bluuebunny/crossref_metadata_2025 huggingface dataset:
β‐Cyclodextrin‐Catalyzed Monosulfonylation of Amines and Amino Acids in Water
Authors: Sridhar R. , Srinivas B. , Kumar V. Pavan , Narender M. , Rao K. Rama
Published: August 2007

A mild and efficient procedure has been developed for the first time under biomimetic conditions for the monosulfonylation of various amines and amino acids catalyzed by β‐cyclodextrin in water at room temperature to afford the corresponding sulfonamides in high yields.
Mechanochemical Aminochlorination of Electron‐Deficient Olefins with Chloramine‐T Promoted by (Diacetoxyiodo)benzene
Authors: Wang Guan‐Wu , Wu Xue‐Liang
Published: August 2007

A direct and convenient procedure for the solvent‐free mechanochemical aminochlorination of electron‐deficient olefins promoted by (diacetoxyiodo)benzene [PhI(OAc)2] was described using commercially available and cheap chloramine‐T as a nitrogen and chlorine source. The vicinal chloramine derivatives were obtained in high regio‐ and stereoselectivity with good yields. PhI(OAc)2 was superior to metal salts for the aminochlorination of electron‐deficient olefins.
Supported Ultra Small Palladium on Magnetic Nanoparticles Used as Catalysts for Suzuki Cross‐Coupling and Heck Reactions
Authors: Yinghuai Zhu , Peng Ship Chee , Emi A. , Zhenshun Su , Monalisa  , Kemp Richard A.
Published: August 2007

Application of transition metal nanoparticles as catalysts for organic transformations has been attracting wide interest as nanoparticle‐based catalytic systems might exhibit superior catalytic activities than the corresponding bulk materials. However, the main difficulty is that such small particles are almost impossible to separate by conventional means, which can lead to the blocking of filters and valves by the nanoparticle catalyst. We have conveniently prepared ultra small palladium(0) particles (less than 1 nm) on magnetic nanoparticle supports, in which immobilized auxiliaries are used as stabilizing ligands. These catalysts were active for Suzuki cross‐coupling and Heck reactions giving isolated yields of 83 % and 56 %, respectively. In addition, the catalyst can be easily separated using a magnet and reused several times with sustained activity.
Heterogeneous Palladium Catalysts for a New One‐Pot Chemical Route in the Synthesis of Fragrances Based on the Heck Reaction
Authors: Climent Maria Jose , Corma Avelino , Iborra Sara , Mifsud Maria
Published: August 2007

The one‐pot synthesis of the fragrance 4‐(p‐methoxyphenyl)butan‐2‐one, with raspberry scent, has been carried out using palladium on different supports such as magnesium oxide (MgO), hydrotalcite, hydroxyapatite (HA), aluminium oxide (γ‐Al2O3) and titanium dioxide (TiO2). The first pathway consists of a Heck coupling between 4‐methoxyiodoanisole and methyl vinyl ketone followed by hydrogenation. Palladium supported on titanium dioxide showed the best performance for carrying out both consecutive steps giving 4‐(p‐methoxyphenyl)butan‐2‐one with high yields and selectivity. The Pd‐TiO2 catalyst is more active than a homogeneous palladium complex that is well accepted in the literature as being highly active for performing Heck reactions.
Superior Performance of a Nanostructured Platinum Catalyst in Water: Hydrogenations of Alkenes, Aldehydes and Nitroaromatics
Authors: Maity Prasenjit , Basu Susmit , Bhaduri Sumit , Lahiri Goutam Kumar
Published: August 2007

The hydrogenations of >CC<, >CO and nitro groups in ArNO2, with a water‐soluble, polymer [poly(diallyldimethylammonium chloride)] supported, platinum carbonyl cluster {[Pt30(CO)60]2−} derived catalyst 1, have been studied. The performance of 1 has been compared with that of two other platinum catalysts: catalyst 2 prepared by the hydrogen reduction of [PtCl6]2− supported on the same water‐soluble polymer, and 3, a commercial platinum catalyst (5 % Pt on alumina). Our catalyst 1 has been found to be more active than 2 and 3, and by TEM it has been shown that the nanoparticles in 1 are much smaller than those in 2. In the hydrogenation of o‐chloronitrobenzene both 1 and 2 were found to be more selective (no hydrodehalogenation) than 3. To evaluate the advantages of water as a solvent, comparative studies have been carried out in three different solvent systems: water, methanol and a 1:1 mixture of water and toluene. Hydrogenations in methanol have been found to be accompanied by induction times while no such induction time is observed in water. Both liquid (methyl pyruvate, benzaldehyde, safflower oil and styrene) and water‐insoluble solid nitroaromatics (o‐ and m‐chloronitrobenzene and p‐aminonitrobenzene) have been tested as substrates, and for all the substrates the activity in water was found to be higher.
Efficient Reduction of Nitroarenes over Nickel‐Iron Mixed Oxide Catalyst Prepared from a Nickel‐Iron Hydrotalcite Precursor
Authors: Shi Qixun , Lu Rongwen , Lu Lianhai , Fu Xinmei , Zhao Defeng
Published: August 2007

Nickel‐iron mixed oxide prepared from a nickel‐iron hydrotalcite precursor was found to be a highly efficient catalyst for the chemoselective reduction of nitroarenes under mild reaction conditions.
1,3,5‐Triaza‐7‐phosphaadamantane (PTA): A Practical and Versatile Nucleophilic Phosphine Organocatalyst
Authors: Tang Xiaofang , Zhang Bo , He Zhengrong , Gao Ruili , He Zhengjie
Published: August 2007

In this paper, the air‐stable and readily available 1,3,5‐triaza‐7‐phosphaadmantane (PTA) is reported as a practical and versatile nucleophilic phosphine organocatalyst. Under the mediation of 15–30 mol % of PTA, various electrophiles like aldehydes and imines readily undergo the Morita–Baylis–Hillman reactions with a variety of activated olefins, giving the corresponding adducts in high yields. In the phosphine‐catalyzed [3+2] cycloaddition reaction of 4‐substituted 2,3‐butadienoates with N‐tosylimines, PTA is also proven to be a comparable catalyst as tributylphosphine (PBu3). By systematic comparison with other structurally similar N,P catalysts, it is concluded that the superiority of PTA in the above nucleophilic catalysis is attributable to its comparable nucleophilicity with that of trialkylphosphines. The feasibility to use PTA as an alternative catalyst in place of the air‐sensitive trialkylphosphines is also discussed.
Asymmetric Amplification in the Amino Acid‐Catalyzed Synthesis of Amino Acid Derivatives
Authors: Ibrahem Ismail , Sundén Henrik , Dziedzic Pawel , Rios Ramon , Córdova Armando
Published: August 2007

The origins of biological homochirality have intrigued researchers since Pasteur’s discovery of the optical activity of biomolecules. Herein, we present the first example of asymmetric amplification in the amino acid‐catalyzed enantioselective synthesis of amino acid derivatives that provides support for a synergistic model for the evolution of homochirality by amino acid catalysis.
An Efficient and Versatile Approach for the Immobilization of Carbene Precursors via Copper‐Catalyzed [3+2]‐Cycloaddition and their Catalytic Application
Authors: Zeitler Kirsten , Mager Ina
Published: August 2007

Different classes of alkynyl‐substituted heterazolium derivatives could be covalently immobilized on an azide‐functionalized support via copper‐catalyzed 1,3‐dipolar cycloaddition, which efficiently yields a rigid and robust 1,2,3‐triazole linkage. The catalytic performance of the corresponding nucleophilic carbenes (NHCs) was examined in intramolecular Stetter reactions (chroman‐4‐one products) and organocatalytic redox esterifications (α,β‐unsaturated esters). The MeOPEG‐immobilized organocatalysts are highly active, and show comparable diastereoselectivities to non‐supported derivatives. Additionally, they allow simplified work‐up procedures and also have proven to be recyclable.
A population balance model of the solution‐mediated phase transition of citric acid
Authors: Févotte Gilles , Alexandre and Sheibat Othman Nida Caillet
Published: August 2007

The Solvent‐Mediated Anhydrous to Monohydrate Phase Transition (SMPT) of citric acid in water was monitored using in situ Raman spectroscopy and image analysis. The solid phase composition, solute concentration, and crystal size distribution were measured during experiments designed to investigate the different steps of the SMPT process: dissolution of the metastable form, nucleation, and growth of the stable form. A Population Balance Model (PBE) was developed to depict the time evolutions of the two populations of particles involved. Nucleation and growth phenomena were analyzed and described through simplified kinetic laws. The related kinetic parameters were estimated through the nonlinear least squares minimization of model‐experiments prediction errors. The overall PBE model was finally found to satisfactorily describe the SMTP process; the time variations of the solute concentration and solid phase composition in particular. It is clearly shown that the secondary nucleation of stable monohydrate particles depends on both the supersaturation and the overall solid content. Surprisingly, as far as the nucleation of stable particles in the presence of metastable solid is concerned, the rate of particle generation was found to exhibit identical dependency on the metastable and stable content, a feature which remains to be further investigated and explained. © 2007 American Institute of Chemical Engineers AIChE J, 2007
Robust optimal control of polymorphic transformation in batch crystallization
Authors: Hermanto Martin Wijaya , Chiu Min‐Sen , Woo Xing‐Yi , Braatz Richard D.
Published: August 2007

One of the most important problems that can arise in the development of a pharmaceutical crystallization process is the control of polymorphism, in which there exist different crystal forms for the same chemical compound. Different polymorphs can have very different properties, such as bioavailability, which motivates the design of controlled processes to ensure consistent production of the desired polymorph to produce reliable therapeutic benefits upon delivery. The optimal batch control of the polymorphic transformation of L‐glutamic acid from the metastable α‐form to the stable β‐form is studied, with the goal of optimizing batch productivity, while providing robustness to variations in the physicochemical parameters that can occur in practice due to variations in contaminant profiles in the feedstocks. A nonlinear state feedback controller designed to follow an optimal setpoint trajectory defined in the crystallization phase diagram simultaneously provided high‐batch productivity and robustness, in contrast to optimal temperature control strategies that were either nonrobust or resulted in long‐batch times. The results motivate the incorporation of the proposed approach into the design of operating procedures for polymorphic batch crystallizations. © 2007 American Institute of Chemical Engineers AIChE J, 2007
Fibrinogen deficiency, but not plasminogen deficiency, increases mortality synergistically in combination with sickle hemoglobin SAD in transgenic mice
Authors: Roszell Nancy J. , Danton Mary Jo , Jiang Maorong , Witte David , Daugherty Cynthia , Grimes Timothy , Girdler Benjamin , Anderson Kathleen P. , Franco Robert S. , Degen Jay L. , Joiner Clinton H.
Published: August 2007

Patients with sickle cell disease exhibit both acute and chronic activation of the coagulation and fibrinolytic systems. To test the relationship between sickle cell pathology and activation of the hemostatic system, mice with targeted deletions of plasminogen (Plg) or fibrinogen (Fib) were crossed with transgenic mice expressing Hb SAD [β6Glu‐Val (HbS), β23Val‐Ile (HbAntilles), and β121Glu‐Gln (HbD‐Punjab)]. Fibrinogen deficiency dramatically reduced the survival of mice with Hb SAD to a much greater degree than mice with normal hemoglobin. The combination of Hb SAD and fibrinogen deficiency had a greater effect on mortality than that obtained by adding the mortality risks of each defect alone. The deleterious effect of the combination of Hb SAD and fibrinogen deficiency on mortality was accelerated by hypoxia. The excess mortality associated with plasminogen deficiency was identical in SAD and control mice. The adverse effect of fibrinogen deficiency on mortality in SAD mice is not consistent with the simple hypothesis that fibrin deposition is uniformly deleterious in the context of vaso‐occlusive sickle cell disease. Rather, our findings suggest that the contribution of fibrinogen to tissue repair may in some contexts limit sickle cell disease pathophysiology. Am. J. Hematol., 2007. © 2007 Wiley‐Liss, Inc.
Self‐reported health‐related quality of life in adults with chronic immune thrombocytopenic purpura
Authors: McMillan Robert , Bussel James B. , George James N. , Lalla Deepa , Nichol Janet L.
Published: August 2007

Adult chronic immune thrombocytopenic purpura (ITP) is a disorder manifested by varying degrees of purpura and mucosal bleeding, rarely including intracranial hemorrhage. Therapy is aimed at increasing the patient's platelet count to safe levels and includes a wide variety of treatments. While the diagnosis, treatment, and prognosis of chronic ITP have been extensively discussed, the effect of ITP and its treatment on patient quality of life has not been evaluated in adults. In this study, the Short‐Form 36 questionnaire was used to evaluate the health‐related quality of life (HRQOL) of 73 adult ITP patients compared with that of the general U.S. population and of patients with six other relatively common chronic disorders. This study shows that the HRQOL of adult patients with ITP is significantly worse than that of the general U.S. population. It is also worse than that of patients with hypertension, arthritis, or cancer; similar to that of patients with diabetes; but better than that of patients with congestive heart failure or a missing or paralyzed limb. Future studies need to address the effects of treatment not only on the platelet count and bleeding but also on HRQOL. Am. J. Hematol., 2008. © 2007 Wiley‐Liss, Inc.
G‐CSF‐mobilized haploidentical peripheral blood stem cell transplantation in children with poor prognostic nonmalignant disorders
Authors: Arpacı Fikret , Tezcan İlhan , Kuzhan Okan , Yalman Nevin , Uçkan Duygu , Kürekçi Ahmet Emin , İkincioğulları Aydan , Özet Ahmet , Tanyeli Atilla
Published: August 2007

Haploidentical hematopoietic stem cell transplantation (HSCT) is currently one of the alternative curative treatment options for some nonmalignant but also for malignant diseases. However, concerns regarding its safety cause delays in time and a successful outcome. Between 2000 and 2005, twenty‐one children with poor prognostic nonmalignant disorders, 13 boys and 8 girls, with a median age of 12 months, underwent 28 haploidentical peripheral HSCT. Immunomagnetic bead depletion device (CliniMACS) was used for indirect T‐cell depletion. Indications for transplant were severe combined immunodeficiency (n = 16), osteopetrosis (n = 2), MDS (n = 1), amegakaryocytic thrombocytopenia (n = 1), and aplastic anemia (n = 1). Five patients (24%) had lung infection at the time of transplantation. The patients received a median of 25.67 × 106 G‐CSF‐mobilized peripheral CD34+ progenitor cells and a median of 4.19 × 104 T‐lymphocytes per kilogram of body weight with a T‐cell depletion rate of median 4.59 logs. The rate of total engraftment was 66.6%. Median times for leukocyte and platelet engraftment were 14 and 16 days, respectively. The 6‐year projected survival was 32% for all patients and 29.76% for patients with severe combined immunodeficiency (SCID). The rates of transplant‐related mortality, graft failure, and severe GvHD were 14.2, 33.4%, and 8.3%, respectively. Infection was the main cause of death. The poor outcome may be explained with the poor prognostic factors of our patients such as the type of SCID in most cases (T‐B− SCID), the median age over 6 months and the presence of lung infection in some children at the time of transplantation. Am. J. Hematol., 2008. © 2007 Wiley‐Liss, Inc.
Heparin‐induced skin necrosis associated with thrombocytopenia and acquired protein C and protein S deficiency
Authors: Prasad H. Keshava , Govindarajan Rangaswamy
Published: August 2007

We have described a patient with colon cancer and liver metastases who developed heparin‐induced thrombocytopenia and skin necrosis. We believe that the skin necrosis caused by the heparin/platelet factor 4 antibody was exacerbated by the acquired protein C and protein S deficiency. After the heparin was discontinued and infection treated, the skin necrosis and thrombocytopenia resolved. This case illustrates the fact that, in patients with heparin‐induced skin necrosis, a search must be undertaken for an underlying pro‐thrombotic state, which may precipitate the microthrombosis responsible for skin necrosis. We could not find any previous case reports of heparin‐induced skin necrosis associated with isolated protein C deficiency, or combined protein C and protein S deficiency. Am. J. Hematol., 2007. © 2007 Wiley‐Liss, Inc.
Pharmacogenetics of morphine: Potential implications in sickle cell disease
Authors: Darbari Deepika S. , Minniti Caterina P. , Rana Sohail , van den Anker John
Published: August 2007

Morphine is frequently used to treat painful episodes associated with sickle cell disease (SCD) but may fail to provide adequate analgesia in many patients. This concise review focuses on unique disease related changes in physiologic variables associated with SCD that impacts pharmacokinetics and pharmacodynamics of morphine and may contribute to the variability in analgesia. Emerging evidence suggests that the allelic variants in the genes involving the opioid (UGT2B7, OPRM1, and ABCB1 genes) and nonopioid system (COMT gene) can alter the efficacy of morphine. Am. J. Hematol., 2008. © 2007 Wiley‐Liss, Inc.
Splenectomy for immune thrombocytopenic purpura: Surgery for the 21st century
Authors: Dolan James P. , Sheppard Brett C. , DeLoughery Thomas G.
Published: August 2007

Although immune thrombocytopenic purpura (ITP) is the most common autoimmune hematological disorder, there is still controversy regarding the optimal management of this condition. Medical therapy may cure a proportion of patients with ITP but there are still a significant number of these individuals who are at risk for bleeding events. Surgery has become the least popular therapeutic option for ITP as other medical therapies have become available that attempt to avoid splenectomy and its morbidity. However, the clinical response to these therapies has not been overwhelming based on the fairly small number of trials conducted to date. With current minimally invasive surgical techniques, splenectomy should be again regarded as a viable therapeutic option in patients with ITP. The laparoscopic approach avoids much of the morbidity and complications seen with the conventional open surgical approach and studies have demonstrated similar, if not better, outcomes. In addition, the risk of infection following splenectomy is not as high as may be suspected, particularly with current vaccination regiments. It should be a priority for both the hematology and medical community to advocate for clinical trials to rationally study alternatives to splenectomy. In the interim, laparoscopic splenectomy should be considered as an additional front line therapeutic option in ITP patients. Am. J. Hematol., 2008. © 2007 Wiley‐Liss, Inc.
Peripheral blood monocytes from patients with HBV related decompensated liver cirrhosis can differentiate into functional hepatocytes
Authors: Yan Li , Han Ying , Wang Jingbo , Liu Jingmei , Hong Liu , Fan Daiming
Published: August 2007

Peripheral blood monocytes (PBMCs) have the potential to differentiate into various progenitor cells. Here we have investigated the differentiation potential of PBMCs derived from patients with HBV related decompensated liver cirrhosis into hepatocyte‐like cells. In our clinical trial, the PBMCs from 2 patients were mobilized by the recombinant human granulocyte colony stimulating factor, followed by leukapheresis and transplantation of PBMCs. PBMCs, induced by recombinant human hepatocyte growth factors, were identified by the expression of hepatocyte markers and specific biological functions with biochemical assays in vitro. Patients showed a lasting clinical amelioration for more than one year after transplantation, and hepatocyte‐like cells were identified by expressing liver specific genes, synthesizing albumin, urea, aspirate transaminase, and glycogen, which were all similar to the human normal hepatic cell line QZG. Our results clearly demonstrated that mobilized PBMCs from patients with HBV related decompensated liver cirrhosis could differentiate into functional hepatocyte‐like cells, indicating the possibility of autologous cell transplantation for treating patients with HBV related decompensated liver cirrhosis. Am. J. Hematol., 2007. © 2007 Wiley‐Liss, Inc.
What is the potential for overdiagnosis of heparin‐induced thrombocytopenia?
Authors: Lo Gregory K. , Sigouin Christopher S. , Warkentin Theodore E.
Published: August 2007

Heparin‐induced thrombocytopenia (HIT) is caused by platelet‐activating antibodies that recognize platelet factor 4//heparin (PF4/H) complexes. According to the “iceberg model,” only a subset of anti‐PF4/heparin antibodies of IgG class evincing strong platelet‐activating properties cause clinical HIT. Since many centers rely predominantly on an anti‐PF4/polyanion enzyme‐immunoassay (EIA) to diagnose HIT, we estimated the potential for overdiagnosis when only this single test is available. We examined a database of 100 patients in whom the probability of HIT had been estimated using a clinical scoring system (4Ts), and where patients underwent systematic testing for HIT antibodies using three assays: the platelet serotonin release assay (SRA), an “in‐house” EIA that detects IgG anti‐PF4/heparin antibodies (EIA‐IgG), and a commercial EIA that detects anti‐PF4/polyanion antibodies of all three immunoglobulin classes (EIA‐GTI). Whereas 16 of 100 patients fulfilled a “classic” definition of HIT (intermediate/high probability plus strong platelet‐activating anti‐PF4/heparin IgG antibodies), an additional 16 patients fulfilled a “liberal” definition in which any investigated patient (irrespective of the pretest probability) who had a positive EIA‐GTI was considered to have HIT. The clinical features of these 16 additional patients—including generally weak antibodies and low risk for thrombosis—suggest underlying non‐HIT explanations for thrombocytopenia. Patients with a positive SRA generally corresponded to those with intermediate or high pretest probability of HIT who also had strong EIA‐GTI reactivity (>1.20 OD units). We conclude there is the potential to overdiagnose HIT by ∼100% if any positive EIA is considered to “confirm” the diagnosis of HIT irrespective of the clinical scenario. Am. J. Hematol., 2007. © 2007 Wiley‐Liss, Inc.
Immunotherapy in mantle cell lymphoma: Anti‐CD20‐based therapy and beyond
Authors: Zhou Yuhong , Zhang Liang , Romaguera Jorge , Delasalle Kay , Han Xiaohong , Du Xin , Kwak Larry , Yi Qing , Wang Michael
Published: August 2007

Mantle cell lymphoma (MCL), an aggressive non‐Hodgkin's lymphoma characterized by t(11; 14)(q13; q32) chromosomal translocation and overexpression of cyclin D1, has the worst prognosis among all lymphomas. Recent advances in biology, genetics, and immunology have supported the development of immunotherapy in MCL. Rituximab monotherapy in MCL has limited activity. It is more effective when used in combination with chemotherapy such as R‐CHOP, R‐hyperCVAD/MTX‐Ara‐C, or R‐FCM as front‐line or salvage therapy for mantle cell lymphoma. Maintenance with Rituximab was shown to prolong response duration. Although most results have suggested that combining autologous stem cell transplantation with Rituximab may lead to durable remission, the sample size was not sufficient to declare survival benefit. Anti‐CD20 radioimmunoconjugates (RICs) 90Yttrium‐ibritumomab tiuxetan and 131Iodine‐tositumomab have been used in mantle cell lymphoma even when patients are relatively resistant to Rituximab‐based therapy. Allogeneic stem cell transplantation is a treatment modality in advanced or relapsed MCL, particularly using reduced‐intensity conditioning. MCL may have high response rates and sustained remissions after donor lymphocyte infusion. Dendritic cells (DCs) fused with MCL cells for immunostimulation have preliminarily shown anti‐lymphoma effects as well. Idiotype vaccination in MCL patients following Rituximab‐containing chemotherapy induced tumor‐specific T‐cell immunity in the absence of B cells. Other immunotherapy, such as the combination of thalidomide with Rituximab, has shown substantial antitumor activity. A Phase I/II study is ongoing to determine the maximum tolerated dose (MTD) and the efficacy of lenalidomide in combination with Rituximab for relapsed/refractory MCL. This review summarizes the latest and exciting advances in MCL. Am. J. Hematol., 2008. © 2007 Wiley‐Liss, Inc.
A coalescent simulation of marker selection strategy for candidate gene association studies
Authors: Cole Suzanne M. , Long Jeffrey C.
Published: August 2007

Recent efforts have focused on the challenges of finding alleles that contribute to health‐related phenotypes in genome‐wide association studies. However, in candidate gene studies, where the genomic region of interest is small and recombination is limited, factors that affect the ability to detect disease‐susceptibility alleles remain poorly understood. In particular, it is unclear how varying the number of markers on a haplotype, the type of marker (e.g., single nucleotide polymorphism (SNP), short tandem repeat (STR)), including the causative site (cs) as a genetic marker, or population demographics influences the power to detect a candidate gene. We evaluated the power of association tests using coalescent‐modeled computer simulations. Results show that an effective number of markers on a haplotype is dependent on whether the cs is included as a marker. When the analyses include the cs, highest power is achieved with a single‐marker association test. However, when the cs is excluded from analyses, the addition of more nonfunctional SNPs on the haplotype increases power to a certain point under most scenarios. We find a rapidly expanding population always has lower power compared to a population of constant size; although utilizing markers with a frequency of at least 5% improves the chance of detecting an association. Comparing the mutational properties of a nonfunctional SNP versus an STR, multi‐allelic STRs provide more or comparable power than a bi‐allelic SNP unless SNP frequencies are constrained to 10% or more. Similarly, including an STR with SNPs on a haplotype improves power unless SNP frequencies are 5% or more. © 2007 Wiley‐Liss, Inc.
An association study of RGS4 polymorphisms with clinical phenotypes of schizophrenia in a Chinese population
Authors: So Hon‐Cheong , Chen Ronald Y.L. , Chen Eric Y.H. , Cheung Eric F.C. , Li Tao , Sham Pak C.
Published: August 2007

The regulator of G‐protein signaling 4 (RGS4) has been suggested as a candidate gene for schizophrenia. However, following an initial positive report, subsequent association studies between RGS4 and schizophrenia have yielded inconclusive results. Also, few studies have investigated the association of RGS4 polymorphisms with the phenotypic subgroups of schizophrenia. To further clarify the role of RGS4 in this disease, we performed a case‐control study (504 cases and 531 controls of Han Chinese descent) to examine the association of RGS4 with schizophrenia and with clinical and neurocognitive profiles. The four markers (SNPs 1, 4, 7, and 18) implicated in the original association study were genotyped. We detected significant association of four‐marker haplotypes with schizophrenia (UNPHASED: globalP = 0.037; PHASE: globalP = 0.048). The haplotype G‐G‐G‐G, which was implicated in at least three previous studies, was the major risk haplotype (UNPHASED:P = 0.019; PHASE:P = 0.010). Regarding the clinical phenotypes, the Wechsler Adult Intelligence Test (WAIS) information subtest score was associated with SNP4 genotypes (P = 0.001). PANSS total and global psychopathology scores were also associated with SNP4, but may not reliably reflect the general severity of disease as the scores may be affected by confounders like medication response. Our study provides further support for a role of RGS4 in the pathogenesis of schizophrenia. We identified G‐G‐G‐G as the risk haplotype in our Chinese sample. The association with information subtest score suggests an effect of RGS4 on premorbid functioning, which may be related to neurodevelopmental processes. Further independent studies are required to verify our findings. © 2007 Wiley‐Liss, Inc.
Dissocial behavior, the 5HTTLPR polymorphism, and maltreatment in women with bulimic syndromes
Authors: Steiger Howard , Richardson Jodie , Joober Ridha , Israel Mimi , Bruce Kenneth R. , Ng Ying Kin N.M.K. , Howard Heidi , Anestin Annelie , Dandurand Cathy , Gauvin Lise
Published: August 2007

We recently reported that, among bulimic women, previously abused carriers of the 5HTTLPR S allele showed special propensities towards novelty seeking (implying recklessness or impulsivity) and interpersonal insecurity. We subsequently re‐analyzed our data, to examine the bearing of the 5HTTLPR polymorphism and prior sexual or physical maltreatment upon validated, higher‐order personality‐traits. Ninety women with bulimic syndromes were genotyped for 5HTTLPR “short” (S) and “long” (LG and LA) alleles, and then assessed for eating symptoms, history of sexual or physical abuse, and the higher‐order personality traits Emotional Dysregulation, Dissocial Behavior, Inhibition, and Compulsivity. With a classification based on a biallelic model of 5HTTLPR (i.e., presence or absence of at least one S‐allele copy), multiple regression indicated a significant proportion of variance in Dissocial Behavior to be explained by an abuse × genotype interaction—greater psychopathology occurring in abused S‐allele carriers. A parallel analysis applying a triallelic model of 5HTTLPR (i.e., presence or absence of at least one copy of presumably low‐function S or LG alleles) produced a similar pattern, but no statistically significant effect. The finding that bulimic 5HTTLPR S‐allele carriers who are previously abused display elevations on Dissocial Behavior corroborates previous observations concerning phenomenological correlates of traumatic stress in 5HTTLPR S allele carriers. © 2007 Wiley‐Liss, Inc.
No association between common variants in glyoxalase 1 and autism spectrum disorders
Authors: Rehnström Karola , Ylisaukko‐oja Tero , Vanhala Raija , von Wendt Lennart , Peltonen Leena , Hovatta Iiris
Published: August 2007

The autism spectrum disorders (ASDs) are complex diseases with a strong genetic component. Numerous candidate gene studies have tested association between various functional and positional candidate genes and autism, but no common variation predisposing for autism has been identified to date. It has been previously proposed, that glyoxalase 1 (GLO1) might be involved in the pathogenesis of autism as GLO1 protein polarity was significantly changed in the brains of autism patients compared to controls. GLO1 harbors a functional polymorphism that affects the polarity and the enzymatic activity of the protein. In the same study, this polymorphism showed a suggestive association to autism. To investigate whether common variants in GLO1 predispose to autism in the Finnish population, we have genotyped six polymorphisms in GLO1 in families with more than 230 individuals affected with ASDs and carried out both linkage and association analyses. We did not observe significant linkage or association between any SNP and ASDs. Therefore, we suggest that common variants in GLO1 are not significant susceptibility factors for ASDs in the Finnish population. © 2007 Wiley‐Liss, Inc.
Evidence of normal hearing laterality in familial schizophrenic patients and their relatives
Authors: Toulopoulou Timothea , Chua Siew E. , Lam Isabel , Cheung Vinci , Murray Robin M. , David Anthony S.
Published: August 2007

Dichotic listening (DL) has been used as a tool to investigate possible left cerebral dysfunction in schizophrenia. However, the wide range of DL tests (e.g., words, emotions, sentences) as well as patient groups (“heterogeneity”) has introduced several confounders. Assessing relatives of patients with schizophrenia may overcome some of these problems, and may be more useful in determining if loss of functional cerebral laterality in schizophrenia is a state or a trait phenomenon. The fused consonant‐vowel DL test was administered to 114 subjects: 20 individuals with familial schizophrenia, 42 of their healthy relatives, and 52 healthy volunteers. We did this to investigate whether the normal language processing asymmetry—a right ear advantage (REA)—is present, and whether it could serve as a marker for genetic liability. General performance accuracy level was lower in schizophrenia patients and their relatives but the expected REA was present in all groups. Adjusting for age, accuracy, and obligate status made no difference. In conclusion, familial schizophrenic patients and their relatives have normal REA and hearing laterality on the fused DL test. © 2007 Wiley‐Liss, Inc.
The ADHD resource: Creation of an online tool for attention deficit hyperactivity disorder information and research
Authors: Martin N.C.
Published: August 2007

With the ever growing quantity of information generated by research into attention deficit hyperactivity disorder (ADHD) and the growth of international cooperation and collaboration, a need has arisen for a simple reference resource. The ADHD Resource was created to be this tool. It has been designed to act as the first point of reference for researchers in the field. It has also been created to facilitate the collaborative effects amongst the research groups. © 2007 Wiley‐Liss, Inc.
Behavioral variation and reproductive success of male baboons (Papio anubis × Papio hamadryas) in a hybrid social group
Authors: Bergman Thore J. , Phillips‐Conroy Jane E. , Jolly Clifford J.
Published: August 2007

We take advantage of an array of hybrid baboons (Papio anubis × Papio hamadryas) living in the same social group to explore the causes and consequences of different male mating strategies. Male hamadryas hold one‐male units and exhibit a sustained, intense interest in adult females, regardless of the latter's reproductive state. Anubis baboons, by contrast, live in multi‐male, multi‐female groups where males compete for females only when the latter are estrous. These two taxa interbreed to form a hybrid zone in the Awash National Park, Ethiopia, where previous work has suggested that hybrid males have intermediate and ineffective behavior. Here, we first examine male mating strategies with respect to morphological and genetic measures of ancestry. We found significant relationships between behavioral measures and morphology; males with more hamadryas‐like morphology had more hamadryas‐like behavior. However, genetic ancestry was not related to behavior, and in both cases intermediates displayed a previously unreported level of behavioral variation. Furthermore, male behavior was unrelated to natal group. Second, we evaluated reproductive success by microsatellite‐based paternity testing. The highest reproductive success was found for individuals exhibiting intermediate behaviors. Moreover, over nine years, some genetically and morphologically intermediate males had high reproductive success. We conclude that the behavior of hybrid males is therefore unlikely to be an absolute barrier to admixture in the region. Am. J. Primatol. 70:136–147, 2008. © 2007 Wiley‐Liss, Inc.
RGD domains neuroprotect the immature brain by a glial‐dependent mechanism
Authors: Peluffo Hugo , González Pau , Arís Anna , Acarin Laia , Saura Josep , Villaverde Antoni , Castellano Bernardo , González Berta
Published: August 2007

Objective

Integrin binding to extracellular matrix ligands, including those presenting RGD motifs, modulate diverse cellular processes. In the brain, many endogenous RGD‐containing molecules are induced after damage. Previously, the gene therapy vector termed NLSCt, which displays an RGD motif, was shown to neuroprotect after immature brain excitotoxicity. We analyze whether neuroprotection is mediated by the RGD motif.

Methods

RGD‐containing synthetic peptide GPenGRGDSPCA (GPen) was injected 2 hours after N‐methyl‐D‐aspartate–mediated excitotoxicity to the postnatal day 9 rat brain. Damage and glial/inflammatory response were evaluated 3 days later. In addition, the neuroprotective effect of GPen and NLSCt after N‐methyl‐D‐aspartate–induced cell death was also analyzed in vitro using neuron‐purified and mixed neuron‐glia primary cultures. To further characterize whether the neuroprotective effect was mediated by glial‐derived soluble factors, we also tested the protective ability of conditioned media from RGD‐treated microglia, astrocyte, or mixed glia cultures.

Results

Animals treated with GPen peptide showed functional improvement, a significant reduction in lesion volume up to 28%, and a decrease in the number of degenerating neurons. In addition, N‐methyl‐D‐aspartate–injected animals treated with both RGD‐containing molecules at the neuroprotective doses showed a significant increase in microglial reactivity and microglia/macrophage cell number, but no differences in neutrophil infiltration and the astroglial response. Finally, in vitro studies showed that the neuroprotective effect was observed in mixed neuron‐glia, but not in neuron‐purified cultures. Conditioned media from RGD‐treated microglial, astroglial, and mixed‐glial cultures were not protective.

Interpretation

These results suggest that RGD‐containing molecules neuroprotect by a glial‐dependent mechanism. Ann Neurol 2007
Mirror neuron system: basic findings and clinical applications
Authors: Iacoboni Marco , Mazziotta John C.
Published: August 2007

In primates, ventral premotor and rostral inferior parietal neurons fire during the execution of hand and mouth actions. Some cells (called mirror neurons) also fire when hand and mouth actions are just observed. Mirror neurons provide a simple neural mechanism for understanding the actions of others. In humans, posterior inferior frontal and rostral inferior parietal areas have mirror properties. These human areas are relevant to imitative learning and social behavior. Indeed, the socially isolating condition of autism is associated with a deficit in mirror neuron areas. Strategies inspired by mirror neuron research recently have been used in the treatment of autism and in motor rehabilitation after stroke. Ann Neurol 2007
An intriguing “silent” mutation and a founder effect in antiquitin (ALDH7A1)
Authors: Salomons Gajja S. , Bok Levinus A. , Struys Eduard A. , Pope Lorna Landegge , Darmin Patricia S. , Mills Philippa B. , Clayton Peter T. , Willemsen Michèl A. , Jakobs Cornelis
Published: August 2007

Recently, α‐aminoadipic semialdehyde (α‐AASA) dehydrogenase deficiency was shown to cause pyridoxine‐dependent epilepsy in a considerable number of patients. α‐AASA dehydrogenase deficiency is an autosomal recessive disorder characterized by a neonatal‐onset epileptic encephalopathy in which seizures are resistant to antiepileptic drugs but respond immediately to the administration of pyridoxine (OMIM 266100). Increased plasma and urinary levels of α‐AASA are associated with pathogenic mutations in the α‐AASA dehydrogenase (ALDH7A1/antiquitin) gene. Here, we report an intriguing “silent” mutation in ALDH7A1, a novel missense mutation and a founder mutation in a Dutch cohort (10 patients) with α‐AASA dehydrogenase deficiency. Ann Neurol 2007
Twinkle helicase (PEO1) gene mutation causes mitochondrial DNA depletion
Authors: Sarzi Emmanuelle , Goffart Steffi , Serre Valérie , Chrétien Dominique , Slama Abdelhamid , Munnich Arnold , Spelbrink Johannes N. , Rötig Agnès
Published: August 2007

Objective

Mitochondrial DNA (mtDNA) depletion syndrome (MDS) is a clinically and genetically heterogeneous group of autosomal recessive diseases characterized by a reduction in mtDNA copy number. Several nuclear genes have been shown to account for these severe oxidative phosphorylation disorders, but the disease‐causing mutations remain largely unknown.

Methods

By virtue of homozygosity mapping, we tested candidate genes involved in mtDNA maintenance in patients born to consanguineous parents.

Results

We found homozygosity for microsatellite markers flanking the PEO1 gene, encoding the mitochondrial Twinkle helicase, in two sibs presenting a hepatocerebral form of MDS. Sequencing the PEO1 gene showed a homozygous mutation at a conserved position of the protein in the two patients (T457I). The modeling of the Twinkle protein showed that T457 is located in the interface between two monomers of the hexameric enzyme. Finally, using purified recombinant protein, we demonstrated that the T457I mutant Twinkle has a defective helicase activity.

Interpretation

Although dominant Twinkle mutations have been previously reported in patients with autosomal dominant progressive external ophthalmoplegia and multiple mtDNA deletions, we report here the first recessive Twinkle mutation in patients with hepatocerebral form of MDS. Identifying other Twinkle mutations in MDS and/or autosomal dominant progressive external ophthalmoplegia and studying their impact on the isolated proteins should help in understanding why some mutations are recessive and others are dominant. Ann Neurol 2007
Gen‐Stummschaltung durch doppelsträngige RNA (Nobel‐Vortrag)
Authors: Fire Andrew Z.
Published: August 2007

Ich danke der Nobelversammlung des Karolinska‐Instituts für die Gelegenheit, einige neuere Arbeiten zur RNA‐aktivierten Gen‐Stummschaltung vorstellen zu können. Eines muss ich aber vorausschicken: Die gesamte Geschichte der Gen‐Stummschaltung zu erzählen, wäre ein gigantisches Unternehmen, das den Rahmen dieses Vortrags weit übersteigen würde. Es wird daher nicht zu vermeiden sein, dass ich die Geschichte mehr als nur ein bisschen verkürze. Des Weiteren befinden sich unsere Kenntnisse der Gen‐Stummschaltung noch in den Anfängen, weshalb Sie den Vortrag nur als Einführung in das Thema betrachten sollten – so gut es eben geht an diesem 8. Dezember 2006. Als drittes sollten Sie wissen, dass die Geschichte, die ich erzählen werde, die Arbeiten mehrerer Generationen von Biologen und Chemikern (und sämtlichen Schattierungen dazwischen) zusammenfasst. Ich bin geschmeichelt, dass Arbeiten meiner Forschungsgruppe zu diesem Feld beitragen konnten und dazu geführt haben, dass ich nun hier über diese Entwicklungen berichten darf. Gleichzeitig hoffe ich, dass man unsere bescheidenen Beiträge nicht mit den sehr viel größeren Errungenschaften der RNAi‐Forschungen gleichsetzt.
Gene Silencing by Double‐Stranded RNA (Nobel Lecture)
Authors: Fire Andrew Z.
Published: August 2007

I would like to thank the Nobel Assembly of the Karolinska Institute for the opportunity to describe some recent work on RNA‐triggered gene silencing. First a few disclaimers, however. Telling the full story of gene silencing would be a mammoth enterprise that would take me many years to write and would take you well into the night to read. So we'll need to abbreviate the story more than a little. Second (and as you will see) we are only in the dawn of our knowledge; so consider the following to be primer …︁ the best we could do as of December 8th 2006. And third, please understand that the story that I am telling represents the work of several generations of biologists, chemists, and many shades in between. I'm pleased and proud that work from my laboratory has contributed to the field, and that this has led to my being chosen as one of the messengers to relay the story in this forum. At the same time, I hope that there will be no confusion of equating our modest contributions with those of the much grander RNAi enterprise.
Generalization of the effects of solvent–polymer interactions with linear multiparameter equations
Authors: Makitra R. G. , Yevchuk I. Y. , Musiy R. Y. , Prystansky R. E. , Zaikov G. E.
Published: August 2007

A quantitative generalization of the indices of swelling process of polymers, containing the nonhydrocarbon groups (polyurethanes, fluoropolymers) in organic solvents, as well as of the process of dissolution of poly(methy1 methacrylate) was successfully realized by means of multiparametric equations, which take into account the solvents capacity for specific and nonspecific solvation of polymers and solvents' molar volumes. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 2007
Preparation of hydroxyapatite/poly(vinyl alcohol) composite fibers by wet spinning and their characterization
Authors: Chung Yong Sik , Kang Sung Il , Kwon Oh Wook , Shin Dong Soo , Lee Se Geun , Shin Eun Joo , Min Byung Gil , Bae Han Jo , Han Sung Soo , Jeon Han Yong , Noh Seok Kyun , Lyoo Won Seok
Published: August 2007

To prepare hydroxyapatite (HA)/poly(vinyl alcohol) (PVA) composite fibers with high processibility applicable to various biomedical fields, HA/PVA composite powders were synthesized through a coprecipitation method and then mixed with pure PVA in dimethyl sulfoxide at 90°C for 2 h to prepare wet‐spinning dopes. HA/PVA solutions with HA contents of 0, 1, 3, 5, 10, and 15 wt % were analyzed with a rheometer to elucidate the effect of HA particles on the shear viscosities of the spinning dopes. The spinning dopes with pure PVA and an HA/PVA concentration of 12 wt % showed non‐Newtonian flow behaviors, and as the HA content increased from 1 to 15 wt %, the shear viscosities increased simultaneously because of the complex formation between PVA chains, citric acid, and HA particles acting as crosslinkers. The increased viscosities of the spinning dopes diminished the breakage of PVA fibers and enhanced the spinnability. Through the addition of citric acid interacting with both PVA and HA particles, the aggregation of HA particles was suppressed, and it was possible to prepare HA/PVA composite fibers with smooth surfaces. An adequate amount of HA in the PVA fibers improved the thermal and mechanical properties of the fibers because uniformly dispersed HA particles interacting with PVA chains through hydrogen bonding in the PVA matrix complemented the structural defects. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 2007
Improvement of the water resistance of atactic poly(vinyl alcohol) nanowebs by a heat treatment
Authors: Lee Sung Jun , Lee Se Geun , Kim Hoyoung , Lyoo Won Seok
Published: August 2007

Nanoscale materials can be rationally designed to exhibit significantly changed physical, chemical, and biological properties because of the extremely small dimensions. Therefore, atactic poly(vinyl alcohol) (a‐PVA) nanowebs by an electrospinning technique have very high water solubility because of their nanoscale in comparison with microscale materials such as fibers and films. In this study, a‐PVA nanowebs were prepared via electrospinning under suitable conditions to form PVA webs with uniform nanofibers (fiber average diameter = 200 ± 50 nm), not a bead or bead‐and‐string morphology. Furthermore, to improve the water resistance of the water‐soluble a‐PVA nanowebs, the PVA nanowebs were heat‐treated at various heat‐treatment temperatures. The melting temperature of the heat‐treated PVA nanowebs shifted toward a lower temperature with an increase in the heat‐treatment temperature, and this indicated that micronetwork domains formed. Moreover, with the exception of a PVA nanoweb treated at an excessive heat‐treatment temperature, the heat‐treated PVA nanowebs showed higher crystalline and mechanical properties than a pure PVA nanoweb. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 2007