Low density lipoprotein retention by aortic tissue. Contribution of extracellular matrix

We compared in vitro heparin binding activity and in vivo intravascular clearance and aortic uptake in rabbits of native, reductively methylated and heparin-complexed low density lipoprotein (LDL) in order to explore the extracellular matrix binding vs cellular metabolism of LDL. Reductively methylated LDL formed soluble and insoluble complexes with heparin which was comparable to native LDL. Reductive methylation of LDL produced only 30% reduction in aortic uptake vs 60% reduction in plasma clearance, reflecting the relatively smaller contribution of receptor-mediated pathway in aortic tissue vs whole animal. The intravascular clearance of native and heparin-complexed LDL remained essentially the same, indicating similarities in cellular metabolism of LDL in both cases. But the aortic uptake of the heparin bound LDL was 30% less than the native LDL, suggesting an inhibition in binding of heparin-complexed LDL to tissue proteoglycans. Saline extraction accounted for only part (53-66%) of the LDL preparations that were retained by the tissue while subsequent collagenase and elastase treatments extracted 3-5% and 17-22% of the materials respectively. These results favor the contribution of arterial extracellular matrix components to the retention of LDL.     

Serum lipoprotein profile in children from a biracial community: the Bogalusa Heart Study.

Serum lipoprotein profiles in 3182 children, ages 5-14 years, were studied in a biracial community as part of the Bogalusa Heart Study to describe the early natural history of atherosclerosis. White and black children showed similar mean levels of beta-lipoproteins. Pre-beta-lipoprotein levels, however, were significantly higher in white shildren, while significantly higher levels of alpha-lipoprotein were found in black children. Girls had generally higher levels of beta- and pre-beta-lipoprotein and lower levels of alpha-lipoprotein than boys, although the differences were not significant at each age group. With age there was little change in alpha-lipoprotein levels, a significant increase in pre-beta-lipoprotein levels and a slight but significant decrease between 11 and 14 years in beta-lipoprotein levels. The correlation of alpha-lipoprotein was negative with beta-lipoprotein and, to a greater extent, with pre-beta-lipoprotein. The above inverse relationships were significantly greater in white children than in black children, suggesting differences in lipoprotein profiles in the two groups. Lipoprotein values from a total community study are now available for comparison with the currently recommended upper normal limits for lipoproteins. Since only a very small percentage of children could be considered as hyperlipoproteinemic by those specific levels in this community, we suggest that distributions and percentiles be used to evaluate children for hyperlipoproteinemia.     

The Diagnostic Dilemma of a Parasympathetic Schwannoma in the Submandibular Gland

Schwannomas are benign soft tissue tumours that arise from nerve sheath cells. They are rare in the salivary glands and are thought to arise from the parasympathetic nerves. We report the case of a 69-year-old man who presented with a painless right submandibular mass that appeared to resemble a pleomorphic adenoma on ultrasonography and, on this basis, proceeded to surgical excision of the gland. We review the relevant literature and highlight the diagnostic pitfalls.     

A physical basis for protein secondary structure

A physical theory of protein secondary structure is proposed and tested by performing exceedingly simple Monte Carlo simulations. In essence, secondary structure propensities are predominantly a consequence of two competing local effects, one favoring hydrogen bond formation in helices and turns, the other opposing the attendant reduction in sidechain conformational entropy on helix and turn formation. These sequence specific biases are densely dispersed throughout the unfolded polypeptide chain, where they serve to preorganize the folding process and largely, but imperfectly, anticipate the native secondary structure.     

Nodal Langerhans cell histiocytosis with prominent eosinophilic emperipolesis

Multinucleated giant cells of osteoclastic type are known to occur in nodal and extranodal lesions of Langerhans cell histiocytosis (LCH). These giant cells are thought to be derived from phagocytic histiocytes, which correlate with the degree of necrosis in LCH lesions. Emperipolesis commonly seen in Rosai–Dorfman disease is a distinct phenomenon characterized by intact phagocytosed cells in an intracytoplasmic vacuole protected from proteolytic digestion. We present a case of emperipolesis of inflammatory cells especially of eosinophils by multinucleated giant cells of Langhans type in a lymph node involved by LCH—a finding that has not been described previously in the literature. Diagn. Cytopathol. 2015;43:1000–1002. © 2015 Wiley Periodicals, Inc.     

Sotatercept in patients with osteolytic lesions of multiple myeloma

This phase IIa study evaluated the safety and tolerability of sotatercept, and its effects on bone metabolism and haematopoiesis in newly diagnosed and relapsed multiple myeloma (MM) patients. Patients were randomized (4:1) to receive four 28‐d cycles of sotatercept (0·1, 0·3, or 0·5 mg/kg) or placebo. Patients also received six cycles of combination oral melphalan, prednisolone, and thalidomide (MPT). Thirty patients were enrolled; six received placebo and 24 received sotatercept. Overall, 25% of patients received all four sotatercept doses; 71% of sotatercept‐treated patients had ≥1 dose interruption mainly due to increases in haemoglobin levels. Grade ≥3 adverse events (AEs) were reported in 17% of patients receiving placebo and 58% receiving sotatercept. Grade 4 AEs in sotatercept‐treated patients were neutropenia, granulocytopenia, and atrial fibrillation (one patient each). In patients without bisphosphonate use, anabolic improvements in bone mineral density and in bone formation relative to placebo occurred, whereas bone resorption was minimally affected. Increases in haemoglobin levels, versus baseline, and the duration of the increases, were higher in the sotatercept‐treated patients, with a trend suggesting a dose‐related effect. Multiple doses of sotatercept plus MPT appear to be safe and generally well‐tolerated in MM patients.