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Biomedical subjects

B Kennes

Publications and source records attributed to B Kennes.

At least 37 records · Page 2Linked to original sources

Immune senescence: effect of age, sex and health on human blood mononuclear subpopulations.

The respective influence of age, sex and health states on peripheral blood mononuclear subpopulations has been investigated in 194 institutionalized subjects. The "ill group' includes patients with various diseases and the "reference group' was referred to admission criteria for immuno-gerontological disease. A decline of total mature T-cell (OKT3) and helper T-cell (OKT4) proportions with ageing has been found only in the ill group and remains stable in the reference group. This age-dependent decline should represent either a susceptibility for illness or a consequence of higher incidence of illness with ageing. Suppressor-cytotoxic (OKT8), B- and T-activated (OKIa1), null (OKM1), and early E-rosette forming cells do not vary with ageing in both groups. It has been established previously that women have higher values of the percentages of early E-rosette forming cells.

Aged↗

Sheep-erythrocyte-capping by human T-lymphocytes. Pharmacological inhibition by phenothiazine drugs.

In our previous studies it was found that E-rosette dissociation and sheep-erythrocyte capping were active processes involving the cytoskeleton. These cellular functions are now shown to be very sensitive to phenothiazine-drugs whose activities can be differentiated as follows: trifluoperazine greater than chlorpromazine greater than sulfoxide derivatives, suggesting a role for calmodulin-mediated events. These findings are in contradiction to prior reports pointing to the inefficacy of chlorpromazine to inhibit slow kinetic capping. However, no co-capping of trifluoperazine fluorescence (as a probe of calmodulin) and sheep erythrocytes could be observed. No requirement in extracellular calcium was evident for E-rosette formation and dissociation.

Adult↗

Admission criteria for immunogerontological studies in man: the SENIEUR protocol.

Immunogerontological studies in man have often led to conflicting results. One of the main reasons is the selection of the subjects to be studied. Admission criteria such as "apparently healthy" or "without overt disease" seem insufficient to exclude underlying disease which might influence the immune system and thereby the results. In an attempt to solve this problem, the SENIEUR protocol described in this paper was developed by a working party in the framework of the EURAGE Concerted Action Programme on Ageing of the European Community. This protocol establishes strict admission criteria for immunogerontological studies in man based on clinical information and laboratory data, and it sets limits to pharmacological interference. The use of this protocol will lead to standardization between centers and also to a closer study of the influence of age as such on the immune system. These findings in the immunologically "optimally aged" can also serve as reference values for immunogerontological studies in subjects who do not meet the SENIEUR criteria. In this way the use of this protocol can contribute to the dissection of the influence of disease versus ageing on the immune system.

Adult↗

Lymphocyte activation in human ageing: V. Acquisition of response to T cell growth factor and production of growth factors by mitogen-stimulated lymphocytes.

In order to ascertain why the T cell proliferative response declines with ageing, the age-related quality of the interleukin II (Il-2)-mediated signal during lymphocyte activation was investigated in mitogen-stimulated peripheral blood mononuclear cells (PBMC) from old (over 70 years) and adult (20-40 years) subjects. Both the Il-2 properties of supernatants produced by phytohaemagglutinin (PHA)-stimulated PBMC on Il-2 sensitive cells and the PHA-induced transformation in Il-2 sensitive T cells were decreased in the old subjects. Supplements with human Il-2 enhanced the DNA synthesis by PHA-, concanavalin-A-, or pokeweed-mitogen-activated lymphocytes in the two groups of subjects. The addition of Il-2 to old cultures restored a response similar to that observed in adults cells cultured without exogenous Il-2. The similarity of the dose-response curves to interleukin II indicated the unaltered affinity of the specific membrane receptors to the humoral factors. These findings strongly suggest that the immune deficiency commonly found in the elderly results principally from a selective alteration of the hormonal step of lymphocyte activation.

Adult↗

Effect of vitamin C supplements on cell-mediated immunity in old people.

Both ageing and vitamin C (VC) deficiency result in immune defect. Since low serum and tissue levels of VC are found in the elderly, we have in a placebo-controlled study, tested the effect of VC supplements (500 mg/day i.m. for 1 month) on various immune parameters. Indeed, VC enhances the proliferative response of T lymphocytes in vitro, and the tuberculin skin hypersensitivity in vivo. Neither the serum concentrations of IgA, IgG and IgM, nor the proportion of E-rosette-forming cells were modified. No significant change was observed in the placebo-treated group.

Aged↗

Increased stability of E-rosettes and restricted capping of sheep erythrocytes by lymphocytes of aged humans.

The processes of E-rosette dissociation and sheep red blood cell (SRBC) capping provide simple assays for studying age-related changes in membrane dynamics of T-lymphocytes. After incubation at 4 degrees C, no significant difference is observed between young-adult and elderly subjects, either in the number of rosette-forming-cells (E-RFC) or in the distribution of SRBC at the lymphocyte surface. However, when the E-RFC are incubated at 22 or 37 degrees C after resuspension, the rosettes disintegrate to a larger extent forming fewer morula-like structures and more caps in young donors. An inverse relationship is noted between the number of E-RFC and the percentage of capping cells, suggesting a role for the lateral movement of the SRBC receptors in the dissociation process. In the elderly, rosette disintegration seems to be related only to the random release of SRBC. It is speculated that this increased stability of the E-rosettes represents some locking of the T-lymphocyte membrane receptors, which could alter the transduction of cell-cell signals.

Adult↗

E rosette dissociation: evidence for a role of the cytoskeleton.

When put into 37 degrees C incubation, the E rosettes dissociate spontaneously and the sheep erythrocytes (SRBC) form caps at one pole of the lymphocytes. This process is associated with changes in cell morphology such as uropod formation or membrane budding. The disintegration of E rosettes and the capping of SRBC can be retarded by addition of cytochalasin B plus colchicine, chlorpromazine or sodium azide. These findings suggest a pivotal role of the cytoskeleton in the dissociation process of E rosettes. However, other mechanisms of disintegration are to be considered since none of the drugs can prevent the dissociation of E rosette entirely.

Adolescent↗

Asthma from plexiglas powders.

A patient with severe asthma induced by the inhalation of plexiglas dusts is reported. Inhalation testing against various industrial products to which he was exposed at work, showed a specific and reproducible asthmatic reaction to plexiglas dusts. Complete pulmonary investigations after positive challenge excluded associated alveolitis and demonstrated an immediate and a late obstructive response. The patient was not atopic and his clinical history did not suggest occupational disease due to chronic exposure. Reduction of the plexiglas dust exposure resulted in progressive improvement.

Adult↗

Early biochemical events associated with lymphocyte activation in ageing. I. Evidence that Ca2+ dependent processes induced by PHA are impaired.

The requirement for Ca2+, a divalent ion which plays a fundamental role in cell activation, has been analysed in cultures of PHA-stimulated human peripheral blood lymphocytes (PHA-PBL) from adult (range: 20-35 years) and old (over 70 years) subjects. For this purpose, increasing concentrations of Ca2+ chelators (EGTA and EDTA) were added to cultures in order to compare the effect of progressive extracellular Ca2+ (Ca2+EC) depletion on [3H]-Tdr incorporation by PHA-PBL. Kinetic analysis showed that Ca2+EC requirement was restricted to the first 24 h after culture initiation. At optimal doses of PHA, the PHA-PBL from old subjects were more sensitive than those from adult subjects to increasing concentrations of both chelators. They also required larger amounts of Ca2+ supplements to restore their normal response after total inhibition by EGTA. Furthermore, the PHA-PBL from the elderly were hypersensitive to verapamil (Isoptin), a drug which instigates a reversible inhibition of Ca2+-dependent processes associated with lymphocyte transformation, by a quite similar reaction to that induced by chelators. We conclude that the Ca2+-dependent processes in lymphocyte activation are impaired with ageing. Following further experiments and recent work suggesting that lymphocytes need more than one signal to proliferate, the authors speculate on a deficiency of a late activation signal requiring cell-cell interactions in the elderly.

Adult↗