Phagocytic cell function in active brucellosis.

In this study, we analyzed phagocytic cell function in 51 patients with active brucellosis and its relationship with different clinical, serological, and evolutionary variables. A control group was made up of 30 blood donors of similar geographic extraction, age, and sex, with no previous history of brucellosis or known exposure ot the infection or specific antibodies. The investigations were carried out at the time of diagnosis, at the conclusion of treatment, and after 6 months of follow-up. Polymorphonuclear leukocyte adherence and nitroblue tetrazolium reduction in response to Brucella antigen were significantly increased in the patients at the time of diagnosis with respect to the control group. In contrast, chemotaxis in response to Brucella antigen and phagocytosis were significantly reduced in the patients with respect to the control group. The alterations in phagocytic cell function were greater in patients with bacteremia, with focal forms of the disease, or with a longer diagnostic delay. Most of these initial alterations tended to normalize with treatment, indicating their transient character.     

Microneurographic assessment of C-fibre function in aged healthy subjects

Physiological changes in the nervous system occur with ageing. Both a decline of function and a decrease in the number of C-fibres in the skin have been reported for healthy aged subjects. With the use of microneurographic recordings from single C-fibres in humans we have compared the sensory and axonal properties of these neurones in young and aged healthy subjects. A total of 146 C-fibres were recorded from the common peroneal nerve in young subjects (mean age 24.7 years) and 230 C-fibres were recorded in aged subjects (mean age 56.2 years). In aged subjects, changes were found in the composition of the C-fibre population and in sensory and axonal properties. The relative incidence of afferent to efferent C-fibres was relatively constant independent of the age of subjects. The ratio of mechano-responsive to mechano-insensitive nociceptors was approximately 8 : 2 in the young controls while in aged subjects it was 7 : 3. In aged subjects 13% of the fibres showed atypical discharge characteristics, while this was not observed in young subjects. Spontaneous activity, sensitization and loss of sensory function were found regularly. Changes in functions of the conductile membrane were also observed in fibres from aged subjects. The degree of activity-dependent conduction velocity slowing in response to high frequency stimulation (2 Hz) was more pronounced, while the normalization of conduction velocity subsequent to high frequency stimulation was protracted. We found that both sensitization and desensitization or degeneration of afferent C-fibres occur with age, but are still rare compared to patients with neuropathy. The changes in the axonal properties of C-fibres in aged subjects are compatible with hypoexcitability of the fibres. These findings are important for the understanding and differential diagnoses regarding pathological processes and normal ageing.     

Thyroid function in normal aged subjects or with auricular fibrillation

Free T4, free T3 and TSH before and 30 min after TRH administration have been evaluated in 35 elderly patients with atrial fibrillation (AF), in 35 elderly normal subjects (AN) and compared with results obtained in 36 young men (YN). No significant differences were evidenced between AF and AN, especially no mild hyperthyroidism was discovered in AF. In comparison with YN, there was no alteration of free T4 with age but free T3 is dramatically decreased; concerning TSH, there is a significant decrease before and after TRH in AN males whereas TSH levels in other subgroups are similar to those in YN.     

Lung function in sickle cell hemoglobinopathy patients compared with healthy subjects

Previous studies of lung function tests performed on patients with sickle cell disease have shown a restrictive ventilatory defect, usually a diffusion defect, and mild hypoxia at rest. The present study was undertaken to explain the pathophysiology of these changes and to extend these studies to include functional measurements not reported previously.     

T cell function in the aged: Lessons learned from animal models

The deterioration of immune function with advancing age contributes to the increased incidence of morbidity and mortality among the elderly from infectious disease and possibly cancer. The innate and adaptive arms of immunity are affected by the deleterious effects of aging, but it is adaptive immunity, and in particular T lymphocytes, that is most susceptible to these effects. The aging of the immune system, referred to as immunosenescence, is associated with a dramatic decline in responsiveness as well as functional dysregulation. Age-associated alterations in T cells are evident at all stages of its development, and it is these changes that contribute to the overall increased susceptibility to infection and possibly cancer. Although there is an enormous effort worldwide to develop vaccines, much of the research is performed with young animals. Because the immune system of the aged is different from that of the young, many of the findings cannot be extrapolated. In this review, we will discuss those differences in T cell immunity of the aged, relate how these differences influence the immune response of the aged to pathogens as well as to tumors, and describe the current approaches to rejuvenate the aged immune response. Although the majority of the conclusions on T cell immunity in the aged are based on studies in the murine model, many of these findings can be extended to the human model. Throughout this review, we have noted those findings that are specific to humans.     

Immune function in aged mice. IV. Loss of T cell and B cell function in thymus-dependent antibody responses.

The decline in antibody-forming potential with age was studied in mice by analyzing the relative contributions of T and B cells in collaborative PFC responses to the T cell-dependent antigens, dinitrophenylated (DNP) keyhole limpet hemocyanin, DNP-human IgG, fowl IgG and sheep red blood cells. The experimental system involved the adoptive transfer of purified lymphocyte populations derived from the spleens of old and young mice into young irradiated recipients. An unequivocal reduction in B cell function was demonstrated in both primary and secondary antibody responses. In the former, young T cells failed to restore responsiveness to old B cells, while in the latter, similar results were obtained, even if old B cells were primed in the presence of young T cells. Despite the lower level of antibody production in old mice compared with young, no decrease in the number of antigen-binding cells (detected by resetting and autoradiography) was observed. Taken together, these results suggest that a defect exists in B cells which is independent of T cell help, and that it is not due to cell depletion but rather to a qualitative abnormality in the cells themselves. Old T cells did not collaborate with young B cells as well as young T cells did, indicating a loss of helper T cell activity. Spleen cells from old mice, when mixed with young spleen cells at a 1:1 ratio, caused a reduction in their antibody-forming potential which was consistent with the presence of cells with suppressive activity. The suppressor cells were shown to be T cells since their effect was abrogated by treatment with anti-Thy-1.2 serum plus complement and enriched by passage through nylon wool columns. These findings emphasize the need to use purified cell populations in analysis of responsiveness in old animals and highlight the multifactorial nature of the mechanisms involved in the ageing process.     

The control of vertical saccades in aged subjects

In real life we produce vertical saccades at different distances and eccentricities, and while our fixation is more or less actively engaged. The goal of this study is to examine vertical saccades in aged and young subjects, taking into consideration all these parameters. Eleven adults (20–28 years) and 11 aged subjects (63–83 years) were recruited. We used LED targets at 7.5° or 15°, up or down in four conditions: gap and overlap tasks, each done at two distances—at near (40 cm) and at far (150 cm). In the gap task fixation target extinguishes prior to target onset, while in the overlap condition it stays on after target onset; consequently, visual attention and fixation are employed differently in the two tasks. Eye movements were recorded with the Chronos video eye tracker. Results showed that vertical saccades were longer for aged subjects than for young adults under almost all conditions. For both aged and young subjects, latencies were shorter under the gap than under the overlap task. Latencies for eccentric targets at 15° were significantly longer than those at 7.5° but for aged subjects only; this effect was more pronounced for upward saccades under the overlap condition. Express type of latencies (80–120 ms) occurred frequently in the gap task and at similar rates for young adults (16%) and aged subjects (12%); in the overlap task express latencies were scarce in young adults (0.4%) and aged subjects (1.8%). Age deteriorates the ability to trigger regular volitional saccades but not the ability to produce express type of saccades. Latency increase with aging is attributed to the degeneration of central areas, e.g. oculomotor cortical areas involved in the initiation of vertical saccades.Grant/financial support: European Union (QLK6-CT-2002-00151: EUROKINESIS) and CNRS/CTI, Handicap contract CR:N.     

Divergent effects of human lymphokine derived oligopeptides on PMNLs function of young and aged healthy subjects

The effects of low molecular weight lymphokine-derived oligopeptides (LK-OPs) on PMNLs effector functions and receptor mediated biochemical events were studied in the case of healthy young and aged subjects. In the case of young subjects the low mol. wt. LK-OPs stimulated the Fc gamma receptor-mediated effector functions of PMNLs, whereas an inhibition was observed in PMNLs of the elderly (extracellular cytotoxicity and intracellular killing). The underlying biochemical events, induced by low mol. wt. LK-OPs stimulation, were also investigated. In PMNLs of young subjects the oxidative metabolism was stimulated (enhanced O2 consumption, O2 and H2O2 production) by low mol. wt. LK-OPs, while in elderly subjects it was inhibited. The cyclic nucleotides regulating the Fc gamma receptor mediated effector functions and the oxygen radicals formation showed an altered dynamic response under low mol. wt. LK-OPs stimulation with aging i.e. the cGMP level could not be changed at all. Our results suggest that low mol. wt. LK-OPs induced inhibition of Fc gamma receptor mediated effector functions with aging could be partly explained by an altered post receptorial coupling switch and as a consequence the lymphokines could not play their role of immunomodulators further impairing the altered immune response with aging.     

Phagocytic, lambda light chain, plasma cell myeloma

A case of phagocytic, lambda light chain, plasma cell myeloma was characterized by its clinical, morphologic, cytochemical, immunologic, and cell kinetic features. A 40-year-old man presented with Coombs-negative hemolytic anemia, hepatosplenomegaly, lytic bone lesions, lambda light chain monoclonal gammopathy, and infiltration of the bone marrow by dysplastic plasma cells, 10% of which demonstrated phagocytosis of erythroid cells. Electron microscopy demonstrated myeloma cells with prominent cytoplasmic microfilaments and erythroid cells in intracytoplasmic vacuoles. The myeloma cells did not phagocytose staphylococci in vitro. Phagocytic and nonphagocytic myeloma cells were tartrate-sensitive, acid-phosphatase positive, alpha-napthyl butyrate esterase negative, and did not form E rosettes or EAox(IgG) rosettes. The tumor cells were Tdt, Ia antigen, and SIg negative. Immunofluorescent staining for cytoplasmic light chains showed a monoclonal lambda pattern in nonphagocytic myeloma cells, and a probable monoclonal lambda pattern in phagocytic myeloma cells. These findings characterize the neoplasm as a monoclonal proliferation of differentiated plasma cells with the capability of erythrophagocytosis. Erythrophagocytosis by myeloma cells may have been responsible for the hemolytic anemia. The tritiated thymidine labeling index (LI%) was high (8%), suggesting a poor prognosis, despite a dramatic initial response to chemotherapy.     

Impairment of lymphocyte activities in depressed aged subjects.

Lymphocyte activities were determined in a population of 26 institutionalized aged subjects, selected as healthy according to the SENIEUR protocol and previously reported to display immunological and endocrinological abnormalities correlated with depressive disorders. The lymphocyte mitotic response to PHA, which was reduced in aged as compared to adult subjects, was found to be significantly lower and negatively correlated with the depression score in the elderly subjects. In supernatants of PHA-stimulated lymphocyte culture from aged subjects, IL-2, IL-4 and gamma-IFN levels were very low and more severely affected in the depressed aged group. Each cytokine production was negatively correlated with age and depression score. NK activity was lower in the aged and it could be augmented by the addition of IL-2 or alpha-IFN, even though to a lesser extent than in the adult subjects. The nondepressed aged displayed higher levels of IL-2 inducible NK activity than the depressed aged subjects. IL-2 and alpha-IFN stimulated NK activities were negatively correlated with depression score. The present work indicates that the psychological status could affect lymphocyte reactivity in the aged. Given the relatively high frequency of affective disorders in these subjects, the psychological status should be considered in studies of immune senescence.     

Phagocytic function of monocytes in children with human immunodeficiency virus type 1 infection

We investigated the phagocytic function of monocytes in 7- to 10-year-old children horizontally infected with human immunodeficiency virus type 1 (HIV-1) in comparison to that in healthy sex- and age-matched controls. CR3-mediated phagocytosis was increased in patients with HIV-associated pulmonary tuberculosis, independently of CD4 counts and p24 antigenemia.