week after infection. Parasites predominated on the endocardial and epicardial side but were also present in the valves, the conducting system, and the lymphatic system draining the heart, the latter being particularly evident in late infection. At the time of parasite invasion, deposits of IgM and IgG and of complement (C3) appeared in the tissues. Also at this time parasitemia reached a plateau, and the circulating specific antitrypanosomal antibodies, the serum Ig and C3, as well as the Clq activity, reached pathologic levels. Cellular response followed parasite invasion and appeared to be similar to that described in human African trypanosomiasis. In late infection, the draining lymph nodes showed a marked histiocytic proliferation, and the vessels became convoluted and distended. The suggested pathogenic mechanisms involve immunologic and mechanical factors. It is possible that the immunologic process prepares for a simultaneous or subsequent parasite invasion of the tissues with an associated inflammatory response. The partial obstruction of the lymphatic cardiac draining system probably accounts at least in part for the peculiar distribution of the parasite-induced lesions. A therapeutic trial was unsuccessful, but the persistence of trypanosomes in the tissues when circulating parasites were no longer detectable may account for relapses.

Animals↗
PubMed2003

Comparison of dendrimer-based macromolecular contrast agents for dynamic micro-magnetic resonance lymphangiography.

Few methods are currently available to visualize the entire lymphatic system. A method known as micro-magnetic resonance lymphangiography (MRL), which employs a dendrimer-based MRI contrast agent (PAMAM-G8) and a clinical-grade 1.5T MRI instrument, was recently developed for use in mice. In the present study, three dendrimer-based MRI contrast agents (PAMAM-G8, DAB-G5, and PAMAM-G4) with different pharmacokinetic characteristics were compared to determine the best reagent to visualize the lymphatic system under physiological or pathological conditions. In addition, two established MRI contrast agents (Gadomer-17 and Gd-[DTPA]-dimeglumine (Magnevist)) were used as control agents. In experiments with mice, most of the deep lymphatic system was visualized by micro-MRL with all agents except Gd-[DTPA]-dimeglumine. PAMAM-G8 was best for visualizing lymphatic vessels, whereas DAB-G5 was better for visualizing lymph nodes. PAMAM-G4 was intermediate in character between PAMAM-G8 and DAB-G5, except in exhibiting a low background signal (especially in the liver). The lymphatic system was not clearly visualized with Gd-[DTPA]-dimeglumine; however, the lymph nodes were visualized with Gadomer-17, although not as well as with dendrimer-based agents. In conclusion, DAB-G5 and PAMAM-G4 can be used to identify lymph nodes and lymphatic vessels, respectively. Their rapid excretion makes these compounds potentially attractive for human use.

Animals↗
PubMed1998

Lymphangioma circumscriptum.

Two children with lymphangioma circumscriptum (LC), a rare cutaneous lymphangioma, are described. One was diagnosed antenatally as having a right axillary cystic hygroma; in addition, postnatally LC was noted on the right forearm. A few years later a mediastinal lymphangioma was diagnosed. This combination of LC associated with additional malformations of the lymphatic system has not been reported previously, and may point to a generalized developmental disorder of the lymphatic system. The pathophysiology of the lesion is discussed with a review of the pertinent literature. It appears that LC primarily affects the subcutaneous tissue in the form of cystic dilatation of lymphatic channels without systemic lymphatic communication. The skin lesions are probably secondary to the increased intraluminal pressure. The typical clinical appearance is manifested by multiple skin vesicles and lymphorrhea. The main treatment modality is surgical excision. Recurrences are not unusual and require re-excision.

Child, Preschool↗
PubMed1985

Passive movement of radioactive microspheres from bone and soft tissue in an extremity.

Bone biopsy is the definitive method for bone tumor diagnosis. Unfortunately, the procedure is not without risk and may substantially increase the rate and extent of tumor cell metastasis. This study used radioactive microspheres (15 micron diameter) to explore the spread of cell-sized particles from the distal femur into the lymphatic system, venous drainage, and local tissue following a simulated biopsy in the canine model procedure. In the initial group of test animals the microspheres rapidly moved from the femur through the venous system to the lungs. There was no movement from the femur into the lymphatic system within 4 days. The lungs effectively filtered the 15 micron microspheres, thus preventing arterial dissemination. Additional groups were used to explore the movement of the cell-sized particles from the soft tissue surrounding the bone. At the end of the 4 day experimental period, microspheres were found in the iliac lymph nodes in two of nine animals. Microspheres were not detected in the lungs of any of these nine animals. These results suggest that tumor cell-sized particles can move rapidly from the bone venous system to the lungs following a bone biopsy. It appears that the lymphatic system does not contribute to this rapid dissemination. However, the role of lymphatics in a more chronic process remains unclear.

Animals↗
PubMed2005

Lymphangiogenesis-mediated shedding of LAM cell clusters as a mechanism for dissemination in lymphangioleiomyomatosis.

Lymphangioleiomyomatosis (LAM) affects exclusively women of reproductive age, involves the lungs and axial lymphatic system, and is frequently complicated with renal angiomyolipomas. LAM lesions are generated by the proliferation of LAM cells with mutations of one of the tuberous sclerosis complex (TSC) genes. Recent studies indicate that LAM cells can migrate or metastasize to form new lesions in multiple organs, although they show a morphologically benign appearance. In the previous study, we reported LAM-associated lymphangiogenesis and implicated its role in the progression of LAM. In this study, we further focused on the lymphatic abnormalities in LAM: LAM-associated chylous fluid (5 pleural effusion and 2 ascites), surgically resected diaphragm (1 patient), and axial lymphatic system including the thoracic duct, lymph nodes at various regions, and diaphragmatic lymphatic system (5 autopsy cases). We demonstrated that LAM cell clusters enveloped by lymphatic endothelial cells (LCC) in all chylous fluid examined. We identified LAM lesion in the diaphragm (2 of 5 autopy cases and one surgical specimen), thoracic duct (5 of 5), and lymph nodes (retroperitoneal (5 of 5), mediastinal (4 of 5), left venous angle (5 of 5) with total positive rate of 68% to 88% at each region of the lymph node, but less frequent or none at remote lymph nodes located away from the axial lymph trunk (cervical [1 of 5] and axillary [0 of 5]). LCCs were identified in intra-LAM lesional lymphatic channels where LAM cells proliferate along lymphatic system. In in vitro culture system, LCC can fragment into each proliferating LAM cell. These findings suggest that LAM-associated lymphangiogenesis demarcates LAM lesion into bundle- or fascicle-like structure and eventually shed LCC into the lymphatic circulation and that LCCs play a central role in the dissemination of LAM lesion.

Adult↗
PubMed2002

Lymphatic vessel activation in cancer.

Metastasis of most cancers occurs primarily through the lymphatic system, and the extent of lymph node involvement is the most important prognostic indicator. While the importance of the lymphatic system as a pathway for metastasis has been well recognized, there is very little information available about the mechanisms by which tumor cells interact with the lymphatics. Recently, production of the lymphangiogenic factor VEGF-C has been detected in tumors, and the significance of VEGF-C-mediated lymphangiogenesis for tumor metastasis has been demonstrated. Increased lymphatic vessel density has been found associated with certain tumors. The mechanisms by which tumor cells gain access to and enter lymphatic vessels are critical issues that need to be addressed in the future. In contrast to the prevailing view that has assigned to the lymphatic system a passive role in the metastatic process, our results indicate the importance of lymphatic vessel activation in tumor dissemination.

Angiogenesis Inducing Agents↗
PubMed1990

Description and clinical importance of the lymphatics of the vocal fold.

Findings of the presence of lymphatics in the subepithelial connective tissue layer of the true vocal cord range from the statement that lymphatics are absent to the observation that a dense lymphatic network exists. This is undoubtedly a result of the different methods of examination. The entire extent of a lymphatic system can be shown by either an enzyme histochemical demonstration of the 5'-nucleotidase activity in the lymphatics, or electron microscopy, which is more elaborate. These two methods are used to describe a subepithelial lymphatic network of varying density in 80 human vocal folds, which--contrary a frequent assumption--is not interrupted in the area of the free margin of the true vocal cord. Under the squamous epithelium, the density of the lymphatic system, which is very high in the arytenoid region, decreases continuously toward the anterior portion of the true vocal cord. It is exactly in the region in which the lymphatic system is the sparsest that almost all cancers of the true vocal cord develop. This finding is highly significant, in view of the low incidence of lymphogenous metastasis formation in T1-glottic cancers.

5'-Nucleotidase↗
PubMed2006

Real-time imaging of lymphogenic metastasis in orthotopic human breast cancer.

Metastatic spread to regional lymph nodes is one of the earliest events of tumor cell dissemination and presents a most significant prognostic factor for predicting survival of cancer patients. Real-time in vivo imaging of the spread of tumor cells through the lymphatic system can enhance our understanding of the metastatic process. Herein, we describe the use of in vivo fluorescence microscopy imaging to monitor the progression of lymph node metastasis as well as the course of spontaneous metastasis through the lymphatic system of orthotopic MDA-MB-231 human breast cancer tumors in severe combined immunodeficient mice. High-resolution noninvasive visualization of metastasizing cancer cells in the inguinal lymph nodes was achieved using cells expressing high levels of red fluorescent protein. Sequential imaging of these lymph nodes revealed the initial invasion of the tumor cells through the lymphatic system into the subcapsular sinuses followed by intrusion into the parenchyma of the nodes. FITC-dextran injected i.d. in the tumor area enabled simultaneous tracking of lymphatic vessels, labeled in green, and disseminated red cancer cells within these vessels. Fast snapshots of spontaneously metastasizing cells in the lymphatic vessels monitored the movement of a few tumor cells and the development of clumps clustered at lymphatic vessel junctions. Quantification of high interstitial fluid pressure (IFP) in the tumors and fast drainage rates of the FITC-dextran into the peritumoral lymphatic vessels suggested an IFP-induced intravasation into the lymphatic system. This work presents unprecedented live fluorescence images that may help to clarify the steps occurring in the course of spontaneous lymphogenic metastasis.

Animals↗