PubMed · 15445203
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J F FRIED, J SCHUBERT. 1960. Progress report: thorium removal.. https://pubmed.ncbi.nlm.nih.gov/15445203/
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A two-thiol reactive lanthanide-DOTA (1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid) chelate, CLaNP-3 (CLaNP=caged lanthanide NMR probe), was synthesized for the rigid attachment to cysteine groups on a protein surface, and used to obtain long-range-distance information from the {15N,1H} HSQC spectra of the protein-lanthanide complex. The DOTA ring exhibits several isomers that are in exchange; however, single resonances were observed for most amide groups in the protein, allowing determination of a single, apparent magnetic-susceptibility tensor. Pseudocontact shifts caused by Yb-containing CLaNP-3 were observed for atoms at 15-35 A from the metal. By using Gd-containing CLaNP-3, relaxation effects were observed, allowing distances up to 30 A from the paramagnetic center to be determined accurately. Similar results were obtained with a Gd-DTPA (diethylene-triaminepentaacetic acid) chelate, CLaNP-1, bound in the same bidentate manner to the protein. This study demonstrates that bidentate attachment of a paramagnetic probe enables determination of long-range distances.
Positron emission tomography (PET) is becoming a dominating method in the field of molecular imaging. Most commonly used radionuclides are accelerator produced 11C and 18F. An alternative method to label biomolecules is the use of metallic positron emitters; among them 68Ga is the most promising as it can be produced from a generator system consisting of an inorganic or organic matrix immobilizing the parent radionuclide 68Ge. Germanium-68 has a long half-life of 271 days which allows the production of long-lived, potentially very cost-effective generator systems. A commercial generator from Obninsk, Russia, is available which uses TiO2 as an inorganic matrix to immobilize 68Ge in the oxidation state IV+. 68Ge(IV) is chemically sufficiently different to allow efficient separation from 68Ga(III). Ga3+ is redox-inert; its coordination chemistry is dominated by its hard acid character. A variety of mono- and bifunctional chelators were developed which allow immobilization of 68Ga3+ and convenient coupling to biomolecules. Especially peptides targeting G-protein coupled receptors overexpressed on human tumour cells have been studied preclinically and in patient studies showing high and specific tumour uptake and specific localization. 68Ga-radiopharmacy may indeed be an alternative to 18F-based radiopharmacy. Freeze-dried, kit-formulated precursors along with the generator may be provided, similar to the 99Mo/99mTc-based radiopharmacy, still the mainstay of nuclear medicine.
Vesico-ureteral reflux (VUR) is the most common inherited disorder of the lower urinary tract. Children with VUR are at risk for ongoing renal damage with subsequent infections. IL8 is an important inflammatory mediator which can be produced by epithelial cells of the renal tract in response to a variety of inflammatory stimuli. High serum concentrations of IL-8 have been reported in patients with chronic renal failure. Elevated IL-8 levels have been reported in the urine of patients with VUR and renal parenchymal scarring (RPS). More recently it was reported that urine IL-8 levels remain elevated in infants with VUR even in the absence of a urinary tract infection (UTI). Increased IL-8 expression has been shown to be associated with polymorphism at position -251 (rs4073) of the IL-8 promoter. The aim of this study was to examine the association of IL-8 gene polymorphism with familial VUR in a cohort of 219 siblings from 109 families affected with VUR, the largest such cohort tested to date. RPS was assessed using dimercaptosuccinic acid scintigraphy. Genotyping was performed in 219 siblings with VUR (157 without RPS, 62 with RPS) and 292 controls for the position -251 of IL-8 gene by polymerase chain reaction with tetra primers and gel analysis. Genotype was compared using the chi square test. Statistical significance was taken as a value of P < 0.05. There were no significant differences in IL-8 -251 genotype frequency between VUR patients and controls. Similarly, gender, severity of VUR and renal parenchymal scarring had no effect on IL-8 -251 genotype frequency. Although IL-8 urinary levels have been reported to be elevated in VUR, our data indicate that IL-8 gene is not involved in the pathogenesis of familial VUR or reflux nephropathy.