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The molecular mechanisms involved on the interaction of anthracycline antibiotic drug used in cancer chemotherapy with chromatin and its components, DNA and histones are reviewed. The study suggests that one very important component of the activity of these drugs is the result of these manifold interactions that lead to a chromatin unfolding and aggregation.

Conclusive evidence is obtained that the daunomycin drug is also able to interact with chromatin-bound linker histones without any noticeable binding to core histones, using a compositionally defined chicken erythrocyte chromatin fraction. The drug can interact in an equal fashion with both histone H1 and H5 and to a greater extent with core histones H3/H4 and H2A/H2B as free proteins in solution.

TmPuL13, a family 13 glycoside hydrolase from 'Thermotoga maritima', is a four-module protein having pullulanase activity. Dissection of the functions of the three unknown modules revealed hat the 100 amino acid module at the extreme N-terminus of TmPuL13 comprises a new family of carbohydrate-binding modules (CBM) that a bioinformatic analysis shows are most frequently found in pullulanase-like sequences from bacterial pathogens.

Several biochemical and biophysical studies are conducted to explain the properties, as well as the structural role played by the H2A.Z and H3.3 histone variants. These histones are shown to be widely involved in the creation of new positions and the alteration of relative occupancy of the existing nucleosome position space.

A study on the interaction of nucleoplasmin with chromatin is described. It shows that highly phosphorylated Xenopus laevis egg nucleoplasmin can unfold sperm and somatic chromatin in a way that involves the removal of chromosomal proteins from linker DNA regions without stable interaction with the nucleosome.

TmPuIl 3, a family 13 glycoside hydrolase from Thermotoga maritima, is a four-module protein having pullulanase activity; the three N-terminal modules are of unknown function while the large C-terminal module is likely the catalytic module. Dissection of the functions of the three unknown modules revealed that the 100 amino acid module at the extreme N-terminus of TmPul 13 comprises a new family of carbohydrate-binding modules (CBM) that a bioinformatic analysis shows are most frequently found in pullulanase-like sequences from bacterial pathogens. Detailed binding studies of this isolated CBM, here called TmCBM41, reveals a preference for α-(1 ,4)-linked glucans, but occasional α-(1,6)-linked glucose residues, such as those found in pullulan, are tolerated. UV difference, isothermal titration calorimetry, and analytical ultracentrifugation binding studies suggest that maltooligos accharides longer than four glucose residues are able to bind two TinCBM41 molecules per oligosaccharide when sugar concentrations are below the CBM concentration. This is explained in terms of an equilibrium expression involving the formation of both a 1 to 1 sugar to CBM complex and a 1 to 2 sugar to CBM complex (i.e., a CBM dimer ligated by an oligosaccharide). The presence of an α-(1-6) linkage in the oligosaccharide appears to prevent this phenomenon. [ABSTRACT FROM AUTHOR]

Analytical ultracentrifugation (AUC) is a first principles based method to determine absolute sedimentation coefficients and buoyant molar masses of macromolecules and their complexes, reporting on their size and shape in free solution. The purpose of this multi-laboratory study was to establish the precision and accuracy of basic data dimensions in AUC and validate previously proposed calibration techniques. Three kits of AUC cell assemblies containing radial and temperature calibration tools and a bovine serum albumin (BSA) reference sample were shared among 67 laboratories, generating 129 comprehensive data sets. These allowed for an assessment of many parameters of instrument performance, including accuracy of the reported scan time after the start of centrifugation, the accuracy of the temperature calibration, and the accuracy of the radial magnification. The range of sedimentation coefficients obtained for BSA monomer in different instruments and using different optical systems was from 3.655 S to 4.949 S, with a mean and standard deviation of (4.304 ± 0.188) S (4.4%). After the combined application of correction factors derived from the external calibration references for elapsed time, scan velocity, temperature, and radial magnification, the range of s-values was reduced 7-fold with a mean of 4.325 S and a 6-fold reduced standard deviation of ± 0.030 S (0.7%). In addition, the large data set provided an opportunity to determine the instrument-to-instrument variation of the absolute radial positions reported in the scan files, the precision of photometric or refractometric signal magnitudes, and the precision of the calculated apparent molar mass of BSA monomer and the fraction of BSA dimers. These results highlight the necessity and effectiveness of independent calibration of basic AUC data dimensions for reliable quantitative studies.

Unlabelled: This trial was performed to determine the maximum tolerated whole-body radiation-absorbed dose of fractionated (131)I-cG250., Methods: This was a phase 1 dose escalation trial. Dose escalation refers here to the escalation of average whole-body absorbed dose. Fifteen patients with measurable metastatic renal cancer were studied. For each treatment cycle, patients initially received a "scout" administration consisting of 5 mg of cG250 antibody labeled with 185 MBq (5 mCi) of (131)I. Whole-body and serum activity was measured for 1 wk, and a simple pharmacokinetic model was fitted to the measured data. The pharmacokinetic model was used to calculate the required activities, administered in a fractionated pattern with 2-3 d between fractions, projected to deliver the prescribed whole-body absorbed dose. The initial cohort of 3 patients was prescribed an average whole-body absorbed dose of 0.50 Gy. In subsequent cohorts this was increased in 0.25-Gy increments. The first fraction in each cycle was 1,110 MBq (30 mCi) of (131)I conjugated to 5 mg of antibody. Subsequent fractions consisted of variable activities depending on the patient-specific whole-body clearance rates and the times between fractions. Patients without evidence of disease progression were retreated after recovery from toxicity if there was no evidence of altered pharmacokinetics or serum human antichimeric antibody titers, for a total of no more than 3 treatments., Results: For the initial treatment course, the pharmacokinetics of the scout dose accurately predicted the pharmacokinetics of fractionated (131)I-cG250 therapy. In 2 patients, altered clearance accurately predicted development of human antichimeric antibody. Targeting to known disease >or= 2 cm in diameter was noted in all patients. Dose-limiting toxicity was hematopoietic, and the maximum tolerated dose per cycle was 0.75 Gy., Conclusion: Measurements of whole-body and serum clearance of cG250 antibody can be used to accurately predict the clearance of subsequent administrations, thus enabling rational treatment planning. An additional practical benefit of real-time pharmacokinetic monitoring is that therapy can be altered dynamically to reduce toxic side effects. However, there was no evidence for fractionation-induced sparing of the hematopoietic system in this study.

A 61-year-old non-diabetic woman underwent a non-diagnostic FDG PET study due to ingestion of milk and sugar 150 minutes prior to injection of FDG despite being euglycaemic. A repeat study 2 days later showed 4 pathological foci of FDG uptake, of which only two could be seen retrospectively on the original study. The loss of lesion perspicuity and suppression of FDG uptake in the pathological lesions was corrected by fasting for more than 6 hours. The calculated SUV suppression due to eating could be corrected by normalizing according to the average of the patient's liver SUV. Proper patient preparation is essential in any medical procedure but even more so in FDG PET imaging, as small pathological lesions may be missed if the patient is improperly prepared.