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Effects of ornithine on neutrophil (PMN) free amino acid and alpha-keto acid profiles and immune functions in vitro.

The objective of this study was to determine the effects of ornithine on polymorphonuclear leucocyte (PMN) free amino- and alpha-keto acid profiles, superoxide anion (O2-) generation, hydrogen peroxide (H2O2) formation and released myeloperoxidase activity (MPO). Exogenous ornithine significantly increased PMN asparagine, glutamine, aspartate, glutamate, arginine, citrulline, alanine, alpha-ketoglutarate and pyruvate as intracellular ornithine increased. Concerning PMN immune function markers ornithine increased H2O2-generation and MPO activity while O2- -formation was decreased. We believe therefore that ornithine is important for affecting PMN "susceptible free amino- and alpha-keto acid pool" although the mechanisms are not yet clear. This may be one of the determinants in PMN nutrition considerably influencing and modulating PMN host defense capability.

Adult↗

Analysis of partial variance to control for day-to-day variability in functional immune tests in depression.

Recently, analysis of partial variance (APV) was proposed as a technique to control for day-to-day variance in mitogen-induced lymphoproliferative responses whereby data obtained from controls, run in the laboratory on the same day, are used as covariates in regression analysis. In order to check the utility of the APV method in the interpretation of functional immune tests, we have reanalyzed lymphoproliferative responses in experimental subjects with depression (n = 38) stimulated by phytohemagglutinin (PHA), pokeweed mitogen (PWM) and concanavalin A (Con A) in relation to responses obtained in laboratory controls. There were no significant relationships between the depressed patients' and laboratory controls' lymphoproliferative responses to PHA, PWM or Con A. Controlling for day-to-day variation by means of regression analysis did not significantly alter the significant relationships between the patients' lymphoproliferative responses and clinical variables, such as depressive classification and severity of illness. It is argued that the APV method may not be used to adjust for an inappropriately high day-to-day variability in immune assays.

Adult↗

Role for mucosal immune responses and cell-mediated immune functions in protection from airborne challenge with Venezuelan equine encephalitis virus.

Venezuelan equine encephalitis virus (VEEV) replicates in lymphoid tissues following peripheral inoculation and a high titre viraemia develops. Encephalitis develops after the virus enters the central nervous system from the blood, with the earliest neuronal involvement being via the olfactory nerve. Following aerosol challenge with virulent VEEV, the virus is thought to replicate in the nasal mucosa and there could be direct entry into the olfactory nerve via infected neuroepithelial cells. Protection from VEEV infection is believed to be primarily mediated by virus specific antibody. The correlation between protection and neutralising serum antibody titres is, however, inconsistent when the virulent virus is administered by the airborne route. This study demonstrates a link between antibody in serum and the nasal mucosa and protection by means of passive immunisation studies. Intra-nasal administration of antibody increased protection against airborne virus in Balb/c mice. Vaccination of mu MT strain mice that do not have functional B cells and cannot produce antibody revealed normal proliferation of spleen cells in vitro and robust cytokine production. Aerosol challenge of mu MT mice demonstrated that complete protection was only achieved when passive immunisation with antibody was supplemented with active immunisation with the TC-83 vaccine strain of the virus. This implies that cell-mediated immune functions are required for protection against airborne challenge with virulent VEEV.

Administration, Intranasal↗

Immune functions in the Fisher rat fed beluga whale (Delphinapterus leucas) blubber from the contaminated St. Lawrence estuary.

In order to assess the immunotoxic potential of food naturally contaminated with PCBs and other organohalogens, Fisher rats were fed a diet in which the lipids originated from the blubber of either a highly polluted St. Lawrence beluga or a relatively uncontaminated Arctic beluga. After a period of 2 months, different immune functions were evaluated, including lymphoblastic transformation, natural killer cell activity, plaque-forming cells, phagocytosis, oxidative burst, and immunophenotyping. For all assays, rats fed a St. Lawrence beluga blubber diet or a mixture of Arctic and St. Lawrence beluga blubber diet were not different from control rats fed a diet containing Arctic beluga blubber. These results are inconsistent with the well-known immunosuppressive effects of organochlorines in numerous species and with the lesions suggestive of organochlorine-related immunosuppression that are observed in St. Lawrence belugas. The lack of observable immunotoxic effects in rats fed contaminated beluga blubber might be explained by antagonistic effects in the organohalogen mixture, by a response specific to the rat, by a strain-related lack of sensitivity to organochlorines, or by insufficient dose due to the shortness of the exposure period or the route of exposure.

Adipose Tissue↗

Polymorphisms in immune function genes and risk of non-Hodgkin lymphoma: findings from the New South Wales non-Hodgkin Lymphoma Study.

Recent findings suggest that genetic polymorphisms in TNF and IL10 are associated with an increased risk of non-Hodgkin lymphoma (NHL), particularly for diffuse large B-cell lymphoma (DLBCL). To further investigate the contribution of common genetic variation in key cytokine and innate immunity genes to the etiology of NHL, we genotyped participants in a case-control study of NHL conducted in Australia (545 cases, 498 controls). We investigated 36 single nucleotide polymorphisms in IL10, TNF and 21 other immune function genes. We observed an elevated risk of DLBCL with the IL10 -3575T>A polymorphism [TA genotype: odds ratio (OR)=1.32, 95% confidence interval (CI)=0.86-2.02; AA, OR=1.84, 95% CI=1.10-3.08; trend test, P=0.02]. Our most noteworthy TNF finding was an association between -857C>T and a decreased risk of NHL (CT or TT, OR=0.59, 95% CI=0.42-0.84, P=0.003) and particularly follicular lymphoma (OR=0.40, 95% CI=0.23-0.68, P=0.0009). Additionally, TNF -863C>A was associated with an elevated risk of DLBCL (CA, OR=1.45, 95% CI=0.95-2.21; AA, OR=2.06, 95% CI=0.88-4.83; trend test, P=0.02). Our findings offer further evidence that variation in the IL10 and TNF loci influences NHL risk. Additional studies are needed to clarify the genetic and biologic basis for these relationships.

Adult↗

[Study of anti-tumor action and influence on immune function of Allium stativum].

Applying mice test on cancer model of S180 and Lewis cancer by using method clystered stomach(oral), observs the Anti-tumor function. Experiments showed that Allium sativum can inhibit tumor growth and Lengthen lift duration of mice, the rate of inhibiting tumor was 74.35% and life lengthening rate were 42.4%, with control grou comparison. There was profund difference between them. Besides, we discoved Allium sativum can raise immune function of mice.

Allium↗

Characterization of immune function and analysis of RAG gene mutations in Omenn syndrome and related disorders.

Omenn syndrome was recently found to be caused by missense mutations in RAG1 or RAG2 gene that result in partial V(D)J recombination activity. Although the clinical hallmarks of the disease are well defined, there have been several cases with clinical findings similar to, but distinct from Omenn syndrome. The data on immune functions and RAG gene mutations of such cases are limited. We described five Japanese infants from four unrelated families, including two cases of Omenn syndrome and three cases of related disorders. Sibling cases with typical Omenn phenotype were found to be compound heterozygotes of R396C and L885R mutations in RAG1. The former has been reported in European cases and may constitute a hot spot. The latter is a novel missense mutation. Infants with related disorders exhibited erythroderma, eosinophilia, hypogammaglobulinaemia, decreased number of B cells and skewing to Th2, and their lymph node specimens showed architectural effacement, lymphocyte depletion and histiocytic hyperplasia, each of which is seen characteristically in Omenn syndrome. However, in these cases serum IgE levels were low or undetectable. We found no mutation in RAG genes except for a K820R substitution in RAG1, which was regarded to be a functional polymorphism, in two of these cases. Our study suggests that RAG missense mutation may be a genetic abnormality unique to Omenn syndrome with characteristic clinical and laboratory findings. Variations of Omenn syndrome, or related disorders, may represent a different type of immunodeficiency, distinct from abnormalities in lymphoid-specific recombinase activity.

Apoptosis↗

Changes in immune function in patients receiving natural leukocyte interferon.

Highly purified human lymphoblastoid interferon derived from virus-stimulated Namalwa cells was administered daily by 6-h i.v. infusion or i.m. injection to 40 patients with a variety of disseminated malignancies refractory to standard therapy. Each patient received escalating doses of 0.1-50 X 10(6) U for up to 5 weeks. Extensive monitoring for changes in various immune functions revealed no sustained elevation in natural killer cell activity, elevated monocyte-mediated antitumor cytostatic activity in approximately 30% of the patients, and depressed lymphoproliferative responses to mitogens and mixed leukocyte culture.

Cytotoxicity, Immunologic↗

Immune function in congenital osteopetrosis: defective lymphocyte function in microphthalmic mice.

Osteopetrosis is a prominent feature of a congenital mutation described in microphthalmic mice and is thought to be due to defective osteoclast function which causes a generalized lack of bone resorption. Reversal of defective bone resorption in osteopetrotic mutants has been achieved by hematopoietic cell transplantations; and conversely, defective bone resorption has been transferred to normals by hematopoietic cells from osteopetrotic littermates. This suggested that osteopetrotic mutants might also demonstrate defective immune functions which could in turn be related to the lack of normal bone resorption. To that end, aspects of in vitro lymphocyte function in microphthalmic mice were compared to those of their phenotypically normal littermates. There was a significant diminution in the proliferative response of splenocytes to mitogens in microphthalmic mice. Microphthalmic splenocytes also were less responsive in an in vitro assay which measured the capacity to form antibody forming cells.

Animals↗

Nutrient modulation of inflammatory and immune function.

The metabolic response to injury occurs after a diverse group of surgical injuries including major surgical intervention, shock, infection, and sources of inflammation such as pancreatitis. The response is mediated by the macroendocrine system, the autonomic nervous system, and the cell-cell communication system. The clinical manifestations include now well-described clinical, physiologic, and metabolic characteristics. The approach of aggressive source control, invasive circulatory resuscitation, and nutrition/metabolic support has been associated with an overall reduction in morbidity and mortality. In those patients who do not respond to this approach, the disease process progresses to multiple organ failure syndrome with its associated high mortality. Altering the route of feeding, preventing single nutrient and generalized nutrient deficiency, and reducing nosocomial infections with selective gut decontamination have not significantly altered the course or outcome of the disease process in this latter group of patients with persistent hypermetabolism. The available data support the position that this persistent hypermetabolism represents abnormal metabolic regulation resulting in persistence of the inflammatory response with associated suppression of the immune defenses. A number of research approaches are being taken to understand and modulate this abnormal state of regulation. Because of the role of specific nutrients in these regulatory processes, beyond their role in classic nutrition support, nutrients such as arginine n-3 polyunsaturated fatty acids, and RNA are being evaluated for their ability to modulate inflammation and to improve immune function. Preliminary results are encouraging.

Arginine↗

[Normal immune function in centroblastic-centrocytic and centroblastic lymphoma].

We tested in vitro lymphocyte reactivity using 5 mitogens and 9 antigens, measured lymphocyte and lymphocyte subpopulation counts, granulocyte chemotaxis and adherence in 10 patients with centroblastic-centrocytic lymphoma (CB-CC), 7 patients with centroblastoma (CB) and 88 healthy controls. The control group could be divided into 3 clusters with significantly different lymphocyte reactivity by means of cluster and discrimination analysis (BMDP2N): 21 high-, 18 medium- and 49 low responders. Comparing lymphocyte reactivity of CB-CC and CB patients to each of the 3 immunofunctional different control groups yielded the surprising result that both malignant lymphomas are equivalent to the low responding control group and show a low, but still normal in vitro immune function.

Adult↗

Peripheral mononeuropathy affects hypothalamic and splenocyte beta-endorphin levels but not immune function in the rat.

Beta-endorphin and substance P levels were measured in the hypothalamus of rats 14 days after chronic constriction injury of right sciatic nerve. Furthermore, beta-endorphin concentrations in splenocytes, phytoemoagglutinin-induced proliferation of splenocytes, and natural killer activity were assessed. We observed a significant increase of beta-endorphin and substance P hypothalamic levels, and a significant decrease of beta-endorphin concentrations in the immune cells. In contrast, the peripheral mononeuropathy did not affect the immune function. This study presents a picture of central and peripheral peptide changes consistent with a painful condition, but different from what previously observed in rats which underwent peripheral nerve deafferentation or stressful conditions.

Animals↗

Effect of pentachlorophenol on immune function.

The organochlorine compound, pentachlorophenol, was evaluated for effects on immune system function in male Fisher 344 rats. Pentachlorophenol was prepared in an olive oil vehicle and was administered by oral gavage twice weekly for 28 days at a dose of 2.0 mg/kg per treatment. Exposure to pentachlorophenol increased body weight gains (P=0.024) during the treatment period. Liver (P=0.034) and kidney (P=0.012) body weight ratios were also increased. Pentachlorophenol exposure enhanced T-lymphocyte blastogenesis induced by concanavalin A (Con A)(P=0.0001) and phytohemagglutinin (PHA)(P=0.048) evaluated using stimulation indices. Corresponding B-lymphocyte blastogenesis induced by lipopolysaccharide/dextran (LPS/dex)(P=0.0034) was also enhanced by pentachlorophenol exposure. Pentachlorophenol suppressed the antibody response against sheep red blood cells (SRBCs) by 39% when the response was expressed per viable spleen cell (P=0.006). This suppression was not evident when the response was expressed per spleen (P=0.22), suggesting that a compensatory mechanism or extramedullary splenic hemopoiesis was occurring minimizing the overall impact on humoral immunity. The enhanced B- and T-lymphocyte blastogenesis may also reflect compensatory or hemopoietic activity. Pentachlorophenol exposure had no effect on peritoneal macrophage phagocytosis (P=0.31) or lymphocyte cell surface antigen expression. The observed alterations in lymphocyte blastogenesis and humoral immunity subsequent to pentachlorophenol exposure do not appear to be associated with phagocytosis or lymphocyte cell surface antigen expression.

Animals↗

Effects of sleep deprivation on human immune functions.

The effect of 40 h of wakefulness on a variety of immunological parameters in the peripheral blood from 10 normal male subjects was studied. Sleep deprivation led to enhanced nocturnal plasma interleukin 1-like and interleukin 2-like activities. The rise in nocturnal response of lymphocytes to pokeweed mitogen stimulation during a normal 24 h sleep-wake cycle was delayed by sleep deprivation, but the response to the phytohemagglutinin mitogen was unaffected. With resumed nocturnal sleep, there was a prolonged decline in natural killer cell activity (measured as spontaneous cytolytic activity for human tumor cells) and return of an increased response to pokeweed mitogen. The altered patterns in immune functions occurred independently of the cortisol circadian rhythm, which remained unchanged.

Adult↗

Immune function, telomerase, and angiogenesis in patients with primary, operable nonsmall cell lung carcinoma: tumor size and lymph node status remain the most important prognostic features.

BACKGROUND: Lung carcinoma usually is advanced at the time of presentation and frequently shows metastatic spread. In recent times, prognostic factors such as c-erbB-2 in patients with breast carcinoma have provided useful information and beneficial therapeutic targets. The objective of this study was to evaluate angiogenesis, immune function, and telomerase expression in patients with nonsmall cell lung carcinoma (NSCLC) to determine their prognostic significance. METHODS: Immunohistochemistry was used to evaluate the expression of human telomerase reverse transcriptase (hTERT; n = 115 patients), interleukin-2r (IL-2r; n = 40 patients), microvessel density (MVD; n = 81 patients), and vascular endothelial growth factor (VEGF; n = 61 patients). Three-year survival follow-up information was available for most patients, and a comprehensive review of clinicopathologic features was carried out. RESULTS: Fifty percent of tumors showed nuclear staining for hTERT, 55% of tumors showed some degree of lymphocyte IL-2r expression, 33% of tumors were recorded with an MVD that was higher than average, and VEGF staining was detected in 85% of tumors. None of the parameters measured had an impact on survival. hTERT expression was correlated with lymph node status. Lymph node status and tumor size were identified as independent prognostic factors. CONCLUSIONS: This study failed to identify a marker of prognosis for patients with NSCLC other than tumor size and lymph node status in this population. Telomerase expression was associated with metastases, raising the possibility that this enzyme is involved in the metastatic process. Tumor cell VEGF expression was identified frequently: This growth factor may have potential as a target for antiangiogenic therapy. Lung carcinoma typically is the result of large numbers of mutations. Further understanding of the biologic implications of these mutations will lead to the development of effective prognostic markers and treatments for patients with NSCLC.

Adult↗

Impaired cell-mediated immunity function in thyroid cancer.

Immunological parameters were studied in 31 patients with thyroid cancer. Serum immunoglobulin levels, T and B cell percentages in peripheral blood, showed no significant difference as compared with those of control group. The blastogenesis with phytohemagglutinin P (PHA) was significantly reduced, especially, in those having larger tumor size or metastasis or in those over age 60. The positive rate of skin test with purified-protein-derivative (PPD) and Streptokinase-Streptodornase (SK-SD) was also markedly reduced. The impaired blastogenesis of lymphocyte and reduced positive rate of skin test in those cancer patients suggested that the cell-mediated immunity function, in spite of adequate count of T-cells, was impaired.

Adult↗

[The primary observation of effect on immune function of human body by YAG laser tonsillocoagulation].

Tonsillocoagulation was performed on 50 patients with chronic tonsillitis by virtue of YAG Laser. The patients' serum IgG, IgA, IgM, C3level and some acute phase reactant proteins (APRPs) including alpha 1-AGP, alpha 1-AT, Tf were measured pre- and postoperatively. In addition, tonsillar morphology was observed with light and electron microscope before and after tonsillocoagulation. Following up the patients for six to twelve months, we discovered that their immune function remained normal and that their symptoms of chronic tonsillitis had been controlled, it suggests that YAG Laser tonsillocoagulation can be a practical therapy for chronic tonsillitis.

Acute-Phase Proteins↗

Prematurity, immune function and infant feeding practices.

Recently, there has been much interest in the literature in the role of early nutrition and the health of the individual in adulthood. A majority of infants in the UK are born full term, while preterm infants account for 4-6% of the total births. Milk feeding practices are divided into three groups: breast, combination (breast-fed with formula as 'top-up') and bottle (formula). In studies conducted by our group and other researchers immune function in full-term and preterm infants has been assessed by monitoring total and specific immunoglobulin E and specific immunoglobulin G levels. Dietary modification by the pregnant mother with a history of allergy in the family has been shown to have a positive effect with respect to allergy outcome and prevention of atopic disease in the infant. However, this dietary modification has to occur before week 22 of pregnancy and continue until the end of lactation to achieve a beneficial outcome to the infant. The stress of mothers restricting their diets may be disadvantageous to the fetus, and therefore any gain due to the dietary restriction may be lost. Researchers have shown that the early introduction of complementary foods and the greater diversity of these foods appeared to result in an increase in the incidence of atopic disease in the infant. In conclusion, in order to reduce the risk in their babies, mothers with a family history of atopic disease should breast-feed for more than 15 weeks and introduce solid foods after 4 months, limiting the variety until at least 6 months.

Aging↗