Development of Immunosorbents for apoB-Containing Lipoproteins Apheresis

Abstract: Three types of sorbents were developed for the specific removal of atherogenic apoB-containing low-density lipoprotein (LDL) and lipoprotein LDL(a) (Lp[a])from human plasma. Two sorbents contained monospecific sheep polyclonal or mouse monoclonal antibodies against human apoprotein B-100. The third one was intended for specific removal of Lp(a) and contains sheep antibodies against human Lp(a). Thirty patients were treated for up to 9 years by LDL apheresis with anti-LDL immunosorbents. A pilot study of Lp(a) apheresis with 3 patients was conducted during 3 years. The results showed that extracorporeal immunosorption is safe and effective for lowering LDL and Lp(a). These procedures may be used both for metabolic investigations and for studies on possible regression of atherosclerosis.     

Early-onset ataxia with cardiomyopathy and retained tendon reflexes maps to the friedreich's ataxia locus on chromosome 9q

Absence of lower limb tendon reflexes has been considered an essential diagnostic criterion for Friedreich's ataxia (FA). However, preservation of knee and ankle jerks has been reported in a few patients. Linkage analysis to FA locus (FRDA) on chromosome 9q13-21.1 was performed in 11 patients from 6 families with FA phenotype, including cardiomyopathy, but retained reflexes (FARR). A maximal lod score of 3.38 at recombination fraction theta equal to 0.00 was obtained demonstrating that FARR maps to the FRDA locus. These results suggest that FARR is a variant phenotype of FA.     

Polymer genomics: shifting the gene and drug delivery paradigms.

Pluronic, the A-B-A amphiphilic block copolymers of poly(ethylene oxide) and poly(propylene oxide), can up-regulate the expression of selected genes in cells and alter genetic responses to antineoplastic agents in cancer. Two key new findings are discussed in relation to current drug and gene delivery strategies. First, these block copolymers alone and in combination with a polycation, polyethyleneimine, can up-regulate the expression of reporter genes in stably transfected cells. This underscores the ability of selected synthetic polymers to enhance transgene expression through a mechanism that augments improved DNA delivery into a cell. Second, although, when used alone, Pluronic is "genetically benign," when combined with an antineoplastic agent, doxorubicin, it drastically alters pharmacogenomic responses to this agent and prevents the development of multidrug resistance in breast cancer cells. Collectively, these studies propose the need for a thorough assessment of pharmacogenomic effects of polymer therapeutics to maximize the clinical outcomes and understand the pharmacological and toxicological effects of polymer-based drugs and delivery systems.     

Molecular structure of 1,7-dichlorotetradecaphenylheptasilane as a model of poly(diphenylsilane)

The molecular and crystal of 1,7-dichlorotetradecaphenylheptasilane Cl(SiPh₂)₇Cl

1 Dedicated to Prof. Dr. H. Sinn on the occasion of his 60th birthday

(I) was determined. The molecule has a helical conformation with the torsion angles SiSiSiSi in the range of 154°–162°. Crystal I is built of infinite polysilane chains extended along the [111] direction and separated by solvating benzene and toluene molecules.     

Orbital hydatid cyst manifested as expanding exophthalmos following blunt orbital trauma

A 14-year-old boy suffered right blunt orbital trauma. X-ray revealed a compressed fracture of the right ethmoidal sinuses. Three months after the trauma, progressive, painless right proptosis developed. Ocular examination revealed a severe proptosis and pronounced down displacement of the right globe without signs of orbital inflammation. A well-demarcated, extraconal right orbital cystic mass was seen on computerized tomography scan. The cyst contents were aspirated and found to contain echinococcal scolices and "hydatid sand." Hypertonic saline was injected and the cyst was excised. Progressive proptosis after blunt orbital trauma in patients from endemic areas should be suspected of being an orbital hydatid cyst.     

Acute endotoxemia in rats induces down-regulation of V2 vasopressin receptors and aquaporin-2 content in the kidney medulla

BACKGROUND: Endotoxemia can lead to fluid metabolism alterations despite unchanged or elevated plasma vasopressin (VP) levels, suggesting a refractoriness of the kidney to the effect of the peptide. To test this hypothesis, we examined the effect of lipopolysaccharide (LPS) injection on the expression of V2 receptors and aquaporin-2 in the kidney. METHODS: Plasma VP and urine osmolality, and binding of [3H]VP to kidney membranes, Western blot, and immunohistochemical analysis of aquaporin-2, in situ hybridization for V2 VP receptors and cytokines mRNAs were measured in the kidney 3 to 24 hours after LPS injection, 250 microg/100 g, intraperitoneally. RESULTS: LPS injection caused prolonged decreases in urine osmolality (up to 24 hours) without significant changes in plasma levels of sodium or VP. This was associated with marked decreases in V2 VP receptor mRNA and VP receptor number in the kidney, which were evident for up to 12 hours after LPS injection. Aquaporin-2 in kidney inner medulla was also reduced by about 50%. LPS induced interleukin (IL)-1beta in the kidney medulla by 3 hours, reached maximum at 6 hours, and started to decline by 12 hours, while it increased IL-6 mRNA significantly only at 3 hours. Interleukin mRNA expression was absent in kidneys of control rats. In vitro incubation of kidney medulla slices with IL-1beta reduced VP binding. CONCLUSION: The inflammatory response to acute endotoxemia down regulates V2 VP receptors and aquaporin-2 of the kidney inner medulla resulting in prolonged impairment of the renal capacity to concentrate urine.     

Polyomavirus simian virus 40 infection associated with nephropathy in a lung-transplant recipient

BACKGROUND: Between 1955 and 1963, millions of individuals worldwide received vaccines contaminated with polyomavirus simian virus (SV)40. Recent data suggest that some individuals may develop renal dysfunction related to SV40 infection, including individuals too young to have received contaminated vaccines. CASE REPORT AND RESULTS: Three years after bilateral lung transplantation, a 32-year-old man with cystic fibrosis developed nephrotic syndrome and progressed to end-stage renal failure over 1.5 years. He was shown to have nephropathy caused by SV40. The diagnosis was documented by detecting and confirming sequences of SV40 (but not BK or JC virus) in his kidney biopsy and urine by polymerase chain reaction, Southern blot, and DNA sequencing. Positive immunohistochemistry for SV40 was found in his kidney, and neutralizing antibodies for SV40 were detected in his serum, before and after the onset of renal dysfunction. A source for the virus was not determined. His household contacts did not have serologic or molecular evidence of SV40 infection. No serum or tissue samples were available from his 27-year-old donor. DISCUSSION: This report shows that SV40 is circulating in the community and can cause nephropathy in transplant patients.