Oxygen storage module with physisorption technology for closed-circuit respirators.

The new Cryogenic Flux Capacitor (CFC) technology employs nano-porous aerogel composites to store large quantities of fluid molecules in a physisorbed solid-state condition at moderate pressures and cryogenic temperatures. By its design architecture, a CFC device can be "charged" and "discharged" quickly and on demand according to standby/usage requirements. One of three main application areas is the CFC-Life for breathing air or oxygen supply to meet new demands in life support systems. Through the Liquid Oxygen Storage Module (LOXSM) Project, the National Institute for Occupational Safety and Health, and Cryogenics Test Laboratory have partnered to test the feasibility of applying the CFC technology to Closed-Circuit Escape Respirators (CCER), or respirators operating on the closed-circuit principle in general. The envisioned Cryogenic Oxygen Storage Module (COSM) is an innovative concept to store oxygen in solid-state form, according to physisorption processes at any cryogenic temperature, and deliver it as a gas using the CFC as the core storage element. Gaseous oxygen would be admitted into the breathing loop of the CCER by introducing heat into the storage module. Potentially replacing the gaseous or chemical based oxygen supply used in today's closed-circuit respirators, the COSM is a high capacity, conformal, small-size solution for future life support equipment of all kinds. In particular, are the CCER devices that must to be carried on the person, ready to be quickly deployed and used for escape in an emergency. Initial test data for physisorption of oxygen in aerogel materials and CFC core modules are presented. The basic operational parameters for charging and discharging are summarized through prototype testing of the cryogenic oxygen storage module.

Final Test Results for the Ground Operations Demonstration Unit for Liquid Hydrogen.

Described herein is a comprehensive project-a large-scale test of an integrated refrigeration and storage system called the Ground Operations and Demonstration Unit for Liquid Hydrogen (GODU LH2), sponsored by the Advanced Exploration Systems Program and constructed at Kennedy Space Center. A commercial cryogenic refrigerator interfaced with a 125,000 liter liquid hydrogen tank and auxiliary systems in a manner that enabled control of the propellant state by extracting heat via a closed loop Brayton cycle refrigerator coupled to a novel internal heat exchanger. Three primary objectives were demonstrating zero-loss storage and transfer, gaseous liquefaction, and propellant densification. Testing was performed at three different liquid hydrogen fill-levels. Data were collected on tank pressure, internal tank temperature profiles, mass flow in and out of the system, and refrigeration system performance. All test objectives were successfully achieved during approximately two years of testing. A summary of the final results is presented in this paper.

The effect of aggressive and moderate lowering of LDL-cholesterol and low dose anticoagulation on plasma lipids, apolipoproteins and lipoprotein families in post coronary artery bypass graft trial.

The reported results (The Post Coronary Artery Bypass Graft Trial Investigators. The effect of aggressive lowering of low-density lipoprotein cholesterol levels and low-dose anticoagulation on obstructive changes in saphenous-vein coronary-artery bypass grafts. New Engl J Med 1997;336:153-162) of the Post Coronary Artery Bypass Graft (Post CABG) trial have shown that aggressive lowering was more effective than moderate lowering of low density lipoprotein (LDL) cholesterol in reducing the progression of atherosclerosis in saphenous-vein grafts (27 vs. 39%; P < 0.001); low dose warfarin had no effect on the progression of atherosclerosis. The present report describes the effect of long-term (an average of 4.3 years) aggressive treatment with high (40-80 mg/day) and moderate treatment with low (2.5-5 mg/day) doses of lovastatin on lipids, apolipoproteins (apo) and apoA- and apoB-containing lipoprotein families. To achieve the target LDL-cholesterol levels (60-85 mg/dl for aggressive group and 134-140 mg/dl for moderate group), cholestyramine (8 g/day) was given to 25% of subjects on aggressive and 5% of subjects on moderate treatment. Although with both treatment strategies there were significant decreases (P<0.001) in the levels of total cholesterol, LDL-cholesterol, apoB, LDL-apoB and cholesterol-rich Lp-B family, percent changes in the levels of these variables were greater in the aggressive- than in the moderate-treatment groups. These treatments had only marginal effects in increasing the levels of high density lipoprotein cholesterol, apoA-I and Lp-A-I and Lp-A-I:A-II families. The long-term aggressive treatment exerted no effect on the concentrations of triglycerides, apoC-IlI, apoC-III in VLDL + LDL and triglyceride-rich Lp-Bc families. Neither treatment affected the levels of Lp(a). The potentially modifying influence of warfarin and apoE phenotypes on lovastatin-induced changes in lipoprotein variables was found to be of little significance. It is likely that the beneficial effect of lovastatin in reducing the progression of atherosclerosis in grafts is mediated through its specific lowering effect on cholesterol-rich Lp-B particles.

Lipoprotein changes in relation to body mass index in Native American adolescents.

In view of their known high incidence of noninsulin dependent diabetes (NIDDM), we sought to determine whether Native American (Plains Indian) children and adolescents show evidence of risk factors for both NIDDM and cardiovascular disease. Children and adolescents between the ages of 4 and 19 y were recruited, and field days were organized for data collection, which included height, weight [to compute body mass index (BMI)], waist and hip circumference, family histories, quantum of Native American ancestry, and blood sampling for fasting lipids, apolipoproteins, insulin, and glucose. BMI increased with age in boys and girls and tended to be higher than in Caucasian children. The difference was significant in 5-9-y-old (p < 0.05) and 10-14-y-old (p < 0.05) boys and 10-14-y-old girls (p < 0.001). Ten- to 14-y-old girls in the highest quartile for BMI had higher triglyceride levels (p < 0.05) and lower HDL cholesterol (p < 0.001) when compared with those in the lower quartiles. In contrast, 15-19 y olds in the highest quartile for BMI had higher cholesterol, LDL cholesterol, and apolipoprotein B (p < 0.001). The mean fasting insulin levels were not related to BMI. The data suggest that, within this Plains Indian population, obesity associated with elevated lipid levels tends to begin at an early age in Native American children. Insulin levels do not appear to be related to BMI, a putative index of adiposity, in this population of children known to be prone to NIDDM in adult life.

Triglyceride enriched lipoprotein particles correlate with the severity of coronary artery disease.

A group of 100 male normotensive, non-obese, non-diabetic subjects who had undergone coronary angiography were studied to determine relationship between the severity of coronary artery disease (CAD) and plasma lipids, apolipoproteins and lipoprotein particles defined by their apolipoprotein composition. CAD was found in 84 and no measurable lesions were found in 26 subjects. The severity of CAD was determined on the basis of size and number of lesions and expressed in terms of a global CAD score. Low density lipoprotein (LDL)-cholesterol showed a tendency to be higher in CAD patients than in CAD-free subjects (216 vs. 205 mg/dl, P = 0.07). HDL-cholesterol showed a tendency towards lower values in CAD patients compared to CAD-free subjects 35 vs. 41 mg/dl, P = 0.07). In univariate analysis the severity of CAD correlated with (i) complex, apolipoprotein (apo) B containing particles (Lp-B-complex, r = 0.31, P = 0.005), (ii) HDL-cholesterol (r = -0.30, P = 0.005), (iii) apoC-III in heparin precipitate (r = 0.30, P = 0.005) and (iv) plasma triglycerides (r = 0.25, P = 0.02), all of which are related to triglyceride-rich lipoproteins. A comparison between the two subspecies of complex lipoprotein particles revealed that those containing apolipoproteins B, C-III and E (Lp-B:C:E complex) were more closely associated with CAD score (r = 0.27, P = 0.01) than those containing apolipoproteins A-II, B, C, D and E (Lp-A-II:B-complex). LDL-cholesterol also correlated with the global CAD score (r = 0.23, P = 0.03). In multiple regression analysis only HDL-cholesterol (P = 0.003), apoC-III-ratio (P = 0.007), Lp-B-complex (P = 0.02) and Lp-B:C:E-complex (P = 0.04) showed significant correlation with CAD score. The results of this study demonstrate that some of the triglyceride rich lipoprotein particles represent a risk factor for CAD and support the clinical usefulness of specific assays capable of distinguishing lipoprotein particles on the basis of apolipoprotein composition.

Lipids and apolipoproteins in growth hormone-deficient children during treatment.

The role of growth hormone (GH) in regulating the transport of plasma lipoproteins has not been clearly defined, but past studies suggest that GH may influence cholesterol levels. This protocol was designed to evaluate possible changes in lipid and apolipoprotein status in GH-deficient children and children with neurosecretory dysfunction (NS) before GH therapy and at intervals after GH therapy was started. Twenty children with classic GH deficiency were evaluated, and 28% were hyperlipidemic at the onset of the study. Seven children were evaluated in the NS group, and only one (14%) showed an elevated total cholesterol (TC) greater than 200 mg/dL. The mean TC for all the GH-deficient children was elevated above the normal range, but not for the NS group. The mean apolipoprotein (apo) C-III level and its heparin-precipitated fraction (HP) were also elevated in the GH-deficient group, but only the apo C-III HP was elevated in the NS group. A standard replacement dose of recombinant methionyl GH was used, and therapy had no significant effect on TC or triglyceride (TG) levels. Apo C-III HP, a marker of hypertriglyceridemia, increased after the start of therapy, but no other lipoprotein levels changed significantly in the GH-deficient group. No changes were seen with treatment in the NS group. The longitudinal design of this study allowed demonstration of the later changes in the apolipoproteins and the presence of a distinct subset of patients with both GH deficiency and hypercholesterolemia. This study supports the role of GH in modulating lipid metabolism.

Lack of effect of probucol on atheroma formation in cholesterol-fed rabbits kept at comparable plasma cholesterol levels.

Rabbits were fed cholesterol for 14 weeks to study the effect of probucol on atheroma formation. Three groups of animals were investigated: group CHOL was fed 1% cholesterol and served as control for group P + CHOL. fed 1% cholesterol and 1% probucol from the onset till the end of the experiment: group CHOL + P received 1% cholesterol throughout the experiment and 1% probucol during the last 4 weeks only. Plasma cholesterol concentrations were monitored at frequent intervals and were modulated by dietary perturbations so that the areas under the curve expressing plasma cholesterol changes with time, were similar in probucol and non-treated rabbits. The efficacy of long-term probucol treatment was evidenced by a significant reduction in plasma apolipoprotein A-I throughout the experiment and lower plasma TBARs during the first 6 weeks, when the hypocholesterolemic effect of probucol was also seen. Two weeks prior to the termination of the experiment, the rabbits were injected with rabbit plasma labeled with [3H]cholesteryl linoleyl ether [( 3H]CLE). Aortic atheromatosis was quantified by determination of total and cholesteryl ester (CE). The aortic cholesterol content was related to the arch, thoracic and abdominal segments, to the surface area of each segment or its dry defatted weight. Total and esterified cholesterol were highest in the aortic arch in all 3 groups when related to any of the above mentioned parameters. No statistically significant difference in aortic total cholesterol and CE content was seen among the three groups studied. The [3H]CLE recovered in the aortic segment correlated with the CE content and the [3H]CLE (dpm)/mg CE in all segments was similar. No statistically significant difference in the [3H]CLE recovered in the aortic segments among the 3 groups was seen. We conclude that in cholesterol-fed rabbits, in which the plasma cholesterol levels were maintained at comparable levels, probucol treatment did not affect plasma CE influx into the aorta and did not attenuate development of aortic atherosclerosis.

Plasma apolipoprotein C-III levels in children with type I diabetes.

The serum concentrations of apolipoproteins C-III, B, and A-I were determined in children with type I diabetes mellitus to establish whether they correlated with the level of glycosylated hemoglobin (Hb A1) and to determine whether these values differ between diabetic children and a population of normal children. Triglyceride (TG), total cholesterol (TC), and apolipoprotein (Apo) levels were studied in 95 children with type I diabetes; 51 of the children were attending a diabetes clinic and 44 were attending a diabetes summer camp. The level of Hb A1 correlated with Apo C-III (P less than .001) and TC (P less than .001) values in the clinic group, but not with Apo A-I or TG levels in either group. The Apo C-III level was higher in both groups of diabetic children (8.0 +/- 0.5 and 9.5 +/- 0.4 mg/dl) (P less than .01) than in normal subjects (6.1 +/- 0.2 mg/dl). We conclude that the Apo C-III level tends to be higher in diabetics than in normal subjects, even in the normotriglyceridemic camp group. The Apo C-III level correlated with both the TC level and Hb A1, suggesting that Apo C-III determinations in type I diabetic patients may permit early identification of atherosclerotic risk.

Plasma lipoprotein abnormalities in heterozygotes for familial lecithin:cholesterol acyltransferase deficiency.

Measurement of plasma lecithin:cholesterol acyltransferase (LCAT) activity was used to segregate unaffected family members (n = 8) from heterozygotes (n = 8) and homozygotes (n = 2) in a large LCAT-deficient kindred. The activity was absent in the homozygotes and was decreased to 50% of normal in the heterozygotes. Endogenous cholesterol esterification rate measurements did not differentiate the heterozygotes from the unaffected family members or normal subjects. The heterozygotes had significantly higher fasting plasma triglycerides, apo B, and lower HDL-cholesterol and apo AI than the unaffected family members. The HDL of the heterozygotes had the same mass of free cholesterol and triglyceride, but the mass of cholesteryl ester was reduced by 47%. The differences were not related to abnormal postheparin lipolytic activities. However, cholesteryl ester transfer activity in the lipoprotein-free (d greater than 1.21 bottom) fraction of plasma was significantly (P less than .05) decreased in the heterozygotes when compared to unaffected members. We conclude that the low LCAT activity is the likely cause of the qualitative and quantitative differences in the plasma lipoproteins of the heterozygotes in this family with LCAT deficiency. However, the low HDL and apo A-I levels are not associated with either a family or personal history of premature atherosclerosis.

Quantification of two different types of apolipoprotein A-I containing lipoprotein particles in plasma by enzyme-linked differential-antibody immunosorbent assay.

We describe a method for measuring apolipoprotein A-I (ApoA-I) associated and unassociated with apolipoprotein A-II (ApoA-II) in plasma. To directly determine associated ApoA-I, we coated microtiter plates with antibody to ApoA-II, blocked the nonspecific binding sites, and incubated the plate with plasma, immobilizing the lipoprotein particles containing both ApoA-II and ApoA-I. The unbound constituents of plasma were washed away, peroxidase-labeled antibody to ApoA-I was added, the plate rewashed, peroxidase substrate added, and the resulting color measured. ApoA-I unassociated with ApoA-II was evaluated by subtracting the concentration of associated ApoA-I from the total ApoA-I concentration. The method is specific, rapid, and precise. Within- and between-assay CVs were 5.6 and 9.8%, respectively. Analytical recovery of ApoA-I was 94%. The average normolipidemic concentration of ApoA-I associated with ApoA-II in 50 women was 790 mg/L; in 50 men, it was 788 mg/L. The corresponding values for unassociated ApoA-I were 644, 577 mg/L. Both lipoprotein forms of ApoA-I were detected in all major density classes, but were most abundant in high-density lipoproteins. The technique is applicable to measurement of any two apolipoproteins that occur in both associated and unassociated forms in plasma.

Plasma lipids and apolipoproteins in a 13-year-old boy with diabetic ketoacidosis and extreme hyperlipidemia.

A 13-year-old boy with untreated diabetes presented in severe ketoacidosis (DKA) for the first time with an initial triglyceride (TG) level of 14,461 mg/dl. Serial blood samples were drawn to determine the interrelationships of changes in lipids and apolipoproteins during treatment with insulin and intravenous fluids. The TG level declined to 122 mg/dl in 7 days concomitant with a lowering of apolipoproteins C-II, C-III, E, D, and F. Further observations suggested that the TG-rich lipoproteins underwent degradation associated with a decline in the levels of apolipoproteins associated with very low density lipoprotein (VLDL) in contrast to an increase in high density lipoprotein-cholesterol (HDL-C), ApoA-I and ApoA-II. ApoB and low density lipoprotein cholesterol (LDL-C) were increased transiently. Subsequent therapy with continuous subcutaneous insulin infusion (CSII) were effective in maintaining glucose homeostasis and normolipidemia for 6 months.

Increased levels of HDL-cholesterol and apolipoprotein A-I after intensified insulin therapy for diabetes.

Sixteen subjects with insulin-dependent diabetes mellitus were studied to determine whether changes in plasma lipids and apolipoproteins follow intensified control using preprandial doses of regular insulin with an additional dose of NPH insulin before bedtime. The mean total dialy dose of insulin was increased from 1.03 +/- 0.09 to 1.17 +/- 0.44 units/kg throughout the six-month period. Levels of HDL-cholesterol and apolipoprotein A-I increased without significant changes in hemoglobin A1 (HbA1), triglyceride, or cholesterol. These findings suggest that increases in HDL-cholesterol and apolipoprotein A-I were a result of the intensified insulin delivery.

Quantitative determination of human plasma apolipoprotein A-I by a noncompetitive enzyme-linked immunosorbent assay.

A noncompetitive enzyme-linked immunosorbent assay (ELISA) for human plasma apolipoprotein A-I (ApoA-I) was developed. Microtiter plates were coated with purified antibodies to ApoA-I and blocked. Plasma samples from normolipidemic and hypertriglyceridemic subjects were added and ApoA-I was allowed to bind to coating antibodies. After washing, the amount of ApoA-I bound to microtiter plates was estimated with horseradish peroxidase-labeled antibodies to ApoA-I. A single step delipidization procedure was included to expose masked antigenic sites of ApoA-I in plasma. The average concentration of ApoA-I in plasma of normolipidemic subjects was 1.37 g/l. Recovery of ApoA-I added to plasma varied from 93-107%. Intra- and inter-assay coefficients of variations were 4 and 8%, respectively. The assay was also used for quantifying ApoA-I in lipoprotein density classes. There was a good correlation between this assay and electroimmunoassay (r = 0.84-0.92). The described sandwich ELISA is a specific, precise, sensitive and relatively simple method for measuring ApoA-I levels in human plasma.

Studies of lipids, lipoproteins, and apolipoproteins in Menkes' disease.

Three patients with Menkes' disease, an inherited disorder of copper transport, were studied to determine whether the copper deficiency was associated with a lipoprotein disorder. Hypocuprinemia was documented in all three cases. Two patients had severe copper and ceruloplasmin deficiencies, whereas the third patient had a less severe deficiency. Hypertriglyceridemia was observed in the first patient, and elevations in triglyceride, cholesterol, apolipoprotein B (ApoB), and apolipoprotein C-III (ApoC-III) occurred predominantly in the very low density lipoprotein fraction (VLDL). This patient had normal lipoprotein lipase activity but mild glucose intolerance. The second patient had a borderline high cholesterol level with normal plasma triglycerides and apolipoproteins, whereas the third patient appeared to have normal total cholesterol but slightly higher triglycerides with elevated plasma apolipoprotein E (ApoE). No striking differences were observed in the chemical composition of all lipoprotein subfractions between patients and controls except that the neutral lipid content of VLDL was higher in patients than in controls. The ApoB was initially normal in molecular weight but degraded faster than the controls during storage. The appearance of the major low density lipoprotein (LDL) fraction of the first two patients was opaque white, in contrast to clear yellow in the third patient and in the age- and diet-matched controls. This abnormal appearance of LDL in these patients was associated with low plasma levels of beta-carotene and ceruloplasmin. These findings suggest that decreased serum copper levels may be associated with lipid and lipoprotein abnormalities and may enhance lipid peroxidation of LDL accounting for the color change.(ABSTRACT TRUNCATED AT 250 WORDS)

Use and significance of reference serum as a secondary standard for electroimmunoassay of apolipoprotein A-I.

This study was designed to show the effect of different primary standards and antisera on the variability of concentrations of apolipoprotein A-I (ApoA-I) in plasma and to document the usefulness of reference sera as a secondary standard in the electroimmunoassay of this apolipoprotein. We compared the reactivities of two separate ApoA-I samples and a preparation of high-density lipoprotein (HDL3) with seven different antisera to ApoA-I. The antisera reacted differently with each of the three standards, as shown by the different slopes of their standard curves. The resulting inconsistencies in the ApoA-I values for unknown plasma samples were shown to be corrected by the use of a reference serum. When ApoA-I analyses were carried out with the reference serum as a standard, all seven antisera gave statistically indistinguishable results for concentrations of plasma ApoA-I. The use of reference sera thus represents the simplest and most convenient means of standardizing the electroimmunoassay for ApoA-I.