Systemic mastocytosis associated with t(8;21)(q22;q22) acute myeloid leukemia

Although KIT mutations are present in 20–25% of cases of t(8;21)(q22;q22) acute myeloid leukemia (AML), concurrent development of systemic mastocytosis (SM) is exceedingly rare. We examined the clinicopathologic features of SM associated with t(8;21)(q22;q22) AML in ten patients (six from our institutions and four from published literature) with t(8;21) AML and SM. In the majority of these cases, a definitive diagnosis of SM was made after chemotherapy, when the mast cell infiltrates were prominent. Deletion 9q was an additional cytogenetic abnormality in four cases. Four of the ten patients failed to achieve remission after standard chemotherapy and seven of the ten patients have died of AML. In the two patients who achieved durable remission after allogeneic hematopoietic stem cell transplant, recipient-derived neoplastic bone marrow mast cells persisted despite leukemic remission. SM associated with t(8;21) AML carries a dismal prognosis; therefore, detection of concurrent SM at diagnosis of t(8;21) AML has important prognostic implications

Identifying metabolite markers for preterm birth in cervicovaginal fluid by magnetic resonance spectroscopy

Introduction Preterm birth (PTB) may be preceded by changes in the vaginal microflora and metabolite profiles. Objectives We sought to characterise the metabolite profile of cervicovaginal fluid (CVF) of pregnant women by 1H NMR spectroscopy, and assess their predictive value for PTB. Methods A pair of high-vaginal swabs was obtained from pregnant women with no evidence of clinical infection and grouped as follows: asymptomatic low risk (ALR) women with no previous history of PTB, assessed at 20–22 gestational weeks, g.w., n = 83; asymptomatic high risk (AHR) women with a previous history of PTB, assessed at both 20–22 g.w., n = 71, and 26–28 g.w., n = 58; and women presenting with symptoms of preterm labor (PTL) (SYM), assessed at 24–36 g.w., n = 65. Vaginal secretions were dissolved in phosphate buffered saline and scanned with a 9.4 T NMR spectrometer. Results Six metabolites (lactate, alanine, acetate, glutamine/glutamate, succinate and glucose) were analysed. In all study cohorts vaginal pH correlated with lactate integral (r = -0.62, p\0.0001). Lactate integrals were higher in the term ALR compared to the AHR (20–22 g.w.) women (p = 0.003). Acetate integrals were higher in the preterm versus term women for the AHR (20–22 g.w.) (p = 0.048) and SYM (p = 0.003) groups; and was predictive of PTB\37 g.w. (AUC 0.78; 95 % CI 0.61–0.95), and delivery within 2 weeks of the index assessment (AUC 0.84; 95 % CI 0.64–1) in the SYM women, whilst other metabolites were not. Conclusion High CVF acetate integral of women with symptoms of PTL appears predictive of preterm delivery, as well as delivery within 2 weeks of presentation

Anti-sera raised in rabbits against crotoxin and phospholipase A(2) from Crotalus durissus cascavella venom neutralize the neurotoxicity of the venom and crotoxin

Crotoxin, the principal neurotoxin in venom of the South American rattlesnakes Crotalus durissus terrificus and Crotalus durissus cascavella, contains a basic phospholipase A(2) (PLA(2)) and an acidic protein, crotapotin. In this work, we examined the ability of rabbit anti-sera against crotoxin and its PLA(2) subunit to neutralize the neurotoxicity of venom and crotoxin from C. d. cascavella in mouse phrenic nerve-diaphragm and chick biventer cervicis preparations. Immunoblotting showed that the anti-sera recognized C. d. cascavella crotoxin and PLA(2). This was confirmed by ELISA, with both anti-sera having end-point dilutions of 3 x 10(-6). Anti-crotoxin serum neutralized the neuromuscular blockade in phrenic nerve-diaphragm muscle preparations at venom or crotoxin:anti-serum ratios of 1:2 and 1:3, respectively. Anti-PLA(2) serum also neutralized this neuromuscular activity at a venom or crotoxin:anti-serum ratio of 1:1. In biventer cervicis preparations, the corresponding ratio for anti-crotoxin serum was 1:3 for venom and crotoxin, and 1:1 and 1:2 for anti-PLA(2) serum. The neutralizing capacity of the sera in mouse preparations was comparable to that of commercial anti-serum raised against C. d. terrificus venom. These results show that anti-sera against crotoxin and PLA(2) from C. d. cascavella venom neutralized the neuromuscular blockade induced by venom and crotoxin in both nerve-muscle preparations, with the anti-serum against crotoxin being slightly less potent than that against crotoxin. (C) 2004 Elsevier Ltd. All rights reserved.44214114

Neurotoxic and myotoxic actions of crotoxin-like and Crotalus durissus cascavella whole venom in the chick biventer cervicis preparation

Crotoxin from Crotalus durissus cascavella venom was purified by a combination of molecular exclusion chromatography (Superdex 75 column) and HPLC molecular exclusion (Protein Pack 300SW column). Neurotoxic and myotoxic effects from C. durissus cascavella whole venom and its main fraction, the crotoxin-like, were studied in the chick biventer cervicis (CBC nerve-muscle preparation. Both venom and its crotoxin showed significant (1) < 0.05) blockade of neuromuscular transmission at concentrations as low as 0.2-1, 5 and 25 mug/ml, but no significant effect has been shown with a concentration of 0.04 mug/ml (n = 5 each). The time required to produce 50% neuromuscular blockade with the venom and its crotoxin was 53.6 +/- 8.2 and 65.9 +/- 4.9 min (0.2 mug/ml), 29.7 +/- 1.9 and 34.3 +/- 1.9 min (1 mug/ml), 24.8 +/- 1.6 and 21.1 +/- 1.5 min (5 mug/ml), 20.9 +/- 3.7 and 20.1 +/- 1.4 min (25 mug/ml), respectively. The addition to the incubation bath of acetylcholine (55 and 110 muM) or KC1 (20.1 mM), either before or after the venom or the crotoxin induced contracture in the presence of a total blockade, in all the concentrations used. Morphological analysis showed that the damage caused by C. durissus cascavella venom is stronger than that caused by crotoxin. The myonecrotic picture was more marked at higher venom and crotoxin doses (4, 5 or 25 mug/ml). Only at 25 mug/ml concentrations of the venom and crotoxin, marked muscle fiber changes were detected. We concluded that the crotoxin-like and the whole venom from C. durissus cascavella possess a preponderant and quite potent neurotoxic action in this preparation, and a myotoxic action which is observed only at higher doses. (C) 2004 Elsevier Ltd. All rights reserved.43325526

Ability of rabbit antiserum against crotapotin to neutralize the neurotoxic, myotoxic and phospholipase A(2) activities of crotoxin from Crotalus durissus cascavella snake venom

The toxicity of crotoxin, the major toxin of Crotalus durissus terrificus (South American rattlesnake) venom, is mediated by its basic phospholipase A(2) (PLA(2)) subunit. This PLA(2) is non-covalently associated with crotapotin, an acidic, enzymatically inactive subunit of the crotoxin complex. In this work, rabbit antiserum raised against crotapotin purified from Crotalus durissus eascavella venom was tested for its ability to neutralize the neurotoxicity of this venom and its crotoxin in vitro. The ability of this antiserum to inhibit the enzymatic activity of the crotoxin complex and PLA(2) alone was also assessed, and its potency in preventing myotoxicity was compared with that of antisera raised against crotoxin and PLA(2). Antiserum to crotapotin partially neutralized the neuromuscular blockade caused by venom and crotoxin in electrically stimulated mouse phrenic nerve-hemidiaphragm preparations and prevented the venom-induced myotoxicity, but did not inhibit the enzymatic activity of crotoxin and purified PLA(2). In contrast, previous findings showed that antisera against crotoxin and PLA(2) from C. d. cascavella effectively neutralized the neuromuscular blockade and PLA(2) activity of this venom and its crotoxin. The partial neutralization of crotoxin-mediated neurotoxicity by antiserum to crotapotin probably reduced the binding of crotoxin to its receptor following interaction of the antiserum with the crotapotin moiety of the complex. (c) 2007 Elsevier Ltd. All rights reserved.22124024

Cross-neutralization of the neurotoxicity of Crotalus durissus terrificus and Bothrops jararacussu venoms by antisera against crotoxin and phospholipase A(2) from Crotalus durissus cascavella venom

We have previously demonstrated that rabbit antisera raised against crotoxin from Crotalus durissus cascavella venom (cdc-crotoxin) and its PLA(2) (cdc-PLA(2)) neutralized the neurotoxicity of this venom and its crotoxin. In this study, we examined the ability of these antisera to neutralize the neurotoxicity of Crotalus durissus terrificus and Bothrops jararacussu venoms and their major toxins, cdt-crotoxin and bothropstoxin-1 (BthTX-1), respectively, in mouse isolated phrenic nerve-diaphragm preparations. Immunoblotting showed that antiserum to cdc-crotoxin recognized cdt-crotoxin and BthTX-1, while antiserum to cdc-PLA(2) recognized cdt-PLA(2) and BthTX-1. ELISA corroborated this cross-reactivity. Antiserum to cdc-crotoxin prevented the neuromuscular blockade caused by C d. terrificus venom and its crotoxin at a venom/crotoxin: antiserum ratio of 1:3. Antiserum to cdc-PLA(2) also neutralized the neuromuscular blockade caused by C. d. terrificus venom or its crotoxin at venom or toxin:antiserum ratios of 1:3 and 1: 1, respectively. The neuromuscular blockade caused by B. jararacussu venom and BthTX-1 was also neutralized by the antisera to cdc-crotoxin and cdc-PLA(2) at a venom/toxin:antiserum ratio of 1: 10 for both. Commercial equine antivenom raised against C.d. terrificus venom was effective in preventing the neuromuscular blockade typical of B. jararacussu venom (venom: anti venom ratio of 1:2), whereas for BthTX-1 the ratio was 1:10. These results show that antiserum produced against PLA(2) the major toxin in C durissus cascavella venom, efficiently neutralized the neurotoxicity of C. d. terrificus and B. jararacussu venoms and their PLA(2) toxins. (c) 2005 Published by Elsevier Ltd.46660461

Dual mutations in the AML1 and FLT 3 genes are associated with leukemogenesis in acute myeloblastic leukemia of the M0 subtype

10.1038/sj.leu.2403160Leukemia17122492-2499LEUK

Nature and decay of a Jp=36+ resonance in the 24Mg+24Mg reaction

It has been proposed to associate the narrow (\u393=170 keV) and high spin (J\u3c0=36+) resonance in the 24Mg + 24Mg reaction at Ec.m= 45.7 MeV with a hyperdeformed molecular state in 48Cr. Such a description has important consequences for the resonance decay into the favoured inelastic channels. Through fragment\u2010\u3b3 coincidence measurements performed ON and OFF resonance using the PRISMA\u2010CLARA array, we have established that the 24Mg states selectively populated are the 2+ and 4+ members of the ground state band