Cobalamin (vitamin B12) is an essential nutrient derived exclusively from bacterial sources. It is an essential cofactor for three known enzymatic reactions. Untreated deficiency, caused by either the autoimmune disease pernicious anemia or nutritional lack, results in a macrocytic anemia and/or subacute combined degeneration of the spinal cord and is eventually fatal. Cobalamin in serum is bound to two proteins, transcobalamin and haptocorrin. The former is responsible for the essential delivery of cobalamin to most tissues. Inadequate tissue availability of cobalamin results in increased concentration of methylmalonic acid and homocyst(e)ine due to inhibition of methylmalonyl-CoA mutase and methionine synthase, respectively. Strict vegetarians have long been known to be at risk of cobalamin deficiency, which develops insidiously over many years. It is now clear that a significant number of the elderly and HIV-positive individuals are also at increased risk of deficiency. Any individual with reduced ability to split cobalamin from food-protein may also become deficient even though intrinsic factor is present. Diagnosis of cobalamin deficiency has frequently relied on total serum cobalamin and the Schilling test. Newer approaches such as analysis of methylmalonic acid, homocyst(e)ine, holotranscobalamin, anti-intrinsic factor antibodies, and serum gastrin may provide more cost-effective testing, as well as identify those with a covert deficiency.
One hundred thirty-eight men aged less than or equal to 39 years had coronary bypass grafting during a 13 year period. Angina was the presenting symptom in 77% and of these patients, one-third had unstable angina. More than half of the patients had experienced at least one myocardial infarct. There was a high incidence of coronary risk factors, especially smoking. Nineteen patients (13.8%) had left main coronary artery stenosis (it was isolated in two); 13.8, 24.6 and 60.2% had single, double and triple vessel disease, respectively. Left ventriculograms showed serious functional impairment in 42%. A total of 461 coronary bypass grafts, 3.34 per patient, were placed; almost all were vein grafts. There were no operative deaths. Transmural myocardial infarction occurred in 4.3% of patients. All bypass grafts were opacified angiographically early after operation, 95% at 1 year, 56% at 5 years and 26% at 10 years after operation. Some patients also had coronary angiograms, dictated by clinical events, between 1 and 5 and between 5 and 10 years postoperatively. Patency rates for bypass grafts were comparable with those previously reported and were acceptable, although they decreased with time. However, increasing evidence of atherosclerosis of bypass grafts was seen beyond 1 year, particularly beyond 5 years. Of 23 subjects with a coronary bypass reoperation, 2 died and 44% had perioperative transmural myocardial infarction. During follow-up, 13.8% of the patients died, survival being 95, 84 and 76% at 5, 10 and 12 years, respectively. It is considered that the patients were advantageously treated with coronary bypass grafting especially in the short-term. However, bypass graft patency steadily decreased with the passage of time and graft atherosclerosis became an increasingly important problem.
Material which specifically binds oxytocin was prepared from a crude preparation of lactating rabbit mammary gland by purification on a sucrose density gradient. On examination of activities of enzyme markers and the molar ratio of cholesterol to phospholipid, this material was considered to be a highly purified plasma membrane fraction. For the determination of specificity and time course of oxytocin binding, a Scatchard plot analysis was carried out for the crude and purified fractions. Dissociation constant (Kd) and binding capacity values were found to be as follows: crude, Kd equals 1.83 X 10(-9) M, capacity equals 670 fmol/mg protein; purified, Kd equals 2.8 X 10(-9) M, capacity equals 1700 fmol/mg protein. Treatment of the purified material with different detergents resulted in loss of all [3H]oxytocin binding capacity. However, preincubation of this material with [3H]oxytocin prior to detergent treatment resulted in solubilization of a receptor-hormone complex. This complex remained in the supernatant even after centrifugation at 210 000 X g for 30 min. Using oxytocin analogs, we have shown this solubilized complex to be oxytocin specific.
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