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Biomedical subjects

M Marion

Publications and source records attributed to M Marion.

At least 37 records · Page 2Linked to original sources
PubMed1989

Inhibition of binding of 2-acetylaminofluorene to DNA by butylated hydroxytoluene and butylated hydroxyanisole in vitro.

Numerous studies have shown that the food antioxidants butylated hydroxytoluene (BHT) and butylated hydroxyanisole (BHA), under specific exposure conditions, can inhibit hepatocarcinogenesis induced by various carcinogens. The purpose of the present work was to study the biochemical mechanisms responsible for the anticarcinogenic activity of BHA and BHT using in vitro systems. The effects of BHA and BHT on the binding of 2-acetylaminofluorene (2-AAF) to DNA was determined in a microsomal system and in primary cultures of rat hepatocytes. It was found that both antioxidants reduce the binding of 2-AAF and that of N-OH-2-acetylaminofluorene (N-OH-2-AAF) to calf thymus DNA in the presence of liver microsomes. The inhibition was however more pronounced with the parent compound. Lower levels of DNA binding were also detected in hepatocytes incubated with 2-AAF along with BHA or BHT. These results suggest that phenolic antioxidants can exert anticarcinogenic activity through modulation of carcinogen interaction with DNA which may reflect on alteration in carcinogen metabolic activation.

2-Acetylaminofluorene↗
PubMed1987

The modulation by metallothionein of cadmium-induced cytotoxicity in primary hepatocyte cultures.

The cytotoxicity of CdCl2 and 2 isoforms of hepatic cadmium-metallothionein (CdMT I and II), was investigated using primary cultures of rat hepatocytes. The cell cultures were exposed to cadmium as CdCl2 or as either isoform of CdMT for a 20-h period at concentrations ranging from 50 to 500 ng Cd X ml-1. Cytotoxicity was assessed by determining the amount of lactic dehydrogenase released from the cells into the incubation medium and the incorporation of [3H] arginine into cell protein. The uptake of Cd by the cells was also measured. Cadmium chloride and both isoforms of CdMT were found to be toxic to hepatocytes although partial protection was afforded by the binding of cadmium to metallothionein (MT). At the higher exposure concentrations and in accordance with the toxicity data, the cells exposed to CdCl2 were found to accumulate more cadmium than those exposed to CdMT. The distribution of cadmium in the culture medium was examined using Sephadex G-75 chromatography. The speciation of cadmium is discussed in relation to its cytotoxicity.

Animals↗
PubMed1985

Absence of genotoxic effects of nonasbestos mineral fibers.

The biological activity of natural and synthetic mineral fibers has been examined. Natural attapulgite [(Mg, Al)2Si4O10(OH).4H2O], synthetic xonotlite [Ca3Si3O8(OH)2] and natural sepiolite [Mg2Si3O8.2H2O] were selected. Genotoxic effects were investigated by means of a well established cellular model based upon the measurement of unscheduled DNA synthesis (UDS) in rat hepatocytes in primary culture. The intrinsic capacity of the fibers (1 and 10 micrograms/ml) to induce UDS was first tested. None of the fiber types showed detectable UDS-eliciting activity. Also, the possible modulation of the cellular response to genotoxic agents by the materials was examined by exposing the cells to mixtures of 2-acetylaminofluorene (AAF) (0.05 and 0.25 micrograms/ml) and fibers (1 and 10 micrograms/ml). In these experiments, the UDS response was significantly diminished in the presence of xonotlite. This phenomenon may reflect changes in the uptake and/or metabolism of AAF or may result from an inhibition of DNA repair processes, the latter suggesting a possible cocarcinogenic potential for this synthetic silicate. These results point to the immediate necessity of studying more extensively the biological effects of fibrous materials that can be used as substitutes for asbestos.

Animals↗
PubMed1985

Ultrastructural study of mineral fiber uptake by hepatocytes in vitro.

Cellular interactions of a series of fibrous materials were examined by the use of a well established in vitro system. Primary cultures of hepatocytes were exposed to natural attapulgite, synthetic xonotlite and natural sepiolite. Ultrastructural analyses revealed that hepatocytes can engage in the phagocytosis of all 3 types of fibers over an exposure period of 20 h. Attapulgite fibers were found in plasma membrane invaginations, and deeper in the cytoplasm, in vesicles exhibiting various shapes. Xonotlite was also incorporated in plasma membrane invaginations; furthermore, these fibers were present in large vacuoles where they were circumscribed by membranes and appeared somewhat isolated from the cytoplasm. Sepiolite fibers were also taken up by the cells and could likewise be identified in the previously described structures. These observations point to the relevance of the hepatocyte model for investigating the effects of fibrous materials at the cellular level.

Animals↗
PubMed1985

Genotoxicity of dimethylnitrosamine in the presence of chrysotile asbestos UICC B and xonotlite.

Interactions of particulates with chemical genotoxic agents may play an important role in the induction of carcinogenesis. With respect to bronchogenic cancer, the synergism associated with combined exposure to asbestos and tobacco smoke is a well-documented phenomenon. The present work focused on chrysotile asbestos and xonotlite. The latter is a fibrous calcium silicate which is increasingly being used to replace asbestos in various industrial applications. The study was aimed at testing the possible interaction of these materials with dimethylnitrosamine (DMN), a genotoxic component of tobacco smoke. The capacity of fibers to interfere with the genotoxic response elicited by DMN in the UDS/hepatocyte assay system specifically designed for sensitive detection of short-patch DNA repair, was looked for. The properties of the selected fibers with respect to binding affinity towards DMN were also examined.

2-Acetylaminofluorene↗
PubMed1985

Temporal bone fractures: a histopathologic study.

Trauma or injury to the skull, if of sufficient force, may produce a temporal bone fracture. However, terms such as basilar skull fracture, labyrinthine hemorrhage, or labyrinthine concussion are inadequate in that they do not describe the precise histopathologic lesion. We carried out a histopathologic study of the 14 ears in seven patients; all the patients suffered at least one temporal bone fracture. Our objective was to review the histopathologic findings of various fracture lines through the base of the skull and correlate these with the history and clinical findings.

Adult↗
PubMed1985

Persistence of the stapedial artery: a histopathologic study.

Persistence of the stapedial artery is a rare event. Fewer than 30 cases have been reported since the discovery of this artery in 1836. We carried out a histopathologic study on three temporal bones from two patients who had this anomaly, and were able to trace the full course of the artery. In two specimens a large stapedial artery persisted and substituted for the middle meningeal artery. In the third, a small, persistent stapedial artery ended in the arterial plexus surrounding the facial nerve. Persistence is discussed in terms of embryogenesis, developmental theories, histologic findings, and clinical significance. The material suggests that the stapedial artery can persist to varying degrees.

Arteries↗
PubMed1983

Histopathology of profound sensorineural deafness.

In all the cases of profound deafness that we examined, the sensory epithelium along the basilar membrane had severely degenerated. However, ganglion cell counts and peripheral fiber estimates demonstrated a high degree of variability when analyzed with respect to the state of the organ of Corti or the etiology of the original cochlear disorder. We conclude that a complex interplay of factors determines the number of cells remaining in the spiral ganglion at a given time. It appears impossible at present to predict which diseases or toxic states produce primarily a sensory loss while leaving a uniform and adequate number of cochlear neurons functionally intact. We would like to emphasize that although the ganglion cell counts were consistently reduced in all our cases of profound sensorineural deafness, it has always been a surprise to us to find that the actual numbers of surviving cells are considerable. Of 15 patients, all of whom were totally deaf, only 3 had ganglion cell counts less than 10,000, whereas the majority had counts well above 15,000. Observations of this kind are possible only if accurate ganglion cell counts are carried out. Estimating the number of spiral ganglion cells by only looking at microscopic sections usually results in estimates of greater cell loss than is actually present.

Adolescent↗
PubMed1979

Mode of action of carbimazole in Graves' disease.

In a series of hyperthyroid subjects treated with a high dose 'block-replace' regime, mean thyroidal technetium uptake was shown to fall progressively over an 18 month period. Furthermore, sub-total inhibition of hormone biosynthesis could be demonstrated, without evidence of proportionate inhibition of organification, the regression of radio-iodine on technetium thyroid uptake showing similar slopes in euthyroid, treated and untreated hyperthyroid subjects. Together with the reported differential in remission rates between propranolol and anti-thyroid drugs, it is concluded that carbimazole does not act solely by inhibiting intrathyroid hormono-genesis, but more definitively by affecting thyroid hyperstimulation at a pre-biosynthetic level. The inability to demonstrate normal suppressibility of trapping in any subject in the present series despite extended therapy with a 'block-replace' regime, further suggests that current concepts of 'suppressibility' are invalid, the progressive fall in technetium uptake being unlikely to represent spontaneous restoration of a normal pituitary-thyroid axis, but rather a direct influence or prolonged therapy with anti-thyroid drugs on the natural history of the disease.

Adolescent↗
PubMed1973

Single dose, "block-replace" drug therapy in hyperthyroidism.

In 30 consecutive hyperthyroid patients with diffuse goitre divided dose therapy with carbimazole 40 mg and triiodothyronine 80 mug daily was shown to produce total or subtotal block in thyroid hormonogenesis. Once produced, this block could be invariably maintained with an equivalent single daily dose for periods up to three years. Its notable acceptability to patients, a more stable degree of euthyroid control, ease of assessing suppressibility of trapping, and ability to treat patients in remote areas all support a wider use of this mode of therapy.

Adult↗