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Biomedical subjects

M R Adams

Publications and source records attributed to M R Adams.

At least 145 records · Page 8Linked to original sources
PubMed1987

Contraceptive steroids and coronary artery atherosclerosis in cynomolgus macaques.

The influence of two types of steroidal contraception on the extent of coronary, aortic, carotid, and iliaco-femoral atherosclerosis was assessed in 57 cynomolgus macaques with moderate diet-induced hyperlipoproteinemia. Thirteen animals were treated with an intravaginal ring that released 17 beta-estradiol and levonorgestrel. Fifteen females were treated with an oral contraceptive (OC) composed of ethinyl estradiol and norgestrel. Fifteen females received placebo vaginal rings, and 14 males were untreated. The contraceptive treatments resulted in similar large reductions in plasma high-density lipoprotein (HDL) cholesterol concentrations. Neither treatment influenced the prevalence of coronary artery atherosclerosis. However, treatment with the contraceptive vaginal ring was associated with increased extent of coronary artery atherosclerosis (plaque size) relative to untreated females, whereas treatment with the OC was not. The contrasting effects of the two treatments could not be explained by differences in total plasma cholesterol, HDL cholesterol, or blood pressure. The results suggest that the greater estrogenic influence associated with the ethinyl estradiol-containing OC resulted in inhibition of coronary artery atherosclerosis despite a pronounced progestin-induced lowering of plasma HDL cholesterol concentration and, further, that hormonal balance may have a marked influence on the relationship between plasma lipids and atherogenesis.

Animals↗
PubMed1987

The effects of beta-adrenergic blocking agents on atherosclerosis and its complications.

Epidemiologic and experimental data are reviewed to determine whether treatment with beta-adrenergic blocking agents ('beta blockers') is likely to be antiatherogenic. Both indirect and direct evidence are considered. Indirect evidence is derived from studies of the effects of beta blockers on the risk factors for atherosclerosis, or on the disease sequelae of atherosclerosis. Direct evidence refers to studies in which atherosclerosis is an endpoint. Regarding indirect evidence, the data generally are consistent with a retarding or neutral effect of beta blockers on atherosclerosis. For example stroke incidence is reduced when hypertension is treated with beta blockers. About half of these same studies also show a reduction in the incidence of myocardial infarction, a complication that may be more closely related to atherosclerosis extent and severity than is stroke, which can have a nonatherosclerosis origin. The most important potential negative effect of beta blockers occurs with respect to serum lipid concentrations. However, there is no evidence that atherosclerosis is worsened as a result of pharmacologically induced alterations of serum lipids. The direct evidence more clearly indicates a retarding effect of beta blockers on atherosclerosis, with 11 of 13 studies having outcomes in this direction. However, interpretation of these studies is complicated by the fact that all of the data are derived from animal models, some of which are not similar to human beings in the development of atherosclerosis. Also, the studies are diverse, not only in the research designs and species utilized, but also in the type of beta blocker employed, the degree of beta blockade achieved, and the anatomic location of lesions. In summary, the data suggest that treatment with beta blockers may retard atherosclerosis. A more definitive answer requires efforts in two directions: (a) studies on atherosclerosis in selected populations of human beings, using cineangiography or autopsy material; and (b) additional, well-controlled studies in appropriate animal models.

Adrenergic beta-Antagonists↗
PubMed1987

A note on shelf-life extension of British fresh sausage by vacuum packing.

Vacuum packing of British fresh sausage in a low oxygen permeability film (Diolon) extended the product shelf-life at 6 degrees C to more than 20 d compared with 9-14 d in conventional packs. After 10 d storage, counts of key spoilage organisms such as yeasts and Brochothrix thermosphacta were generally 2 log cycles lower in vacuum packs. Vacuum-packed sausages also displayed a slower rate of loss of free sulphite. Variations in pack permeability to SO2 were not responsible for this. Losses of free SO2 in stored sausages are largely due to the production of sulphite-binding agents by yeasts. Selective enumeration of these yeasts showed them to be inhibited by conditions of vacuum packing. The extension of shelf-life observed is ascribed to the reduction in growth rate of the spoilage flora in vacuum packs coupled with the consequent maintenance of inhibitory levels of sulphite for a longer period.

Animals↗
PubMed1987

Inhibition of coronary atherosclerosis by propranolol in behaviorally predisposed monkeys fed an atherogenic diet.

We studied the effect of propranolol on the diet-induced coronary artery atherosclerosis (CAA) in 30 adult male cynomolgus monkeys living in social groupings of five animals each. Animals in the "treated" segment (n = 15) consumed propranolol, which was mixed into an atherogenic diet. Animals in the "untreated" group (n = 15) consumed only the atherogenic diet. Finally, the social groupings were subjected to disruption through monthly redistribution of monkeys among the groups within each treatment segment. The experiment lasted 26 months, following which all animals underwent autopsy during which the coronary arteries were evaluated for atherosclerosis. Regarding atherosclerosis, we observed a significant interaction between social status and experimental condition (p less than .03). Socially dominant animals had (as in previous studies) significantly exacerbated CAA, but only in the untreated segment; the effect of social dominance on CAA was abolished by long-term administration of propranolol. The antiatherogenic effect of propranolol on dominant animals was independent of the influences of serum lipid concentrations, blood pressure, and resting heart rate. We conclude that treatment with beta-adrenergic-blocking agents may confer a degree of protection against CAA among individuals behaviorally predisposed to coronary heart disease.

Aggression↗
PubMed1987

Mechanisms of atherogenesis.

Recently the nature of the cellular and molecular events in atherogenesis have been elucidated better. Some of these findings may be important in explaining individual differences in susceptibility to atherosclerosis that are independent of known risk factors. Nonhuman primates are valuable models for the study of mechanisms of diet-induced atherosclerosis. Cynomolgus macaques are useful for studies of male-female differences in atherosclerosis, since they share with premenopausal white women a relative protection against coronary atherosclerosis compared with males. These animals are also useful for psychosocial atherosclerosis research since social status affects the extent of atherosclerosis, and experimentally induced social stress increases extent of coronary artery atherosclerosis. Nonhuman primates have also been useful for studies of individual differences in susceptibility to diet-induced atherosclerosis and its risk factors. These studies have indicated that about 75% of the variability in the plasma cholesterol response to dietary cholesterol is attributable to genetically determined differences in cholesterol absorption and lipoprotein catabolism. There is preliminary evidence suggesting the existence of "mesenchymal susceptibility" in nonhuman primates; i.e., differences in risk of atherosclerosis that are independent of exposure to known risk factors. Efforts are being made to establish colonies of rhesus monkeys that possess contrasting degrees of mesenchymal susceptibility.

Animals↗
PubMed1987

Psychosocial influences on the pathogenesis of atherosclerosis among nonhuman primates.

Epidemiologic and clinical evidence derived from studies of human beings suggests that psychosocial phenomena may account for much of the variability in atherosclerosis extent and severity that is unexplained by the "traditional" risk factors (serum lipids, hypertension, and smoking). Animal preparations provide an opportunity to test hypotheses concerning the role of psychosocial phenomena in atherogenesis and to explore the mechanisms by which the effects of such phenomena are mediated. Here we review a relatively large series of studies of cynomolgus monkeys (Macaca fascicularis), a 5 kg animal having a complex social organization. The data indicate that, among male animals, individual behavior characteristics (social status and aggressiveness), physiologic responsiveness to psychological challenge, and stability of the social environment all interact to affect atherogenesis. Among female animals, individual patterns of aggressiveness appear to influence ovarian function, which in turn affects atherosclerosis. Future advances in the behavioral medicine aspects of atherogenesis are likely to arise through elucidation of the pathophysiologic pathways by which these behavioral responses and characteristics contribute to the events (endothelial injury, smooth muscle cell proliferation, lipid accumulation, calcification, and necrosis) associated with plaque pathogenesis. Such research can be pursued in studies utilizing nonhuman primates as well as in complementary studies involving human subjects.

Aggression↗
PubMed1986

Effects of age and/or puberty on coronary artery atherosclerosis in cynomolgus monkeys.

In this retrospective study of diet-induced atherosclerosis in male cynomolgus macaques, juvenile (2.5-3.5 years) and adult (6-12 years) monkeys that had consumed comparable atherogenic diets resulting in similar plasma lipid concentrations showed marked differences in coronary artery atherosclerotic lesion characteristics and extent. Adult animals (n = 16) developed more extensive lesions characterized predominantly as proliferative atherosclerotic plaques, while juveniles (n = 10) had minimal lesions that consisted primarily of fatty streaks. These differences in lesion characteristics and extent were not explained by differences in blood pressure. It is uncertain if these quantitative and qualitative differences in susceptibility to diet-induced atherosclerosis are due to intrinsic age-related changes in the arterial wall and/or related to the endocrine and metabolic changes associated with puberty. These findings may have relevance to the natural history of atherosclerosis in human beings.

Aging↗
PubMed1986

Effects of ovariectomy, social instability and social status on female Macaca fascicularis social behavior.

The effects of ovariectomy, social instability and social status on affiliative and agonistic behavior were studied in 44 females housed in 10 unimale groups. Five of the groups contained ovariectomized females and five groups contained intact females. The membership among three groups of intact females (n = 13) and three groups of ovariectomized females (n = 13) was reorganized every three months (unstable), and the other groups were left undisturbed (stable) for the 22 month study. The behavior of each female was recorded during 160 (stable) or 190 (unstable) 15 min focal observations of each subject. The social status of each female was determined by outcomes of agonistic interactions. It was hypothesized that the effects of social instability and status would be more pervasive than the effects of ovariectomy. It was found that ovariectomy reduced interfemale affiliation and increased male-female agonism. Social instability increased submissions to males and females and time spent alone, and decreased interfemale affiliation. Dominant animals were more aggressive and less submissive than subordinates. Thus, ovariectomy influenced both isosexual and heterosexual social interaction, implying mediation of these behaviors, at least in part, by ovarian hormones.

Animals↗
PubMed1985

Psychosocial influences on ovarian endocrine and ovulatory function in Macaca fascicularis.

Social subordination is associated with impaired reproductive success among female macaques living in natural or "semi-natural" environments. We studied the relationship between social status and ovarian function in female cynomolgus macaques living in socially stable single-male harem groups or in groups of like composition in which social instability was induced by the frequent redistribution of female group members. Compared to socially dominant females, socially subordinate females had fewer ovulatory menstrual cycles, more cycles with deficient luteal phase plasma progesterone concentrations, increased adrenal weights and increased heart weights. Social instability influenced none of these variables. In fact, females living in the situations of induced social instability had higher luteal phase plasma progesterone concentrations; this may be the result of frequent exposure to novel males. The results indicate that impaired reproductive success observed in socially subordinate female macaques may be related, at least in part, to changes in ovarian endocrine and ovulatory function.

Adrenal Glands↗
PubMed1985

The role of individual differences in lipoprotein, artery wall, gender, and behavioral responses in the development of atherosclerosis.

Striking individual differences exist in the response of animals to atherogenic diets. In this communication, we have summarized the accumulated data that relate to a better understanding of this individuality in susceptibility to atherosclerosis. Described herein, are the accumulated data concerning individual differences in the ways in which animals respond to dietary cholesterol. Also contained in this review, are beginning efforts to understand individual differences in susceptibility to coronary artery atherosclerosis at the level of the artery wall ("mesenchymal susceptibility"). We have placed special emphasis on individual differences that exist among cynomolgus macaques in certain psychosocial variables that contribute to individual differences in susceptibility. Among male cynomolgus macaques both status and social condition contribute to these individual differences. Additionally, individual differences in cardiovascular reactivity contribute to varying degrees of atherosclerosis development largely independent of plasma lipid concentrations. Among cynomolgus macaque females, stress-ovarian function relationships have a major influence on the relative degree to which these female animals are protected against diet-induced coronary artery atherosclerosis.

Animals↗
PubMed1984

Psychosocial and reproductive influences on plasma lipids, lipoproteins, and atherosclerosis in nonhuman primates.

Until recently, research in experimental atherosclerosis focused primarily on nutritional influences on plasma lipids, lipoproteins, and atherosclerosis. We review here the results of recent studies of independent and interactive influences of psychosocial and reproductive influences on atherosclerosis in nonhuman primates. These studies have produced evidence that, as in human beings, individuals with certain personality characteristics who are frequently faced with stressful or challenging situations are at increased risk of coronary artery disease. Preliminary evidence suggests that this relationship may be mediated, in part, by heightened sympathetic arousal, i.e., cardiovascular hyperresponsiveness, to the environmental challenge. Also, as in human beings, evidence has been produced that certain negative behavioral and psychosocial variables can have a significant independent influence on plasma lipids. As regards reproductive influences, the cynomolgus macaque seems to share with premenopausal white women a relative protection against coronary artery atherosclerosis. This "female protection" against diet-induced atherosclerosis is abolished by ovariectomy, which also results in increased total plasma and low density lipoprotein (LDL) cholesterol concentrations. Subordinate social status also seems to abolish female protection in some individuals. Preliminary evidence suggests that subordinate females most liable to this loss of protection are those with apparent stress-induced chronic ovarian endocrine dysfunction, which, in turn, is associated with increased plasma LDL cholesterol and decreased plasma high density lipoprotein (HDL) cholesterol concentrations.

Animals↗
PubMed1984

Psychosocial influences on female 'protection' among cynomolgus macaques.

We evaluated atherosclerosis (coronary artery, aortic and carotid bifurcation), plasma lipids, and blood pressure in 15 male and 23 female cynomolgus macaques (Macaca fascicularis). In addition, female social behavior and ovarian function were monitored. The females lived in stable (unmanipulated) or unstable (periodically altered composition) social groups while males lived in stable groupings. All animals were fed for 30 months an atherogenic diet which resulted in moderate hyperlipoproteinemia (median total plasma cholesterol congruent to 275 mg/dl). Socially dominant females had less extensive and severe coronary artery atherosclerosis than males or socially subordinate females; atherosclerosis extent and severity were similar in these latter two groups. Importantly, dominant females also had regular ovarian function and relatively small adrenal glands while subordinate females had impaired ovarian function (increased frequency of anovulatory cycles and luteal phase deficiencies) and relatively large adrenal glands. The dominant and subordinate females did not differ in plasma lipids. These results suggest that female 'protection' from coronary artery atherosclerosis may be influenced as much by behavioral and hormonal characteristics as by plasma lipids. Among other findings, males had more extensive atherosclerotic lesions at the carotid bifurcations than females. In addition, males had lower high density lipoprotein cholesterol concentrations and higher blood pressures than females. The gender difference in extent of atherosclerosis at the carotid bifurcation was unrelated to social factors or plasma lipids; it may have been due, in part, to the higher blood pressures of the males.

Adrenal Glands↗
PubMed1984

Erectile failure in cynomolgus monkeys with atherosclerosis of the arteries supplying the penis.

We evaluated by direction observation the sexual behavior of normal and atherosclerotic adult male cynomolgus monkeys (Macaca fascicularis) toward sexually receptive female cynomolgus monkeys. Marked deficits in erectile and ejaculatory function were found in the atherosclerotic monkeys. These animals were normal in other aspects of social and sexual behavior and had normal concentrations of circulating testosterone. At necropsy, histopathologic evaluation of the urogenital vasculature revealed atherosclerotic lumen obstruction of internal iliac, internal pudendal and penile arteries which apparently resulted in diminished in vivo capacity of these vessels to accommodate the large increases in blood flow required for the production of an erection. These findings provide further evidence for the existence of an association between atherosclerotic obstruction of the internal iliac, pudendal and penile arteries and the occurrence of erectile failure, and suggest the usefulness of the nonhuman primate as an animal model for clinical studies of atherosclerotic sexual dysfunction of man.

Animals↗
PubMed1984

Hemobartonellosis in squirrel monkeys (Saimiri sciureus) in a domestic breeding colony: case report and preliminary study.

Infection with Hemobartonella sp was diagnosed in a colony-born squirrel monkey with normocytic, normochromic anemia and pronounced punctate erythrocytic basophilic stippling on Wright's-Giemsa stained blood films. The diagnosis was confirmed using transmission electron microscopy. Two randomly selected colony-born squirrel monkeys were splenectomized in an effort to activate and detect possible latent hemobartonellosis . One monkey became parasitemic 12 days following splenectomy. The second monkey was inoculated on day 14 with 1 ml of whole blood from an infected, but nonparasitemic monkey and developed overt parasitemia 3 days later (day 17 following splenectomy). Infections in the latter two monkeys were confirmed using scanning electron microscopy.

Anaplasmataceae↗
PubMed1983

Influence of a levonorgestrel-containing contraceptive vaginal ring on plasma lipids and lipoproteins in cynomolgus monkeys.

The effect of a contraceptive vaginal ring (CVR) containing levonorgestrel on plasma lipid and lipoprotein concentrations and characteristics was assessed in ten cynomolgus monkeys. The animals were fed a diet similar to the average American diet in fat (40% of calories) and cholesterol (0.2 mg/kcal) content. The objective of this study was to determine if changes in lipids and lipoproteins caused by progestogen administration parallel those seen in human females. A parallel pattern would recommend the cynomolgus monkey as a model for studying the effects of progestogens on the atherosclerotic process. Treatment with the CVR resulted in significant decreases in total plasma, VLDL + ILDL + LDL, and HDL cholesterol concentrations and a decrease in the percentage of HDL2 in total HDL. Plasma triglyceride concentrations were low throughout the study and consistent effects of the CVR were not seen. CVR treatment resulted in increases in TPC:HDL-C ratios and in the flotation rate of the LDL particle. The patterns of effects on HDL cholesterol, total plasma cholesterol, and HDL2 concentrations were similar to the progestogen-induced changes observed in human plasma lipids and lipoproteins. Based on these effects, the cynomolgus monkey appears to be a suitable model for the study of progestogen-induced changes in plasma lipids and lipoproteins and their consequent influences on coronary artery atherosclerosis.

Animals↗
PubMed1983

Glycosylation pathways of two major Epstein-Barr virus membrane antigens.

Monoclonal antibodies to the Epstein-Barr virus (EBV) membrane antigens (MA) were used to delineate the sequence of events occurring during MA maturation. Immunoprecipitation experiments performed with B95-8 virus infected 1605L cells, pulse labeled in the presence of tunicamycin or 2-deoxyglucose, suggest that the nonglycosylated forms of the mature 236,000 (236K) and 86K MA have molecular weights of 149K and 69K, respectively. Monensin treatment results in the accumulation of a 189K antigen which is converted to the mature 236K MA after a 2 hr chase in the absence of monensin. Experiments with monensin also suggest that an 84K intermediate is involved in the formation of the mature 86K MA. The mature 236K MA is resistant to endoglycosidase H while the 189K intermediate and the mature 86K MA are partially sensitive to this enzyme. The mature 236K and 86K MA and the 189K intermediate are resistant to endoglycosidase D.

Antibodies, Monoclonal↗