Search PubMed⌕ Search

Biomedical subjects

M R Malinow

Publications and source records attributed to M R Malinow.

At least 91 records · Page 5Linked to original sources

Prevalence of hyperhomocyst(e)inemia in patients with peripheral arterial occlusive disease.

A micromethod adapted for automated determinations was used to measure basal plasma levels of homocyst(e)ine [H(e)]. These levels included the sum of free and bound forms of homocysteine, its disulfide oxidation product, homocystine, and the homocysteine-cysteine-mixed disulfide. Two groups of subjects were studied: apparently healthy individuals (n = 103) and patients with peripheral arterial occlusive disease (PAOD) (n = 47). Because age in PAOD patients was higher than in control subjects, the control subjects were subdivided into younger and older groups (aged 60 years or less and more than 60 years, respectively). The H(e) levels in the younger groups were 11.18 +/- 3.58 (mean +/- SD, expressed as homocysteine) and 8.58 +/- 2.82 nmol/ml in men and women, respectively; in the older groups, the levels were 10.74 +/- 2.16 and 9.04 +/- 2.16 nmol/ml in men and women, respectively. There was a positive correlation of H(e) levels with age in the younger control women (r = 0.373; p less than 0.02); no significant correlations were present in the other three control groups. Levels of H(e) in PAOD patients (15.44 +/- 5.76 and 17.04 +/- 8.26 nmol/ml in men and women, respectively) were significantly higher than those indicated above in the older controls. Next, the PAOD patients were assigned to two subgroups: 1) those with normal levels of H(e) (within two standard deviations of the mean of the control values) and 2) those with elevated levels of H(e). Age, cholesterolemia, and the prevalence of smoking and diabetes were similar in both subgroups. These results suggest that elevated plasma H(e) is an independent risk factor for arterial occlusive disease.

Age Factors↗

Inhaled tobacco sterols: uptake by the lungs and disposition to selected organs of rats.

Tobacco sterols (cholesterol, beta-sitosterol, campesterol, and stigmasterol) are present in tobacco smoke and appear in plasma of mammals exposed to cigarette smoke. Because tobacco sterols may be important in the pathogenesis of smoking-induced lung and vascular diseases, we studied the pattern of deposition of cigarette sterols in the lungs and appearance of cigarette sterols in plasma and body organs of rats. After exposure to twenty 5 ml "puffs" of smoke from tobacco labeled with [4-14C]cholesterol or beta-[4-14C]sitosterol, rats were killed just after exposure (day 0) and on days 2, 5, 8, 11, 15, and 30, and the lungs and selected body organs analyzed for activity. We found that cigarette sterols are associated with particulates in cigarette smoke, deposited mostly in distal airspaces and parenchyma of the lungs, and appear in plasma and several body organs for more than 30 days after this single exposure to cigarette smoke. Bronchoalveolar lavage fluid contained relatively small amounts of radiolabel for only the first few days, suggesting that most of the sterols were rapidly incorporated in lung parenchyma. Because disorders of sterol metabolism have been implicated in a variety of diseases including atherosclerosis and cancer, the significance of tobacco sterols to human smoking-induced diseases deserves further study.

Animals↗

Effects of synthetic glycosides on steroid balance in Macaca fascicularis.

The predominantly beta-anomer of diosgenin glucoside (DG) was synthesized and its effects on cholesterol homeostasis were tested in monkeys. Cynomolgus macaques (Macaca fascicularis) were fed, during two 3-week periods, a semipurified diet with 0.1% cholesterol and a similar ration containing 1% DG, respectively. A Chow diet was given for 5 weeks between the experimental periods. Cholesterol and bile acid balance were analyzed during the last week of each semipurified diet. Diosgenin glucoside reduced cholesterolemia from 292 mg/dl to 172 mg/dl, decreased intestinal absorption of exogenous cholesterol from 62.4% to 26.0%, and increased secretion of endogenous cholesterol from -0.8 to 93.5 mg/day. The fecal excretion of neutral steroids rose from 40.7 to 157.3 mg/day; that of bile acids changed, nonsignificantly, from 23.1 to 16.0 mg/day. The cholesterol balance was -44 mg/day in the control period, and 88 mg/day in the DG-fed animals. No toxic signs were observed. Thus, when long-term studies demonstrate that the glucoside is well tolerated, DG and other synthetic glycosides with similar activities may be of use in the management of hypercholesterolemia and atherosclerosis.

Animals↗

Absorption of cholesterol and beta-sitosterol from cigarette smoke in Macaca mulatta.

When smoke from single cigarettes containing [4-14C]cholesterol or beta-[4-14C]sitosterol was delivered to the lungs of Rhesus macaques, plasma contained radiolabeled sterols up to 50 days later. Since cholesterol, as well as plant sterols (campesterol, stigmasterol and beta-sitosterol), are normally present in cigarette smoke, our observations suggest that protracted absorption of sterols occurs after cigarette smoking.

Animals↗

Adverse effects of the treatment for hyperlipidemia.

A variety of treatments to lower elevated plasma lipid levels in patients with hyperlipidemia are available. Adverse side effects ranging from mere annoyances to uncommon serious consequences may be associated with dietary modification, recreational physical exercise, and drug intervention. As in other clinical circumstances, risk-to-benefit ratios must be taken into consideration in the management of hyperlipidemia.

Anion Exchange Resins↗

Elimination of toxicity from diets containing alfalfa seeds.

Cynomolgus macaques were fed autoclaved alfalfa seeds for up to 1 yr. There were no humoral signs of a syndrome resembling systemic lupus erythematosus. The data are in contrast to those previously reported in monkeys fed raw alfalfa seeds, in which a systemic lupus erythematosus-like syndrome was induced in a shorter interval. The autoclaved seeds retained antihypercholesterolaemic effects.

Anemia↗

Experimental models of atherosclerosis regression.

Regression of atherosclerosis has been demonstrated in several species of animals, including rabbits, chickens, rats, dogs, pigeons, pigs, and nonhuman primates. Regression has been associated with withdrawal of cholesterol from the diet or with the ingestion of cholestyramine, alfalfa meal, or alfalfa saponins in monkeys fed high-cholesterol diets. Although regression of atherosclerosis has been documented by sequential contrast arteriography in humans, the correspondence of regression in animals and in humans needs to be established.

Animals↗

Systemic lupus erythematosus-like syndrome in monkeys fed alfalfa sprouts: role of a nonprotein amino acid.

Hematologic and serologic abnormalities similar to those observed in human systemic lupus erythematosus (SLE) developed in cynomolgus macaques fed alfalfa sprouts. L-Canavanine sulfate, a constituent of alfalfa sprouts, was incorporated into the diet and reactivated the syndrome in monkeys in which an SLE-like syndrome had previously been induced by the ingestion of alfalfa seeds or sprouts.

Animals↗

Ultrastructure of experimental coronary artery atherosclerosis in cynomolgus macaques. A comparison with the lesions of other primates.

We studied the ultrastructure of the left anterior descending coronary artery in 6 female cynomolgus macaques fed atherogenic food containing 0.5% cholesterol for 6 months, and in 2 female cynomolgus macaques that had received food low in cholesterol. Animals given the atherogenic food had coronary artery lesions of a characteristic two-level architecture consisting of a lipid-poor upper cap, and of a lipid-rich lower core. The cap consisted of layers of smooth muscle cells that were rich in rough endoplasmic reticulum and contained few myofilaments and relatively few lipid droplet inclusions. The core consisted mainly of macrophages overloaded with droplet inclusions (macrophage foam cells), droplet-laden smooth muscle cells, and extracellular lipid and cell debris. Some macrophage foam cells were in mitosis. The largest lipid cores contained multinucleate giant cells with large intracellular crystal clefts. Dead macrophage foam cells were the source of the extracellular lipid and debris particles. Intimal cores often extended into the adjacent media. The adventitia was involved in the intima-media lesions in 3 of the animals. Compared with the coronary artery lesions of rhesus macaques and patas monkeys given similar atherogenic diets, cynomolgus monkey lesions were morphologically closer to human atherosclerotic plaques with respect to their stratification into a cap and a core.

Adolescent↗

Diet-induced systemic lupus erythematosus (SLE) in primates.

Ten adult, female cynomolgus macaques were randomly assigned to two equal groups: (1) semipurified diet (SPD); and (2) SPD with 45% ground alfalfa seed (AS). Both groups were studied at monthly intervals after 5 mo on their respective diets. Control animals had a mean hematocrit (Hct) of 43 +/- 2%, negative antiglobulin (AG), antinuclear antibody (ANA) and LE cell tests. Mean values for C3 and C4 were 309 +/- 47 mg/dl and 35 +/- 7 mg/dl, respectively. Mean serum binding to radiolabeled double stranded deoxyribonucleic acid (dsDNA) was 1.9 +/- 0.2%. Three of five animals fed AS developed signs of an SLE-like illness characterized by AG-positive anemia (lowest Hct 30%), positive ANA (highest titer greater than 1:15, 360; rim pattern) and elevated anti-dsDNA binding (highest 96%) with variable degrees of hypocomplementemia. One animal had granular deposition of immunoglobulin and complement at the dermal-epidermal junction of clinically normal skin the presence of immune complex-induced glomerulonephritis.

Animals↗