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G J Ligthart

Publications and source records attributed to G J Ligthart.

12 recordsLinked to original sources
PubMed1991

Longevity and heredity in humans. Association with the human leucocyte antigen phenotype.

Several arguments support the idea of a link between longevity and heredity, both in experimental animals and in the human species. In mice, genes in the major histocompatibility complex (MHC) are associated with a significant effect on life span. Results of analogous studies in man are confusing and contradictory. We have therefore investigated the question of an association of the human leucocyte antigen (HLA) and longevity in a large and ethnically homogeneous population. Our study population consisted of all 964 available inhabitants aged 85 years and over in the Dutch community of Leiden (pop. 104,000). Our control group comprised 2444 young inhabitants, aged 20-35 years, with an identical ethnic and demographic background. In addition, control groups of different age-brackets from the same region were used. Two antigens differed in frequency: HLA-B40 was lower and HLA-DR5 was higher in the group of 85 years and over, as compared to the control group, aged 20-35 years. Both differences were more evident in females. No major disease associations with HLA-B40 or HLA-DR5 have been reported. It is unlikely that these results are a chance observation: the overall similarity of the HLA pattern of the old and young age groups is a confirmation of their identical ethnic and demographic background and the changes as observed in the different age-groups were gradual. The biological meaning of these results is still unclear.

Adult↗
PubMed1990

Gating of the so-called 'lymphocytic' cell population for the quantification of natural killer cells (CD16+) by flow cytometry causes loss of CD16 positive cells.

Natural killer cells can phenotypically be identified as CD16 positive with a specific monoclonal antibody (B73.1 = Leu-11c) by either immunofluorescence microscopy or by flow cytometry. The standard procedure in flow cytometry is to set a window or gate around the so called lymphocytic population, based on scatter characteristics. In this paper we demonstrate that a substantial part of the NK cell population is situated outside this gate in the total mononuclear cell population. We therefore recommend that the number of CD16+ cells is determined in the total mononuclear cell population. However, in the total mononuclear cell population, a group of dimly CD16 positive cells, probably monocytes, interferes with a clear separation of cells with a positive and negative fluorescence. We describe two methods to overcome this problem.

Adult↗
PubMed1990

Monoclonal gammopathies in human aging: increased occurrence with age and correlation with health status.

To determine the incidence of monoclonal gammopathies (MG) in relation to the aging process as such, and to evaluate the influence of disease on the occurrence of MG, we studied 439 elderly subjects aged 75-84 years. These individuals were categorized into 4 groups on the basis of their health status. There was a group of "optimally healthy" elderly, a group of "apparently healthy" residents of homes for the aged, a group of geriatric outpatients and a group of randomly chosen inpatients from a general hospital. Whereas no MG were detected in a control group of healthy young subjects aged 25-34 years, the frequency of MG in the aged groups ranged from 11% in the "optimally healthy" aged group to 38% in the inpatients group. In a tentative classification according to possible cause, most of the MG belonged to the pathogenetic category of immunodeficiency. There was a clear association of the occurrence of monoclonal gammopathies of this category with the health status.

Adult↗
PubMed1990

Necessity of the assessment of health status in human immunogerontological studies: evaluation of the SENIEUR protocol.

Disease is frequent in ageing, and the many conflicting results in studies of the ageing process can be due to the presence of factors such as underlying disease or the use of medication. For immunogerontology, a solution to this problem was initiated in 1984 by a working party of EURAGE, the European Community's Concerted Action Programme on Ageing and Diseases. A protocol defining strict admission criteria to studies of ageing, the SENIEUR protocol, was elaborated. This protocol intends to limit the influence of disease and/or medication and to standardize admission criteria to immunogerontological studies. In subjects fulfilling the SENIEUR criteria, we found less immunological defects with ageing than generally stated. This could mean that many studies performed in not-optimally healthy subjects describe defects that are not a consequence of the ageing process, but could be a result of underlying disease or of the influence of medication. For lymphocyte subsets, certain changes are only found in the comparison of SENIEUR groups of young and aged, while other changes are only found when non-healthy groups are compared. The occurrence of monoclonal gammopathies and autoantibodies was increased in ageing, but was also influenced by health status. Experience of other groups, and the objections against the protocol are discussed.

Adult↗
PubMed1990

[Extension of life, at what price? Consequences for health care of the elderly].

Prolonging life only makes sense if quality of life is maintained. In biomedical terms this means that life extension should not be accomplished at the cost of an increase of morbidity and dependence. The survival curve must maintain its rectangular shape and compression of morbidity should be sought for. Ageing is not synonymous with disease, and a healthy old age certainly is possible. Many disorders of old age are a result of extrinsic, avoidable factors such as drinking, smoking, eating habits, and inactivity. Prevention must begin in youth. This is the price to be paid by the individual. The medical and scientific community should increase its efforts to develop health care for the aged and increase investments in the study of the ageing process itself. Society as a whole can give support by funding the development of geriatrics and gerontology, and by improving the position and the acceptance of the elderly in daily life.

Aged↗
PubMed1989

Single- and multiple-dose nisoldipine kinetics and effects in the young, the middle-aged, and the elderly.

Pharmacokinetics of nisoldipine and the drug's effects on blood pressure and heart rate were investigated in healthy young (20 to 23 years of age), middle-aged (49 to 57 years of age), and elderly (75 to 84 years of age) subjects after single-dose and short-term multiple-dose oral administration (10 mg twice daily). No age-dependent differences in pharmacokinetic parameters were observed. Decreases in blood pressure were comparable in the three groups, but reflex tachycardia was less pronounced in the elderly subjects. Side effects mainly occurred on the first day of drug administration. Dose adaptation of nisoldipine does not seem to be necessary in elderly subjects.

Administration, Oral↗
PubMed1989

Natural killer cell function is not diminished in the healthy aged and is proportional to the number of NK cells in the peripheral blood.

We studied natural killer (NK) cell subsets and NK function in young (25-35 years) and aged (75-84 years) persons by means of the single-cell assay. The subjects admitted to the study all fulfilled the SENIEUR health criteria in order to avoid confounding factors such as underlying disease or the influence of medication. We found no significant difference in the NK function between healthy young and aged persons on a per cell basis. A new application of the two-wavelength immunofluorescence technique during the single cell assay made it possible to define the phenotypes of the conjugate-forming cells responsible for the natural killer function. Most of the conjugate-forming cells were CD 16-positive, and half of these were also positive for Leu 7. The CD 16 antigen disappeared from the cell surface during the effector:target interaction. T-cell markers were found on some of the conjugate-forming cells but not on the strongly bound effector cells. The NK cell function was directly proportional to the number of NK (CD 16) cells in the peripheral blood.

Aged↗
PubMed1986

The expanded null cell compartment in ageing: increase in the number of natural killer cells and changes in T-cell and NK-cell subsets in human blood.

Analysis of the subpopulations of mononuclear cells in human blood in ageing has revealed a striking increase in the number of null cells, defined as non-T, non-B, non-monocyte cells, and a decrease in the number of T and B cells. By using recently developed monoclonal antibodies against natural killer cells in combination with T-cell markers in two-wavelength immunofluorescence, we were able to define 13 subpopulations of mononuclear cells and compare them in two groups of persons, respectively aged 25-34 and 75-84 years, all fulfilling the stringent admission criteria for immunogerontological studies described in the SENIEUR protocol, and thus all to be considered as optimally healthy and immunologically uncompromised. We found that the increased null cell population in the aged is a result of an increase in the numbers of NK cells, mostly the CD16+Leu7+ subset. The number of CD8+ suppressor/cytotoxic cells is decreased. This is due to a decrease of the number of CD8+Leu7- cells. All NK and T-cell subsets bearing the Leu7 antigen, namely CD16+ Leu7+, CD4+Leu7+ and CD8+Leu7+, are increased. These changes can be due to defects of the ageing immune system, but they can also represent the optimal state of the immune system in the healthy aged and may be linked to survival. These values can be used as reference values for the 75-84 years age group and serve to monitor attempts to reconstitute the immune defects in ageing.

Adult↗
PubMed1985

Subpopulations of mononuclear cells in ageing: expansion of the null cell compartment and decrease in the number of T and B cells in human blood.

Study of the immune system in ageing has yielded conflicting results. These controversies are mainly due to the selection of the subjects studied. We investigated the mononuclear cell subpopulations in the peripheral blood of subjects fulfilling strict admission criteria meant to exclude persons with diseases that influence the immune system. These criteria are described in the SENIEUR protocol devised by a working group in the framework of EURAGE, the Concerted Action Programme on Ageing of the European Community. We compared two groups of volunteers aged 25-34 years, and 75-84 years. Mononuclear cells were investigated by two-wavelength immunofluorescence combined with phase-contrast microscopy. We found a striking increase in the number of 'null' cells (non-T, non-B, non-monocyte) in the blood of the aged persons. The number of T cells was decreased, especially in the suppressor/cytotoxic subset. The number of B cells was slightly, but significantly, decreased; the number of monocytes did not change. The changes in these cell populations may be related to functional changes, and their quantification could be used to monitor attempts to reconstitute the immune defects in ageing. These findings can also serve as reference values in the study of aged persons not fulfilling the SENIEUR criteria, which, in turn, can contribute to the dissection of the influence of disease versus age on the immune system.

Adult↗