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Role of the regional lymph node in neoplasia: cellular mediated reactivity in vitro by autologous regional or distant lymph nodes or peripheral blood lymphocytes of dogs with spontaneous neoplasms.

This report concerns the in vitro reactivity of lymphocytes obtained from regional (draining) lymph nodes, distant nodes and peripheral blood against autochthonous spontaneous neoplasms. Tumors, blood and lymph nodes were collected aseptically prior to necropsy. Primary tumor cultures were established. Viable tumor cells were first incubated with media or autologous sera and then various numbers of lymphocytes were added. The mixtures were rotated for 60 minutes and then plated. Two and/or five days later cultures were terminated and viable target cells counted. The results of the tests were similar regardless of the lymphocyte source utilized. In vitro tumor cell cytotoxicity by high numbers (1000:1 lymphocytes to tumor cells) of any autologous lymphocytes and interference of such reactivity by autologous sera were demonstrated. Low numbers (100:1) of any lymphocyte source lead to tumor growth stimulation. Animals with spontaneous neoplasms are probably the best model for the study of human clinical oncology. Our data demonstrate that in these animals lymphocytes obtained from regional nodes were not unique in their reactivity to tumors. It is possible that early in the disease the draining node may play a vital role in initiation of host response; however, later its importance probably diminishes.

Adenocarcinoma↗

Studies on the transfer of lymph node cells. III. Effects of variation in the interval between the injection of antigen into the donor and collection of its lymph node cells.

At various intervals, from 10 minutes to 21 days, after the injection of dysentery bacilli into the hind foot pads of rabbits the popliteal lymph nodes were excised. The cells of the lymph nodes were teased free, washed, and injected intravenously into normal rabbits. In each case aliquots of the same cell suspension were either incubated at 37 degrees C. for 24 hours or heated at 52 degrees C. for 20 minutes and then injected into other normal rabbits, as controls. In the case of lymph node cells obtained 4 or 3 days after the injection of antigen, antibody was found in the serum of recipients on the 1st day after the transfer of untreated cells. The titer increased until the 3rd day and then began to decline after the 5th or 7th day. In the sera of recipients of incubated cells antibody was not found, except on occasion after the 4th day and in low titer. This late appearance of antibody was attributed to the presence of small amounts of antigen in the original cell suspension. As the interval between injection of antigen and collection of cells was increased beyond 4 days the effectiveness of the transfer decreased progressively until at 14 days no transfer effect was obtained. When cells which were obtained 2 days after the injection of antigen were transferred, antibody appeared on the 2nd day after transfer and then followed the characteristic curve, whereas in the case of incubated cells antibody did not appear until the 3rd day after transfer. After the transfer of untreated 1 day cells antibody did not appear in the recipient until the 3rd day, and then followed the type of curve seen with 2, 3, and 4 day cells. Following transfer of incubated 1 day cells antibody also appeared on the 3rd day. To establish the possibility of eliciting the cell transfer effect as early as 1 day after the injection of dysentery bacilli, recipient rabbits were x-irradiated 24 hours prior to the injection of cells. It was found that in the sera of such recipients of untreated cells antibody appeared on the 3rd day following transfer, while irradiated recipients of incubated cells did not develop any measurable amounts of agglutinin for the first 10 days. It was concluded that a total of 3 days was required between the injection of antigen into the donor and the appearance of measurable antibody in the serum of the recipient, regardless of the fraction of that time spent by the cells in each of the animals involved, donor or recipient. Following the transfer of untreated cells removed from lymph node as early as 10 minutes after the injection of antigen distal to them, antibody could be found in the sera of x-irradiated recipients 4 days later, whereas antibody did not appear following the transfer of heated cells to such recipients.

Animals↗

Principles of surgical treatment for carcinoma of the esophagus: analysis of lymph node involvement.

Extensive lymph node dissections in the posterior mediastinum and abdomen were performed during resections of esophageal carcinomas. Analysis of lymph nodes demonstrated a widespread distribution of positive lymph nodes regardless of the location of the tumor. The distribution of positive lymph nodes was noticed in the area between the superior mediastinum and the celiac region. The studies were also made on the distribution of positive lymph nodes in the superior gastric region, particularly in the region of the lesser curvature of the stomach. The following principles should be followed when carcinoma of the esophagus is surgically treated. 1) Lymph node dissection of the whole length of the posterior mediastinum, superior gastric region, and celiac region must be performed. 2) Total thoracic and abdominal esophagectomy with resection of the proximal lesser curvature and cardia, including the first to fourth branches, and preferably the fifth branch of the left gastric artery, is mandatory in order to remove possible lymphatic and intramural spread of tumors. 3) Satisfactory esophageal replacement in one stage must follow. Of the Toranomon Hospital, 210 underwent resections and reconstructions, for a resectability rate of 59.3%. The operative mortality rate was 1.4% and the overall five-year survival rate was 34.6%.

Adult↗

Lymph node accessory cells in the immune response. The primary response to paratyphoid vaccine in rat parathymic lymph nodes.

The immune response in the rat parathymic lymph node was studied after administration of antigen into the peritoneal cavity. Special attention was paid to the accessory cells, which might induce the response. During the induction phase of the response a heterogeneous population of non-lymphoid mononuclear cells was present in the subcapsular sinus and the cortex of the node. These cells resemble "veiled cells" described in skin draining lymph and interdigitating cells in the paracortex of skin draining lymph nodes, but they do not contain Birbeck granules. It is concluded that the appearance of these granules depends on the site of the exudate provocation and that the presence of the organelles in these accessory cells is not obligatory for lymphocyte stimulation.

Animals↗

The architecture of rat lymph nodes. IV. Distribution of ferritin and colloidal carbon in the draining lymph nodes after foot-pad injection.

Rat popliteal and the iliac lymph nodes were examined after foot-pad injections of colloidal carbon and ferritin-tetramethylrhodamine isothiocyanate. Carbon rapidly entered medullary sinuses, but the entry of carbon into the interstitium was prohibited by avid phagocytosis, by sinus macrophages and by the lymphoendothelium, which apparently formed a barrier to diffusion. In contrast, little carbon was phagocytosed in subcapsular sinuses, from where the particles entered the underlying cortex through holes in the lymphoendothelium created by penetrating frilly cells. The distribution of ferritin was similar to that of carbon. Both carbon and ferritin localized poorly in follicles; however, preinjection of specific antibody caused enhanced follicular localization of ferritin. By electron microscopy clusters of ferritin molecules were found on the surface of dendritic cells. These cells showed different morphology from that of the interdigitating cells of the paracortex. The latter cells did not bind ferritin to their surface, even in the presence of specific antibody.

Animals↗

Light and electron microscopic studies of postcapillary venules in developing human fetal lymph nodes.

Developing lymph nodes from 30 human fetuses with crownrump lengths (CRL) of 38 mm (8.7 wk) to 245 mm (26 wk) were studied by light and electron microscopy. Blood vessels that appear to be postcapillary venules (PCV) are present in nodes of 47 mm CRL and older fetuses. These venules first appear in nodes whehn the nodal population of lymphocytes is sparse. In these early nodes PCV are distributed randomly and consist of a low endothelium, underlying basal lamina and incomplete pericyte sheath. Early nodal PCV are distinguised from other nodal blood vessels by the presence of lymphocyte diapedesis and several luminal lymphocytes. In the late stages of nodal development PCV are the more common non-capillary blood vessel and appear in the parenchyma near the periphery of the node. Late nodal PCV are generally characterized by a cuboidal endothelium that is rich in Golgi apparatus, lysosomes and Weibel-Palade bodies. The lumen and wall of late nodal PCV contain lymphocytes. The relationship between the development of the parenchyma of fetal nodes and the appearance and activity of PCV, the passage of lymphocytes through the PCV wall and the fine structure of developing PCV are described. It is suggested that the lymphocytes that first appear in developing nodes, and the majority of the lymphocytes found in late nodes, migrate to the node via the blood vascular system and enter the nodal parenchyma by passing across PCV endothelium.

Abortion, Spontaneous↗

The narrowing of high endothelial venules of the rat lymph node.

The lymph node contains blood vessels of a special type, termed "high endothelial venules" (HEVs), which are involved in the process of lymphocyte recirculation. In standard tissue sections, many HEVs exhibit a nearly closed or closed lumen containing small lymphocytes but few, if any, erythrocytes. The question arose as to whether the appearance of HEVs in tissue sections is influenced by the routine method of animal sacrifice and/or of tissue processing. Therefore, the present work investigated the effects on HEVs of sacrificing rats as well as of excising and fixing their nodes with various procedures. It was observed that procedures involving animal bleeding or blood loss from nodes increase the percentage of HEVs exhibiting a nearly closed or closed lumen. The results further revealed that the endothelial thickness and other morphological features of HEVs are modified by this artifactual narrowing of HEVs. The possible significance of the phenomenon is discussed.

Animals↗

[A case of lymph node aspergillosis].

Lymph node aspergillosis in an otherwise healthy patient receiving neither antibiotic corticosteroid or immunodepressive drug treatment is an uncommon event. In addition the case reported revealed no deficiency in humoral or cellular immunity. The possibility that aspergillosis may occur in cases without identifiable immunodeficiency is therefore put forward.

Adolescent↗

Cytodiagnosis of metastatic melanoma in the lymph nodes.

Lymph-node aspirates performed over ten years numbering 1,555 showed 8.2 percent of metastatic tumors. Of these, only six percent were metastatic melanomas. Clinical diagnosis was made in three cases. Melanin in the cells made the diagnosis easy. But even in the absence of the pigment as in two amelanotic melanomas, the cytologic features were characteristic.

Adolescent↗

Virological examination of bovine mammary lymph nodes.

Mammary lymph nodes from 42 Hereford cows culled for poor reproductive performance were examined for cytopathogenic virus and hemadsorption. No evidence of viral infection was detected using the methods employed. Serum from all the animals gave positive reactions to the hemagglutination-inhibition test for bovine myxovirus parainfluenza 3. Six of 12 had neutralizing antibody against bovine virus diarrhea virus, but none of the 12 had neutralizing antibodies against infectious bovine rhinotracheitis virus.

Animals↗

L-selectin and beta7 integrin synergistically mediate lymphocyte migration to mesenteric lymph nodes.

Mesenteric lymph nodes (MLN) drain the gut where nutritive antigens and pathogens are encountered by lymphocytes of the gut-associated lymphoid tissue. We sought to determine how lymphocytes enter the MLN by studying mice double deficient for beta7 integrins and L-selectin. beta7/L-selectin double-deficient lymphocytes did not migrate into MLN. Most importantly, MLN formation was drastically impaired in beta7/L-selectin double-deficient mice. Lymphocyte numbers in MLN from beta7/L-selectin double-deficient mice were tenfold reduced compared to control mice. A high percentage of the few lymphocytes still detected in MLN from beta7/L-selectin double-deficient mice were CD44hi CD18hi, suggesting alternate migration pathways independent of L-selectin and beta7 integrin for these cells. We conclude that the combination of both molecules, L-selectin and beta7 integrin, is indispensable for MLN formation and that these molecules may mediate lymphocyte migration to MLN in a sequential and synergistical manner.

Animals↗

[Doppler ultrasonography of superficial lymph nodes].

Normal lymph nodes (l.n.) are elongated and hypoechoic, with central echogenic hilum on B-mode, while color-doppler (CD) shows central hilar vascularization. Chronic inflammatory l.n. are elongated, with echogenic hilum, hilar vascularization on CD and resistance index (RI) 0.60-0.70. Acute lymphadenitis shows intensive hilar flow with RI<0.60; abscess of l.n. is anechoic with through transmission. Tuberculous l.n. are inhomogenously hypoechoic and rounded, with deformed hilar vascularization on CD, occasionally with centripetal flow. They may mimick malignant l.n. on CD due to vessel dislocation by granulomatous masses. L.n. in stage of micrometastasis are of similar structure as reactive l.n., with preserved hilar vascularization; as the metastasis grows, focal cortical expansion and/or destruction of intranodal structure with dislocation and compression of blood vessels may occur; vascular resistance is consecutively increased; in advanced stage of metastatic growth l.n. becomes rounded, hilum is not visible, cortex is heterogenous, occasionally with hyperechoic keratin deposits, unsharp nodal margin is the sign of extranodal neoplastic spread; mainly peripheral vascularization, with fragmentation, deformation and dislocation of intranodal vessels are seen on CD, with increased RI>0.80; necrotic areas are anechoic and avascular on CD. Lymphomatous nodes have preserved internal structure, sharp margins, hypoechoic cortex, frequently with through transmission; large arborized hilum may be displaced; abundant hilar flow is seen on CD, with normal or slightly increased vascular resistance. Although the sensitivity of B-mode and Doppler features of l.n. is mostly limited (false negative rate is significant), high specificity of some of them establishes sonography as a valuable complementary method in differential diagnosis of lymphadenopathy: the presence of hilar vascularization with RI<0.40 accurately indicates acute lymphadenitis, while predominantly peripheral flow pattern and RI>0.80 are typical of metastatic l.n. High enddiastolic velocities (EDV>9 cm/s) are only rarely seen in metastases, while very low EDV<1 cm/s indicates metastatic lymphadenopathy. As sonography is very suitable imaging method for puncture guidance, B-mode and CD analysis of l.n. need to be combined with aspiration cytology whenever possible, as it may considerably improve the accuracy of non-invasive patient diagnostic work-up. Literature on sonography of l.n. was reviewed, and selection of most relevant articles was made.

Humans↗

Production of interleukin 2 by human lymph nodes.

Perigastric lymph node cells (LNC) from patients with gastric carcinoma or benign lesions were tested for interleukin 2 (IL 2) production upon stimulation with phytohemagglutinin (PHA), in comparison with that of peripheral blood mononuclear cells (PBM) or spleen cells (SPC). IL 2 activity in the supernatants of LNC cultures from patients with either carcinoma or benign lesions was significantly higher than that of PBM cultures from the same person. There was no significant difference in IL 2 activity between PBM cultures or LNC cultures from patients with carcinoma and patients with benign lesions. Supernatants from LNC cultures were also more active than those obtained from SPC cultures. The production of interleukin 1 (IL 1) in LNC was lower than that in PBM. In LNC, the proportion of OKT3+ cells was similar to that found in PBM, with a prevalence of OKT4+ cells over OKT8+ cells. No differences were found between lymphatic cells from patients with carcinoma and from patients having benign lesions.

Humans↗

Electron microscopic observations on antibody-producing lymph node cells.

Lymph node cells of rabbits injected with sheep erythrocytes, identified as antibody-producing by their ability to produce plaques of hemolysis in erythrocyte-containing agar layers, have been examined by electron microscopy, by the use of a procedure devised for subjecting single cells to such examination. The antibody-producing cells thus examined were found to fall into two classes, according to the current terminology: some were in the category of lymphocytes, and others, in the category of plasma cells. Within each class, cells were found to vary in certain characteristics, especially in the degree of development of such organelles as the nucleolus, Golgi apparatus, and the endoplasmic reticulum. In the case of the endoplasmic reticulum especially, it could be seen that a series of these plaque-producing cells, ranked in order of increasing size and development of the endoplasmic reticulum, would extend over a considerable range from those lymphocytes with the least developed organelles to the mature plasma cells with the greatest development of these structures.

Animals↗

Immunohistochemical analysis of nm23-H1 gene product in node-positive lung cancer and lymph nodes.

The nm23-H1 gene product has been considered as an anti-metastatic protein and the level of its expression has been reported to correlate inversely with metastatic potential in some cancers. However, the expression of nm23-H1 gene product in the metastatic sites have not been studied in detail. We examined the expression of nm23-H1 gene product in surgically resected 46 pairs of primary lung cancers and metastatic lymph nodes by immunohistochemistry. The positive staining of nm23-H1 gene product in primary cancers and metastatic lymph nodes were observed in 56.5 and 67.4%, respectively. The heterogeneity of nm23-H1 gene product expression between primary cancers and metastatic lymph nodes was observed in 41.3%. No correlations were found between the nm23-H1 gene product expression in lung cancers and the patients survival. No significant association was also observed between nm23-H1 gene product expression in lymph nodes and the patients survival. There was, furthermore, no correlation between the heterogeneity of nm23-H1 gene product expression and the patients survival. In conclusion, the level of nm23-H1 gene product expression does not significantly reveal prognostic value in node-positive lung cancers. Expression of nm23-H1 gene product in metastatic lymph nodes was also unrelated to patients survival.

Adenocarcinoma↗