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Biomedical subjects

S Yannai

Publications and source records attributed to S Yannai.

At least 19 recordsLinked to original sources
PubMed2004

Induction of apoptosis in human prostate cancer cell line, PC3, by 3,3'-diindolylmethane through the mitochondrial pathway.

Prostate cancer is the most common malignancy and the second leading cause of male death in Western countries. Prostate cancer mortality results from metastases to the bones and lymph nodes and progression from androgen-dependent to androgen-independent disease. Although androgen ablation was found to be effective in treating androgen-dependent prostate cancer, no effective life-prolonging therapy is available for androgen-independent cancer. Epidemiological studies have shown a strong correlation between consumption of cruciferous vegetables and a lower risk of prostate cancer. These vegetables contain glucosinolates, which during metabolism give rise to several breakdown products, mainly indole-3-carbinol (I3C), which may be condensed to polymeric products, especially 3,3'-diindolylmethane (DIM). It was previously shown that these indole derivatives have significant inhibitory effects in several human cancer cell lines, which are exerted through induction of apoptosis. We have previously reported that I3C and DIM induce apoptosis in prostate cancer cell lines through p53-, bax-, bcl-2- and fasL-independent pathways. The objective of this study was examination of the apoptotic pathways that may be involved in the effect of DIM in the androgen-independent prostate cancer cell line, PC3, in vitro. Our results suggest that DIM induces apoptosis in PC3 cells, through the mitochondrial pathway, which involves the translocation of cytochrome c from the mitochondria to the cytosol and the activation of initiator caspase, 9, and effector caspases, 3 and 6, leading to poly ADP-ribose polymerase (PARP) cleavage and induction of apoptosis. Our findings may lead to the development of new therapeutic strategies for the treatment of androgen-independent prostate cancer.

Androgens↗
PubMed2003

Indole-3-carbinol and 3,3'-diindolylmethane induce apoptosis in human prostate cancer cells.

Cruciferous vegetables contain glucobrassicin which, during metabolism, yields indole-3-carbinol (I3C). In a low pH environment I3C is converted into polymeric products, among which 3,3'-diindolylmethane (DIM) is the main one. The apoptotic effects of I3C and DIM were exhibited in human breast cancer cells. The objectives of this study were: (a) examination of the potential effects of I3C and DIM on the proliferation and induction of apoptosis in human prostate cancer cell lines with different p53 status; (b) to try to characterise the mechanism(s) involved in these effects. Our results indicate that both indole derivatives suppress the growth of these cells in a dose- and time-dependent manner, by inducing apoptosis. It appears that these indolic compounds may offer effective means against prostate cancer. Induction of apoptosis was p53-independent. Moreover, the indole derivatives employed did not affect the levels of bcl-2, bax and fasL.

Anticarcinogenic Agents↗
PubMed2003

The 10 basic requirements for a scientific paper reporting antioxidant, antimutagenic or anticarcinogenic potential of test substances in in vitro experiments and animal studies in vivo.

There is increasing evidence that chemicals/test substances cannot only have adverse effects, but that there are many substances that can (also) have a beneficial effect on health. As this journal regularly publishes papers in this area and has every intention in continuing to do so in the near future, it has become essential that studies reported in this journal reflect an adequate level of scientific scrutiny. Therefore a set of essential characteristics of studies has been defined. These basic requirements are default properties rather than non-negotiables: deviations are possible and useful, provided they can be justified on scientific grounds. The 10 basic requirements for a scientific paper reporting antioxidant, antimutagenic or anticarcinogenic potential of test substances in in vitro experiments and animal studies in vivo concern the following areas: (1) Hypothesis-driven study design; (2) The nature of the test substance; (3) Valid and invalid test systems; (4) The selection of dose levels and gender; (5) Reversal of the effects induced by oxidants, carcinogens and mutagens; (6) Route of administration; (7) Number and validity of test variables; (8) Repeatability and reproducibility; (9) Statistics; and (10) Quality Assurance.

Animals↗
PubMed2003

Allergy to sesame in humans is associated primarily with IgE antibody to a 14 kDa 2S albumin precursor.

The goal of this study was to identify and characterise the major allergen(s) of sesame seed. Detection of specific IgE to sesame proteins was performed with Pharmacia CAP System and Western blotting, after separation of sesame proteins by SDS-PAGE, using sera from 28 subjects diagnosed as allergic to sesame. The major allergen was separated by gel filtration chromatography and identified by selective proteolysis followed by peptide sequence analyses, employing electrospray-ionization mass spectrometer. Twenty-four of the 28 subjects had sesame-specific IgE. A 14 kDa protein belonging to the 2S albumin family was recognised by 22 of the 24 sera used. Subjecting the 14 kDa after HPLC separation to proteolysis with Lys C yielded 3 peptides, but only one reacted positively in the dot blot test. This peptide, corresponds in the whole protein chain to residues 24-94. The reactivity of the 14 kDa protein with most of the sera indicates that this is the major sesame allergen, later identified as 2S albumin precursor; and its peptide which reacted positively in the dot blot test evidently contains an epitope(s). Some minor sesame allergens, of higher molecular weight, were also revealed.

Adolescent↗
PubMed1999

Fixation of spent Saccharomyces cerevisiae biomass for lead sorption.

Spent Saccharomyces cerevisiae cells from a beer fermentation process were evaluated for lead cation sorption. The crude biomass was washed with water and acetone prior to any other treatment. Although the washed biomass showed substantial lead ion sorption it was susceptible to microbial spoilage. Different aldehydes were tested as chemical fixation agents; however, most of them caused drastic lowering of the metal uptake capacity. However, benzaldehyde was not only an excellent fixation agent, but the biomass treated with it also retained its original lead sorption capacity. A mechanism for the fixation process is suggested.

Adsorption↗
PubMed1998

Characterization of flavonoids as monofunctional or bifunctional inducers of quinone reductase in murine hepatoma cell lines.

The ability of flavonoid compounds to induce the activity of the phase II anticarcinogenic marker enzyme, quinone reductase (QR), has been studied in a wild-type murine hepatoma cell line (Hepalclc7) and in an Ah-receptor-defective mutant of the same cell line (Hepalclc7 bp(r)cl). The results showed that 10 (beta-naphthoflavone, kaempferide, tamarixetin, rhamnetin, quercetin, kaempferol, quercetin-4'-glucoside, isorhamnetin, daidzein and genistein) of the 13 flavonoids tested induced QR activity in the wild-type cells. Only the latter six also showed such activity in the bp(r)cl mutant, which indicates that they induce phase II enzymes directly (monofunctional inducers), whereas the others induce phase 11 enzymes only in cells with an operative Ah receptor system (bifunctional inducers). The metabolism of representatives of monofunctional (quercetin) and bifunctional (tamarixetin and rhamnetin) flavonol inducers were studied in both wild-type and bp(r)cl cells. In all cases, the major metabolites were glucuronides. Quercetin produced identical metabolites in both cell types, whereas one glucuronide of tamarixetin and two glucuronides of rhamnetin were not formed in the mutant cells. This shows that flavonoids can be mono- or bifunctional inducers depending on their chemical structure, and that the glucuronidation pattern of bifunctional inducers is altered by the presence of a functional Ah receptor system.

Animals↗
PubMed1996

3,3'-Diindolylmethane induces apoptosis in human cancer cells.

3,3'-Diindolylmethane is a dimer of indole-3-carbinol formed both in vivo and in vitro. In this study, human cancer cells MCF-7 (with wild-type p53), T47-D (mutant p53), and Saos-2 (deficient in p53 gene), were used to examine the anticancer activities of 3,3'-diindolylmethane. The dose-dependent growth inhibitory effect was found in all these cell lines. Exposure of the cells to 50 microM solution of 3,3'-diindolylmethane for 48 h, apoptosis (programmed cell death) was evidenced by the characteristic morphology of cell nuclei under fluorescence microscope and the DNA "ladder" in agarose gel electrophoresis. The percentage of apoptotic cells in each cell line was found to be 12% for MCF-7, 14% for T47D and 13% for Saos2 cells. Exposure of MCF-7 cells to 100 microM 3,3'-diindolylmethane for 24 h, 19% of apoptotic cells were detected by flow cytometry analysis. The lowest dose required for induction of apoptosis in MCF-7 cells was found to be 10 microM after 72 h incubation. Western blot showed that wild-type p53 protein was unchanged after MCF-7 cells had been exposed to 50 microM 3,3'-diindolylmethane for 8 h. This study provides evidences that 3,3'-diindolylmethane induces apoptosis in human cancer cells and that the induction of apoptosis is independent of p53 pathway.

Anticarcinogenic Agents↗
PubMed1996

Effects of exposure to lead on selected biochemical and haematological variables.

Blood and urine samples were taken from 34 persons occupationally exposed to lead and from 56 non-exposed control persons and blood lead and haemoglobin concentrations, red blood cell count, erythrocyte glutathione peroxidase (GSH-peroxidase) and acetylcholinesterase (AChE), and urinary delta-aminolevulinic acid were determined. Blood lead concentrations of the lead-exposed subjects were within the range of generally accepted as safe for occupationally-exposed adults in many countries (i.e. below 50 micrograms Pb/dl blood). Yet, significant dose-dependent elevations were found in erythrocyte GSH-peroxidase and urinary delta-aminolevulinic acid. The urinary delta-aminolevulinic acid concentration of lead-exposed smokers was significantly elevated over that of lead-exposed non-smokers. Smoking did not effect the urinary delta-aminolevulinic acid concentration of control persons. In addition, a statistically significantly lower red blood cell count was observed in the lead-exposed group. Our results indicate that the above described safety standard for blood lead concentrations in occupationally exposed adults, although generally accepted, needs revision.

Acetylcholinesterase↗
PubMed1995

Formation of organic cadmium by marine microorganisms.

This research was designed with a view to finding out whether or not there is a microbial or spontaneous transformation of inorganic cadmium into a highly toxic organic derivative of this metal by microorganism obtained from the Eastern Mediterranean marine environment. Sterile and nonsterile marine bottom sediment samples were incubated at ambient temperature for different time intervals, under aerobic and anaerobic conditions, with different concentrations of CdCl2, and the medium, the atmosphere in the incubation flasks, and the sediments were assayed for their organic cadmium contents. The results were: (a) There was microbial growth in all systems containing up to 250 micrograms cadmium per milliliter of growth medium; however, with higher concentrations a complete growth-inhibition was observed. (b) Organic cadmium was found in the bottom sediments, at all cadmium levels permitting considerable microbial growth, but not in the systems' atmospheres or in the liquid growth media. (c) Under aerobic conditions higher levels of organic cadmium were found than in the anaerobic systems. (d) The microorganisms occurring in the different experimental systems were isolated and identified. The predominating species in all systems were bacteria.

Bacteria, Aerobic↗
PubMed1995

Visual evoked potentials N75 and P100 latencies correlate with urinary delta-aminolevulinic acid, suggesting gamma-aminobutyric acid involvement in their generation.

Pattern reversal visual evoked potentials were recorded from 31 subjects who were occupationally exposed to lead and 54 non-exposed controls. No significant effects of lead were observed in the general subject population. However, when only non-smokers (17 lead-exposed and 27 controls) were evaluated, significant effects were found. The P100, but not the N75, latency was significantly prolonged in the lead-exposed group, and this correlated with both blood lead level and age. Nevertheless, both the N75 and P100 latencies correlated with the concentration of delta-aminolevulinic acid (delta-ALA) in urine and age. This, at least in part, could be due to elevated delta-ALA levels competing at gamma-aminobutyric acid (GABA) receptor neurons. This is consistent with the fact that GABA receptor neurons are involved along the entire length of the visual pathway. The results indicate that lead affects neural function even at permitted levels of exposure, and that this level should be reduced.

Aminolevulinic Acid↗
PubMed1995

The effect of lead exposure on target detection and memory scanning differs.

Visual event-related potentials were measured in lead-exposed and control subjects, while they were performing a target detection as well as a memory scanning task. Blood lead and urinary delta-aminolevulinic acid (delta-ALA) were determined in samples taken on the same day. Lead exposure did not affect the memory scanning P300 latency, but it did delay the target detection P300 latency in a dose-dependent fashion. The P300 amplitude of lead-exposed subjects was significantly reduced for both tasks, but not in a dose-dependent fashion. The target detection, but not the memory scanning, P300 latency correlated with urinary delta-ALA. No correlation of P300 with age was found, even though the subjects ranged from 20 to 60 years of age. The difference in the effect of lead exposure on the target detection and memory scanning P300 adds to the evidence that the P300 for the two tasks arises from different generators. The absence of a correlation of the measured P300 latency for each task with age in the present study raises the possibility that this extensively reported observation might, in part, be due to inappropriately matched younger and older subjects. This study indicates that evaluation of subjects exposed to toxic substances can increase our basic understanding of evoked potentials, as well as providing evidence of their toxic manifestations.

Analysis of Variance↗
PubMed1994

A multidisciplinary study of lead-exposed subjects. I. Delayed target detection P-300 latency, an electrophysiological parameter, correlates with urinary delta-ALA.

Visual event-related potentials, generated while performing a target detection (oddball) task, were successfully evaluated in 21 out of 34 individuals occupationally exposed to lead and 40 out of 56 nonexposed controls who were examined. The blood lead level of the lead-exposed subjects ranged from a mean of 29 to 53 micrograms Pb/dl blood in three exposed subgroups, while that of the control group was 7.7 micrograms Pb/dl blood. The latencies of the N2 and P300 components of the visual event-related potential were significantly longer in the lead-exposed subjects. Both the N2 and P300 latencies significantly correlated with the blood lead levels of the subjects. In addition, the P300 latency correlated with the concentration of delta-aminolevulinic acid (delta-ALA) in urine. This in part could be due to elevated delta-ALA levels interacting with gamma-aminobutyric acid (GABA) receptor neurons. The results indicate that lead affects mental function even at permitted levels of exposure. They strengthen the conclusion, based on biochemical and hematological assays, that the maximum permitted blood lead level of 50 micrograms Pb/dl blood is not safe and should be reduced.

Adult↗
PubMed1993

Susceptibility of different yeast species to environmental toxic metals.

The purpose of the study reported here was to investigate the relative resistance of yeast species to various metallic and metalloid ions, with a view to gaining more knowledge on this subject, as resistant species may become dominant in habitats contaminated with the relevant metals. Saccharomyces cerevisiae, Candida albicans and Candida tropicalis were grown in media containing different concentrations of mercury (as HgCl(2)), cadmium (as CdCl(2)), lead (as Pb(CH(3)COO)(2)), arsenic (as Na(2)HAsO(4)) and selenium (as Na(2)SeO(3)) for various intervals. Invariably, the two Candida species turned out to be more resistant to all the metals studied than S. cerevisiae. The metal showing the highest toxicity for these species was mercury, with cadmium being the second, lead, the third and arsenic and selenium being the least toxic elements. Strains showing resistance to mercury were isolated, even in the case of S. cerevisiae.

Journal Article↗
PubMed1993

Absorption and accumulation of cadmium, lead and mercury from foods by rats.

The purpose of this study was to estimate the apparent absorbability of cadmium (Cd), lead (Pb) and mercury (Hg) from different foods by young rats when these elements occur intrinsically. The study consisted of three independent experiments. In the first experiment rats were fed a casein control diet, a corn-silage diet or an activated-sludge diet. Although the amount of Cd, Pb and Hg ingested from the sludge diet was orders of magnitude higher than that from the casein or corn-silage diet, the absorption of the metals was significantly less (P < 0.02) because these were present as poorly-soluble phosphates. In the second experiment, rats were fed either a commercial fish-meal control diet or an experimental fish-meal diet, with or without the addition of sodium phytate, based on catches from metal-polluted waters. No reduction in absorption resulted from the diet containing phytate as compared with the diet without phytate. The third experiment used the radioactive tracers Cd-115m, Pb-210 and Hg-203 intrinsically incorporated individually into maturing corn ears, on which the three experimental diets were based. The liver and kidney were the main target organs for all three elements (liver: Cd 0.6%, Pb 1.4% and Hg 0.6%; kidney: Cd 0.8%, Pb 0.9% and Hg 1.3%).

Administration, Oral↗
PubMed1992

Secretion of human chorionic gonadotropin in superfused young placental tissue exposed to cadmium.

The effect of various concentrations of cadmium (Cd) in levels ranging from 0.75 to 12 micrograms/ml medium, on the secretion of human chorionic gonadotropin (hCG) in first-trimester placental explants, after 6 or 24 h incubation, employing both static and dynamic systems was examined. Later the unbound Cd was washed for 45 min with fresh medium devoid of Cd, followed by superfusion with the latter medium for 75 min, during which time samples were collected for hCG assay. For the superfusion experiments the parameters used for evaluating the hCG secretion pattern were: mean peak amplitude (MPA), pulse frequency (PF) and the area under the hCG secretion curve (AUC). The results indicate that in the dynamic system the hCG secretion increased significantly, and this increase was dose dependent. There was also a dose-related increase in mean total hCG secreted by the explants exposed to Cd. Maximal hCG secretion was observed after 24 h exposure of explants to 6 micrograms of the metal/ml. Both the MPA and AUC parameters showed a statistically significant increase for this dose level. At 12 micrograms/ml, the pulsatile secretion of hCG decreased, the value for the mean hCG secretion being comparable to that observed for 0.75 micrograms/ml. After 6 h incubation, however, there were no significant changes from the control, as judged by all of the above parameters. The levels of hCG secreted by the explants into the media in the static system were not significantly different from their respective controls, for both incubation periods and Cd levels. These results indicate that Cd may affect the normal placental function, as reflected in its hCG secretion pattern.

Cadmium↗
PubMed1992

In vitro exposure to mercury and cadmium alters term human placental membrane fluidity.

The effect of incubation with mercury (Hg) as HgCl2 and cadmium (Cd) as CdCl2, at levels of 6 or 12 micrograms/ml of medium, on explants of term human placental microvillus membrane fluidity were studied. After incubation for 6 or 24 hr explants for each dose level were pooled and washed with fresh medium to remove any unbound metal. Placental membranes were separated by differential centrifugation and fluidity was studied by steady-state fluorescence polarization, expressed as the fluorescence anisotropy, r, with 1,6-diphenyl-1,3,5-hexatriene as a probe. The results show that membranes derived from explants incubated for 24 hr with either 6 or 12 micrograms/ml medium of either metal showed fluorescence anisotropy values (i.e., decreased fluidity) significantly higher than that of their respective controls. With 6 micrograms/ml of either metal the decrease in fluidity was highly significant for both metals and with 12 micrograms/ml a further decrease in membrane fluidity was observed with either metal. Both metals accumulated in placental membranes in proportion to their level in the medium. Membrane accumulation of Cd was higher than that of Hg. The cholesterol, phospholipid, and cholesterol-to-phospholipid mole ratios in membranes derived from metal-treated explants were unchanged, compared to their respective controls. However, no changes in membrane fluidity were observed in the samples incubated for 6 hr. In conclusion, exposure of placental cells to Hg and Cd caused accumulation of the metals in the membranes and lowered the membrane fluidity, which may affect membrane function and cause damage to the developing fetus.

Alkaline Phosphatase↗
PubMed1992

Effect of cadmium on some enzyme activities in first-trimester human placentae.

Explants from first-trimester placentae obtained from non-smoking women were incubated with doses of 0, 0.75, 1.5, 3, 6 and 12 micrograms of cadmium (Cd) as CdCl2 for 6 or 24 h. At the end of the incubation period, the activities of placental aryl hydrocarbon hydroxylase (AHH) (a phase I enzyme), quinone reductase (QR) and catecholamine-O-methyltransferase (COMT) (both phase II enzymes) and glucose-6-phosphate dehydrogenase (G-6-PD) were determined. Cd at low dose levels increased significantly the activities of placental phases I and II enzymes in a time- and dose-dependent manner. Of the first 3 enzymes, only AHH showed a biphasic response for the two time periods, with the activities of QR and COMT continually increasing at all the dose levels tested for the two incubation periods. However, the G-6-PD activity was inhibited at all the dose levels of Cd, the effect being very drastic after exposure to 0.75 ppm Cd for both incubation periods.

Aryl Hydrocarbon Hydroxylases↗