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Biomedical subjects

D Danon

Publications and source records attributed to D Danon.

At least 19 recordsLinked to original sources
PubMed2006

Prostaglandin E2 induction of labor for isolated oligohydramnios in women with unfavorable cervix at term.

OBJECTIVE: To evaluate the maternal and neonatal outcomes of pregnancies complicated with isolated oligohydramnios at term, managed by induction of labor. METHODS: We conducted a retrospective case-control study. 138 women with uncomplicated oligohydramnios at term [amniotic fluid index (AFI) < or =5 cm] and a low Bishop score (< or =6) underwent induction of labor with prostaglandin E2. These women were compared to 67 women who underwent induction of labor at 42 weeks' gestation and 276 women at low-risk pregnancy and spontaneous onset of labor, matched for parity and race. RESULTS: Cesarean section (CS) rate was similar in the study and the post-date group (17.4 and 17.9%, respectively), but significantly higher than the spontaneous labor group (5.8%, OR 3.42, 95% CI 1.75-6.68). No differences were found with other outcomes. CONCLUSION: Pregnancies with isolated oligohydramnios at term apparently are not at higher risk of perinatal complications, but induction of labor is associated with increased rate of CS.

Case-Control Studies↗
PubMed2004

Macrophage suspensions prepared from a blood unit for treatment of refractory human ulcers.

This paper presents an innovative method for the treatment of refractory wounds, starting with a blood unit, that is based on a biological approach. Local wound repair is one of the major unresolved clinical problems. Age, infection, clinical conditions such as diabetes mellitus, cardiac, renal, lung and liver failure, malnutrition and immunological deficiencies are among the reasons for wound repair delay or failure. Many chronic ulcers resist conventional treatment and do not heal for months and years, thus causing substantial morbidity and even mortality. The method for macrophage suspension treatment consists of introducing into the wound live cells that play a major role in the process of wound healing. The suspension is prepared from a blood unit of a healthy donor in a cost-effective, closed, sterile system. In the process of preparation, the macrophages are activated by hypo-osmotic shock to enhance their various functions in wound repair. The cells are applied to the wound either by local injection or by direct deposition into the wound. In most cases (90%), only one treatment is sufficient. Since 1995, macrophage suspensions have been used successfully in more than 1000 patients in several hospitals in Israel, without any side effects. Our results show that the use of a macrophage suspension is a safe and effective therapeutic strategy that shortens the healing period, reduces risk of complications and morbidity and improves the quality of life for long-suffering patients. This treatment requires no hospitalization and can be given on an ambulatory basis.

Adolescent↗
PubMed2002

Activated macrophages for treating skin ulceration: gene expression in human monocytes after hypo-osmotic shock.

Macrophages play a major role in almost all stages of the complex process of wound healing. It has been previously shown that the incorporation of a hypo-osmotic shock step, in the process of monocyte-concentrate preparation from a blood unit, induces monocyte/macrophage activation. As the macrophages are produced using a unique, closed and sterile system, they are suitable for local application on ulcers in elderly and paraplegic patients. Enhanced phagocytosis by the activated cells, as well as increased secretion of cytokines such as IL-1, IL-6, were detected in a recent study which are in accord with the very encouraging clinical results. In the present study, we used DNA microarrays to analyse the differential gene expressions of the hypo-osmotic shock-activated monocytes/macrophages and compare them to non-treated cells. Of the genes that exhibited differences of expression in the activated cell population, 94% (68/72) displayed increased activity. The mRNA levels of 43/68 of these genes (63%) were found to be 1.5-fold or higher (1.5-7.98) in the activated macrophages cell population as compared to the non-treated cells. Only four genes were found to have lower mRNA levels in the activated cells, with ratios of expression of 0.62-0.8, which may suggest that the changes are insignificant. A significant number of the genes that showed increased levels of expression is known to be directly involved in macrophage function and wound healing. This may correlate with the increased secretion of different cytokines by the activated macrophages depicted previously. Other groups of genes expressed are known to be involved in important pathways such as neuronal growth and function, developmental defects and cancer. The hypo-osmotic shock induces a gene expression profile of cytokines and receptors in the activated cells. These may evoke potential abilities to produce a variety of protein products needed in the wound healing process and may bring to light possibilities for other therapeutic applications of these cells.

Cell Culture Techniques↗
PubMed2001

Lack of known hepatitis virus in hepatitis-associated aplastic anemia and outcome after bone marrow transplantation.

Viral infection has been shown to induce aplastic anemia, unidentified types of hepatitis being the most common cause for aplastic anemia-associated viral hepatitis. The survival rate for this group of patients after bone marrow transplantation with stem cells from an HLA-matched sibling is not well known. The aim of this study was to determine the prevalence of hepatitis G virus (HGV) and transfusion transmitted virus (TTV) infection in non-A, non-B, non-C hepatitis associated-aplastic anemia (HAAA) patients, and to define the role of bone marrow transplantation (BMT) as a therapeutic modality for this disease. Sixty-eight patients (43 males and 25 females) with aplastic anemia, underwent allogeneic BMT at the Hadassah University Hospital between 1981 and 1997. Onset of hepatitis was defined as jaundice and elevated alanine aminotransaminase (ALT) levels. Onset of aplastic anemia was defined as the first date on which varying degrees of pancytopenia occurred: hemoglobin level below 10 g/dl, WBC below 2 x 10(9)/l and low platelet count 10 x 10(10)/l. Serial serum samples from HAAA patients were assayed for virological and/or serological markers of hepatitis A, B, C, D, E, G viruses, TTV and parvovirus B19. Seventeen of the 68 patients with aplastic anemia (25%) suffered from hepatitis, 12 males and five females, ages 5 to 36 years. The mean interval between onset of hepatitis and first indication of aplastic anemia was 62 days (range 14-225 days). The development of aplastic anemia was unrelated to age, sex or severity of hepatitis. Ten of the 17 patients (59%) achieved complete ALT recovery prior to the diagnosis of aplastic anemia. Serum samples were available for 15 patients; none had evidence of acute or active hepatitis A, B, C, D, E, G and TTV virus infection at the time of diagnosis. Parvovirus B19 DNA sequences were not detectable in 10 of 12 tested cases; two positive results were detected in serum samples obtained after blood transfusion, making the analysis of these positive results difficult. All 17 patients underwent BMT. The mean post-BMT follow-up period was 38 months (range 1 day-123 months), five patients (30%) died 1 to 160 days post BMT, and 12 (70%) are alive 31 to 123 months after BMT. Relapsing hepatitis was not observed in any of the patients. In conclusion, HAAA is a disease of the young and the etiologic agent associated with HAAA remains unknown. HGV, TTV and parvovirus B19 sequences were not detected in any of the HAAA cases. The survival rate after BMT with stem cells from an HLA-matched sibling is similar to that for patients with non-hepatitis-associated aplastic anemia.

Adolescent↗
PubMed2001

Activation of human monocytes/macrophages by hypo-osmotic shock.

Phagocytosis and secretion of interleukins and growth factors put the macrophage in the centre of the wound healing process. For the last four years over 400 human ulcers have been treated in elderly and paraplegic patients by local application of monocytes prepared from a blood unit, in a unique, closed, sterile system. The process of preparation includes a step of hypo-osmotic shock, which induces monocyte/macrophage activation. This is different from any other known method of activation. In the present study we evaluated the efficacy of the hypo-osmotic shock. We found enhanced levels of IL-1 (P = 0.004) and IL-6 (P = 0.001) in the incubation medium (100% autologous serum) of the activated cells, as compared with controls, prepared in the same system. The IL-1 reached a plateau after 6 and 12 h incubation at 37 degrees C, in both experimental and control incubation medium. The level of IL-6 was further elevated after 12 and 24 h incubation in experimental and control incubation mediums (P = 0.001). The phagocytosis of fluorescent beads was markedly enhanced after hypo-osmotic shock (P = 0.005). The osmotic shock induced macrophages were compared to those stimulated with LPS, and osmotic shock was proved to be at least as efficient method of stimulation as LPS.

Culture Media, Conditioned↗
PubMed1999

Maze learning impairment is associated with stress hemopoiesis induced by chronic treatment of aged rats with human recombinant erythropoietin.

Mean cell volume (MCV) of erythrocytes has been reported to increase with age in humans, and to be negatively correlated with memory performance in humans and rats. We evaluated hematological changes in 21-mo old male Fischer 344 rats undergoing a 3-mo twice weekly subcutaneous injection of human recombinant erythropoietin (EPO). A baseline hematocrit (HCT) was obtained initially and repeated at monthly intervals to determine the effectiveness of EPO treatment. At 24-mo of age and after 3 mo EPO treatment, the rats were tested for their ability to learn a 14-unit T maze. Following maze testing, blood was drawn for hematologic analyses, including HCT, MCV, maximum swollen cell volume (MCVS), mean cell transit time (MCTT), and the membrane shear modulus of elasticity (G), the latter a derived measure of the relative elasticity of the red cell membrane. After 1 mo EPO treatment, HCT significantly increased compared to saline-injected controls. After 2 mo treatment, HCT began to decline but remained elevated above baseline levels even after 3 mo treatment. After 3 mo EPO treatment, MCV was significantly lower in EPO-treated rats compared to controls. These changes imply altered hemopoiesis to produce cells which undergo shrinkage associated with accelerated cellular aging. The lower MCV would have predicted a shorter MCTT which instead was unchanged. This observation suggested the presence of an additional factor contributing to the MCTT. The G, which measures the membrane contribution to deformability, very significantly increased with EPO treatment. This finding indicates an increased contribution of membrane properties to the MCTT after EPO treatment, which cancels the expected decrease in MCTT for smaller cells. After 3 mo of EPO treatment, aged rats exhibited significantly impaired maze learning compared to controls. A relationship between, changes in erythrocyte membrane properties and impaired function was indicated by a significant correlation (r=0.67, p <0.04) between G and errors in the 14-unit T-maze. These findings suggest that stress-induced erythropoiesis produces accelerated aging in the red blood cell population that may have functional implications (i.e., impaired learning ability).

Aging↗
PubMed1996

Chronic treatment with human recombinant erythropoietin increases hematocrit and improves water maze performance in mice.

Erythropoietin is a glycoprotein produced endogenously in the kidney, which stimulates red blood cell production. We evaluated the effects of chronic treatment with recombinant human erythropoietin (epoetin alfa: EPO) on the performance of 6-month-old male C57BL/6J mice in a spatial learning task, the Morris water maze. Mice were treated with either EPO (1.5 U injected SC every other day) or vehicle (PBS also injected SC every other day). Results indicated that the treatment had no effect on maze performance after 8 weeks, but after 19 weeks the EPO-treated mice showed better performance compared to controls as measured by mean distance (centimeters) to reach the goal platform. The improved performance in EPO-treated mice at 19 weeks was accompanied by an increased hematocrit. After 32 wk of EPO-treatment, the hematocrit returned to baseline levels even though the size and density of the red blood cells were increased.

Animals↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1991

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↗
PubMed1990

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↗
PubMed1989

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↗
PubMed1988

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↗
PubMed1987

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↗
PubMed1986

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↗
PubMed1985

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↗