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Biomedical subjects

W Hijmans

Publications and source records attributed to W Hijmans.

At least 19 recordsLinked to original sources

Rheumatoid arthritis in a population of persons aged 85 years and over.

A Dutch urban population of 977 persons aged 85 years and over was examined for the presence of rheumatoid arthritis (RA). Prevalence rates for definite RA, past polyarthritis with joint deformation and past polyarthritis without joint deformation were 0.3%, 0.3% and 0.7%, respectively. The polyarthritis patients did not differ from age-matched controls with respect to crude scores of physical disability, the presence of serum rheumatoid factor or the presence of HLA-DR4. Although these data should be interpreted with caution because of the small patient groups, we conclude that in persons aged 85 years and over the prevalence of RA is low, and the disease is relatively mild.

Age Factors

Age-related changes of the antigen-specific antibody formation in vitro and PHA-induced T-cell proliferation in individuals who met the health criteria of the Senieur protocol.

The antigen-specific antibody secretion in vitro after immunisation with the primary T-cell dependent antigen Helix pomatia Haemocyanin (HPH) was investigated in both young and elderly individuals, who all met the health admission criteria for immunogerontological studies as detailed in the SENIEUR protocol. In addition, elderly non-Senieur persons were incorporated in this study. Young and elderly Senieur volunteers were fully comparable in terms of the occurrence of anti-HPH antibody secreting cells after in vitro simulation of peripheral blood mononuclear cells with variable doses of the antigen. In contrast, the non-Senieur elderly showed a lower number of anti-HPH antibody secreting cells in vitro. PHA-conditioned medium did enhance this in vitro response, whereas the addition of IL-2 remained ineffective. The PHA-induced T-cell proliferation was found to be somewhat impaired in elderly Senieur individuals and significantly lower in elderly non-Senieur individuals compared to young healthy persons. Using an immunofluorescence double staining technique after BrdU incorporation, the phenotype of the proliferating cells was determined. Again the total number of proliferating cells was impaired in the non-Senieur elderly. No changes in the relative contribution of CD4+ or CD8+ cells to the number of proliferating cells were found in the different age groups. On the other hand, a significantly lower number of proliferating cells with IL-2 receptor expression were detected in the non-Senieur individuals, which could account for the lack of response to IL-2 in this group. Our study clearly shows that so-called age-associated immune deficiency can be the result of disease and not necessarily of the ageing process itself.

Adult

Influence of ageing on antibody formation in vivo after immunisation with the primary T-cell dependent antigen Helix pomatia haemocyanin.

The in vivo antibody response to the primary T-cell dependent antigen Helix pomatia Haemocyanin (HPH) was studied, in order to detect the possible presence of a humoral immune deficiency in ageing. The IgG subclass distribution of the specific antibodies was also determined. In order to define a dose of HPH which could be used to discriminate between the responsiveness of healthy and immunocompromised individuals, we first established a dose-response curve for this antigen in 60 healthy young volunteers. Their responses were compared with the responses of a group of patients suffering from end stage renal failure. The patients who were treated with haemodialysis showed a significantly lower IgM, IgG and IgA anti-HPH antibody response after immunisation with a dose of 30 micrograms HPH, which could be restored by increasing the antigen dose. Patients treated with continuous ambulant peritoneal dialysis and a group of elderly persons, selected according to the Senieur protocol, showed no impairment of antibody formation after immunisation with 30 micrograms HPH, but in the non-Senieur elderly the anti-HPH antibody response was significantly lower. Furthermore, Senieur and non-Senieur elderly persons showed a diminished IgG2 anti-HPH antibody formation, whereas in the elderly non-Senieur individuals and in the patients with renal insufficiency, IgG1 and IgG3 anti-HPH antibodies were also diminished. This study clearly shows that the so-called age-associated immune deficiency can be the result of disease and is not necessarily due to the ageing process itself.

Adult

Serum immunoglobulin class and IgG subclass levels and the occurrence of homogeneous immunoglobulins during the course of ageing in humans.

Serum levels of IgM and IgA classes and of IgG subclasses were determined and related to the presence of homogeneous immunoglobulin components (H-Ig) in volunteers equally distributed in age groups from 25 to 98 years, who all met the Senieur admission criteria for immunogerontological studies. In addition, sera of non-Senieur volunteers aged 75 years and older were included. Furthermore, the amount of IgD was determined in sera of Senieur individuals equally distributed in age groups from 15 to 98 years. In the Senieur persons, the contribution of the IgG subclasses and the IgM and IgA classes to the pool of serum immunoglobulins remained relatively unchanged during the course of ageing. In comparison with Senieur individuals aged 25-34 years, a slight increase in IgM and IgA levels was observed from the age 35 to 44 onwards and in IgG1 from the age 55 to 64 onwards. The variability of the immunoglobulin concentrations increased during ageing. The most prominent observation was the continuous decline of serum IgD starting in young adults. The non-Senieur persons differed from their Senieur age-matched counterparts mainly by the elevated IgG2 and IgA levels. During the course of ageing, H-Ig mainly of low concentration were detected at an increasing frequency in the Senieur persons and even more frequently in the elderly non-Senieur volunteers. Although in some individuals the elevation of immunoglobulin levels correlated with the appearance of H-Ig within the corresponding isotype, this relationship was not conclusive for all sera investigated. These results suggest that the rise of serum levels of individual immunoglobulin isotypes associated with ageing is usually the consequence of a polyclonal B cell activation. The occurrence of H-Ig and the decline of serum IgD in aged Senieur persons indicate that these are, at least partly, true phenomena of ageing and not always the consequence of disease.

Adolescent

Prevalence of dementia in the 'oldest old' of a Dutch community.

OBJECTIVE: To estimate the prevalence rate of dementia in subjects 85 years of age and over. DESIGN: A two-phase design with the Mini-Mental State Examination (MMSE) in the screening phase and the Geriatric Mental State Schedule (GMS) in the diagnostic phase. SETTING: Community survey including subjects in residential care. SUBJECTS: All (n = 1,259) inhabitants of Leiden, The Netherlands, aged 85 years and over on December 1, 1986. First phase participation rate was 71% (17% dropout due to death); second phase participation rate was 82%. MAIN OUTCOME MEASURE: DSM-III diagnosis of dementia without further specification of the etiology of the dementia. RESULTS: An overall prevalence rate of 23% (95% C.I.: 19%-26%) was found. This included 12% mild dementia, 7% moderate and 4% severe dementia. The prevalence rate was higher among women (24%) than among men (18%). It increased with age from 19% (95% C.I.: 16%-22%) in the group of 85-89 years to 32% (95% C.I.: 26%-39%) in the group of 90-94 years to 41% (95% C.I.: 25%-58%) in the 95+ group. CONCLUSION: A fifth of the 85+ and a third of the 90+ population suffer from dementia with an indication that half of the 95+ population is affected. With the expected steep rise in the number of the oldest old, dementia will stay a major health problem in the near future.

Aged

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

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

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

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

Reference values for the Mini-Mental State Examination (MMSE) in octo- and nonagenarians.

The Mini-Mental State Examination (MMSE) was used in a population survey of all inhabitants of Leiden, the Netherlands, over 85 years (n = 1258). In this paper we report on 532 subjects without neurological or psychiatric disease. Results show that the median score and lowest quartile cut-off score remain high until the tenth decade (median score = 28, lowest quartile cut-off score = 26). Thus age, in itself, is not a major limitation in using the MMSE. In this study a comparatively low level of education (the majority had 6 to 7 years of education) did not affect the results on the MMSE in a negative way, nor did we find an association with the use of psychoactive drugs.

Aged

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

Intracellular immunoglobulin G 'pseudocrystals' in a patient with chronic B-cell leukemia.

A patient with chronic B-cell leukemia in whom the malignant lymphocytes showed intracellular inclusions of immunoglobulin (Ig) G kappa molecules is described. Electron microscopy revealed filamentous material in the nuclear envelopes and in the cisternae of the rough endoplasmic reticulum. These in vivo surface Ig-negative, nonexcreting cells could be stimulated in vitro to excrete immunoglobulin-free light chain molecules into the supernatant, which were not found in the cytoplasm after stimulation.

Aged

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

Chronic B-cell leukemias: relation between morphological and immunological features.

To better understand the heterogeneity of chronic B-cell leukemias we correlated morphological and immunological features by studying the peripheral blood from 80 patients with a panel of anti-immunoglobulin and fourteen monoclonal antibodies, which hitherto were studied separately or with respect to one single morphological entity only. Of these the surface immunoglobulins (sIg) and monoclonal antibodies (McAb) BA-1, BA-2, FMC7, OKM1, and anti-T65 allowed a fair distinction between five cytological subtypes: chronic lymphocytic (CLL), "lymphoplasmacytoid" (LPL), centrocytic (CL), prolymphocytic (PLL), and hairy cell leukemia (HCL). In that order the sIg showed a decreasing number of cases of mu +/- delta class and an increase of alpha or gamma positivity. The number of BA-1-positive cases was decreased in PLL and HCL. There was a decline of BA-2- and anti-T65-positive cases in the order mentioned, while this was accompanied by an increase of FMC7 and OKM1 positivity. A significant mutual exclusion between anti-T65 and FMC7 was observed and the same was true for FMC7 and BA-2. The antibodies FMC7 and OKM1, and anti-T65 and BA-2 were linked to each other. Also FMC7 positivity was related to sIg of the alpha and gamma classes. On the basis of this unique combination of markers a differentiation scheme of B lymphocytes is proposed, in which prolymphocytic leukemia and hairy cell leukemia seem to represent a maturation arrest at a more advanced stage than chronic lymphocytic or "lymphoplasmacytoid" leukemia.

Adult

Light and electron microscopic studies of the rat hyalocyte after perfusion fixation.

The characteristic morphology of a not intentionally stimulated hyalocyte is described, using TEM and perfusion fixation. The best results were obtained by retrograde perfusion via the abdominal aorta with a glutaraldehyde- and formaldehyde-containing fixative. The cells, situated in the cortical area of the vitreous body, show mostly an indented nucleus, primary and secondary lysosomes, mitochondria, cisterna, clusters of free ribosomes and a Golgi apparatus. Bristle-coated micropinocytotic vesicles can also be distinguished and in some cells a centriole is visible. Sometimes the cells show many cytoplasmic protuberances. Morphologically the majority of those cells can be considered as resting macrophages.

Animals

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