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Biomedical subjects

D Anderson

Publications and source records attributed to D Anderson.

At least 559 records · Page 31Linked to original sources

Changes in the expression of HLA and beta 2-microglobulin by cultured lymphoid cells.

Changes in the expression of HLA and beta 2-microglobulin (beta 2-m) antigens by cultured human lymphoid cell lines were investigated. HLA expression was assayed by indirect trace binding radioimmunoassay (RIA) with monoclonal antibodies and by determining sensitivity to complement-dependent lysis by alloantisera. Lymphoid cells in culture were found to undergo changes in the expression of HLA and beta 2-m antigens characterized by decreased membrane expression of these antigens at high cell densities or after a prolonged period of cultivation. The decreased expression of HLA and beta 2-m antigens apparently is due neither to a masking phenomenon nor to a lack of nutrients or an accumulation of metabolites in the culture media but is perhaps mediated by a cell-to-cell contact mechanism. Human interferon was found to enhance the expression of HLA and beta 2-m, apparently overriding the effects on major histocompatibility complex (MHC) expression induced by cell density.

Antibodies, Monoclonal↗

Clonidine and lidamidine (WHR-1142) stimulate sodium and chloride absorption in the rabbit intestine.

The effects of clonidine and lidamidine on ion transport in the intestine of the rabbit were determined. In the ileum both clonidine (10(-6) M) and lidamidine (10(-3) M) (a) decreased the short circuit current (-1.9 +/- 0.3 and -2.0 +/- 0.4 muEq/h . cm2, respectively) and potential difference; (b) increased net sodium absorption (2.0 +/- 0.6 and 1.8 +/- 0.4 muEq/h . cm2) and chloride absorption (3.4 +/- 0.5 and 3.4 +/- 0.6 muEq/h . cm2); and (c) increased tissue conductance (8.7 +/- 1.7 and 10.0 +/- 1.6 mmho/cm2). The increase in net sodium and chloride absorption was primarily due to an increase in mucosal-to-serosal movement of the ions and a decrease in serosal-to-mucosal movement of chloride. The action of clonidine on the short circuit current was quantitatively similar to the action of epinephrine. Both were readily reversed by yohimbine, a specific alpha 2-adrenergic antagonist. Further, methoxamine, an alpha 1-adrenergic agonist has no effect on the short circuit current up to the concentration of 10(-5) M; and prazosin, an alpha 1-adrenergic antagonist, did not affect the change of the short circuit current induced by epinephrine. The results indicate the presence of alpha 2-adrenergic receptors on the intestine and suggest that alpha 2-adrenergic stimulation may account for the effect of epinephrine on ion transport. Lidamidine was studied because it is structurally related to clonidine and has many similar actions. Yohimbine transiently reversed the effect of lidamidine. alpha 1-Adrenergic or dopaminergic antagonists did not reverse the effect of lidamidine, suggesting that it may affect alpha 2-adrenergic receptors. The results indicate that both clonidine and lidamidine stimulate electrolyte absorption and may be clinically useful.

Action Potentials↗

The monitoring of environmental mutagens/carcinogens. A perspective on tests predicting chemical mutagens/carcinogens in man.

The current interest in the subject of environmental mutagenesis/carcinogenesis has prompted much investigation into ways of identifying chemicals which may pose a genotoxic risk to man and his progeny. Various systems have been developed which measure gene mutation, chromosome damage and DNA repair. The main test systems are briefly discussed as well as their usage and limitations.

Animals↗

Scapular manipulation for reduction of anterior shoulder dislocations.

Scapular manipulation is an effective, safe method to reduce an acute anterior shoulder dislocation. The method described by Bosley and Miles in 1979 has been used by the Orthopaedic Staff at Henry Ford Hospital since February 1979. It was the initial reduction method used in 51 patients and was successful in 47. With experience, and a properly executed technique, the method is relatively simple and can be applied to all patients.

Female↗

Clear cell adenocarcinoma of the vagina and cervix in black females.

Twenty-eight black females with clear cell adenocarcinoma of the vagina and cervix have been accessioned in the Registry for Research on Hormonal Transplacental Carcinogenesis. Most were born in the southern United States and histories of prenatal exposure to diethylstilbestrol were less frequent than with white patients. The characteristics of these cases were similar to those among whites in stage, variety of cell type, and patient survival.

Adenocarcinoma↗

Electroconvulsive therapy and memory dysfunction: is there evidence for prolonged defects?

The authors reviewed 39 papers which concern the long-term effects of electroconvulsive therapy (ECT) on human memory. Although the authors caution that methodological considerations preclude a decisive assessment, the majority of the studies suggest that ECT does not normally produce prolonged memory defects. Some recent studies do document subtle but persistent defects several months after ECT, especially in personal autobiographical material. These defects appear to be more annoying than seriously incapacitating. Variables considered important in an ideal design of studies on ECT and memory are discussed.

Amnesia↗

The relationship between early deaths and implants in control and mutagen-treated CD-1 mice in dominant lethal assays.

In dominant lethal assays it has been assumed that the number of early deaths per pregnancy is a function of the germ cells and is independent of maternal influence. It has also been assumed that there is a direct relationship between the number of early deaths and the total number of implants, which in turn has influenced dominant lethal studies. The present communication supports the view that at least this second assumption is erroneous. Data from dominant lethal assays using CD-1 mice in 2 laboratories have been compared and early deaths per implantation as a function of implantations were examined and the implications of the results generated have been considered. It was found in negative control data that a direct relationship between the numbers of early deaths and total implantations was true only at very low, possibly, very high total implantation numbers. Between 4 and 15 implant (based on over 7500 females) the average number of early deaths remained constant. After treatments the direct relationship seen at low implant numbers extended over a larger implant range, but above this range the average number of early deaths again tended to remain constant. It followed, therefore, that, when early deaths per implantation as a function of implantations was considered the average values were dependent on total implantation number over the whole range decreasing as implantations per pregnancy increased. The effect of the mutagens on the frequency of early deaths per implant was greater at low implant numbers. Approaches to statistical analysis of the data from these studies are discussed in the light of the findings and a model is proposed whereby these unexpected relationships between the number of early deaths and the numbers of implantations are explicable in terms of the properties of the germ cells in CD-1 mice, but they may also be affected by some aspect of the female's physiology.

Animals↗

Chromosomal analysis in vinyl chloride exposed workers: comparison of the standard technique with the sister-chromatid exchange technique.

A group of 21 workers occupationally exposed to vinyl chloride and 6 controls were examined for the presence of chromosomal aberrations or sister-chromatid exchanges in their peripheral lymphocytes. These people comprised a second sampling from a group of exposed workers and controls first examined 18 months earlier. The vinyl chloride exposed workers showed levels of chromosomal aberrations elevated above those of the controls, but there was only a slight increase in sister-chromatid exchanges (per cell or per chromosome) and this increase was not statistically significant. Sister-chromatid exchanges (SCEs) were also examined from in vitro cultures of lymphocytes exposed in G0/early G1 and late G1/early S phase to vinyl chloride, both with and without metabolic activation. There was no increase in SCEs in vitro without metabolic activation but there was a marked increase with metabolic activation and this increase was shown to be independent of cell-cycle phase. It thus was apparent that the small increases of SCEs in workers were not due to the inability of vinyl chloride to induce SCEs in human lymphocytes but were probably because of low exposures and SCE levels could have returned to normal relatively quickly after exposure. The present study suggested that the analysis of longer-living conventional chromosomal aberrations appeared to be a more sensitive monitor of exposure to vinyl chloride in exposed workers than the estimation of SCEs; however, it should be noted that in a 3rd sampling taken 24 months later the exposed workers had chromosomal aberration levels similar to the controls.

Cells, Cultured↗

Irradiated laboratory animal diets: dominant lethal studies in the mouse.

In 4 separate dominant lethal experiments groups of mice of either Charles River CD1 or Alderley Park strains were fed laboratory diets (Oakes, 41B, PRD, BP nutrition rat and mouse maintenance diet No. 1). The diets were either untreated (negative control diets) or irradiated at 1, 2.5 and 5 megarad and were freshly irradiated, or stored. The animals were fed their test diets for a period of 3 weeks prior to mating. Groups of mice given a single intraperitoneal injection of 200 mg cyclophosphamide per kg body weight served as the positive controls. Freshly irradiated PRD diet fed to male mice of both strains caused an increase in early deaths in females mated to the males in week 7 and to a lesser extent in week 4. The increase due to irradiation was small by comparison with that produced by the positive control compound. The responses for the other irradiated diets showed no significant increases in early deaths although some values for Oakes diet were high. The effect of storage was examined with PRD and BPN diet on one occasion and produced conflicting results. Thus there was some evidence that irradiated PRD diet has weak mutagenic activity in the meiotic and/or pre-meiotic phase of the spermatogenic cycle which appeared to be lessened on storage; the inclusion of such a diet in toxicological studies would therefore need to be carefully considered.

Animal Feed↗

Comparison of dominant lethal and heritable translocation methodologies.

Groups of male Alderly Park mice of proven fertility were dosed by gavage for 5 consecutive days per week for 8 weeks or 5 consecutive days only with 100 or 150 mg/kg body weight ethyl methanesulphonate (EMS) or by intraperitoneal injection once a week for 8 weeks or once only with 500 mg/kg shikimic acid. Animals dosed in this manner were compared in the dominant lethal and heritable translocation assays. Animals were mated for 2 consecutive weeks following the 8-week treatment and for 8 consecutive weeks after the 1-week treatment: regimes which were thus non-specific and specific respectively for the stages of spermatogenesis. An additional method of measuring dominant lethality involving counting uterine scars after weaning (Soares (1972) Mutation Res., 16, 425-427) was used and also compared with the conventional method. EMS was clearly confirmed as a mutagen but this was not the case for shikimic acid. For screening purposes the dominant lethal 8-week mating assay was much more efficient in return for the same effort for detecting mutagenic responses than an 8-week mating heritable translocation assay, since the induction of dominant lethal effects paralleled the induction of heritable translocations. 8-week treatment with EMS showed increased dominant lethality but severely reduced fertility and the small numbers of male offspring born made potential heritable effects difficult to assess. The 1-week treatment with EMS produced both dominant lethal and heritable effects. Soares' method can be useful for determining dominant lethal effects in a heritable translocation assay. The "sieving" method of mating to determine partial and total sterility questions the necessity for a negative control in a heritable translocation study.

Animals↗

Issues relevant to the assessment of chemically induced chromosome damage in vivo and their relationship to chemical mutagenesis.

Rats have been exposed by different routes of administration (inhalation, orally and intraperitoneally) to known mutagens and their bone-marrow cells sampled at different times to determine the extent of chromosome damage. The mutagens investigated were ethyl methanesulphonate, mitomycin C, trimethylphosphate, benzene and vinyl chloride, at single and/or multiple doses (5 consecutive daily). Various categories of chromosome damage were observed in all cases. However, the extent of damage due to chromosome and chromatid gaps was greater than, and generally increased in parallel with, other categories of damage. It has been suggested tht chromosome and chromatid gaps are indicative of toxic phenomena but this study suggests that such aberrations could be useful and sensitive indicators of chemically induced genetic damage. In addition the study has also confirmed that single exposure is as effective as multiple exposure in producing chromosome damage and that the correct sampling time is necessary to detect this damage. Therefore for screening purposes a time course sampling after a single treatment regime would be suitable for detecting the mutagenic potential of a chemical.

Animals↗

The genotoxic potential of bases and nucleosides.

This study was conducted to determine if naturally occurring cell constituents could themselves cause mutation. All the bases and their corresponding nucleosides have been shown to produce chromosome damage in P338 mouse lymphoma and Chinese hamster ovary cells in culture. In addition thymidine has produced an increase in V79 cells resistant to 8-azaguanine and ouabain. Such damage probably arises as a result of imbalanced DNA-precursor pools. Thus mutagenic events may arise by mechanisms unrelated to direct alterations to DNA.

Animals↗

Meningioma and the ophthalmologist. A review of 80 cases.

We reviewed the charts of all patients with pathologically proven meningiomas who were admitted to the Montreal General Hospital between 1960 and 1977. Of the 80 patients reviewed, we found approximately one third of them had ophthalmological symptoms of which visual loss, field defect, and diplopia were the most common. Most of these patients also had neurological symptoms, but they were often nonspecific. One half of the patients presented with chronic symptomatology such as headache, mental change, and visual loss. One third of the patients presented acutely with seizures, hemiplegia, or dysphasia. Of the investigations done, the angiogram and brain scan were most often diagnostic, while the skull x-ray and EEG were often normal. Meningioma of the sphenoidal ridge, parasellar area, and occiput most often produced visual deficits. In almost one half of these patients, the visual deficit was initially misdiagnosed.

Adolescent↗