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Biomedical subjects

D Danon

Publications and source records attributed to D Danon.

At least 19 recordsLinked to original sources

Memory performance of young and old subjects related to their erythrocyte characteristics.

Several papers reported in recent years on a change in the age population distribution of the circulating erythrocytes in old mice, rats, rabbits, and humans. The results indicate the presence of a chronologically younger cell population in old animals and humans. The cells are typically lower in density and larger. In some reports, the cells have higher levels of enzymatic activity. We wanted to know whether changes in the characteristics of the circulating erythrocytes in old people are related to the changes in cognitive performance often observed in the elderly. Twenty young (20-40) and 21 old (70-90) volunteers submitted to memory and blood tests. Density and size distribution, aspartate aminotransferase/glutamic oxalacetic transaminase (AST/GOT) activity, and the level of glycosylated hemoglobin (HbA1) of erythrocytes were determined. The Wechsler Memory Scale--Revised (Wechsler, 1987) was used to determine general memory and delayed recall scores for each subject. We have confirmed that old subjects have larger and less dense cells. Erythrocyte volume was the only blood parameter examined that revealed statistically significant correlations with memory performance. The old subjects with no age-related memory impairment had significantly smaller cells than the other old subjects.

Adult

Life span of erythrocytes in late pregnancy.

OBJECTIVE: Based on previous studies that demonstrated lighter and larger erythrocytes in late pregnancy, we hypothesized that the life span of erythrocytes in late pregnancy is shorter than in nonpregnant women. METHODS: We used the density distribution of cells to evaluate the age distribution of erythrocytes in pregnant versus nonpregnant women and rats. The life span of erythrocytes was compared between pregnant rats and nonpregnant syngeneic rats of the same age using 51Cr for labeling erythrocytes. RESULTS: Based on the density distribution of cells, a similar shift to lighter erythrocytes was found comparing pregnant to nonpregnant women and rats. The pregnant rat erythrocytes had a shorter life span by 9.2% (33.6 versus 36.9 days; P = .0010). CONCLUSIONS: The life span of erythrocytes in pregnant rats is shorter than in nonpregnant ones. A similar shift in the age distribution of pregnant rat and pregnant human erythrocytes is probably associated with a similar life span of pregnant rat and pregnant human erythrocytes. The shorter life span of erythrocytes in late pregnancy may be attributed to higher erythropoietin levels in pregnancy, which induce "emergency hematopoiesis" resulting in younger reticulocytes and macrocytic erythrocytes, which are known to have a shorter life span.

Adult

The effect of selective desalivation on wound healing in mice.

The effectiveness of wound licking in the acceleration of wound healing was evaluated in selectively desalivated mice. Rate of healing of experimentally induced cutaneous wounds was evaluated macroscopically by photography at 0, 2, 4, and 6 days after wounding. Sialadenectomy of submandibular and sublingual glands significantly slowed down wound healing in animals caged together compared to sham-operated controls. Separate caging as compared to caging in groups slowed down healing in sham-operated animals at day 2 but not at day 4 and 6. No effect on the rate of healing in sialadenectomized mice was observed in separate caging compared to mice caged in groups. Ligation of the parotid duct had an insignificant effect. The rate of wound healing of sublingual sialadenectomized mice was slower than that of sham-operated controls, but not as slow as those of sublingual and submandibular sialadenectomized mice. The results suggest that the rate of healing of experimentally induced cutaneous wounds of mice is slowed down when licking is prevented by separate caging which confirms previous reports. Licking with submandibular saliva seems to be more effective than sublingual saliva. Parotid saliva or minor salivary glands secretions are the least effective.

Animals

Age population distribution of erythrocytes in young and old healthy donors.

Reports from several laboratories on a shorter life span of erythrocytes (E) in old animals and humans, induced the authors to search for a simple method for determining the younger age distribution of E in the blood of 20 old (over 70), as compared to 20 young (below 40), healthy donors. The following tests were performed: 1) Density Distribution of Cells (DDC), 2) Osmotic Fragility, 3) Agglutinability of E by Poly-L-lysine, 4) Analysis of Aspartate Amino Transferase (AST) activity, 5) Test for the presence of immunoglobulin on the surface of E (rosette formation on K562 cells); and 6) All the usual clinical and hematological tests were performed in order to avoid pathology. The most significant difference between the blood of the young and the old was found in the DDC. The shift of the cumulative curve indicated a younger population of cells in the blood of the elderly. The activity of AST was higher in the blood of the elderly, also indicating a younger cell population. The rosette formation was higher with the E from the blood of the elderly, indicating that the E, had more immunoglobulins on their surface than the E from the blood of the younger donors.

Agglutination Tests

Promotion of wound repair in old mice by local injection of macrophages.

Application of peritoneal macrophages to experimentally induced cutaneous wounds of old mice accelerates healing to levels almost comparable to those of untreated young animals. Slightly greater acceleration is observed when macrophages are obtained from young as opposed to old donors. These findings are consistent with a defect in macrophage function as a cause of impaired wound healing in senescence and suggest a possible therapeutic strategy.

Aging

The aging of the red blood cell. A multifactor process.

Red blood cell (rbc) senescence is associated with loss of surface sialic acid, which is the principal carrier of surface negative charge and determines the electrokinetic behavior of old rbcs. Loss of sialic acid in an old rbc is demonstrated in its decreased electric mobility and lower negative charge density, determined topographically with cationic particle labeling. Surface sialic acid determines also the mutual attraction--repulsion forces, as demonstrated in enhanced aggluinability with cationic molecules, lectins, and blood group antibodies. Loss of sialic acid accompanies ATP-depletion in vitro; thus, a T-antigen site is unmasked. Macrophages have specific receptors to the site as to newly exposed galactose and N-acetyl galactosamine sugars. Furthermore, the involvement of complement molecules in the recognition of old RBCs by macrophages has been shown. This is possibly due to loss of sialic acid or at least a regrouping--relocation of surface anionic sites due to cell shape changes from discocytes to crenated forms, which accompany both in vivo and in vitro rbc aging. In turn, shape changes are apparently controlled by the cytoskeletal network underlying the rbc membrane, which undergoes structural alteration with physiologic aging in changing the dimensions of oligomeric spectrin and the thickness of the spectrin-actin cytoskeletal assembly.

Animals

Wound repair in mice as influenced by age and antimacrophage serum.

The closure of bilateral, full-thickness cutaneous wounds made over the back with a sharp paper punch was measured with calipers and assessed histologically in C57BL/6J male mice for 10 days after wounding. Young (6 months) mice exhibited a significantly more rapid rate of wound closure and repair than did mature (15 months) or aged (26 or 27 months) mice. The repair rate in mature and aged mice did not differ. Young mice, injected subcutaneously at the wound sites with rabbit antimouse macrophage serum (RAMMS) 5 min before wounding and on days 1 and 3 after wounding, exhibited slow delayed closure of cutaneous wounds during days 1 to 4 after wounding, similar to that of untreated aged mice. The early closure rate of mice injected with normal rabbit serum or physiological saline was rapid, resembling that of untreated young mice. The results suggest that cutaneous wound repair in mice is another physiological phenomenon whose rate of change is age related, but not necessarily progressive to senescence. The results also imply that macrophage functional decline may contribute to the slowing of wound repair in middle-aged and aged mice compared to young mice.

Aging

The natural anti-alpha-galactosyl IgG on human normal senescent red blood cells.

A highly sensitive antiglobulin test based on rosette formation due to the interaction between IgG bearing red blood cells (RBC) and Fc receptors on K562 cells, was used to study the immunoglobulin molecules present on human senescent RBC. Normal human RBC were separated into young and senescent subpopulations on the basis of age-dependent differences in density by centrifugation on a discontinuous density Percoll gradient, and by flotation on phthalate ester mixtures. The senescent but not the young RBC were found to bear membrane bound IgG. Most of the bound IgG molecules could be specifically eluted by galactose in its alpha-anomeric form. Antigalactosyl (anti-Gal) IgG antibodies with similar reactivity were found to be present in high titres in every one of the 400 normal human sera tested. The natural anti-Gal antibodies isolated from normal sera by affinity chromatography could bind to IgG depleted senescent RBC but not to young RBC. Erythrophagocytosis experiments indicated that the anti-Gal bound to the senescent RBC induced their destruction by macrophages. It is suggested that the natural anti-Gal antibodies interact with cryptic alpha-galactosyl residues which are exposed in the course of the RBC senescence and mediate the removal of these RBC from circulation by cells of the reticuloendothelial system.

Carbohydrates

The relationship between sialic acid content and peanut agglutinin binding on senescent and enzyme treated human erythrocytes.

Young, old and neuraminidase treated human red blood cells (RBC) were investigated with peanut agglutinin (PNA), a lectin with a specificity similar to that of serum T-agglutinin. The effect of serum agglutinins on this interaction was also investigated. The density and distribution of PNA receptors were evaluated by agglutination with PNA and binding of ferritin-conjugated PNA (PNA-F), or PNA labeled with radioactive iodine [( 131I] PNA). The results were correlated with the distribution of membrane bound sialic acids, as evaluated by chemical analysis and rate of agglutination with poly-L-lysine (PLL). Untreated RBC of all ages did not agglutinate with PNA and failed to bind PNA-F and [131I] PNA. Treatment of young RBC with neuraminidase, which resulted in reduction of membrane-bound sialic acids to an extent similar to that of physiologically aged RBC, resulted in the concomitant exposure of PNA binding sites and in the agglutination of these cells by autologous serum. Pretreatment of the neuraminidase treated RBC with autologous serum resulted in partial inhibition of the binding capacity of PNA on the RBC. The results indicate that the normal age-related loss of sialic acids in circulating RBC is not identical with enzymatic removal of sialic acids by neuraminidase. The observations suggest that different mechanisms are functional in the recognition and sequestration of old RBC and of RBC treated with neuraminidase.

Erythrocyte Aging

Changes of cell shape and surface charge topography in ATP-depleted human red blood cells.

ATP depletion crenates human red blood cells. With ferritin-avidin (FA) and cationized ferritin (CF) cell surface labeling, it is demonstrated that the discocyte----crenated shape transformation alters the two-dimensional topography of negative charge sites. With restoration of ATP levels, cell shape and charge topography return to normal. Concurrent changes in red cell shape and surface charge topography can be explained by associations between membrane integral proteins and the red cell cytoskeleton.

Adenosine Triphosphate

Promotion of wound healing by yeast glucan evaluated on single animals.

The effectiveness of yeast glucan in the acceleration of wound healing was evaluated in mice, rats and guinea pigs. In all experiments comparison between glucan treatment in one hind leg and saline treatment as control on the other leg was made on identical wounds. The degree of healing in the two legs was evaluated macroscopically and classified as follows: 1. healing more advanced in glucan treated wound marked by (+). 2. No significant difference between the two legs marked by (0). 3. Healing more advanced in the control wound, marked by (-). During the days when the differences were most obvious, 60% to 80% of the animals showed more advanced healing in the glucan treated wound, 20% to 40% showed no significant difference; and 0 to 15% showed more advanced healing in the control, saline treated wound. The average time for complete wound healing was reduced by about 18% as a result of glucan treatment. The histological analysis shows that the acceleration of wound healing was mediated by early arrival of macrophages to the wound area in the glucan treated wounds.

Animals

Separation of human spermatozoa from a single ejaculate into various age-groups.

Ejaculated human spermatozoa were separated into various age-groups on the basis of their different specific gravity. Salt-poor 25% human serum albumin was used as a separation medium. The separation process had no detectable harmful effect on the spermatozoa. The motility and penetration abilities of the separated cell fractions were tested by means of a new method using a fragiligraph. The younger group of spermatozoa demonstrated better motility and penetration ability in comparison with the older age-groups.

Adult

Phagocytosis of nucleated and mature beta thalassaemic red blood cells by mouse macrophages in vitro.

Physiological or experimental decrease in sialic acid (SA) content on the red blood cell (RBC) membrane is believed to play an important role in the recognition of these cells by macrophages. Since there is a 20-30% decrease in the SA content on the membrane of thalassaemic RBC, the interaction between macrophages and these RBC was studied in vitro. Using mouse peritoneal macrophages, it was found that these macrophages 'recognize' and phagocytize thalassaemic RBC while RBC from normal donors are hardly phagocytized. The average level of phagocytosis of thalassaemic RBC from splenectomized patients was found to be 22-fold higher than that of RBC from normal donors. The phagocytized cells consisted of both mature and nucleated RBC. Mouse peritoneal macrophages seem to be a useful in vitro system for the study of the accelerated sequestration and shortened life span of thalassaemic RBC.

Animals

Surface charge characteristics of cells from malignant cell lines and normal cell lines of the human hematopoietic system.

Cells from malignant and normal lines of human hematopoietic origin were studied for their surface charge characteristics with the use of the following criteria: 1) the electron microscopic appearance of cell membranes after labeling with cationized ferritin (CF) either before or after glutaraldehyde fixation, 2) electrophoretic mobility, 3) total sialic acid content, and 4) agglutinability with poly-L-lysine (PLL). CF induced a time-dependent redistribution of surface receptors in unfixed malignant cells but not in unfixed normal cells. After 10 seconds of labeling with CF, both normal and malignant unfixed cells showed a uniform and even labeling pattern. After 5 minutes of labeling, malignant cells exhibited a highly pronounced pattern of clusters and patches, as distinct from a random and even pattern exhibited by normal cells. Both normal and malignant cells after fixation exhibited an equivalent random and even labeling pattern with CF, independent of the duration of labeling. The malignant cells studied possessed less sialic acid, had a lower electric mobility, and were agglutinated more readily with PLL than were the normal cells.

B-Lymphocytes