Biomedical subjects

B Cinader

Publications and source records attributed to B Cinader.

At least 37 records · Page 2Linked to original sources

PubMed1989

Economic correction; quantity and age-related rate of change.

Correlation between the relative magnitude of activity or concentration in youth and the relative magnitude of age-related decrease occurs in several systems. We have observed this correlation in density of D2-dopamine receptors of the striatal membrane, activity of lymphocyte activated killer cells, relative density of CD8 on thymocytes, augmenting activity of T splenocytes and mRNA, coding for IL-1 in Langerhans cells. We have suggested that this correlation should be considered in the context of balanced investment in lifespan and reproductive efficiency, that it may be the result of feedback regulation and have designated it as "economic correction".

Age Factors↗

PubMed1989

Age-related changes in contact photosensitivity differ among mouse strains.

There are differences among mouse strains in the age-related changes in reactivity to the contact photosensitizer tetrachlorosalicylanilide (TCSA). We found a tendency to lower reactions in older mice, with some strains showing declines from an early age (BALB/cJ, MRL/MpJ +/+, MRL/MpJ lpr/lpr and SJL/J). Others had increasing reactions until about 30-50 weeks of age before declining (DBA/1J, C3H/HeJ, and A/J) and one strain (C57BL/6J) had increased reactivity with age. There are also differences in the role of cyclophosphamide-sensitive T-suppressor cells in these age-related changes. In some mouse strains, BALB/cJ, C57BL/6J, A/J, DBA/1J and C3H/HeJ, age-related changes in reactivity to TCSA are independent of changes in cyclophosphamide-sensitive suppressor cells. In other strains, MRL/MpJ +/+, MRL/MpJ lpr/lpr and SJL/J, the development of cyclophosphamide-sensitive suppressor cells is responsible for the initial, though not later, stages of the age-related decline in reactivity.

Aging↗

PubMed1989

Strain polymorphism in progression of aging: changes in CD4, CD8 bearing subpopulations.

Polymorphism of age-related changes in CD4 (L3T4) and CD8 (Lyt-2) determinants of spleen and thymus cells was assessed by fluorescence-activated flow cytometry. Cells from mice ranging from 5 weeks to greater than 2 years of age were examined. There is little age-related change in the proportion of CD4+ CD8- splenocytes in A, C57BL/6, DBA/1, DBA/2, and SJL mice (slopes 0.04, 0.06, 0.08, 0.17 and 0.17, respectively, when age in weeks was plotted against % of positive cells). Changes in the composition of the thymus are much more profound: CD4+ CD8+ cells of SJL mice decrease from 70% to less than 10% as the animals age from 5 to 69 weeks (slope -1.03), and in DBA/2 mice from 5 to 110 weeks (slope -0.88). While this decrease in CD4+ CD8+ cells occurs, there is a compensatory increase in CD4+ CD8- and CD4- CD8+ cells; this is a shift in the relative proportion of subpopulations rather than an increase in absolute cell numbers of a particular subpopulation. In contrast to the age-related changes of SJL and DBA/2 mice, there is relatively little change in the proportion of CD4+ CD8+ thymus cells in mice of strains C57BL/6, DBA/1 and A (slopes -0.03, -0.14 and -0.15, respectively).

Aging↗

PubMed1989

Aging, evolution and individual health span: introduction.

The effect of autologous and environmental wear and tear on genes and gene products will be considered in systems renewed by self-replicating stem and precursor cells as well as in systems that do not have the capacity for self-renewal. Aging will be discussed in terms of speciation and in terms of health-span differences between individuals of the same species. The analysis of speciation involves early as well as late-acting genes. The intraspecies analysis is primarily concerned with the second half of life and thus is not affected by selective pressures. Analysis of individual aging is concerned with health span, qualified by identification of the particular system that is responsible for the limit of health span in subpopulations; it depends on a subset of allelic products of many genes and their relative functional capacity. The identification of such alleles can provide the starting point for reverse genetics. Results will be presented, which have been obtained by analysis of age-related events in inbred mice, where regulation, involved in degenerative disease of old age, can be studied in groups of individuals with a relatively constant genetic background. It should be possible to identify appropriate probes for degenerative diseases of old age that can be used for detection of corresponding human genes. Worldwide demographic changes have created the need for a new type of public health policy. To respond to this need, we should learn how to identify individuals at risk from degenerative diseases of old age and how to treat them preventively.

Aging↗

PubMed1989

Compartmental and intracompartmental regulation of aging.

Individual differences of aging occur in systems of regulation and communication. Different types of suppressor capacity can change in opposite directions as an individual ages. The progression of these changes in suppressor capacity can be changed to different extents by hormones or diets differing in fatty acid composition. It seems reasonable to conclude that these two activities depend on different precursors which age under the control of two different genes, although the two precursors are almost certainly derived from a common stem cell line. A variety of molecules and activities undergo age-related reductions, which are completed by middle age; the resulting levels of a given gene product are remarkably similar in different individuals, while the levels at a young age show very great individual differences. This correlation between the youthful quantity of a given gene product and the rate of change in later life has been designated as "economic correction." The study of multicentricity of different controlling and of functional competencies of different alleles is an important component in the development of preventive geriatric medicine.

Aging↗

PubMed1989

Age-dependent changes of isotype and idiotype expression in the antibody response to the phosphorylcholine hapten in BALB/c mice.

The distribution of antibodies among different isotypes in an immune response to a given antigen reflects the immunoregulatory linkage of T and B cell compartments, the genetic background of an individual and the functional state of its immune system. In addition, idiotypes are markers for the clonal origin of antibodies and their genetic relationship. Therefore, we have analyzed the isotype patterns and development of the major idiotype (T15) in BALB/c mice of different ages, immunized with a T-cell-dependent phosphorylcholine conjugate. The response was dominated by mu, gamma 3 and gamma 1 isotypes. The proportion of these antibodies changed in the progress of immunization but not with age in the primary response. An age-dependent change of the isotype distribution was observed only in the memory response. The T15 idiotype was dominantly expressed in the primary response and decreased in the memory response by 80-95% independently of the age of the mice. The results demonstrate that 2 populations of anti-phosphorylcholine antibodies which both prefer particular isotypes are expressed according to the functional state of the T and B cell compartments with age.

Aging↗

PubMed1988

Fluorescence-activated cell sorter (FACS) analysis of rabbit cells.

Monoclonal antibodies RB1, RB2, RT1, RT2 and RB3 were prepared against rabbit lymphoid cells by immunization with various fractions of rabbit lymphoid cells. The antigens detected by the antibodies are found on B and T cells in different densities. High proportions of polymorphonuclear and bone marrow cells which do not carry the RABELA and RTLA antigens carry the antigens of the RB and RT series. A subpopulation of appendix sIg-negative, RTLA-negative cells has a relatively high concentration of RT2. In general, B and T cells of the appendix show relatively small differences in the membrane densities of RB and RT antigens.

Animals↗

PubMed1988

Strain differences of age-dependent changes in the responsiveness to a T-independent type-2 antigen in mice.

We have assessed age-associated early changes in antibody response to a T-independent type-2 (TI-2) antigen, dinitrophenylated ficoll (DNP-Ficoll). Mice of most strains, including long-lived and autoimmune-prone strains, give a high response when approximately 2 months old; thereafter the response declines sharply to the 3rd-4th month of age and continues to do so, more gradually, up to the age of 6 months. Age-related changes in the response of C57BL/6 mice follows a different course: the response remains unchanged up to the first year of life, i.e. to middle age. The in vitro anti-DNP-Ficoll antibody response of B cells could be increased by the addition of young syngeneic T cells. The augmenting activity of splenic T cells of C3H/He mice declines clearly as a function of age. In contrast, splenic T cells of C57BL/6 mice have low augmenting activity whether the T cells are obtained from young or middle-aged donors. Unlike the augmenting capacity of T cells, B-cell responsiveness to DNP-Ficoll increases until middle age in all strains examined. We conclude that early age-associated changes in antibody response to the TI-2 antigen is polymorphic and that the early age-related decline in in vivo responsiveness is attributable to an age-associated decline in augmenting T helper cell activity.

Aging↗

PubMed1988

Effects of aging on neuronal electrical membrane properties.

The electric membrane properties (EMP) of dorsal root ganglion (DRG) neurons in cell cultures prepared from control mice (8-14 weeks) and old mice (90-92 weeks) were compared. The old neurons had a number of significant alterations in EMP compared to controls including decreased electrical excitability, increased action potential duration and more pronounced biphasicity of the repolarization phase. The old neurons also had larger action potential overshoot and afterhyperpolarization. The pattern of altered electric membrane properties was consistent with an age-induced shift from voltage-sensitive sodium channels to less excitable voltage-sensitive calcium channels and also a decrease in potassium permeability during the repolarizing phase of the action potential.

Aging↗

PubMed1988

Cross-reaction of a monoclonal antibody to human MHC class II molecules with rabbit B cells.

Monoclonal antibodies, 21w4 and 44H10, against human MHC class II determinants, were analysed for their reactivity with rabbit lymphoid cells. Both MAb bind to all human B lymphoblastoid lines, irrespective of their HLA-DR phenotype. HLA-DR antigens, purified by affinity to 21W4 IgG Sepharose, can be precipitated with 44H10 MAb, indicating that both antibodies react with the same molecules. Competitive inhibition studies with purified MAb IgG show that 44H10 and 21w4 recognize different epitopes of HLA-DR molecules. The 21w4 MAb, previously shown to cross-react with cells of pig, mouse and sheep, does not react with rabbit lymphoid cells. The 44H10 MAb binds to lymphoid cell suspensions prepared from rabbit appendix, spleen and mesenteric lymph nodes. Its reactivity correlates with that of RABELA, a polyclonal antibody specific for rabbit B cells. Mesenteric lymph node and spleen cell suspensions, depleted of sIg+ cells, are devoid of 44H10+ cells, while similarly-treated appendix B cells still contain a subset of B cells which are sIg-, RABELA+ and 44H10+. These studies thus report on the presence of MHC class II determinants on rabbit B cells, cross-reacting with human HLA-DR.

Animals↗

PubMed1988

Effect of dietary fat on antibody response and on down-regulation.

Diets differing in the ratios of polyunsaturated to saturated fatty acids (P/S) have dramatically different effects on the extent to which pretreatment with aggregate-freed form of a foreign protein augments or diminishes (by sensitization or down-regulation) the subsequent response to an immunogenic form of the same protein. We have examined this phenomenon in terms of both down-regulation (acquired immunological tolerance) and sensitization induced in 87-week-old female C57BL/6 mice. Antibody response in these mice, fed on low P/S diets, could be down-regulated by pretreatment with aggregate-free rabbit gamma globulin, as manifested by antibody to aggregated rabbit gamma globulin of isotypes IgG3 and IgG2b. Animals fed high P/S diets were not down-regulated by the pretreatment, but were sensitized; there was a 2-3-fold increase in IgG3, IgG1, IgG2a and IgA antibody to rabbit gamma globulin.

Animals↗

PubMed1988

Influence of genotype on the phospholipid fatty acid composition of splenic T and B lymphocytes in MRL/MpJ-lpr/lpr mice.

The MRL/MpJ-lpr/lpr mice manifest a T cell proliferative and autoimmune disorder. Similar changes occur much later in the life of MRL/MpJ-+/+ mice. MRL/MpJ-lpr/lpr (lpr/lpr) and MRL/MpJ-+/+ (+/+) mice were fed for six weeks nutritionally adequate semipurified diets containing 20% (w/w) fat, but differing in linoleic acid content. The phospholipid fatty acid composition of T and B cells was found to be dependent on genetic background of mice and level of linoleic acid in the diet. Changes in the levels of specific fatty acids like 16:0, 18:2 omega 6, 22:5 omega 3 and 22:6 omega 3 in some of the phospholipid components were observed in the MRL/MpJ-lpr/lpr strain in both the B and T cell types as compared with their normal +/+ counterpart strain. T cells of lpr/lpr mice exhibited significantly higher levels of 20:4 omega 6 than did T cells of other strain. High levels of dietary linoleic acid significantly increased incorporation of 18:2 omega 6 in T and B cells, while the effect on other fatty acids of the two types of cells varied with the phospholipid classes and fatty acids when compared with the low linoleic acid fed-group. Differences observed in the phospholipid fatty acid composition of the T and B cells of the congenic mice might contribute to differences in rate of progression of age-related changes suggesting that the autoimmune disorder might be mitigated by dietary manipulation.

Animals↗

PubMed1988

Antibody response and acquired tolerance of A/J mice: age- and immunogen-related isotype differences.

In earlier work we have observed strain- and age-related diversity of immunological ageing in inbred mice pretreated with tolerogen or left without pretreatment and then immunized. Different isotypes show different age- and strain-related changes. Here, we extend this isotype analysis from C57BL/6 and SJL to A/J. By comparison with the first two of these, animals of strain A/J show very little age-related change, as judged by indirect plaque-forming response. We have found that in A/J, as in SJL and C57BL/6 mice, age-related changes are isotype-dependent. The age-related changes in isotype predominance and magnitude differ for different determinants. They depend on the structural relation between the tolerance-inducing or -sensitizing macromolecule and the immunogen.

Age Factors↗

PubMed1987

Friend virus replication as a function of age.

We have investigated the effect of age on the replication of Friend spleen focus-forming virus (SFFV). Recovery of SFFV from the spleens of four strains of mice was determined following intravenous infection with NB-tropic Friend virus (FV) complex at ages ranging from 6 to 134 weeks. In C57BL/6 mice, the virus did not replicate in adults up to 40 weeks of age, but beyond that there was a steep exponential increase with age in the amounts of SFFV recoverable. In C3H/He mice, which replicate the virus as young adults, the amount of SFFV recovered was 6-fold greater in old than in young mice. Recovery of virus was biphasic with age in SJL mice; in A strain mice no consistent change with age was noted. In C57BL/6 mice, reconstitution of lethally irradiated recipients with syngeneic marrow cells, followed by i.v. infection with FV, showed that the amounts of SFFV recovered depended on the age of the recipient. The present work shows that Friend SFFV replication is a sensitive indicator and can be used as a tool for the investigation of aging processes. The mechanisms responsible for the age-dependent change in regulation of virus replication and for the polymorphism remain to be determined.

Aging↗

PubMed1987

Variations in age-related decline in striatal D2-dopamine receptors in a variety of mouse strains.

To determine the importance of inheritance on the age-associated decline in D2-dopamine receptor number, the binding of [3H]spiperone to mouse striatal membranes was measured in animals ranging from 7 to 104 weeks of age from 5 murine strains (C57BL/6J, C3/HeJ, A/J, SJL/J and DBA/1J). In young mice, receptor number (Bmax) was influenced by genetic background such that C57BL/6J less than SJL/J less than A/J = DBA/1J = C3H/HeJ. A 50-60% decline in Bmax with age was found in all strains except for C57BL/6J. Bmax in the C57BL/6J mice were lower than in the other strains of young animals (7-15 weeks) but remained relatively constant throughout life (measured up to 104 weeks of age). Furthermore, the maximal decline in receptor number was observed relatively early in life (16-30 weeks) and remained constant thereafter. Neither age nor genetic background influenced ligand affinity (Kd). Thus the results of this study suggest that the maximal decline in Bmax for the dopamine receptor occurs before the second half of life and that the magnitude of this decline is polymorphic.

Aging↗

PubMed1987

Lymphokine-activated killer (LAK) cells: I. Age-dependent decline of LAK cell-mediated cytotoxicity.

Experiments were designed to assess age-related changes in generation of lymphokine-activated killer (LAK) cells and to test whether these changes can be modified by diets differing in the proportion of polyunsaturated to saturated fatty acids (P/S). Ficoll-Hypaque-isolated spleen lymphocytes of rodent chow-fed, 6-85-week-old C57BL/6 (H-2b), 8-81-week-old C57BL/10 (H-2b) and 6-62-week-old SJL (H-2s) mice were cultured in IL-2-containing medium and examined in 51Cr cytotoxicity assay. Similarly, Ficoll-Hypaque-isolated spleen lymphocytes of 6-36-week-old SJL mice fed diets which differed in the ratio of polyunsaturated/saturated fatty acids were cultured in IL-2-containing medium and assayed for cytotoxicity. Age-related decline of LAK cell-mediated cytolysis was observed in mice of both H-2b and H-2s haplotype. The age-related decline of LAK cell-mediated cytolysis was the consequence of age-related decrease in the rate of LAK cell precursor maturation. SJL mice fed from birth with diets differing in P/S did not differ in LAK cell-mediated cytolysis.

Aging↗

PubMed1987

Developmental change in the second half of life--strategies for modification of selected compartments of aging.

Age-related changes of different individuals multicentric and polymorphic. We have approached this problem of age-related changes by examining (1) membrane densities of receptors of various ligands in different organs, and (2) changes in different classes of T cells and of antibody response. Three strategies have been developed to modify progression of age-related changes to different extents in different compartments in which age-related changes occur. The first is based on administration of hormones, the second on administration of purine analogues and the third on administration of diets which differ in fatty acid content. Details of this last approach are reviewed in this paper. Lifespan of different species is a component of the evolution of each species. The variables which are decisive in the evolutionary processes which affect lifespans of different species are not necessarily variables which play a decisive role in the different health span of different individuals of the same species. For each individual of a given species, relative health span represents variations within the limits of the evolved lifespan of the species and depends on alleles of many different genes.

Aging↗

PubMed1987

Age-dependent changes in isotype expression and down-regulation of C57BL/6 mice.

Age-related changes in antibody response and tolerance inducibility are polymorphic; in this paper isotype changes in ageing C57BL/6 mice are examined. Female C57BL/6 mice of various ages were immunized with either heat-aggregated RGG (a-RGG) or phosphorylcholine conjugate of RGG (PC-RGG); other animals of the same ages were given aggregate free RGG, followed by injections with either aggregated RGG or haptenated RGG. Sera from these four groups were analysed for antibody isotype. The data presented here indicate that age-related changes in isotype predominance and magnitude are different for different determinants. The capacity to be down-regulated appeared to undergo different age-related changes with different isotypes: there is split tolerance in isotypes. Age-dependent changes in T- and B-cell tolerance could be deduced by comparing responses of animals to hapten and to carrier determinants. In 5-week-old animals tolerance to hapten was more profound than tolerance to carrier. It was concluded that T-cell regulation dominated the response at this age. With advancing age, i.e. by 95 weeks, tolerance is observed in response to hapten but not in response to carrier determinants. We concluded that suppressor cells were induced by aggregate free RGG and affected the response of 'naive' but not of 'experienced' B cells.

Aging↗