How physicians deal with their own impending death.
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Biomedical subjects
Publications and source records attributed to E D Rees.
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Estrogen and progesterone receptors prepared from mouse, rat, and human uteri, as well as from human breast cancers, have been characterized by gel-exclusion high-performance liquid chromatography. The qualitative relationships previously established by sedimentation analysis between the cytoplasmic [aggregated (approximately 8S), deaggregated (approximately 4S), and trypsinized (approximately 3.6S)] and nuclear (approximately 5S) forms of the rat uterine estrogen receptor were maintained by this technique. Differences in the partition of estrogen and progesterone receptors from the same species as well as interspecies differences in these receptors were reproducibly observed. Multiple forms of human estrogen and progesterone receptors could clearly be resolved in a single analysis and were distinct from serum steroid binding tissue contaminants. Separation analyses, performed at flow rates up to 2 mL min-1, were capable of resolving all receptor forms in 10--12 min with the column returning to base line in 25 min. With this exclusion gel column (TSK-G3000SW) as a background upon which to reference different receptor forms, eight distinct partitions or elution positions have been enumerated. This approach has considerable promise for the rapid characterization of different forms of steroid-receptor proteins. Moreover, it should provide a critical advantage in minimizing the opportunities for receptor modification during separation analysis and in maximizing the opportunity to study short-lived interactions between receptors and physiologic or pharmacologic ligands.
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To evaluate selected metabolic effects of plant fibers, we fed control and oat-bran diets in an alternating sequence to eight men with previously documented hypercholesterolemia. The two solid diets differed only in the inclusion of 100 g of oat bran in the test diet. We randomized diet sequences and the measured intakes of carbohydrate, protein, fat, and cholesterol were virtually identical on the two diets. Serum total cholesterol concentrations were stable on control diets whereas a progressive reduction was observed in seven men on oat-bran diets. On oat-bran diets, average reductions in serum total cholesterol concentrations were 13% (p less than 0.01, N = 8); plasma low-density lipoprotein cholesterol concentrations were 14% lower (p less than 0.05) while high-density lipoprotein cholesterol concentrations were not changed. Fasting and postprandial serum glucose, insulin, and triglyceride concentrations were similar on the two diets. Fecal excretion of total bile acids was 54% higher (p less than 0.001) on oat-bran diets than on control diets but neutral steroid excretion was slightly lower while on oat bran. Palatable and inexpensive high-fiber foods such as oat bran may have a role in the treatment of certain patients with hypercholesterolemia.
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We have previously reported a low prevalence of hyperlipidemia in renal transplant recipients who were treated with alternate-day corticosteroid. To determine whether alternate-day prednisone per se is associated with lower plasma lipids than is daily prednisone, we studied 14 renal transplant recipients with good allograft function (serum creatinine less than 2.5 mg/dl) who were normolipidemic on alternate-day prednisone. All patients were treated with 6 months of daily prednisone (10.9 +/- 0.4 mg, mean +/- S.E.) and then returned to 6 months of alternate-day prednisone (21.6 +/- 1.0 mg). Mean plasma triglyceride, cholesterol, and cholesterol fractions on either regimen were normal and not different. There were no differences in fasting or 2 hr postprandial glucose and insulin levels. Twelve patients gained weight on daily prednisone, and 11 patients lost weight on reversion to alternate-day prednisone. The changes in ideal body weight in both periods correlated (p less than 0.05) with changes in plasma triglycerides. These data suggest that a daily prednisone regimen per se as compared to an alternate-day regimen does not dispose normolipidemic patients to hyperlipidemia. The factors contributing to the low prevalence of hyperlipidemia in our renal transplant recipients remain obscure.
To explain the sensitivity of uterine leiomyomata to endogenous and exogenous estrogens, specific cytosol receptor proteins for estradiol-17 beta and progesterone were found in tissue from uterine leiomyomata and compared with the concentrations of receptors in normal myometrium and endometrium from the same patient. The concentration of cytoplasmic estrogen receptors in leiomyomata (40.5 +/- 7.6 cytoplasmic estrogen receptors in leiomyomata (40.5 +/- 7.6 fmole/mg cytosol proteins, mean +/- SEM) was significantly greater than that found in myometrium (16.5 +/- 1.5) and significantly less than that found in endometrium (131 +/- 15.1). The concentration in leiomyomata of cytoplasmic progesterone receptors (104.4 +/- 41.2 fmole/mg cytosol protein, mean +/- SEM) was also greater than that found in myometrium (80.8 +/- 29.9) and less than that of endometrium (194.7 +/- 5.5); however, individual variation precluded statistical significance. The presence of cytoplasmic receptor proteins in myomatous tissues explains the sensitivity of the leiomyoma to endogenous or exogenous steroids and may provide information useful in the clinical management of this neoplastic disorder.
Since the radioimmunoassay for serum prolactin became available eight years ago, prolactin has become a hormone of considerable clinical interest. An elevated serum prolactin concentration is the most frequent hormone marker for pituitary tumors. Secreted in excess, prolactin causes dysfunction of the hypothalamic-pituitary axis, the gonads, and the adrenal cortex. In women, menstrual disturbances, galactorrhea, infertility, and hirsutism result. Impotence, oligospermia, and decreased libido are common in men. These metabolic abnormalities attributed to prolactin excess are corrected when prolactin concentrations are lowered by either medical or surgical therapy. The availability of effective therapy mandates early recognition and proper management of the patient with hyperprolactinemia.
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After infusion of 250 ml of essential L-amino acids, plasma levels of alpha-amino nitrogen (alpha-AN2) in six chronic renal failure (CRF) patients were not different from those in six carefully matched control (CON) subjects. Plasma insulin increments increased significantly within both groups but were higher in the CRF group (p less than 0.05 at 40 min, p less than 0.005 at 55 min). Growth hormone levels were also higher in the CRF group. Previous studies have shown delayed clearance of plasma alpha-AN2 after casein hydrolysate infusion, despite similarly increased insulin and growth hormone levels in CRF patients. We conclude that essential amino acids are probably more easily metabolized than casein hydrolysate in uremic subjects, but that normal metabolism occurs at the expense of higher plasma levels of insulin and growth hormone.
A double-blind study comparing halofenate, a new lipid-lowering investigation drug, with an established drug, clofibrate, was conducted on 33 clinic patients with Type II hyperlipoproteinemia for a period of 48-96 weeks. All but 10 patients had some type of symptomatic major vascular disease. With respect to serum cholesterol levels, a comparable proportion (56-59%) of patients in each group responded to the respective treatment but the magnitude of lowering was substantially less for the halofenate responders (12% mean decrease versus 25%). Type IIa patients in both groups were more likely than Type IIb patients to have a favorable cholesterol-lowering response. Weight gain of 5% or greater was prejudicial to cholesterol lowering. In the case of serum triglycerides, the proportion of patients responding to clofibrate treatment was somewhat greater (87% versus 57% for halofenate) but the mean magnitude of lowering (27-34%) was comparable for responders in the two groups. Weight gain did not influence appreciably the triglyceride-lowering effect. Elevated concentrations of triglyceride (Type IIb) in the control period favored a triglyceride lowering response by clofibrate but was only a moderate influence on the response to halofenate.
An experiment has been carried out to test the rotating carrier mechanism of the translocation event in membrane transport. To the Ca-ATPase in intact sarcoplasmic reticulum membranes, 2,4-[3H]dinitrophenyl-cadaverine has been covalently attached by the action of the enzyme, transglutaminase. The binding of anti-2,4-dinitrophenyl antibodies to the 2,4-dinitrophenyl-modified membranes was found to have no effect on either the Ca-ATPase activity or the Ca ion transport rate of the membranes. These results rule out the rotating carrier mechanism in this system. A different scheme for the translocation process, the aggregate rearrangement mechanism, is discussed.
Both alpha zein purified from a commericial preparation and beta zein prepared fresh from corn are soluble in the nonaqueous solvents formamide and dimethylformamide; in this regard zein resembles water soluble proteins such as insulin, ribonuclease, and lysozyme. On the basis of osmotic pressure measurements made in both formamide and dimethylformamide, alpha zein has a number average moleular weight of 21000-24000 daltons and shows no tendency to aggregate or dissociate. Beta zein exists in an aggregated state (dimer and higher forms) in dimethylformamide. Formamide dissociates the beta zein dimer into monomer units but aggregation to higher species occurs with increasing protein concentration.
The conformation of zein, a seed protein from corn, was determined by optical rotary dispersion measurements in a wide variety of nonaqueous solvents. Over a wide range of dielectric constants, in pure and mixed solvent systems, the helical content was independent of dielectric constant. Determination of the helical content of insulin and ribonuclease in several of these solvents indicated a variation in secondary structure comparable of that of zein. Though virtually insoluble in water, zein not only is a globular protein in nonaqueous solutions, but has conformational properites characteristic of more conventionally behaving globular proteins.
In contrast to previous reports, most patients (78%) with a successful renal transplant being followed up at the University of Kentucky Medical Center had a normal serum-lipid profile. The patients with hyperlipidaema (22%) had normal fasting insulin levels; they received similar immunosuppressive therapy but were significantly older and more obese than those with normal lipids. This lower prevalence of hyperlipidaemia and the absence of fasting hyperinsulinaemia are tentatively attributed to the use of alternate-day corticosteroid therapy in stable renal-transplant patients. If confirmed, the relative infrequency of hyperlipidaemia in patients of alternate-day corticosteroid therapy would be an additional advantage of that therapy over a daily regimen.
The mean serum antitrypsin (AT) activity for 1,829 patients hospitalized with medical problems exceeded the mean for a group of blood bank donors by 51%. Analysis of data from individual patients in terms of the general category (there were 16) of their disease and smoking status (smoker, nonsmoker, former smoker) indicated significant differences due to disease status and smoking status. The highest mean AT levels were associated with infectious, respiratory, and neoplastic diseases. Smokers had significantly higher mean levels than nonsmokers, and lung cancer patients had significantly higher mean levels than those with other malignant neoplasms. Among smokers (as a group) mean AT levels. through elevated relative to nonsmokers were not significantly related to duration or intensity of smoking; but former smokers showed a decline (with time following cessation of smoking) in their mean AT level to the mean level for nonsmokers. These findings provide further evidence of the sensitivity of serum antitrypsin activity to environmental influences.