Minimal uranium accumulation in lymphoid tissues following an oral 60-day uranyl acetate exposure in male and female C57BL/6J mice.

High levels of uranium (U) exist in soil, water, and air in the Southwestern United States due, in part, to waste generated from more than 160,000 abandoned hard rock mines located in this region. As a result, many people living in this region are chronically exposed to U at levels that have been linked to detrimental health outcomes. In an effort to establish a relevant in vivo mouse model for future U immunotoxicity studies, we evaluated the tissue distribution of U in immune organs; blood, bone marrow, spleen, and thymus, as well as femur bones, kidneys, and liver, following a 60-d drinking water exposure to uranyl acetate (UA) in male and female C57BL/6J mice. Following the 60-d exposure, there was low overall tissue retention of U (<0.01%) at both the 5 and the 50 ppm (mg/L) oral concentrations. In both male and female mice, there was limited U accumulation in immune organs. U only accumulated at low concentrations in the blood and bone marrow of male mice (0.6 and 16.8 ng/g, respectively). Consistent with previous reports, the predominant sites of U accumulation were the femur bones (350.1 and 399.0 ng/g, respectively) and kidneys (134.0 and 361.3 ng/g, respectively) of male and female mice. Findings from this study provide critical insights into the distribution and retention of U in lymphoid tissues following chronic drinking water exposure to U. This information will serve as a foundation for immunotoxicological assessments of U, alone and in combination with other metals.

Efficacy and safety of far infrared radiation in lymphedema treatment: clinical evaluation and laboratory analysis.

Swelling is the most common symptom of extremities lymphedema. Clinical evaluation and laboratory analysis were conducted after far infrared radiation (FIR) treatment on the main four components of lymphedema: fluid, fat, protein, and hyaluronan. Far infrared radiation is a kind of hyperthermia therapy with several and additional benefits as well as promoting microcirculation flow and improving collateral lymph circumfluence. Although FIR therapy has been applied for several years on thousands of lymphedema patients, there are still few studies that have reported the biological effects of FIR on lymphatic tissue. In this research, we investigate the effects of far infrared rays on the major components of lymphatic tissue. Then, we explore the effectiveness and safety of FIR as a promising treatment modality of lymphedema. A total of 32 patients affected by lymphedema in stage II and III were treated between January 2015 and January 2016 at our department. After therapy, a significant decrease of limb circumference measurements was noted and improving of quality of life was registered. Laboratory examination showed the treatment can also decrease the deposition of fluid, fat, hyaluronan, and protein, improving the swelling condition. We believe FIR treatment could be considered as both an alternative monotherapy and a useful adjunctive to the conservative or surgical lymphedema procedures. Furthermore, the real and significant biological effects of FIR represent possible future applications in wide range of the medical field.

Splenic adherent cells, stimulated in vitro, induce the reactive formation of lymphoid follicles and germinal centres in draining lymph nodes after subcutaneous transfusion into syngeneic mice.

The reactive formation of lymphoid follicles and germinal centres in lymph nodes, induced by subcutaneous transfer of in vitro activated splenic adherent cells into syngeneic mice, were studied. Adherent cells were obtained by incubating spleen cell suspensions for 24 h and activated by incubating for 1 h in the medium containing keyhole limpet haemocyanin (KLH) absorbed onto alumina. Some of the treated adherent cells were irradiated with 10 Gy x-rays, while others were either not stimulated or were stimulated with alumina-KLH but killed by repeated freezing and thawing. Examination of adherent cell smears immunostained with antibodies against, F4/80, Mac-1, Mac-2 and NLDC-145 indicated that many adherent cells displayed macrophage markers but few displayed the interdigitating cell marker. Animals transfused with KLH-treated adherent cells with or without irradiation showed a marked increase in the number of lymphoid follicles and germinal centres in draining lymph nodes, whereas those transfused with adherent cells which had not been KLH-treated or which had been killed after KLH treatment displayed no significant change in the number of follicles. These results were interpreted as indicating that following transfusion, antigen-activated adherent macrophages migrated into the draining lymph nodes and induced the reactive formation of lymphoid follicles and germinal centres outside preexisting follicles.

Selective radiation of hematolymphoid tissue delivered by anti-CD45 antibody.

The ability to deliver radiation selectively to lymphohematopoietic tissues may have utility in conditions treated by myeloablative regimens followed by bone marrow transplantation. Since the CD45 antigen is the most broadly expressed of hematopoietic antigens, we examined the biodistribution of radiolabeled anti-CD45 monoclonal antibodies in normal mice. Trace 125I or 131I-labeled monoclonal antibodies 30G12 (rat IgG2a), 30F11 (rat IgG2b), and F(ab')2 fragments of 30F11 were injected i.v. at doses of 5 to 1000 micrograms. For both intact antibodies, a higher percentage of injected dose/g (% ID/g tissue) in blood was achieved with higher antibody doses. However, as the dose of antibody was increased, the % ID/g in the target organs of spleen, marrow, and lymph nodes decreased. At doses between 5 and 10-micrograms, % ID/g in these tissues exceeded that in lung, the normal organ with the highest concentration of radiolabel. In contrast, thymus was the only hematopoietic organ in which the % ID/g increased with increasing antibody dose, although at high dose the % ID/g was still far below that achieved in the other hematopoietic organs. Antibody 30F11 F(ab')2 fragments were cleared more quickly than intact antibody from blood and from both target and nontarget organs, although the relationship between increasing antibody dose and decreasing % ID/g in spleen, marrow, and lymph nodes was observed. The time-activity curves for each dose of antibody were used to calculate estimates of radiation absorbed dose to each organ. At the 10-micrograms dose of 30G12, the spleen was estimated to receive a radiation dose that was 13 times more than lung, the lymph nodes 3 to 4 times more, and the bone marrow 3 times more than lung. For each antibody fragment dose, the radiation absorbed dose per MBq 131I administered was lower because the residence times of the fragments were shorter than those of the intact antibody. Thus these estimates suggested that the best "therapeutic ratio" of radiation delivered to target organ as compared to lung was achieved with lower doses of intact antibody. We have demonstrated that radiolabeled anti-CD45 monoclonal antibodies can deliver radiation to lymphohematopoietic tissues with relative selectivity and that the relative uptake and retention in different hematolymphoid tissues change with increasing antibody dose.

Immunological consequences of ultraviolet radiation exposure.

Depending on the dose and conditions of administration, ultraviolet radiation (UVR) can function as either a complete carcinogen, a co-carcinogenic agent, or an immunologic modulator. Although much is known about its carcinogenic properties, only recently have investigations been aimed at defining the mechanisms by which UVR mediates its effect on the immune system. The objective of this article is to present the necessary background and results of recent studies that provide the basis for defining some of the local and systemic effects that UVR has on an individual's immunologic potential. This discussion focuses on: the histologic alterations in the skin and draining lymph nodes, the changes in lymphocyte localization, the increased release of the immunologic (and physiologic) mediator ETAF/IL-1, and the induction of antigen-specific immunoregulatory circuits that occur subsequent to UVR exposure. It is our hypothesis that the detrimental effects that UVR has on the host's immunologic competence may represent a normal defense mechanism to protect the individual against the adverse consequences of chronic inflammatory stimuli. In this regard, a better understanding of photoimmunology may lead to the development of more effective means of immunologic modulation for altering the clinical course of various human diseases that are either immunologically mediated, photoinduced, or responsive to phototherapy.

In vitro assay of the effects of psoralens plus ultraviolet radiation on human lymphoid cells.

An in vitro assay system that mimics some of the features of in vivo oral methoxsalen photochemotherapy (PUVA) in relation to human lymphoid cells was developed. In this assay, suspension cultures of human lymphoid cells were subjected to therapeutic concentrations of 8-MOP and to a UVA radiation spectrum modified to approximate the dermal exposure. The assay permitted correlation and quantitation of multiple 8-MOP plus UVA-induced biological and physical alterations in the same assay system. Thus were demonstrated inhibition of DNA synthesis, reduction of cell survival, production of DNA cross-links, and loss of mixed leukocyte reactivity induced by combinations of 8-MOP and UVA in or near the presumed therapeutic range. This assay may be useful for predicting lymphoid cellular toxicity of other photoactive agents as well as for examining the molecular effects of these agents.