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Killer cell (K) activity in human normal lymph node, regional tumour lymph node and inflammatory lymph node.

Human normal lymph nodes, irrespective of their anatomical site of origin, have a low K cell activity, which may not be detected except with the appropriate target cell and at high lymphocyte to target cell ratios (100:1). This very low killer cell activity is also found in all the homolateral axillary nodes of patients with clinical stage I and II carcinoma of the breast and in the regional draining nodes of a variety of solid tumours, whether small and localized or large and with extensive spread. In all cases proximity to the tumour and obious hyperplastic changes in the nodes have no modifying effect. This pattern of minimal reactivity is similarly found with tonsillar lymphocytes and with nodes draining inflammatory foci. The Fc and C3 receptors on surface membranes are dectected with ease, and pretreatment of lymphocytes by incubation, washing and enzymatic treatment fail to alter their reactivity, thus excluding effector cell inhibition by immune complexes. The killer cell activity of lymphocytes from the blood of breast tumor patients is similar to the activity of lymphocytes from healthy controls.

Binding Sites

The influence of the lymph node on the protein concentration of efferent lymph leaving the node.

1. Experiments have been performed in sheep to determine the contribution of lymph formed within a lymph node to the total protein output in lymph leaving the node. 2. The lymphatic duct leaving the popliteal lymph node was cannulated and the protein and lymphocyte output in efferent lymph determined. The afferent lymph flow to the popliteal node was then diverted and lymph formed only within the lymph node collected from the efferent cannula. It appeared from the results that the popliteal lymph node forms lymph at the rate of approximately 1 ml. per hour and may contribute 30-50% of the protein output observed in efferent lymph. 3. The importance of lymph formation within the lymph node varied between nodes found in different regions of the body. This was due in part to the different protein concentrations in the afferent lymph to the different nodes. 4. A positive correlation was found between the protein and lymphocyte concentrations in efferent lymph from the popliteal lymph node in seven out of eleven sheep and in lymph formed within the popliteal lymph node in two out of three sheep. It is suggested that this relationship may be due to an increased transfer of plasma proteins through the post-capillary venules in the lymph node accompanying the continual traffic of lymphocytes across the wall of these vessels. The results indicated that the protein transfer across the post-capillary venules was not an indiscriminate transfer of plasma per se but a selective transport from the blood plasma compartment based on molecular size.

Animals

Lymph node involvement by direct extension in adenoid cystic carcinoma. Absence of classic embolic lymph node metastasis.

Thirty-four cases of adenoid cyctic carcinoma seen at the University of Virginia Hospital from 1946 to 1974 were reviewed, with special emphasis on lymph node involvement by tumor. Lymph node involvement was found in three cases of primary tumors of the submaxillary gland, and all of the affected lymph nodes were in the immediate vicinity of the primary tumor. Two lymph nodes were involved in two of the cases, and one node was involved in the third case. In all of these lymph nodes, adenoid cystic carcinoma was present in the soft tissue surrounding the node, and the tumor extended into the node. No metastatic tumors were observed in 46 lymph nodes removed incidentally at the time of local excision of the primary tumors in 10 additional cases or in 212 lymph nodes examined after unilateral radical neck dissections in six other cases. Five autopsies in this series showed no lymph node metastases. In this series of cases adenoid cystic carcinoma only invades lymph nodes in the immediate vicinity of the primary tumor. When lymph node involvement does occur, it does not result from embolic lymph node metastasis; rather, a direct invasion of the lymph node from tumor in the perinodal soft tissue occurs. Obviously, this small study does not completely exclude the possibility of embolic metastasis; however, if it does occur, it must be extremely rare.

Carcinoma, Adenoid Cystic

Proportions of dog lung lymph in the thoracic and right lymph ducts.

We studied the external lymphatic drainage of the lung in anesthetized dogs, by simultaneously measuring lymph flows from the thoracic duct (TD) and right lymph duct (RLD) during base line and during pulmonary edema. We measured lymph flow for a 2-h base-line period, for 2 h after tying off the thoracic duct above the diaphragm to eliminate nonthoracic lymph contributions, and after giving alloxan. Following alloxan, all dogs developed moderately severe pulmonary edema. In eight dogs the average TD flows were 24.0, 0.9, and 8.2 ml/h and RLD flows were 1.1, 1.3, and 8.4 ml/h, respectively. If we assume that all increases in lymph flow after giving alloxan are due to increased lung lymph flow, then, on the average, 50% of lung lymph drains into the TD and 50% into the RLD. However, among the eight dogs, four had significant increases in TD flow after alloxan (8.9-24.6 ml/h), and four did not. RLD flow increased in all dogs following alloxan. It appears the fraction of lung lymph draining into the TD and RLD can vary greatly amone individual dogs but, on the average, the TD and RLD receive about equal fractions of the pulmonary lymph. In shamoperated control animals TD and RLD lymph flows did not change over a 5-h period.

Alloxan

[Cytokinetics of lymph nodes in lymph nodes in lymphatic system diseases (author's transl)].

Untreated malignant lymphatic system diseases are characterized by a preponderance of cell new formation (proliferation) against the destruction of lymphatic cells. If the lymph nodes are enlarged during these diseases, then cell new formation occurs largely or mostly in these lymph nodes. The proliferating cells of the lymph node are bigger than small lyphocytes and have, in general, a mean diameter of the nucleus of 10 mu and more. In normal lymph nodes they belong morphologically to the big lymphocytes, immunoblasts and plasmoblasts. In pathological lymph nodes they have to be looked for among the bigger cells of the disease-specific cell population. Whereas in healthy lymph nodes and in chronic lymphatic leukemia only about 1% of lymph node cells was found to proliferate, they amount on the average to 5% in lymphomas of lymphogranulomatosis and mostly to 30--50% in the lympho-reticulosarcoma (lymphoblast and immunoblast sarcoma, corresponding to large-cell, poorly differentiated lymphomas). The proliferating cells often appear as foci in the lymphomas. The generation times of the proliferating cells both in normal and pathological lymph nodes are about 24 hrs. or slightly longer. In lymphatic proliferation, apart from plasma cells big and smallymphocytes are produced in the normal lymph node; in CLL, big and small lymphocytes, in lymphogranulomatosis, big and small lymphocytes and Hodgkin-cells, and in poorly differentiated lymphomas, the corresponding lymphoma cells are produced. The clinicist is at the beginning of drawing conclusions from prevalent kinetic disturbances.

Cell Division

[Regional neck lymph nodes and primary tumors. 2. The reactive neck lymph node lesion].

Topographic classification of lymphatic nodes with reactive changes and with metastasis makes evident, that the regional lymph nodes have not only changes, caused by inflammation but also by growth of tumor. Thus, the lymph nodes are accomodation of defense and in the second place as an accommodation of discharge. The regional lymph nodes respond independent of the extent of the primary tumor. The regional metastasis are nearly always localized in the center of lymph nodes with reactiv changes. Lymph nodes with follicular lymphatic hyperplasia are situated in the immediate environment of the metastasis. Lymph nodes with sinus-reaction are extended before the metastasis, in direction of lymph discharge. By super imposed projection of the results of histological evaluation of cervical glands with metastasis in the neck, one obtains to some extent an impression of the defense activity by the lymph nodes at the time of the operation.

Head and Neck Neoplasms

[Studies on the lymph drainage of the eye 5. Quantitative registration of the lymph drainage from the subconjunctival space with a radioactive tracer (author's transl)].

In 7 rabbits the drainage from the subconjunctival space to the cervical lymph nodes was observed after subconjunctival injection of 99mTc-micro-colloid. Measurements of the activity distribution were made in vivo with an Anger type camera (pho-Gamma-IV Hp, Searle Nuclear Chicago) and in vitro after dissection with a sodium iodine crystal well counter (Clinimat-200, Picker). 6 hours after the injection into the subconjunctival space of the right eye an average of 53.7% of the applied activity had drained off. A significant accumulation of activity could constantly be registrated in the cervical lymph nodes. Its amount was generally up to 2.08% of the applied total activity per animal, with a large individual spreading. In detail, activity was found in all 7 cases in the right superficial cervical lymph node, in 5 cases moreover in the right mandibular lymph node, additionally in 2 animals in the right or left deep cervical lymph node respectively and in one animal as well in the right as in the left deep cervical lymph node. Besides, in all cases high activity was registered in the right retrobulbar and subconjunctival spaces just as in the right eye. A small activity in the right optic nerve could be pointed out in three of our seven cases.

Animals

[Phospholipid composition of lymphocytes from normal and leukemic blood, lymph, lymph nodes and spleen of cattle].

The phospholipid composition and cholesterol content of lymphocytes from bovine blood, lymph, lymph-nodes and spleen were studied. The cholesterol/phospholipid molar ratio in the normal lymphocytes of blood and spleen was found to be about two times higher than that in the normal lymphocytes from lymph and lymph-nodes. On lymphocytic leukemia the cholesterol/phospholipid molar ratio of the blood lymphocytes decreased sharply, whereas that in lymph and lymph-nodes lymphocytes was unaffected.

Animals

Lymph node activating factor from mixed cultures of allogeneic lymphoid cells: effect on the lymph nodes of euthymic and athymic mice.

The action of "lymph node activating factor" (present in supernatants from 4hr cultures of allogeneic lymphocytes) on the lymph nodes of athymic nu/nu mice, nu/+ hybrids and euthymic BALB/c mice was studied. An increase in lymph node weight, cellularity and changes in lymph node morphology, i.e. an increase of the dense lymphatic tissue of the cortex and paracortex and appearance of follicles with light centers, were found in all mice. Lymphocyte activation evaluated by the presence of lymphocytes with RNA synthesizing nucleoli occurred only in nu/nu mice and nu/+ hybrids. Marked changes in lymph node morphology found in nu/nu homozygotes suggest relation of the lymph node activating factor to mediators acting directly on B cells.

Animals

Studies on lymph humoral factor. Biological characteristics of a lymphocytopoietic factor in rat thoracic duct lymph.

The biological characteristics of a lymphocytopoietic factor obtained from rat thoracic duct lymph (Yamashita, Fukumoto & Miyamoto, 1976) were further investigated. The lymph extract from normal rats failed to stimulate both large pyroninophilic cell-proliferation and mitotic response in the spleen and lymph node of the thymectomized, irradiated and marrow reconstituted rat (B rat). This suggests that target or responsive cells for the factor are not marrow-derived (B) cells, but thymus-derived (T) cells. On the other hand, the lymph extract from the lymphopenic lymph-drained B rats showed similar high lymphopoietic activity to those of normal rats, indicating that the existence of a thymus is not essential for the production or secretion of the factor. The fact that lymphocytotic rats produced by syngeneic lymphocyte transfusion are most sensitive to the lymph extract suggests that liver endogenous level of this factor and the responsiveness of target cells are regulated by the number of circulating T lymphocytes.

Animals

[Morphology of the lymph vessels and axillary and mediastinal lymph nodes of the white rat (Rattus norvegicus)].

In this work, the authors studied the morphology of the axillary and mediastinal lymph nodes and their efferent branches in the white rat (Rattus norvegicus). The main characteristics observed were: The presence of two groups of axillary lymph nodes, one in the lateral and the other in the medial portion, and the presence of two groups of mediastinal lymph nodes, one being ventrolateral and the other dorsoventral relating to cranial precava veins. Usually, in both sides, there is a lymphatic plexus dorsally to the jugulsubclavian angle, formed by reunion of internal jugular and subclavian trunks and the thoracic duct (to the left) or the right lymphatic trunk (to the right). From this plexus, one or two branches run off and flow into the venous jugulosubclavian angle. The subclavian trunk begins in the medial axillar lymph nodes and joins to the lymphatic plexus at the internal jugular trunk or at the thoracic duct or yet at the right lymphatic trunk according to the site, and finally it may link itself directly to the venous system. The mediastinal lymph nodes at the side send branches forming the right lymphatic trunk and branches adhering to the lymphatic plexus; the left lymph nodes join to the plexus or the thoracic duct.

Animals

Functional anatomy of lymph nodes. II. Peripheral lymph-borne mononuclear cells.

In the rabbit a number of large mononuclear cells with ruffled surface membranes travel from the skin and superficial tissues of the leg, via the lymphatics, to the popliteal lymph node: they constitute 40-50% of the total cell population in the afferent lymph. About 10% of these cells are actively phagocytic when tested in vitro and about 3% are found to contain Langerhans granules. After isotopic labelling the majority of lymph-borne mononuclear cells can be detected within the regional node for at least 24 hours; most being located in the paracortex and a few in the interfollicular cortex. It is proposed that these cells, including those containing Langerhans granules, belong to the "mononuclear phagocyte system." Possible functions of these lymph-borne cells are discussed with particular reference to antigen transport.

Adenosine

Lymph macrophages enter the germinal center of lymph nodes of guinea pigs.

To determine the fate of macrophages within the afferent lymph stream, the popliteal lymph nodes at various times (3 h to 6 months) after subcutaneous injection of india ink into the footpads of guinea pigs were examined. Two types of cells which had phagocytized india ink were observed in the germinal centers. A small number of type I phagocytes (engulfing india ink as small particles which were often found together with tingible bodies in their cytoplasm) were scattered through the germinal center. A large number of type II phagocytes (packed full of india ink) presented preferentially in the medullary portion of the germinal center, together with many pyroninophil lymphoblastoid cells. In the second experiment, the afferent lymphatics of the popliteal lymph node were ligated 15-20 min after india ink injection. Although the type I phagocytes were distributed as in the first experiment, the type II phagocytes were scanty. In the third experiment, the afferent lymphatics of the popliteal lymph node were ligated 7 days after india ink injection. The type II phagocytes disappeared rapidly from the germinal center, whereas the type I phagocytes remained and were not affected by ligature. These results suggest that the type I phagocytes are the fixed macrophages or tingible body macrophages in the germinal center, and that the type II phagocytes are the macrophages migrating from the peripheral tissues. It was also shown that many macrophages reaching the regional node via afferent lymphatics entered the germinal center through the medullary pole where the cap of small lymphocytes became thinner or disappeared.

Animals

The appearance of non-specific antibody-forming cells in the efferent lymph draining antigen-stimulated single lymph nodes.

Immunization of single lymph nodes with various antigens led to the appearance of cells in the efferent lymph that secreted antibody specific for the antigen which induced their formation and for a number of unrelated, non-crossreacting antigens. Immunization of single lymph nodes with mitogens led to the appearance of cells secreting antibodies specific for an even greater number of antigens, including one (TNP) that in all probability is not present in the animals' natural environment. When the node was primed with one antigen, a subsequent challenge with an unrelated antigen 12 weeks later led to the appearance of greater numbers of cells containing and secreting antibody against the previously experienced antigen, than was the case in unprimed lymph nodes. These findings indicate that the immune response to antigen provokes the maturation of lymphocytes of specificities unrelated to that of the injected immunogen. Such a mechanism may be important in maintaining immunological memory. Mitogens may directly activate lymphocytes into maturation and expression as antibody-secreting cells, whereas antigens appear to act indirectly.

Animals

[Morphologic features of lymph and blood circulation in lymph nodes in leukemia].

In studies of the lymphatic microcirculation bed in 300 neck and mesenterian lymph nodes taken from 27 patients who had died of systemic diseases, its transformation into lymphatic channels histogenetically connected with various processes in the nodes, was established. The rearrangement of the lymphatic microcirculation bed of the node developed concomitantly with that of the blood circulation bed. In the process of their transformation it seems possible to single out three phases with characteristic stereomorphological (macro-microscopic) and pathomorphological changes - compensation, decompensation and reduction. In reduction of the lymphatic microcirculatory bed around the lymph nodes, as manifestation of compensation, there were formed collaterals. Due to chronic congestion of the lymph, non-affected lymph nodes drastically dilatated and in their walls developed secondary changes in the form, of hyperthophy, varicosis sclerosis and hyalinosis. In the affected lymphatic vessels infiltrative-destructive processes developed.

Hodgkin Disease

[Contrast retention in retroperitoneal lymph nodes after lymphography; the effect of lymph node abnormalities, radiotherapy and contrast quantity].

The rate of contrast loss from retroperitoneal lymph nodes after lymphography was studied radiologically over a prolonged period in 302 patients. It varied remarkably, even in normal persons who were not receiving any treatment. Lymph nodes empty more quickly if only a small quantity of contrast has been used. Irradiation accelerates contrast transport, not only in the irradiated, but also in the neighbouring, group of nodes. This effect is dose dependent. There is evidence that pathological lymph nodes empty more quickly than normal ones.

Adult

[Studies on the lymph drainage of the eye. 1. Quantitative registration of the lymph drainage from the orbita of the rabbit with radioactive tracers (author's transl)].

For the investigation on the lymph drainage from the orbita 99mTc-microcolloid, 99mTc-albumin and 198Au-colloid have been injected into the retrobulbar space of 24 rabbits. Measurements of the activity's distribution have been made in vivo with an Anger type camera (pho-Gamma-IV Hp, Searle Nuclear Chicago) and in vitro after section with a sodium iodine crystal well counter (Clinimat-200, Picker). A significant concentration of the activity could be observed for the most part in the equilateral Lymphonoduli cervicales profundi and superficiales and for the less part also in the equilateral Lymphonoduli mandibulares and contralateral Lymphonoduli cervicales profoundi. Furthermore significant activities could be pointed out in the optic nerves as well as in the contralateral retrobulbar space. The data substantiate a lymph drainage from the orbita as well as a partly reverse "prelymphatic-lymphatic" flow and are of importance for discussions about lymphostatic ophthalmopathy and sympathetic ophthalmitis. For application on man 99mTc-microcolloid (Lymphoscint) shoud be preferred, because with this tracer 1. the lymph drainage can be measured quantitatively quite exactly by extern measurement with the Anger-camera, 2. the allowable radiation dosis for the lens is lying between 0.5-1.0 rad/mCi.

Animals

[Antigen-specific lysis in vitro of lymph node cells of intact mice injected with RNA from viable lymph node cells of immunized animals].

Supernatant fluid obtained after centrifugation of the suspension of viable lymph node cells of immunized animals proved to induce in vivo in the lymph node cells of intact mice sensitivity to lysis with a specific antigen in vitro. This property was possessed after chromatography of the supernatant fluid on Sephadex G-200 by the 3rd fraction (MW about 30000 dalton). DNA-ase, trypsin or deproteinization failed to influence whereas RNA-ase inactivated this fraction in respect to the inducing properties.

Animals