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At least 685 records · Page 38Linked to original sources
PubMed1996

Peripheral blood mononuclear cells of a patient with advanced Hodgkin's lymphoma give rise to permanently growing Hodgkin-Reed Sternberg cells.

A novel Hodgkin's disease (HD) derived cell line, L1236, was established from the peripheral blood of a patient with advanced Hodgkin's disease. Analysis of immunoglobulin (Ig) gene rearrangements revealed a biallelic Ig heavy chain and a monoallelic Ig kappa light chain gene rearrangement, pointing to a B-lymphoid origin of these cells. No DNA of Epstein-Barr virus was detected in L1236. The cells expressed the HD-associated surface antigens CD30 and CD15 as well as the transferrin receptor (CD71). Cytogenetic analysis of early passages of L1236 cells revealed a grossly disordered karyotype including cytogenetic aberrations described previously in other HD-derived cell lines. The Hodgkin/Reed-Sternberg (H-RS) cell origin of L1236 cells is further confirmed by Kanzler et al (Blood 87:3429, 1996), who found identical Ig gene rearrangement sequences in L1236 cells and H-RS cells of the same patient's bone marrow. L1236 cells expressed antigens necessary for efficient antigen presentation to T cells including HLA class I and II, B7.1 and B7.2, as well as adhesion molecules ICAM 1 and LFA 3. The cells secreted the interleukins (IL)-6, -8, -10, tumor necrosis factor (TNF) alpha, interferon (IFN) gamma, transforming growth factor (TGF) beta, and the granulocyte-macrophage colony stimulating factor (GM-CSF). After subcutaneous inoculation into SCID mice, a necrotic regression of initially growing tumors at the injection site was followed by disseminated intralymphatic growth. Our findings, together with the results of Kanzler et al, demonstrate that H-RS cells of B-lymphoid origin were present in the peripheral blood of a patient with advanced HD. These cells exerted a malignant phenotype with regard to their in vitro and in vivo characteristics.

Adult↗
PubMed1989

Clinical responses with active specific intralymphatic immunotherapy for cancer--a phase I-II trial.

We evaluated the method of active specific intralymphatic immunization to treat cancer in 32 patients with various tumor types as part of a broad-based phase I-II evaluation and describe the results of 3 sequential series. In series 1, the patients (n = 13) received 2 or more injections of autologous, cryopreserved, irradiated tumor cells directly into the lymphatic system through the cannulation of a dorsal pedal lymphatic channel. In series 2, the patients (n = 7) received low-dose cyclophosphamide, 300 mg per m2, 3 days before the autologous cell vaccine was administered. Series 3 (12 patients) was similar to series 2 except that the tumor cells were treated with cholesteryl hemisuccinate immediately before irradiation. Patients received from 2 to 6 injections of cells, depending on availability, at 2-week intervals. In all, 91 treatments are evaluated in this study. Clinical responses occurred in 7 of the 32 patients and were seen in all 3 series with about the same frequency. These responses occurred in cases of melanoma, lung cancer, colon cancer, and sarcoma. Regressions occurred in both visceral and subcutaneous sites. There was little toxicity, the chief side effect being local discomfort or inflammation. This experience indicates that active specific intralymphatic immunotherapy is safe, produces antitumor effects, and requires more investigation to increase the frequency and duration of observable tumor regression.

Adult↗
PubMed1989

Immunolymphoscintigraphy.

Immunolymphoscintigraphy (ILS) refers to lymphatic administration of radiolabeled antibodies for lymph node imaging. Macromolecules such as immunoglobulins are preferentially taken up by lymphatic vessels rather than venous capillaries following interstitial injection. They then travel to regional nodes by lymph flow where they can interact with tumor cells, lymphocytes, or macrophages residing within the node. A variety of radiolabeled antibodies and their fragments have been studied, both in animals and humans, to test their ability to selectively target cells in lymph nodes. Preliminary clinical trials in patients with lymphoma, melanoma, and breast cancer suggest that immunolymphoscintigraphy holds great potential for accurate staging of early malignant disease. The procedure is safe and simple to perform, and offers a noninvasive means to detect small deposits of tumor in regional lymph nodes. Furthermore, direct intralymphatic administration results in even more efficient delivery of immunospecific agents, raising the possibility of radiotherapy by this route.

Animals↗
PubMed1990

Kynurenate and 2-amino-5-phosphonovalerate alter the spinal seizures evoked by sudden cooling of toad isolated cords.

Sudden cooling of the isolated spinal cord of toads results in characteristic seizure-like activity in the hindlegs. In the present investigation, kynurenate (KYN), a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist and 2-amino-5-phosphonovalerate (APV), a competitive NMDA receptor antagonist, were tested in the pattern, latency and duration of the spinal seizures. APV, 1.3-2.5 mmol/kg and KYN, 2.6 mmol/kg, inhibited the tonic phase of the spinal seizures and prolonged the duration of the clonic phase after intralymphatic (i.l.) administration. The same effect was observed after intrathecal injection of either 10 or 20 mumol/20 microliter of each drug. The clonic phase was markedly attenuated by KYN at high doses of 5.3 or 10.6 mmol/kg, i.l., suggesting that non-NMDA receptors may have some mediation in the generation of that phase. Both antagonists retarded the onset of seizures indicating that activation of NMDA receptors is likely involved in the beginning of this convulsive-like activity. This model may be a useful technique to assay other excitatory amino acid antagonists.

2-Amino-5-phosphonovalerate↗
PubMed1995

Indium-111 labeled leukocytes in evaluation of active specific immunotherapy responses.

Active immunization of patients utilizing viral oncolysates (VO) has been studied in clinical trials. VO are extracts of cultured tumor cells that have been infected with certain types of viruses, particularly surface budding varieties. The objectives of the current studies were to examine the trafficking patterns of Indium (In)-111-labeled leukocytes or lymphocytes in two groups of patients with gynecologic malignancies to determine whether these cells migrate to sites of active immunization after VO. Eight patients with ovarian cancer received VO intraperitoneally followed by In-111-labeled leukocytes or lymphocytes (500 &mgr;Ci) intravenously. In a separate trial, three patients with cervical cancer received In-111-labeled lymphocytes after they had been treated with VO administered by the intralymphatic route. Gamma camera imaging was performed to evaluate the distribution patterns of the labeled cells at several time intervals after injection. Results indicate that metastatic tumor sites exposed to VO therapy show significant uptake of In-111 cells. These sites of malignancies were confirmed by computerized tomography and ultrasound scans. In patients with ovarian cancer no uptake of the radiolabeled cells was observed in metastatic tumors of the liver and lymph nodes. In patients with cervical cancer, lymph node metastases exposed to intralymphatic VO therapy were visualized very well. Other known tumor sites not exposed to VO therapy showed no uptake of radioactivity. These findings confirm that VO induces immune responses. This diagnostic nuclear medicine technique may prove to be a useful method for following-up responses to immunotherapy.

Journal Article↗
PubMed2003

Injection by various routes of melanoma antigen-associated macrophages: biodistribution and clinical effects.

Patients' autologous macrophages (AM) were used as antigen-presenting cells (APC) in a vaccination protocol against malignant melanoma. AM were administered by various routes, including intralymphatic, since these cells did not express CCR7, a molecule required for APC migration to lymph nodes. Seven HLA-A2 patients with metastatic melanoma-two classified as M1 and five as M3-were included in the study. AM were produced from leukapheresis-separated mononuclear cells by 7-day culture with granulocyte-macrophage colony-stimulating factor. After separation by elutriation, AM were frozen in aliquots and subsequently thawed at monthly intervals, exposed to MAGE-3(271-279) peptide and injected subcutaneously into lymph nodes or into one peripheral lymph vessel. Intradermal tests were performed before and after treatment to determine peptide reactivity. No acute toxicity was observed following injection. One M1 patient had a 7-mm induration intradermal reaction response and was stabilized for 64 weeks. The M3 patients did not show any immunological or clinical response. In 11 patients, the biodistribution of 111In-labeled AM was investigated. There was no clear evidence that AM injected intradermally or subcutaneously left the site of injection. After injection into a lymph vessel of the foot region, scintigraphs showed five to ten popliteal and inguinocrural lymph nodes. This appeared to be the most efficient way to administer rapidly and safely large amounts of peptide-loaded APC into lymph nodes.

Adult↗
PubMed2005

Detection of lymph node involvement in hematologic malignancies using micromagnetic resonance lymphangiography with a gadolinum-labeled dendrimer nanoparticle.

Animal models of lymphoma should reflect their counterparts in humans; however, it can be difficult to ascertain whether an induced disease is intralymphatic or extralymphatic based on direct visualization. Current imaging methods are insufficient for identifying lymphatic and intralymphatic involvement. To differentiate intralymphatic from extralymphatic involvement, we have developed a magnetic resonance imaging-based lymphangiography method and tested it on two animal models of lymphoma. A gadolinium (Gd)-labeled dendrimer nanoparticle (generation-6; approximately 220 kDa/ approximately 10 nm) was injected interstitially into mice bearing hematologic malignancies to perform dynamic micromagnetic resonance lymphangiography (micro-MRL). Both a standard T1-weighted 3D fast spoiled gradient echo and a T2/T1-weighted 3D fast imaging employing steady-state acquisition (3D-FIESTA-C) were compared in an imaging study to differentiate intralymphatic from extralymphatic involvement of tumors. The lymphatics and lymph nodes were visualized with both methods in all cases. In addition, 3D-FIESTA-C depicted both the lymphatic system and the extralymphatic tumor. In an animal model, 3D-FIESTA-C demonstrated that the bulk of the tumor thought to be intralymphatic was actually extralymphatic. In conclusion, micro-MRL, using Gd-labeled dendrimer nanoparticles with the combined method, can define both the normal and abnormal lymphatics and can distinguish intralymphatic from extralymphatic diseases in mouse models of malignant lymphoma.

Animals↗
PubMed1991

Spinal seizures evoked by sudden cooling of amphibian isolated spinal cords: involvement of excitatory amino acids.

Sudden cooling of the isolated spinal cord of frogs results in characteristic seizure-like activity in the hind legs. In the present investigation, these spinal seizures induced by sudden cooling (SSSC) were studied to determine whether excitatory amino acids (EAAs) are involved in the mediation of this activity. The nonspecific EAA antagonist, L-glutamic acid diethyl ester and cis-2,3-piperidine dicarboxylic acid inhibited the clonic and tonic phase of SSSC after intralymphatic or intrathecal administration. The antagonist gamma-D-glutamylaminomethylsulfonic acid and gamma-D-glutamyltaurine also suppressed both phases after intrathecal injections. The NMDA receptor antagonist DL-2-amino-5-phosphonovaleric acid, DL-2-amino-7-phosphonoheptanoic acid, and 3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid were effective inhibitors of the tonic phase and actually prolonged the duration of the clonic phase, an effect similar to that observed after low doses of gamma-D-glutamylglycine. SSSC were resistant to spinal perfusion to tetrodotoxin (1 microM). The concentrations of glutamate, aspartate, and glycine were increased in the Ringer's solution surrounding rapidly cooled spinal cord slices, but only in cords from species that elicited some magnitude of SSSC, not in cords from species resistant to induction of SSSC. Our data support the hypothesis that EAAs play a role in SSSC via activation of quisqualate receptors.

Amino Acids↗
PubMed2004

Transmural pressure during cardiogenic oscillations in rodent diaphragmatic lymphatic vessels.

BACKGROUND: The mechanism of initial lymphatic filling and the role of cardiogenic tissue motion in promoting lymph formation and propulsion are at present still controversial issues, in particular when considering interstitial tissues whose fluid pressure is well below atmospheric. To elucidate these aspects, the micropuncture technique was used to record interstitial (P(int)) and intralymphatic pressure (P(lymph)) simultaneously in the diaphragmatic lymphatic plexus draining the pleural cavity. METHODS AND RESULTS: The diaphragmatic lymphatic network was identified in anesthetized rabbits and rats through fluorescent dextrans injected intrapleurally. All P(lymph) and P(int) traces were pulsatile, oscillating either in-phase (33% of traces) or out-of-phase (67%) during cardiogenic swings. P(lymph) swept between -4.1 +/- 0.9 (SE) mmHg and 3.5 +/- 1.1 mmHg in rabbits, and between -5.1 +/- 1.0 mmHg and -2.7 +/- 1.1 mmHg in rats. P(int) oscillated between -0.8 +/- 0.7 mmHg and 4.9 +/- 0.7 mmHg in rabbits, and between -0.6 +/- 0.8 mmHg and 0.9 +/- 0.7 mmHg in rats. CONCLUSIONS: The data revealed a great functional complexity of the diaphragmatic lymphatic network and suggested that cardiogenic oscillations may play an important role in promoting lymph formation and propulsion from interstitial tissues with subatmospheric tissue pressure.

Animals↗
PubMed1985

Antibody guided lymphangiography in the staging of cervical cancer.

Iodine-123-labelled tumour associated monoclonal antibody HMFG2 was administered intralymphatically at a time that cannulation of pedal lymphatic vessels was performed for standard lymphangiography in 6 patients with cervical cancer. Gamma camera images were taken at 2 h and 24 h after injection of antibody and at a similar time that X-ray lymphangiography was performed. Five out of the 6 standard lymphangiograms were reported as normal whilst one showed definite evidence of metastasis. Antibody guided analysis of the abnormal lymphangiogram confirmed the presence of abnormality. Also, marked non-specific uptake of antibody was seen on all lymphangiograms. It is concluded that, in order for monoclonal antibody guided lymphangiography to become a useful adjunct to standard lymphangiography, further improvements are needed to reduce non-specific uptake by normal lymphatics.

Adult↗
PubMedDate not supplied

Lymphagogue and pulsatile activities of Daflon 500 mg on canine thoracic lymph duct.

An earlier report proved that Daflon 500 mg constituted of 90% diosmin and 10% hesperidin exerts a lymphagogue effect on dogs. The aim of the present work is to investigate whether the lymphagogue effect of Daflon 500 mg is associated with an increase in pulsatile activity of lymphatic vessels. The investigation was carried out on mongrel dogs anaesthetised by pentobarbital (10 mg/kg); the lymph was collected by a fistula on the thoracic lymphatic duct; using this fistula the pulsatile activity of lymphatic vessels was estimated by Campbell and Health methodology. The lymphatic volume was measured every ten-minutes in graduated tubes for 2 hours and the pulsatile component of intralymphatic pressure (MPC) was estimated from measurements of the area (expressed in mm2) enclosed by the part of the tracing due to the pulsatile component during one minute. Daflon 500 mg was intravenously injected after having been dissolved in DMSO + TRIS; three doses were injected: 12.5, 6.25 and 3.125 mg/kg. Regarding the lymphagogue effect, Daflon 500 mg induced an increase in lymphatic flow correlated with the administered doses. The maximal 10-minute period lymphatic flows were 191% (12.5 mg/kg), 171% (6.25 mg/kg) and 91% (3.125 mg/kg); the peak of the effect was, in each case, reached between 20 and 25 minutes after the injection. Regarding the pulsatile activity, Daflon 500 mg induced an increase of MPC. The MPC was correlated with the increase in lymph flow (r = 0.877).

Animals↗
PubMed1997

Dopaminergic modulation of visual responses in toads. I. Apomorphine-induced effects on visually directed appetitive and consummatory prey-catching behavior.

This study confirms for a phylogenetically basal terrestrial vertebrate that dopaminergic modulations interfere with the visually directed appetitive and consummatory feeding behaviors orienting and snapping, respectively. (1) In common toads Bufo bufo, intralymphatic administration of the dopamine D2/D1-receptor agonist apomorphine led to a dose-dependent facilitation of prey-snapping in response to moving objects. The snapping activity reached a maximum 15-35 min after apomorphine injection. (2) To changes in configurational stimulus features, the basic pattern of discrimination was maintained; however, the acuity of discrimination was reduced due to the high snapping response level. (3) The apomorphine-induced facilitation of snapping was accompanied by a suppression of prey-oriented lunging and turning. Toads snapped only if prey occurred frontally in the visual field at a relatively short distance. The snapping behavior was fixed in its form and stereotyped regarding its immediate release. (4) About 90 min after apomorphine administration, prey-oriented turning behavior was restored and displayed a facilitatory rebound. (5) In comparative experiments with the species B. marinus, both prey-oriented turning and snapping responses were suppressed by apomorphine in a dose-dependent manner. (6) After pre-treatment with the dopamine antagonist haloperidol, apomorphine showed no measurable effect on the visual release of prey orienting or snapping. (7) The results contribute to the sensorimotor and the motivation hypothesis of dopamine function proposed for higher vertebrates and stimulate a comparative discussion of anatomic homologies and functional analogies.

Animals↗
PubMed1979

An experimental study of the spread of tumor cells through the lymph node.

Intralymphatic inoculation of rat ascites hepatoma AH 130 was carried out to elucidate the function of the regional lymph node as a barrier against tumor spread. Tumor cells reaching regional lymph nodes decreased in number 48 to 72 hr after inoculation. Ten percent of tumor cells injected into lymphatic vessels appeared in the thoracic duct within 3 hr after injection. Bioassay tests revealed that transnodal tumor cells were viable in the thoracic duct.

Animals↗
PubMed2005

Hyaluronan promotes tumor lymphangiogenesis and intralymphantic tumor growth in xenografts.

Hyaluronan (HA), a high molecular weight glycosaminoglycan in the extracellular matrix, has been implicated in the promotion of malignant phenotypes, including tumor angiogenesis. However, little is known about the effect of HA on tumor-associated lymphangiogenesis. In this study, mouse hepatocellular carcinoma Hca-F cells combined with or without HA were injected subcutaneously into C3H/Hej mice, then angiogenesis and lymphangiogenesis of implanted tumors were examined by immunostaining for platelet-endothelial cell adhesion molecule-1 and lymphatic vascular endothelial hyaluronan receptor-1 respectively. Interestingly, we found HA promotes tumor lymphangiogenesis and the occurrence of intratumoral lymphatic vessels, but has little effect on tumor angiogenesis. Moreover, HA also promotes intralymphatic tumor growth, although it is not sufficient to potentiate lymphatic metastasis. These results suggest that HA, which is elevated in most malignant tumor stroma, may also play a role in tumor progression by promoting lymphangiogenesis.

Animals↗
PubMed1991

Altered adult worm location in young male jirds infected with Brugia pahangi.

Male jirds (Meriones unguiculatus) were inoculated subcutaneously with 100 Brugia pahangi L3 each at 2, 6, 10, and 15 wk of age to compare their susceptibility and pathologic reactivity to infection. Adult worm recoveries (mean +/- SD) ranged from 24.1 +/- 15.1 to 36.4 +/- 13.9 at 60 days postinfection. No significant difference in susceptibility was measured among the 4 age groups. Jirds infected at 2 wk of age had significantly fewer (alpha less than or equal to 0.025) testicular and intralymphatic worms than all other age groups. Numbers of intralymphatic thrombi were significantly lower (alpha less than or equal to 0.01) in jirds infected at 2 wk of age. Lymphatic lesion severity, expressed as the number of intralymphatic thrombi per intralymphatic worm, was similar between age groups. These data indicate no differences in susceptibility or lymphatic lesion formation following B. pahangi infection in 2-wk-old male jirds, despite altered adult worm location.

Aging↗
PubMed1978

[Radionuclide therapy of malignant tumors].

A survey is given on the modern possibilities of the therapy of malignant tumours with radiopharmaca. In detail the following methods of treatment introduced into the nuclearmedical therapy are described: 1. Radioiodine therapy in folliculary and papillary carcinomas of the thyroid gland, 2. Radiophosphorus therapy in polycythaemia vera and myeloproliferative syndrome, 3. Radiogold therapy in peritoneal and pleural carcinoses, 4. Intrathecal radionuclide application in meningeosis leucaemica, 5. Intralymphatic radionuclide application to the therapy of malignant lymphomas, 6. Radionuclide therapy of multiple bone metastases. With the help of literature and own experiences the author enters the indication and the performance of the therapy as well as the possible successes of treatment, when using the therapy forms mentioned.

Aged↗