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Biomedical subjects

I Emerit

Publications and source records attributed to I Emerit.

At least 73 records · Page 4Linked to original sources
PubMed1982

Tumor promoter phorbol 12-myristate 13-acetate induces a clastogenic factor in human lymphocytes.

The mechanism of the clastogenic action--i.e., the ability to induce chromosomal aberrations--of the tumor promoter phorbol 12-myristate 13-acetate (PMA) was investigated. PMA at 10 and 100 ng/ml induced the formation of a low molecular weight (less than 10,000) clastogenic factor (CF) in phytohemagglutinin-stimulated human blood and lymphocyte cultures. Bovine erythrocyte Cu-Zn superoxide dismutase strongly inhibited PMA clastogenicity, both the formation of CF and the action of previously formed CF. The nonsteroidal anti-inflammatory agents indomethacin, imidazol, and 5,8,11,14-icosatetraynoic acid inhibited PMA clastogenicity and the clastogenic activity of previously formed CF. These results suggest that superoxide radicals and stimulation of the arachidonic acid cascade play a role in PMA-induced clastogenicity and the mechanism of action of the CF. The CF may relate the initial interaction of PMA with the cell membrane to the genome.

Arachidonic Acids↗
PubMed1982

Diverse xenotropic virus expressions in two NZB mouse breeding lines that differ in chromosome breakage.

Two breeding lines of the NZB/BI mouse strain, which was originated from Bielschowsky's stock and maintained as a conventional inbred colony since 1963, were developed by selective matings according to chromosome breakage incidence in bone marrow cells. These breeding lines were used because they represent an interesting experimental model, since they differ in the manifestations of the autoimmune process and the incidence of lymphomas. The present study showed that embryos from both breeding lines differed in the expression of the xenotropic type C RNA virus, characteristic of NZB mice. All 17 cultures initiated with embryos from the line showing high chromosome breakage (HB) had positive reverse transcriptase (RT) reactions after cocultivation with an indicator cell line (SIRC). On the contrary, only 3 of the 22 embryos from the line showing low chromosome breakage (LB) had RT activity at late passages (7-10). The chromosome studies done on these embryo cultures showed highly significant differences in the chromosome breakage incidence for the 2 breeding lines [10.6 and 20.5% of cells with aberrations for LB and HB embryos, respectively (P less than 0.001)].

Animals↗
PubMed1982

Chromosomal instability in NZB/BL mice. A dominant trait.

The descendance of 2 lines from NZB/bl mice which differ by the frequency of chromosome breaks has been studied. The analysis of reciprocal crosses and of "back cross" shows that the character of the chromosome breaks is perhaps dominant. This result is correlated with the observation that the autoimmunity (17) and viral expression (1, 13, 17) are also dominant.

Animals↗
PubMed1981

Clastogenic activity from Bloom syndrome fibroblast cultures.

Media from cultures of fibroblasts of six patients with the autosomal recessive disease Bloom syndrome (BS) and from four normal fibroblast strains were analyzed for clastogenic activity towards phytohemagglutinin-stimulated human blood lymphocytes from healthy donors. Clastogenic activity was detected in concentrated ultrafiltrates of media from all six BS strains but none of the normal fibroblast strains. The frequencies of chromosomal aberrations that were induced depended on the concentration of the ultrafiltrates. Addition of bovine superoxide dismutase to the blood lymphocyte cultures strongly suppressed the clastogenic potency of the ultrafiltrates. Unconcentrated conditioned BS media were inactive. From the pore size of the ultrafilters and Sephadex G-10 chromatography it is concluded that the clastogenic material is in the molecular weight range of 1000 to 10,000. The concentrated ultrafiltrates of BS culture media also possessed the capacity to induce sister chromatid exchanges in normal human blood lymphocytes, but with relatively low efficiency. On the basis of these results and by analogy to certain collagen diseases such as systemic lupus erythematosus, we speculate that BS cells are deficient in the detoxification of active oxygen species.

Cells, Cultured↗
PubMed1981

Mechanism of photosensitivity in systemic lupus erythematosus patients.

Patients who have systemic lupus erythematosus have increased numbers of chromosome breaks and rearrangements correlated with a low molecular weight chromosome-damaging agent that is released from their lymphocytes into the serum. This clastogenic factor also produces chromosome breaks and sister chromatid exchanges in healthy persons' lymphocytes when they are incubated in the presence of lupus patients' serum or lymphocytes or purified factor. The lymphocytes from lupus patients are sensitive to near-UV (360- to 400-nm light. This sensitivity seems to be related to the presence of the clastogenic factor in these cells; lymphocytes of healthy persons exposed to the factor also become sensitive to light of the same wavelengths. A significant increase in nonviable cells (trypan blue exclusion test) was observed after 5 min of irradiation with 360- and 380-nm light in the presence of the factor. The number of chromosome aberrations observed after stimulation of the irradiated lymphocytes with phytohemagglutinin was also maximal after irradiation at 380 nm in presence of the factor. The combined action of near-UV light plus clastogenic factor was inhibited by superoxide dismutase if the enzyme were present during irradiation, suggesting that activation involves photoproduction of superoxide ions. Irradiation of the purified factor and immediate addition of it to lymphocytes gave the same results whereas preirradiation of cells or of medium was without effect. The presence of this photoactivated agent explains why patients who have lupus erythematosus show an aggravated condition after exposure to sunlight and the appearance of typical skin lesions.

Cell Survival↗
PubMed1980

Chromosome damaging agent of low molecular weight in the serum of New Zealand black mice.

Two substrains of NZB mice were developed by selective matings according to chromosome breakage frequencies in direct bone marrow preparations: HB, a line with increased chromosome breakage, and LB, a line with low or normal breakage rates. The serum of NZB mice from the HB strain contains a chromosome breaking factor that produces chromosome abnormalities in human lymphocytes. This clastogenic substance could not be detected in serum of NZB line. Nor does it exist in serum of Balb, C3H, C57 B1, Swiss, or AKR mice, in which no chromosomal breakage was observed in bone marrow. The breakage factor has a molecular weight between 1000 and 10,000 daltons.

Animals↗
PubMed1980

Tumor incidence and development of autoimmune hemolytic anemia in two breeding lines of the NZB mouse strain that differ in chromosome breakage.

Increased chromosome breakage observed in NZB mice was studied. Breeding experiments with mice selected according to breakage frequencies provided evidence that the proportion of mice with high breakage (HB) and low breakage (LB) figures in the progeny depends on the phenotype of the parents. Selective breeding for the "chromosome breakage" characteristic was successful and resulted in the separation of a breeding line with LB incidence. However, the selection could not be continued beyond the fourth generation for the mice with HB incidence because of lethal factors. Comparative studies of HB mice from the HB line and LB mice from the LB line showed significant differences for tumor incidence and positivity of the Coombs' test.

Age Factors↗
PubMed1980

Chromosome instability in human and murine autoimmune disease: anticlastogenic effect of superoxide dismutase.

Increased chromosome breakage is observed in lymphocyte cultures from patients with so-called autoimmune diseases also in the animal model, the NZB mouse. A clastogenic agent was detected in the serum of patients and of NZB mice, that induces also chromosome breaks in cells of healthy individuals. In simultaneous cultures set up with or without superoxide dismutase in 5 patients with progressive systemic sclerosis, 5 patients with systemic lupus erythematosus and 5 patients with rheumatoid arthritis, highly significant differences in the incidence of chromosome breakage were observed. The aberration rate produced in blood cultures of healthy individuals by the breakage factor from patients was also reduced essentially to control values by addition of SOD in vitro, but were reduced also in vivo by injection of SOD in lupus patients as well as in NZB mice.

Animals↗
PubMed1979

Chromosomal breakage in Crohn's disease: anticlastogenic effect of D-penicillamine and L-cysteine.

The incidence of chromosome breakage was found to be elevated in 42 patients with Crohn's disease. This phenomenon was much more striking in cultures set up with TCM 199 than in cultures set up with RPMI 1629 rich in L-cysteine. The drug D-penicillamine, a close analog of L-cysteine, gave an apparent therapeutic response in several patients and reduced the chromosome breakage frequency in the lymphocytes of these patients in vitro and in vivo.

Cells, Cultured↗
PubMed1979

The influence of culture medium composition on the incidence of chromosomal breakage.

In patients with chromosomal instability and healthy subjects, significant differences were observed in the chromosomal breakage incidence in simultaneous lymphocyte cultures set up with TC medium 199, Eagle's Minimum Essential Medium, or RPMI, or RPMI 1629. The importance of the choice of culture medium for mutagenicity testing and studies of so-called spontaneous breakage is shown. Cultures incubated with TC Medium 199 showed the highest chromosomal breakage incidence.

Ascorbic Acid↗
PubMed1979

Chromosome breakage and xenotropic C-type virus in embryonic cultures from New Zealand black mice.

A considerable increase in chromatid and chromosome breaks, as well as excessive fragmentation and "pulverization" of whole metaphase plates was observed in embryonic fibroblast cultures from New Zealand black mice. A C-type RNA virus with a xenotropic host range was isolated from the supernatant fluid of co-cultures of NZB cells and heterologous permissive cells (SIRC cell line). One of the NZB cultures produced this virus without amplification by co-cultivation after spontaneous transformation of the cells. NZB cells are supposed to lack normal restriction of complete xenotropic virus expression and to release this endogenous virus spontaneously at a high level. It is hypothesized that the excessive chromosome damage observed in these cell cultures is related to the permanent production of virus, thus indicating a chromosome breaking effect of endogenous viruses.

Age Factors↗
PubMed1978

[Incontinentia pigmenti. Chromosomal study of a family (author's transl)].

After lymphocyte culture, chromosomic study has been performed on a woman and her daughter suffering from incontinentia pigmenti as well as on the two healthy brothers. This study has shown a high rate of chromosomic breakage in the four subjects, which confirms the facts mentioned in several previous reports. As far as genetic advice is concerned, the discovery of an excess of chromosomic breakage in a healthy subject who is a close relative of a patient, should prompt caution.

Abnormalities, Multiple↗
PubMed1977

[Chromosome breakage in incontinentia pigmenti].

Two cases of incontinentia pigmenti in a mother and her daughter are reported. An increase in structural chromosome aberrations of the chromatid type was observed, as already described by other authors. The aberrations rate in the same individual varied from culture to culture. Chromosomal breakage was also increased in apparently healthy family members.

Abnormalities, Multiple↗