Comparison of total body irradiation versus non-total body irradiation containing regimens for de novo acute myeloid leukemia in children

With limited data comparing hematopoietic cell transplant outcomes between myeloablative total body irradiation (TBI) containing and non-TBI regimens in children with de novo acute myeloid leukemia, the aim of this study was to compare transplant-outcomes between these regimens. Cox regression models were used to compare transplant-outcomes after TBI and non-TBI regimens in 624 children transplanted between 2008 and 2016. Thirty two percent (n=199) received TBI regimens whereas 68% (n=425) received non-TBI regimens. Five-year non-relapse mortality was higher with TBI regimens (22% vs. 11%, P<0.0001) but relapse was lower (23% vs. 37%, P<0.0001) compared to non-TBI regimens. Consequently, overall (62% vs. 60%, P=1.00) and leukemia-free survival (55% vs. 52%, P=0.42) did not differ between treatment groups. Grade 2-3 acute graft versus host disease was higher with TBI regimens (56% vs. 27%, P<0.0001) but not chronic graft versus host disease. The 3-year incidence of gonadal or growth hormone deficiency was higher with TBI regimens (24% vs. 8%, P<0.001) but there were no differences in late pulmonary, cardiac or renal impairment. In the absence of a survival advantage, the choice of TBI or non-TBI regimen merits careful consideration with the data favoring non-TBI regimens to limit the burden of morbidity associated with endocrine dysfunction.     

Wound infection,dressings and pain,is there a relationship in the chronic wound?

The focus on quality of life issues in wound care has justly taken a far greater importance. With the acceptance that pain can be a major factor to the patient, and in particular, pain at dressing change comes the opportunity for avoidance and/or reduction strategies. Whilst pain has been associated with wound infection for millennia, it is only much more recently that this has received due attention from research and clinical practice. In this study, the nature of pain, changes in pain and pain associated with infection are the focal points. A Delphi approach, now a frequently used tool in wound care research, has been used to obtain expert opinion on these aspects of management.     

Role of law enforcement response and microbial forensics in investigation of bioterrorism

The risk and threat of bioterrorism and biocrime have become a large concern and challenge for governments and society to enhance biosecurity. Law enforcement plays an important role in assessing and investigating activities involved in an event of bioterrorism or biocrime. Key to a successful biosecurity program is increased awareness and early detection of threats facilitated by an integrated network of responsibilities and capabilities from government, academic, private, and public assets. To support an investigation, microbial forensic sciences are employed to analyze and characterize forensic evidence with the goal of attribution or crime scene reconstruction. Two different molecular biology-based assays – real time polymerase chain reaction (PCR) and repetitive element PCR – are described and demonstrate how molecular biology tools may be utilized to aid in the investigative process. Technologies relied on by microbial forensic scientists need to be properly validated so that the methods used are understood and so that interpretation of results is carried out within the limitations of the assays. The three types of validation are preliminary, developmental, and internal. The first is necessary for rapid response when a threat is imminent or an attack has recently occurred. The latter two apply to implementation of routinely used procedures.     

Maturation stage and proliferation-dependent expression of dUTPase in human T cells.

We have developed a database of lymphoid polypeptides detected by two-dimensional polyacrylamide gel electrophoresis to aid in studies of leukemogenesis and of mutation affecting protein structure. In prior studies, we observed a 19-kDa phosphopolypeptide which was induced with proliferation in mature T cells and constitutively expressed in immature thymocytes. In this report we describe the identification of this polypeptide as the phosphorylated form of dUTPase (EC 3.6.1.23), following cDNA cloning of the gene, based on a partial amino acid sequence of the phosphopolypeptide. Studies of the expression and phosphorylation of dUTPase in human T cells indicate that accumulation and phosphorylation of dUTPase in mature T cells occur in a cell cycle-dependent manner. Interestingly, noncycling immature thymocytes express constitutively high levels of phosphorylated and unphosphorylated dUTPase. These results suggest an important role for dUTPase in immature thymocytes that is independent of proliferation.     

Protein-tyrosine-phosphatase SHPTP2 couples platelet-derived growth factor receptor beta to Ras.

Protein-tyrosine-phosphatase SHPTP2 (Syp/PTP-1D/PTP2C) is the homologue of the Drosophila corkscrew (csw) gene product, which transmits positive signals from receptor tyrosine kinases. Likewise, SHPTP2 has been implicated in positive signaling from platelet-derived growth factor receptor beta (PDGFR). Upon PDGF stimulation, SHPTP2 binds to the PDGFR and becomes tyrosine-phosphorylated. We have identified tyrosine-542 (pY542TNI) as the major in vivo site of SHPTP2 tyrosine phosphorylation. The pY542TNI sequence conforms to the consensus binding site for the SH2 domain of Grb2, which, by association with Sos1, couples some growth factor receptors to Ras. Following PDGF stimulation, Grb2 binds tyrosine-phosphorylated SHPTP2. Moreover, a mutant PDGFR lacking its SHPTP2 binding site displays markedly reduced Grb2 binding. These data indicate that phosphorylation of SHPTP2 couples Grb2 to PDGFR in vivo, providing a mechanism for Ras activation by PDGFR and for positive signaling via SHPTP2 and Csw.     

Isolation of 16L virus: a rapidly transforming sarcoma virus from an avian leukosis virus-induced sarcoma.

We have isolated a replication-defective rapidly transforming sarcoma virus (designated 16L virus) from a fibro-sarcoma in a chicken infected with td107A, a transformation-defective deletion mutant of subgroup A Schmidt-Ruppin Rous sarcoma virus. 16L virus transforms fibroblasts and causes sarcomas in infected chickens within 2 wk. Its genomic RNA is 6.0 kilobases and contains sequences homologous to the transforming gene (fps) of Fujinami sarcoma virus (FSV). RNase T1 oligonucleotide analysis shows that the 5' and 3' terminal sequences of 16L virus are indistinguishable from (and presumably derived from) td107A RNA. The central part of 16L viral RNA consists of fps-related sequences. These oligonucleotides fall into four classes: (i) oligonucleotides common to the putative transforming regions of FSV and another fps-containing avian sarcoma virus, UR1; (ii) an oligonucleotide also present in FSV but not in UR1; (iii) an oligonucleotide also present in UR1 but not in FSV; and (iv) an oligonucleotide not present in either FSV, UR1, or td107A. Cells infected with 16L virus synthesize a protein of Mr 142,000 that is immunoprecipitated with anti-gag antiserum. This protein has protein kinase activity. These results suggest that 16L virus arose by recombination between td107A and the cellular fps gene.