In vivo turnover study demonstrates diminished clearance of lipoprotein(a) in hemodialysis patients

Lipoprotein(a) (Lp(a)) consists of a low-density lipoprotein-like particle and a covalently linked highly glycosylated protein, called apolipoprotein(a) (apo(a)). Lp(a) derives from the liver but its catabolism is still poorly understood. Plasma concentrations of this highly atherogenic lipoprotein are elevated in hemodialysis (HD) patients, suggesting the kidney to be involved in Lp(a) catabolism. We therefore compared the in vivo turnover rates of both protein components from Lp(a) (i.e. apo(a) and apoB) determined by stable-isotope technology in seven HD patients with those of nine healthy controls. The fractional catabolic rate (FCR) of Lp(a)-apo(a) was significantly lower in HD patients compared with controls (0.164+/-0.114 vs 0.246+/-0.067 days(-1), P=0.042). The same was true for the FCR of Lp(a)-apoB (0.129+/-0.097 vs 0.299+/-0.142 days(-1), P=0.005). This resulted in a much longer residence time of 8.9 days for Lp(a)-apo(a) and 12.9 days for Lp(a)-apoB in HD patients compared with controls (4.4 and 3.9 days, respectively). The production rates of apo(a) and apoB from Lp(a) did not differ significantly between patients and controls and were even lower for patients when compared with controls with similar Lp(a) plasma concentrations. This in vivo turnover study is a further crucial step in understanding the mechanism of Lp(a) catabolism: the loss of renal function in HD patients causes elevated Lp(a) plasma levels because of decreased clearance but not increased production of Lp(a). The prolonged retention time of Lp(a) in HD patients might importantly contribute to the high risk of atherosclerosis in these patients.     

Effect of a nonlactose diet on human intestinal disaccharidase activity

Summary Total lactose abstinence for 42 days in 7 subjects failed to induce a deficiency in intestinal lactase or clinical lactose intolerance. Therefore, dietary lactose content does not appear to be an important factor in determining the level of intestinal lactase in humans for this period of time.Further reproduction is authorized to satisfy the needs of the U. S. Government.Supported in part by Training Grant T1 AM-5179 from the National Institutes of Health, U. S. Public Health Service.The authors wish to acknowledge the technical assistance of Anthony Walker, who did the enzyme assays.     

Characterization of the acute clinical illness associated with human immunodeficiency virus infection

The clinical and serologic features and immune status of 39 homosexual men who had seroconversion to human immunodeficiency virus positivity were compared with 26 homosexual men who remained seronegative during a six-month period. An acute clinical illness occurred in 92.3% of seroconverted subjects and 40% of controls. The duration of illness was significantly greater in the seroconverters than the controls (10 + 4.4 days). A general practitioner was consulted by 87.2% of the seroconverters because of the illness, including 12.8% who were admitted to hospital, compared with 20% of controls. The most frequently reported symptoms in the seroconversion group were fever (76.9%); lethargy and malaise (66.7%); anorexia, sore throat, and myalgias (56.4% each); headaches and arthralgias (48.7% each); weight loss (46.2%); swollen glands (43.5%); retro-orbital pain (38.5%); and dehydration and nausea (30.8% each). Lymphadenopathy developed in 75% of seroconverters compared with 4% of controls. Changes in T-cell subsets were not found in controls, but the number of T4+ cells and the T4+/T8+ ratio decreased significantly in seroconverters.     

Loss of Gsα Early in the Osteoblast Lineage Favors Adipogenic Differentiation of Mesenchymal Progenitors and Committed Osteoblast Precursors

In humans, aging and glucocorticoid treatment are associated with reduced bone mass and increased marrow adiposity, suggesting that the differentiation of osteoblasts and adipocytes may be coordinately regulated. Within the bone marrow, both osteoblasts and adipocytes are derived from mesenchymal progenitor cells, but the mechanisms guiding the commitment of mesenchymal progenitors into osteoblast versus adipocyte lineages are not fully defined. The heterotrimeric G protein subunit G_sα activates protein kinase A signaling downstream of several G protein‐coupled receptors including the parathyroid hormone receptor, and plays a crucial role in regulating bone mass. Here, we show that targeted ablation of G_sα in early osteoblast precursors, but not in differentiated osteocytes, results in a dramatic increase in bone marrow adipocytes. Mutant mice have reduced numbers of mesenchymal progenitors overall, with an increase in the proportion of progenitors committed to the adipocyte lineage. Furthermore, cells committed to the osteoblast lineage retain adipogenic potential both in vitro and in vivo. These findings have clinical implications for developing therapeutic approaches to direct the commitment of mesenchymal progenitors into the osteoblast lineage. © 2014 American Society for Bone and Mineral Research     

Impact of Food Intake on Liver Stiffness Determined by 2-D Shear Wave Elastography: Prospective Interventional Study in 100 Healthy Patients

The aim was to evaluate the influence of food intake on liver stiffness measurement (LSM), performed with 2-D shear wave elastography (Logiq E9, GE Medical Systems, Wauwatosa, WI, USA). One hundred healthy volunteers were prospectively enrolled. Mean age was 25.8 (19–55) y, and mean body mass index was 22.43 (17.3–30.8) kg/m². Patients fasted for at least 3 h and subsequently ingested a liquid meal of 800 kcal. Liver stiffness and portal vein velocity were measured before and after food intake. Food intake resulted in significantly higher LSM values compared with baseline LSM (5.74 ± 0.94 kPa vs. 4.80 ± 0.94 kPa, p < 0.001). On multiple linear regression analysis, body mass index was significantly positively correlated with the LSM increase after food intake (p?=?0.01). No correlation between the increase in LSM and the increase in post-prandial portal vein velocity was observed (r?=?0.09). In summary, food intake has a significant influence on LSM. There is an 11% risk of misclassifying non-fasting, healthy patients as having significant fibrosis.