RESUMO
PURPOSE: In a phase II trial with paclitaxel and simultaneous radiotherapy in non-small-cell lung cancer (NSCLC) patients, an unexpected high incidence of interstitial pneumonias was observed. The type of immunodeficiency associated with this treatment approach is characterized. PATIENTS AND METHODS: Fifteen patients with inoperable stage IIIA/B NSCLC were treated with paclitaxel as a 3-hour infusion on day 1 in weeks 1 to 3 and 6 to 8 at dose levels between 50 mg/m2 and 86 mg/m2 and with simultaneous radiotherapy in daily doses of 2 Gy, 5 days per week, in weeks 1 to 3 and 6 to 8 up to a total dose of 56 Gy. Hematologic parameters and lymphocyte subsets were monitored. RESULTS: Fourteen patients are assessable for response. The overall response rate was 78%, with four major responses, six partial remissions, and four minor responses. The major toxic effect observed was a moderate to severe protracted lymphocytopenia (380 +/- 310/microL) in all patients. Seven patients developed moderate to severe interstitial pneumonia; one had an additional herpes zoster infection, while an eighth patient had a cytomegalovirus infection. During treatment, all lymphocyte subsets were reduced, as follows (n = 9, mean +/- SD): CD4+ T cells (100 +/- 90/microL), CD8+ T cells (130 +/- 160/microL), natural killer (NK) cells (70 +/- 80/microL), and B cells (20 +/- 10/microL). Thus, the most pronounced toxicity was seen in CD4+ T and B cells. There was no recovery of lymphocyte subsets during a 3-month follow-up period. CONCLUSION: Paclitaxel with simultaneous radiation induces lymphocytopenia and promotes opportunistic infections. Long-term antibiotic and antimycotic prophylaxis is recommended. Whether the lymphocytopenia is an additive effect of paclitaxel and radiation or whether it can be induced by low-dose weekly paclitaxel alone remains to be determined.
Assuntos
Antineoplásicos Fitogênicos/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Doenças Pulmonares Intersticiais/etiologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/radioterapia , Linfopenia/etiologia , Infecções Oportunistas/etiologia , Paclitaxel/efeitos adversos , Adulto , Idoso , Antineoplásicos Fitogênicos/administração & dosagem , Quimioterapia Adjuvante , Esquema de Medicação , Citometria de Fluxo , Humanos , Doenças Pulmonares Intersticiais/induzido quimicamente , Contagem de Linfócitos/efeitos dos fármacos , Contagem de Linfócitos/efeitos da radiação , Linfopenia/induzido quimicamente , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Radioterapia AdjuvanteRESUMO
Xeroderma pigmentosum group A gene-deficient mice easily develop skin cancers by ultraviolet radiation. Natural killer cells play an important part in tumor surveillance. To study whether ultraviolet radiation-induced suppression of natural killer cell function is involved in the high incidence of skin tumors in patients with xeroderma pigmentosum, we analyzed the number and activity of natural killer cells in ultraviolet B-irradiated xeroderma pigmentosum A model mice. The number of natural killer cells in peripheral blood significantly decreased after ultraviolet B-irradiation only in xeroderma pigmentosum A mice, but those in the spleen were not affected. As compared with the wild-type mice, the xeroderma pigmentosum A mice displayed a higher level of spontaneous splenic natural killer cell activity (10%-15% vs 3%) and inducible natural killer activity (30%-50% vs 20%-25%) after injection of polyinosinic:polycytidylic acid. At 24 h after the last irradiation of three and five daily consecutive exposures to 500 mJ per cm2-ultraviolet B, however, the natural killer activity in xeroderma pigmentosum A mice decreased to 60 and 30% of the preirradiated level, respectively, but it did not in the wild-type mice. The depression of natural killer activity in xeroderma pigmentosum A mice recovered to a normal level at 10 and 15 d after the last irradiation, respectively. The high incidence of skin cancers in xeroderma pigmentosum patients may be mainly due to a defect in the repair of ultraviolet-damaged DNA of cutaneous cells, and possibly also due to an intensified ultraviolet-induced immunosuppression. Moreover, the present study suggests that the enhanced ultraviolet-induced impairment of natural killer function could be partially involved in cancer development.
Assuntos
Modelos Animais de Doenças , Células Matadoras Naturais/imunologia , Raios Ultravioleta , Xeroderma Pigmentoso/imunologia , Animais , Tolerância Imunológica/efeitos da radiação , Células Matadoras Naturais/efeitos dos fármacos , Contagem de Linfócitos/efeitos da radiação , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos CBA , Poli I-C/farmacologia , Baço/citologiaRESUMO
In the determination of alloreactive helper T lymphocyte precursor frequencies (HTLpf) by limiting dilution analysis (LDA), peripheral blood mononuclear cells (PBMC) are used as stimulating cells. Interleukin-2 (IL-2) production by stimulating T cells constitute a source of error in these assays. We found that 100-150 Gy of gamma irradiation was required to abrogate IL-2 production by stimulating PBMC. This dose of irradiation, however, greatly reduced their allostimulatory capability. Here we describe how non-irradiated PBMC, immunomagnetically depleted of T cells and thus of IL-2 producing cells, can be used as stimulators in assays to determine alloresponsive HTLpf.
Assuntos
Interleucina-2/fisiologia , Ativação Linfocitária , Células-Tronco/imunologia , Linfócitos T Auxiliares-Indutores/imunologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Relação Dose-Resposta à Radiação , Raios gama , Humanos , Separação Imunomagnética , Interleucina-2/biossíntese , Interleucina-2/efeitos da radiação , Ativação Linfocitária/efeitos da radiação , Contagem de Linfócitos/efeitos da radiação , Teste de Cultura Mista de Linfócitos , Células-Tronco/metabolismo , Células-Tronco/efeitos da radiação , Linfócitos T Auxiliares-Indutores/metabolismo , Linfócitos T Auxiliares-Indutores/efeitos da radiaçãoRESUMO
PURPOSE: Bone marrow transplantation has often been closely linked with accidental or intentional therapeutical irradiation. In both situations, study of the radiosensitivity of human blood cell subsets is of interest. Using one-color flow cytometry analysis of B lymphocytes, T cell subsets, and natural killer cells, we previously reported that lymphocyte subsets exhibit equal radiosensitivity. Taking advantage of recent developments in the knowledge of leukocyte differentiation antigens and flow cytometry technology we undertook a study of blood cell subsets to search for rare populations exhibiting different radiosensitivity. METHODS AND MATERIALS: Thirty patients, who were delivered a 12 Gy fractionated total body irradiation as part of their conditioning regimen before transplantation for malignant disorders, were studied using multicolor flow cytometry. RESULTS: T and B lymphocytes showed a sharp, radiation-induced decrease, with the B lymphocytes (cluster of differentiation (CD) 19+) being the most sensitive. When analyzed by multicolor flow cytometry, all major lymphocyte subsets appeared equally sensitive to the in vivo irradiation; that is, CD3+4+45RO+, CD3+4+45RA+, CD3+4+8-, CD3+4-8+. Therefore, all major lymphocyte subsets sharing the helper phenotype (naive or memory) and the cytotoxic phenotype appeared equally sensitive to in vivo whole body irradiation. In parallel, the CD34+ cell subset remained basically unchanged after whole body irradiation. Finally, the CD3-, 56+, 16+ natural killer cell subset was relatively radioresistant (91 and 74% of its initial value, after 2 and 4 Gy, respectively) as compared to other lymphocyte subsets. CONCLUSION: Our study provides evidence that T and B cell subsets seem to be highly radiosensitive in vivo. The CD34+ progenitor/stem cells and NK cells seem to be more radioresistant. This latter result might provide clues to the understanding of the pathophysiogeny of radiation-induced aplasia and of the engrafment/rejection process following bone marrow transplantation.
Assuntos
Subpopulações de Linfócitos B/efeitos da radiação , Citometria de Fluxo/métodos , Contagem de Linfócitos/efeitos da radiação , Subpopulações de Linfócitos T/efeitos da radiação , Irradiação Corporal Total , Adolescente , Adulto , Antígenos CD , Feminino , Humanos , Células Matadoras Naturais/efeitos da radiação , Contagem de Leucócitos/efeitos da radiação , Masculino , Pessoa de Meia-Idade , Fenótipo , Dosagem Radioterapêutica , Fatores de TempoRESUMO
Immune cells subsets were prospectively analyzed after localized radiotherapy (LRT). LRT reduced the levels of all lymphocyte subsets, with B-cells and naive T-cells being most sensitive. Lymphocyte function was suppressed, but still within the normal range. Rapid recovery of cytotoxic T-cells/natural killer cells after LRT and the functional suppression within normal levels explains the low incidence of infections after LRT.
Assuntos
Linfócitos B/imunologia , Subpopulações de Linfócitos/imunologia , Seminoma/radioterapia , Linfócitos T/imunologia , Neoplasias Testiculares/radioterapia , Adolescente , Adulto , Linfócitos B/efeitos da radiação , Humanos , Ativação Linfocitária/imunologia , Ativação Linfocitária/efeitos da radiação , Contagem de Linfócitos/efeitos da radiação , Subpopulações de Linfócitos/efeitos da radiação , Masculino , Pessoa de Meia-Idade , Orquiectomia , Estudos Prospectivos , Seminoma/imunologia , Seminoma/cirurgia , Linfócitos T/efeitos da radiação , Neoplasias Testiculares/imunologia , Neoplasias Testiculares/cirurgiaRESUMO
As part of the study to investigate the mechanism of radiation-induced immunosuppression, the survival and functional ability of bone marrow cells was analyzed by exposing C57B1/6 mice whole body to 2.0-Gy gamma-rays. There was a rapid induction of DNA fragmentation in the total bone marrow cells and the kinetics indicated that apoptosis reached a peak by 4 h and then dropped back to normal control levels within 10 h after irradiation. To determine the functional ability of bone marrow cells which survive the radiation treatment, animals were immunized with antigen trinitrophenyl (TNP)-lipopolysaccharide. There was a significant decrease of anti-TNP plaque-forming cells in the bone marrow of irradiated mice compared to control animals. Flow cytometric analysis of bone marrow revealed a significant depletion of both immature (B220+, Ig-) as well as mature (B220+, Ig+) B cells compared to control group. In summary, the present study showed that sublethal whole body irradiation inhibits antibody responses elicited by bone marrow cells. This decreased immune response may have been due to depletion of B lineage subsets as well as generalized apoptosis in the entire bone marrow cells.
Assuntos
Células da Medula Óssea/efeitos da radiação , Animais , Formação de Anticorpos/efeitos da radiação , Apoptose/efeitos da radiação , Linfócitos B/citologia , Linfócitos B/efeitos da radiação , Células da Medula Óssea/citologia , Células da Medula Óssea/imunologia , Fragmentação do DNA/efeitos da radiação , Relação Dose-Resposta à Radiação , Feminino , Células-Tronco Hematopoéticas/citologia , Células-Tronco Hematopoéticas/efeitos da radiação , Contagem de Linfócitos/efeitos da radiação , Camundongos , Camundongos Endogâmicos C57BL , Irradiação Corporal TotalRESUMO
Low power laser irradiation has been shown to have various immune-modulatory effects under in vitro conditions but little is known about such effects in animal models. Escherichia coli endotoxin-preimmunized rabbits were used to determine the influence of transcutaneously applied low power laser light on differential blood count and rectal temperature. After three initial immunizations animals were either boostered with 5 ng/kg of endotoxin or injected with pyrogen-free saline and subsequently underwent irradiation using two different wavelengths of red laser light and sham irradiation, respectively. Differential blood count of laser-treated animals was characterized by significantly higher lymphocyte values and lower neutrophil values at twenty hours (boostered rabbits) and twenty-three hours (non-boostered rabbits) after irradiation. Differential blood cell counts returned to baseline values within 23 hours in the boostered animals, whereas in the non-boostered rabbits lymphocytes showed a trend to further increase. Recording of rectal temperature revealed a further rise after laser application, changes being of greater magnitude and longer duration in the non-boostered animals. These results seem to indicate that a single low power laser irradiation can modulate immune-responses depending on the immunological status of the organism.
Assuntos
Temperatura Corporal/efeitos da radiação , Endotoxinas/imunologia , Imunização , Lasers , Contagem de Leucócitos/efeitos da radiação , Animais , Contagem de Linfócitos/efeitos da radiação , Masculino , Monócitos , Neutrófilos , Coelhos , Distribuição AleatóriaRESUMO
The circulating lymphocytes of patients treated for cervical cancer were examined by four independent manners: by evaluation of T-cell proportion in peripheral blood, proliferative response upon PHA stimulation, PHA-induced leukocyte migration inhibition, and by concomitant chromosome aberration frequency. The immediate and longer-term effects of pelvic irradiation on T lymphocytes were investigated in 19 patients prior to, during, and immediately after radiotherapy, and then at subsequent intervals of two, three and five months. Radiotherapy caused profound depression of already diminished T-cell number and their proliferative response; both parameters gradually recovered during post-treatment period, and achieved their pretreatment values at the end of follow-up. The leukocyte migration inhibition was much less affected; it slightly deteriorated in the middle of post-treatment period, but reached the pretreatment level at the end of monitoring. The chromosome aberration frequency increased during irradiation in dose-dependent manner; it decreased gradually thereafter, but remained high during follow-up. Their elimination rate correlated with the recovery of T-cell number and proliferative response. However, at the end of monitoring, when all immunological parameters were completely recovered from harmful effect of irradiation, the percentage of chromosome aberrations remained high (12.5%), although significantly lower than the post-treatment one.
Assuntos
Cromossomos Humanos/efeitos da radiação , Neoplasias Pélvicas/imunologia , Neoplasias Pélvicas/radioterapia , Linfócitos T/imunologia , Linfócitos T/efeitos da radiação , Neoplasias do Colo do Útero/imunologia , Neoplasias do Colo do Útero/radioterapia , Adulto , Idoso , Inibição de Migração Celular , Aberrações Cromossômicas , Feminino , Seguimentos , Humanos , Ativação Linfocitária/efeitos da radiação , Contagem de Linfócitos/efeitos da radiação , Pessoa de Meia-Idade , Neoplasias Pélvicas/sangue , Fito-Hemaglutininas/farmacologia , Linfócitos T/fisiologia , Neoplasias do Colo do Útero/sangueRESUMO
Ionizing radiation induces both quantitative and qualitative changes in the lymphoid cells of both man and experimental animals, including inhibition of antibody responses. However, the cellular basis of this immunological lesion is not clear. In the present study, groups of mice were exposed to 2.0 Gy gamma-rays or sham irradiated, and 2 days later animals were killed and spleen cells were cultured with TNP-Ficoll and assayed for antibody responses. Results indicated a significant decrease in the number of anti-TNP, plaque-forming cells in cultures from the irradiated mice compared with cultures from the control. When lymphocytes were stimulated in vitro with anti-IgM or anti-CD3, there was a decreased proliferation in spleen cell cultures derived from the irradiated mice compared with those from the control. Since radiation treatment was found to deplete both T and B cells in equal proportions in spleen and an equal number of both control or treated cells were used in culture, the immunological abnormalities may have been due to intrinsic defects in irradiated cells. Addition of IL-6 to irradiated spleen cell cultures was able to augment anti-TNP, plaque-forming cell responses indicating the possibility that in the future this cytokine can be used in vivo to induce protection from infectious diseases in irradiated individuals.
Assuntos
Linfócitos B/imunologia , Linfócitos B/efeitos da radiação , Interleucina-6/farmacologia , Ativação Linfocitária/efeitos dos fármacos , Ativação Linfocitária/efeitos da radiação , Linfócitos T/imunologia , Linfócitos T/efeitos da radiação , Animais , Formação de Anticorpos/efeitos dos fármacos , Formação de Anticorpos/efeitos da radiação , Linfócitos B/citologia , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/efeitos da radiação , Sobrevivência Celular/efeitos da radiação , Células Cultivadas , Feminino , Contagem de Linfócitos/efeitos dos fármacos , Contagem de Linfócitos/efeitos da radiação , Camundongos , Camundongos Endogâmicos C57BL , Mitógenos/farmacologia , Receptores de Antígenos de Linfócitos B/antagonistas & inibidores , Receptores de Antígenos de Linfócitos B/fisiologia , Receptores de Antígenos de Linfócitos T/antagonistas & inibidores , Receptores de Antígenos de Linfócitos T/fisiologia , Baço/citologia , Baço/imunologia , Baço/efeitos da radiação , Estimulação Química , Linfócitos T/citologia , Irradiação Corporal TotalRESUMO
Disseminated neuroendocrine tumours are difficult to treat and are generally not responsive to radiotherapy or chemotherapy. Nuclear medicine techniques using a radiolabelled somatostatin analogue, 111In-Octreotide, have been used for the diagnosis of neuroendocrine tumours. It has been suggested that high activities of such an agent may have a therapeutic effect. The aims of this study were to assess toxicity and to determine if there had been evidence of efficacy. Eight patients with known disseminated neuroendocrine tumours were enrolled in the study; six had carcinoid tumours, one had a medullary cell carcinoma of the thyroid and one patient had a malignant gastrinoma. Between 1.3 and 4.6 GBq of 111In-Octreotide were administered to each patient for up to five administrations over 12 months. A total of 23 administrations were given. Tests of vital signs, renal, liver and endocrine function as well as haematological markers were taken before and after treatment. The treatment was well tolerated with only one patient suffering from a sensation of flushing during the infusion but no changes in vital sings. There was a transient (up to 48 h) drop in circulating lymphocytes in four patients and platelets in two patients; no supportive therapy was needed. One patient with severe renal impairment had a slight reduction in glomerular filtration rate. We conclude that high-activity 111In-Octreotide is well tolerated with low toxicity and can be considered for use in patients with disseminated neuroendocrine tumours. Further work is now being performed to assess efficacy.
Assuntos
Tumor Carcinoide/radioterapia , Gastrinoma/radioterapia , Neoplasia Endócrina Múltipla/radioterapia , Tumores Neuroendócrinos/radioterapia , Octreotida/análogos & derivados , Ácido Pentético/análogos & derivados , Compostos Radiofarmacêuticos/efeitos adversos , Adulto , Idoso , Osso e Ossos/diagnóstico por imagem , Tumor Carcinoide/diagnóstico por imagem , Feminino , Gastrinoma/diagnóstico por imagem , Taxa de Filtração Glomerular/efeitos da radiação , Humanos , Contagem de Linfócitos/efeitos da radiação , Masculino , Pessoa de Meia-Idade , Neoplasia Endócrina Múltipla/diagnóstico por imagem , Tumores Neuroendócrinos/diagnóstico por imagem , Octreotida/efeitos adversos , Octreotida/uso terapêutico , Ácido Pentético/efeitos adversos , Ácido Pentético/uso terapêutico , Cintilografia , Compostos Radiofarmacêuticos/uso terapêuticoRESUMO
The effects of locoregional postoperative radiation therapy (60 Gy on average) on cellular immunity were investigated in 11 patients with squamocellular carcinomas of the oral cavity, pharynx, or larynx. During radiation treatment, the total lymphocyte counts, CD8+ T-lymphocyte count, and especially CD4+ T-lymphocyte count decreased significantly. The mean CD4+ T-lymphocyte counts dropped from an average of 739/microl to 183/microl (p <0.001), and the CD4+/CD8+ quotient also decreased significantly. Not only the lymphocyte counts but also the in vitro lymphocyte stimulation responses to several mitogens decreased, with reductions averaging 10% to 50% of normal responses by the end of radiation therapy. Within 3 to 4 weeks after radiation therapy, the CD4+ T-lymphocyte counts and the in vitro lymphocyte stimulation responses showed a tendency toward normalization. This study shows that postoperative locoregional radiation therapy in patients with head and neck cancer induces a severe generalized impairment of cellular immunity.
Assuntos
Carcinoma de Células Escamosas/radioterapia , Neoplasias de Cabeça e Pescoço/radioterapia , Linfócitos T/efeitos da radiação , Contagem de Linfócito CD4/efeitos da radiação , Relação CD4-CD8/efeitos da radiação , Linfócitos T CD4-Positivos/efeitos da radiação , Linfócitos T CD8-Positivos/efeitos da radiação , Carcinoma de Células Escamosas/cirurgia , Seguimentos , Neoplasias de Cabeça e Pescoço/cirurgia , Humanos , Interferon gama/sangue , Interleucina-2/sangue , Interleucina-6/sangue , Neoplasias Laríngeas/radioterapia , Neoplasias Laríngeas/cirurgia , Ativação Linfocitária/efeitos da radiação , Contagem de Linfócitos/efeitos da radiação , Mitógenos , Neoplasias Bucais/radioterapia , Neoplasias Bucais/cirurgia , Neoplasias Faríngeas/radioterapia , Neoplasias Faríngeas/cirurgia , Dosagem Radioterapêutica , Radioterapia Adjuvante , Receptores de Interleucina-2/sangue , Receptores de Interleucina-6/sangueRESUMO
To investigate the influence of thoracic irradiation on immunological competence in patients with lung cancer, we examined the changes in peripheral blood lymphocyte subsets in 15 patients before and after radiation therapy by two-color flow cytometry techniques. After radiation therapy, the percentage and the absolute number of CD4+CD45RA+ cells (naive T cells) and CD56+ and/or CD16+ cells (NK cells) decreased. The percentage of CD4+human leukocyte antigen-DR(HLA-DR)+ cells (activated CD4T cells) and CD8+HLA-DR+ cells (activated CD8T cells) increased, although the absolute number did not change significantly. Naive T cells may be more selectively damaged than memory T cells by thoracic irradiation, through their recirculation behavior. The reduction of natural killer (NK) cells is disadvantageous for anti-tumor immunity. The percentage of HLA-DR positive T lymphocytes was significantly increased, and thus the possibility of HLA-DR enhancement by irradiation cannot be excluded. Therefore, thoracic irradiation has numerous varied effects on the immunological system of lung cancer patients.
Assuntos
Neoplasias Pulmonares/radioterapia , Subpopulações de Linfócitos/efeitos da radiação , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfócitos T CD4-Positivos/efeitos da radiação , Linfócitos T CD8-Positivos/efeitos da radiação , Terapia Combinada , Feminino , Citometria de Fluxo/métodos , Antígenos HLA-DR/imunologia , Humanos , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/efeitos da radiação , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia , Contagem de Linfócitos/efeitos dos fármacos , Contagem de Linfócitos/efeitos da radiação , Subpopulações de Linfócitos/efeitos dos fármacos , Subpopulações de Linfócitos/imunologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Linfócitos T/imunologia , Linfócitos T/efeitos da radiaçãoRESUMO
The present study recorded a considerable excess of recommended exposure limits in the vicinity of shortwave diathermy devices used for medical treatment of patients. Different kinds of field probes were used to measure electric and magnetic field strength and the whole body exposure of medical personnel operating shortwave, decimeter wave and microwave units was calculated. To investigate the influence of chronic exposure on the immune system of operators, blood was sampled from physiotherapists working at the above mentioned devices. Eighteen exposed and thirteen control persons, matched by sex and age, were examined. Total leucocyte and lymphocyte counts were performed and leucocytic subpopulations determined by flow cytometry and monoclonal antibodies against surface antigens. In addition, to quantify subpopulations of immunocompetent cells, the activity of lymphocytes was measured. Lymphocytes were stimulated by mitogen phytohemagglutinin and their proliferation measured by a flow cytometric method. No statistically significant differences between the control and exposed persons were found. In both study groups all immune parameters were within normal ranges.
Assuntos
Campos Eletromagnéticos/efeitos adversos , Imunidade/efeitos da radiação , Exposição Ocupacional/efeitos adversos , Adulto , Áustria , Estudos de Casos e Controles , Relação Dose-Resposta à Radiação , Monitoramento Ambiental , Feminino , Pessoal de Saúde , Humanos , Contagem de Leucócitos/efeitos da radiação , Contagem de Linfócitos/efeitos da radiação , Masculino , Pessoa de Meia-Idade , Probabilidade , Doses de Radiação , Valores de Referência , Estatísticas não ParamétricasRESUMO
A significant decrease in mean number of CD5+, CD8(+)-lymphocytes in persons, who worked in 30-km zone of Chernobyl nuclear power station was revealed. A significant increase in percent of CD5+, CD4(+)-cell percents was observed in workers, who worked for 1,2-2,5 years in zone, but absolute number, were decreased comparing a control and data received in people, who have just arrived to work in 30-km zone. The positive correlation exists between the percent of lymphocytes and years of service in 30-km zone. The lower level of alpha 1-thymosine was revealed in serum of the persons, who worked in zone for 4.5-5 years than data received in people, who worked for 0.5 year. Increase level of serum autoantibodies reacting with thymic epithelial cell was detected in men, who worked in zone for 3-3.5 years. In persons, who worked more 5 years and have just arrived in zone identical data were received.
Assuntos
Autoanticorpos/efeitos da radiação , Centrais Elétricas , Liberação Nociva de Radioativos , Subpopulações de Linfócitos T/efeitos da radiação , Timosina/análogos & derivados , Timo/imunologia , Timo/efeitos da radiação , Adulto , Autoanticorpos/sangue , Epitélio/imunologia , Epitélio/efeitos da radiação , Humanos , Imunidade Celular/efeitos da radiação , Contagem de Linfócitos/efeitos da radiação , Pessoa de Meia-Idade , Timalfasina , Timosina/sangue , Timosina/efeitos da radiação , Fatores de Tempo , UcrâniaRESUMO
Investigation of the action of mid-frequency ultraviolet radiation (302 nm) on isolated lymphocytes of mice spleen pointed out that intracellular pH of lymphocytes starts decreasing from 0.3 J/cm2. Dose rise above 2.5 J/cm2 increases the number of cells with damaged plasmatic membrane within the lymphocyte population and aggravates the ability of cells to accumulate fluorescein fluorochrome as a product of intracellular fluorescein diacetate hydrolysis.
Assuntos
Linfócitos/efeitos da radiação , Lesões Experimentais por Radiação/patologia , Baço/efeitos da radiação , Raios Ultravioleta/efeitos adversos , Animais , Membrana Celular/metabolismo , Membrana Celular/efeitos da radiação , Permeabilidade da Membrana Celular/efeitos da radiação , Relação Dose-Resposta à Radiação , Fluoresceínas/farmacocinética , Concentração de Íons de Hidrogênio , Líquido Intracelular/metabolismo , Líquido Intracelular/efeitos da radiação , Contagem de Linfócitos/efeitos da radiação , Linfócitos/metabolismo , Linfócitos/patologia , Masculino , Camundongos , Lesões Experimentais por Radiação/etiologia , Lesões Experimentais por Radiação/metabolismo , Baço/metabolismo , Baço/patologiaAssuntos
Formação de Anticorpos/efeitos da radiação , Exposição Ambiental/efeitos adversos , Imunidade Celular/efeitos da radiação , Adulto , Criança , Relação Dose-Resposta à Radiação , Feminino , Nível de Saúde , Humanos , Contagem de Linfócitos/efeitos da radiação , Masculino , Centrais Elétricas , Liberação Nociva de Radioativos , UcrâniaRESUMO
The survival of non-dividing (G0) leukaemic lymphocytes in culture is generally too short for their radiosensitivity to be quantitatively assessed, since lethally X-irradiated cells may show a long delay before manifestations of cell death ("interphase death") are seen. Counts of surviving cells will therefore include both lethally-hit cells (apparent survivors), and real survivors which have not been lethally hit. Death rates of irradiated leukaemic and normal cells show great variation between individuals, so that comparisons of radiosensitivity between different cell populations based on surviving cell counts at a single time-point are invalid. In this study the supposed radioresistance of prolymphocytic leukaemia lymphocytes was examined in 6 patients with B-cell disease. Survival curves were plotted from serial observations made over several days after graded X-irradiation (0-1000 cGy). We attempted to interpret these radiation responses in terms of their dose dependence (intrinsic radiosensitivity) and time dependence (cell death rate) characteristics using the best-fitting of four mathematical models, all based on classical "single-hit" target theory. The apparent radioresistance shown in 4 cases could be explained by very slow death rates (T1/2 values 55-205 h) of cells proving otherwise radiosensitive (D37 values 38-123 cGy). Genuine radioresistance was found in only 1 case (actual D37 value above 2000 cGy). By ignoring delayed cell death in clinical assessments, pathological lymphocytes could be mistakenly categorised as resistant to elimination by radiotherapy.
Assuntos
Morte Celular/efeitos da radiação , Leucemia Prolinfocítica/patologia , Linfócitos/efeitos da radiação , Linfócitos B/efeitos da radiação , Ciclo Celular , Humanos , Contagem de Linfócitos/efeitos da radiação , Modelos Biológicos , Doses de Radiação , Tolerância a Radiação , Células Tumorais CultivadasRESUMO
Total lymphoid irradiation (TLI) has been reported to delay deterioration in patients with progressive multiple sclerosis and other autoimmune disorders. METHODS--In an open trial, the effect of TLI combined with a one year course of low dose prednisone was compared to the effect of sham TLI and TLI only in a prior double-blind study of patients with progressive multiple sclerosis. RESULTS--Twenty-seven patients receiving TLI combined with corticosteroids had significantly greater lymphocytopenia in the year post-therapy than those receiving TLI only or sham TLI and Kaplan Meier product-limit survival analysis showed significantly less progression in the TLI plus steroid group over 4 years of follow-up. No difference in lymphocytopenia or progression was found with TLI plus corticosteroid therapy when the spleen was removed from the field of irradiation. CONCLUSION--These results lend further support to the hypothesis that TLI may be effective in progressive MS, and indicates that adding low-dose prednisone may enhance this effect. The study also suggests that TLI may be equally effective whether or not the spleen is irradiated.
Assuntos
Relação Dose-Resposta a Droga , Irradiação Linfática/efeitos adversos , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla/radioterapia , Prednisona/administração & dosagem , Prednisona/uso terapêutico , Adulto , Feminino , Seguimentos , Humanos , Contagem de Linfócitos/efeitos da radiação , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
BACKGROUND: Growing evidence indicates that unilateral lung irradiation for breast cancer may "prime" the development of migratory lung infiltrates with histologic features of bronchiolitis obliterans organizing pneumonia. OBJECTIVE: Our purpose was to evaluate the cytologic and immunocytologic features of bronchoalveolar lavage in this condition. METHODS: We analyzed the profile bronchoalveolar lavage cell differentials and lymphocyte subpopulations of 11 women with bronchiolitis obliterans organizing pneumonia syndrome after radiation therapy for breast cancer in comparison to 9 healthy women. RESULTS: The bronchoalveolar lavage analysis demonstrated a significant increase in the percentage of lymphocytes (36.7% +/- 5.4% vs 8.6% +/- 1.1%, P =.0002), neutrophils (3.8% +/- 1.2% vs 0.6% +/- 0.2%, P =.005), eosinophils (2.4% +/- 1% vs 0.3% +/- 0.1%, P =.01), and mast cells (1.4% +/- 0.6% vs 0.1% +/- 0.02%, P =.05) with a significant decrease in the percentage of macrophages (56.1% +/- 6% vs 90.3% +/- 1.4%, P =.0002) in patients with bronchiolitis obliterans organizing pneumonia compared with the control subjects. The percentage of CD3(+) cells was significantly increased in patients with bronchiolitis obliterans organizing pneumonia (93.7% +/- 1.3% vs 70.9% +/- 4%, P =.0004), with a significant decrease in CD4(+) cells (32.7% +/- 4.7% vs 55.4% +/- 2. 6%, P =.002) and a significant increase in CD8(+) cells (61.2% +/- 4. 8% vs 37.5% +/- 2.9%, P =.003) in comparison to control subjects. The CD4/CD8 ratio was significantly reduced in patients with bronchiolitis obliterans organizing pneumonia compared with control subjects (0.6% +/- 0.1% vs 1.5% +/- 0.1%, P =.001). CONCLUSION: These data add to the view that unilateral lung irradiation for breast cancer may "prime" the development of a syndrome quite similar to idiopathic bronchiolitis obliterans organizing pneumonia.
Assuntos
Neoplasias da Mama/radioterapia , Líquido da Lavagem Broncoalveolar/citologia , Líquido da Lavagem Broncoalveolar/imunologia , Pneumonia em Organização Criptogênica/etiologia , Lesões por Radiação/etiologia , Idoso , Lavagem Broncoalveolar , Pneumonia em Organização Criptogênica/imunologia , Pneumonia em Organização Criptogênica/patologia , Feminino , Humanos , Pulmão/fisiopatologia , Pulmão/efeitos da radiação , Contagem de Linfócitos/efeitos da radiação , Subpopulações de Linfócitos/efeitos da radiação , Pessoa de Meia-Idade , Lesões por Radiação/imunologia , Lesões por Radiação/patologia , Testes de Função RespiratóriaRESUMO
Previous studies have indicated that suberythemal ultraviolet B (UV-B) irradiation of C3H mice before primary infection with herpes simplex virus (HSV) type 1 does not result in increased morbidity or mortality, but a suppressed delayed type hypersensitivity (DH) to the virus can be demonstrated. Any effect of UV radiation on pathogenesis during secondary epidermal HSV infection has not been previously examined. Mice were immunized by subcutaneous injection of inactivated HSV and, 5 days later, one group was UV-B-irradiated. The next day all mice were challenged epidermally with HSV. Most of the mice (92%) in the irradiated group developed severe lesions, whilst 59% of the non-irradiated group had mild lesions and 30% no lesions. Infectious virus was not isolated from the adrenal glands after challenge in either group. In addition, the DH to the virus was not affected by the UV exposure. The numbers of lymphocytes and dendritic cells in the lymph nodes draining the site of epidermal infection were increased in the UV group compared with the non-irradiated group. Following challenge, the percentage of CD4+ and CD8+ lymphocytes in lymph nodes was unaltered but the MHC class II expression on dendritic cells in these lymph nodes was reduced by UV exposure. The lymphoproliferative response in vitro of lymph node cells revealed a suppressed response to HSV and to the mitogen concanavalin A in the irradiated group. Thus, UV irradiation prior to epidermal secondary infection with HSV led to more severe infections due, perhaps, to a modulation in local antigen presentation.