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Biomedical subjects

A Aviram

Publications and source records attributed to A Aviram.

At least 19 recordsLinked to original sources
PubMed1992

Novel anticancer prodrugs of butyric acid. 2.

The antitumor activity of novel prodrugs butyric acid was examined. The in vitro effect of the compounds on induction of cytodifferentiation and on inhibition of proliferation and clonogenicity showed that (pivaloyloxy)methyl butyrate (1a) (labeled AN-9) was the most active agent. SAR's suggested that its activity stemmed from hydrolytically released butyric acid. In vivo, 1a displayed antitumor activity in B16F0 melanoma primary cancer model, manifested by a significant increase in the life span of the treated animals. Murine lung tumor burden, induced by injection of the highly metastatic melanoma cells (B16F10.9), was decreased by 1a. It also displayed a significant therapeutic activity against spontaneous metastases which were induced by 3LL Lewis lung carcinoma cells. Moreover, 1a has the advantage of low toxicity, with an acute LD50 = 1.36 +/- 0.1 g/kg (n = 5). These results suggest that 1a is a potential antineoplastic agent.

Animals↗
PubMed1991

Derivatives of butyric acid as potential anti-neoplastic agents.

A novel derivative of butyric acid, pivalyloxymethyl butyrate (AN-9) has been shown, in vitro, to: (a) induce cytodifferentiation and inhibit the proliferation of leukemic cells; (b) inhibit the growth and formation of Lewis lung carcinoma colonies in semi-solid agar. AN-9 affect cells at about 10-fold lower concentration and at a faster rate than does butyric acid. The pivalyloxymethyl esters of propionic, isobutyric and valeric acids do not elicit effects similar to those of AN-9, while the isobutyryloxymethyl butyrate does, which strongly suggests that the activity of AN-9 stems from intracellular metabolic degradation of the pro-drug to butyric acid. In vivo, AN-9, increased the survival of mice in Lewis lung carcinoma primary cancer model and significantly decreased the number of lung lesions of the animals inoculated with highly metastatic cells, but did not affect their life span. Acute LD50 studies have shown that AN-9 possesses low toxicity. These results suggest that AN-9 is a potential anti-neoplastic agent as well as a tool for investigation of the differentiation induction mechanism.

Animals↗
PubMed1990

Proliferation-associated changes of Ca2+ transport in myeloid leukemic cell lines.

Proliferation-associated changes in calcium metabolism were investigated employing the promyelocytic HL-60 and monoblastic U-937 cell lines. The cells were stimulated to proliferate employing mitogenic factors as follows. 1) Transferrin or insulin: HL-60 cells were adjusted for growth in serum-free medium, and 24 h prior to the experiment, the cells were deprived of transferrin or insulin. The re-addition of either one of them stimulated cell proliferation as was evident by increased [3H]-tymidine incorporation activity. Cell proliferation was associated with an enhanced Ca2+ influx rate, measured by 45Ca2+ uptake activity. 2) Granulocyte-monocyte colony-stimulating factor (GM-CSF): addition of GM-CSF to proliferating or quiescent HL-60 cells resulted in increased cell proliferation, which was also accompanied by increased rate of Ca2+ influx. 3) Serum: HL-60 and U-937 were grown for 24 h in serum-depleted medium. Re-addition of serum to the cells was not associated with immediate or delayed change in calcium influx rate but rather with an immediate increase in the cytosolic free calcium concentration, measured employing the fluorescent probe, fura-2AM. This increase was independent of extracellular calcium, unaffected by verapamil, diltiazem, and lanthanum, and associated with enhanced 45Ca2+ efflux. Thus, in all three cases evoked cell proliferation was accompanied by quantitative changes in Ca2+ metabolism. While the transferrin-, insulin-, and GM-CSF-stimulated cell proliferation was accompanied by delayed increases in 45Ca2+ influx, the serum-stimulated cell proliferation was accompanied by an immediate elevation of free cytosolic Ca2+.

Biological Transport↗
PubMed1990

The role of increased calcium influx rate in receptor mediated function of differentiating HL-60 cells.

In this study we have investigated the link between increased Ca2+ influx rate, acquired upon the differentiation of HL-60 cells, to changes in cytosolic free Ca2+ ([Ca2+]i], evoked by the chemotactic peptide-FMLP and the mitogen Con-A. Although differentiating and undifferentiated HL-60 cells exhibited similar steady-state levels of [Ca2+]i, cells induced to differentiate by dibutyryl-cAMP, at 48 h, exhibited enhanced Ca2+ influx rate, measured by non-steady state 45Ca2+ uptake, and augmentation of FMLP-stimulated Ca2+ influx. At 120 h the above cells responded to FMLP but not to Con-A, by a marked augmentation of Ca2+ influx, and elevated levels of [Ca2+]i. On the other hand HL-60 cells induced to differentiate by retinoic acid responded, as described above, to Con-A but not to FMLP. HL-60 cells grown in the presence of cholera-toxin, were reported to express high levels of FMLP-receptors without expressing cell differentiation. We have demonstrated that, in these cells the Ca2+ influx rate was unchanged, moreover, FMLP-stimulated Ca2+ influx and [Ca2+]i rise were low. These findings strongly suggest that the presence of receptor is not sufficient for FMLP-mediated changes in [Ca2+]i. A link between increased Ca2+ influx rate, acquired upon induction of differentiation, and receptor mediated response in these cells is proposed.

Bucladesine↗
PubMed1990

The role of calcium in differentiation of leukemic cell lines.

Increased calcium influx associated with differentiation of four human myeloid leukemic cell lines: HL-60, KG-1, U-937 and K-562, to either monocytic or granulocytic direction was demonstrated. Calcium influx was measured employing two methods; measurement of radioactive calcium influx rate at 4 degrees C and employing the fluorescent probe, fura-2 acetoxymethyl ester. The increase in Ca2+ influx was demonstrated with three chemically unrelated differentiation inducers: retinoic acid, 1 alpha, 25 dihydroxy vitamin D3 and dimethyl sulfoxide. Inhibitors of calcium uptake such as verapamil diltiazem and cromolyn, partially reduced differentiation, suggesting that differentiation of myeloid leukemic cell lines is dependent on the availability of extracellular calcium.

Calcitriol↗
PubMed1989

Newly recognized ectrodactyly/deafness syndrome.

A 7-year-old non-Ashkenazi Jewish girl is described having asymmetrical ectrodactyly (split hand and foot deformity), short stature, mental retardation, sensorineural deafness, and abnormal facies. Because this constellation of findings has not been reported previously, the authors believe that this represents a new congenital malformation syndrome, most probably of genetic etiology.

Abnormalities, Multiple↗
PubMed1989

Protein intake and kidney function in humans: its effect on 'normal aging'.

The effect of dietary protein on kidney function expressed by creatinine clearance was studied in healthy subjects following a "normal" unrestricted protein diet and compared with a group of vegetarians maintained on a long-term low-protein diet. Both groups had similar kidney function and displayed the same rate of progressive deterioration in renal function with age. These results suggest that, in contrast with the important therapeutic effect of low-protein intake on the progressive deterioration of kidney function in diseased kidneys, such a diet does not significantly affect kidney function with "normal aging" in healthy subjects.

Adult↗
PubMed1988

Differentiation-associated changes of cation-transport activities in myeloid leukemic cell lines.

Induction of differentiation in HL-60 and U-937 leukemic cell lines, resulted in 1.5-10-fold increase in 45Ca2+ uptake. The increased 45Ca2+ uptake in the differentiating cells was inhibited by verapamil, cromolyn and amiloride. Elevation in Ca2+ uptake in differentiating cells was also demonstrated using the fluorescent probe, fura-2 acetoxymethyl ester. The increased 45Ca2+ uptake was accompanied by a decrease in ouabain-insensitive and -sensitive 86Rb+ uptake. Furthermore, correlation between the changes in these activities was observed. Modulation of extracellular pH affected differentiation: higher pH increased the extent of differentiation.

Amiloride↗
PubMed1987

Fluoride-mediated activation of guinea pig neutrophils.

In guinea pig peritoneal neutrophils NaF at a concentration of above 5 mM elicited a dose-dependent, delayed and sustained activation of NADPH oxidase. Unlike in human neutrophils, in guinea pig cells, this response was independent of extracellular calcium. Fura2 fluorescence measurements indicated also a fluoride-mediated moderate elevation in the level of cytosolic calcium concentration. Pretreatment of neutrophils with pertussis toxin, blocked fluoride-promoted activation of NADPH oxidase, indicating that NaF stimulation was mediated by a G protein which is a pertussis toxin substrate. NaF-elicited calcium elevation was insensitive to the toxin. Upon transfer of NaF-stimulated cells to a fluoride-free medium, superoxide release declined and calcium levels diminished. The response of the deactivated, fluoride-prestimulated guinea pig neutrophils to a secondary stimulation with phorbol myristate acetate (PMA) or fMet-Leu-Phe, was either unaffected by the previous challenge with NaF (PMA) or augmented by it (the chemotactic peptide). In parallel to the activation of NADPH oxidase, NaF also induced translocation of protein kinase C to cell membranes. This effect was also abolished by a pretreatment with pertussis toxin.

Animals↗
PubMed1987

Prolonged volume depletion imitating end-stage renal failure.

Four patients with chronic renal insufficiency were erroneously diagnosed as reaching the "end stage" of their disease. All of them had had insidious salt and water depletion prolonged over a period of 5 to 8 weeks. The correct diagnosis was missed because the signs and symptoms of slowly developing volume depletion were indistinguishable from the clinical picture of terminal uremia. Correction of the salt and water depletion was followed by marked clinical improvement and return of renal function to baseline values. Postural hypotension and hyponatremia are important clues for the diagnosis of insidiously developing mild or moderate volume depletion super-imposed on chronic renal insufficiency.

Aged↗
PubMed1987

Cardiac arrhythmia during chronic ambulatory peritoneal dialysis.

Repeated bouts of ventricular tachycardia were triggered by the inflow of dialysate during acute peritoneal dialysis performed in a 79-year-old woman. Subsequent continuous Holter monitoring of 21 patients, many elderly and with cardiac disease, undergoing chronic ambulatory peritoneal dialysis (CAPD) revealed atrial and/or ventricular premature beats in 19 out of them. However, there were no differences in the type and frequency of the extrasystoles between the recordings performed on a day of dialysis or on a day on which dialysis was deliberately withheld. No new arrhythmias were seen in the 2 patients who were previously free of arrhythmias, in whom CAPD was undertaken. It seems that CAPD does not provoke or aggravate arrhythmias, even in elderly or cardiac patients.

Adult↗
PubMed1987

Hypertension in European immigrants to Israel--the possible effect of the holocaust.

To examine the effect of stressful life events and chronic emotional distress in the development of hypertension, we compared the blood pressure of 1,150 Israelis (aged 50 to 80) who immigrated from Europe before 1939 with that of 2,159 European-born Israelis who immigrated to Israel after World War II. Most of the subjects were examined as part of a periodical health examination offered by their employers. There were only minor differences in age, height, country of origin and level of education between the two groups. There was no difference in the prevalence of hypertension between the two immigration groups, and a similar percentage of both groups were receiving treatment. Hypertension was defined as any one or more of the following: supine systolic greater than or equal to 160 mm Hg, diastolic greater than or equal to 95 mm Hg, or treatment with antihypertensive medications. Analysis of variance showed that age, sex and degree of obesity were the main factors contributing to the blood pressure. Although the degree of emotional stress was greater in the Holocaust survivors, there was no correlation between level of emotional distress, satisfaction with life or number of psychosomatic complaints and level of blood pressure or prevalence of hypertension.

Aged↗
PubMed1987

Routine urinalysis (dipstick) findings in mass screening of healthy adults.

We present results of simple urinalysis examinations (dipstick) in a large (approximately 21,000 people) working population. In about 10% of the screened individuals at least one abnormality was found. In men the most common finding was proteinuria (4.9%). Hematuria was found in 2.6% and glycosuria in 0.6%. The most prevalent finding in women was hematuria (8.1%), followed by proteinuria (3.9%) and glycosuria (0.6%). Only about 1% of the examinees had two or more abnormalities in their urine examinations. These findings attest to the utility and practicability of incorporating urine testing into various screening and clinical examinations.

Adult↗
PubMed1986

Bilateral metachronous xanthogranulomatous pyelonephritis in end-stage renal failure.

We report a case of bilateral metachronous xanthogranulomatous pyelonephritis (XGP) in a hemodialyzed patient with end-stage renal failure due to bilateral nephrolithiasis. The XGP was initially diagnosed by computed tomographic (CT) scan, and right nephrectomy was performed. The patient remained clinically stable for the next year. Involvement of the contralateral kidney was again confirmed by CT examination. Both kidneys showed histologic changes compatible with XGP. A coexisting nephrogenic adenoma of the bladder has been attributed to chronic urinary tract infection.

Female↗
PubMed1985

Activation of guinea-pig and bovine neutrophil NADPH oxidase by N,N'-dicyclohexylcarbodiimide.

Dicyclohexylcarbodiimide (DCCD) is a potent stimulant of superoxide generation in guinea-pig peritoneal and bovine blood neutrophils. The dependence of DCCD-elicited respiratory burst on the composition of the medium was investigated. At 37 degrees C, the superoxide generation was short-lived and a rapid losses of enzymatic activity was observed; at 0 degree C, the activity could be preserved for hours. Superoxide generation by whole cells was accompanied by exocytic degranulation. Prolonged incubation with DCCD at 37 degrees C resulted also in a progressive loss of cellular integrity evidenced by the release of a fraction of lactate dehydrogenase. Km values of the particulate NADPH oxidase isolated from DCCD-triggered guinea-pig and bovine cells were 31.7 and 50.0 microM, respectively. Cells pre-equilibrated with the potential sensitive dye Di-S-C3-(5) exhibited changes in the transmembrane potential upon stimulation. Stimulation with DCCD resulted also in the release of membrane-associated calcium, indicated by quenching of the fluorescence of chlortetracycline-loaded neutrophils. Both effects were observed also in human neutrophils which did not generate superoxide upon exposure to DCCD. The mechanism of DCCD-induced responses is discussed.

Animals↗
PubMed1985

Inhibition of lymphocyte response to mitogens by dipyridamole: preliminary findings.

It has been recently noted that dipyridamole (DP) may be involved in certain immunological reactions, in addition to its antiplatelet action. In the present investigation the mitogenic response of human lymphocytes from three groups of subjects to 3 different lectins was examined. In both the experimental group treated over a short period and in the controls a highly significant decrease in the mean lymphocyte response to all 3 mitogens was noted following 3 days of DP administration. The response remained low after an additional 3 days of treatment. Discontinuation of drug administration was followed by a significant increase in response to two mitogens, concanavalin A (Con A) and pokeweed mitogen (PWM). The response to phytohaemagglutinin (PHA) extent only increased to a small, non-significant. No change in the mean mitogenic response was detected in the group undergoing long-term treatment. The mechanism by which DP alters lymphocyte activity is as yet unknown.

Adult↗
PubMed1985

Gentamicin serum half-life: a comparison between pregnant and non-pregnant women.

The serum half-life of gentamicin following an intravenous dose was compared between 19 pregnant women (28-34 weeks of pregnancy) with premature rupture of the membranes and 17 non-pregnant women with pelvic inflammatory disease, the groups being age and weight matched. A significant reduction of gentamicin half-life was found in the pregnant group.

Adult↗