Biomedical subjects
Publications and source records attributed to F Q Nuttall.
A flexible system for diet education and meal planning for diabetic patients is presented. Although this program may be accomplished by interested, knowledgeable physicians, it is best done by a diet counselor (registered dietitian or nurse educator). Nevertheless, physicians should be intimately involved by discussing the patient's progress with the diet counselor and by providing reinforcement of the efforts of the counselor.
The presence of two interconvertible forms of phosphorylase kinase has been confirmed in rat liver extracts. The pH optimum of the nonactivated form (PhK b) was lower than the pH optimum of the activated form (PhK a) as reported by others (2). In the absence of calcium the Km of PhK b for phosphorylase b was 53 +/- 10 U/ml with a Vm of 17 +/- 1 U/gm of tissue. The Km of PhK a for phosphorylase b was 20 +/- 2 U/ml with a Vm of 65 U/gm. Calcium stimulated both forms of phosphorylase kinase (A0.5 approximately 0.03 micro). In the presence of 0.1 microM calcium the Km for phosphorylase b of both forms of the enzyme was reduced. In addition, calcium increased the Vm of both forms, but the effect was greater for PhK b than for PhK a. The Km of both forms of phosphorylase kinase for ATP was 0.05 mM and was unaffected by calcium. All of these studies were done using liver phosphorylase b as substrate. Conditions for assaying PhK a activity virtually independent of PhK b activity also are indicated. This will enable the monitoring of interconversion reactions in tissue extracts. Phosphorylase kinase a was purified to near homogeneity using DEAE-cellulose, Sepharose 4B gel filtration and ATP affinity chromatography. The molecular weight was approximately 1 x 10(6). The pH profile, calcium requirements and kinetic constants were the same as those for PhK a in the crude extract.
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Methods for obtaining and processing rat liver for determination of glycogen phosphorylase a and synthase I activity were studied. An extremely rapid and profound increase in phosphorylase was induced by hypoxia. The effect on synthase I was slower and less striking. Using alpha- and beta-adrenergic antagonists, a catecholamine-depleting agent, and a ganglionic blocking agent, it was determined that adrenergic stimulation secondary to the surgical procedure required to obtain the liver was not a significant factor. The anesthetic agent used also had a significant effect on the proportion of phosphorylase in the a form. Seconal anesthesia resulted in lower phosphorylase a levels than did ether or urethan anesthesia.
Two indices of free thyroxine (T4) and four methods of free T4 measurement were compared in 85 patients with acute illness, hospitalized in intensive care units. All of the methods of free T4 measurement in critical illness were nonspecific, and two of the methods failed to suggest hypothyroidism in two patients with primary hypothyroidism and another associated critical illness. Since the ideal screening test should be both sensitive and specific, all tests for free T4 used in this study should be interpreted with caution in severely ill patients.
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We have previously shown that synthase phosphatase activity was decreased in starved animals and was rapidly restored by insulin administration (1). In order to determine whether the decreased phosphatase activity was due to a decrease in phosphatase enzyme per se or to a change in the substrate, synthase D, phosphatase activity has been determined using purified synthase D substrate. Using purified heart or liver synthase D, phosphatase activity was lower in extracts from starved animals than in fed animals. Insulin administration rapidly increased phosphatase activity in extracts from the starved animals. The total amount of endogenous synthase D which was convertible to synthase I was lower in extracts from starved animals, but this was rapidly increased within 15 minutes following insulin administration. These data suggest that starvation and insulin have a direct effect on the phosphatase enzyme activity per se and probably on the substrate suitability of synthase D as well.
Thyroid function was measured in 86 patients hospitalized in an intensive care unit. Two patients were found to have primary hypothyroidism and were excluded from the study. Hypothyroxinemia with normal thyroid-stimulating hormone (TSH) levels was found in 22% of the patients and was associated with a high mortality (thyroxine [T4] levels less than 3.0 micrograms/dL, 84% mortality; T4 levels of 30 to 5.0 micrograms/dL, 50% mortality; and T4 levels greater than 5.0 micrograms/dL, 15% mortality). There was a high correlation between low T4 levels and mortality.
Cortisol and ACTH secretion was studied in 52 healthy subjects who were fasted of fed various diets: standard, high fat, high carbohydrate, high protein. Subjects fed high protein diet (4 gm/kg body weight) showed significant increases in cortisol both at 30 and 60 min after the 1200 hr meal and 30 min after the 1600 hr meal. Increases in cortisol, of a smaller magnitude, were also seen after both the 1200 and 1600 hr meals in each of the diets with 1 gm protein/kg body weight (standard, high fat, high carbohydrate). ACTH was significantly increased following the 1200 hr and 1600 hr meals with the high protein diet. We conclude that dietary protein plays an important role in meal stimulated cortisol release.
We have previously shown that the synthase D (UDPglucose:glycogen 4-alpha-D-glucosyltransferase, EC 1.4.1.11) present in the liver of the adrenalectomized fasted rat was not converted to synthase I by synthase phosphatase from normal animals, suggesting the presence of a non-substrate form of synthase D (Tan, A.W.H. and Nuttall, F.Q. (1976) Biochim. Biophys. Acta 445, 118--130). The enzymatic properties of this synthase D have now been examined. Using optimal assay conditions, the total amount of synthase D activity in the adrenalectomized fasted rats was similar to that of normal fed rats when 1% glycogen was included in the homogenizing buffer. However, the two enzymes appeared to have different affinities for the substrate, UDPglucose and the modifier, glucose-6-P. The changes in kinetic properties were not due to differences in glycogen or to a dialyzable modifier in the extracts. Synthase D from adrenalectomized fasted and from normal fed rats was partially purified. After DEAE-cellulose chromatography, modification appeared to have occurred such that the enzyme from the adrenalectomized fasted rat had properties similar to that of the normal fed rat. The enzymes were cold-labile, had different properties from enzymes in the crude extract and they were both converted to synthase I by synthase phosphatase. We conclude from these studies that the phosphorylation site in the synthase is in a flexible region of the protein. Changes in the ability of the synthase D to interact and be dephosphorylated by synthase phosphatase can occur readily in vivo and in vitro. The molecular basis for the modification remains unknown.
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Fructose and glucose, when administered as a single, large intravenous dose (500 mg/kg) produced opposite effects on key regulatory enzymes of glycogen metabolism in intact normal fed animals. Glucose rapidly stimulated glycogen synthase phosphatase activity and increased the proportion of glycogen synthase in the active (I) form as expected; fructose reduced synthase phosphatase activity and the proportion of synthase in the I form. Glucose also stimulated a reduction in the proportion of phosphorylase in the active (a) form, whereas fructose stimulated an increase in the proportion of phosphorylase in thea form. The effect of fructose was not mediated by an increase in cyclic adenylate (cAMP) concentration nor by a conversion of phosphorylase kinase b to phosphorylase kinase a. As expected, the concentration of ATP decreased significantly. The increase in proportion of phosphorylase in the a form may be due to stimulation of phosphorylase kinase b activity by a decrease in the intracellular ATP:Mg++ ratio or by increase in intracellular Ca++ concentration. The mechanism of the fructose-induced change in synthase phosphatase activity and in synthase I activity is unknown.
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The prevalence of palpable gynecomastia was determined in 306 normal adult men ranging in age from 17-58 yr. Palpable breast tissue was present in 36% and was bilateral in all but 7 subjects. In the great majority of cases, the gynecomastia was 4 cm or less in diameter. A diameter greater than 5 cm was distinctly unusual. With advancing age there was a progressive increase in the prevalence of gynecomastia. This increase was most striking in those over the age of 44 and in the 20- to 24-yr-old group compared to those 19 yr old or less. In those over the age of 44, the prevalence was 57%. These data indicate that palpable gynecomastic is common in normal adult men. This high prevalence must be taken into consideration when attributing gynecomastia to a drug or disease state.
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