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At least 325 records · Page 18Linked to original sources
PubMedDate not supplied

Drug depots in lymph nodes: which carrier is most appropriate?

Different drug carriers for endolymphatic use (suspensions, emulsions, solutions, liposomes) were investigated in animal experiments to find the preparation which is best tolerated by lymph tissue, and which allows low release of highly concentrated drugs from nodal depots. The large unilamellar liposomes produced with detergent dialysis technique were found to be most appropriate for this purpose since they fulfill all the above criteria.

Animals↗
PubMed1993

Chemocoagulation of metastatic lymph nodes using a suspension of mitomycin C-adsorbing activated carbon particles in 80% ethanol.

Chemocoagulation therapy was evaluated in an experimental model of metastasis of murine lymph nodes following injection of a suspension of mitomycin C--containing activated carbon particles in 80% ethanol (MMC-CH-ET) into the popliteal lymph node. Lymph node metastasis was induced in the left popliteal and the lumbar lymph nodes 8 days after injection of mouse leukemia P388 cells into the footpad of the left hindleg of BDF1 mice. When MMC-CH-ET was injected into the left popliteal lymph node, it immediately left this site and entered the lumbar lymph node via lymphatic vessels. When compared with tissue concentrations of mitomycin C following injection of an aqueous solution of this drug, the mitomycin C concentration of MMC-CH-ET was maintained at significantly higher levels for 2 hr following injection both at the site of injection and at secondary lymph nodes. Furthermore, coagulative necrosis was identified histologically throughout the injected lymph node and the secondary lymph node, including the metastatic site. The mortality of mice treated with MMC-CH-ET injection was significantly reduced and lymph node metastasis was controlled with MMC-CH-ET when compared with the results for mice treated with an aqueous solution of mitomycin C or treated by surgical lymph node dissection. In this report, we suggest that the use of MMC-CH-ET as a therapeutic agent may be useful in targeting lymph node metastasis.

Animals↗
PubMed1994

Effect of whole Staphylococcus aureus and mode of immunization on bovine opsonizing antibodies to capsule.

Exopolysaccharide capsule is a major virulence factor of Staphylococcus aureus because it inhibits neutrophil recognition of antibodies to highly antigenic S. aureus cell wall. To circumvent this inhibition, two modes of immunization were tested for ability to induce anticapsular opsonins. Cows were immunized at drying off and boosted on d 14 and 28 by injection of Smith diffuse S. aureus plus dextran sulfate in the area of the supramammary lymph node or intramammarily. In cows immunized in the area of the supramammary lymph node, IgG1 and IgG2 sera antibody titers to capsule increased and remained elevated to the end of the study, 120 d postcalving. The IgM titers increased during the dry period but declined to preimmunization levels at calving. Response of serum IgG1 and IgM to intramammary immunization was similar to that with supramammary lymph node immunization, but more delayed and lower in magnitude. Antibodies of all four isotypes, IgG1, IgG2, IgA, and IgM, increased in dry secretions following immunization via lymph node. In cows immunized in the lymph node, IgG1 antibodies remained elevated throughout the study, but IgG2 antibodies dropped to baseline 15 d postcalving. In cows immunized intramammarily, only IgA antibodies increased significantly in lacteal secretions and remained elevated throughout the study. Immunization of cows in the lymph node during the dry period enhanced the ability of dry secretions and colostrum to support phagocytosis.

Analysis of Variance↗
PubMed2004

Reevaluation of bone marrow-derived cells as a source for hepatocyte regeneration.

We have investigated the contribution of intrasplenic bone marrow transplants or in vivo mobilized hematopoietic stem cells to the formation of hepatocytes in normal and injured liver. Direct intrasplenic injections of bone marrow mononuclear cells (5 x 10(5) cells), Scal+/lin- hematopoietic stem cells (5 x 10(3)) cells, and highly purified "side population" hematopoietic stem cells (5 x 10(3)) derived from enhanced green fluorescent protein (EGFP)-transgenic mice [C57Bl/6-TgN(ActbEGFP)1Osb] were performed in normal C57Bl/6 mice (n = 6) and in C57Bl/6 mice following two thirds hepatectomy (n = 8). To test the effect of mobilized stem cells on transdifferentiation, C57Bl/6 mice (n = 12) were lethally irradiated and reconstituted with EGFP-positive bone marrow mononuclear cells in a second series of experiments. Eight to 12 weeks after bone marrow transplantation a subset of mice (n = 3 in each group) received either rhG-CSF for hematopoietic stem cell mobilization, rhG-CSF combined with an intraperitoneal application of carbon tetrachloride (CCl4) as hepatocyte regeneration stimulus, or CCl4 alone. All mice were completely perfused with PBS to remove circulating nonorgan cells for analyses 4 weeks later. Liver as well as heart, intestine, spleen, and kidney tissue was analyzed for the presence of EGFP-transgenic cells. In 100 sections (2.3 x 10(7) cells) of any recipient mouse no EGFP-positive hepatocytes were detected either by analysis of native EGFP fluorescence or by immunofluorescence analysis with anti-EGFP and antidipeptidyl peptidase (DPP) IV antibodies. EGFP-transgenic cells resembling heart, kidney, or intestinal cells could also not be proven. The results demonstrate that there is little or no contribution of bone marrow-derived cells to the regeneration of normal and injured liver in the animal models used. Thus, potential therapeutic prospects of hematopoietic stem cell therapy for liver disease have to be critically reassessed.

Animals↗
PubMed2000

[Vestibular symptoms and ENG findings during periods of convalescence after endolymphatic sac drainage and steroid-instillation surgery (EDSS)].

Understanding the appearance of vestibular symptoms during periods of convalescence after surgery for the treatment of Meniere's disease is important for determining when a patient can return to work as well as the long-term results of the operation. We have treated 20 cases of intractable Meniere's disease with endolymphatic sac drainage & steroid-instillation surgery (EDSS) [Kitahara T, et al., Ann Otol Rhlnol Laryngol in press, 2000] and observed the subjective symptoms and objective vestibular findings using electronystagmogram (ENG) during the subsequent period of convalescence. The average postoperative durations of subjective static and evoked vestibular symptoms were 1.7 and 6.7 days, respectively. Those of spontaneous, positional and positioning nystagmus observed using ENG were 1.2, 2.0 and 7.9 days, respectively. In cases with a long history of Meniere's disease, postoperative static vestibular sensation and positional nystagmus lasted significantly longer than in cases with short histories. In cases with poorly developed temporal bony pneumatization in the area behind the posterior semicircular canal, postoperative evoked vestibular sensations and positioning nystagmus lasted significantly longer than in cases with well developed temporal bony pneumatization. Vestibular symptoms resulting from direct invasion during EDSS were considered to be slighter than those resulting from vestibular neurectomy or gentamicin treatment and almost the same as those resulting from endolymphatic sac surgery.

Adult↗
PubMed2000

An intra-Peyer's patch gene transfer model for studying mucosal tolerance: distinct roles of B7 and IL-12 in mucosal T cell tolerance.

Development of mucosal immunity and tolerance requires coordinated expression of a number of genes within the mucosa-associated lymphoid tissue (MALT). To study the roles of these genes in the MALT, we have established a MALT-specific gene transfer model using replication-defective adenovirus as vector. In this model, the target gene of interest is directly delivered into the Peyer's patch by intra-Peyer's patch injection of the recombinant virus. Using this gene transfer model, we investigated the roles of B7-1 and IL-12 in the development of mucosal tolerance. We found that intra-Peyer's patch injection of OVA induced Ag-specific T cell hyporesponsiveness, as manifested by decreased T cell proliferation and IL-2/IFN-gamma production upon subsequent immune challenge. Intra-Peyer's patch B7-1 gene transfer at the time of OVA administration partially reversed the inhibition of T cell proliferation and IL-2 secretion, but had no effect on IFN-gamma production. By contrast, intra-Peyer's patch IL-12 gene transfer completely restored T cell proliferation and IFN-gamma secretion and partially reversed IL-2 inhibition. Using an adoptive TCR transgenic model, we further demonstrated that B7 and IL-12 played distinct roles during the inductive phase of mucosal tolerance. B7 selectively increased T cell proliferation and IL-2 secretion without affecting IFN-gamma production, whereas IL-12 increased both IL-2 and IFN-gamma production. These results indicate that B7 alone may not be sufficient to abrogate mucosal tolerance, and that cytokines such as IL-12 may also be required. Based on these findings, we propose a new model to explain the paradoxical roles of B7 in mucosal immunity and tolerance.

Adenoviruses, Human↗
PubMed2000

A profound deficiency in thymic progenitor cells in mice lacking Jak3.

Humans and mice with genetic deficiencies that lead to loss of signaling through common gamma-chain (gammac)-containing cytokine receptors have severe defects in B and T lymphocytes. In humans, these deficiencies lead to a complete absence of T cells, whereas in mice, small thymuses give rise to normal numbers of peripheral T cells. We have examined the first wave of developing T cells in Jak3-/-, IL-7-/-, and IL-7Ralpha-/- fetal mice, and have found a near absence of thymic progenitor cells. This deficiency is highlighted by the complete inability of Jak3-/- progenitor cells to reconstitute T cell development in the presence of competing wild-type cells. These data clearly demonstrate a strong common basis for the T cell deficiencies in mice and humans lacking gammac/Jak3 signaling pathways.

Animals↗
PubMed2002

Stromal cells provide the matrix for migration of early lymphoid progenitors through the thymic cortex.

During steady state lymphopoiesis in the postnatal thymus, migration of precursors outward from the deep cortex toward the capsule is required for normal differentiation. Such migration requires, at a minimum, expression of adhesive receptors on the migrating lymphoid cells, as well as a stable matrix of their ligands persisting throughout the region of migration. In this study, we address the nature of this adhesive matrix. Although some precursor stages bound efficiently to extracellular matrix ligands, a specific requirement for the cell surface ligand VCAM-1 was also found. In situ analysis revealed that early precursors are found in intimate contact with a matrix formed by stromal cells in the cortex, a proportion of which expresses VCAM-1. In vivo administration of an anti-VCAM-1 Ab resulted in decreased thymic size and altered distribution of early precursors within the cortex. These results indicate that precursors migrating outward through the cortex may use a cellular, rather than extracellular, matrix for adhesion, and suggest that the VCAM-1(+) subset of cortical stroma may play a crucial role in supporting the migration of early precursors in the steady state thymus.

Animals↗
PubMed2003

CD25+ immunoregulatory CD4 T cells mediate acquired central transplantation tolerance.

Transplantation tolerance is induced reliably in experimental animals following intrathymic inoculation with the relevant donor strain Ags; however, the immunological mechanisms responsible for the induction and maintenance of the tolerant state remain unknown. We investigated these mechanisms using TCR transgenic mice (TS1) that carry T cells specific for an immunodominant, MHC class II-restricted peptide (S1) of the influenza PR8 hemagglutinin (HA) molecule. We demonstrated that TS1 mice reject skin grafts that have transgene-encoded HA molecules (HA104) as their sole antigenic disparity and that intrathymic but not i.v. inoculation of TS1 mice with S1 peptide induces tolerance to HA-expressing skin grafts. Intrathymic peptide inoculation was associated with a dose-dependent reduction in T cells bearing high levels of TCR specific for HA. However, this reduction was both incomplete and transient, with a full recovery of S1-specific thymocytes by 4 wk. Peptide inoculation into the thymus also resulted in the generation of immunoregulatory T cells (CD4+CD25+) that migrated to the peripheral lymphoid organs. Adoptive transfer experiments using FACS sorted CD4+CD25- and CD4+CD25+ T cells from tolerant mice revealed that the former but not the latter maintain the capacity to induce rejection of HA bearing skin allografts in syngeneic hosts. Our results suggest that both clonal frequency reduction in the thymus and immunoregulatory T cells exported from the thymus are critical to transplantation tolerance induced by intrathymic Ag inoculation.

Adoptive Transfer↗
PubMed2003

Adenovirus-transduced dendritic cells injected into skin or lymph node prime potent simian immunodeficiency virus-specific T cell immunity in monkeys.

Adenoviral vectors can be used to deliver complex Ag to dendritic cells (DC), and thus may be ideal for stimulating broad T cell responses to viral pathogens and tumors. To test this hypothesis in a relevant primate model, we used recombinant adenovirus serotype 5 vectors expressing SIV Gag Ag to transduce monocyte-derived DC from rhesus macaques, and then immunized donor animals either by intradermal or intranodal injections. T cell responses were evaluated by ELISPOT assay using previously frozen PBMC pulsed with pools of 15-mer peptides representing the Gag sequence. Immunization resulted in rapid and potent induction of T cell responses to multiple regions of Gag, with frequencies approaching 1 Gag-specific T cell per 500 uncultured PBMC. Surprisingly, intradermal and intranodal injections generated a similar intensity and breadth of response, indicating that administration of Ag-expressing DC by either route may be equally effective at inducing immune responses. Detailed analysis of two monkeys revealed CD8(+) T cell responses to several peptide epitopes of Gag not previously described, at least two of which are restricted by MHC class I alleles not currently identified. Repeated vaccination did not induce T cell responses to the adenoviral vector and did not prevent Ag-expressing DC injected under the capsule of the lymph node from migrating to the paracortex and interposing between T cells. However, boost injections of adenovirus-transduced DC were generally limited in efficacy. These findings support the use of adenovirus-transduced DC in the therapy of HIV infection and cancer.

Adenoviridae↗
PubMed1999

[Complications of indirect lymphotropic therapy in patients with suppurative wounds].

With the aim to reveal the frequency of complications in indirect lymphotropic therapy, retrospective analysis of 2136 case records of patients with festering wounds was carried out. In 1.59% of patients the following complications in the area of introduction of preparation were detected: protracted oedemas of hands and feet, severe painful syndrome, infiltration, necroses of soft tissues and the areas of atrophy and aseptic inflammation. Most commonly the complications arose in patients with peripheral circulation disturbances. The authors suggested this method of treatment to be contraindicated in peripheral blood flow disturbances and before its application the additional examination for revealing vascular disturbances is obligatory. In cases of painful syndrome, oedema, infiltration, hyperemia in the area of introduction of the drugs one day after the injection, indirect lymphotropic therapy should be discontinued.

Anti-Bacterial Agents↗
PubMed1999

[The determination of individual sensitivity to 5-fluorouracil in patients with malignant tumors in different locations].

Possible determination of individual chemosensitivity of tumors to 5-fluorouracil was investigated using new original data and suggestions that lymphocytes of the tumor carrier have an ability to assimilate chemical drugs. Such an ability is likely due to the fact that 5-fluorouracil as an antimetabolite converted its action by inclusion of lymphocytes to the nucleic acid metabolism. The relation between the phenomenon and the chemotherapy efficacy is possibly realized through two mechanisms. One of them is the direct cytotoxic action of chemical drugs on lymphocyte tumor-associated clones resulting in impairment of the tumor growth control. The other is possible participation of lymphocytes in transport of chemical drugs to the tumor tissue. The in vitro model for estimation of tumor carrier chemosensitivity by the level of the nucleic acid metabolism reflects the impact of the immune system on realization of the antitumor effect of chemical drugs.

Antimetabolites, Antineoplastic↗
PubMedDate not supplied

[Lymphotherapy of early postoperative period in intraocular cataract correction].

Potentialities of lymphotropic method of drug administration for arresting inflammation after intraocular cataract correction were studied in 60 patients aged 48-63 years. Extracapsular cataract extraction with implantation of posterior-chamber Alexeev's intraocular lens (IOL) was carried out in all of them. Patients with complications of surgery and a history of inflammations in the operated eye were not included in the study. For assessing lymphotherapy effect on drug concentration in the blood, bloodflow aggregation gradient in the bulbar conjunctiva venules was estimated in the operated on eye. The data indicate that lymphotherapy is an effective method for treating early postoperative inflammations after IOL implantation, shortening the treatment terms in comparison with traditional therapy.

Anti-Bacterial Agents↗
PubMed1999

[Peritoneal sorption and lymphotropic therapy of postoperative diffuse purulent peritonitis].

New method for treatment of postoperative diffuse purulent peritonitis is proposed and used in 30 patients. It is based on combined application of sanation relaparotomies, peritoneosorption by the sorbent SUMS-1 with metronidazole, adsorbed on it, and lymphotropic antibacterial therapy. The treatment resulted in quicker restoration of clinical and laboratory values, reduced in frequency of pyoinflammatory complications and decreased lethality rate to 20% in comparison with conventional treatment.

Adolescent↗