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Biomedical subjects

M A Bender

Publications and source records attributed to M A Bender.

At least 73 records · Page 4Linked to original sources
PubMed1986

Concordance of a point mutation 5' to the A gamma-globin gene with A gamma beta + hereditary persistence of fetal hemoglobin in Greeks.

In the Greek A gamma beta + type of hereditary persistence of fetal hemoglobin (HPFH), adult heterozygotes produce about 20% fetal hemoglobin (HbF), which is predominantly of the A gamma chain variety. The affected beta-globin gene cluster produces near normal amounts of beta-like globin, but in a A gamma to beta ratio of 20:80 instead of 0.5:99.5. Gelinas et al and Collins et al have shown a G to A change 117 nucleotides 5' to the A gamma gene in two Greeks with A gamma beta + HPFH. To demonstrate that this change is not a neutral polymorphism, we carried out hybridization with oligonucleotide probes (19mers) specific for the normal and the mutant sequences. While normal probe identified the A gamma fragment in genomic DNA of all subjects studied, mutant probe was positive only in Greeks with A gamma beta + HPFH. In sum, 108 beta-globin gene clusters of individuals without HPFH were negative when tested with mutant probe, but all 11 affected individuals of six families with Greek A gamma beta + HPFH (two previously sequenced and four new families) were positive with mutant probe. These data support the conclusion that the -117 mutation is causative of A gamma beta + HPFH in Greeks.

Fetal Hemoglobin↗
PubMed1985

G2 chromosomal radiosensitivity in ataxia telangiectasia lymphocytes.

The peripheral lymphocytes from 7 patients affected with ataxia telangiectasia (AT) were found to be about twice as sensitive to the induction of chromatid-type aberrations by X-rays administered during the G2 phase of the cell cycle as cells from normal controls. Peripheral lymphocytes from 6 AT heterozygotes were no more sensitive than the controls. Using labelling of peripheral lymphocytes with tritiated thymidine, followed by autoradiography, it was determined that cells from affected patients, heterozygotes and normal controls, whether irradiated or not, all had similar percent labeled mitoses (PLM) curves, so the increased induced aberration yields seen in the AT cells is not simply the consequence of a longer than normal G2 phase, nor of G2 delay induced by the radiation. Peripheral lymphocytes from two affected patients and two controls were irradiated in culture, labeled with tritiated thymidine and collected with colcemid over various intervals so that by scoring unlabeled cells in autoradiographs the time course of aberration yield over all of G2 could be determined. The curve for chromatid aberrations for the AT cells differ significantly from that for the controls in intercept, suggesting that in the AT cells the radiation induces more lesions capable of resulting in aberrations, but that their repair may be similar.

Ataxia Telangiectasia↗
PubMed1984

Cytogenetic findings in persons living near the Love Canal.

Cytogenetic analyses were performed on peripheral blood from 46 present or past residents of the area surrounding Love Canal, a former dump site for chemical wastes in Niagara Falls, NY. Participants included 17 persons in whom cytogenetic analyses had been performed in 1980 and 29 persons who had been living in 1978 in seven homes that directly adjoined the canal and in which environmental tests showed elevated levels of chemicals spreading from the canal. Frequencies of chromosomal aberrations and of sister chromatid exchange (SCE) did not differ significantly from control levels. For all participants, cigarette smoking was associated with an increase in sister chromatid exchange frequency.

Chromosome Aberrations↗
PubMed1984

Chromosome aberration types in Chinese hamster (CHO) cells X-irradiated in S and G1.

The different types of chromosome aberrations found after a single dose of 2.5 Gy of hard X-rays were scored in Chinese hamster (CHO) cells irradiated in early G1, late G1, early S and late S phase. Chromatid-type aberrations were found throughout S, and chromosome-type aberrations were found in early S. Sister unions were found in early S and G1, and were more common in early than in late G1. Sister unions manifested themselves as an increase in the number of apparent acrocentric chromosomes, with an accompanying apparent increase in chromosome number. It is suggested that previous studies have failed to observe sister unions in this cell type because of the difficulty of distinguishing between sister unions and acrocentric chromosomes.

Animals↗
PubMed1984

Sister chromatid exchange frequency in human lymphocytes exposed to ionizing radiation in vivo and in vitro.

This paper reports statistically significant elevations in peripheral blood lymphocyte sister chromatid exchange frequencies in persons occupationally exposed to low levels of ionizing radiation when compared with unexposed persons. Low doses of X or gamma rays administered in vitro also produce significant elevations in sister chromatid exchange frequencies, though the magnitude of the increases is dependent upon culture medium and other factors.

Adult↗
PubMed1984

Increased yields of exchanges but not of deletions in X-irradiated human peripheral lymphocytes following phytohemagglutinin stimulation.

We have irradiated human peripheral lymphocytes after various intervals of phytohemagglutin stimulation to determine the time course for exchange induction and to determine whether or not deletion yields increase with increasing intervals of stimulation. We found no increase in deletion yields for intervals up to 12 hr, and rings and dicentric yields increased by about 60% in the interval between 0 and 6 hr but then reached a plateau. We also measured induced unscheduled DNA synthesis during the same interval and found it generally increased during the first 6 hr like exchange yields, but then tended to decrease again.

Chromosome Aberrations↗
PubMed1983

Love canal.

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Chromosome Aberrations↗
PubMed1983

No liquid holding recovery for chromosomal aberrations or sister-chromatid exchanges in irradiated G1 human lymphocytes.

We have tested G0 phase human peripheral lymphocytes for liquid holding recovery (LHR) mediated decreases in X-ray-induced chromosomal aberration yields and increases in sister-chromatid exchange (SCE) levels such as have been demonstrated for confluency-inhibited mouse cells in culture (Nagasawa and Little, 1981). No influence on either aberration yields or SCE levels was demonstrated. However, an effect at least superficially similar to the LHR effect was seen for rings and dicentrics, but not for deletions or SCE in lymphocytes in transition between G0 and G1 following PHA stimulation.

Chromosome Aberrations↗
PubMed1983

Characterization of a T-antigen-negative revertant isolated from a mouse cell line which undergoes rearrangement of integrated simian virus 40 DNA.

A transformation revertant has been isolated from an unusual line of simian virus 40 (SV40)-transformed BALB/c-3T3 cells in which rearrangements of integrated viral sequences are common. The revertant produces no SV40 T antigens, yields no virus on fusion with permissive cells, and can be retransformed by SV40 virions. SV40 DNA sequences are present within the cellular DNA, but interruption of the viral early transcription region by deletion and recombination with cellular sequences precludes the synthesis of T antigens. Analysis of this revertant lends further support to the notion that large T antigen plays an essential role in the maintenance of transformation in SV40-transformed BALB/c-3T3 cells. Examination of integration of SV40 DNA in this revertant, as well as in a temperature-sensitive A transformant, after retransformation by SV40 confirms that sequence homology plays little role in the insertion of SV40 DNA into cellular chromosomes.

Animals↗
PubMed1982

Intraperitoneal chromic phosphate in peritoneoscopically confirmed stage I ovarian adenocarcinoma.

From December 15, 1975 to June 16, 1980, 20 evaluable patients with International Federation of Gynaecology and Obstetrics Stage I invasive adenocarcinoma of the ovary were entered into a prospective study, including pretherapy restaging peritoneoscopy followed by treatment with intraperitoneal chromic phosphate if there was no evidence of residual macroscopic tumor. During a follow-up of 1 1/2 to 6 years (median, 3 years and 1 month), the survival rate without evidence of recurrent ovarian carcinoma was 95%. Moreover, there was a total absence of complications with the use of the sequential steps of pretherapy peritoneoscopy, a normal preinjection peritoneogram, injection of chromic phosphate in large volumes of solution, frequent change of position of the patient after injection, and abdominal scans after injection. This method appears to be safe and is associated with a significantly high survival rate.

Adenocarcinoma↗
PubMed1982

Abilities of extracts of human lymphocytes to remove O6-methylguanine from DNA.

O6 MeGua is a presumptive mutagenic and carcinogenic product in DNAs treated with methylating agents. The abilities of lymphocyte extracts from 34 apparently normal individuals to remove O6 MeGua from exogenous DNA have been measured. The activity in extracts is stable to freezing and so permits repeat determinations and hence high precision in the assays. The data on removal are consistent with the idea that the removal is accomplished by the transfer of a methyl group to a methyl-accepting protein and that the protein acts in a stoichiometric fashion. Extracts from lymphocytes stimulated with PHA show on the average more activity than from unstimulated ones, although some extracts show no increase as a result of PHA stimulation of cells. There are large variations in the abilities of human lymphocytes to remove O6 MeGua, but the differences are not correlated significantly with sex or age. Unstimulated lymphocytes show a bimodal distribution of removing activity, whereas stimulated ones show a predominant single peak of activity. Extracts of T lymphocytes are more proficient than those of B lymphocytes and of any other white cells. On the average the number of presumptive acceptor molecules per cell in unstimulated lymphocytes is between 14 000 and 110 000 and in stimulated lymphocytes between 40 000 and 140 000.

B-Lymphocytes↗
PubMed1982

Radiogallium scan in P. carinii pneumonia.

A gallium scan performed on a patient with fever of unknown origin (FUO) revealed an abnormal uptake of radiotracer in the lungs despite negative chest roentgenographic examination and other routine diagnostic studies. Subsequent lung biopsy results confirmed the presence of Pneumocystis (P.) carinii infection. A repeat gallium scan obtained following appropriate antibiotic therapy was essentially normal. The importance of radiogallium scanning in an immunosuppressed patient with FUO is emphasized.

Adult↗
PubMed1982

Necropsy of a cadaver containing 50 mCi of sodium131 iodide.

A patient who received an oral dose of iodine-131 for the treatment of metastatic thyroid carcinoma unexpectedly died with a large total-body retention of the radioiodine. An autopsy was required and the family requested the body to be transported out of state to their home town. Since the radiation intensity near the surface of the cadaver was above 200 mR/hr, advanced planning and special precautions were necessary in order for the autopsy to proceed safely. This required the immediate cooperation of the pathologists, nuclear medicine physicians, health physicists, an endocrine oncologist, and other hospital staff. As a result of team efforts, personnel radiation exposures were kept as low as reasonably achievable, contamination of the autopsy room was minimal, and the radiation level of the cadaver was adequately reduced for safe transport and burial.

Adult↗
PubMed1981

Mammalian in vivo and in vitro cytogenetic assays: a report of the U.S. EPA's gene-tox program.

This report presents an assessment made by the U.S. Environmental Protection Agency Gene-Tox Program's Work Group on mammalian cytogenetics of the clastogenic effects of chemicals in in vivo and in vitro mammalian cell assays. This assessment is based on information provided by the Environmental Mutagen Information Center, Oak Ridge National Laboratory, with the proviso that the experimental protocol used in these papers was adjudged to be acceptable by standards outlined by the Work Group. Some data were accepted as "qualitative only" because the protocol used was fairly close to that proposed as suitable. Using these criteria, 177 papers were selected for review. 6 assays were reviewed: bone marrow (32 papers, 31 chemicals), spermatogonial (10 papers, 10 chemicals), spermatocyte (25 papers, 25 chemicals), oocyte or early embryo (18 papers, 19 chemicals), in vitro cell culture (30 papers, 66 chemicals), and leukocyte (66 papers, 53 chemicals). Each assay was considered separately, and comparisons were then made between them for their similarities or differences in producing a positive or negative clastogenic effect of a particular chemical or chemical class. A large proportion of the available cytogenetic data was not suitable for inclusion in the final data base because of poor experimental design or unsatisfactory reporting of the information. It was not possible to recommend any one assay for determining potential clastogenicity because each had its own particular advantages and limitations and provided unique information. For demonstrating in vivo effects, the bone-marrow assay is probably the simplest and most economical. If only in vitro exposures were considered, leukocytes or cultured mammalian cell lines would be suitable. However, there are advantages to using leukocytes because they are a synchronous population, at least through their cell division, and because of the ready availability of human cells. In general, there was good agreement between clastogenicity and carcinogenicity.

Animals↗
PubMed1981

Rearrangement of integrated viral DNA sequences in mouse cells transformed by simian virus 40.

The organization of viral DNA sequences in several cell lines derived from a primary colony of simian virus 40 (SV40)-transformed mouse cells was analyzed to examine the origin of the various distinctive patterns of SV40 sequence arrangement present in transformed cells. This analysis revealed a complex arrangement of viral sequences in the uncloned transformed cells but simplified arrangements in cloned derivatives of the primary transformant. The cell lines studied had certain SV40 sequence arrangements in common, but the cloned lines had lost some parental arrangements and acquired new arrangements. These results indicate that the arrangement of viral sequences in some SV40-transformed cells is not fixed but that alterations occur after integration, creating a heterogeneous population of transformants. In the process, expression of viral genes may be altered. Possible causes for and implications of this genetic instability are discussed.

Animals↗
PubMed1980

Relationship of DNA lesions and their repair to chromosomal aberration production.

Though the roles of some specific DNA lesions in the production of chromosomal aberrations is clearly established, those of others remain unclear. While the study of aberration production in human genetic DNA repair deficiency diseases has been extremely rewarding already, eukaryotic repair systems are obviously complex, and one is tempted to feel that such studies may have raised as many questions as they have provided answers. For example, the "standard" sort of xeroderma pigmentosum is chromosomally sensitive to ultraviolet light and to those chemical agents inducing ultraviolet-type DNA repair. But both it and the variant form have been reported to also be sensitive to the crosslinking agent mitomycin C in one study [18], implying a common step or steps in the repair of pyrimidine cyclobutane dimers and DNA crosslinks. However, just to complicate matters, another study of chromosomal aberration production in xeroderma pigmentosum cells had found them no more sensitive to mitomycin C than normal cells [50]. Similarly, Fanconi's anemia cells, which are chromosomally sensitive to crosslinking agents, and appear to be defective in the "unhooking" of linked polynucleotide strands [15, 16, 49, 51], are reported to be chromosomally sensitive to ethyl methanesulfonate as well [29], and to be sensitive to ionizing radiation [7, 19, ]0], again implying overlapping repair systems. It seems certain that further study of chromosomal aberration production in repair deficient cells by agents inducing various DNA lesions will reveal even greater complexity in eukaryotic DNA repair systems and their role in chromosomal aberration production. Nevertheless, there seems hope, at least, that such studies may also ultimately lead to a complete understanding of the molecular mechanisms involved.

Animals↗
PubMed1980

Effects of inhibitors of DNA synthesis on spontaneous and ultraviolet light-induced sister-chromatid exchanges in Chinese hamster cells.

Effects of inhibitors of DNA synthesis on spontaneous and ultraviolet light (UV)-induced sister-chromatid exchanges (SCE) were examined in a Chinese hamster cell line, V79 B-1. The inhibitors used were hydroxyurea (HU), 1-beta-D-arabinofuranosylcytosine (ara-C), aphidicolin (APC), 2',3'-dideoxythymidine triphosphate (ddTTP), neocarzinostatin (NCS), novobiocin (NB) and cycloheximide (CHX). HU, ara-C, and APC increased spontaneous SCE frequency, and had a synergistic effect on UV-induced SCE frequency. DdTTP, NCS and NB failed to show any statistically significant effect on either spontaneous or UV-induced SCE frequencies, though NCS and NB did slightly increase both spontaneous and UV-induced SCE frequencies. On the contrary, CHX decreased spontaneous SCE frequency, and more drastically, also UV-induced SCE frequency. These results are interpreted with respect to the replicating fork of DNA, a structure postulated to be involved in the formation of spontaneous and UV-induced SCE. A new model for SCE formation is proposed.

Animals↗