The distribution of erythrocyte phospholipids in hereditary spherocytosis demonstrates a minimal role for erythrocyte spectrin on phospholipid diffusion and asymmetry

In the human erythrocyte membrane phosphatidylcholine and sphingomyelin reside mainly in the outer leaflet, whereas the aminophospholipids, phosphatidylethanolamine and phosphatidylserine, are mainly found in the inner leaflet. Maintenance of phospholipid asymmetry has been assumed to involve interactions between the aminophospholipids and the membrane skeleton, in particular spectrin. To investigate whether spectrin contributes to maintaining the phospholipid transbilayer distribution and kinetics of redistribution, we studied erythrocytes from hereditary spherocytosis patients whose spectrin levels ranged from 34% to 82% of normal. The phospholipid composition and the accessibility of membrane phospholipids to hydrolysis by phospholipases were in the normal range. Spin-labeled phosphatidylserine and phosphatidylethanolamine analogues that had been introduced into the outer leaflet were rapidly transported at 37 degrees C to the inner leaflet, whereas the redistribution of spin-labeled phosphatidylcholine was slower. The kinetics of transbilayer movement of these spin-labeled phospholipid in all samples was in the normal range and was not affected by the level of spectrin. Although these erythrocyte membranes contained as little as 34% of the normal level of spectrin and were characterized by several physical abnormalities, the composition, distribution, and transbilayer kinetics of the phospholipids were found to be normal. We therefore conclude that spectrin plays, at best, only a minor role in maintaining the distribution of erythrocyte membrane phospholipid.     

Anomalous origin of the left circumflex coronary artery from the right aortic sinus: A familial clustering

Origin of the left circumflex coronary artery from the right sinus of Valsalva or the right coronary artery is a well-described anomaly. We report 3 cases which suggest a familial association of this anomaly. The familial clustering that we report has not been previously demonstrated. © 1993 Wiley-Liss, Inc.     

Somatostatin does not alter insulin-mediated glucose disposal

We examined the effect of somatostatin (SRIH) infusion on insulin-mediated glucose disposal (Rd) in normal young subjects (n = 8) to determine the influence of SRIH on insulin action. Paired 3-h euglycemic insulin clamp studies were performed in random order employing insulin alone (25 mU/m2 X min) or insulin with SRIH (250 micrograms/h) and replacement of basal glucagon (0.4 ng/kg X min). Basal plasma glucose, insulin, glucagon (IRG), and GH concentrations, hepatic glucose production, and Rd were similar on each occasion. Steady state (10-180 min) plasma insulin insulin alone, 283 +/- 10 (+/- SEM); insulin, IRG, and SRIH, 284 +/- 10 pmol/L) and glucagon levels (insulin alone, 84 +/- 7; insulin, IRG, and SRIH, 82 +/- 7 ng/L) were similar. Hepatic glucose production (insulin alone, 0.66 +/- 0.12; insulin, IRG, and SRIH, 0.78 +/- 0.48 mg/kg X min) and Rd (insulin alone, 8.16 +/- 0.62; insulin, IRG, and SRIH, 8.17 +/- 0.61 mg/kg X min) were not different at steady state. We conclude that SRIH infusion with glucagon replacement does not augment insulin-mediated glucose disposal in normal young subjects at physiological insulin levels.     

De novo purine synthesis in cultured rat embryos undergoing organogenesis.

The cultured rat embryo undergoing organogenesis (9.5-11.5 days of gestation) together with its associated yolk sac synthesize purine nucleotides via the de novo synthetic pathway. Although both the embryo and its yolk sac contain significant levels of the purine base salvage enzymes adenine phosphoribosyltransferase and hypoxanthine phosphoribosyltransferase, the culture medium that consists largely of rat serum contains no measurable quantities of salvageable purine bases or nucleosides but high activity levels of purine catabolic enzymes. Short-term pulse-chase experiments with adenine and guanine, carried out under virtually serum-free conditions, confirmed that purine base salvage mechanisms were active and that there was no significant net transfer of purines between the embryo and its yolk sac. A comparison between the specific radioactivities of the [14C]glycine added to the culture medium for the studies of the de novo synthetic pathway and the purine bases in both the cellular nucleotides and the nucleic acids indicated the existence of a large glycine pool, which almost certainly was derived from the degradation of medium serum proteins by the yolk sac. Although there are no clear-cut data available on the in vivo plasma levels of purines that could be potentially utilized to meet the demands of the embryo, it is evident that the de novo pathway is adequately developed to meet these needs.     

Phospholipase A2 levels in acute chest syndrome of sickle cell disease

Acute chest syndrome (ACS) is associated with significant morbidity and is the leading cause of death in patients with sickle cell disease (SCD). Recent reports suggest that bone marrow fat embolism can be detected in many cases of severe ACS. Secretory phospholipase A2 (sPLA2) is an important inflammatory mediator and liberates free fatty acids, which are felt to be responsible for the acute lung injury of the fat embolism syndrome. We measured SPLA2 levels in 35 SCD patients during 20 admissions for ACS, 10 admissions for vaso-occlusive crisis, and during 12 clinic visits when patients were at the steady state. Eleven non-SCD patients with pneumonia were also evaluated. To determine if there was a relationship between sPLA2 and the severity of ACS we correlated SPLA2 levels with the clinical course of the patient. In comparison with normal controls (mean = 3.1 +/- 1.1 ng/mL), the non- SCD patients with pneumonia (mean = 68.6 +/- 82.9 ng/mL) and all three SCD patient groups had an elevation of SPLA2 (steady state mean = 10.0 +/- 8.4 ng/mL; vaso-occlusive crisis mean = 23.7 +/- 40.5 ng/mL; ACS mean = 336 +/- 209 ng/mL). In patients with ACS sPLA2 levels were 100- fold greater than normal control values, 35 times greater than values in SCD patients at baseline, and five times greater than non-SCD patients with pneumonia. The degree of SPLA2 elevation in ACS correlated with three different measures of clinical severity and, in patients followed sequentially, the rise in SPLA2 coincided with the onset of ACS. The dramatic elevation of SPLA2 in patients with ACS but not in patients with vaso-occlusive crisis or non-SCD patients with pneumonia and the correlation between levels of SPLA2 and clinical severity suggest a role for SPLA2 in the diagnosis and, perhaps, in the pathophysiology of patients with ACS.     

Impairment of noninsulin-mediated glucose disposal in the elderly

While normal aging is characterized by resistance to insulin-mediated glucose disposal (IMGU), the effect of age on noninsulin-mediated glucose disposal (NIMGU), which is responsible for the majority of basal glucose uptake, has not been completely evaluated. These studies were conducted on healthy nonobese young (n = 10; age, 20-30 yr) and old (n = 10; age, 62-80 yr) men. Each subject underwent two paired studies in random order. In all studies a [3H]glucose infusion was used to measure glucose uptake and production rates, and somatostatin (500 micrograms/h) was infused to suppress endogenous insulin release. In study A, plasma glucose was kept close to fasting levels (approximately 5.6 mmol/L) using an euglycemic clamp protocol for 4 h. Plasma insulin decreased to less than 20 pmol/L within 15 min and remained suppressed thereafter in all studies. Steady state (15-240 min) plasma glucagon levels were slightly greater in the elderly [young, 86 +/- 5 (+/- SE); old, 98 +/- 2 ng/L; P less than .05]. Basal glucose uptake was similar in both groups (young, 877 +/- 21; old, 901 +/- 24 mumol/min). Glucose uptake during the last hour of the study (180-240 min) was used to represent NIMGU, because insulin action was assumed to be absent by this time. NIMGU was less in the elderly (young, 744 +/- 18; old, 632 +/- 32 mumol/min; P less than 0.01). In study B, plasma glucose was kept at about 11 mmol/L for 4 h using a hyperglycemic clamp protocol. Plasma insulin decreased to less than 20 pmol/L within 15 min and remained suppressed thereafter in all studies. Steady state plasma glucagon levels were slightly but not significantly higher in the elderly (young, 88 +/- 6; old, 100 +/- 4 ng/L). Basal glucose uptake (young, 910 +/- 27; old, 883 +/- 25 mumol/min) and NIMGU (young, 933 +/- 36; old, 890 +/- 16 mumol/min; P = NS) were similar in both young and old subjects. We conclude that aging is associated with impairment in NIMGU only in the basal state, which may explain in part the increase in fasting glucose with age.