Modification of the United States' diet to effect changes in blood lipids and lipoprotein distribution

Twenty men, 19 premenopausal and 14 postmenopausal women consumed a diet for 13 weeks that supplied 35% of the calories from fat, 50% from carbohydrate, and 15% from protein. The diet was low in cholesterol, saturated fat, and salt, and high in complex carbohydrate and fiber. The 7-day menu was composed of common well-accepted foods prepared in a simple attractive manner. Plasma total cholesterol, LDL cholesterol, and VLDL cholesterol were reduced, but triglyceride levels were not different than after self-selected diets. When 20% of the complex carbohydrate was replaced by simple carbohydrate and other diet components remained optimal, triglyceride and VLDL cholesterol levels increased in men and premenopausal women and total cholesterol increased in premenopausal women. These results suggest that beneficial effects on the blood lipids and lipoprotein distribution of men and women may be obtained by minimal modification of a typical U.S. diet.     

Mutation of a conserved serine in TM4 of opioid receptors confers full agonistic properties to classical antagonists.

The involvement of a conserved serine (Ser196 at the mu-, Ser177 at the delta-, and Ser187 at the kappa-opioid receptor) in receptor activation is demonstrated by site-directed mutagenesis. It was initially observed during our functional screening of a mu/delta-opioid chimeric receptor, mu delta2, that classical opioid antagonists such as naloxone, naltrexone, naltriben, and H-Tyr-Tic[psi,CH2NH]Phe-Phe-OH (TIPPpsi; Tic = 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid) could inhibit forskolin-stimulated adenylyl cyclase activity in CHO cells stably expressing the chimeric receptor. Antagonists also activated the G protein-coupled inward rectifying potassium channel (GIRK1) in Xenopus oocytes coexpressing the mu delta2 opioid receptor and the GIRK1 channel. By sequence analysis and back mutation, it was determined that the observed antagonist activity was due to the mutation of a conserved serine to leucine in the fourth transmembrane domain (S196L). The importance of this serine was further demonstrated by analogous mutations created in the mu-opioid receptor (MORS196L) and delta-opioid receptor (DORS177L), in which classical opioid antagonists could inhibit forskolin-stimulated adenylyl cyclase activity in CHO cells stably expressing either MORS196L or DORS177L. Again, antagonists could activate the GIRK1 channel coexpressed with either MORS196L or DORS177L in Xenopus oocytes. These data taken together suggest a crucial role for this serine residue in opioid receptor activation.     

An anisotropy of human tactile sensitivity and its relation to the visual oblique effect

Summary The ability of humans to detect striated stimuli on the distal phalanges was found to be highly anisotropic. Observers were much more sensitive to stripes presented in the proximal-distal orientation than to stripes in any other orientation. This tactile anisotropy was contrasted with the well-known visual anisotropy in which sensitivity is greatest for stripes at the horizontal and vertical orientations. We suggest that both the tactile anisotropy and the visual anisotropy are caused by corresponding anisotropies in the distribution of preferred orientations of orientation-selective neurons with in the respective modalities.     

Viruses as an Aid to Cancer Therapy: Regression of Solid and Ascites Tumors in Rodents After Treatment with Bovine Enterovirus

Treatment of ascites and solid tumors in mice (Sarcoma-1 and Ehrlich ascites carcinoma) with bovine enterovirus-1 resulted in regression of the tumors without any pathological effect on the animals. Death of mice with lymphatic-leukemia L4946 was delayed after such treatment. The oncolytic specificity of the virus does not appear to involve the production of interferon, but requires specific adsorption of virus to the tumor cells. The specificity of killing extends to cells in culture, since viral-transformed cells and oncogenic cells are susceptible to the virus, in contrast to cells of untransformed lines and cells of primary cultures, which are resistant.The possibility of utilizing the specificity of nonvirulent viruses in therapeutic treatment of human cancers is considered.     

Metabolic consequences of glucose-insulin-potassium infusion in treatment of acute myocardial infarction

Eighteen patients treated with glucose-insulin-potassium infusion for anaerobic support of acutely ischemic myocardial tissue were studied to ascertain the metabolic consequences of this therapy for acute myocardial infarction. Twelve patients with acute myocardial infarction were treated in a conventional manner and served as control subjects. The glucose-insulin-potassium solution was composed of 300 g of glucose, 50 units of regular insulin and 80 mEq of potassium ion per liter, and was infused at a rate of 1.5 ml/kg per hour through the right atrial port of an indwelling Swan-Ganz thermodilution catheter. Serial measurements of serum electrolytes, cardiac and hepatic enzymes, glucose and osmolality were obtained every 4 to 6 hours for 4 days. Twenty-four hour urinary volume and potassium levels were measured daily. Pulmonary arterial end-diastolic pressure was measured hourly and the cardiac index daily for the duration of the study. Serum potassium increased to 5 mEq/liter during the infusion and to more than 6 mEq/IHer after infusion in 28 percent of patients. No recognizable complications or arrhythmias accompanied this transient hyperkalemia. Potassium balance studies revealed a net total body potassium ion gain of 120 mEq during the study. The second most frequent finding was an elevation of serum glucose (mean 175 mg/100 ml); in all instances this was controlled with supplemental administration of insulin. The serum osmolality and fluid balance remained normal in all patients during the study. Serum glutamic oxaloacetic transaminase (SGOT) and fraction 5 of lactic dehydrogenase (LDH) were Increased in 34 percent of the patients during the last 12 to 18 hours of the glucose-insulin-potassium infusion. Characterization of these enzymes suggested a hepatic origin for these changes. This study suggests that glucose-insulin-potassium infusion is a relatively safe procedure in which postinfusion hyperkalemia is the most serious potential complication.