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Biomedical subjects

M Aharon

Publications and source records attributed to M Aharon.

18 recordsLinked to original sources

Synergistic effect of interferon-gamma and phorbol myristate acetate on superoxide production by human monocytes.

This study demonstrates a synergistic effect of IFN gamma and PMA on superoxide generation by human monocytes. A strict correlation was observed between the induction of superoxide production and PK-C activation by PMA alone. No such correlation was evident for IFN gamma. However, exposure of the cells to IFN gamma for 10 to 15 hr prior to PMA treatment enhanced both superoxide production and PK-C activation. Using protein kinase inhibitors, we noticed that while PMA exerted its effect by activating PK-C, IFN gamma operated via activation of calcium/calmodulin-dependent or some other calcium-dependent protein kinases. These kinases appeared to be involved in the effect of IFN gamma on superoxide production, as well as in its potentiation of PMA activity.

Cells, Cultured↗

A novel agarose acrobeads protein A column for selective immunoadsorbance of whole blood: performance, specificity and safety.

The present study describes the performance and safety parameters of a novel column composed of protein A linked to acrobeads. Hemoperfusion of anticoagulated whole human blood was carried out in a closed system. Specific adsorption of IgG was documented in whole blood, plasma and IgG diluted in saline. Specific activity of the column was 3.52 mg/ml beads. These studies revealed slight changes in platelet counts and minor hemolysis. The relatively short period needed for maximal hemoperfusion effect and safety may enable the use of this novel therapeutic approach in clinical practice.

Biocompatible Materials↗

Plasma and urine beta-thromboglobulin in severe preeclampsia.

Beta-thromboglobulin (BTG) has been shown to be a specific platelet protein and can be used as a marker of platelet activation in preeclampsia. Concomitant studies of BTG levels in plasma and urine were performed with eight primiparous severe preeclamptic patients and eight normal primiparous women matched for age. The mean plasma BTG in the severe preeclamptic patients was 186.62 +/- 29.93 ng/ml, and in the control group 45.38 +/- 31.84 ng/ml. The P-value for the difference was highly significant (P = 0.000). In contrast, the mean urine BTG in the study group was 8.42 +/- 4.61 ng/ml, while the mean value for the control group was similar, 5.00 +/- 3.20 ng/ml. The P-value for the difference was not significant (0.05 less than P less than 0.10). These results show that urinary BTG cannot be considered an indicator of platelet activation in severe preeclampsia. A low urinary BTG concentration in the presence of high plasma BTG levels may rather express renal impairment. Failure of BTG renal clearance would contribute to further raising the level of plasma BTG.

Adult↗

Plasma antithrombin III levels in pre-eclampsia and chronic hypertension.

Plasma levels of antithrombin III were tested during pregnancy in a control group of normal patients and in a study group that included patients with moderate and severe pre-eclampsia and chronic hypertension. The control group showed mean antithrombin III activity of 97.9 +/- 20.9%, the severe pre-eclamptic patients 22.33 +/- 18.22%, the moderate pre-eclamptic patients 56.0 +/- 7.56%, and the chronic hypertensive patients 77.5 +/- 6.69%. The difference between normal pregnancy and moderate pre-eclampsia was significant at P less than 0.002, normal pregnancy and severe pre-eclampsia P less than 0.002, moderate and severe pre-eclampsia P less than 0.002, chronic hypertension and normal pregnancy P less than 0.1, and chronic hypertension and severe pre-eclampsia P less than 0.002. All the severe pre-eclamptic patients and 2 out of 6 of the moderate pre-eclamptic women were below 55.7% (mean - 2S.D.) of normal antithrombin III activity. Patients with heavy proteinuria had depressed antithrombin III activity. However, chronic hypertensive pregnancies, although rather a small group, had almost normal values of plasma antithrombin III activity. The plasma antithrombin III value may thus help to distinguish between chronic hypertension and severe pre-eclamptic disease.

Adult↗

Beta-thromboglobulin in pre-eclampsia.

Beta-thromboglobulin was tested in blood and urine in a study group of pre-eclamptic patients. The control group comprised a subgroup of normal non-pregnant women and a second subgroup of normal pregnant women. The results of the plasma beta-thromboglobulin blood test revealed no significant difference between the groups, whereas the urine of the pre-eclamptic group showed a significantly increased concentration of beta-thromboglobulin. This difference may reflect renal involvement in the pre-eclamptic patients; the turnover of platelets may be increased but the plasma level of beta-thromboglobulin is apparently maintained by the increased renal clearance.

Adult↗

Impairment of platelet aggregation by Echis colorata venom mediated by L-amino acid oxidase or H2O2.

Echis colorata bites cause impairment of platelet aggregation and hemostatic disorders. The mechanism by which the snake venom inhibits platelet aggregation was studied. Upon fractionation, aggregation impairment activity and L-amino acid oxidase activity were similarly separated from the crude venom, unlike other venom enzymes. Preparations of L-amino acid oxidase from E. colorata and from Crotalus adamanteus replaced effectively the crude E. colorata venom in impairment of platelet aggregation. Furthermore, different treatments known to inhibit L-amino acid oxidase reduced in parallel the oxidase activity and the impairment potency of both the venom and the enzyme preparation. H2O2 mimicked characteristically the impairment effects of L-amino acid oxidase and the venom. Catalase completely abolished the impairment effects of the enzyme and the venom. It is concluded that hydrogen peroxide formed by the venom L-amino acid oxidase plays a role in affecting platelet aggregation and thus could contribute to the extended bleeding typical to persons bitten by E. colorata.

Amino Acid Oxidoreductases↗

Protein kinase activity in liver of heat-acclimated hamsters.

Protein kinase activity in incubated liver slices from 35 degrees C heat-acclimated (HA) hamsters was 70% higher than in similar slices from 23 degrees C control (C) hamsters. Adding glucagon to the incubation medium increased protein kinase activity by 65% in slices from C animals, but by only 30% in slices from HA animals. Binding of [3H]cAMP to proteins of a low-speed supernatant fraction of incubated and homogenized slices was 30% lower for HA than for C hamsters. For each acclimation group this binding was reduced 30% by incubation of the slices with glucagon. The activities of phosphorylase kinase, phosphorylase phosphatase, and phosphorylase alpha in slices incubated with or without glucagon did not differ between groups. Addition of glucagon increased phosphorylase kinase by 30% and phosphorylase alpha by 40% but caused no change in phosphorylase phosphatase activity. These results suggest that heat acclimation of the hamster increases the amount of a species of liver protein kinase that is different from the one that mediates the effect of glucagon on glycogenolysis.

Acclimatization↗

Effect of cannabinoids on the activity of monoamine oxidase in normal human platelets.

Platelet MAO activity was affected by preincubation with cannabinoid derivatives in vitro. The psycho-active derivative delta 1-THC inhibited MAO activity in platelets to an extent varying according to its concentration while CBD and (+) delta 6-THC had no inhibitory effect. (-) delta 6-THC, which is minor psychomimetic component, had less inhibitory effect on MAO activity than delta 1-THC. However, (-) DMH delta 6-THC revealed no attenuation effect on MAO inspite of its well-known psychomimetic activity.

Adolescent↗

Sonographic features of gastrointestinal leiomyosarcoma.

Five cases of gastrointestinal leiomyosarcoma were studied by ultrasound. Sonographic features of a huge mass with a thick echogenic rim and central sonolucent cavitation were seen in four cases with presenting symptoms of an abdominal mass. In a fifth case necrotic metastasis was seen in the liver after removal of a leiomyosarcoma. Although not pathognomonic, such features should strongly suggest the diagnosis of leiomyosarcoma.

Aged↗

Splenic abscess in infancy--diagnosis by ultrasonography.

Splenic abscess is a rare entity in children, and definite diagnosis is seldom made before operation. A case of splenic abscess in a high-risk infant is reported. An accurate diagnosis has been made preoperatively by ultrasonography. Characteristic sonographic findings are described.

Heart Defects, Congenital↗

Congenital hepatic fibrosis with congenital heart disease. A family study with ultrastructural features of the liver.

A family with congenital hepatic fibrosis (CHF) and congenital heart disease (CHD) is presented. The consanguineous healthy parents gave birth to 12 children of whom 10 survived. One son had CHF and CHD, one daughter had CHF and a second daughter had CHD. Three other siblings probably had small a ventricular septal defect and another one probably had mild pulmonary valve stenosis. Development of portal hypertension and hypersplenism necessitated performing shunt operation on both siblings suffering from congenital hepatic fibrosis. Ultrastructural findings were giant mitochondria with large laminar inclusions in hepatocytes, and excess of villi and whorls of membranes and collagen fibrils between hepatocytes.

Adolescent↗

The effect of glucagon and prostaglandin E1 on cyclic AMP levels in liver of heat exposed hamsters.

Cyclic AMP levels in liver slices of hamsters exposed to 35 degrees C for 21 days and controls maintained at 22 degrees C was found to be similar in basal conditions. Glucagon (10 microgram/ml) caused 3.5 times elevation of cyclic AMP levels in control hamsters and 9 times elevation in 35 degrees C exposed hamsters, thus a difference of 150% of the nucleotide concentration was found between the two experimental groups. When 10(-2)M theophylline was added, the cyclic AMP levels were 80% higher in 35 degrees C exposed hamsters both in the presence and absence of 10 microgram/ml glucagon. The difference between controls and heat exposed animals was found to be the same when various concentrations of both glucagon or prostaglandin E1 were added to the liver slices. Adenylate cyclase activity was similar in both experimental groups, while low Km phosphodiesterase was significantly less active in the liver of 35 degrees C exposed animals when compared to the controls.

Adenylyl Cyclases↗

Evaluation of a new polyacrolein microsphere (acrobead) protein A column: an in vitro study using the blood of patients with immune thrombocytopenia or malignancies.

The present study describes the use of a new polyacrolein microsphere (acrobead) protein A column. This method enables immunomodulation by the perfusion of whole blood. The efficacy of the column and its adverse effects following perfusion of blood of patients with immune thrombocytopenic purpura (ITP) or malignancies were investigated. Concurrent experiments in which blood was perfused through an acrobead lactoglobulin column were carried out. Cellular blood components were mildly affected during the procedure. A moderate decrease in platelet number, to a nadir of 90 x 10(3) per microL (90 x 10(9)/L), was documented. During the hemoperfusion of ITP patients' blood, plasma hemoglobin reached levels of 25 to 40 mg per dL, a level similar to that found in banked blood during storage. Plasma tumor necrosis factor level, which serves as an indicator of monocytic activation, increased after 90 minutes of hemoperfusion. IgG and immune complexes were removed. The specific activities (removal of mg Ig/mL bead) of acrobead protein A columns, using blood from patients with ITP or malignancies, were 4.9 and 4.5 mg IgG per mL of bead, respectively. The diminution of platelet-specific IgG in the plasma of patients with ITP was documented as well. There was no activation of the fibrinolytic system as examined by D-dimers. The use of this new technique, which incorporates the method of direct hemoperfusion, is suggested for future clinical studies.

Antigen-Antibody Complex↗

TPK inhibitors differentially affect IFN-gamma activities.

The effect of various tyrosine protein kinase inhibitors on processes involved in the antiproliferative effect of interferon-gamma on WISH cells was studied. Following 24 hr treatment interferon-gamma inhibited thymidine incorporation into DNA and thymidine kinase activity, but no significant effect on cell number was observed. The isoflavonoid, genistein, which is a specific inhibitor of tyrosine protein kinase, reversed the inhibition in thymidine incorporation caused by the cytokine in a dose dependent manner. Prunetin, a member of the same group, did not significantly antagonize this effect. N alpha-tosyl-L-lysyl-chloromethane, a serine protease inhibitor which also serves as a tyrosine protein kinase inhibitor, partially reversed the effect of interferon-gamma at a concentration of 100 microM. The bioflavonoid, quercetin, a non-specific tyrosine protein kinase inhibitor, at a concentration of 30 microM completely abolished the action of interferon-gamma on thymidine incorporation. Genistein completely reversed the inhibition of thymidine kinase exerted by interferon, while quercetin had only a slight effect. However, the drugs could not antagonize the antiproliferative effect of interferon following 48 hr incubation, as measured by reduction of cell number. The results indicate that tyrosine protein kinase may play a role in the effects of interferon on thymidine metabolism and thymidine kinase activity. The differential effects of the inhibitors on thymidine metabolism and cell proliferation could support dissociation between the effect of interferon-gamma on these processes. Alternatively, this dissociation of effects could point to the limited use of inhibitors in clarifying modes of action as described.

Cell Division↗