UMP kinase from Escherichia coli is one of the four regulatory enzymes involved in the de novo biosynthetic pathway of pyrimidine nucleotides. This homohexamer, with no counterpart in eukarya, might serve as a target for new antibacterial drugs. Although the bacterial enzyme does not show sequence similarity with any other known nucleoside monophosphate kinase, two segments between amino acids 35 to 78 and 145 to 194 exhibit 28% identity with phosphoglycerate kinase and 30% identity with aspartokinase, respectively. Based on these similarities, a number of residues of E. coli UMP kinase were selected for site-directed mutagenesis experiments. Biochemical, kinetic, and spectroscopic analysis of the modified proteins identified residues essential for catalysis (Asp146), binding of UMP (Asp174), and interaction with the allosteric effectors, GTP and UTP (Arg62 and Asp77).
We identified a 35.7% prevalence of thyroid abnormalities, emphasizing the need for a long-term surveillance of thyroid function and morphology even in this group of patients who were not exposed to TBI.
BackgroundMonitoring minimal residual (MRD) in paediatric pacients with ALL is the most important way to detect relapse, to individualised the treatment (selection of the intensity and the duration of chemotherapy), to evaluate the early response on chemotherapy, to see the long term prognostic and also to decide the indication/moment of stem cell transplantationMRD is detect by three methods: flow cytometry- detect the abnormal immunophenotypes and polymerase chain reaction (PCR) detect the amplification of antigen- receptor genes/amplification of fusion transcripts. MRD sensitivity must be : minimal 10-4 to be taken in to account, must be affordable, fast, accurate and applicable. The positivity is defined by the presence of 0.01% or more, the risk of relapse is proportional to the level of MRD, especialy on day 33 and 78. Most studies establish the importance of MRD in children with ALL and also in adults.aims :The present study evaluated the monitoring MRD in accordance with the ALL- BFM 2002 protocolMethodspaediatric patients with ALL – diagnosed in Fundeni Clinical Institute, during 2014–2016 were included in this prospective study, after performing consent procedure. The diagnosis was based on CBC with peripheral blood smear, bone marrow exam, flow cytometry- to detect the abnormal immunophenotypes, cytogenetics(to detect the number) and molecular biology (to detect the presence of abnormal genes). The MRD have been taken in day15, 33(induction- therapy), day 78 (first day of consolidation ), in the first day of reinduction and in the last one, and in the mentenance therapy also fallow up MRD (at 3,6,9 and 12 month). The most common method used was flow cytometry, but also the molecular for the pacient with abnormal gene(BCR-ABL, TEL-AML1, E2A-PBX)ResultsIn the 3 –years interval, we diagnosed 114 patients with ALL between 1.01.14 until 1.01.17. Major was ALL- B lineage 98%,ALL- T lineage13,15%, B and T lineage 1,7%, repartition by subtypes: L1 93,9%, L2 4,38%, L3 0,87%. Abnormal genes detection was positive for E2A-PBX 3,5%, BCR-ABL 6,14%, TEL-AML 16,66%, MLL 3,5%, SIL-TAL 0,8%, without abnormal genes 67,54%. Monitoring MRD the results was 11, 4% positive in day 33, and remained positive in day 78 in 2.63% cases- in present they are in remission. The HRG was 13,15% cases, we obtain the molecular remission of all and they remained under our close supervision for the eventuality stem cell transplantation. The survival of HRG therapy was 73,33% cases.CoclussionOur patients had favourable outcome following ALL-BFM 2002 protocol, at TP1 88,6% obtained molecular remission. The results are remarcable the remission at TP2 was in 97,3% and remained in remission until present. They will be closly monitoring in our clinic until they will became adults??In this 3 years study we also included one pacient with relapse, at 5 years from the first diagnosis. Was a girl, with ALL, B lineage, L1 subtypes, TEL-AML1 positive. We obtained the second remission but unfortunate she died because of severe infection (Pseudomonas Aeru...
BackgroundChildren with chronic refractory Immune Thrombocytopenia are a small, but demanding group, representing 5% of the total cases of Immune thrombocytopenia. Changing the nomenclature itself, from idiopathic to immune, is evidence of the increasing awareness and improvements in the management of immune thrombocytopenia. Treatment for this disease is always a challenge taking into consideration that the few known therapies have significant side effects and toxicities.AimTo evaluate treatment strategies and the effect on heterogenous evolution of children with chronic Immune Thrombocytopenia.MethodsChronic refractory Immune Thrombocytopenia is defined as disease that does not respond to or relapses after first 2 lines of treatment, with over one year of evolution. Based on 8 cases within our clinic, we discuss treatment options available for children with chronic refractory Immune Thrombocytopenia. In addition to detailed history and physical examination, there were analized full blood count, review of the peripheral blood smear, routine tests of hemostasis and bone marrow examination was performed to search for myelodysplastic syndromes. At the same time, infections (CMV,EBV, HIV, HP) and autoimmune disorders (LES, APS) were ruled out. All patients who failed prior treatment, meaning first 2 lines of treatment (multiple steroids, intravenous immunoglobulins, splenectomy) underwent treatment with molecule targeting therapy (Rituximab), nonspecific immunosuppresive agents (Cyclosporin, Mycophenolat Mofetil, Sirolimus) or thrombopoietin receptor agonists.ResultsA total of 8 patients with chronic refractory Immune Thrombocytopenia were analised. The median age at diagnosis was 6,5 and sex ratio 1:1. Disease evolution is between 3 and 10 years. Treatment for the studied cases consisted of multiple courses of steroids and intravenous immunoglobulins (all patients), splenectomy (4 patient), Rituximab (4 patients), Cyclosporin (6 patients), Mycophenolat Mofetil (6 patients) and Sirolimus (3 patients). 2 patients underwent therapy with thrombopoietin receptor agonist (Romiplostin), with only one favourable response. At present time, 6 patients are receiving combined immunosupressive therapy and steroids, while 2 are stable with one immunosupressive agent. In spite of abnormal platelet count, for these patients is most significant to have no risk factors nor haemorrhagic events. Among immunosupressive agents, early relapse was frequently seen after administration of Cyclosporin, compared to other immunosupressive agents.ConclusionsThe goal of long-term immunosupressive treatment strategies for Immune Thrombocytopenia is to achieve a platelet count that is associated with adequate hemostasis, rather than normal platelet count. As outcomes vary from one patient to another, aspects regarding age, clinical features, bleeding risks, likely side-effects, economic considerations, life quality as well as the physicians concerns are essential.
Background and aimMarginal zone lymphomas represent 3% of all lymphomas and are divided into extranodal (ENMZL), splenic and nodal. ENMZL is characterised by indolent natural history, is usually diagnosed in localised stages (70%) and chronic antigen stimulation seems to be involved in its pathogenesis. Typically seen in the 6th decade of life, it is responsible for 8% of adult non-Hodgkin lymphoma. According to multicentre NHL-BFM studies, the incidence of ENMZL in children is 0.1%, most commonly found in the gastrointestinal tract (44%). The salivary gland is involved only in 5% of paediatric patients, being preceded in 1/3 cases by Sjogren syndrome (SS). Herein, we report a 15-year-old girl with advanced ENZML of salivary glands following SS, a very rare diagnosis in children.METHOD AND ResultsFemale patient, 13y, presented with enlarged jaw area, was evaluated by an oral-maxillofacial surgeon and cherubism was excluded. Laterocervical ultrasound, head and neck MRI: hypertrophic parotid glands with cystic images, small adenopathies. Based on parotid swelling, dry mouth and eyes, bilateral hypo-lacrimation on Schirmer’s test, positive anti-Ro, anti-La and anti-nuclear antibodies, she was diagnosed with primary SS. At age 15: progressive parotid swelling, no ‘B’ symptoms, leucopenia 3.38 × 10^9/l, anaemia 10.5 g/dl, sedimentation rate 33 mm/h, LDH 225UI (n<200 UI), B2-microglobulin 2.62 mg/L (n=0,9–2 mg/L), normal bone marrow biopsy. Right parotid biopsy, immunohistochemistry and molecular biology: lymphoid proliferation of small-sized monocytoid cells, with lympho-epithelial lesions and marginal zone pattern (incorporating residual reactive germinal centre), CD20+, CD3-, kappa/lambda 5/1, FR2-JH+ in heavy-chain IG. PET-CT scan showed active sites in left parotid gland, supra and subdiaphragmatic lymph nodes. The patient was diagnosed with B-cell ENMZL of parotid glands, stage III A. She received 6 cycles of R-CHOP regimen (rituximab, cyclophosphamide, vincristine, doxorubicin, prednisone), at 3 week interval, had negative PET-CT after 4 and 6 courses and she is in complete remission 6 months after the end of therapy.ConclutionENMZL of parotid glands following SS is rarely seen, especially in paediatric patients, thus the knowledge about this lymphoma type is limited. It is low-grade and responds well to R-CHOP chemotherapy, even in advanced stages. Nevertheless, regular follow-up is required, as relapses can occur during the course of the disease.
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