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PubMedDate not supplied

[Relationship of immune imbalance with the development of multiple organ failure in patients with complicated postoperative period after the cardiac surgery].

A relationship of the functional status of the viscera with the immune system was studied in 38 cardiac surgical patients with septic complications and multi-organ failure in the postoperative period. In deceased patients (n = 13), the total functional organ compensation index was lower whereas the total functional decompensation index was higher than those in survivors (n = 25). In the deceased patients, each vital organ was more commonly decompensated than that in the survivors, but a definite discrepancy was ascertained only in the immune system (92% versus 16%, p < 0.0001). The average number of decompensated organs was found to increase with the severity of immunological disorders. Therefore, there is a rather high correlation between the functional status of vital organs and the degree of immunological imbalance. The authors show it necessary to use immunity-corrective drugs (splenopid) to enhance the efficiency of treatment organ failure.

Adjuvants, Immunologic↗
PubMed1985

Immunological determination of phosphoenolpyruvate carboxylase and the large and small subunits of ribulose 1,5-bisphosphate carboxylase in leaves of the c(4) plant pearl millet.

The light-dependent development of the photosynthetic apparatus in the first leaf of the C(4) plant pearl millet (Pennisetum americanum) was monitored by immunologically determining the concentration of phospho-enolpyruvate carboxylase and ribulose 1,5-bisphosphate carboxylase. A competitive enzyme-linked immunosorbent assay procedure using antibodies to the monomeric subunit of phosphoenolpyruvate carboxylase and the large and small subunit of ribulose 1,5-bisphosphate carboxylase was used to quantitate the amounts of these polypeptides in the first leaf of etiolated seedlings and etiolated seedlings exposed to light for varying periods of time. Phosphoenolpyruvate carboxylase was present in etiolated tissue; however, light stimulated its synthesis nearly 23-fold. Maximum accumulation of phosphoenolpyruvate carboxylase occurred approximately 4 days after etiolated plants were placed in the light. Both the large subunit and the small subunit of ribulose 1,5-bisphosphate carboxylase were present in leaves of etiolated seedlings. Light also stimulated the synthesis of both of these polypeptides, but at different rates. In etiolated leaves there was approximately a 3-fold molar excess of the small subunit to large subunit. Exposure of the etiolated leaves to light resulted in the molar ratio of the large subunit to the small subunit increasing to approximately 0.72. These data indicate that the net synthesis of these two polypeptides is not coordinately regulated at all times.

Journal Article↗
PubMed1990

Interferon activation of latent natural killer cells and alteration in kinetics of target cell lysis: clinical implications for oral precancerous lesions.

Reduced natural killer cell activity was observed in patients with oral leukoplakia and submucous fibrosis compared with normal control subjects. However, the number of target binding lymphocytes was found to be normal in these precancers. Treatment of effector cells with interferon-alpha resulted in highly elevated active killer cell activity, although no change was observed in target binding lymphocyte counts. This finding could imply that precytotoxic cells that are activated by interferon exist in peripheral blood or that direct recruitment of a new cell population takes place. In addition, altered target lysis kinetics was observed, with interferon-activated killer cells demonstrating a tremendous lytic activation that is completed so quickly that a statistical kinetic analysis could not be accurately done. Because natural killer cell activity is an important effector system in immunosurveillance against tumors, its modulation with interferon may be an exciting clinical possibility in the control of malignant transformation or oral precancers.

Analysis of Variance↗
PubMed2006

Serum immunologic markers in multiple sclerosis patients on continuous combined therapy with beta-interferon 1a, prednisone and azathioprine.

Break-through symptoms (BTS) in multiple sclerosis (MS) patients on beta-interferon (beta-IFN) monotherapy are most frequently treated with a brief administration of steroids. Here, we report the results of monitoring serum immunologic markers recorded at three-month intervals for 1.5 years in responders to beta-INF 1a (Avonex) monotherapy (n =21) and MS patients placed on Avonex with prednisone (n =83) and Avonex, prednisone and azathioprine (AZA) (n =21) because of BTS. Compared to 23 healthy controls, patients on Avonex monotherapy and Avonex with prednisone, in individuals on Avonex, prednisone and AZA, a significant decrease in serum concentration of soluble intercellular adhesion molecule-1 (sICAM-1) (P=0.001) was established. Combined therapy with Avonex, prednisone and AZA was associated with a significant increase in the serum level of interleukin (IL)10 (P <0.001). Compared to Avonex monotherapy, combined therapy suppressed the serum level of IL12p40, antagonized elevation in the serum concentration of soluble IL2 receptor (sIL2R) and inhibited an increase in the serum soluble CD95 (sCD95) molecule. In patients studied, no significant differences in the serum level of IL18 and tumor necrosis factor-alpha (TNF-alpha) were established. These findings are important in understanding some of the immunoregulatory mechanisms induced by combined therapy in MS.

Adult↗
PubMedDate not supplied

Associations of dichlorodiphenyltrichloroethane (DDT) 4.4 and dichlorodiphenyldichloroethylene (DDE) 4.4 blood levels with plasma IL-4.

DDT (dichlorodiphenyltrichloroethane) reportedly induces cancer in animals, mimics estrogen activity, induces antiandrogen effects, and impairs Natural Killer (NK) cells and T lymphocyte responses. In this study, the authors attempted to determine associations of DDT, dichlorodiphenyldichloroethylene (DDE), and dichlorodiphenyldichloroethane (DDD) blood levels with several immune parameters in patients occupationally exposed to insecticides. The study subjects were 49 patients who worked as farmers or farmhands in the former German Democratic Republic and who had been occupationally exposed to insecticides for at least 6 mo; 80% of them had been exposed for more than 20 yr. Blood levels of DDT, DDE, DDD, 2,3,4,5,6-pentachlorophenol (PCP), polychlorinated biphenyls (PCBs), hexachlorobenzene (HCB), and gamma-hexachlorocyclohexanes (HCHs) were determined, and blood lymphocyte subpopulations, in vitro responses to mitogens or pooled allogeneic stimulator cells, plasma neopterin, and cytokine and soluble cytokine receptor levels were studied. The majority of patients were contaminated with more than 1 chemical--most commonly DDE, PCBs, and HCB. Linear-regression analysis showed that interleukin-4 (IL-4) plasma levels were associated with plasma levels of DDT 4.4 (p = .0001) and DDE 4.4 (p = .001). The data in this study suggest that PCBs, PCP, HCB, HCHs, DDE, and DDD suppress TH1 cytokines, such as IL-2 and interferon-gamma (IFN-gamma), and induce TH2 cytokines, such as IL-4. The authors hypothesized that clinical symptoms, such as the frequent infections reported by many patients, could be a consequence of these immunological abnormalities.

Adult↗
PubMedDate not supplied

[Kemantan treatment of patients with recurrent aphthous stomatitis].

The authors assess the therapeutic efficacy of kemantan, an immunomodulator, used in the treatment of 30 patients with severe stubborn recurrent aphthous stomatitis (RAS). The blood immunological and biochemical characteristics were checked up over the course of treatment. Clinical and laboratory studies have shown that this immunocorrective agent is sufficiently effective for fibrous and cicatrizing RAS running a permanent course: the periods of the pathologic elements epithelialization are shortened, the permanent course of the condition is interrupted and the remissions are prolonged; clinical cure has been achieved in a number of cases. Kemantan is indicated for RAS patients only in cases with immunologic insufficiency, with immunologic responses monitored over the course of the treatment.

Adamantane↗
PubMed1993

Late T cell deficiency in victims of the Chernobyl radiation accident: possible mechanisms of induction.

T cell number, serum concentrations of thymic hormones and anti-epithelial autoantibodies were studied in people affected at Chernobyl NPP. Group 1 took part in the clearing-up operation and had no clinical manifestations of acute radiation sickness. Group 2 worked at the NPP during the accident; they survived acute radiation sickness (degree I-II, subgroup 2a; degree III-IV, subgroup 2b). The total doses of external radiation were 0.1-0.5 Gy in group 1, up to 4 Gy in subgroup 2a and up to 9 Gy in subgroup 2b. Total T cell number, serum thymic activity and alpha 1-thymosin concentration were decreased in all groups of affected persons. CD8+ cell number decreased only in group 1; CD4+ cell number in subgroup 2b. A decrease in thymic hormone level was most prominent in subgroup 2b. The titres of anti-epithelial antibodies were increased in all groups of affected persons independently of radiation dose. The titres were higher in patients with subnormal levels of alpha 1-thymosin. It has been proposed that radiation alters the function of thymic epithelial cells by direct action and/or through indirect mechanisms including participation of autoantibodies. The observed complex of alterations is similar to that in the normal process of immunological ageing.

Accidents↗
PubMed2005

Complete remission of liver metastasis of pancreatic cancer under vaccination with a HLA-A2 restricted peptide derived from the universal tumor antigen survivin.

PURPOSE: As prognosis of advanced pancreatic cancer remains gloomy, novel therapeutic modalities have to be developed. Immunotherapy, which targets tumor-associated antigens of tumor cells or tumor stroma, is currently under investigation. As survivin is expressed by neoplastic and tumor endothelial cells, but rarely by normal cells, this antigen appears as an intriguing target molecule. METHODS: A 72-year old patient, suffering from pancreatic cancer refractory to gemcitabine therapy, received the survivin-based peptide vaccinations consisting of 100 mug of a modified HLA-A2 restricted survivin(96-104) epitope in Montanide(R). Each visit the patient was assessed for adverse events, quality of life and immunological response. Immuno-monitoring was performed by IFN-gamma-ELISPOT analysis of peripheral blood lymphocytes. Clinical outcome was evaluated by repetitive computed tomography. RESULTS: Under vaccination with survivin peptides the patient initially underwent partial remission of liver metastasis which proceeded after 6 months into a complete remission with a duration of 8 months. Immunological monitoring revealed strong vaccine-induced immune-reactivity against survivin. Unfortunately, after the patient was weaned from vaccination in state of no evidence of disease, he developed recurrent disease. CONCLUSION: T-cell responses against survivin-expressing cells of the tumor itself and tumor endothelium should impact tumor growth and metastasis. The presented patient with pancreatic cancer is the first example of a successful application of a survivin-based vaccination in the clinical setting. An ongoing phase I/II trial with HLA-A1, -A2 and -B35 restricted survivin peptides for patients with advanced cancer will provide further information towards this notion.

Adenocarcinoma↗
PubMed1991

[Immunity disorders and the increased fatigability syndrome in the residents of the city of Kiev].

A clinical and immunological study is presented of 1030 practically healthy persons inhabiting Kiev from the moment of the Chernobyl accident. It was established clinically that during the last 5 years more frequent became acute respiratory viral infections, exacerbation of existing infection foci, appearance of complaints of reduced working capacity, somnolence apathy, increased fatiguability, worsening of memory, periodic subfebrility and oth. This symptom complex was determined as the "increased fatiguability syndrome". It was characterized immunologically by different changes showing most frequently a reduction of the functional activity of natural killers. The authors analyze different variants of immunological disorders in this group of subjects and give practical recommendations on using immunotropic drugs. They emphasize the importance of a service of clinical immunology in Ukraine able to organize special services to the population.

Accidents↗
PubMed1994

Naive idiotype-specific CD4+ T cells and immunosurveillance of B-cell tumors.

The immunosurveillance hypothesis suggests that lymphocytes can recognize tumor-specific antigens expressed by transformed cells and initiate their elimination. Immunosurveillance implies that lymphocytes of naive phenotype can home to a tumor site and become activated by tumor-specific antigens. In this study, we have employed T-cell receptor transgenic mice as a source of naive, tumor-specific T cells. The transgenic, CD4+ T cells recognize a 91- to 101-residue fragment of the lambda 2(315) immunoglobulin light chain presented by I-Ed class II molecules. Such naive, idiotype-specific, CD4+ T cells protected against tumor development of a class II negative plasmacytoma (MOPC315) and a class II positive B lymphoma (F9), which both secrete lambda 2(315) immunoglobulin. Adoptive transfer experiments demonstrated that 2 x 10(6) lymph node cells were sufficient for protection against MOPC315. Depletion of T-cell subsets indicated that transgenic CD4+ cells were indispensable for tumor resistance. However, an additional role of CD8+ T cells is not ruled out. In contrast to the resistance against the secreting MOPC315 and F9 cells, transgenic mice were not protected against B lymphoma cells (F67), which do not secrete lambda 2(315) but express a truncated lambda 2(315) chain intracellularly. The results suggest that lambda 2(315) is processed and presented by host antigen-presenting cells, which in turn activate naive, idiotype-specific T cells.

Animals↗
PubMed1993

Immunomodulatory effects of interferon-gamma in patients with metastatic malignant melanoma.

Interferon-gamma (IFN-gamma) is a potent monocyte/macrophage activating agent that in animal models exhibits a bell-shaped dose-response curve of immunomodulatory activity and antitumor efficacy. Previous clinical trials of IFN-gamma conducted at the maximal tolerated dose (MTD) have been associated with low response rates that may have been due to failure to treat at an optimal immunomodulatory dose (OID). The objective of this study was to test the hypothesis that optimal immunomodulatory activity of IFN-gamma in patients with metastatic melanoma would be obtained at a dose below the MTD. Groups of five patients each were given daily subcutaneous injections of IFN-gamma at doses of 0.01, 0.1, or 0.25 mg/m2. In vivo immunomodulation was assessed by serial measurement of serum neopterin and by flow cytometry. IFN-gamma doses of 0.1 or 0.25 mg/m2 induced significantly greater immunomodulation of monocyte-associated immune parameters than 0.01 mg/m2. Changes in immunologic parameters included marked elevation of serum neopterin levels, significant increases in monocyte expression of CD64, beta 2-microglobulin, and HLA-ABC, and decreased monocyte expression of CD14. The most dramatic decreases in CD14 expression were observed on monocytes obtained from patients treated at 0.25 mg/m2. The 0.25-mg/m2 dose group had significantly lower white blood cell counts on day 14. No bell-shaped curve of immunologic response was observed over the dosage range tested. Based on the similarity of the immunologic effects at 0.1 and 0.25 mg/m2, treatment at the MTD of IFN-gamma (0.25 mg/m2) represents treatment at the OID for patients with metastatic malignant melanoma.

Adjuvants, Immunologic↗