Carboplatin binding to a model protein in non-NaCl conditions to eliminate partial conversion to cisplatin, and the use of different criteria to choose the resolution limit

Hen egg white lysozyme (HEWL) co-crystallisation conditions of carboplatin without sodium chloride (NaCl) have been utilised to eliminate partial conversion of carboplatin to cisplatin observed previously. Tetragonal HEWL crystals were successfully obtained in 65% MPD with 0.1M citric acid buffer at pH 4.0 including DMSO. The X-ray diffraction data resolution to be used for the model refinement was reviewed using several topical criteria together. The CC1/2 criterion implemented in XDS led to data being significant to 2.0{\AA}, compared to the data only being able to be processed to 3.0{\AA} using the Bruker software package (SAINT). Then using paired protein model refinements and DPI values based on the FreeR value, the resolution limit was fine tuned to be 2.3{\AA}. Interestingly this was compared with results from the EVAL software package which gave a resolution limit of 2.2{\AA} solely using crossing 2, but 2.8{\AA} based on the Rmerge values (60%). The structural results showed that carboplatin bound to only the N{\delta} binding site of His-15 one week after crystal growth, whereas five weeks after crystal growth, two molecules of carboplatin are bound to the His-15 residue. In summary several new results have emerged: - firstly non-NaCl conditions showed a carboplatin molecule bound to His-15 of HEWL; secondly binding of one molecule of carboplatin was seen after one week of crystal growth and two molecules were bound after five weeks of crystal growth; and thirdly the use of several criteria to determine the diffraction resolution limit led to the successful use of data to higher resolution.Comment: 14 pages; submitted to Acta Cryst D Biological Crystallography reference number tz504

Погляд на архіви

The International Union of Crystallography has for many years been advocating archiving of raw data to accompany structural papers. Recently, it initiated the formation of the Diffraction Data Deposition Working Group with the aim of developing standards for the representation of these data. A means of studying this issue is to submit exemplar publications with associated raw data and metadata. A recent study on the effects of dimethyl sulfoxide on the binding of cisplatin and carboplatin to histidine in 11 different lysozyme crystals from two diffractometers led to an investigation of the possible effects of the equipment and X-ray diffraction data processing software on the calculated occupancies and B factors of the bound Pt compounds. 35.3 Gb of data were transferred from Manchester to Utrecht to be processed with EVAL. A systematic comparison shows that the largest differences in the occupancies and B factors of the bound Pt compounds are due to the software, but the equipment also has a noticeable effect. A detailed description of and discussion on the availability of metadata is given. By making these raw diffraction data sets available via a local depository, it is possible for the diffraction community to make their own evaluation as they may wish

Rituximab administration in third trimester of pregnancy suppresses neonatal B-cell development

We describe the effect on the neonate of administration of rituximab to a woman with idiopathic thrombocytopenic purpura (ITP). Rituximab, an anti-CD20 antibody, was given weekly for 4 weeks to a woman with ITP in her third trimester of pregnancy. One month after the last rituximab administration a healthy girl was born. She had normal growth and development during the first six months. At birth, B-lymphocytes were not detectable. Rituximab levels in mother and neonate were 24000 and 6700 ng/mL, respectively. Only 7 cases of rituximab administration during pregnancy were described. No adverse events are described for fetus and neonate. We demonstrate that rituximab passes the placenta and inhibits neonatal B-lymphocyte development. However, after 6 months B-lymphocyte levels normalized and vaccination titres after 10 months were adequate. No infection-related complications occurred. Rituximab administration during pregnancy appears to be safe for the child but further studies are warranted. Copyright © 2008 D. T. Klink et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 1

Cisplatin coordination chemistry determination at hen egg white lysozyme His15 with ligand distances and angles, and their standard uncertainties, and also reporting a split occupancy effect

Following the interest of L Messori and A Merlino 2016 Coordination Chemistry Reviews in the platinum ions coordination geometries in our PDB entries 4dd4 and 4dd6 we have extended our original analyses.Comment: 10 pages. One figure with two stereos and two further separate (identical to the stereos) figures with atom labels. This arXiv article is the first part of a Data Revie

Good results with cemented total hip arthroplasty in patients between 40 and 50 years of age: 168 hips followed for 2–19 years

Background and purpose Total hip arthroplasties in young patients have lower long-term survival rates than in older patients. We evaluated the use of a unique treatment protocol in patients aged between 40 and 50 years. In all cases we used a cemented THA, and for acetabular deficiencies we also used impacted bone grafts together with a cemented cup

Revisions of Extensive Acetabular Defects with Impaction Grafting and a Cement Cup

Item does not contain fulltextBACKGROUND: Loosening of acetabular components often leads to bony defects. Management of extensive acetabular bone loss in hip revision arthroplasty can be a tremendous challenge. QUESTIONS/PURPOSES: We asked whether a reconstruction with impacted bone grafts will provide a durable and pain-free function in extensive acetabular defects. We specifically determined the (1) survival rates with the end point of revision for any reason, aseptic revision, and radiographic loosening; (2) visual analog scale (VAS) pain score, Harris hip score (HHS), and the Oxford Hip Questionnaire score (OHQS); (3) number of repeat revisions; (4) complications; and (5) radiographic loosening, wear, and radiolucencies. PATIENTS AND METHODS: We retrospectively followed 25 patients (27 hips) with extensive acetabular defects. No patient was lost to followup. Two patients died during followup. Minimum followup was 3 years (mean, 8.8 years; range, 3-14.1 years). RESULTS: Three patients (three hips) underwent repeat revision surgery and another two patients (two hips) had radiographically loose hips. The 10-year survival rate was 88% (95% confidence interval, 74.2%-100%) with the end point acetabular revision for any reason and 95% (95% confidence interval, 86.0%-100%) with the end point acetabular revision for aseptic loosening. The mean HHSs were 55 points before surgery and 72 points postoperatively. CONCLUSIONS: Acetabular reconstruction with impaction bone grafting and a cemented cup is a reliable technique with a 10-year survival rate of 88% in patients with extensive acetabular deficiencies. LEVEL OF EVIDENCE: Level IV, case series. See the Guidelines for Authors for a complete description of levels of evidence

Long-term follow-up, quality of life, and survival of patients with Lambert-Eaton myasthenic syndrome

ObjectiveTo study survival and to characterize long-term functional impairments and health-related quality of life (HRQOL) of patients with Lambert-Eaton myasthenic syndrome (LEMS).MethodsIn this observational study, survival of patients with LEMS, separately for nontumor (NT) and small cell lung cancer (SCLC), was compared to that of the Dutch general population and patients with SCLC. Disease course in patients with LEMS was recorded retrospectively. Several scales for functional impairments and health-related quality of life were assessed.ResultsWe included 150 patients with LEMS. Survival was similar to that of the general population in 65 patients with NT-LEMS. Tumor survival was significantly longer in 81 patients with SCLC-LEMS compared to patients with non-LEMS SCLC (overall median survival 17 vs 7.0 months, p <0.0001). At diagnosis, 39 (62%) of 63 patients with complete follow-up data were independent for activities of daily living, improving to 85% at the 1-year follow-up. The physical HRQOL composite score (55.9) was significantly lower than in the general population (76.3, p <0.0001) and comparable to that of patients with myasthenia gravis (60.5). The mental HRQOL composite score was 71.8 in patients with LEMS, comparable to that of the general population (77.9, p = 0.19) and patients with myasthenia gravis (70.3).ConclusionsThis study shows that patients with NT-LEMS have normal survival. Patients with SCLC-LEMS have an improved tumor survival, even after correction for tumor stage. A majority of patients with LEMS report a stable disease course and remain or become independent for self-care after treatment