Journals
2014 EN
Poe Michele D. · Chag Sarah L. · Escolar Maria L.
Objective Hurler syndrome is the most clinically severe form of an autosomal recessive lysosomal disorder characterized by the deficiency of α‐L‐iduronidase. The resulting accumulation of glycosaminoglycans causes progressive multisystem deterioration, resulting in death in childhood. Umbilical cord blood transplantation from unrelated donors has been previously shown to improve neurological outcomes of children <2 years of age and prolong life. The purpose of this article is to determine whether age at transplantation can predict cognitive outcomes. Methods Between June 1997 and February 2013, 31 patients with Hurler syndrome underwent umbilical cord blood transplantation and were evaluated at baseline and every 6 to 12 months thereafter. All 31 patients underwent complete neurodevelopmental evaluation (median follow‐up = 7.3 years, range = 2–21.7) and a median of 7.0 evaluations (range = 3–18). Results Younger age at transplantation was associated with improved cognitive function ( p = 0.001), receptive and expressive language ( p = 0.004 and p = 0.01), and adaptive behavior ( p = 0.03). Interpretation Early age at transplantation is a strong predictor of cognitive, language, and adaptive behavior outcomes. Children younger than 9 months at the time of transplant showed normal cognitive development. Our results demonstrate that early diagnosis is necessary for optimal outcomes and support the need for newborn screening, because most patients are not identified at this young age. Ann Neurol 2014;76:747–753
Journals
2014 EN
Broomall Eileen · Natale JoAnne E. · Grimason Michele
+6 more
Super‐refractory status epilepticus is a life‐threatening condition. Resistance to benzodiazepine and barbiturate treatment for this disorder is thought to be due to internalization of synaptic γ‐aminobutyric acid (GABA) A receptors, and withdrawal of benzodiazepines and barbiturates during treatment often triggers seizure recurrence. The neurosteroid allopregnanolone acts as a positive allosteric modulator of synaptic and extrasynaptic GABA A receptors. Here we describe the use of allopregnanolone in 2 pediatric patients with super‐refractory status epilepticus. This treatment allowed the general anesthetic infusions to be weaned with resolution of status epilepticus. This is the first report of allopregnanolone use to treat status epilepticus in children. Ann Neurol 2014;76:911–915
Journals
2014 EN
Chiarucci Michel · Ciogli Alessia · Mancinelli Michele
+2 more
The weak electrostatic interaction between nitro and carbonyl moieties has been observed by means of variable‐temperature NMR spectroscopy. Its energetic contribution was evaluated to be about 3 kcal mol −1 by DFT calculations, and confirmed by the measurement of internal energy barriers to the rotation of suitable nitroaryl rings.
Journals
2014 EN
Ung Gaël · Rittle Jonathan · Soleilhavoup Michele
+2 more
The CAAC [CAAC=cyclic (alkyl)(amino)carbene] family of carbene ligands have shown promise in stabilizing unusually low‐coordination number transition‐metal complexes in low formal oxidation states. Here we extend this narrative by demonstrating their utility in affording access to the first examples of two‐coordinate formal Fe 0 and Co 0 [(CAAC) 2 M] complexes, prepared by reduction of their corresponding two‐coordinate cationic Fe I and Co I precursors. The stability of these species arises from the strong σ‐donating and π‐accepting properties of the supporting CAAC ligands, in addition to steric protection.
Journals
2014 EN
Pedroni Julia · Boghi Michele · Saget Tanguy
+1 more
β‐Lactams are very important structural motifs because of their broad biological activities as well as their propensity to engage in ring‐opening reactions. Transition‐metal‐catalyzed CH functionalizations have emerged as strategy enabling yet uncommon highly efficient disconnections. In contrast to the significant progress of Pd 0 ‐catalyzed CH functionalization for aryl–aryl couplings, related reactions involving the formation of saturated C(sp 3 )C(sp 3 ) bonds are elusive. Reported here is an asymmetric CH functionalization approach to β‐lactams using readily accessible chloroacetamide substrates. Important aspects of this transformation are challenging C(sp 3 )C(sp 3 ) and strain‐building reductive eliminations to for the four‐membered ring. In general, the β‐lactams are formed in excellent yields and enantioselectivities using a bulky taddol phosphoramidite ligand in combination with adamantyl carboxylic acid as cocatalyst.
Journals
2014 EN
Richichi Barbara · Thomas Baptiste · Fiore Michele
+5 more
Abstract Tumor‐associated carbohydrate antigens (TACAs) are key components of cancer vaccines. A variety of vaccines based on native TACAs such as α‐Tn have shown immunogenicity and protection in preclinical animal studies, however, their weak immunogenicity, low in vivo instability, and poor bioavailability, have discouraged their further evaluations in clinical studies. A new improved vaccine prototype is reported. It is composed of four clustered Tn‐antigen mimetics and a immunogenic peptide epitope that are conjugated to a cyclopeptide carrier. The immunization of mice with this vaccine 1) was safe, 2) induced a strong and long‐lasting Tn‐specific response with IgM/IgG antibodies able to recognize native carbohydrate antigens; 3) produced high titers of IgG1, IgG2a, and IgG3 antibodies; and 4) produced a significant antibody‐dependent regression of tumors and conferred protection. Altogether, these findings pave the way for the clinical development of safe and effective therapeutic vaccines against Tn‐expressing cancers.
Journals
2014 EN
Chiarucci Michel · Ciogli Alessia · Mancinelli Michele
+2 more
The weak electrostatic interaction between nitro and carbonyl moieties has been observed by means of variable‐temperature NMR spectroscopy. Its energetic contribution was evaluated to be about 3 kcal mol −1 by DFT calculations, and confirmed by the measurement of internal energy barriers to the rotation of suitable nitroaryl rings.
Journals
2014 EN
Ung Gaël · Rittle Jonathan · Soleilhavoup Michele
+2 more
The CAAC [CAAC=cyclic (alkyl)(amino)carbene] family of carbene ligands have shown promise in stabilizing unusually low‐coordination number transition‐metal complexes in low formal oxidation states. Here we extend this narrative by demonstrating their utility in affording access to the first examples of two‐coordinate formal Fe 0 and Co 0 [(CAAC) 2 M] complexes, prepared by reduction of their corresponding two‐coordinate cationic Fe I and Co I precursors. The stability of these species arises from the strong σ‐donating and π‐accepting properties of the supporting CAAC ligands, in addition to steric protection.
Journals
2014 EN
Pedroni Julia · Boghi Michele · Saget Tanguy
+1 more
β‐Lactams are very important structural motifs because of their broad biological activities as well as their propensity to engage in ring‐opening reactions. Transition‐metal‐catalyzed CH functionalizations have emerged as strategy enabling yet uncommon highly efficient disconnections. In contrast to the significant progress of Pd 0 ‐catalyzed CH functionalization for aryl–aryl couplings, related reactions involving the formation of saturated C(sp 3 )C(sp 3 ) bonds are elusive. Reported here is an asymmetric CH functionalization approach to β‐lactams using readily accessible chloroacetamide substrates. Important aspects of this transformation are challenging C(sp 3 )C(sp 3 ) and strain‐building reductive eliminations to for the four‐membered ring. In general, the β‐lactams are formed in excellent yields and enantioselectivities using a bulky taddol phosphoramidite ligand in combination with adamantyl carboxylic acid as cocatalyst.
Journals
2014 EN
Richichi Barbara · Thomas Baptiste · Fiore Michele
+5 more
Abstract Tumor‐associated carbohydrate antigens (TACAs) are key components of cancer vaccines. A variety of vaccines based on native TACAs such as α‐Tn have shown immunogenicity and protection in preclinical animal studies, however, their weak immunogenicity, low in vivo instability, and poor bioavailability, have discouraged their further evaluations in clinical studies. A new improved vaccine prototype is reported. It is composed of four clustered Tn‐antigen mimetics and a immunogenic peptide epitope that are conjugated to a cyclopeptide carrier. The immunization of mice with this vaccine 1) was safe, 2) induced a strong and long‐lasting Tn‐specific response with IgM/IgG antibodies able to recognize native carbohydrate antigens; 3) produced high titers of IgG1, IgG2a, and IgG3 antibodies; and 4) produced a significant antibody‐dependent regression of tumors and conferred protection. Altogether, these findings pave the way for the clinical development of safe and effective therapeutic vaccines against Tn‐expressing cancers.