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At least 253 records · Page 14Linked to original sources
PubMed1999

Immunological disorders in men exposed to metallic mercury vapour. A review.

The awareness of the effects of metallic mercury vapour on the human immune system has increased only in the last decade. The regulatory guidelines relating to testing for immunotoxicity of metals are not standardized so far. A full understanding of the relevance of the tests to man is still incomplete. Immunotoxicity investigation of metals in rodents, with subsequent extrapolation to man, forms the basis of human risk assessment. Human contact with mercury vapour is mainly in chloralkali plants and in factories producing controlling and measuring devices. When the immune system acts as a target of xenobiotic insults, the result can be a decreased resistance to infection, cancers, or immune disregulation that can induce the development of allergy, or autoimmunity (Fig. 1). This article reviews literature data and our studies concerning the immunotoxicity of metallic mercury vapour. A number of data shows that mercury exerts a suppressing effect but another data suggest stimulating effects on the human immune system. The results of immunological monitoring of individuals exposed to mercury vapour were either positive or negative as well as borderline and uncertain as to the influence of mercury vapour on human immune system. The positive data had no influence on the resistance of workers to infections and neoplasms. Skin and mucosa hypersensitivity to metallic mercury is rare. No positive report that mercury vapour could be carcinogenic in man has appeared up to now.

Air Pollutants, Occupational↗
PubMed2001

Clinical translation of peptide-based vaccine trials: the HER-2/neu model.

In the development of targeted cancer immunotherapies, the choice of antigen is obviously critical to the design of any therapeutic strategy, but particularly so for tumor vaccines, which must distinguish malignant cells from normal cells. Investigations a decade ago focused on mutated tumor antigens, or viral tumor antigens, with the belief that these foreign or abnormal proteins would be best recognized by the host immune system. Within the last 10 years, however, several tumor antigens have been identified on the basis of recognition by infiltrating T cells in tumor samples. Studies on melanoma, in particular, have revealed that in addition to some mutated tumor antigens, several aberrantly expressed normal proteins, as well as tissue-specific differentiation factors, are recognized by the host immune system. Similar studies in other solid tumors have revealed that certain oncogenes overexpressed in malignant cells, such as p53 and HER-2/neu, are also recognized by host T cells. Our group has been investigating the HER-2/neu oncogenic protein as a vaccine target in patients with HER-2/neu-overexpressing cancers. However, several issues unique to the design of human clinical trials of cancer vaccines must be addressed when translating preclinical experiments to human clinical trials. First, HER-2/neu protein expression can vary depending on the tumor type. How would expression differences impact clinical trial design? Secondly, what are the issues in clinical trial design that are critical to the successful execution of a phase I study of a peptide-based vaccine? Thirdly, what types and amounts of clinical material are readily available for immunologic analysis and can be obtained with little distress and risk to the patients enrolled in the study? Finally, what steps must be implemented for a laboratory assay to evolve to meet the validation criteria needed for application as an immunologic monitoring tool?

Cancer Vaccines↗
PubMed2002

European best practice guidelines for renal transplantation. Section IV: Long-term management of the transplant recipient. IV.2.2 Chronic graft dysfunction. Immunological factors (alloimmunity).

GUIDELINE: All recipients of an allogeneic kidney graft should take life-long maintenance immunosuppressive medication. Whereas there is no immunological test to diagnose chronic allograft dysfunction, circumstantial evidence suggests that immunological factors play an important role in its pathogenesis. This evidence is based on experimental data, the beneficial effect of sharing HLA antigens between donor and recipient and post-transplantation immunological monitoring studies.

Chronic Disease↗
PubMed2002

[Salvage thermochemotherapy in advanced refractory malignant tumors in children].

The data are presented on polychemotherapy given to 17 children with advanced refractory malignant tumors using whole body hyperthermia and hyperglycemia. All patients suffered tumor progression throughout treatment and afterwards. Adjuvant Roncoleukin (interleukin-2) was administered in 5. Such salvage therapy was followed by overall tumor regression in 29.3%. Overall 4-year survival in such cases was 19%. Immunological monitoring of adjuvant whole body hyperthermia and interleukin-2 was carried out.

Adolescent↗
PubMed1991

[Multimodal treatment of pancreatic cancer].

The experience with combined treatment of 122 patients with pancreatic cancer in the clinic of the Institute of Clinical & Experimental Surgery for the period of from 1988 to 1990 is summarized. Radical operations were performed in 54 patients, the palliative ones--in 68. After performance of a palliative operation, the patients underwent polychemotherapy, 5--in combination with UHF-hyperthermia. To study the effect of chemotherapy on the immune system, the immunologic monitoring was carried out. It was established that under the influence of chemotherapy and hyperthermia, the indices of immunity in patients with pancreatic cancer improved. In cancer of the pancreatic head with involvement of pancreatic body, the performance of subtotal pancreatoduodenal resection with subsequent regional chemotherapy is expedient. Chemotherapy and hyperthermia in combination with creation of a shunt permit to improve the results of treatment of inoperable tumors. The use of regional chemotherapy in subtotal resection contributed to increase in 2-year survival of the patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

[Determination of antibodies to cross-reacting antigens of microorganisms in oncological diseases].

It was studied antibodies to saprophytic microorganism Bacillus megaterium H glycoprotein in healthy, oncological, non-oncological gastrointestinal patients and animals. High level of antibodies to microbial glycoprotein in blood sera was revealed in cancer and precancer patients. Analogical results were obtained in mice A/Sn and Balb/c with inductive or transplanted tumors. It has been suggested the use of Bacillus megaterium H glycoprotein (M. m. 65-70 kD) for immunological monitoring.

Animals↗
PubMedDate not supplied

[The immunological implications of breast cancer: the physiopathological aspects and possible therapeutic strategies in our experience].

The authors, after a short review on the physiopathological patterns which regulate the function of the immunological system in patients with neoplastic disease, report their clinical prospect study, performed on a population of 71 patients affected by breast cancer. The study has the aim to demonstrate the advantage of a complete immunological monitoring, and the efficacy of a prophylactic and therapeutic treatment with thymic hormones. Results of the study can be summarized as follow: 1) very low rate of septic complications. 2) Better results as to blood cells impairement in the group submitted to both chemo- and immunotherapy. 3) In the same group, the performance status (Karnofsky index) remained above 80% in most of cases. It is underlined in this study, the hypothesis of the prognostic value pertaining to the indexes of functionality of the immune system. Authors have indeed pointed out that early metastatic spread has been observed in the two patients, treated in 1st stage with surgery and immunotherapy, but not responding with improvement of biological data. This topic has to be developed in further studies, with the aim of changing and increasing the criteria for the staging of tumors, as the authors suggest.

Adult↗
PubMed1998

Development of lymphocytotoxic antibodies among lung transplant recipients: preliminary results.

The aim of this study was to evaluate the incidence of postoperative lymphocytotoxic antibodies (LA) formation and to assess their potential utility in immunologic monitoring after lung transplantation. We determined prospectively the percentage LA against a reference panel reactive antibody in a complement-dependent microlymphocytotoxicity test in 137 sequential serum samples obtained from 14 consecutive lung transplant recipients who survived over the first postoperative year. Four patients developed high titers of LA (greater than 10% panel reactive antibody reactivity in at least 3 consecutive samples) by 2 to 24 months after surgery. Antibodies were mostly immunoglobulin M isotype, without any specificity against the donor's human leukocyte antigen and were correlated with the development of bronchiolitis obliterans syndrome (p=.01) and with chronic bronchial infectious colonization (p=.03). In conclusion, a polyclonal immunoglobulin M antibody production can be detected in serum samples from lung transplant recipients and seems to be involved in the progression of chronic rejection process. These preliminary results incline to carry on the cytotoxicity screening of a panel of lymphocytes to better understand the significance of such reactivity.

Adenosine Triphosphate↗
PubMed1989

Long-term monitoring of immunological profile in children with immunodeficiency disorders.

1. The fulfillment of research project allowed us to make deeper scope of literature sources with the children IDS topic. The proper experience with children IDS management has been acquired in the specialized service for immunodeficient children at Pediatric Clinic of Teaching Hospital in Hradec Králové. 2. IDS screening and diagnostic in children were studied with participation of immunologic laboratories, and the development of available immunologic indices in IDS children has been monitored at long-term. Problems mentioned were the content of partial research project VII-6-6/19 for 1976-1980, VII-6-6/9 for 1980-1985, VIII-6-5/11 starting from 1986 and resolved till now by Pediatric Clinic of Teaching Hospital in Hradec Králové. The immunodeficient conditions were studied minutely at long-term and with complex relations. 3. Authors were involved in management of life threatening infectious complications and performed both control and moderation of diseases manifested as such. Applied management approaches were then evaluated from the scope of actual therapy. Our pathophysiologic IDS concept is more extended. The individual IDS represents a complex real situation developing in time. Therefore, the long-term monitoring is of benefit in detecting certain developmental IDS tendencies such as, e. g., occurrence of autoimmune diseases and malignancies in children with IDS. 4. We stated that thymectomy in infants: --was of no expressed disturbing influence on health of two children at least for 12 years of long-term monitoring; --manifested the transient decrease of circulating T-lymphocyte percentage which was detected in one child 2 years after TE, in other up 10 years after TE, respectively. However, both of them showed a constant decreasing tendency; --is responsible of changes in subpopulations of T-lymphocytes; --changes of laboratory tests provided after TE 12 years till now show no clinical significance. 5. Selective IgA deficiency has been diagnosed in a total of 14 children, and the development of their immunologic indices was monitored at long-term. Several literature data were proved as well as enlarged and extended: --IgA deficiency is a constant defect; --this is a simultaneous deficiency of both serum and secretory IgA in a majority of cases; --selective IgA deficiency is most pronounced and complex immunity disorder involving not only humoral, but also cellular immunity; --in IgA deficiencies, mainly respiratory infections are predominant though having neither serious course nor complications; --immunoglobulins are not necessary in managing infections in IgA deficient cases for as much as an appropriate antiinfection therapy is of choice. Dispensary care is needed similarly to other IDS conditions due to recurrent infections and risk of autoimmune diseases and tumors.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1984

Diagnostic concepts in clinical organ transplantation: histocompatibility testing and T cell monitoring.

Immunological rejection is still the most important problem in clinical organ transplantation requiring the lifelong immuno-suppressive treatment of the allograft recipient. The clinical success rate however can be improved by a variety of diagnostic procedures: The reduction of the histocompatibility barrier between donor and recipient by HLA-typing and organ exchange in order to obtain the best possible match; posttransplant monitoring of donor specific immune responsiveness towards donor antigens; monitoring of T-cell subsets by monoclonal antibodies and cytofluometry. T-cell subset monitoring is a rapidly developing new technique with great potential. With the presently available first generation reagents already a detailed analysis of the major T-cell population in circulation is possible, which can markedly facilitate the diagnosis of rejection and viral infection. New monoclonal antibodies, defining certain activation stages of T-cells or permitting a more refined differentiation of functionally distinct subsets will lead to increased relevance of this diagnostic approach. A particularly interesting aspect of monoclonal antibodies against T-cell differentiation antigens is their potential therapeutic use as immunosuppressive drugs with a highly selective action on defined T-cell subsets.

Antibodies, Monoclonal↗
PubMed1999

[The monitoring of immunological indices in odontogenic abscesses and phlegmons and their differential diagnostic meaning].

The immune homeostasis parameters have been monitored in 31 patients with odontogenic abscesses and phlegmons. Immunological values possessing differential diagnostic significance have been detected. Activation of phagocytosis, spontaneous and stimulated activity of phagocytes in parallel with a moderate decrease in the cellular functional reserve, increased immunoregulatory index, and moderate shifts in the concentrations of IgG and IgM are characteristic of odontogenic abscesses, while odontogenic phlegmons are characterized by deep depression of the phagocyte function and failure of cellular and humoral immunity. The disorders in the immune functions of patients with odontogenic phlegmons normalized 2 weeks later than in those with odontogenic abscesses. Both diseases run a wave-like course and are characterized by phasic changes in immunological parameters, which is significant for determining pathogenesis and choosing appropriate immunocorrective therapy.

Abscess↗
PubMedDate not supplied

Workshop on cancer biometrics: identifying biomarkers and surrogates of cancer in patients: a meeting held at the Masur Auditorium, National Institutes of Health.

The current excitement about molecular targeted therapies has driven much of the recent dialog in cancer diagnosis and treatment. Particularly in the biologic therapy of cancer, identifiable antigenic T-cell targets restricted by MHC molecules and the related novel stress molecules such as MICA/B and Letal allow a degree of precision previously unknown in cancer therapy. We have previously held workshops on immunologic monitoring and angiogenesis monitoring. This workshop was designed to discuss the state of the art in identification of biomarkers and surrogates of tumor in patients with cancer, with particular emphasis on assays within the blood and tumor. We distinguish this from immunologic monitoring in the sense that it is primarily a measure of the tumor burden as opposed to the immune response to it. Recommendations for intensive investigation and targeted funding to enable such strategies were developed in seven areas: genomic analysis; detection of molecular markers in peripheral blood and lymph node by tumor capture and RT-PCR; serum, plasma, and tumor proteomics; immune polymorphisms; high content screening using flow and imaging cytometry; immunohistochemistry and tissue microarrays; and assessment of immune infiltrate and necrosis in tumors. Concrete recommendations for current application and enabling further development in cancer biometrics are summarized. This will allow a more informed, rapid, and accurate assessment of novel cancer therapies.

Alternative Splicing↗
PubMed2004

Direct measurement of peptide-specific CD8+ T cells using HLA-A2:Ig dimer for monitoring the in vivo immune response to a HER2/neu vaccine in breast and prostate cancer patients.

HER2/neu is a proto-oncogene and a member of the epidermal growth factor receptor family of proteins that is overexpressed in numerous types of human cancer. We are currently conducting clinical trials with the HER2/neu E75 peptide vaccine in breast and prostate cancer patients. We have evaluated the use of HLA-A2 dimer molecule for the immunological monitoring of cancer patients receiving the E75 peptide vaccine. Peripheral blood samples from patients receiving the vaccine were stained with HLA-A2 dimers containing the vaccine peptide E75 or control peptides and analyzed by flow cytometry. We compared the HLA-A2 dimer assay to standard methods of immunologic monitoring (IFN-gamma release, lymphocyte proliferation, and cytotoxicity). The HLA-A2 dimer assay was also compared with the HLA-A2 tetramer assay. E75 peptide-specific CD8 T cells were detected directly in the peripheral blood of patients by staining with E75-HLA-A2 dimers and CD8 antibodies. T cell cultures generated by repeated stimulations using E75 peptide-pulsed dendritic cells showed increased staining with E75-peptide loaded HLA-A2 dimers. Simultaneously analysis by the dimer assay and standard immunologic assays demonstrated that the dimer-staining assay correlated well with these methods of immunologic monitoring. A direct comparison using E75-specific HLA-A2 tetramers and HLA-A2 dimers for the detection of E75-specific CD8 T cells in peripheral blood showed comparable results with the two assays. Our findings indicate that the HLA-A2 dimer is a powerful new tool for directly quantifying and monitoring immune responses of antigen-specific T cells in peptide vaccine clinical trials.

Antibody Formation↗
PubMed2004

Serial monitoring of immunological parameters following human hand transplant.

BACKGROUND: Although early successes have been achieved in human hand transplant, the changes of immunological parameters in the recipients and their relations to clinical events were not yet known. METHODS: In two patients undergoing hand transplantation, we prospectively determined lymphocyte subsets using flow cytometry as well as the serum levels of interleukin (IL)-2, IL-10, tumor necrosis factor (TNF)-alpha, and interferon (IFN)-gamma using enzyme linked immunosorbent assays during the first 6 months after transplantation. RESULTS: The decreases in CD, CD, CD T cell, the activated T cell (CD/CD, CD/HLA-DR(+)) as well as IL-2, IFN-gamma and corresponding significant peak in IL-10 in human hand transplant during the first post-transplant week were observed. Then these parameters recovered to the pre-transplant level except for an even higher level of CD T cell. The low CD/CD ratio was been maintained constantly. After 7 wk, IL-2, IFN-gamma, and IL-10 decreased to be maintained at a low or undetectable level except for slight increase in IL-10 at post-transplant month 5. There are no significant variation in TNF-alpha early after transplant. After 3 months, IL-10 was not detected again. CONCLUSIONS: The immunosuppressive agents had significantly effects on the immunological status in human hand transplant recipients. These profiles of immunological parameters would be useful data for the future immunomonitoring in human hand transplant recipients.

Adult↗
PubMed2005

Quantitative detection of changes in cytokine gene expression in peripheral blood mononuclear cells correlates with and precedes acute rejection in renal transplant recipients.

Immunological monitoring of transplant recipients is an attractive concept. Cytokines provide an obvious focus for research, as they are central to the human immune response. This study aimed to identify cytokines whose sequential gene expression differentiated rejectors from non-rejectors immediately following renal transplantation. Forty-five renal transplant recipients (15 rejectors) and 13 living donors were recruited. Total RNA was extracted from the peripheral blood mononuclear cells and reverse transcribed. Cytokine gene expression levels of IL-4, IL-10, TNF-alpha and TGF-beta1 were measured using TaqMan. IL-10 expression increased significantly following donor surgery. IL-4 and TNF-alpha patterns clearly differentiated between rejectors and non-rejectors. In the rejectors significant increases occurred more than 48 h before clinical graft dysfunction. Negative predictive values were 76% and 80% for IL-4 and TNF-alpha, respectively. This study has identified two cytokines (IL-4 and TNF-alpha) whose gene expression patterns differentiate between rejecting and non-rejecting renal transplant recipients making immunological monitoring possible.

Cells, Cultured↗