Allogeneic hematopoietic SCT in children with ALL: current concepts of ongoing prospective SCT trials

The definition of indications for allogeneic SCT in children with high-risk (HR) ALL in the first remission or after the first or subsequent relapse depends on biological features, response to treatment and survival after chemotherapy alone. As the results of frontline and relapse protocols are improving over time, there is a strong need for prospective SCT trials, ensuring a well-standardized procedure regarding all relevant components that are potentially responsible for heterogeneity in post-SCT outcome. Therefore, in 2003, the ALL-BFM and the ALL-REZ BFM Study Group initiated a prospective, international, multicenter trial (ALL-SCT-BFM 2003). This trial will now be extended to a larger consortium, trial ALL-SCT-BFM-international (ALL-SCT-BFMi). Strict rules define HLA-typing, donor selection, conditioning regimen, GvHD prophylaxis and therapy as well as standards of supportive care to reduce treatment-related mortality and establish an early GVL effect. Moreover, comprehensive and closely reviewed documentation and serious adverse event reporting shall ensure high study quality. Case-by-case discussions of any fatal or critical course during annual meetings will improve the culture of failure management and lead to modifications of guidelines of supportive care. Finally, the results of these prospective trials will determine the current potential of the different SCT procedures in HR or relapsed childhood ALL.     

Sequential analysis of 43 patients with non-Hodgkin's lymphoma: clinical correlations with cytogenetic, histologic, immunophenotyping, and molecular studies

Few reports correlating specific cytogenetic abnormalities with distinct subtypes of lymphoma have performed serial studies at diagnosis and at tumor recurrence or progression. In our file of 325 cytogenetically analyzed non-Hodgkin's lymphoma (NHL) patients studied over the past decade, 43 had serial biopsies, 39 of whom had at least two successful preparations; of the 43, nine had one and 32 had two or more cytogenetically abnormal specimens. In this study, we correlated cytogenetic, histopathologic, molecular, and clinical parameters. Patients with low-grade lymphomas were as likely as patients with intermediate- or high-grade lymphomas to acquire new chromosomal abnormalities with time (16 of 23 patients as compared with 7 of 16; P2 = .11, chi 2 test). In four patients, originally diagnosed indolent disease progressed to aggressive disease; all had t(14;18), all gained additional chromosomal abnormalities with disease progression, and three of the four expressed abnormalities associated with disease progression and/or short survival: der(18), +7, and/or +12. Cytogenetic results from early disease were compared with those obtained later in disease: in the t(14;18) group, the most common abnormalities were +7 (eight patients) and der(18) (five patients), both seen later in disease. The most common abnormalities in patients without t(14;18) were 6q deletions; they were seen in both early and late disease and were associated with significantly shorter survivals (P2 = .0014) compared with all patients without 6q deletions. Secondary chromosomal abnormalities, observed after at least one previous abnormal study, were seen in 19 of 22 t(14;18) patients and in 11 of 21 patients without t(14;18) and were associated with a poor survival (P2 = .13) compared with patients without any secondary chromosomal abnormalities. Chromosome 1 abnormalities were seen in almost half of the patients and were observed in initial specimens and early in disease as well as late in disease and as secondary abnormalities; 1q involvement was more frequent than 1p (15 versus eight patients) and was significantly associated with poor survival only in patients with intermediate-/high- grade disease; the most common breakpoints were 1q21-q22 (nine patients) and 1p36 (six patients). Breakpoints at 2q21 and 3q27-q29 were limited to patients with t(14;18) and were almost exclusively secondary in nature. Molecular studies in 24 of our patients showed discrepancies with the cytogenetic results in only three patients: two had t(14;18) but no molecular rearrangements while two patients had no visible t(14;18) but were positive for major breakpoint region (MBR) rearrangement. The presence of MBR or minor breakpoint cluster (MCR) rearrangement had no apparent effect on survival.(ABSTRACT TRUNCATED AT 400 WORDS)     

Epidemiologic background of blood donors with antibody to human T-cell lymphotropic virus. Transfusion Safety Study Group

We interviewed 51 blood donors in four major US metropolitan areas subsequently found to have had antibodies to human T-cell lymphotropic virus (anti-HTLV) in late 1984-early 1985. Sixteen donors (31%) reported that they or a sexual contact had a history of blood transfusion. Twelve donors (24%) reported that they or a sexual contact used intravenous drugs. Ten donors (20%) were blacks born in the southeastern US. Four of the male donors (15%) reported homosexual contact. The most common characteristic was an association with Japan or the Caribbean basin (61%). These results show a broader variation of epidemiologic backgrounds than anticipated.     

Heterologous expression,chaperone mediated solubilization and purification of parasitic nematode-specific growth factor-like protein of Setaria digitata

Objective:To clone,express and purify a putative parasitic nematode specific protein of Setaria digitata(S.digitata),filarial nematode that infects livestock and cause significant economic losses in Far East and Asia to he used for structural and functional analyses.Methods:To characterize uneharacterized gene of,S.digitata(SDUG),the herterologous expression of SDUG was carried out in the pET[cloned into pET45b(+)]expression system initially and co-expression of SDUC using chaperoiie plasmids pG-KJE8,pGro 7,pKJE7,pG-Tf2 and pTf16 containing chapcrone proteins of dnaK-dnaJ-grpE-groES-gro-E,groES-groEL,dnaK-dnaJ-grpE,groES-groEL-tig,and tig respectively,was carried out subsequently.Results:Expression of SDUG was seen when Escherichia coli strain BI.21(DE3)is used,while concentrating protein largely into the insoluble fraction.The co-expression of SDUG using chaperoiie plasmid mediated system indicated a significant increase of the protein in the soluble fraction.Of the chaperon plasniid sets,the highest amount of recombinant SDUP in the soluble fraction was seen when pGro7 was used in the presence of2 mg/mL L-arabinosc and 0.6M IPTG concentration in the culture medium and for 3 h of incubation at the temperature of 28℃.Recombinant SDUG was purified both from soluble and insoluble fractions using Ni affinity chromatography.SDS-PAGE and western blot analyses of these proteins revealed a single band having expected size of~24 kDa.Conclusions:SDUG seems to be more aggregate-prone and hydrophobic in nature and such protein can make soluble by correct selecting the inducer concentrations and induction temperature and its duration.     

高密度脂蛋白胆固醇的检测方法及标准化研究进展

高密度脂蛋白胆固醇的检测方法及标准化研究进展鄢盛恺林其燧众多流行病学研究证实，高密度脂蛋白胆固醇（ＨＤＬ－Ｃ）水平与动脉粥样硬化（ＡＳ）呈负相关。美国Ｆｒａｍｉｎｇｈａｍ的研究显示，ＨＤＬ－Ｃ每减少０．０２６ｍｍｏｌ／Ｌ（１ｍｇ／ｄｌ），冠心病（ＣＨ...     

9-cis retinoic acid induces complete remission but does not reverse clinically acquired retinoid resistance in acute promyelocytic leukemia

9-cis retinoic acid (RA) is a high-affinity ligand for both retinoic acid receptors (RARs) and retinoid "X" receptors (RXRs). Although all- trans RA does not bind to RXRs, RAR/RXR heterodimers or RXR/RXR homodimers bind to specific DNA response elements and modulate proliferation and differentiation of normal and malignant cells. Because the development of clinical resistance to all-trans RA has been associated with a progressive decrease in plasma drug concentrations, we evaluated the ability of 9-cis RA to induce in vitro cytodifferentiation in subclones of a retinoid-sensitive and resistant APL cell line (NB4) and in short-term cultures of fresh leukemic cells aspirated from patients. We also evaluated the clinical activity and pharmacokinetics of 9-cis RA (LGD 1057) in patients with APL who were previously treated with all-trans RA. In vitro tests of both retinoid- sensitive NB4 cells, as well as samples of fresh cells from 11 patients with APL, showed relatively equivalent degrees of sensitivity to both 9- cis RA and all-trans RA at concentrations ranging from 10(-6) to 10(-8) mol/L; however, no substantial cytodifferentiation was observed using either drug alone or in combination (10(-6) mol/L of each) in retinoid- resistant NB4 cells. Seven patients with APL who had previously relapsed from a remission induced by all-trans RA were treated with 9- cis RA at daily oral doses ranging from 30 to 230 mg/m2. Pharmacokinetic studies showed that the mean terminal plasma half-life of 9-cis RA (1.3 hours) changed very little after several weeks of dosing, although the mean change per dose level in area under the plasma concentration x time curves and peak plasma concentrations showed a decrease by 49% and 45%, respectively. Peak plasma concentrations equaled or exceeded concentrations that were effective against retinoid-sensitive cells in vitro. Despite these favorable pharmacokinetic results, only one of the seven patients achieved complete remission, corroborating in vitro studies of blasts from three of the nonresponders that showed a relatively equivalent degree of resistance to both retinoids. Our results suggest that while 9-cis RA may not induce its own catabolism to the same degree as all-trans RA, this feature does not appear to overcome clinically acquired resistance to all-trans RA in APL. Nonetheless, the drug can induce complete remissions in patients with APL and may be useful for extended therapy in other diseases. Future studies should address the use of lower doses in patients who have not previously received retinoid therapy.(ABSTRACT TRUNCATED AT 400 WORDS)     

Influenza vaccination for healthy children

Influenza virus infections cause vaccine-preventable but uncontrolled epidemic disease in the United States. Population dynamics dictate that the burden of disease will increase dramatically over the next 20 years if new strategies are not implemented. New weapons for the diagnosis, treatment and prevention of influenza are now available and should be implemented immediately. The impact of disease in children has been largely overlooked. Control measures should be focused on the prevention of disease in children, who have the highest annual attack rates. The new live attenuated nasal spray influenza vaccine is particularly effective in healthy children who would benefit most from universal immunization.     

Control of influenza

Influenza is the classic emerging infection. Despite the availability of relatively inexpensive vaccines and specific treatments, influenza is the least controlled vaccine-preventable disease. Vaccination coverage of high-risk patients has improved, but all-cause mortality attributable to influenza continues to increase. A supplemental strategy is to vaccinate the principal disseminators of influenza in the community: school children and working adults. The availability of the live, attenuated, cold-adapted nasal spray vaccine should facilitate this goal.     

胆汁返流与Barrett食管及食管肿瘤

Barrett食管是一类公认的食管腺癌癌前病变, 在西方国家常见．近年来在中国也有上升的趋势．目前有研究显示胆汁返流与Barrett食管及食管腺癌有关联．有研究显示胆汁返流可能导致Barrett食管发病率上升,从而食管腺癌发生率亦上升．其可能的机制涉及到返流时胆盐在 Barrett食管过程中对有关癌基因的影响、慢性炎症在其中的作用、胆囊切除术后相应的解剖学改变等．本文就此作一综述．