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Sense of humor, childhood cancer stressors, and outcomes of psychosocial adjustment, immune function, and infection.

The diagnosis, treatment, and side effects of childhood cancer have been described as extremely stressful experiences in the life of a child. Anecdotally, children report that a sense of humor helps them cope with the daily experiences of living with cancer; however, no research has examined sense of humor and childhood cancer stressors. This study investigated the effect of sense of humor on the relationship between cancer stressors and children's psychosocial adjustment to cancer, immune function, and infection using Lazarus and Folkman's theory of stress, appraisal, and coping. A direct relationship was observed between sense of humor and psychosocial adjustment to cancer, such that children with a high sense of humor had greater psychological adjustment, regardless of the amount of cancer stressors. A moderating effect was observed for incidence of infection. As childhood cancer stressors increase, children with high coping humor scores reported fewer incidences of infection than low scorers.

Adaptation, Psychological↗

[An experimental study of immune function effect of rats irradiated with the complex field cure instrument].

The complex field cure instrument is a new medical instrument with which an experiment was carried out. Rats were continuously irradiated by the complex field for 90 days, with a day's total dose of 285.9 M.T.G. while other rats weren't irradiated for control group. The animals were respectively killed at 7d, 14d, 30d, 60d and 90d, and their blood samples were taken for cell and humoral immune analysis. The results show that values of lymphocyte transform rate, soluble receptor (SIL-2R), total hemolytic complement levels (CH50) and immunoglobulin (A.G.) after irradiation are more than those of the control group having proved that the instrument may improve immune function of rats.

Animals↗

Copper status and enzyme, hormone, vitamin and immune function in heifers.

A survey was conducted in 10 districts of Northern India to record the copper deficiency in soil, fodder and serum samples. Significant deficiency of copper was observed in soil, fodder and serum samples of heifers. The copper deficient animals were listless, showed depigmentation of skin, stiff gait and were anaemic and diahorric. The purpose of the study was to evaluate the magnitude of copper deficiency in Northern India and to examine the various haematobiochemicals, enzymes, vitamin and immune function which are affected by the deficiency of copper, so as to identify the parameters which can be of diagnostic importance in copper deficiency. Forty hypocuperemic heifers were selected from these areas and were randomly divided into two groups A and B. The heifers in group A were provided with mineral mixture containing copper sulphate and in group B without copper sulphate. Significant improvement (P<0.01) was observed in the haemoglobin (Hb), total leukocyte count (TLC) and total erythrocyte count (TEC) level at the 30th day of treatment in the animals of group A. Significant (P<0.01) improvement in serum. Ceruloplasmin (Cp) level was observed within 30 days of treatment, while significant (P<0.01) improvement in monoamine oxidase and liver cytochrome oxidase was observed at the 60th day of treatment in group A animals. Regarding hormones significant improvement was observed in T(3) and T(4), in the animals of group A within 60 days of treatment. The values of vitamin A and E showed significant (P<0.01) improvement within 30th days of treatment. The phagocytic activity of neutrophils against Candida albicans significantly (P<0.01) improved in group A within 60 days of treatment. Similarly significant improvement in superoxide dismutase activity in RBC was observed at the 30th day, and WBC and whole blood at 60th day in group A animals. Significant improvement in liver Cu level was observed at the 30th day of treatment, while in group B the liver Cu was significantly (P<0.01) depleted at the 60th day of experimentation. Additional Cu supplementation improved growth performance significantly in group A.

Animals↗

[Effects of Bacillus Calmette-Guerin vaccination on immune functional development of splenic T cell in neonatal mice].

OBJECTIVE: Almost every neonate receives Bacillus Calmette-Guerin (BCG) vaccination in China. The authors' previous study showed that BCG promoted cord blood monocyte-derived dendritic cells maturation and induced high level of interleukin (IL)-10, medium level of interferon (IFN)-gamma, but low level of IL-4 production by cord naive T cells. The experiments in the present study were designed to explore the effects of neonatal BCG vaccination on immune functional development of splenic T cells in mice in vivo. METHODS: Neonatal BALB/c mice were inoculated with BCG intraperiotoneally. Four weeks later, spleen cells of mice were isolated and surface molecular markers of CD4, CD25 and CD44 and intracellular IFN-gamma, IL-10, and IL-4 in CD3(+) T cells were detected by flow cytometry. Furthermore, mRNA expression of transcription factor T-bet, Foxp3 and GATA-3 were analyzed by RT-PCR. RESULTS: The percentage of total CD4(+) T cells decreased [(23.50 +/- 2.59)% vs. (47.38 +/- 10.41)%, P < 0.01] but the percentage of CD25(+) [(24.92 +/- 2.74)% vs. (20.27 +/- 2.85)%, P < 0.05] and CD44(+) [(89.29 +/- 2.56)% vs. (82.98 +/- 5.51)%, P < 0.05] T cells in CD4(+) T cells was higher in BCG-vaccinated mice than that in controls. Meanwhile, the percentage of IFN-gamma positive [(6.52 +/- 2.40)% vs. (3.13 +/- 2.03)%, P < 0.05] and IL-10 positive [(14.81 +/- 3.65)% vs. (10.90 +/- 1.61)%, P < 0.05] but not IL-4 positive [(1.17 +/- 0.46)% vs (1.51 +/- 0.75)%, P > 0.05] cells in CD3(+) T cells of BCG-vaccinated mice was significantly higher than that of non-BCG-vaccinated mice. In comparison with BCG-naive mice, T-bet was significantly high in BCG-vaccinated mice [T-bet/beta-actin 0.44 +/- 0.11 vs. 0.28 +/- 0.06, P < 0.05], but there was no significant difference in GATA-3 [GATA-3/beta-actin 0.46 +/- 0.08 vs. 0.50 +/- 0.10,P > 0.05] and Foxp3 [Foxp3/beta-actin vs. 0.27 +/- 0.11 and 0.30 +/- 0.16, P > 0.05] mRNA expression between the two groups. CONCLUSION: Neonatal BCG vaccination could induce strong Th1 but weak Th2 response as reported previously. Though neonatal BCG vaccination was not capable of inducing CD4(+)CD25(+) regulatory T cell response with Foxp3 expression, it caused increase of IL-10(+) CD3(+) cells which might represent some regulatory T cells producing IL-10.

Animals↗

CXCR3+CD4+ T cells mediate innate immune function in the pathophysiology of liver ischemia/reperfusion injury.

Ischemia-reperfusion injury (IRI), an innate immune-dominated inflammatory response, develops in the absence of exogenous Ags. The recently highlighted role of T cells in IRI raises a question as to how T lymphocytes interact with the innate immune system and function with no Ag stimulation. This study dissected the mechanism of innate immune-induced T cell recruitment and activation in rat syngeneic orthotopic liver transplantation (OLT) model. Liver IRI was induced after cold storage (24-36 h) at 4 degrees C in University of Wisconsin solution. Gene products contributing to IRI were identified by cDNA microarray at 4-h posttransplant. IRI triggered increased intrahepatic expression of CXCL10, along with CXCL9 and 11. The significance of CXCR3 ligand induction was documented by the ability of neutralizing anti-CXCR3 Ab treatment to ameliorate hepatocellular damage and improve 14-day survival of 30-h cold-stored OLTs (95 vs 40% in controls; p < 0.01). Immunohistology analysis confirmed reduced CXCR3+ and CD4+ T cell infiltration in OLTs after treatment. Interestingly, anti-CXCR3 Ab did not suppress innate immune activation in the liver, as evidenced by increased levels of IL-1beta, IL-6, inducible NO synthase, and multiple neutrophil/monokine-targeted chemokine programs. In conclusion, this study demonstrates a novel mechanism of T cell recruitment and function in the absence of exogenous Ag stimulation. By documenting that the execution of innate immune function requires CXCR3+CD4+ T cells, it highlights the critical role of CXCR3 chemokine biology for the continuum of innate to adaptive immunity in the pathophysiology of liver IRI.

Amino Acid Sequence↗

A novel nonanticoagulant heparin improves splenocyte and peritoneal macrophage immune function after trauma-hemorrhage and resuscitation.

Recent studies have shown that heparinization of animals prior to or even after hemorrhagic shock improves tissue perfusion and organ function. However, the anticoagulant properties of conventional heparin preclude its clinical use in trauma care. The aim of our study, therefore, was to determine whether chemically modified heparin, i.e., a novel nonanticoagulant heparin (GM1892), which does not have significant anticoagulant activity (approximately 2% of the anticoagulant activity of conventional heparin), produces any beneficial effects on splenocyte and macrophage immune function following trauma-hemorrhage and resuscitation. To determine this, following the induction of tissue trauma (i.e., a midline laparotomy), mice were bled to and maintained at a mean arterial pressure of 35 mm Hg for 1 hr. The animals then received GM1892 (7 mg/kg body wt), conventional heparin (7 mg/kg body wt), normal saline prior to resuscitation with three times the volume of shed blood with Ringer's lactate. Two hours after resuscitation the animals were sacrificed, splenocytes were isolated, and splenic, as well as peritoneal macrophage, cultures were established. The ability of the splenocytes to release IL-2 and IL-3 in response to mitogen was markedly improved in hemorrhaged animals which were treated with GM1892 or conventional heparin compared to saline-treated mice. Furthermore, the capacity of splenic and peritoneal macrophages to release IL-6 was restored in the hemorrhaged animals that received GM1892 or conventional heparin.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Possible interaction between new quinolones and immune functions in macrophages.

Some of the immunological effects of a variety of new quinolones on chemotaxis and the production of superoxide anion in rat macrophages were studied. All of the new quinolones examined at a dose range of 0.5 to 50 microg/ml significantly inhibited chemotaxis in a dose-dependent manner in rat macrophages. Moreover, the new quinolones at a dose of 0.5 microg/ml were effective in markedly potentiating the generation of superoxide anion. These results indicate that the new quinolones may modulate immune functions in rat macrophages.

Animals↗

[Changes in DNA and purine nucleotide synthesis in lymphoid cells and sensitivity to glucocorticoids associated with the impairment of differentiation and immune function in mice during tumor growth. Spleen T- and B-lymphocytes].

Biochemical impairments in spleen immunocompetent cells (T- and B-lymphocytes) were revealed in host (C3HA mice) of transplantable and ortoaminoazotoluol-induced hepatomas in the course of their growth. As soon as hepatoma emerged (chemical carcinogenesis), the activity of adenosine deaminase and purine nucleoside phosphorylase in T- and B-lymphocytes were found to be reduced 2-6 and 7-10-fold, respectively in parallel with the impairment of their immune system. These alterations were accompanied by the increase in concentrations of dGTP in T-lymphocytes (5.4-fold) and of dATP in B-lymphocytes (4-fold) as well as with the inhibition of DNA synthesis, predominantly in T-lymphocytes. In both T- and B-lymphocytes, the dCTP pool was decreased. In the spleen, T- and B-lymphocytes of mice carrying transplantable 22 hepatoma 22 by the moment of its maximal growth (5th day), the DNA synthesis was inhibited as revealed by the reduction of (a) thymidine kinase activity, (b) rate of the labeled thymidine incorporation into DNA, and (c) intracellular dTTP and dCTP concentrations. In latter periods (from 8th day up to the moment of death), drastic stimulation of DNA synthesis in spleen T- and B-lymphocytes was observed irrespective of the impairments in the immune function and the decrease of the adenosine deaminase activity. In the course of growth of both transplantable and induced solid hepatomas in host spleen T- lymphocytes, the activity of the CTP-dependent thymidine kinase isoenzyme increased, coinciding in time with the activation of antigen-specific T-suppressors in the same organ.

Adenosine Deaminase↗

Stress-induced changes in immune function are associated with increased production of an interleukin-1-like factor in young domestic fowl.

Investigation of the effects of stress on the immune system in young developing animals is hampered by many variables such as maternal interactions and physical size of immune organs. Young, precocial domestic fowl were used to overcome these difficulties. Domestic fowl, 14 days posthatch, served as an animal model to investigate the effects of stress (acute social isolation) on a rapidly developing immune system. Group-housed animals were isolated for 30, 60, or 90 min and assayed for numerative and functional changes in immune parameters in spleen and blood. The socially isolated birds showed an increase in body temperature, indicative of stress. The number of leukocytes/ml of blood increased in a time-dependent fashion, but the number of leukocytes in the spleen did not. The stress of isolation resulted in a significant increase in B-lymphocyte mitogen proliferation at 30 min, which decreased with time. Social stress also induced a time-dependent decrease in T-lymphocyte mitogen proliferation, which was significant by 90 min. Associated with changes in mitogen responsiveness was a significant increase in the production of an IL-1-like factor by splenic adherent cells from animals isolated for 30 min, which decreased in a time-dependent manner to return to baseline by 90 min. Thus, young domestic fowl represent a practical model for the examination of the effects of stress on immune function in a developing animal.

Animals↗

Ovarian cancer: a solid tumor with evidence of normal cellular immune function but abnormal B cell function.

Immunologic assays of B and T lymphocyte function were performed on 21 patients with epithelial ovarian cancer prior to either chemotherapy or radiotherapy. The results were compared to similar studies on 12 age-matched normal women. The total peripheral blood lymphocyte counts, proportion of E rosette positive cells, stimulation of T cells by phytohemagglutinin and concanavalin A, recall skin tests, and the ability to have a primary delayed hypersensitivity response to keyhold limpet hemocyanin did not differ between patients and controls. However, patients with ovarian cancer had statistically significant reduction in surface immunoglobulin positive cells, proliferative response to pokeweed mitogen and primary antibody response to keyhole limpet hemocyanin. In contrast to results in patients with other solid tumors, these data indicate that untreated patients with ovarian cancer have evidence of normal cellular immune function but abnormal B cell function.

Adult↗

Impairment of cell-mediated immunity functions by dietary zinc deficiency in mice.

Several immunologic features were analyzed in mice on a zinc-deficient diet [Zn(-)], in mice pair-fed a diet containing zinc [Zn(+)], in mice fed a Zn(+) diet ad lib, and in mice fed laboratory chow ad lib. When placed on a Zn(-) diet, 6- to 8-week-old A/Jax, C57BL/Ks, and CBA/H mice showed loss of body weight, low lymphoid tissue weight, and profound involution of the thymus within 4-8 weeks after initiation of the regimen. Approximately 50% of the mice on the Zn(-) diet developed severe acrodermatitis enteropathica (lesions on tail and paws) and diarrhea. Pair-fed mice on the Zn(+) diet did not show any of these symptoms. Mice on the Zn(-) diet showed the following immune deficiencies: (i) depressed plaque-forming cells against sheep erythrocytes after in vivo immunization; (ii) depressed T killer cell activity against EL-4 tumor cells after in vivo immunization; and (iii) low natural killer cell activity. However, antibody-dependent cell-mediated cytotoxicity against chicken erythrocytes was normal in the mice on the Zn(-) diet. Deficiency of T killer cell activity was not observed when immunization with EL-4 allogeneic lymphoma cells was carried out in vitro. Progressive loss of relative and absolute number of Thy 1.2+ cells and a proportionate relative increase in cells bearing Fc receptors was seen in spleen and lymph nodes of Zn(-) animals. It appears that zinc is an essential element for maintenance of normal T cell and other immune functions in vivo.

Animals↗

The duration of latent infection and functional immunity in droughtmaster and hereford cattle following natural infection with Babesia argentina and Babesia bigemina.

Tne Droughtmaster and 9 Hereford cattle were born in an enzootic babesiasis area and became naturally infected with Babesia argentina and B.bigemina during a 3 year period. They were then kept free of cattle ticks (Boophilus microplus) for the remainder of the experiment. Annually for the next 3 years their individual infection status with Babesia was determined by sub-inoculation of blood into splenectomised calves. At the end of this period the functional immunity of all cattle was challenged by blood inoculation of heterologous strains of B. argentina and B. bigemina. Infection with B. argentina persisted in all Herefords for 2 years and in 7 for 3 years after they had been freed of B. microplus. The number of Droughtmasters with detectable B. argentina infection progressively declined, and at the end of 3 years only 2 of 10 were still infected. No Herefords were shown to be infected with B. bigemina following 1 year's freedom from B. microplus but latent B. bigemina infection of at least 2 year's duration was demonstrated in one of the Droughtmasters. A marked degree of resistance was apparent in all cattle when they were challenged with an heterologous strain of B. argentina. There were no differences between the response to challenge of the Herefords and Droughtmasters nor between the reactions of cattle which had apparently naturally sterilised B. argentina infection and those which were still infected. The heterologous strain of B. bigemina produced parasitaemia in the majority of animals but only minimal fever and anaemia resulted with no significant differences between the breeds.

Age Factors↗

Impaired bone marrow microenvironment and immune function in T cell protein tyrosine phosphatase-deficient mice.

The T cell protein tyrosine phosphatase (TC-PTP) is one of the most abundant mammalian tyrosine phosphatases in hematopoietic cells; however, its role in hematopoietic cell function remains unknown. In this report, we investigated the physiological function(s) of TC-PTP by generating TC-PTP-deficient mutant mice. The three genotypes (+/+, +/-, -/-) showed mendelian segregation at birth (1:2:1) demonstrating that the absence of TC-PTP was not lethal in utero, but all homozygous mutant mice died by 3-5 wk of age, displaying runting, splenomegaly, and lymphadenopathy. Homozygous mice exhibited specific defects in bone marrow (BM), B cell lymphopoiesis, and erythropoiesis, as well as impaired T and B cell functions. However, myeloid and macrophage development in the BM and T cell development in the thymus were not significantly affected. BM transplantation experiments showed that hematopoietic failure in TC-PTP -/- animals was not due to a stem cell defect, but rather to a stromal cell deficiency. This study demonstrates that TC-PTP plays a significant role in both hematopoiesis and immune function.

Animals↗

Immune function in cigarette smokers who quit smoking for 31 days.

A group of 28 healthy, white, male, light-to-moderate smokers, 21 to 35 years of age, were offered a financial inducement to abstain from smoking for 31 days. A matched control group of 11 smokers were paid to continue smoking during the same period. Nonspecific parameters of immune system function were monitored before and at various times after smoking abstinence. Abstinence increased natural killer cell cytotoxic activity but did not alter mitogen-induced T-lymphocyte proliferation as measured by responses to concanavalin A or phytohemagglutinin. Serum cortisol concentrations also decreased after smoking cessation; however, changes in immune function were not correlated with serum cortisol change, nor with indices of smoking such as plasma nicotine and cotinine levels. Responses to concanavalin A and phytohemagglutinin were positively correlated with change in self-reported alcohol ingestion during smoking abstinence. Results indicate that elevation in natural kill cell cytotoxic activity is detectable within 1 month of smoking cessation, even in light-to-moderate smokers. However, elevation in natural killer cell cytotoxic activity appears not to be directly related to cessation-induced reductions in plasma nicotine, cotinine, or circulating cortisol levels.

Adult↗

Lewis lung tumor system as a model for studying the immune function in syngeneic in equillibrium allogeneic chimeras.

Lewis lung tumor (LLT) passaged in F1 hybrids of the original C57B1/6 strain, where it arose spontaneously, is rejected by allogeneic SWA (Swiss albino) mice. However, aggregation chimeras derived from these SWA mice and the F1 hybrids of C57B1/6 developed an increased growth of primary tumor and reduced number of metastases when compared with the F1 hybrids. In the present study LLT passaged in C57B1/6 mice is not rejected by SWA mice. It is demonstrated that in aggregation chimeras now derived from two strains both taking the tumor, primary tumor growth was enhanced and the number of metastases reduced as in the former experiment. The tendency of reactions of lymphatic orgains in chimeras to tumor burden was comparable with the SWA and F1 hybrid (C57B1/6 multiplied by SWA and SWA multiplied by C57B1/6) recipients' response. Furthermore, chimeras had the highest spleen enlargement. Possible alternations in immune functions of chimeras due to their differing genotype combination are discussed in the LLT model.

Animals↗

Antitumor response to recombinant murine interferon gamma correlates with enhanced immune function of organ-associated, but not recirculating cytolytic T lymphocytes and macrophages.

The mechanism of therapeutic activity for recombinant murine interferon-gamma (rMu IFN gamma) in the treatment of metastatic disease was investigated by comparing effector cell augmentation with therapeutic activity in mice bearing experimental lung metastases (B16-BL6 melanoma). Effector cell functions in spleen, peripheral blood, and lung (the tumor-bearing organ) were tested after 1 week and 3 weeks of rMu IFN gamma administration (i.v. three times per week). Natural killer (NK), lymphokine-activated killer (LAK), cytolytic T lymphocyte (CTL) activities against specific and nonspecific targets, and macrophage tumoristatic activity were measured. rMu IFN gamma demonstrated immunomodulatory activity in most assays of immune function. The optimal therapeutic protocol of rMu IFN gamma (2.5 x 10(6) U/kg, three times per week) prolonged survival and decreased the number of pulmonary metastatic foci. This therapeutic activity was correlated with specific CTL activity from pulmonary parenchymal mononuclear cells (PPMC), but not from spleen or blood. Macrophage tumoristatic activity in PPMC also correlated with therapeutic activity, but activity in alveolar macrophages did not. However, therapeutic activity did not correlate with NK or LAK activity at any site. These results demonstrate that the optimal therapeutic protocol is the same as the optimal immunomodulatory dose for pulmonary CTL and macrophage activities. Furthermore, while immunological monitoring may help to optimize treatment protocols, current monitoring procedures that use readily accessible sites, particularly peripheral blood, may not accurately predict the therapeutic efficacy of biological response modifiers in clinical trials.

Animals↗

Yogurt consumption does not enhance immune function in healthy premenopausal women.

Fermented milk products may protect against breast cancer by stimulating immunologic activity. Twenty-five women [24.0 +/- 0.7 (SE) yr] were assigned randomly to two groups: control (n = 12) and yogurt treatment (n = 13). Controls refrained from yogurt products for three months, whereas the yogurt treatment group consumed two cups (454 g/day) of commercially produced yogurt for three consecutive months. Prior yogurt consumption did not exceed 4-6 cups/mo, and subjects consumed their usual diet during the study. Three-day diet records and fasting midluteal blood samples were obtained during subjects' first, second, and fourth menstrual cycles (baseline, Month 1, and Month 3, respectively). Macronutrient intakes differed between groups only for carbohydrate. Calcium intake increased for yogurt consumers during intervention. Lymphocyte proliferation induced by concanavalin A, phytohemagglutinin, and pokeweed mitogen, interleukin 2 production, and cytotoxic T lymphocyte-mediated cytotoxicity was assessed after baseline and Months 1 and 3 for both groups. No significant immune differences between the control and yogurt treatment group were observed for concanavalin A, phytohemagglutinin, pokeweed mitogen, interleukin-2, or cytotoxicity. In conclusion, three months of yogurt consumption did not enhance ex vivo cell-mediated immune function in young women.

Adult↗

A controlled study of cellular immune function in affective disorders before and during somatic therapy.

Lymphocyte blastogenesis induced by lectins (PHA, Con A, and PWM) was assessed in 27 drug-free patients with unipolar (n = 21) or bipolar (n = 5) depression and 13 normal controls. Fifteen patients were restudied after clinical remission. Symptomatic patients did not differ from controls nor did endogenous and nonendogenous depressions differ in their lymphocyte blastogenesis response to any of the three lectins. However, a significant reduction in lymphocyte blastogenesis with both PHA and Con A stimulation was found following somatic treatment. Cellular immune function appears to be normal in depressed patients, although the somatic therapies are associated with a reduction in this function.

Adult↗