Identification of N-linked oligosaccharides of rat insulin-like growth factor binding protein-4.

Insulin-like growth factor binding protein-4 (IGFBP-4) is, like the other five IGFBPs, a critical regulator of the activity of insulin-like growth factor (IGF)-I and IGF-II. Whereas IGFBP-1 and IGFBP-2 are not glycosylated, IGFBP-3 and IGFBP-4 are N-glycosylated and IGFBP-5 and IGFBP-6 are O-glycosylated. In this study we identified the glycosylation of IGFBP-4 using a nanoflow LC/MS/MS techniques. Although N-linked oligosaccharides are structurally diverse, their variants are well reported in the literature. Based on the molecular weight of the possible oligosaccharide moieties, we identified five different glycosylation isoforms of the protein. Identified glycans were biantennary and differ in the number of sialic acid terminal residues and/or core modification with fucose.     

The evolution of sexually transmitted infections in the Ukraine

OBJECTIVES: To evaluate trends in the national and regional reporting of syphilis, gonorrhoea, chlamydia, genital herpes, trichomoniasis, and HIV in Ukraine. METHODS: Annual notification rates of infection per 10(5) population in three regions of Ukraine--Donetsk, Mikolaiv, Chernivtsi--and also among children, adolescents, and pregnant women were used as indicators for the spread of sexually transmitted infections (STIs) in the Ukraine from 1994 to 2000. The estimates were based on a review of medical literature, reported data from STD clinics, and local epidemiological surveys. An analysis of the trends was made. RESULTS: The notification rate of trichomoniasis rose from 284.3 in 1997 to 330.8 in 2000. The same for syphilis was 68.7 per 100,000 population in 1994 peaked in 1996 with 150.9 falling to 91.5 in 2000. The reported incidence of gonorrhoea has been falling recently to 52.7/10(5) in 2000 (a 104.6% decrease since 1994). Chlamydia notification rates, however, rose 2.4-fold between 1995 and 2000 (16.1/10(5) to 54.2/10(5)). In the same period there was a 218% increase the reported incidence of genital herpes. STIs are more common in the eastern industrial regions. In the period 1994-7 there was a dramatic 179-fold increase in the prevalence of HIV/AIDS which has plateaued in subsequent years. By January 2001 a total of 36,600 cases of HIV infection (including 2040 people with AIDS) have been reported. The proportion of HIV acquired through injecting drug use is falling (72.7% in 1997 to 54.2% in 2000) in relation to that acquired through sexual contact. CONCLUSIONS: STIs and HIV are a common cause of morbidity in Ukraine.     

Impact of measurable residual disease on outcomes of unrelated donor haematopoietic cell transplantation with post-transplant cyclophosphamide in AML in first complete remission

Pre-transplant measurable residual disease (MRD) predicts relapse and outcome of allogeneic haematopoietic cell transplantation (allo-HCT). The impact of MRD on the outcomes of post-transplant cyclophosphamide (PTCy)-based allo-HCT from a matched unrelated donor (UD) is unknown. This study assessed the impact of MRD in acute myeloid leukaemia (AML) in the first complete remission (CR1). A total of 272 patients (MRD negative [MRD−], n = 165; MRD positive [MRD+], n = 107) with a median follow-up of 19 (range: 16–24) months were studied. The incidence of grades II–IV and grades III–IV acute GVHD at day 180 was 25.2% and 25% (p = 0.99), and 10.6% and 6.8% (p = 0.29), respectively, and 2-year chronic GVHD was 35% and 30.4% (p = 0.96) in MRD+ and MRD− cohorts, respectively. In multivariate analysis, MRD+ status was associated with a higher incidence of relapse (RI) (hazard ratio [HR] = 2.56, 95% CI: 1.39–4.72), lower leukaemia-free survival (LFS) (HR = 2.04, 95% CI: 1.23–3.39), overall survival (OS) (HR = 1.83, 95% CI: 1.04–3.25) and GVHD-free, relapse-free survival (GRFS) (HR = 1.69, 95% CI: 1.10–2.58). MRD status did not have a significant impact on non-relapse mortality (NRM), or acute or chronic GVHD risk. Among patients with AML undergoing UD allo-HCT with PTCy, pre-transplant MRD+ status predicted a higher relapse rate, lower LFS, OS and GRFS.