Developmental regulation of perlecan gene expression in aortic smooth muscle cells

The effect of environmental temperatures on immune competence was investigated in carp which were subjected to changes in water temperature. The activity of non-specific cytotoxic cells (NCC) against P815 target cells, and the anti-DNP antibody response were evaluated until day 56 after transfer. Low environmental temperature (12 +/- 0.5 degrees C) enhanced NCC activity and decreased antibody production. In contrast a high environmental temperature (28 +/- 0.5 degrees C) was without effect on these parameters when compared to the standard temperature (20 +/- 0.5 degrees C). The results showed a maximum effect of low environmental temperature on day 28 and an adaptation in these immune responses 56 days following transfer. Collectively, the results indicated that non-specific immunity tends to offset specific immune suppression at low environmental temperatures. To determine the mechanism(s) by which environmental temperature affects cellular immune function, membrane fluidity measurements and sialic acid titration, as well as stress assessment by plasma cortisol measurement, were determined on day 28. Taken together, the results revealed a direct effect of temperature on cellular immune function which is modulated by membrane fluidity and sugar concentration and not by stress induction.     

Immunological evaluation of the mycotoxin patulin in female B6C3F1 mice

Patulin is a mycotoxin produced by many fungal species of the genera Penicillium, Aspergillus and Bryssochamys. Previous literature reports have suggested that patulin is toxic to the immune system. The studies presented were conducted to provide a comprehensive assessment of the effects of patulin on the immune system. Unlike previous reports, the doses of patulin used (0.08, 0.16, 0.32, 0.64, 1.28 and 2.56 mg/kg) were based on predicted human exposure levels. Female B6C3F1 mice were exposed orally to patulin for 28 days. Effects were not observed on final body weight or body weight gain. Relative weight of the liver, spleen, thymus, kidneys with adrenals, and lungs was not affected. Peripheral blood leucocyte and lymphocyte counts were decreased by approximately 30% in the two highest dose groups. The leucocyte differential was not altered. Total spleen cell, total T-cell (CD3+), helper T-cell (CD4+CD8-), B-cell (surface immunoglobulin+) and monocyte (MAC-3+) counts were not changed. Cytotoxic T-cell (CD8+CD4-) counts were increased 50% only by the highest dose. Natural killer cell (NK1.1+CD3-) and monocyte (MAC-1+) counts were increased 30% and 24%, respectively, only in the 0.08 mg/kg group. Humoral immune function as assessed by antibody-forming cell response and serum IgM titre to sheep erythrocytes, and cell-mediated immune function evaluated utilizing natural killer cell activity and the mixed lymphocyte reaction were not altered. Oral exposure to patulin for 28 days did not alter the ability of female B6C3F1 mice to mount either a cell-mediated or humoral immune response.     

Fas ligand-induced apoptosis of infected human macrophages reduces the viability of intracellular Mycobacterium tuberculosis

Mycobacterium tuberculosis-specific cytolytic activity is mediated mostly by CD4+CTL in humans. CD4+CTL kill infected target cells by inducing Fas (APO-1/CD95)-mediated apoptosis. We have examined the effect of Fas ligand (FasL)-induced apoptosis of human macrophages infected in vitro with M. tuberculosis on the viability of the intracellular bacilli. Human macrophages expressed Fas and underwent apoptosis after incubation with soluble recombinant FasL. In macrophages infected either with an attenuated (H37Ra) or with a virulent (H37Rv) strain of M. tuberculosis, the apoptotic death of macrophages was associated with a substantial reduction in bacillary viability. TNF-induced apoptosis of infected macrophages was coupled with a similar reduction in mycobacterial viability, while the induction of nonapoptotic complement-induced cell death had no effect on bacterial viable counts. Infected macrophages also showed a reduced susceptibility to FasL-induced apoptosis correlating with a reduced level of Fas expression. These data suggest that apoptosis of infected macrophages induced through receptors of the TNF family could be an immune effector mechanism not only depriving mycobacteria from their growth environment but also reducing viable bacterial counts by an unknown mechanism. On the other hand, interference by M. tuberculosis with the FasL system might represent an escape mechanism of the bacteria attempting to evade the effect of apoptosis.     

Epidemiologic pathology of gastric ulcer and gastric carcinoma among Japanese in Hawaii

Cell-mediated immunity in rheumatoid arthritis (RA) was assessed by skin testing with six antigens in 107 patients, 94 of whom were age, sex, and race-matched with healthy individuals or patients with diseases unrelated to immunological abnormalities. 20% of RA patients were anergic. Impaired cell-mediated immunity in the RA patients was manifested by a decrease in the magnitude of skin reactivity as well as a decrease in the incidence of positive reactions to multiple antigens. Depression in cell-mediated immunity was related to age but not to sex, duration of disease, or disease activity. A slight correlation was found between absolute peripheral lymphocyte counts and the number of positive skin tests, and was confirmed by finding an association between lymphocyte counts and the size of skin reactions. A correlation was also found between lymphocyte counts and disease activity. Four explanations of the observed depression in cell-mediated immunity in RA were considered: (1) a preoccupation of the immune mechanism of the host with cell-mediated immunity reactions related to the pathogenesis of the disease; (2) a depression of cell-mediated immune reactivity by a virus infection; (3) depression of cell-mediated immunity by therapy; and (4) immune complex suppression of cell-mediated immunity. No effect of gold therapy was found. The near universal use of salicylates or other anti-inflammatory drugs did not permit investigation of the effect of these drugs on cell-mediated immunity.     

Getting old and thinking hard--my favorite things I lost

Benzodiazepines have anxiolytic properties and attenuate behavioral stress responses induced by corticotropin releasing hormone (CRH). To evaluate the effect of benzodiazepines on CRH-induced immune suppression, potent centrally acting benzodiazepines were administered prior to central infusion of CRH (i.c.v.; 1.0 microgram). CRH induced a significant (P < 0.01) reduction of splenic natural killer cell activity which was completely antagonized by pretreatment with either diazepam or alprazolam.     

Cellular immune responses to acute stress in female caregivers of dementia patients and matched controls.

This study investigated whether the stress of caregiving alters cellular immune responses to acute psychological stressors. Twenty-seven women caring for a spouse with a progressive dementia (high chronic stress) and 37 controls matched for age and family income performed a 12-min laboratory stressor. Cellular immune function was assessed by both functional and quantitative measures taken before (low acute stress), immediately after (high acute stress), and 30 min after (recovery from stress) exposure to the laboratory stressors. The laboratory challenges were associated with diminished proliferative responses but elevated natural killer (NK) cell cytotoxicity; however, subsequent analyses suggested that this elevated cytotoxicity was largely attributable to an increase in the number of NK cells in peripheral blood. The results suggest that although the stress of caregiving diminishes cellular immune function, caregiving appears to have little effect on cellular immune responses to or recovery from brief psychological challenges. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Posttraumatic stress symptoms and victimization among Japanese American women.

This study of Japanese American women and immigrant women from Japan investigated the relationship between posttraumatic stress (PTS) symptoms and the perceived abusiveness of partners' emotional and physical violence, with a community-based random sample. Women who experienced injuries and/or fear for their lives, in addition to partners' emotional and physical violence, had significantly higher PTS symptom counts than those with no lifetime experience of partners' violence. Victimization by nonintimates also increased PTS symptom counts. Satisfaction with social support significantly mitigated the negative effect of childhood abuse for reexperiencing and avoidance symptoms. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Meta-analysis of cognitive-behavioral interventions on HIV-positive persons' mental health and immune functioning.

Objective: To evaluate the efficacy of cognitive-behavioral interventions (CBIs) for improving the mental health and immune functioning of people living with HIV (PLWH). Design: Comprehensive searches of electronic databases from 1988 to 2005, hand searches of journals, reference lists of articles, and contacts with researchers. Meta-analytic approaches were used in synthesizing findings. Main Outcome Measures: Intervention effects on symptoms of depression, anxiety, and anger, stress, and CD4 cell counts were assessed. Results: Data from 15 controlled trials were analyzed. Significant intervention effects were observed for improving symptoms of depression (d = 0.33), anxiety (d = 0.30), anger (d = 1.00), and stress (d = 0.43). There is limited evidence suggesting intervention effects on CD4 cell counts (d = 0.08). The aggregated effect size estimates for depression and anxiety were statistically significant in trials that provided stress management skills training and had more than 10 intervention sessions. Conclusion: CBIs are efficacious in improving various psychological states of PLWH. Future research should examine the relationship among interventions, psychological states, medication adherence, and immune functions, and identify other relevant factors associated with intervention effects. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Prognostic risk assessment in primary breast cancer by behavioral and immunological parameters.

Investigated the predictive power of an immunologic effector cell, the natural killer (NK) cell, as well as selected psychological and demographic factors, to breast cancer prognostic risk status. 75 women (aged 28–74 yrs) with Stage I or II breast cancer were interviewed about their perceptions, attitudes, and interpersonal support. Ss also completed the SCL-90 and the Profile of Mood States. Blood was then drawn to assay NK functional activity. All assessments took place after surgery. It was found that NK activity predicted the status of cancer spread to the axillary lymph nodes. Ss who had low levels of NK activity were rated as well-adjusted to their illness; Ss who had higher NK activity appeared to be distressed or maladjusted. Findings are discussed in the light of recent animal findings linking environmental stress and behavioral responsiveness to biological vulnerability via endocrine and immune pathways. (28 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Mifepristone. Auxiliary therapeutic use in cancer and related disorders

A pilot study was carried out to assess the safety and antigen-presenting properties of allogeneic or autologous dendritic cells (DCs) in six HLA-A2+, HIV-infected patients. Allogeneic DCs obtained from the peripheral blood of HLA-identical, HIV-seronegative siblings were pulsed with recombinant HIV-1 MN gp160 or synthetic peptides corresponding to HLA-A2-restricted cytotoxic epitopes of envelope, Gag, and Pol proteins. The antigen-pulsed cells were infused intravenously six to nine times at monthly intervals and HIV-specific immune responses were monitored. One allogeneic DC recipient with a CD4+ T cell count of 460/mm3 showed increases in envelope-specific CTL- and lymphocyte-proliferative responses, as well as in IFN-gamma and IL-2 production. Another allogeneic DC recipient with a CD4+ T cell count of 434/mm3 also showed an increase in HIV envelope-specific lymphocyte-proliferative responses. A recipient of autologous DCs with a CD4+ T cell count of 730/mm3 showed an increase in peptide-specific lymphocyte-proliferative responses after three infusions. Three other allogeneic DC recipients with CD4+ T cell counts <410/mm3 did not show increases in their HIV-specific immune responses. No clinically significant adverse effects were noted in this study and CD4+ T cell numbers and plasma HIV-1 RNA detected by RT-PCR of all six patients were stable during the study period. Thus, both allogeneic and autologous DC infusions were well tolerated and in patients with normal or near normal CD4+ T cell counts administration of these antigen-pulsed cells enhanced the immune response to HIV. However, since no effect on viral load was observed there was no evidence that this approach provided clinical benefit.     

Inflammation alters the effects of mGlu receptor agonists on spinal nociceptive neurones

A number of pro-inflammatory mediators (leukotrienes, platelet activating factor, cytokines) participate in the process of neutrophil-dependent lung injury induced by immune complexes. Here, we studied the role of endothelins (ET) in the reversed passive Arthus reaction (AR) as a model of pneumonitis in CD-1 mice. We examined the broncholaveolar lavage fluid (BALF) for signs of inflammation such as the accumulation of cells, myeloperoxidase (MPO) activity and hemoglobin (Hb) levels, as a measure of hemorrhagic lesions, 24 h after injection. We used a selective ETA (BQ-123) or a non-selective ETA/ETB-R (SB 209670) receptor antagonist at various concentrations (2.5, 5 or 10 mg/kg ip at -8, 0, 8 and 16 h) to assess the involvement of ET. Challenged mice revealed signs of acute inflammation and hemorrhagic lesions. Levels of Hb and MPO, total and neutrophil cell counts increased by 9-, 9-, 3.2- and 63-fold, respectively. The lower dose of SB 209670 reduced Hb levels by 21% (P<0.05), without affecting cell accumulation or MPO. The mid-dose had no effect; the highest dose caused 60, 57 and 70% increases in Hb levels, total cell and neutrophil counts, respectively. Conversely, the highest dose of BQ-123 decreased Hb, total cell and neutrophil counts and MPO levels by 36, 35, 42 and 70%, respectively. These results support a role for ET in AR lung injuries. They also suggests that blocking ETA-R may be beneficial, while blockade of ETB-R (using a high dose of SB 209670) may be detrimental. A beneficial ETB-mediated response may exist that naturally interferes with events triggered by the formation of immune complexes such as cell accumulation and their subsequent activation leading to acute lung injury.     

Infectious diseases in athletes: new interest for an old problem

Interest in infectious disease among athletes has been greatly stimulated over the past decade by the development of modern automated systems that can enumerate specific elements of the immune system. Research has confirmed earlier clinical and animal studies in showing that either a single bout of exhausting exercise or persistent over-training can increase susceptibility to upper respiratory and other viral infections, although resistance to bacterial infections is apparently unaltered. Such findings do not seem a non-specific response to cooling and drying of the tracheal mucosa. Rather, heavy exercise has a depressant effect upon the T cell/interleukin/NK cell system which may persist for a week or more. In contrast, moderate training enhances immune defences. Given the negative impact of acute viral infections upon both competitive performance and morale, plus the occasional incident of sudden death associated with viral myocarditis, it is important that sports physicians minimize the incidence of viral infections in the athletes for whom they are responsible. Potential tactics include maintenance of immunization schedules, minimizing of exposure to infection, avoidance of over-training, maintenance of an adequate diet, and reduction of psychological and environmental stress. In top athletes, the regular monitoring of immune status may also be warranted, with the possible administration of immunoglobulins and prostaglandin inhibitors as required.     

Asthma and oxidant stress: nutritional, environmental, and genetic risk factors

A considerable body of evidence suggests that oxidant stress results in inflammation and tissue damage in the respiratory system, and later in immune damage, and that individuals with lowered cellular reducing capacity are at increased risk to develop asthma. Reducing capacity in the erythrocyte is generated through the pentose phosphate pathway and this pathway also generates a major portion of the reducing capacity in all cells of the body. Therefore, dietary, environmental, and genetic factors which diminish cellular reducing capacity will increase tissue vulnerability to oxidant stress and are likely to increase asthma risk. Dietary selenium deficiency lowers red cell glutathione peroxidase activity and is associated with an increased risk for asthma, and low dietary intakes of vitamins C and E also appear to increase asthma risk. High body iron stores increase free radical production and may also elevate asthma risk. Environmental lead exposure depresses the activities of a several enzyme systems that influence cellular reducing capacity (glucose-6-phosphate dehydrogenase, NAD synthetase, glutathione peroxidase, superoxide dismutase, catalase) and consequently may increase asthma risk. Genetically-determined low activity of glucose-6-phosphate dehydrogenase lowers cellular reducing capacity and may also heighten asthma risk. Simple dietary and environmental interventions may significantly reduce oxidant stress and prevent or minimize the development of asthmatic symptoms and should prove to be a cost effective approach to asthma management in addition to current pharmacological strategies.     

The life-shortening effect of reduced physical activity is abolished by a fat rich diet

In female mice on a control diet (3.6% fat) reduced physical activity leads to a reduction of the average life span. So the average age at death of an inactive group is 500 +/- 166 compared to 565 +/- 175 days in an active control group. If the animals are kept on a fat rich diet (12.4% fat) this effect of physical activity restriction is no longer observable and the average age at death is 570 +/- 142 days, within the range of the control animals. The increased fat intake seems to reduce the stress or to increase the resistance to stress in the activity restricted animals. So stress is a crucial determinant of life span.     

The role of psychoneuroendocrine factors on spaceflight-induced immunological alterations

This paper summarizes previous in-flight infections and novel conditions of spaceflight that may suppress immune function. Granulocytosis, monocytosis, and lymphopenia are routinely observed following short duration orbital flights. Subtle changes within the monocyte and T cell populations can also be noted by flow cytometric analysis. The similarity between the immunological changes observed after spaceflight and other diverse environmental stressors suggest that most of these alterations may be neuroendocrine-mediated. Available data support the hypothesis that spaceflight and other environmental stressors modulate normal immune regulation via stress hormones, other than exclusively glucocorticoids. It will be essential to simultaneously collect in-flight endocrine, immunologic, and infectious illness data to determine the clinical significance of these results. Additional research that delineates the neuroendocrine mechanisms of stress-induced changes in normal immune regulation will allow clinicians in the future to initiate prophylactic immunomodulator therapy to restore immune competence altered by the stress of long-duration spaceflight and therefore reduce morbidity from infectious illness, autoimmune disease, or malignancy.     

Bilateral threshold frequency weighting in hearing disability predictions

The growing size of world cities and ever more competitive working conditions are thought to cause subjective stress, anxiety and depression, with a resulting decrease in the quality of life, sleep disturbances, drug and alcohol abuse and poor productivity. Acute stress may suppress immune function, leading to an increased incidence of infections, and chronic stress may predispose to a number of ailments, including digestive disturbances, hypertension, ischaemic heart disease and neoplasia; jointly, these factors cause a substantial shortening of life expectancy. The control of stress thus makes an important contribution to health. Stress levels can be reduced by anxiolytic drugs, or by a variety of psychological techniques; however, an appropriate programme of physical activity may be the preferred option, since exercise has many positive effects on health that are unrelated to stress. If exercise is to be effective in inducing relaxation, it must be noncompetitive, moderate in intensity, and pursued in pleasant surroundings.     

Collagen-related markers of bone turnover reflect the severity of liver fibrosis in patients with primary biliary cirrhosis

In vitro studies have connected immune cell function to Peptide F. The primary purpose of this investigation was to examine the responses of plasma Peptide F and epinephrine along with the changes in B cell antibody production in vivo in physically fit and unfit women in response to physical exercise on a cycle ergometer at 60% and 80% of peak oxygen consumption. Seven aerobically fit and eight untrained (i.e., unfit) women between the ages of 18 and 30 volunteered to participate in this investigation. Blood samples (analyzed for plasma Peptide F and epinephrine along with the number of antibody-producing B cells) were obtained 24 hours prior to the exercise session, pre-exercise, during each exercise intensity, and five minutes post-exercise. The fit group had a significantly higher plasma Peptide F concentration after the 80% exercise intensity along with significantly higher numbers of antibody producing B cells compared to the unfit group. The results of this investigation show that physically fit women have an enhanced secondary response of B cells to a specific antigen under conditions where Peptide F is increased. Such data demonstrate that physical fitness as promoted by the Public Health Service (e.g., Healthy People 2000) influences the underlying hormonal and immune cell responses when challenged by physical exercise stress.     

The antidepressant fluvoxamine increases natural killer cell counts in cancer patients

Knowing the negative effect of depression on lymphocyte number and activity in humans, we investigated the effect of antidepressant therapy on various lymphocyte subgroups. Cancer patients receiving treatment for at least 6 months were asked to take the antidepressant, fluvoxamine, for 28 days. Before and at the end of the study, physical and psychiatric examinations were performed, and the severity of depression was assessed by the Hamilton Scale for Depression (HAM-D). In addition, a sample of blood was withdrawn from the patients to quantify the following parameters: total leukocyte and lymphocyte counts, T4, T8, and Natural Killer (NK) cells, and lymphocyte response to the mitogens phytohemagglutinin (PHA) and pokeweed (PWM). Ten adult patients completed the study. Five of the 10 responded favorably to fluvoxamine treatment. Mean improvement was 50% from the score on day one. There was a significant correlation between the change in the HAM-D score of the "responders" and the change in NK cell counts (p = 0.02). The mean increment in NK cell number was 53%. In 4 of the 5 "non-responders", NK cell number dropped by 65% (mean). No correlation between the change in HAM-D score and any other immunological parameters was detected. Fluvoxamine increases NK cell counts in cancer patients, probably by its antidepressant effect.