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S Wolff

Publications and source records attributed to S Wolff.

At least 109 records · Page 6Linked to original sources
PubMed1987

Characterization of the adaptive response to ionizing radiation induced by low doses of X rays to human lymphocytes.

In previous studies we have shown that low doses of radiation from incorporated tritiated thymidine can make human lymphocytes less susceptible to the genetic damage manifested as chromatid breakage induced by a subsequent high dose of X rays. We have also shown that this adaptive response to ionizing radiation can be induced by very low doses of X rays (0.01 Gy; i.e., 1 rad) delivered during S phase of the cell cycle. To see if a low dose of X rays could induce this response in cells at other phases of the cell cycle, human lymphocytes were irradiated with 0.01 or 0.05 Gy before stimulation by phytohemagglutinin (G0) or with 0.01 Gy at various times after stimulation (G1), followed by 1.5 Gy (150 rad) at G2 phase. Although G0 lymphocytes failed to exhibit an adaptive response, G1 cells irradiated as early as 4 h after stimulation did show the response. Experiments were also carried out to determine how long the adaptive response induced by 0.01 Gy could persist. A 0.01-Gy dose was delivered to lymphocytes in the first S phase, followed by 1.5 Gy in the same or subsequent cell cycles. Lymphocytes receiving a 1.5-Gy dose at 40, 48, or 66 h after stimulation exhibited an adaptive response, whereas those receiving a 1.5-Gy dose at 90 or 114 h did not. Duplicate cultures containing bromodeoxyuridine showed that at 40 h all the lymphocytes were in their first cell cycle after stimulation, at 48 h half of the lymphocytes were in their first cell cycle and half in their second, and at 66 h 80% of the lymphocytes were in their third cell cycle. Thus the adaptive response persists for at least three cell cycles after it is induced by 0.01 Gy of X rays. In other experiments, the time necessary for maximal expression of the adaptive response was determined by delivering 0.01 Gy at hourly intervals 1-6 h before the 1.5-Gy dose. While a 4-h interval was enough for expression of the adaptive response, shorter intervals were not.

Adaptation, Physiological↗
PubMed1986

'Schizoid' personality and antisocial conduct: a retrospective case not study.

A retrospective case not analysis for 30 boys diagnosed as having a 'schizoid' personality disorder (Asperger's syndrome) in childhood, and for 30 matched clinic attenders (with systematic follow-up data for 19 matched pairs), showed the incidence of antisocial conduct to be the same in the two groups. However, the 'schizoid' boys stole less often and had fewer alcohol problems. In this group antisocial conduct was less related to family disruption and social disadvantage, and more to an unusual fantasy life. Clinical descriptions of a series of 'schizoid' boys and girls with conspicuous antisocial conduct follow. They suggest that characteristic patterns of antisocial conduct in such children are persistent expressions of hostility and, especially in girls, pathological lying, for which environmental circumstances provide no explanation.

Adolescent↗
PubMed1986

Metabolic breakdown of [3H]thymidine and the inability to measure human lymphocyte proliferation by incorporation of radioactivity.

Quantitative measurement of the incorporation of tritiated thymidine into cultures of phytohemagglutinin-stimulated lymphocytes is routinely used as an indication of the immunocompetence of the cells and of their proliferation. The present experiments show that several components of human blood catabolize nucleosides, including thymidine, extensively. Most of the radioactivity from tritiated thymidine, for example, is quickly rendered unincorporable as the compound is metabolized to thymine and further breakdown products. Thus, cells continue to proliferate without incorporating radioactivity from the medium. Furthermore, variability in the degree of catabolism has been found from person to person, so that neither measurement of the depletion of radioactivity from the medium nor measurement of the amount of label incorporated into the cultures can be used as a quantitative indicator of cell proliferation or immunocompetence.

Animals↗
PubMed1986

Evidence that the [3H]thymidine-induced adaptive response of human lymphocytes to subsequent doses of X-rays involves the induction of a chromosomal repair mechanism.

When human lymphocytes are treated with [3H]thymidine ([ 3H]dThd), the observed number of chromosomal aberrations induced by [3H]dThd and subsequent doses of X-rays is less than the number induced by X-rays alone. Experiments in which cells were examined at various times after exposure to the X-rays showed that this phenomenon, termed an adaptive response to the endogenous radiation from tritium, is not an artefact caused by radiation-induced mitotic delays, which could result in the sampling of metaphase cells that were irradiated in different parts of the G2 phase of the cell cycle, where sensitivity to X-rays changes dramatically. Reconstruction experiments in which labelled female cells were co-cultured with unlabelled male cells now show that labelled and unlabelled cells progress to metaphase equally, and therefore that the adaptive response is not the result of selection against a radiosensitive population of cells that have incorporated [3H]dThd. Measurements of chromosomal aberrations induced in the labelled female cells and unlabelled male cells that had been co-cultured show that the adaptive response is restricted to those cells exposed to radiation from the incorporation of [3H]dThd and that diffusible factors are not involved. The results are consistent with the proposal that this adaptive response is the result of the induction of a hitherto unknown chromosomal repair mechanism. It has now been found that this repair mechanism is induced at levels of radiation from [3H]dThd that in themselves are too low to induce any discernible chromosomal aberrations and that its activity is dependent on the enzyme poly(ADP-ribose) polymerase, because 3-aminobenzamide, an inhibitor of poly(ADP-ribosyl)ation, prevents the adaptive response.

Adaptation, Biological↗
PubMed1985

The mechanism and pattern of banding induced by restriction endonucleases in human chromosomes.

The mechanism of chromosome banding induced by restriction endonucleases was analyzed by measuring the amount of radioactivity extracted from [14C]thymidine-labeled chromosomes digested first with restriction enzymes and subsequently with proteinase K and DNase I. Restriction enzymes with a high frequency of recognition sites in the DNA produced a large number short DNA fragments, which were extracted from chromosomes during incubation with the enzyme. This loss of DNA resulted in decreased chromosomal staining, which did not occur in regions resistant to restriction enzyme digestion and thus led to banding. Subsequent digestion of chromosomes with proteinase K produced a further loss of DNA, which probably corresponded to long fragments retained in the chromosome by the proteins of fixed chromatin. Restriction enzymes induce chromatin digestion and banding in G1 and metaphase chromosomes, and they induce digestion and the appearance of chromocenters in interphase nuclei. This suggests that the spatial organization and folding of the chromatin fibril plays little or no role in the mechanism of chromosome banding. It was confirmed that the pattern of chromosome banding induced by AluI, MboI, HaeIII, DdeI, RsaI, and HinfI is characteristic for each endonuclease. Moreover, several restriction banding polymorphisms that were not found by conventional C-banding were detected, indicating that there may be a range of variability in the frequency and distribution of restriction sites in homologous chromosome regions.

Chromosome Banding↗
PubMed1985

The pattern of restriction enzyme-induced banding in the chromosomes of chimpanzee, gorilla, and orangutan and its evolutionary significance.

The pattern of banding induced by five restriction enzymes in the chromosome complement of chimpanzee, gorilla, and orangutan is described and compared with that of humans. The G banding pattern induced by Hae III was the only feature common to the four species. Although hominid species show almost complete chromosomal homology, the restriction enzyme C banding pattern differed among the species studied. Hinf I did not induce banding in chimpanzee chromosomes, and Rsa I did not elicit banding in chimpanzee and orangutan chromosomes. Equivalent amounts of similar satellite DNA fractions located in homologous chromosomes from different species or in nonhomologous chromosomes from the same species showed different banding patterns with identical restriction enzymes. The great variability in frequency of restriction sites observed between homologous chromosome regions may have resulted from the divergence of primordial sequences changing the frequency of restriction sites for each species and for each chromosomal pair. A total of 30 patterns of banding were found informative for analysis of the hominid genealogical tree. Using the principle of maximum parsimony, our data support a branching order in which the chimpanzee is more closely related to the gorilla than to the human.

Animals↗
PubMed1985

Cytosine arabinoside is a potent clastogen and does not affect the repair of X-ray-induced chromosome fragments in unstimulated human lymphocytes.

The metabolic inhibitor of DNA synthesis cytosine arabinoside (ara-C) is known to induce chromosome aberrations in human lymphocytes. It has been recently argued, however, that there is no unequivocal evidence that ara-C can damage chromosomes directly. Therefore, the effect of ara-C on unstimulated human lymphocytes was examined directly by means of the premature chromosome condensation technique. In about 50% of the cells, ara-C effectively induced chromosome fragments, which did not show rejoining even after the chemical was washed out. These results suggest that a possible selection against damaged cells in their progress to mitosis could result in the low yields of ara-C-induced chromosome aberrations reported in the literature. The effect of ara-C on the repair of radiation-induced chromosome aberrations was also examined. Ara-C did not affect the rejoining of the chromosome fragments induced in unstimulated human lymphocytes by 6 Gy of X-rays.

Animals↗
PubMed1985

Magnetic resonance imaging: absence of in vitro cytogenetic damage.

Human lymphocytes and Chinese hamster ovary (CHO) cells in culture were exposed for 12 1/2 hours to a magnetic resonance imaging apparatus with a 2.35-Tesla magnet and 100-MHz radio frequency emission. The cells were examined for cytogenetic damage manifested either as chromosome aberrations or sister chromatid exchanges (SCEs), which constitute very sensitive measures of genetic and cellular damage. In either unstimulated or stimulated human lymphocytes, as well as in exponentially growing CHO cells, no increase in either chromosome aberrations or SCEs was found as a result of exposure to these MR conditions. The data indicate that long-term exposure to MR imaging conditions far exceeding those to be found in the clinical situation does not cause cytogenetic damage.

Animals↗
PubMed1985

Comutagenic effects of 3-aminobenzamide in Chinese hamster ovary cells.

Inhibition of poly (ADP-ribose) synthesis by agents such as 3-aminobenzamide (3-AB) potentiates the cytotoxic, carcinogenic, and clastogenic effects of certain DNA-damaging agents. Experiments were carried out in Chinese hamster ovary cells to compare chromosome aberration production and cytotoxicity with the induction of somatic mutations at the hypoxanthine-guanine phosphoribosyltransferase (HGPRT) and sodium-potassium ATPase loci after treatment with 3-AB in combination with certain monofunctional alkylating agents. On its own, 1 to 10 mM concentrations of 3-AB were not mutagenic, reduced plating efficiencies only slightly, and produced a small elevation in the frequency of chromatid aberrations. In combination with ethyl methanesulfonate (EMS), 3-AB increased cytotoxicity and the frequency of alkylation-induced chromatid aberrations. 3-AB also increased the frequency of EMS and N-methyl-N'-nitro-N-nitrosoguanidine-induced 6-thioguanine-resistant cells (a marker for the HGPRT- phenotype). It had no effect on the frequency of EMS-induced ouabain-resistant cells (a marker for ATPase mutations). All the effects were dose dependent. Larger absolute increases were found with 10 mM 3-AB as compared with 1 mM 3-AB and with 2 mM EMS as compared to 1 mM EMS. The 3-AB-mediated increases in 6-thioguanine-resistant cells, which are often deletion mutations, and the lack of any increase in the frequency of ouabain-resistant cells, which can only arise through point mutation induction, along with the increases in chromosome aberration frequency, suggests that 3-AB increases the frequency of deletion mutations by increasing the frequency and duration of DNA strand breaks.

Animals↗
PubMed1985

[Long-term (10 years) predictive value of the exercise test after myocardial infarct and significance of the longitudinal repetition of the test during follow-up].

Our follow-up after myocardial infarction consists of 321 patients followed for 10 years or until death. 147 patients, free of clinical features associated with high risk of subsequent events, underwent a late exercise test at cycloergometer 6 to 17 months after infarction. Ten year mortality was 48.3% and 10.3% in patients with a positive or a negative test respectively (p less than 0.0001). Incidence of nonfatal reinfarction was 4.6% and 33.3% respectively (p less than 0.001). 108 patients underwent a second test later in the follow-up (2.8 +/- .9 years): in 27 patients who were positive at first test the second test was also positive and mortality was 33.3%. Sixteen out of 81 patients with a former negative test resulted positive at a repeat test and mortality was 37.5% vs a 3% mortality rate among 65 patients who were negative at both tests. Thus long-term prognostic significance of exercise stress testing after acute myocardial infarction is confirmed and extended, despite limitation of a late test. Moreover, the second test along the follow-up allows further stratification. In conclusion, patients with a negative test and without clinical features predictive of poor prognosis constitute a very low risk group who need not undergo invasive testing, whereas patients with a positive result or who become positive at following test deserve further evaluation and may become bypass candidates in the ensuing years.

Evaluation Studies as Topic↗
PubMed1984

Detection of enhanced in vivo platelet alpha-granule release in different patient groups--comparison of beta-thromboglobulin, platelet factor 4 and thrombospondin assays.

During the platelet release reaction beta-thromboglobulin (beta TG), platelet factor 4 (PF4) and thrombospondin (TSP) are released from the platelet into plasma and assays of these proteins can be used to monitor in vivo platelet activation. We have assessed their relative merits as markers of the in vivo platelet alpha-granule release reaction in a number of patient groups which have previously been shown to have elevated plasma beta TG and/or PF4 levels. It is concluded that in diseases or conditions not complicated by its reduced clearance, beta TG is the most sensitive marker of in vivo platelet alpha-granule release. However, the TSP assays may be the least ambiguous when monitoring the platelet alpha-granule release reaction in patients with renal failure who are undergoing haemodialysis with heparin anticoagulation. Under these circumstances plasma beta TG, but not PF4 or TSP, levels are elevated because of impaired renal catabolism, and the presence of a heparin-releasable reservoir of PF4 on the endothelium complicates the use of the PF4 assay. In liver failure none of these assays may accurately reflect platelet alpha-granule release because of impaired hepatic or renal elimination of the proteins.

Adolescent↗
PubMed1984

The autoxidation of glyceraldehyde and other simple monosaccharides under physiological conditions catalysed by buffer ions.

Glyceraldehyde and other simple monosaccharides autoxidise under physiological conditions generating 1-hydroxyalkyl (carbon-centred) free radicals and intermediates of dioxygen reduction: superoxide, hydrogen peroxide and hydroxyl radicals. The major glyceraldehyde-derived product is the alpha-ketoaldehyde, hydroxypyruvaldehyde. Close similarities between the temperature dependence of the kinetics of glyceraldehyde autoxidation and glyceraldehyde enolisation to an ene-diol indicates that enolisation is the rate-determining step in the autoxidative process. Inspection of a wide range of carbonyl compounds showed that the monosaccharide moiety -CH(OH)-C- is conserved in carbonyl compounds reactive towards autoxidation, indicating that the ability to form an ene-diol is a prerequisite to monosaccharide autoxidation. The ene-diol intermediate autoxidises rapidly to the products: hydrogen peroxide, water and alpha-ketoaldehydes: beta-hydroxypyruvaldehyde is produced from glyceraldehyde and dihydroxyacetone, glyoxal from glycolaldehyde autoxidation. Ene-diol autoxidation is catalysed by hydrogen peroxide and trace metal ion contaminants; removal of either of these factors sufficiently retards ene-diol autoxidation such that ene-diol autoxidation rather than enolisation becomes the rate determining step in the overall autoxidative process. Under enolisation control, the rate of monosaccharide autoxidation is influenced by pH and the buffer system used for pH control.

Animals↗
PubMed1984

Adaptive response of human lymphocytes to low concentrations of radioactive thymidine.

When human lymphocytes were cultured with [3H]thymidine, which acts as a source of low-level chronic radiation, and then exposed to 150 rad of x-rays at 5, 7, 9, or 11 hours before fixation, the yield of chromatid aberrations was less than the sum of the yields of aberrations induced by [3H]thymidine and x-rays separately. Often fewer aberrations were found after exposure to radiation from both sources than were found after exposure to x-rays alone. At the same fixation times, nonradioactive thymidine did not affect the yield of x-ray-induced aberrations. The same phenomenon occurred at earlier fixation times, after exposure to 30 or 40 rad of x-rays and [3H]thymidine. This response is analogous to the adaptive response to alkylating agents whereby prior treatment with small doses for a long period reduces the damage occurring from large doses of similar agents given for a short time.

Cells, Cultured↗
PubMed1984

Reduction of sister chromatid exchange frequency with time after mutagen exposure in Chinese hamster ovary cells in the presence of 3-aminobenzamide.

3-Aminobenzamide (3AB) is a potent inhibitor of poly (ADP-ribose) synthesis and has been reported to inhibit DNA repair. Inhibition of poly(ADP-ribose) synthesis by 3AB results in a potentiation of the cytotoxic effects of alkylating agents and synergistically increases the frequency of sister chromatid exchanges (SCEs) induced in Chinese hamster ovary cells by methyl methanesulfonate (MMS). Experiments were carried out to determine if this synergism was related to an inhibition of the repair or the removal of SCE-forming lesions by 3AB. Cells were treated with MMS or ethyl nitrosourea (ENU) and either held in a nonproliferative state or maintained in exponential growth for up to 48 hr before SCE frequencies were measured. During this time, the SCE frequency decreased greatly. 3AB did not affect this decrease in either cycling or noncycling cells. Furthermore, 3AB appears to exert its effect only in cycling cells when bromodeoxyuridine is present. Therefore, the synergism between 3AB and alkylating agents in the induction of SCEs is unrelated to effects of 3AB on the repair or removal of SCE-forming lesions.

Animals↗
PubMed1984

Effect of bromodeoxyuridine on induced sister chromatid exchanges.

Analysis of sister chromatid exchanges (SCEs) is widely used as an assay for mutagenic carcinogens. Visualization of SCEs generally requires that the cells be cultured for 2 cycles of replication with the thymidine analog bromodeoxyuridine (BrdUrd). To see if incorporation of BrdUrd into chromosomal DNA influences the SCE response after treatment with chemical compounds, we have studied the effect of BrdUrd incorporation on SCEs induced by 5 different chemicals: bleomycin (BLM), which causes DNA single- and double-strand breakage; proflavine (PF), which intercalates into DNA; mitomycin C (MMC), a polyfunctional alkylating agent that cross-links DNA and also forms monoadducts; and 2 chemicals that do not appear to interact with DNA directly, aphidicolin (APC), an inhibitor of DNA polymerase alpha; and 3-aminobenzamide (3AMB), an inhibitor of poly-(ADP-ribose)-polymerase. Chemical treatment was for the first, second, or both cell cycles, and BrdUrd was present for the first or both cell cycles. All treatments with BLM, PF, or MMC increased the SCE frequency independently of the BrdUrd labeling protocol. With APC and 3AMB, on the other hand, only small increases in SCE frequency were observed when treatment was for the first cell cycle, but there were far greater increases when the chemical was present for the second or for both successive cell cycles. To further determine at which cycle SCEs were formed after continuous treatment of cells with BrdUrd and a test chemical, we also examined the induction of SCEs in the first cell cycle (twins) and in the second cell cycle (singles) in tetraploid cells. Bleomycin, PF, and APC induced almost equal numbers of SCEs in both cell cycles, but MMC appeared to induce more SCEs in the second cycle than in the first. This is probably caused by long-lived lesions that induce SCEs. 3-Aminobenzamide, which does not form persisting lesions, also induced more single than twin SCEs, suggesting that this compound affects BrdUrd-substituted DNA differently than it does unsubstituted DNA. This type of interaction between a chemical and BrdUrdsubstituted DNA should be taken into consideration when SCE analysis is used as an assay system.

Animals↗