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Biomedical subjects

W F Miller

Publications and source records attributed to W F Miller.

18 recordsLinked to original sources

Regulation of cholesterol 7 alpha-hydroxylase in the liver. Purification of cholesterol 7 alpha-hydroxylase and the immunochemical evidence for the induction of cholesterol 7 alpha-hydroxylase by cholestyramine and circadian rhythm.

Two cholesterol 7 alpha-hydroxylase isozymes were purified from liver microsomes of cholestyramine-treated female rats by using anion exchange high performance liquid chromatography. These two cytochrome P-450 isozymes were similar in electrophoretic mobility, immunocross-reactivity, and Vmax but differed in Km for cholesterol, turnover number, and charges. Antibody against the major isozyme was raised in rabbit. This antibody specifically inhibited microsomal cholesterol 7 alpha-hydroxylase activity. Immunoblot of microsomal polypeptides indicated that microsomal cholesterol 7 alpha-hydroxylase enzyme levels were increased in parallel with cholesterol 7 alpha-hydroxylase activity upon the treatment of rats with diet supplemented with cholestyramine. Both cholesterol 7 alpha-hydroxylase activity and enzyme levels were drastically reduced immediately after the removal of cholestyramine from the diet. Cholesterol 7 alpha-hydroxylase activity was also detected in the microsomes of kidney, heart, and lung in about 7-27% of the level found in the liver. 3-Methylcholanthrene treatment induced cholesterol 7 alpha-hydroxylase activity and enzyme level. In contrast, pregnenolone-16 alpha-carbonitrile or dexamethasone treatment greatly depressed enzyme and activity in rats. Cholesterol 7 alpha-hydroxylase enzyme level was 2-3-fold higher in liver microsomes of rats maintained under the reversed light cycle than under the normal light cycle. In genetically obese Zucker rats, cholesterol 7 alpha-hydroxylase activity and enzyme level did not respond to the change in the light cycle, however, were induced to the same levels as in the lean rats by cholestyramine treatment. This study provided the first direct evidence that the bile acid feedback regulation and circadian rhythm of microsomal cholesterol 7 alpha-hydroxylase activity involved the induction of cholesterol 7 alpha-hydroxylase enzyme level.

Animals

Bronchodilator effect of a new oral beta adrenoreceptor stimulant, Th1165a. A comparison with metaproterenol sulfate.

In a single-blind study the short-term effects of oral administration of Th1165a (5, 10, 15, and 20 mg), metaproterenol sulfate (Alupent) (20 mg), and placebo on ventilatory function, pulse rate, and systolic and diastolic blood pressure were compared over a period of six hours in ten patients with stable, reversible obstructive airway disease. Both Th1165a (5, 10, 15 and 20 mg) and metaproterenol administration caused significant bronchodilation of rapid onset (30 minutes), but the bronchodilator effect of Th1165a (10, 15, and 20 mg) was greater and lasted longer (six hours vs three hours) than that of metaproterenol. A dose-dependent bronchodilator effect was recognizable after administration of Th1165a. The 20-mg dose of metaproterenol sulfate and the 5-mg and 10-mg doses of Th1165a produced minimal side effects. Larger doses (15 and 20 mg of Th1165a caused significant increases in pulse rate. Mild and transient tremors were the most common side effect after administration of Th1165a.

Administration, Oral

Chronic obstructive airway diseases. Current concepts in diagnosis and comprehensive care.

Physicians and paramedical personnel often find the early diagnosis and differentiation of obstructive airway diseases to be a challenging problem. The history and physical examination are often not enough to allow the physician to detect either the presence of, or determine the type of, disease present. Patterns of pulmonary function abnormality to determine the presence of obstructive or restrictive defects are discussed. Guidelines useful in the differentiation of obstructive airway diseases are presented. Once a patient with COAD is assessed, the physician needs to outline a therapeutic program after establishing goals with the patient. These goals include (1) improved ability for the patient to achieve relief from symptoms and (2) improved capacity to carry out the activities of daily living. The therapeutic modalities available for the comprehensive care of patients with COAD are discussed. These include general factors such as patient and family education, avoidance of smoking and other inhaled irritants, avoidance of infection, a minimum stress environment, high fluid intake, and proper nutrition. The appropriate use of the medications most commonly employed in the teatment of these patients, eg, bronchodilators, expectorants, antimicrobials, corticosteroids, cromolyn, digitalis, and diuretics, are individually discussed. The use of such respiratory therapy techniques as aerosol therapy, intermittent positive pressure breathing, and oxygen therapy are considered. Application of the specialty of rehabilitation medicine to patients with obstructive airway disease is described. This includes physical therapy with breathing retraining, clapping and postural drainage, and exercise reconditioning, occupational therapy with attention to energy conservation in activities of daily living, psychological considerations, and vocational rehabilitation. Definite benefits that can be demonstrated if the physician employs this type of systematic respiratory care program include a decrease in the frequency and duration of hospital admissions, socioeconomic gains from reduced hospitalizations, a reduction in anxiety, depression and somatic concern, the return of patients to positions of employment and the establishment of a better quality of life. Persistence in making sure the patient continues in a systematic program, including both pharmacological and nonpharmacological modalities, may be the means of assuring maintenance or even improvement in his health. The day-to-day treatment for the majority of patients should remain in the hands of the primary physician. However, community resources must be established to allow the primary physician to provide these patients with adequate comprehensive respiratory care. Development of three levels of care (the primary physician, community respiratory rehabilitation units, and the regional respiratory center) should make superior respiratory care available to every patient with obstructive airway disease.

Adrenal Cortex Hormones

Evaluation of a new oral beta2-adrenoceptor stimulant bronchodilator, terbutaline.

A double-blind crossover comparison was made of the effect of orally administered terbutaline (a new adrenergic drug with major action on beta2-receptors), ephedrine, and placebo in 15 patients with obstructive airways disease. Serial determination of ventilatory tests, arterial gas tensions, arterial blood pressure, ECG, blood chemistries, and urinalysis were made before and after administration of the tested drug. Terbutaline (5 mg) was found to be an effective bronchodilator with minimal side effects and an earlier onset and longer duration of action than ephedrine (25 mg).

Administration, Oral