bluuebunny/crossref_metadata_2025_split huggingface dataset:
Developing and implementing future stroke therapies: The potential of telemedicine
Authors: Fisher Marc 
Published: October 2005

AbstractStroke is a major public health concern with few positive phase III clinical trials and a shortage of stroke care expertise. Drug development likely can be enhanced by adapting new outcome measures and following guidelines generated by consensus groups. To enhance rates of drug implementation and to improve stroke care, some states are requiring that acute care hospitals obtain primary stroke center certification, and this mandate necessitates that smaller hospitals join larger ones in stroke care networks. Cutting‐edge technology in the form of telemedicine is being implemented in stroke care networks to combat the lack of stroke care expertise by extending the availability of physician stroke expertise. The telemedicine network can be used to transmit real‐time data from stroke care–certified community hospitals (spokes) to a tertiary center (hub). Telemedicine can be used to educate physicians in spoke hospitals about new stroke treatments. The advent and development of telemedicine has the potential to ensure that patients with stroke have a greater opportunity to receive the full range of therapeutic options currently available and those that will become available in the future. The implementation of future drug therapies through telemedicine‐organized stroke networks will likely substantially influence the future of acute stroke therapy. Ann Neurol 2005;58:666–671
DJ‐1 mutations and parkinsonism‐dementia‐amyotrophic lateral sclerosis complex
Authors: Annesi Grazia , Savettieri Giovanni , Pugliese Pierfrancesco , D'Amelio Marco , Tarantino Patrizia , Ragonese Paolo , La Bella Vincenzo , Piccoli Tommaso , Civitelli Donatella , Annesi Ferdinanda , Fierro Brigida , Piccoli Federico , Arabia Gennarina , Caracciolo Manuela , Cirò Candiano Innocenza Claudia , Quattrone Aldo 
Published: October 2005

AbstractDJ‐1 gene mutations have been found to cause early‐onset Parkinson's disease. We report a family from southern Italy with three brothers affected by early‐onset parkinsonism, dementia, and amyotrophic lateral sclerosis. Molecular analysis of the DJ‐1 gene in two living patients showed a novel homozygous mutation in exon 7 (E163K) and a new homozygous mutation (g.168_185dup) in the promoter region of the gene. Both mutations cosegregated with the disease and were detected in a heterozygous state in the patients' mother and their healthy siblings. Our findings expand the spectrum of clinical presentations associated with mutations in DJ‐1 gene. Ann Neurol 2005;58:803–807
Phenotypic heterogeneity within a new family with the MAPT p301s mutation
Authors: Yasuda Minoru , Nakamura Yoshitsugu , Kawamata Toshio , Kaneyuki Hiroshi , Maeda Kiyoshi , Komure Osamu 
Published: October 2005

AbstractMutations in the gene encoding the microtubule‐associated protein tau (MAPT) cause frontotemporal dementia and parkinsonism linked to chromosome 17. Clinical variability is seen not only among families with different mutations, but also among family members with the same mutation. We investigated a newly identified familial frontotemporal dementia and parkinsonism family. The disease was of early onset and was inherited as an autosomal dominant trait. Clinically, parkinsonism was the prominent and often early feature, and it preceded dementia. Three autopsied cases shared involvement predominantly in the frontal and temporal lobes and also in the subcortical nuclei, including substantia nigra, globus pallidus, and subthalamic nucleus, that microscopically consisted of neuronal loss, microvacuolation, and astrocytic fibrosis. Immunohistochemistry demonstrated neuropil threads, ballooned cells, and glial fibrillary tangles. Sequencing analysis of the MAPT gene showed an alteration in one allele, resulting in a P301S substitution. These findings suggest that the MAPT P301S mutation can cause pathologically subcortical‐predominant, neuropil thread‐rich, tau‐containing lesions, which could result in consistent parkinsonism. Our study confirms the notion that the phenotype observed in affected individuals from P301S MAPT mutation families is heterogeneous and is broader than the phenotypes seen to date in affected family members carrying other MAPT mutations. Ann Neurol 2005
The role of the ND5 gene in LHON: Characterization of a new, heteroplasmic LHON mutation
Authors: Mayorov Vladimir , Biousse Valerie , Newman Nancy J. , Brown Michael D. 
Published: October 2005

AbstractLeber's hereditary optic neuropathy (LHON) causes central vision loss from bilateral optic neuropathy. Although 13 mitochondrial DNA (mtDNA) mutations are strongly associated with LHON, only three account for roughly 90% of cases and thus are found in multiple independent LHON families. The remaining LHON mutations are rare. Here, we describe the clinical and genetic characterization of a new LHON mtDNA mutation. The 12848T mutation alters a highly conserved amino acid in the ND5 complex I gene, is not found in controls, and is heteroplasmic. Despite ND5 being the largest of the mtDNA complex I genes, ND5 mutations are quite rare in LHON. Ann Neurol 2005;58:807–811
OPA1 R445H mutation in optic atrophy associated with sensorineural deafness
Authors: Amati‐Bonneau Patrizia , Guichet Agnès , Olichon Aurélien , Chevrollier Arnaud , Viala Frédérique , Miot Stéphanie , Ayuso Carmen , Odent Sylvie , Arrouet Catherine , Verny Christophe , Calmels Marie‐Noelle , Simard Gilles , Belenguer Pascale , Wang Jing , Puel Jean‐Luc , Hamel Christian , Malthièry Yves , Bonneau Dominique , Lenaers Guy , Reynier Pascal 
Published: October 2005

AbstractThe heterozygous R445H mutation in OPA1 was found in five patients with optic atrophy and deafness. Audiometry suggested that the sensorineural deafness resulted from auditory neuropathy. Skin fibroblasts showed hyperfragmentation of the mitochondrial network, decreased mitochondrial membrane potential, and adenosine triphosphate synthesis defect. In addition, OPA1 was found to be widely expressed in the sensory and neural cochlear cells of the guinea pig. Thus, optic atrophy and deafness may be related to energy defects due to a fragmented mitochondrial network. Ann Neurol 2005
Multiple sclerosis in twins from continental Italy and Sardinia: A nationwide study
Authors: Ristori Giovanni , Cannoni Stefania , Stazi Maria Antonietta , Vanacore Nicola , Cotichini Rodolfo , Alfò Marco , Pugliatti Maura , Sotgiu Stefano , Solaro Claudio , Bomprezzi Roberto , Di Giovanni Simone , Figà Talamanca Lorenzo , Nisticò Lorenza , Fagnani Corrado , Neale Michael C. , Cascino Isabella , Giorgi Gabriele , Battaglia Mario A. , Buttinelli Carla , Tosi Roberto , Salvetti Marco ,   Italian Study Group on Multiple Sclerosis in Twins
Published: October 2005

AbstractKnowledge about the balance between heritable and nonheritable risk in multiple sclerosis (MS) is based on twin studies in high‐prevalence areas. In a study that avoided ascertainment limitations and directly compared continental Italy (medium‐prevalence) and Sardinia (high‐prevalence), we ascertained 216 pairs from 34,549 patients. This gives a twinning rate of 0.62% among MS patients, significantly less than that of the general population. In continental Italy, probandwise concordance was 14.5% (95% confidence interval, 5.1–23.8) for monozygotic and 4.0% (95% confidence interval, 0.8–7.1) for dizygotic twins. Results in Sardinia resemble those in northern populations but in limited numbers. Monozygotic concordance was 22.2% (95% confidence interval, 0–49.3) probandwise, but no concordant dizygotic pairs were identified. A questionnaire on 80 items possibly related to disease cause was administered to 70 twin pairs, 135 sporadic patients, and 135 healthy volunteers. Variables positively (7) or negatively (2) associated with predisposition and concordance in twins largely overlapped and were mainly linked to infection. If compared with previous studies, our data demonstrate that penetrance in twins appears to correlate with MS prevalence. They highlight the relevance of nonheritable variables in Mediterranean areas. The apparent underrepresentation of MS among Italian twins draws attention to protective factors, shared by twins, that may influence susceptibility. Ann Neurol 2005
Status epilepticus in mice deficient for succinate semialdehyde dehydrogenase: GABAAreceptor–mediated mechanisms
Authors: Wu Ying , Buzzi Andrea , Frantseva Marina , Velazquez Jose Perez L. , Cortez Miguel , Liu Chunche , Shen Liqing , Gibson K. Michael , Snead O. Carter 
Published: October 2005

AbstractThe epilepsy that occurs in SSADH deficiency has a seizure phenotype similar to that occurring in the SSADH−/−mouse. We examined the expression and function of the GABAAreceptor (GABAAR) in SSADH‐deficient mice. A selective decrease in binding of [35S]tert‐butylbicyclophosphorothionate was observed in SSADH−/−mice at postnatal day 7 that was progressive until the third postnatal week of life when, at the nadir of the decreased [35S]tert‐butylbicyclophosphorothionate binding, generalized convulsive seizures emerged that rapidly evolved into status epilepticus. We also observed a substantial downregulation of the β2subunit of GABAAR, a reduction in GABAA‐mediated inhibitory postsynaptic potentials, and augmented postsynaptic population spikes recorded from hippocampal slices. The SSADH−/−mouse model represents a powerful investigative tool for understanding the pathophysiology of the seizures associated with human SSADH deficiency. These data raise the possibility that progressive dysfunction of the GABAAR may be involved in the development of seizures in SSDAH‐deficient mice. Elucidation of the precise fundamental mechanisms of the perturbation of the GABAAR‐mediated function in SSADH−/−mice could lead to the development of novel treatment modalities designed to reduce the neurological morbidity in children with SSADH deficiency. Ann Neurol 2005
Shikimic acid production by a modified strain of E. coli (W3110.shik1) under phosphate‐limited and carbon‐limited conditions
Authors: Johansson Louise , Lindskog Anna , Silfversparre Gustav , Cimander Christian , Nielsen Kristian Fog , Lidén Gunnar 
Published: October 2005

AbstractShikimic acid is one of several industrially interesting chiral starting materials formed in the aromatic amino acid pathway of plants and microorganisms. In this study, the physiology of a shikimic acid producing strain of Escherichia coli (derived from W3110) deleted in aroL (shikimic acid kinase II gene), was compared to that of a corresponding control strain (W3110) under carbon‐ and phosphate‐limited conditions. For the shikimic acid producing strain (referred to as W3110.shik1), phosphate limitation resulted in a higher yield of shikimic acid (0.059 ± 0.012 vs. 0.024 ± 0.005 c‐mol/c‐mol) and a lower yield of by‐products from the shikimate pathway, when compared to carbon‐limited condition. The yield of the by‐product 3‐dehydroshikimic acid (DHS) decreased from 0.076 ± 0.028 to 0.022 ± 0.001 c‐mol/c‐mol. Several other by‐products were only detected under carbon‐limited conditions. The latter group included 3‐dehydroquinic acid (0.021 ± 0.021 c‐mol/c‐mol), quinic acid (0.012 ± 0.005 c‐mol/c‐mol), and gallic acid (0.002 ± 0.001 c‐mol/c‐mol). For both strains, more acetate was produced under phosphate than the carbon‐limited case. Considerable cell lysis was found for both strains but was higher for W3110.shik1, and increased for both strains under phosphate limitation. The advantages of the latter condition in terms of an increased shikimic acid yield was thus counteracted by an increased cell lysis, which may make downstream processing more difficult. © 2005 Wiley Periodicals, inc.
Effects of terpenoid precursor feeding on Catharanthus roseus hairy roots over‐expressing the alpha or the alpha and beta subunits of anthranilate synthase
Authors: Peebles Christie A.M. , Hong Seung‐Beom , Gibson Susan I. , Shanks Jacqueline V. , San Ka‐Yiu 
Published: October 2005

AbstractAmong the pharmacologically important terpenoid indole alkaloids produced by Catharanthus roseus are the anti‐cancer drugs vinblastine and vincristine. These two drugs are produced in small yields within the plant, which makes them expensive to produce commercially. Metabolic engineering has focused on increasing flux through this pathway by various means such as elicitation, precursor feeding, and introduction of genes encoding specific metabolic enzymes into the plant. Recently in our lab, a feedback‐resistant anthranilate synthase α subunit was over‐expressed in C. roseus hairy roots under the control of a glucocorticoid inducible promoter system. Upon induction we observed a large increase in the indole precursors, tryptophan, and tryptamine. The current work explores the effects of over‐expressing the anthranilate synthase α or α and β subunits in combination with feeding with the terpenoid precursors 1‐deoxy‐D‐xylulose, loganin, and secologanin. In feeding 1‐deoxy‐D‐xylulose to the hairy root line expressing the anthranilate synthase α subunit, we observed an increase of 125% in hörhammericine levels in the induced samples, while loganin feeding increased catharanthine by 45% in the induced samples. Loganin feeding to the hairy root line expressing anthranilate synthase α and β subunits increases catharanthine by 26%, ajmalicine by 84%, lochnericine by 119%, and tabersonine by 225% in the induced samples. These results suggest that the terpenoid precursors to the terpenoid indole alkaloids are important factors in terpenoid indole alkaloid production. © 2005 Wiley Periodicals, inc.
A new approach for modelling simultaneous storage and growth processes for activated sludge systems under aerobic conditions
Authors: Sin Gürkan , Guisasola Albert , De Pauw Dirk J. W. , Baeza Juan A. , Carrera Julián , Vanrolleghem Peter A. 
Published: October 2005

AbstractBy critically evaluating previous models, a new mechanistic model is developed to describe simultaneous storage and growth processes occurring in activated sludge systems under aerobic conditions. Identifiability was considered an important criterion during the model development since it among others helps to increase the realiability and applicability of models to full‐scale WWTPs. A second order model was proposed for description of the degradation of the storage products under famine conditions. The model is successfully calibrated by only using OUR data obtained from batch experiments. Calibrations were performed with biomass from full‐scale WWTPs in Belgium and Spain. Predictions of the calibrated model were successfully confirmed using off‐line PHB measurements, supporting the validity of the model. An iterative experimental design procedure was successfully applied and found to remarkably improve the parameter estimation accuracy for the growth on storage parameters K1 and K2, which used to have large confidence intervals when using standard experiments. The estimated biomass growth yield on substrate (0.58 mgCOD/mgCOD) is quite close to the theoretically expected range for heterotrophic growth. This became possible by properly accounting for the storage process. Moreover, the maximum growth rate was predicted in the range 0.7–1.3 per day. This range, albeit quite lower than the values reported for the growth‐based ASM models, is believed to be more realistic. Finally, the new model is expected to better and more mechanistically describe simultaneous storage and growth activities of activated sludge systems and as such could contribute to improved design, operation and control of those systems. © 2005 Wiley Periodicals, inc.
Cloning of deoxynucleoside monophosphate kinase genes and biosynthesis of deoxynucleoside diphosphates
Authors: Bao Jie , Ryu Dewey D.Y. 
Published: October 2005

AbstractThe genes encoding four deoxynucleoside monophosphate kinase (dNMP kinase) enzymes, including ADK1 for deoxyadenylate monophosphate kinase (AK), GUK1 for deoxyguanylate monophosphate kinase (GK), URA6 for deoxycytidylate monophosphate kinase (CK), and CDC8 for deoxythymidylate monophosphate kinase (TK), were isolated from the genome of Saccharomyces cerevisiae ATCC 2610 strain and cloned into E. coli strain BL21(DE3). Four recombinant plasmids, pET17b‐JB1 containing ADK1, pET17b‐JB2 containing GUK1, pET17b‐JB3 containing URA6, and pET17b‐JB4 containing CDC8, were constructed and transformed into E. coli strain for over‐expression of AK, GK, CK, and TK. The amino acid sequences of these enzymes were analyzed and a putative conserved peptide sequence for the ATP active site was proposed. The four deoxynucleoside diphosphates (dNDP) including deoxyadenosine diphosphate (dADP), deoxyguanosine diphosphate (dGDP), deoxycytidine diphosphate (dCDP), and deoxythymidine diphosphate (dTDP), were synthesized from the corresponding deoxynucleoside monophosphates (dNMP) using the purified AK, GK, CK, and TK, respectively. The effects of pH and magnesium ion concentration on the dNDP biosynthesis were found to be important. A kinetic model for the synthetic reactions of dNDP was developed based on the Bi–Bi random rapid equilibrium mechanism. The kinetic parameters including the maximum reaction velocity and Michaelis–Menten constants were experimentally determined. The study on dNDP biosynthesis reported in this article are important to the proposed bioprocess for production of deoxynucleoside triphosphates (dNTP) that are used as precursors for in vitro DNA synthesis. There is a significant advantage of using enzymatic biosyntheses of dNDP as compared to the chemical method that has been in commercial use. © 2005 Wiley Periodicals, inc.
Meta-analysis of trials comparing ximelagatran with low molecular weight heparin for prevention of venous thromboembolism after major orthopaedic surgery
Authors: Cohen A T , Hirst C , Sherrill B , Holmes P , Fidan D 
Published: October 2005

AbstractBackgroundUse of low molecular weight heparin (LMWH) is standard practice for preventing postoperative venous thromboembolism (VTE). Ximelagatran is a new direct thrombin inhibitor for this indication.MethodsA systematic review was conducted to compare the efficacy and safety of LMWH with ximelagatran in orthopaedic surgery.ResultsSix eligible, well conducted clinical trials (10 051 patients) were identified. Overall, the risk of VTE (OR (odds ratio) 1·22 (95 per cent confidence interval (c.i.) 0·89 to 1·67)) and serious bleeding (OR 0·70 (95 per cent c.i. 0·42 to 1·18)) was not significantly different for LMWH compared with ximelagatran. Exploratory analyses to investigate statistical heterogeneity found that results varied by surgical subtype and treatment regimen. Compared with postoperative ximelagatran, LMWH had a significantly lower rate of VTE (OR 0·68 (95 per cent c.i. 0·56 to 0·82); P &lt; 0·001), with no significant difference in bleeding rate (OR 1·09 (95 per cent c.i. 0·62 to 1·94); P = 0·76), in hip surgery, and no significant differences in knee surgery. When ximelagatran was started immediately before surgery, LMWH had a significantly higher rate of VTE in both hip (OR 1·87 (95 per cent c.i. 1·20 to 2·92); P = 0·006) and knee (OR 1·49 (95 per cent c.i. 1·14 to 1·93); P = 0·003) surgery, but less bleeding: hip OR 0·30 (95 per cent c.i. 0·17 to 0·53; P &lt; 0·001); knee OR 0·71 (95 per cent c.i. 0·30 to 1·67; P = 0·43).ConclusionThis review demonstrated no overall advantage for either LMWH or ximelagatran in thromboprophylaxis following orthopaedic surgery. Benefits in VTE prevention with ximelagatran were gained at the expense of an increased risk of serious bleeding.
Parathyroid carcinoma
Authors: Rawat N , Khetan N , Williams D W , Baxter J N 
Published: October 2005

Abstract

Background
Parathyroid carcinoma is a rare malignancy affecting 0·5–5 per cent of all patients with primary hyperparathyroidism. This article reviews the literature on the pathogenesis, pathology, clinical features, diagnosis and management of parathyroid carcinoma.

Methods
A Medline search was performed and all relevant English language articles published between 1970 and 2005 were retrieved. The search words included ‘parathyroid carcinoma’, ‘pathology’, ‘genetics’, ‘management’ and ‘radiotherapy’. Secondary references were obtained from key articles.

Results and conclusion
The exact aetiology of parathyroid carcinoma remains obscure. Recently, the HRPT2 gene has been implicated in its pathogenesis and may prove to be a genetic target in future. Surgical resection is the accepted ‘gold standard’. There is now a growing consensus on the use of adjuvant radiotherapy as it has been shown to provide a survival benefit.
Binding of Acetylcholinesterase to Multiwall Carbon Nanotube‐Cross‐Linked Chitosan Composite for Flow‐Injection Amperometric Detection of an Organophosphorous Insecticide
Authors: Kandimalla Vivek Babu , Ju Huangxian 
Published: October 2005

AbstractA novel method for immobilization of acetylcholinesterase (AChE) by binding covalently to a cross‐linked chitosan–multiwall carbon nanotube (MWNT) composite is described. In addition a sensitive, fast, cheap and automatizable flow injection detection of an organophosphorous insecticide was developed. The MWNTs were homogeneously distributed in the chitosan membrane which showed a homogeneous porous structure. The immobilized AChE could catalyze the hydrolysis of acetylthiocholine with a ${K{{{\rm app}\hfill \atop {\rm M}\hfill}}}$ value of 177 μM to form thiocholine, which was then oxidized to produce detectable signal in a linear range of 1.0–500 μM and fast response. MWNTs could catalyze the electrooxidation of thiocholine, thus increasing detection sensitivity. Based on the inhibition of an organophosphorous insecticide on the enzymatic activity of AChE, using Sulfotep as a model compound, the conditions for the flow‐injection detection of the insecticide were optimized. Both biocompatibility of chitosan and inherent conductive properties of MWNTs favored the detection of the insecticide from 1.5 to 80 μM along with good stability and reproducibility. 95 % reactivation from inhibited AChE could be regenerated by using 2‐pyridinealdoxime methiodide within 15 min for 15 times. The detection of Sulfotep samples exhibited satisfactory results. The proposed flow‐injection analysis device can be applied to automated determination and characterization of enzyme inhibitors.
Enantioselective Epoxidation of Terminal Alkenes to (R)‐ and (S)‐Epoxides by Engineered Cytochromes P450 BM‐3
Authors: Kubo Takafumi , Peters Matthew W. , Meinhold Peter , Arnold Frances H. 
Published: October 2005

AbstractCytochrome P450 BM‐3 from Bacillus megaterium was engineered for enantioselective epoxidation of simple terminal alkenes. Screening saturation mutagenesis libraries, in which mutations were introduced in the active site of an engineered P450, followed by recombination of beneficial mutations generated two P450 BM‐3 variants that convert a range of terminal alkenes to either (R)‐ or (S)‐epoxide (up to 83 % ee) with high catalytic turnovers (up to 1370) and high epoxidation selectivities (up to 95 %). A biocatalytic system using E. coli lysates containing P450 variants as the epoxidation catalysts and in vitro NADPH regeneration by the alcohol dehydrogenase from Thermoanaerobium brockii generates each of the epoxide enantiomers, without additional cofactor.