What controls plant nutrient use in high elevation ecosystems?

The importance of rock-derived mineral nutrients (P, K, Mn, Mg, and Ca) in plant physiological function is well established. However, one important and relatively unexplored question is whether or not the same rules of plant nutrient use efficiency apply to these essential elements even if they are not limiting to primary production. We examined conifer growth and nutrient use dynamics across sites with contrasting geologies (sedimentary and volcanic) that vary in both rock-derived mineral nutrient and N availability. Differences in bedrock geochemistry generally corresponded to differences in available soil nutrients, such that the volcanic site tended to have greater available nutrients. Foliar nutrient concentrations reflected both differences in bedrock chemistry and indices of available soil nutrients for P, K, and Mn. Aboveground biomass production did not follow expected patterns and was greater for trees growing on low nutrient sites, but only with respect to the annual woody increment. Fine litter production did not differ between sites. Finally, we found evidence for trade-offs between two commonly examined components of nutrient use efficiency (NUE): nutrient productivity (A n) and mean residence time of nutrients. However, we did not find evidence for higher plant NUE in soils with lower nutrient availability for N or rock-derived nutrients.

Impact of age-related immune dysfunction on risk of infections.

The elderly have clearly been found to have both increased risk and severity of infections. Immunosenescence, the state of dysregulated immune function with aging, is felt to be a significant contributor to this increased risk. Extensive studies on inbred laboratory animals and in very healthy elderly humans have identified changes in immunity and have identified primarily phenotypic and functional changes in the T cell component of adaptive immunity. However, no compelling scientific evidence has shown that these changes have direct relevance to the common infections seen in the aged population. This perspective will attempt to shed light on this dilemma. First, it will review clinically relevant infections in the elderly, focusing on influenza and influenza vaccination and how chronic illness contributes to increased risk and severity of infection/failed vaccine response. Next, key changes in immunity will be reviewed, keeping perspective of the impact of confounding variables such as nutrition. If the goal is to prevent serious infections in the elderly, it appears that the field of geriatric immunology/infectious disease is faced with the tremendous challenge of studying a very diverse population of chronically ill individuals in addition to the study of the very healthy elderly. Grouping individuals by disease severity or by level of impairment of specific components of immunity may assist in advancing our ability to improve host defense in an at risk population.

Clinical relevance of age-related immune dysfunction.

Immunosenescence is the state of dysregulated immune function that contributes to the increased susceptibility to infection of the elderly. Extensive studies of inbred laboratory animals and very healthy elderly humans have identified changes in immunity; these studies have identified limited phenotypic and functional changes in the T cell component of adaptive immunity. However, no compelling scientific evidence has shown that these changes have direct relevance to the common infections seen in the aged population. This perspective will attempt to shed light on this dilemma. First, it will review clinically relevant infections in the elderly, focusing on influenza and influenza virus vaccination and how chronic illness contributes to increased risk and severity of infection and/or failed vaccine response. Second, key changes in immunity will be reviewed, keeping a perspective of the impact of confounding variables in addition to age but focusing on age-related changes in the interaction of the innate and acquired components of immunity. If the goal is to prevent serious infections in the elderly, it appears that the field of geriatric immunology and/or infectious diseases is faced with the tremendous challenge of studying a very diverse population, including mildly immunocompromised/chronically ill individuals and very healthy elderly.

Age-related impaired proliferation of peripheral blood mononuclear cells is associated with an increase in both IL-10 and IL-12.

Reflective of age-associated decline in immune function among elderly individuals is a decrease in in vitro T cell proliferative ability. Impaired T cell proliferation in the elderly may result from disruption of the well-balanced network of regulatory cytokines produced during an immune response. The purpose of this study was to identify age-related changes in the production of interleukin (IL)-10 and IL-12, and to determine whether in vitro T cell proliferation can be enhanced in the elderly by modulation of these two key cytokines. The superantigen Staphyloccocus entertoxin B (SEB) was used to stimulate proliferation and IL-10 and IL-12 production in peripheral blood mononuclear cells (PBMC) in vitro. Proliferation was determined by standard tritiated thymidine uptake. Cytokine levels in culture supernatants were measured by ELISA. We observed impaired SEB-induced proliferation of PBMC in the elderly that is comparable to that seen with the polyclonal mitogen Con A. This age-related decline in proliferation was associated with increased production of both IL-10 and IL-12. Modulation of PBMC proliferative response with either recombinant IL-12 or IL-10-neutralizing antibodies can boost proliferation of elderly PBMC to the levels seen in unmodulated young controls.

Antigen presenting cell function is enhanced in healthy elderly.

Aging is associated with a progressive decline in T cell-mediated immune responses. Little is known about the effect of aging on antigen presenting cells (APC). We have recently reported an age-related decline in proliferative response of peripheral blood mononuclear cells from elderly volunteers to Staphylococcus enterotoxin B (SEB). Since SEB-induced stimulation of T cells is not restricted by major histocompatibility complex, experiments were conducted in which T cells and APC from young and healthy elderly subjects were combined. We initially demonstrated the decreased SEB-induced proliferative capacity of elderly T cell elderly APC co-cultures when compared with young T cell young APC co-cultures. Combination of purified T cells from elderly donors with APC from young donors maintained a reduced T cell proliferative response. Age-related decline in T cell function was also established by the reduced proliferative capacity of elderly T cells co-cultured with a reference monocyte cell line. Surprisingly, co-culture of APC from healthy elderly donors with purified T cells from young donors enhanced T cell proliferation. APC from elderly donors also marginally enhanced the proliferative response of an SEB-specific T cell line.

Cross-regulatory roles of interleukin (IL)-12 and IL-10 in atherosclerosis.

T cell cytokines are known to play a major role in determining protection and pathology in infectious disease. It has recently become clear that IL-12 is a key inducer of the type 1 T cell cytokine pattern characterized by production of IFN-gamma. Conversely, IL-10 down-regulates IL-12 production and type 1 cytokine responses. We have investigated whether IL-12 and IL-10 might be involved in a chronic inflammatory reaction, atherosclerosis. In atherosclerotic plaques, we found strong expression of IFN-gamma but not IL-4 mRNAs as compared to normal arteries. IL-12 p40 mRNA and IL-12 p70 protein were also found to be abundant in atherosclerotic plaques. IL-12 was induced in monocytes in vitro in response to highly oxidized LDL but not minimally modified LDL. The cross-regulatory role of IL-10 was indicated by the expression of IL-10 in some atherosclerotic lesions, and the demonstration that exogenous rIL-10 inhibited LDL-induced IL-12 release. These data suggest that the balance between IL-12 and IL-10 production contributes to the level of immune-mediated tissue injury in atherosclerotsis.

The equivalency of infrared tympanic membrane thermometry with standard thermometry in nursing home residents.

OBJECTIVE: To compare the equivalence of infrared tympanic membrane (TM) measure of body temperature with standard electronic oral (PO) and rectal (R) measures in a nursing home population. DESIGN: Randomized repeated-measurement design. METHODS: For the study, 82 randomly selected residents (mean age 79 +/- 10 years) of the Nursing Home Care Unit of the VAMC West Los Angeles had PO, R, and TM temperatures measured before arising (6-8 am). An otoscopic exam and the age, sex, presence of neurologic disease, and compliance with thermometry was noted. Also, repeated measures of PO and TM temperatures were performed three times to assess variability. The Pearson's correlation coefficient was determined for PO versus R and for TM versus R temperatures. Stepwise regression analysis was performed with the dependent variable of R temperature and the independent variables of the mean TM temperature, age, sex, presence of neurologic disease, position of the resident, and extent of ear canal occlusion. RESULTS: The correlation of TM versus R (r = .39, P = .004) was better, though not significantly, than of PO versus R (r = .28, P = .04). TM had less variability than PO (pooled standard deviation .38 vs .45 degrees F, respectively) and TM was implemented successfully more often than PO or R (96% vs 81% vs 81%). CONCLUSION: Therefore, TM was at least equivalent or better than PO measures of temperature in this population. The efficacy of fever detection and the use and durability of long-term use by nursing staff needs to be studied.

Mechanism of immunosuppressive effect of alprazolam: alprazolam suppresses T-cell proliferation by selectively inhibiting the production of IL2 but not acquisition of IL2 receptor.

The purpose of this study was to elucidate the mechanism of action of alprazolam on concanavalin A (Con A)-induced murine T-cell proliferation. Splenic cells of BALB/c mice were first cultured with an optimum dose of Con A in the presence or absence of varying doses of alprazolam to assess effects of alprazolam on T-cell proliferation, interleukin 2 (IL2) production and IL2 receptor (IL2R) expression. Then, Con A-induced T-blast cells from BALB/c mice were cultured with an excess dose of human recombinant IL2 (rIL2) or crude rat IL2 supernate in the presence or absence of alprazolam to assess the effects of alprazolam on the interaction of IL2 and IL2R. The results of these studies clearly demonstrated that alprazolam can inhibit the T-cell proliferation in response to Con A but not to IL2. Alprazolam also reduced the production of IL2 by splenic T-cells, but did not alter the expression of IL2R on Con A-induced T-blast cells. Furthermore, the results also showed that (a) alprazolam did not inhibit the proliferative response of splenic T-cells to a combination of phorbol 12-myristate-13-acetate (PMA) and ionomycin, and (b) the addition of exogenous IL2 reversed the inhibitory effect of alprazolam on T-cell proliferation. Finally, the addition of alprazolam produced a time-dependent inhibiting effect on T-cell proliferation. However, this inhibitory effect of alprazolam was abolished when the drug was added to the cultures of competent cells that fully expressed IL2R. Taken together, these results suggest that alprazolam inhibits murine T-cell proliferation by affecting the mitogenic receptor-mediated events (initiation) rather than the IL2R-mediated events (progression) of ligand-activated T-cells through the cell cycle.

Fever response in elderly nursing home residents: are the older truly colder?

OBJECTIVE: To test the hypothesis that many nursing home residents with an apparently blunted fever response (maximum temperature less than 101 degrees F) may actually have a significant change in temperature (delta T greater than or equal to 2.4 degrees F) which is not recognized because of a low baseline temperature. DESIGN: Retrospective chart review for cases of infection that met specific criteria and for chart-recorded baseline and infection temperatures. Chart-recorded baseline temperatures were prospectively compared with re-measurement of morning temperatures. SETTING: Nursing Home Care Unit of the VAMC West Los Angeles. PATIENTS: Random review of 40 residents' charts resulted in the detection of 69 infections among 26 residents over a 20-month period. Fifty randomly selected residents prospectively underwent comparison of chart-determined and actual re-measurement of baseline temperatures. RESULTS: In 50 randomly selected residents, the mean oral baseline temperature of 97.4 +/- 0.2 (degrees F +/- SEM) closely approximated the mean nurse-recorded measures in the charts (97.6 +/- 0.1). Chart review detected 69 infections among 26 residents, with 53 episodes having a temperature recorded during the infection. The mean maximum temperature (Tmax) during an infection was 101.3 +/- 0.3 (degrees F +/- SEM) but 47% (25/53) of the episodes had a "blunted" fever response (Tmax less than 101 degrees F). Of the 25 "blunted" fevers (Tmax less than 101 degrees F), about one-fourth demonstrated an adequate change in temperature from baseline (delta T greater than or equal to 2.4 degrees F) but failed to reach 101 degrees F because of a low baseline. Most infections (89%) had a Tmax greater than 99 degrees F. CONCLUSION: Establishing a nursing home patient's basal temperature and monitoring for changes in temperature (delta T greater than 2.4 degrees F) and/or lowering the threshold for recognition of fevers (to 99 degrees or 100 degrees F) in nursing home residents with a change in function should assist in early recognition of infections.

Effect of age on fever response to recombinant tumor necrosis factor alpha in a murine model.

Certain elderly humans show a blunted fever response to infection. A study was designed using a murine model to assess the influence of age on the febrile response to the endogenous pyrogen, tumor necrosis factor alpha (TNF alpha). Twenty (10 young: 4-6 months; 10 old: 24-28 months) BALB/c mice were injected with 50 ng of TNF alpha into the intraperitoneal space; the experiments were repeated one week later with 100 ng TNF alpha. Control animals received intraperitoneal injections of pyrogen-free phosphate buffered saline. Temperatures were measured rectally at baseline and at 10-minute intervals for 90 minutes post-injection using a thermistor probe and temperature gauge. In the majority of the time intervals following injection, the mean temperature changes of young mice were significantly higher than old mice for both 50 ng and 100 ng doses of TNF alpha. Similarly, peak temperature changes from baseline were consistently higher in young animals following injection of TNF alpha. Moreover, the peak temperature changes in young mice after 50 ng TNF alpha injection were significantly higher than those in old mice following a 100 ng injection of TNF alpha. These findings confirm that (a) TNF alpha has a role in the pathogenesis of fever; (b) aging alters significantly the febrile response; and (c) a mechanism of this age-related blunted febrile response may involve TNF alpha.

Suppressive effects of alprazolam on the immune response of mice.

The purpose of this study was to examine the effects of alprazolam on the response of murine immune cells. Splenic cells of young BALB/c mice were first cultured with an optimum dose of various mitogens in the presence or absence of varying doses of alprazolam to assess effects of alprazolam on concanavalin A (Con A)-induced T-cell proliferation, bacterial lipopolysaccharide (LPS)-induced B-cell proliferation, and production of interleukin 2 (IL2). Then, peritoneal adherent cells (macrophages) from young BALB/c mice were cultured with an optimum dose of LPS in the presence or absence of alprazolam to assess the effects of alprazolam on the ability of peritoneal adherent cells to produce interleukin 1 (IL1) and tumor necrosis factor (TNF). The results of this study clearly demonstrated that alprazolam is a potent immunosuppressive agent that can inhibit the proliferative responses of both B- and T-cells to LPS and Con A, respectively. It also can reduce production of IL2 by splenic T-cells and production of both IL1 and TNF by peritoneal macrophages. Furthermore, it was also shown that (a) the magnitude of suppression of T-cell proliferation and of IL2 production occurs in a dose-dependent manner and (b) B-cells are more vulnerable than T-cells to the effect of alprazolam.

Analysis of cutaneous delayed-type hypersensitivity reaction and T cell proliferative response in elderly nursing home patients: an approach to identifying immunodeficient patients.

Clinical experience suggests the delayed-type hypersensitivity (DTH) skin test lacks sensitivity in assessing the integrity of systemic cell-mediated immunity (CMI) or the status of recent or remote mycobacterial infections in elderly nursing home residents. In an attempt to clarify this issue, DTH reaction to purified protein derivative (PPD), tetanus toxoid and Candida albicans was compared with circulating thymus-derived lymphocyte (T cell) proliferation (TCP) to stimulation with PPD and anti-CD3 antibody in 24 randomly selected nursing home residents. The DTH reaction and the TCP response correlated reasonably well among the DTH reactors but poorly among DTH nonreactors, suggesting there may be age-related immunologic changes in the skin itself. Also, the DTH skin test to PPD alone was found to be a poor index of the integrity of systemic CMI.

Constipation: endemic in the elderly? Gerontopathophysiology, evaluation, and management.

Chronic constipation in the elderly is most likely a consequence of lifelong patterns of bowel and dietary habits and laxative use along with the interaction of pathophysiologic (from chronic diseases) and, perhaps, senescent changes in gut motility. Gerontopathophysiologic changes of gut motility, the evaluation of, and a step-care approach to the management of constipation are discussed.

Diminished proliferative response of con A-blast cells to interleukin 2 in adult rats exposed to ethanol in utero.

The fetal alcohol syndrome is associated with altered immunity. We attempted to delineate the mechanism of the decline in cell-mediated immunity observed by others by using rats which were exposed to alcohol in utero and tested for immune integrity 3 months after birth. We found that concanavalin A-stimulated T-lymphoblast (Con A T-blast) cells that were obtained from ethanol-exposed rats had significantly diminished proliferative responses to both crude and recombinant interleukin 2 compared to those obtained from normal and nutritional controls. The blunted response of Con A T-blast cells to interleukin 2 may be a biomarker of fetal exposure to alcohol.