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Biomedical subjects

K E Anderson

Publications and source records attributed to K E Anderson.

At least 145 records · Page 8Linked to original sources
PubMed1992

Biochemical characterization of coumarin 7-hydroxylase activity in chick embryo liver microsomes.

Coumarin occurs naturally in the diet and can induce and inhibit cytochrome P450 enzymes. Hepatic coumarin 7-hydroxylase activity is the major pathway for coumarin metabolism in humans but not in rats, most strains of mice, or other laboratory animals. Coumarin 7-hydroxylase activity and the effects of chemical inhibitors and inducers on this activity were studied in 19-day-old chick embryo liver microsomes. Activity was between 35 and 75 nmol/mg protein/hr which is approximately 2-fold higher than reported for human liver microsomes. The pH optimum was 7.8 and the Km determined by both an ether extraction and a high performance liquid chromatography method was 7.3 +/- 0.9 (+/- SD) microM. Substrate inhibition was evident at coumarin concentrations above 250 microM (activities at 1000 and 4000 microM coumarin were 84 and 40% of Vmax, respectively). The Ki values (+/- SD) for inhibitors of microsomal coumarin 7-hydroxylase activity in vitro were: alpha-naphthoflavone, 46.9 +/- 19.8 nM; metyrapone, 0.8 +/- 0.9 microM; aniline, 12.3 +/- 8.2 microM; cimetidine, 70.9 +/- 27.9 microM; N-nitrosodimethylamine, 0.7 +/- 0.9 mM; and dimethyl sulfoxide, 7.9 +/- 1.9 mM. Treatment of chick embryos with pyrazole (40 mumol) increased coumarin 7-hydroxylase by 50% at 24 hr, but this activity was unaffected by treatment of embryos with 3-methylcholanthrene (2 mumol) or glutethimide (8 mumol). Thus, hepatic coumarin 7-hydroxylase activity in 19-day-old chick embryos is higher than in most laboratory animals and has similar biochemical properties as the enzyme in humans and mice. The chick embryo liver may be a useful system for studies on the biochemical effects of coumarin and the regulation of cytochrome P450-dependent coumarin 7-hydroxylase.

Animals↗
PubMed1992

Cancer mortality in the first degree relatives of young breast cancer patients.

In a retrospective cohort study, the mothers and sisters of 740 breast cancer patients aged under 36 at diagnosis have been studied for mortality and cancer incidence. Significantly increased breast cancer mortality was observed below age 60 (30 deaths; SMR = 3.4), but not at older ages (four deaths; SMR = 0.9). The cumulative breast cancer incidence in the relatives was 3.6% by age 50, 7.6% by age 60 and 11.6% by age 70. They also suffered excess mortality below age 60 for cancers of reproductive sites (cervix, ovary and endometrium; 15 deaths; SMR = 2.6) and lung (11 deaths; SMR = 3.2), but not for other sites (12 deaths; SMR = 0.9). This large population-based cohort study provides further confirmation of genetic susceptibility to breast cancer at young ages.

Adult↗
PubMed1992

Removal of plasma porphyrins with high-flux hemodialysis in porphyria cutanea tarda associated with end-stage renal disease.

Plasma porphyrin levels are markedly increased in patients with porphyria cutanea tarda (PCT) associated with end-stage renal disease. Conventional hemodialysis (CHD) with lower blood flow rates (less than 250 mL/min) and cuprophan or cellulose acetate membranes is ineffective in removing significant amounts of porphyrins in this condition. Changes in plasma porphyrin levels and porphyrin clearances during hemodialysis with higher blood flow rates and more-permeable, high-efficiency cellulose acetate and high-flux polysulfone dialyzers were evaluated in a chronic hemodialysis patient with PCT and markedly elevated plasma porphyrins. The polysulfone membrane achieved significantly better fractional porphyrin removal (P = 0.02) and porphyrin clearances (P less than 0.01) than did the high-efficiency cellulose acetate membrane. After conversion from maintenance CHD with a standard cellulose acetate dialyzer to a 4-wk period of high-flux hemodialysis (HFHD) with a polysulfone dialyzer, predialysis plasma porphyrins fell by 37%. After returning to CHD, plasma porphyrins returned to the higher prestudy levels. These observations suggest that HFHD with more permeable membranes and higher blood flow rates removes porphyrins more effectively than does CHD. HFHD may be a useful adjunct to other measures used in treating dialysis patients with PCT.

Cellulose↗
PubMed1992

Intergenerational patterns of teenage fertility.

One of the frequently cited consequences of teen childbearing is the repetition of early births across generations, which thereby perpetuates a cycle of poverty and disadvantage. We use data from the 1988 National Survey of Family Growth (NSFG), Cycle IV, to examine trends and determinants of the intergenerational teen fertility link for women who reached adolescence between the 1950s and the 1980s. We find that daughters of both white and black teen mothers face significantly higher risks of teen childbearing than daughters of older mothers. We also find, more generally, that patterns of teenage family formation (i.e., both marriage and childbearing behaviors) tend to be repeated intergenerationally. The results suggest that the intrafamily propensity for early childbearing is not inherited biologically, at least not through factors related to the timing of puberty. Rather, the intergenerational patterns appear to operate at least in part through the socioeconomic and family context in which children grow up.

Adolescent↗
PubMed1991

Coumarin-induced changes in delta-aminolaevulinic acid synthase and cytochrome P-450 in chick embryo liver.

Coumarin occurs naturally in the diet and inhibits several cytochrome P-450 enzymes in laboratory animals. The effect of coumarin was examined on haem biosynthesis and cytochrome P-450 activities in the 18-day-old chick embryo liver in ovo. At 40 and 50 mumol/embryo coumarin increased delta-aminolaevulinic acid synthase, porphyrins, cytochrome P-450, benzphetamine N-demethylase and benzo[a]pyrene hydroxylase. At 10 mumol/embryo coumarin decreased aniline 4-hydroxylase, and at both 10 and 50 mumol/embryo it decreased 7-ethoxyresorufin O-deethylase, coumarin 7-hydroxylase and nitrosodimethylamine N-demethylase. 7-Hydroxycoumarin and 5, 7-methoxycoumarin at 40 mumol/embryo had none of these effects. Coumarin (5-500 microM) added to liver microsomes inhibited aniline hydroxylase by 45%, but not nitrosodimethylamine N-demethylase, and inhibited 7-ethoxyresorufin O-deethylase in microsomes from 3-methylcholanthrene-treated embryos by 15 and 100% at coumarin concentrations of 250 and 500 microM, respectively. Coumarin 7-hydroxylase activity in chick embryo liver was comparable with that reported for human liver and greater than in the rat. The data indicate that coumarin can both increase and decrease cytochrome P-450 activities in chick embryo liver and can induce haem biosynthesis. Because the chick embryo liver hydroxylates coumarin at position 7 in a manner similar to humans, it may be a more suitable model than the rat for studying some of the metabolic effects of coumarin.

5-Aminolevulinate Synthetase↗
PubMed1991

Effects of protein and carbohydrate content of diet on drug conjugation.

Eight healthy subjects were fed a high-protein-low-carbohydrate diet and, after a 3-day washout period, an isocaloric low-protein-high-carbohydrate diet. They received acetaminophen and oxazepam, drugs metabolized primarily by conjugation, on days 11 and 13, respectively, of each diet. Changing the diets of subjects from the high-protein-low-carbohydrate diet to the low-protein-high-carbohydrate diet resulted in a 14% increase in urinary recovery of acetaminophen glucuronide and a 32% increase in urinary recovery of oxazepam glucuronide (p less than 0.05). The increases in glucuronidation were at the expense of other pathways of metabolism, and there were no significant changes in the metabolic clearance rates of acetaminophen and oxazepam. Mean renal clearances of acetaminophen glucuronide, acetaminophen sulfate, and oxazepam glucuronide decreased 45%, 32%, and 54%, respectively (p less than 0.05), when the subjects were switched to the low-protein-high-carbohydrate diet.

Acetaminophen↗
PubMed1991

Effects of type of cage front and feed trough partitions on productivity and ingestive, agonistic, and fearful behaviors of egg-type hens.

Two groups of White Leghorn pullets reared in floor pens were used to study the effects on performance and behavior in cages of horizontal wire cage fronts with and without feed trough partitions (HP and H, respectively) and vertical wire cage fronts with and without feed trough partitions (VP and V, respectively). In Experiment 1, hens in HP and VP cages consumed more (P less than .05) feed than hens in either H or V cages. This greater feed consumption combined with similar egg production resulted in significantly poorer feed conversion (P less than .05) for hens in VP cages. Hens in HP cages had fewer drinking bouts (P less than .05) and an intermediate amount of feeding time. Hens in H, V, and VP cages did not differ significantly in number of drinking bouts and feeding times. There were differences in feeding location preferences among treatments (P less than .05) but not within treatments. In Experiment 2, effects of horizontal (H) and vertical (V) wire cage fronts were examined to determine their effects on productivity and fearful behavior. Hens in H cages had better feather scores (P less than .05) than hens in V cages. Type of cage front had no significant effects on age at sexual maturity, egg production, mortality rate, average egg weight, and body weight.

Agonistic Behavior↗
PubMed1991

Worksite health promotion. The benefits of providing personal health status feedback and education programs to employees.

Discovering ways to initiate and maintain health related behavior changes is a growing concern to business and industry. This research supports previous data indicating that wellness programs offered at the worksite are significantly beneficial in assisting employees to change behavior. This research did not find significant benefits to the employees who obtained health status information prior to participating in a worksite health program; however, the health assessment tool was informative and may have been adequate to assist in behavior changing activities. Wellness programs are important factors for promoting health related behaviors; failure of this study to support the importance of assessment feedback does not negate the desirability of assessment as an important component of the corporate wellness program.

Adult↗
PubMed1991

Diet and cimetidine induce comparable changes in theophylline metabolism in normal subjects.

This study compared the effects of diet and cimetidine on theophylline metabolism and examined interactions between these effects. Twelve men received a high-protein diet for 15 days and at another time a high-carbohydrate diet also for 15 days. Cimetidine, 800 mg daily at bedtime, was administered on days 10 through 15 of each dietary period. Theophylline metabolism was studied after the administration of a single intravenous 3 mg/kg dose on days 8 and 15 of each dietary period. Changing from a high-protein to a high-carbohydrate diet decreased theophylline clearance by about the same extent (30% +/- 10%) as treatment with cimetidine (37% +/- 5% during a high-protein diet and 30% +/- 5% during a high-carbohydrate diet). Cimetidine did not significantly influence the effects of diet on theophylline clearance. Conversely, dietary composition did not influence the degree of inhibition of theophylline metabolism induced by cimetidine. Depending on the direction of the change in protein/carbohydrate ratio, the effects of diet and cimetidine treatment were either additive (theophylline clearance was most prolonged during the high-carbohydrate regimen with concurrent cimetidine administration) or counteractive (increasing the dietary protein/carbohydrate ratio at least partially counteracted the inhibitory effect of cimetidine). In individual subjects, effects of cimetidine on theophylline metabolism were somewhat more consistent than diet-induced changes. The results are further evidence that diet and drugs can have similar effects on hepatic drug metabolism rates in humans. Variations in diet over time and individual differences in responses to diet may provide the potential for considerable instability of drug metabolism rates in free-living subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

A gonadotropin releasing hormone analogue prevents cyclical attacks of porphyria.

Acute intermittent porphyria is a genetic disease in which endogenous hormones affect clinical expression. Premenstrual exacerbations can occur, sometimes often, in women with this disease. Gonadotropin releasing hormone analogues can prevent ovulation by reducing secretion of luteinizing hormone and follicle-stimulating hormone. In six patients with well-documented acute intermittent porphyria and frequent cyclical exacerbations, daily administration of an agonistic gonadotropin releasing hormone analogue, ([ImBzl]-D-His6,Pro9-NET)gonadotropin releasing hormone, intranasally or subcutaneously for as long as 26 months reduced or eliminated premenstrual attacks and caused only minor side effects. Adjustments in dosage or route of administration were sometimes needed. We conclude that endocrine manipulation by treatment with a gonadotropin releasing hormone agonist will prevent neurovisceral attacks of acute intermittent porphyria due to cyclical changes in endogenous hormones and is a safe alternative to exogenous steroids, which may induce attacks of this disease.

Adult↗
PubMed1990

Success and failure attributions in smoking cessation among men and women.

1. Smoking behavior is intermingled with a very complicated array of social and psychological processes which suggests the presence of sociocultural factors that directly influence smoking behavior. 2. Social and cultural factors which distinguish former smokers from smokers indicate that behavioral factors may be related to the ability to successfully stop smoking. 3. Evidence suggests that attributional patterns differ according to gender, with women being more external and employing more luck attributions than men. 4. When attribution and self-efficacy expectations were combined with demographic variables, increased understanding of the cessation process increased and predictive power of success in smoking cessation improved.

Cultural Characteristics↗
PubMed1989

LHRH analogues for hormonal manipulation in acute intermittent porphyria.

Preliminary studies of LHRH analogue administration in women with acute intermittent porphyria suggest that these agents provide a safe and useful means of hormonal manipulation in this endocrine-related disease. Because a variety of endogenous and exogenous factors can contribute to clinical expression of this disease, it can be expected that this form of treatment will be more useful in some patients with acute intermittent porphyria than in others. Further clinical trials are needed with special attention to the possibility that more than one factor may play an additive role in inciting attacks of this disease in individual patients.

Acute Disease↗
PubMed1988

Influences of diet and nutrition on clinical pharmacokinetics.

The human diet represents a complex and variable mixture of nutrients, many of which have the potential for altering the disposition of drugs. This review highlights progress from a number of laboratories illustrating nutrient influences on drug dispositions and actions. Emphasis is placed on nutritional effects on hepatic drug metabolism studied in humans. Data from animals have sometimes been difficult to extrapolate to humans, as illustrated by reports on the influences of starvation, dietary lipids, and ascorbic acid. From studies in healthy subjects it is now clear that a number of specific dietary factors can influence drug metabolism by the mixed function oxidase system and conjugating enzymes. These include dietary protein, cruciferous vegetables, charcoal-broiled beef containing polycyclic aromatic hydrocarbons, and methylxanthines. The effects of such dietary components have been demonstrated for only a limited number of drug substrates for these enzyme systems. Effects of food on bioavailability have been more widely studied, and depend greatly upon the type of drug. Malnutrition can be associated with variable but potentially important effects on the bioavailability, binding, hepatic metabolism, and renal clearance of drugs. In malnourished patients it is generally difficult to recognise the roles of individual nutrient deficiencies on drug disposition, and clinical predictors of altered pharmacokinetics for various drugs in such patients are not well defined. It is likely that many important interrelationships between nutrition and new or already marketed drugs remain to be recognised, and therefore warrant further research. Nutritional effects on drug metabolising enzymes also have implications for endogenous substances such as hormones and environmental toxins and carcinogens which are metabolised by the same or related enzyme systems, and for diseases likely to be related to the actions of such chemicals.

Age Factors↗