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G Agam

Publications and source records attributed to G Agam.

At least 55 records · Page 3Linked to original sources
PubMed1993

Erythrocyte Li+i-Na+o countertransport in the newborn.

The present study investigates the erythrocyte Li+i-Na+o countertransport (CT) in the newborn. Erythrocytes of term infants exhibit no or very low CT activity at birth (0.025 +/- 0.011 mmol Li/l RBC.h). CT rates increase gradually and reach adult values within the 4th-7th day of life (0.225 +/- 0.018 mmol Li/l RBC.h). CT activity in healthy preterm infants at birth is not significantly different from that in term infants (0.014 +/- 0.007 mmol Li/l RBC.h). Postnatal maturation of CT activity in preterm infants is similar to that found in term infants and is independent of gestational age. However, CT rates at birth of premature infants subjected to prenatal stress are significantly higher (0.082 +/- 0.017 mmol Li/l RBC.h). It is concluded that erythrocyte CT activity in the newborn reaches adult values within the first week of life, apparently reflecting the postnatal maturation of the CT system in the cell membrane. We suggest that prenatal stress induces the synthesis of the CT protein in utero.

Antiporters↗
PubMed1992

Copper metabolism--a factor in gestational diabetes?

The purpose of the present work was to investigate whether there is an involvement of copper metabolism in the mechanism of gestational diabetes mellitus. No statistically significant differences were found in serum copper and ceruloplasmin concentrations between healthy pregnant women and women with gestational diabetes mellitus. The activity of ceruloplasmin in women with gestational diabetes mellitus was slightly higher and its specific activity significantly raised. The CuZn superoxide dismutase activity was significantly increased (P < 0.05) in women with gestational diabetes mellitus, comparing the two groups by matched pairs according to age. The results indicate that oxidative stress may have a role in gestational diabetes mellitus and that reduced concentrations of copper are not the cause of this stress.

Adult↗
PubMed1992

Erythrocytes with covalently bound fibrinogen as a cellular replacement for the treatment of thrombocytopenia.

Thrombocytopenia in general, and autoimmune thrombocytopenia in particular, is a disease of high prevalence with a non-satisfactory regime of treatment. The present study aimed to explore the feasibility of an alternative treatment, based on the rationale that autologous erythrocytes modified to bear covalently bound fibrinogen would participate passively in the aggregation of the remaining platelets, thus augmenting the haemostatic needs, while resisting the autoimmune reaction directed towards the platelets. Several procedures for the cross-linking of fibrinogen to red blood cells (RBCs) were tested. Formaldehyde (33 microM) for 10 min at 23 degrees C attached 58 fibrinogen molecules per erythrocyte. These erythrocytes were indistinguishable from untreated erythrocytes in the following properties: osmotic fragility, bound haemoglobin, sedimentation rate, acetylcholinesterase activity, phagocytosis by macrophages, rosette formation with K562 cells. It is shown that RBCs cross-linked with fibrinogen are capable of participating in the in vitro aggregation of platelets and are indeed effective in the in vivo process of arrest of bleeding in an animal model of autoimmune thrombocytopenia.

Animals↗
PubMed1992

Effect of synthetic enantiomeric cannabinoids on platelet aggregation.

The effect of a synthetic pair of enantiomeric cannabinoids on platelet function was evaluated. The nonpsychotropic enantiomer, the 1,1-dimethylheptyl homolog of (+)-(3S,4S)-7-hydroxy-delta-6-tetrahydrocannabinol (HU-211), was found to be more active in inhibiting ADP-induced platelet aggregation than the highly psychotropic (-)-enantiomer (HU-210). The related (+)-(3R,4R) cannabinoid, HU-213, which lacks the 7-hydroxy moiety, exerted its inhibitory effect within a wider range of concentrations. The results indicate a differentiation between psychotropic activity and inhibition of platelet aggregation in the cannabinoid group of compounds.

Adenosine Diphosphate↗
PubMed1990

Role of inositol-1-phosphatase inhibition in the mechanism of action of lithium.

Li inhibition of noradrenergic adenylate cyclase may be due to inhibition by Li of agonist-induced increases in GTP binding to G-protein. Such inhibition by Li of G-protein function could have effects on phosphatidyl-inositol-mediated second messenger systems as well as on cyclic AMP-mediated systems. However, Sherman, Berridge and others have proposed that Li affects phosphatidylinositol metabolism by inhibiting inositol-1-phosphatase. We recently have been able to measure inositol-1-phosphatase in human red blood cells. Preliminary data on patients treated with Li compared with controls suggests that the enzyme is indeed inhibited in vivo in patients undergoing Li treatment. However, a series of experiments in rats on addition of inositol to Li treatment did not find that inositol could reverse Li effects. Chronic oral high dose inositol does not reverse Li-induced polyuria (measured by polydipsia), Li-induced weight loss or Li-induced depression of exploratory behavior. These results suggest that Li inhibition of inositol-1-phosphatase indeed occurs in vivo. However, the physiological significance of inositol-1-phosphatase inhibition is not yet established.

Animals↗
PubMed1989

Thrombin-induced platelet aggregation is affected by external Na+ independently of the Na+/H+ exchange.

Thrombin affects blood platelets by activation of Na+/H+ exchange and induction of aggregation, but the relationship between these effects is under debate. The present study attempts to clarify whether the activation of the exchanger activity is required for platelet aggregation. In apparent support of such a requirement, thrombin-induced aggregation is higher in Na+ medium than in N-methylglucamine+ medium and is inhibited by sphingosine, an inhibitor of protein kinase C known to regulate the Na+/H+ exchanger. However, the inhibition of aggregation by sphingosine occurs in both Na+-containing and Na+-free media, the aggregation is identical in Na+ and K+-containing media, and is not inhibited by 5-N-(3-aminophenyl)amiloride, at a concentration 10-fold higher than its Ki for platelet Na+/H+ exchange. Furthermore, at low concentration (0.005 U/ml) thrombin induces aggregation but does not activate the exchange. It is concluded that the activation of Na+/H+ exchange is not required for thrombin-induced platelet aggregation and that the apparent augmentation of aggregation by Na+ is due to an inhibitory effect of N-methylglucamine+.

Adult↗
PubMed1989

Inositol-1-phosphatase of human erythrocytes is inhibited by therapeutic lithium concentrations.

Lithium is widely used in psychiatric chemotherapy and is especially effective in the treatment of manic-depressive illness (MDI), but the mechanism for its therapeutic properties and side effects remains to be elucidated. One of the possibilities relates to the inhibitory effect of Li+ on inositol-1-phosphatase (I-1-P'ase) activity. Indeed, the concentration of inositol-1-phosphate (I-1-P) after treatment with Li+ was shown to be increased in various mammalian cells. Yet, no direct study of I-1-P'ase activity in human cells has been reported. Erythrocytes are readily accessible for routine studies and could facilitate the investigation of I-1-P'ase as affected by Li+ in relation to MDI. It is now shown that I-1-P'ase can be measured in lysate of human erythrocytes, using a small blood sample. The enzymatic activity is localized in the soluble fraction. The Km for I-1-P is 0.14 mM. Intriguingly, the Ki for Li+ is 0.86 mM, within the range of therapeutic concentrations in MDI patients.

Bipolar Disorder↗
PubMed1988

Resolution and reconstitution of interplatelet recognition during aggregation.

In previous studies it was shown that fixed platelets bearing covalently-bound fibrinogen participate passively in release-related aggregation, and that thrombospondin is the released compound which specifically and selectively recognizes the affixed fibrinogen. The present study demonstrates that the phenomenon of passive participation is also obtained with fixed platelets bearing covalently-bound thrombospondin. Moreover, a full resolution and reconstitution of interplatelet recognition during aggregation was obtained with two different systems: (a) fixed platelets bearing affixed fibrinogen were caused to aggregate when stirred and supplemented with soluble thrombospondin; (b) fixed platelets bearing fibrinogen and fixed platelets bearing thrombospondin, each uncapable of undergoing aggregation, aggregated when combined and stirred. It is concluded that fibrinogen and thrombospondin play a major role in the molecular mechanism of interplatelet recognition during aggregation.

Blood Platelets↗
PubMed1987

Elevated intracellular Ca2+ affects Lii-Nao countertransport in human red blood cells.

Changes in cytoplasmic Ca2+ concentration and in Lii-Nao countertransport activity have been shown to be associated with essential hypertension. Elevated intracellular free [Ca2+], as well as abnormalities of Ca2+ binding and transport have been reported in cells from different tissues of hypertensive laboratory animals and essential hypertensive patients. Similarly, enhanced rates of Lii-Nao countertransport and the modified pattern of the temperature dependence of this activity in red blood cells from essential hypertensive patients have been previously demonstrated. The aim of the present study was to investigate possible interaction between changes in intracellular free [Ca2+] and the Lii-Nao exchange in human red blood cells. The ionophore ionomycin was used to allow Ca2+ incorporation into the cells in a dose-dependent manner. The elevation of intracellular [Ca2+], in turn, resulted in enhanced Li+ efflux from the cells. At 3 microM, ionomycin selectively and significantly enhanced the Lii-Nao countertransport but not Li+ leakage from the cells. EGTA totally abolished the effect of ionomycin, indicating that the effect is directly related to Ca2+. As low as 0.4 microM Ca2+ caused a statistically significant effect. The maximal effect of Ca2+ on the Lii-Nao countertransport was achieved around the external pH range of 6.8-7.5. In contrast, the leakage of Li+ was significantly enhanced by Ca2+ at a pH of 7.4 and above. Ca2+ did not affect the Km of the Lii-Nao countertransport for Li+. Amiloride, which inhibits Na+/H+ exchange, inhibited only 10% of the Ca2+-enhanced countertransport. It is concluded that Ca2+ may play a role in the regulation of Lii-Nao countertransport in erythrocytes.

Antiporters↗
PubMed1985

Lysine binding to activated human platelets and its similarity to fibrinogen binding.

Platelet surface glycoproteins IIb-IIIa are considered to function as the binding site for fibrinogen. Fibrinogen binding is essential for platelet aggregation and several amines have been shown to inhibit this binding. The present study compares the binding properties of 125I-fibrinogen and [3H]lysine with platelets activated by the Ca2+ ionophore A23187. Many lines of similarities in the binding properties are apparent; however, several differences were also found. The similarities are listed below and the differences are pointed out in parentheses. Marked enhancement by platelet activation; deficiency of binding by thrombasthenic platelets lacking the glycoproteins IIb-IIIa; saturability (fibrinogen binding approaches saturation at more than 12 microM, within 10 min; lysine binding at more than 100 mM within 1 min); Ca2+-dependence (at 1 mM Ca2+ lysine binding is minute and fibrinogen binding is half-saturated); reversibility; the binding achieved within 10 min is exchangeable; dissociation depends upon time and external ligand concentration; inhibition by the oligoamines His-Lys and Lys4; inhibition by serum from a thrombasthenic patient who developed anti-glycoproteins IIb-IIIa antibodies; specificity; alanine neither binds to activated platelets nor inhibits fibrinogen binding; it thus appears that the lysine which associates with activated platelets is mostly bound onto the surface of the cells rather than being incorporated. Moreover, the major site of lysine binding seems to be the complexed glycoproteins IIb-IIIa.

Alanine↗
PubMed1985

Fibrinogen fragment D is a recognition site for release-related platelet aggregation.

The present study probes for the segment of the fibrinogen molecule which interacts with the platelet surface upon induction of release-related aggregation. The capability of platelets affixed with fibrinogen fragment D or fibrinogen fragment E to enhance aggregation of gel-filtered platelets (GFP) was compared with that of platelets affixed with fibrinogen. It is shown that release-related aggregation induced by either A23187, 10 microM ADP or thrombin is enhanced by the addition of fixed platelets bearing covalently bound fragment D by as much as 60-70% of the augmentation obtained by platelets bearing fibrinogen. On the other hand, fixed platelets bearing covalently-bound fragment E have no effect on the aggregation of GFP. It is concluded that fragment D bears the site for the interaction of fibrinogen with activated platelets, apparently, with surface-bound thrombospondin.

Adenosine Diphosphate↗
PubMed1984

Platelet-platelet recognition during aggregation: distinct mechanisms determined by the release reaction.

Fixed platelets, bearing covalently bound fibrinogen, were previously shown to participate passively in aggregation induced by thrombin or A23187. The bound fibrinogen was specifically required for the interaction. The present study examines the role of the release reaction in controlling the passive participation of the fixed platelets in aggregation. Aggregation of fresh platelets induced by low ADP concentration (less than or equal to 2 microM) was not augmented by the fixed platelets, but was augmented when higher concentrations of ADP were employed. Fixed platelets failed to enhance aggregation of aspirin-treated fresh platelets induced by 10 microM ADP; the augmentation capability was reconstituted by a supernatant fraction from platelets activated by 10 microM ADP in the presence of EDTA. The binding of soluble fibrinogen to activated fresh platelets occurred regardless of the release reaction, but the interaction of fragmented fixed platelets bearing bound fibrinogen with aggregating fresh platelets was apparent only when release took place. It is concluded that fibrinogen covalently bound to fixed platelets is selectively recognized by released compound(s).

Adenosine Diphosphate↗
PubMed1984

Inhibition of platelet aggregation and endogenous lectin activity by oligoamines.

Amino sugars and basic amino acids inhibit platelet aggregation and the activity of the endogenous platelet lectin, yet, relatively high concentrations (approximately 30 mM) are required for the inhibition. If cooperative interactions are involved in these platelet surface activities, oligomers of primary amines should be more potent inhibitors than their individual component amines. Accordingly, series of oligomers of basic amino acids, of the polyamines (putrescine, spermidine and spermine) and of aliphatic diamines differing in chain length were tested for potency of inhibition of platelet aggregation and endogenous platelet lectin activity. Indeed, oligoamines were much more potent inhibitors of platelet aggregation than their corresponding monomers or shorter oligomers, more than accountable by an additive effect. For example, 60, 3 and 0.3 mM were needed for 50% inhibition of platelet aggregation by lysine, (lys)3 and (lys)5, respectively. A similar pattern was observed for the effect of the oligoamines on the activity of the endogenous platelet lectin. The inhibition of platelet aggregation by spermine is competitive, since the effect of a given dose of spermine decreased with increasing platelet concentration. Neither inhibition of platelet-inducer interaction nor Ca2+ insufficiency explain the inhibitory effects of the oligoamines. The results are consistent with the hypothesis that cooperative surface interactions underlie platelet aggregation and platelet lectin activity. The cooperative effects may reflect the formation of patches or clusters of positively charged groups on the surface of activated platelets.

Amino Acids↗
PubMed1984

Adenosine deaminase activity in lymphocyte subpopulations of B-16 melanoma and normal C57BL bearing mice.

The activity of adenosine deaminase (ADA) was measured in thymus and spleen subpopulations separated by peanut agglutinin (PNA) of melanoma B-16 C57BL bearing mice and normal age-matched C57BL mice. Groups of 10 mice were used each time and the experiments were repeated 6 times. The adenosine deaminase activity in the PNA+ thymocytes of B-16 bearing mice was about 2.5 times lower than that of the normal C57BL mice while the ADA activity in the PNA+ fraction of spleen of the B-16 melanoma bearing mice was 2.5 times higher. These results demonstrate that the tumor burden probably induces a different redistribution and traffic of lymphocytes from one lymphopoietic organ to another. This traffic can also explain the thymus involution and spleen enlargement found in the B-16 mice.

Adenosine Deaminase↗
PubMed1984

Thrombospondin plays a role in platelet-platelet recognition during release-related aggregation.

Fixed platelets, bearing covalently bound fibrinogen, participate passively in aggregation of fresh platelets when the aggregation process is release related (G. Agam and A. Livne, Thromb Haemostasis 51:145-149, 1984). Inhibition of the release by aspirin abolishes the capability of the fresh platelets activated by 10 microM ADP to interact with the fixed platelets. A supernatant fraction from fresh platelets activated by 10 microM ADP (releasate) reconstitutes the interaction. Purified thrombospondin (TSP) replaces the releasate. Moreover, anti-TSP antibodies abolish the reconstituting effect of the releasate. It is concluded that TSP plays a role in the molecular mechanism of platelet-platelet recognition during release-related aggregation.

Adenosine Diphosphate↗
PubMed1983

Passive participation of fixed platelets in aggregation facilitated by covalently bound fibrinogen.

The role of fibrinogen in interplatelet recognition during aggregation was examined by combining two cell types: fresh platelets (in limiting density) activated by thrombin or A23187, and formaldehyde-fixed platelets, bearing cross-linked fibrinogen. The fixed platelets did not aggregate by themselves, nor with resting platelets, but were capable of interacting with activated platelets and of participating passively in aggregation. The participation, expressed by enhanced aggregation, was assayed by the conventional turbidometric traces and by cosedimentation of fixed 3H-platelets with aggregates of fresh platelets. Platelet suspensions, prepared without special means to avert spontaneous activation, retained plasma fibrinogen to the extent of 50 micrograms/ml of a suspension containing 10(8) platelets, and the derived fixed platelets participated in aggregation, independently of added fibrinogen. The capability of such fixed platelets to participate in aggregation was sensitive to proteolytic digestion and to massive acetylation. When platelet separation was aided by apyrase or aspirin, PGE1 and gel filtration, the residual plasma fibrinogen was limited to 0.4 micrograms/ml of 10(8) platelet suspension. The derived fixed platelets were incapable of participating in aggregation unless fibrinogen was added prior to fixation. The affixed fibrinogen could not be replaced by soluble fibrinogen or affixed albumin. It is concluded that fibrinogen, which binds to platelets upon activation or is linked to them covalently, is a recognition site for platelet-platelet interaction during aggregation.

Apyrase↗