bluuebunny/crossref_metadata_2025 huggingface dataset:
High-resolution kinetics of herbivore-induced plant volatile transfer reveal clocked response patterns in neighboring plants
Authors: Waterman Jamie Mitchel , Cofer Tristan Michael , Wang Lei , Glauser Gaetan , Erb Matthias
Published: February 2024

Volatiles emitted by herbivore-attacked plants (senders) can enhance defenses in neighboring plants (receivers), however, the temporal dynamics of this phenomenon remain poorly studied. Using a custom-built, high-throughput proton transfer reaction time-of-flight mass spectrometry (PTR-ToF-MS) system, we explored temporal patterns of volatile transfer and responses between herbivore-attacked and undamaged maize plants. We found that continuous exposure to natural blends of herbivore-induced volatiles results in clocked temporal response patterns in neighboring plants, characterized by an induced terpene burst at the onset of the second day of exposure. This delayed burst is not explained by terpene accumulation during the night, but coincides with delayed jasmonate accumulation in receiver plants. The delayed burst occurs independent of day:night light transitions and cannot be fully explained by sender volatile dynamics. Instead, it is the result of a stress memory from volatile exposure during the first day and secondary exposure to bioactive volatiles on the second day. Our study reveals that prolonged exposure to natural blends of stress-induced volatiles results in a response that integrates priming and direct induction into a distinct and predictable temporal response pattern. This provides an answer to the long-standing question of whether stress volatiles predominantly induce or prime plant defenses in neighboring plants, by revealing that they can do both in sequence.
The catalytic mechanism of the RNA methyltransferase METTL3
Authors: Corbeski Ivan , Vargas-Rosales Pablo Andrés , Bedi Rajiv Kumar , Deng Jiahua , Coelho Dylan , Braud Emmanuelle , Iannazzo Laura , Li Yaozong , Huang Danzhi , Ethève-Quelquejeu Mélanie , Cui Qiang , Caflisch Amedeo
Published: February 2024

The complex of methyltransferase-like proteins 3 and 14 (METTL3-14) is the major enzyme that deposits N
6
-methyladenosine (m
6
A) modifications on mRNA in humans. METTL3-14 plays key roles in various biological processes through its methyltransferase (MTase) activity. However, little is known about its substrate recognition and methyl transfer mechanism from its cofactor and methyl donor S-adenosylmethionine (SAM). Here, we study the MTase mechanism of METTL3-14 by a combined experimental and multiscale simulation approach using bisubstrate analogues (BAs), conjugates of a SAM-like moiety connected to the N
6
-atom of adenosine. Molecular dynamics simulations based on crystal structures of METTL3-14 with BAs suggest that the Y406 side chain of METTL3 is involved in the recruitment of adenosine and release of m
6
A. A crystal structure with a bisubstrate analogue representing the transition state of methyl transfer shows a direct involvement of the METTL3 side chains E481 and K513 in adenosine binding which is supported by mutational analysis. Quantum mechanics/molecular mechanics (QM/MM) free energy calculations indicate that methyl transfer occurs without prior deprotonation of adenosine-N
6
. Furthermore, the QM/MM calculations provide further support for the role of electrostatic contributions of E481 and K513 to catalysis. The multidisciplinary approach used here sheds light on the (co)substrate binding mechanism, catalytic step, and (co)product release catalysed by METTL3, and suggests that the latter step is rate-limiting. The atomistic information on the substrate binding and methyl transfer reaction of METTL3 can be useful for understanding the mechanisms of other RNA MTases and for the design of transition state analogues as their inhibitors.A combined structural, biochemical, and computational approach reveals two distinct binding conformations of adenosine, the transition state of methyl transfer, and the catalytic mechanism of the human m
6
A RNA methyltransferase METTL3-14.
Antimicrobial Activities of Polysaccharides Isolated from Some Plant Seeds
Authors: Moharib Sorial A. , Adly Rimon S.
Published: February 2024

The present investigation is about the measurement of antimicrobial activity (AMA) of polysaccharides isolated from the seeds of pumpkin (Cucurbita pepo), purslane (Portulaca oleracea), safflower (Carthamu stinctorius),coriander (Coriandrum sativum) and rapeseed (Brassica napus) against Staphylococcus aureus (S.aureus), Escherichia coli (E.coli), Bacillus subtilis (B.subtilis) and (MRSA) at different concentrations using agar diffusion method In vitro. Polysaccharides (PSs) were extracted, isolated and purified from different seeds separately. Paper chromatographic analysis of the purified PSs, revealed the presence of different percentages of monosaccharides constituents per each seed PS. In vitro study was performed to evaluate the obtained PSs activities against 4 microbial strains (S. aureus, E. coli, B subtilis and MRSA) using agar diffusion method. PSs showed AMA against S. aureus and E. coli more than that of B subtilis and MRSA at 10% concentration and inhibition zones were estimated. Minimal inhibitory concentrations (MIC) of PSs against S. aureus, E. coli, B subtilis and MRS were found in the range of 1-5 mg/ml. The result demonstrates the killing effect of PSs against S. aureus, E. coli, B subtilis and MRSA at 10% PS within 24 hours. Inhibition zone diameters exhibited different levels of decreases with the PSs concentrations decreases against S. aureus, E. coli, B. subtilis and MRSA. Inhibition effects of PSs against different microbial strains were found to be depending on PSs concentration. However, the lowest concentration of PSs produced lower inhibitory activity against S. aureus B. subtilis E. coli and MRSA. The results obtained with all PSs showed best AMA against S. aureus and E. coli than the other two microbial strains used in the present study. Results indicated these PSs have AMA against Gram-positive and Gram-negative bacterium at 10% concentration. The common PSs consider important sources of antimicrobial agents with minimal inhibitory concentrations of 100-500µg/ml for treatment some infectious diseases.
Studies on Graded Levels of NPK on Growth and Yield of Parthenocarpic Cucumber (Cucumis sativus L.) under Naturally Ventilated Polyhouse Condition
Authors: Chavan B. R.  , Puri A. N  , Kalalbandi B. M.  , Tribhuwan A. R  , Ighare O. A
Published: February 2024

The present study highlights on graded levels of NPK on growth and yield of parthenocarpic cucumber (Cucumis sativus L.) under naturally ventilated polyhouse condition. The graded level of NPK applied in parthenocarpic Cucumber (Cucumis sativus L.) under naturally ventilated polyhouse condition. The results in nutshell indicated that the growth, yield, quality, nutrient availability, nutrient uptake were significantly influenced by application of 125% NPK RDF of cucumber crop. The growth parameters viz., plant height 74.44, 99.18, 131, 153 and 194.58 cm at 30 DAT, 45 DAT, 60 DAT, 75 DAT and 90 DAT, Number of primary branches 8.24, 10.96, 15.40, 17.60 and 20.02 at 30 DAT, 45 DAT, 60 DAT, 75 DAT and 90 DAT,  leaf area 163, 242.33, 307, 387.33 and 492.33 cm2 30 DAT, 45 DAT, 60 DAT, 75 DAT and 90 DAT, internodal distance, fruit length, fruit weight, fruit diameter, dry matter content, chlorophyll – a, chlorophyll – b and total chlorophyll content, number of leaves significantly increased with application of 125 % RDF with 7 days of intervals. Significantly higher number of fruits plant-1, number of primary branches, fruit yield plot-1, Leaf area and fruit yield ha-1, with application of 125 % RDF with 7 days of intervals. The improvement in quality parameters were recorded with application of 125 % RDF with 7 days of intervals. followed by treatments T6, T7, (100 % RDF with 2 and 7 days of intervals upto 90 DAT) and T8 (125% of RDF 2 days of interval up to 90 DAT).
A Study on the Attitude, Abuse and Addiction to Tramadol among Sudanese University Students in Khartoum State, Sudan
Authors: Ismail Mohamed I.A. , Almardi Mohammed O.J. , Jabir Mohammed M.A. , Brair Sara Lavinia , Bashir Intisar. A. , Abdalla Moneer A. , Hammad Almoeiz Y.
Published: February 2024

Aim: This research was designed to study addiction to the drug Tramadol among university students in Khartoum State.

Introduction: Tramadol is an atypical opioid that binds to μ-opioid receptors on neurons. It has a bioavailability of 70% and undergoes extensive first-pass metabolism in the liver. In most countries, it is a prescription-only medicine. Tramadol abuse has increased recently in the last few years between private universities in Khartoum state, Sudan. Common adverse effects of opioids are nausea, vomiting, relaxation, itching, mental confusion, delirium, urinary retention, sweating.

Methodology: A study was conducted on 176 university students in Khartoum from August to September 2018. Ethical approval was obtained from sudan international university research commette and permission from each academic institution. A questionnaire sheet was developed to collect data related to drug abuse among students, including Sociodemographic data and knowledge about drug use without prescription. The collected data were statistically analyzed using ANOVA - IBM - Statistical Package for the Social Science version 16 programs-2008.

Results: A study of 176 university students found that most were male (79.5%) and female (20.5%), with an age range of 21-25. Most were medical students, with a minority in engineering, literacy, and computing fields. Most were aware of tramadol analgesic "pain killer" effect, but only 53.7% knew its hallucinogenic effect. Most abusers used tramadol for less than a year, with most starting in university life. Most abusers consumed various doses, with most consuming daily. Adverse effects of tramadol included physical symptoms, psychological symptoms, and attempts at quitting. Reasons for failure to quit were mainly compliance.

Conclusion: Tramadol abuse is prevalent among medical students in Sudan. Reasons for initiation include elation desire, avoidance of life conflicts, and curiosity.
Novel karyotypic changes detected by comparative genomic hybridization in a case of congenital cervical immature teratoma
Authors: Miliaras Dimosthenis , Grimbizis Grigoris , Conroy Jeffrey , Psarra Natasha , Miliaras Spyros , Nowak Norma , Bontis John
Published: July 2005

BACKGROUND

Cervical immature teratoma is a rare congenital tumor, and very few cases have been studied cytogenetically.

CASE

In this article, we describe a case of this tumor type and present the findings of the karyotype of the lesion, which was performed with the bacterial artificial chromosome arrays using the comparative genomic hybridization method. The chromosomal abnormalities that we found included an amplification on 1p21.1, a 9p22 deletion, and a 1‐copy gain of 17q21.33.

CONCLUSIONS

None of the identified chromosomal aberrations have been previously associated with congenital extragonadal teratomas. Important genes that lie in these DNA regions may be implicated in the pathogenesis of congenital teratomas. Birth Defects Research (Part A), 2005. © 2005 Wiley‐Liss, Inc.
Amifostine does not protect against the ototoxicity of high‐dose cisplatin combined with etoposide and bleomycin in pediatric germ‐cell tumors
Authors: Marina Neyssa , Chang Kay W. , Malogolowkin Marcio , London Wendy B. , Frazier A. Lindsay , Womer Richard B. , Rescorla Frederick , Billmire Deborah F. , Davis Mary M. , Perlman Elizabeth J. , Giller Roger , Lauer Stephen J. , Olson Thomas A.
Published: July 2005

BACKGROUND

High‐dose cisplatin combined with etoposide and bleomycin (HDPEB) improves event‐free survival (EFS) in advanced pediatric germ‐cell tumors (PGCT), but has significant ototoxicity. Amifostine appears to protect against toxicity. The authors combined amifostine with HDPEB and evaluated the efficacy and toxicity, specifically whether ototoxicity deccreased.

METHODS

Eligibility criteria included age < 15 years and unresectable Stage III/IV extracranial, extragonadal PGCT. Patients received bleomycin 15 IU/m2 on Day 1, then etoposide 100 mg/m2 per day, amifostine 825 mg/m2 per day, and cisplatin 40 mg/m2per day on Days 1–5, intravenously. The cycles were repeated every 3–4 weeks with imaging evaluation after 4 cycles. Patients with residual radiographic abnormalities underwent resection. Patients with residual tumor received two additional HDPEB cycles. Hearing evaluations were required at diagnosis and after two and four cycles. Audiologic results were reviewed and compared with historical controls treated with HDPEB.

RESULTS

Twenty‐five eligible patients were enrolled between April 2000 and April 2002. Their median age was 1.6 years (range, 0.64–13.9 years), 17 patients were female, 11 had metastases, and 24 had a yolk sac carcinoma component histologically. Primary sites included sacrococcygeal area/pelvis (n = 15), vagina (n = 5), and other (n = 5). Two‐year EFS and overall survival were 83.5% ± 12.8% and 85.6% ± 12.3%, respectively. Eight patients were removed from the study (four had progressive disease/disease recurrence and four had ototoxicity). Grade 3/4 toxicities included neutropenia (n = 20), thrombocytopenia (n = 14), electrolyte imbalances (n = 14), and gastrointestinal toxicity (n = 12). Twenty‐four of 25 patients received hearing evaluations, and 75% had significant hearing loss.

CONCLUSIONS

Amifostine did not protect against HDPEB‐associated ototoxicity. Cancer 2005. © 2005 American Cancer Society.
Overexpressed Id‐1 is associated with a high risk of hepatocellular carcinoma development in patients with cirrhosis without transcriptional repression of p16
Authors: Matsuda Yasunobu , Yamagiwa Satoshi , Takamura Masaaki , Honda Yutaka , Ishimoto Yuiko , Ichida Takafumi , Aoyagi Yutaka
Published: July 2005

BACKGROUND

Inhibitor of differentiation/DNA binding protein 1 (Id‐1) plays a pivotal role in the regulation of cell proliferation and carcinogenesis via inhibiting basic helix‐loop‐helix (HLH) transcription factors. Recently, Id‐1 was found to repress p16 in tumorous tissue specimens including hepatocellular carcinoma (HCC), but its relevance in precancerous liver tissues is unknown.

METHODS

Id‐1 expression in the liver tissue specimens of 112 patients with cirrhosis without HCC was studied by immunohistochemical analysis. Correlations were investigated between Id‐1 expression and clinicopathologic features, the status of p16, and the risk of HCC occurrence.

RESULTS

A high expression of Id‐1 was observed in 42 patients (38%). The level of Id‐1 expression was not associated with clinical standard parameters or the status of p16 in cirrhotic tissue specimens. The cumulative incidence of HCC development was significantly higher in a group of patients with high Id‐1 expression (P = 0.0008). Multivariate analysis revealed that increased Id‐1 expression is an independent significant factor for the risk of HCC development in patients with cirrhosis (relative risk = 2.75, P = 0.003).

CONCLUSIONS

The results of the current study suggested that increased expression of Id‐1 may play an important role in the early step of hepatocarcinogenesis, and might serve as a useful marker for determining patients with cirrhosis with a high risk of HCC occurrence. Cancer 2005;104. © 2005 American Cancer Society.
DNA methyltransferase 1 expression and promoter methylation of E‐cadherin in mucoepidermoid carcinoma
Authors: Shieh Yi‐Shing , Shiah Shine‐Gwo , Jeng Hao‐Hsuan , Lee Herng‐Sheng , Wu Cheng‐Wen , Chang Long‐Chang
Published: July 2005

BACKGROUND

Loss of E‐cadherin expression is found frequently in many types of human malignancies, including mucoepidermoid carcinoma (MEC). CpG methylation in the promoter region has proven important in the regulation of gene expression implicated in malignant transformation. DNA methyltransferases (DNMTs) are the major enzymes involved in establishing genomic methylation patterns. The current study was designed to test the hypothesis that CpG methylation of the promoter region of the E‐cadherin gene may inactivate its expression and to examine DNMT 1 (DNMT1) protein expression in MEC.

METHODS

Genomic DNA was obtained from paraffin embedded sections by laser microdissection in 46 MEC specimens. Methylation status of the E‐cadherin promoter was examined by utilizing the methylation‐specific polymerase chain reaction assay. To examine E‐cadherin and DNMT1 proteins expression levels, the MEC specimens and adjacent epithelial tissues were studied immunohistochemically. Chi‐square analysis was used to evaluate the correlation of protein expression and E‐cadherin methylation status with clinicopathologic parameters. Comparisons of the survival rate between patients with DNMT1‐positive and DNMT1‐negative patients were made using Kaplan–Meier analysis.

RESULTS

The data showed that all normal tissues expressed E‐cadherin, and no promoter methylation was detected. Of the MEC samples analyzed, methylation allele was found in 33 of 46 samples (72%), and reduced E‐cadherin expression was found in 21 of 46 samples (45%). DNMT1‐positive expression was observed in 29 of 46 MEC samples (63%). A significant correlation was found between E‐cadherin expression and the methylation status of E‐cadherin promoter (P = 0.021). In addition, increased DNMT1 expression was correlated with histologic grade, clinical stage, and a poor prognosis in patients with MEC.

CONCLUSIONS

Hypermethylation of CpG sites at the 5′ promoter of E‐cadherin was a common event associated with E‐cadherin expression levels in MEC, suggesting an epigenetically mediated loss of E‐cadherin function in these tumors. Increased DNMT1 protein expression may play a critical role in the carcinogenesis and disease progression of MEC. Cancer 2005. © 2005 American Cancer Society.
Femtosecond S3→S1 Conversion and Structural Reorganisation of trans‐3‐Phenylprop‐2‐enaldehyde and Derivatives in Solution
Authors: Lustres J. L. Pérez , Farztdinov Vadim M. , Kovalenko Sergey A.
Published: July 2005

Photoinduced excited‐state relaxation of trans‐3‐phenylprop‐2‐enaldehyde (cinnamaldehyde) and three derivatives was studied in hexane and acetonitrile with the pump–supercontinuum‐probe technique. Transient spectra were measured with 50 fs resolution in the range 260–660 nm after S3←S0 excitation at 288 nm. The early spectra reveal an ultrafast, 0.1–0.5 ps, interchange of intensity between two excited‐state absorption (ESA) bands followed by a ≈3 ps decay of ESA. This behaviour is interpreted with the help of semiempirical calculations, which indicate that the sub‐picosecond evolution is consistent with S3→S1 excited‐state relaxation while the picosecond decay should be due to a structural intramolecular rearrangement. The latter may consist of a twist of the phenyl ring and rotation around the CC bond to a perpendicular conformation which corresponds to the global energy minimum in the S1 state and serves as source for trans and cis isomers in the ground state.
Kinetic and DFT Studies on the Ag/TiO2‐Photocatalyzed Selective Reduction of Nitrobenzene to Aniline
Authors: Tada Hiroaki , Ishida Tetsuji , Takao Ayako , Ito Seishiro , Mukhopadhyay Sudip , Akita Tomoki , Tanaka Koji , Kobayashi Hisayoshi
Published: July 2005

TiO2 particles loaded with silver nanoparticles with a mean diameter of 1.5 nm exhibit a high photocatalytic activity (84 % conversion after 1 h irradiation) for the reduction of nitrobenzene to aniline with 100 % selectivity in the presence of CH3OH (concentration=100 mM). High‐resolution transmission electron microscopic studies of Pt‐photodeposited Ag/TiO2 demonstrate that the Ag nanoparticles act as reduction sites in the photocatalytic reaction. Both spectroscopic measurements and density functional theory (DFT) calculations reveal that nitrobenzene is selectively adsorbed onto the Ag surfaces of Ag/TiO2 via partial electron transfer from Ag to nitrobenzene, whereas the interaction between aniline and Ag/TiO2 is weak. The kinetic analysis indicates that the recombination between the electrons flowing into the Ag nanoparticle and the holes left in the TiO2 valence band is significantly suppressed, particularly in the presence of CH3OH. The high activity and selectivity in the present Ag/TiO2‐photocatalyzed reduction are rationalized in terms of the charge separation efficiency, the selective adsorption of the reactants on the catalyst surfaces, and the restriction of the product readsorption.
Imino‐ and Oxazolino‐Functionalised Pyrrolylphosphanes and Pyrrolylphosphinites: An Unexploited Class of Chiral P,N‐Bidentate Ligands with Unusual Electronic Properties
Authors: Gavrilov Konstantin N. , Tsarev Vasily N. , Konkin Stanislav I. , Lyubimov Sergey E. , Korlyukov Alexander A. , Antipin Mikhail Yu. , Davankov Vadim A.
Published: July 2005

Enantiopure P,N‐bidentate pyrrolylphosphanes and pyrrolylphosphinites have been prepared based upon chiral imino‐ and oxazolino‐containing compounds. Complexation of the new ligands with [Rh(CO)2Cl]2 and [Pd(allyl)Cl]2 has been found to give the chelate complexes [Rh(CO)Cl(η2‐P,N)] and [Pd(allyl)(η2‐P,N)]+BF4–, respectively. Imino‐ and oxazolino‐functionalised pyrrolylphosphanes and pyrrolylphosphinites have been shown to be a novel class of P,N‐bidentate ligands possessing exceptional π‐acceptor and original σ‐donor properties. With these ligands, up to 77 % ee has been achieved in the asymmetric Pd‐catalyzed sulfonylation of 1,3‐diphenyl‐2‐propenyl acetate with sodium p‐toluenesulfinate. In the enantioselective alkylation of 1,3‐diphenyl‐2‐propenyl acetate with dimethyl malonate, up to 93 % enantioselectivity has been achieved by using [Pd(allyl)(η2‐P,N)]+BF4– complexes as chiral catalysts. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
A Pulse Radiolysis Study of Catalytic Superoxide Radical Dismutation by a Manganese(II) Complex with an N‐Tripodal Ligand (Eur. J. Inorg. Chem. 14/2005)
Authors: Durot Stéphanie , Lambert François , Renault Jean‐Philippe , Policar Clotilde
Published: July 2005

The cover picture shows an allegory of bioinorganic chemistry and biomimetic studies. Here, the metalloprotein (human Mn‐SOD, PDB‐code 1MSD) is posing for the painter. As a bioinorganic chemist, he is designing new molecules that would reproduce this protein activity; he is testing the activity of these molecules and deciphering mechanisms. Here, we show the structure of a small MnII complex that has been studied for its SOD‐like activity by pulsed radiolysis. In the painting, the UV/Vis trace of a multipulse experiment at 300 nm is shown, with successive spikes and plateaus. An overall increase in the absorbance of the successive plateaus is observed. The asterisks indicate irradiations. Simulations of the individual growth of the spikes, of the individual decrease down to the plateau and of the overall increase of the absorbance for the successive plateaus leads to the proposition of a mechanism. This is the triangular cycle shown in the painting, involving an {MnOO}6 adduct between MnII and superoxide. This label, {MnOO}6, is proposed by analogy with the nomenclature used for iron−nitroxide adducts. Each event indicated in the cycle has been proven. Moreover, this study shows unambiguously that the MnII compound displays a catalytic activity for superoxide dismutation. Details are presented in the article by J.‐P. Renault, C. Policar et al. on p. 2789 ff. In the original picture by Magritte, the inset in the lower right‐hand corner, is entitled “La clairvoyance” (clear‐sightedness) and was painted in 1936.
Identification of individual genes altered in squamous cell carcinoma of the vulva
Authors: Kunjoonju Josena P. , Raitanen Misa , Grénman Seija , Tiwari Nivedita , Worsham Maria J.
Published: July 2005

Chromosome rearrangements in squamous cell carcinoma of the vulva (SCV) have indicated common consistent regions of loss and gain. The overall aim of our research was to define and characterize individual genes that underlie the pathogenesis of SCV. Thirteen cell lines from 12 SCV patients were evaluated for loss and gain of 122 genes distributed throughout the genome. Individual genes were analyzed for genetic alterations using a novel genomewide strategy, the multiplex ligation‐dependent probe amplification assay. Our candidate gene approach identified several altered loci. Most frequent was the loss of 1 copy of TMSB10, observed in 11 of 12 SCV patients, followed by loss of CTNNB1 and BCL2, which occurred in 7 of 12 patients. Frequent gains/amplifications included CCND1, observed in 8 of 12 patients, and IL12A, in 7 of the 12 patients. Loss and gain of specific genes observed in our study were generally concordant with the results of previous studies of cytogenetics and CGH utilizing the same SCV cell lines. Genetic alterations are hallmarks of tumorigenesis, and there is wide agreement that recurrent altered genomic loci contain genes important for tumor development and progression. Understanding the interplay of cancer genes and the pathways they utilize can lead to the detection of novel molecular targets in the diagnosis, prognosis, and treatment of SCV. © 2005 Wiley‐Liss, Inc.
Molecular and immunohistochemical investigation of protein kinase a regulatory subunit type 1A (PRKAR1A) in odontogenic myxomas
Authors: Perdigão Paola F. , Stergiopoulos Sotirios G. , De Marco Luiz , Matyakhina Ludmila , Boikos Sosipatros A. , Gomez R. S. , Pimenta F. J. G. S. , Stratakis Constantine A.
Published: July 2005

Odontogenic myxomas are rare benign neoplasms affecting the jaw. Myxomas of bones and other sites occur as part of Carney complex (CNC), a multiple neoplasia syndrome caused by mutations in the PRKAR1A gene, which codes for the regulatory subunit of protein kinase A (PKA). In the present study, 17 odontogenic myxomas from patients without CNC were screened for PRKAR1A mutations and PRKAR1A protein expression by immunohistochemistry (IHC). Mutations of the coding region of the PRKAR1A gene were identified in 2 tumors; both these lesions showed no or significantly decreased immunostaining of PRKAR1A in the tumor compared to that in the surrounding normal tissue. One mutation (c.725C>A) led to a nonconservative amino acid substitution in a highly conserved area of the gene (A213D); the other was a single base‐pair deletion that led to a frameshift (del774C) and a stop codon 11 amino acids downstream of the mutation site; both tumors were heterozygous for the respective mutations. Of the remaining tumors, 7 of the 15 without mutations showed almost no PRKAR1A in the tumor cells, whereas IHC showed that the protein was abundant in nontumorous cells. We concluded that PRKAR1A may be involved by its down‐regulation in the pathogenesis of odontogenic myxomas caused by mutations and/or other genetic mechanisms. Of the sporadic, nonfamilial tumors associated with PRKAR1A mutations, the odontogenic type was the first myxomatous lesion found to harbor somatic PRKAR1A sequence changes. Published 2005 Wiley‐Liss, Inc.
CHOP plays a pivotal role in the astrocyte death induced by oxygen and glucose deprivation
Authors: Benavides Amparo , Pastor Dolores , Santos Pablo , Tranque Pedro , Calvo Soledad
Published: July 2005

Ischemia has different consequences on the survival of astrocytes and neurons. Thus, astrocytes show a remarkable resistance to short periods of ischemia that are well known to cause neuronal death. We have used a cell culture model of stroke, oxygen, and glucose deprivation (OGD), to clarify the mechanisms responsible for the exclusive resistance of astrocytes to ischemia. The expression of genes implicated in both ischemia‐induced astrocyte death and post‐ischemic survival was analysed by the RNA differential display technique. Our study revealed that the expression of the CEBP homologous protein (CHOP)‐coding gene is promptly an intensely upregulated following astrocyte oxygen and glucose deprivation. CHOP mRNA induction was accompanied by the activation of other genes (grp78, grp95) that, alike CHOP, are involved in the endoplasmic reticulum (ER) stress response. In addition, drugs that cause ER calcium depletion or protein N‐glycosylation inhibition mimicked the effects of OGD on astrocyte survival, further supporting the involvement of ER in the astrocyte responses to OGD. Our experiments also demonstrated that upregulation of CHOP during the ER stress response is required for ischemia to cause astrocyte death. Not only the levels of CHOP mRNA and protein correlate perfectly with the degree of OGD‐triggered cell injury, but also astrocyte death induced by OGD is significantly overcome by CHOP antisense oligonucleotide treatment. Nevertheless, we observed that astrocytes undergo apoptosis only when CHOP is permanently upregulated, and not when CHOP increases are transient. Finally, we found that the extent of CHOP induction is determined by the length of the ischemic stimulus. Taken together, our results indicate that permanent upregulation of CHOP is decisive for the induction of astrocyte death by OGD. © 2005 Wiley‐Liss, Inc.
Pyruvate protects glucose‐deprived Müller cells from nitric oxide‐induced oxidative stress by radical scavenging
Authors: Frenzel Jochen , Richter Jan , Eschrich Klaus
Published: July 2005

The cellular defense of Müller cells against oxidative and nitrosative stress was examined after the addition of the nitric oxide donor papanonoate. Glucose concentrations of ≥550 μM efficiently protected the Müller cells from cell death by maintaining high ATP and glutathione and allowing only a moderate increase of free radicals. Fluorescence‐activated cell sorting (FACS) analysis showed that 22% of the cells underwent apoptosis whereas necrosis was strongly suppressed. Under glucose deprivation, the intracellular concentration of ATP declined to 15% after 1 h; glutathione dropped to 50% within 2 h after papanonoate addition. Both the number of cells containing excess free radicals and the mean concentration of free radicals increased twofold at 0.5–2 h of incubation with papanonoate. Cell death switched from prevailing apoptosis to massive necrosis and cell viability decreased drastically. Several metabolites of glycolysis, gluconeogenesis, and the pentose phosphate pathway were tested with respect to their capability to protect the stressed Müller cells. 2 mM pyruvate was found to enhance cell viability 1.6‐fold predominantly by reducing the necrotic cell demise. It could be shown that pyruvate did not act by improving the energy status of Müller cells but by scavenging excess free radicals. Inhibition of the monocarboxylate transporters in Müller cells by α‐cyano‐4‐hydroxycinnamate abolished this effect. Other 2‐ketoacids, like oxalacetate, 2‐ketoglutarate and 2‐ketobutyrate had a similar protecting effect as pyruvate. Lactate, glutamate, 2‐deoxyglucose, and ribose 5‐phosphate did not protect Müller cells against oxidative and nitrosative stress. © 2005 Wiley‐Liss, Inc.
Functional magnetic resonance imaging response to increased verbal working memory demands among patients with multiple sclerosis
Authors: Sweet Lawrence H. , Rao Stephen M. , Primeau Margaret , Durgerian Sally , Cohen Ronald A.
Published: July 2005

Multiple sclerosis (MS) patients frequently experience impaired verbal working memory (VWM). Functional magnetic resonance imaging (fMRI) may help identify neural mechanisms underlying these deficits. Neuroimaging studies of healthy adults have characterized responses associated with increased VWM demands during the n‐Back task, suggesting that this experimental paradigm could help identify neural correlates of VWM deficits among MS patients. Fifteen MS patients and 15 matched control participants completed the n‐Back during whole‐brain fMRI. Mean signal during adjacent 0‐Back blocks was subtracted, on a voxel‐wise basis, from mean signal observed during n‐Back blocks. Resulting difference scores for 1‐, 2‐, and 3‐Back were compared across groups and difficulty levels. Signal intensity was positively related to difficulty level in anterior regions, including premotor, supplementary motor, and dorsolateral prefrontal cortices. MS patients exhibited significantly greater intensity in these areas compared to controls during the 1‐Back, while portions of the left superior frontal gyrus, cingulate, and parahippocampal gyri were relatively less intense at more difficult levels. MS group responses were slower during the 1‐Back and tended to be slower during the 3‐Back; however, accuracy did not differ at any level. Lesion load was positively related to only 1‐Back activity and unrelated to any performance measure. Results suggest that compensatory activity occurs among MS patients matched on performance accuracy. Furthermore, compensatory activity occurs predominantly in regions associated with VWM, and this may decline relative to controls as task demands increase. These findings may help to explain why MS patient performance decreases as a function of effort on neuropsychological tests. Hum Brain Mapp, 2005. © 2005 Wiley‐Liss, Inc.
Hyaluronic acid hydrogel added with ibuprofen‐lysine for the local treatment of chondral lesions in the knee: In vitro and in vivo investigations
Authors: Barbucci Rolando , Fini Milena , Giavaresi Gianluca , Torricelli Paola , Giardino Roberto , Lamponi Stefania , Leone Gemma
Published: July 2005

The effect of hyaluronan‐based hydrogel with a cross‐linking degree of 50% (i.e., the amount of carboxylate groups involved in the cross‐lining reaction) (Hyal 50%), loaded with an anti‐inflammatory drug (ibuprofen‐lysine) for local administration in the osteoarthritic knee was evaluated. The kinetic of drug release from Hyal 50% hydrogel was performed in vitro by a continuous flow system. The release was studied at three different rates (0.375, 0.073, and 0.005 mL/s), and for the slowest one a period of 8 days was necessary to receive the complete release of the drug. A chondral defect was caused in the right femoral medial condyle of 24 rabbits. Twelve animals were treated with Hyal 50%+ibuprofen‐lysine and 12 with Hyal 50% by percutaneous injection. The treatments were repeated every 10 days, for three or five times. At 30 and 50 days, no significant differences were observed between the groups (mean score at 30 days: 4.4 ± 0.6 in Hyal 50%‐treated group and 5.1 ± 0.7 in Hyal 50% + Ibuprofen‐lysine‐treated group; mean score at 50 days: 6.9 ± 0.6 in Hyal 50%‐treated group and 7.1 ± 0.6 in Hyal 50% + Ibuprofen‐lysine‐treated group). A significant difference was observed in bone mineral density of the total tibia of rabbits treated by Hyal 50% + Ibuprofen‐lysine in comparison with those treated only by Hyal 50%. The positive effects of Hyal 50% on chondral lesions were maintained in the presence of ibuprofen‐lysine with the adjunctive effect of an increased limb usage, most likely due to less pain and discomfort. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2005
Strength retention of 70:30 poly(L‐lactide‐co‐D,L‐lactide) following real‐time aging
Authors: Moser Rodney C. , McManus Anastasia J. , Riley Susan L. , Thomas Kevin A.
Published: July 2005

This study evaluated the in vitro strength retention and polymer characteristics of plates and screws made from commercially available 70:30 poly(L‐lactide‐co‐D,L‐lactide) over a 2‐year time period. Test samples included three routine manufacturing lots each of plates (1.2 mm thick, 41.70 mm long, with 2.5‐mm holes), which were machined from compression‐molded sheets, and screws (2.4‐mm major diameter and 1.86‐mm minor diameter), which were manufactured by injection molding. All samples were sterilized by e‐beam irradiation prior to in vitro aging following a standard methodology. Mechanical testing and polymer analysis was performed after 0, 6, 13, 26, 39, 52, 65, 78, and 104 weeks. The initial (time zero) tensile strength of the plates averaged 33.2 ± 1.9 MPa; the plates retained 100% of this strength at 6 weeks, 84% at 13 weeks, and 34% at 39 weeks. The screws had an initial (time zero) shear strength of 29.8 ± 4.2 MPa, and maintained 97% of this strength at 26 weeks and 73% of this strength at 39 weeks. The inherent viscosity and molecular weight (Mw) at time zero averaged approximately 1.4 dL/g and 165,000 g/mol, respectively, and decreased at similar rates for both the plates and screws. These results demonstrate excellent strength retention of devices fabricated from 70:30 poly(L‐lactide‐co‐D,L‐lactide) over time periods exceeding those associated with normal bone healing. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2005
Characterization of cortical neuron outgrowth in two‐ and three‐dimensional culture systems
Authors: Lin Po‐Wei , Wu Chi‐Chen , Chen Chien‐Ho , Ho Hsiu‐O , Chen Yi‐Chun , Sheu Ming‐Thau
Published: July 2005

To improve the ability of regeneration by grafting living cells or by adding growth factor to a lesion site, it is important to find good biomaterials for neuron survival and regeneration. This study focused on two‐ and three‐dimensional cultures in a matrix using biomaterials such as agarose, collagen, fibrin, and their mixtures, because these are considered to be suitable biomaterials for neuron outgrowth. Cortical neurons were dissected from E17 rat embryos and cultured in agarose gel, collagen gel, fibrin glue, and mixtures of collagen and fibrin. Results showed that neurons cultured in collagen gel and fibrin glue had longer periods of survival (more than 3 weeks) and better neurite extension than those observed in agarose gels. As to the survival rate according to the MTT and lactate dehydrogenase assays, fibrin glue was the most suitable biomaterial for neuron survival among the biomaterials examined. With two‐dimensional fibrin plating, neuron cells exhibited cell aggregation and stress fibers, but the same results were not observed with collagen gel. There were no differences in neurite extension and survival in the mixtures of collagen and fibrin. The results suggest that collagen and fibrin can provide a suitable substrate for a three‐dimensional culture matrix for neuronal survival and differentiation. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2005
Polyamide/silver antimicrobials: Effect of filler types on the silver ion release
Authors: Kumar Radhesh , Howdle Steve , Münstedt Helmut
Published: July 2005

The efficiency of various silver‐based antimicrobial fillers (elementary silver and silver substituted materials) in polyamide (PA) toward their silver ion (Ag+) release characteristics in an aqueous medium was investigated and discussed. Anode stripping voltammetry (ASV) was used for the quantitative estimation of Ag+ release from these composites. The biocidal (Ag+) release from the composites was found to be dependent on the time of soaking in water and the nature of the filler. The long‐term Ag+ release capability of the elementary silver‐based PA/Ag composite is promising compared with the commercial counterparts. The silver ion release potential of polyamide composites where the silver filling was performed by using supercritical carbon dioxide (scCO2) is also discussed. The composites release Ag+ at a concentration level capable of rendering antimicrobial efficacy and proved to be active against the microbes. A good agreement exists between the Ag+ release experiments and antimicrobial test results. The observed results on the influence of the nature of the filler and crystallinity on the biocidal release and the varying long‐term release properties could be helpful in the design of industrially relevant biomaterials. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2005
Preoperative diagnosis of medullary thyroid carcinoma: Fine needle aspiration cytology as compared with serum calcitonin measurement
Authors: Bugalho Maria João M. , Santos Jorge Rosa , Sobrinho Luís
Published: July 2005

Background and Objectives

Preoperative diagnosis of sporadic medullary thyroid carcinoma (MTC) has mainly relied on fine needle aspiration cytology (FNAC). The present study aimed to compare the sensitivity of this technique with serum calcitonin (CT) measurement and to assess the therapeutic implications of an inadequate preoperative diagnosis.

Methods

We reviewed the clinical records of 91 MTC patients treated and/or followed at our institution between January 1990 and December 2003.

Results

After revision of clinical records, 77 individuals were considered eligible for the study. FNAC was performed in 67 patients (87%) with a sensitivity of 63%; serum CT was measured in 56 patients (73%) with a sensitivity of 98%. Both FNAC and serum CT were assessed in 51 patients (66%). FNAC detected only 74.5% of MTCs suspected by elevated serum CT. Among patients with a cytological diagnosis of MTC, total thyroidectomy (TT) was performed in 95% of patients. Among patients without a cytological diagnosis of MTC, TT was performed in 83% of patients in whom serum CT was evaluated prior to surgery whereas it was performed in only 46% of patients in whom CT evaluation was lacking.

Conclusions

Despite the higher sensitivity of serum CT measurement, as compared with FNAC to diagnose MTC (98% vs. 63%), only 9% of patients might have escaped to surgery based on FNAC results. However, indication for surgery based on suspicious FNAC may not alert the surgeon for the need of a TT and exploration of nodes at least in the central compartment. J. Surg. Oncol. 2005;91:56–60. © 2005 Wiley‐Liss, Inc.
Value of CT criteria in predicting survival in patients with potentially resectable pancreatic head carcinoma
Authors: Phoa Saffire S.K.S. , Tilleman Esther H.B.M. , Delden Otto M. van , Bossuyt Patrick M.M. , Gouma Dirk J. , LamÉris Johan S.
Published: July 2005

Background and Objective

Survival is often poor after resection of pancreatic tumors. We correlated the pre‐operative CTs with survival to find criteria that have prognostic value. To establish the prognostic value of CT in patients with potentially resectable pancreatic head carcinoma.

Methods

In 71 consecutive patients with potentially resectable pancreatic head carcinoma, prognostic factors on CT were scored, for example, tumor size, peripancreatic infiltration, grades of vascular encasement, and local irresectability. All patients underwent surgical exploration. CT findings were compared with results of surgery and histopathology. Prognostic factors for resected and unresected tumors were analyzed using single and multivariate analysis

Results

Forty‐one of 71 tumors were resected (24 radical). The sensitivity, specificity, and positive predictive value of CT for surgical irresectability were 0.67, 0.63, and 0.57, respectively. For a non‐radical resection, these were 0.62, 0.75, and 0.83, respectively. The median survival was 21 months for resectable tumors and 9.7 months for unresectable tumors. For resected tumors, a tumor diameter of > 3 cm (relative hazard 3.8) and CT signs of local unresectability showed a poor survival. The median survival of resected tumors <2 cm was nearly 30 months.

Conclusion

CT signs of local irresectability and a tumor diameter of >3 cm predict a poor survival after resection. J. Surg. Oncol. 2005;91:33–40. © 2005 Wiley‐Liss, Inc.
Head and neck squamous cell carcinoma: The role of post‐operative adjuvant radiotherapy
Authors: Dinshaw Ketayun Ardeshir , Agarwal Jai Prakash , Laskar Sarbani Ghosh , Gupta Tejpal , Shrivastava Shyam Kishore , Cruz Anil D.
Published: July 2005

Background

Head and neck squamous cell carcinoma (HNSCC) is one of the leading cancers in India. Since a large majority present in loco‐regionally advanced stages, surgery followed by adjuvant post‐operative radiotherapy (PORT) has been the mainstay of treatment for resectable HNSCC.

Aim

To identify clinico‐pathologic factors that could have an impact on outcome in HNSCC in the postoperative setting.

Materials and Methods

A retrospective review of 348 previously untreated patients with HNSCC who received PORT following curative surgery. The outcome measures were local control, loco‐regional control, and disease free survival (DFS).

Results

With a median follow‐up of 36 months (range: 2–127 months) for surviving patients, the 5‐year local control, loco‐regional control, and DFS was 79%, 63%, and 56%, respectively for all patients. On univariate analysis, site of primary was an independent prognostic factor for all the outcome measures (P = 0.005, 0.02, and 0.04, respectively) with oral cavity lesions faring the worst. Peri‐nodal extension (PNE) affected loco‐regional control (P = 0.002) and DFS (P = 0.0005), but was not predictive for local control (P = 0.9852). Cut margin positivity predicted for inferior local control alone (P = 0.03), the significance of which was lost on multivariate analysis. Cox regression analysis however confirmed the significance of primary site and PNE as independent prognostic factors.

Conclusion

Primary site and PNE are independent factors predicting outcome in the postoperative radiotherapeutic management of HNSCC. J. Surg. Oncol. 2005;91:48–55. © 2005 Wiley‐Liss, Inc.
Recurrent ovarian carcinoma of low malignant potential: The role of secondary surgical cytoreduction and the prognosis in Chinese patients
Authors: Zang Rong Yu , Yang Wen Tao , Shi Da Ren , Xing Yan , Cai Shu Mo
Published: July 2005

Background and Objectives

The study of pathology and prognosis for patients with ovarian tumors of low malignant potential (LMP) has been well documented. The treatment, particularly the secondary surgery, for recurrent disease is less documented. This study was conducted to investigate the role of secondary surgical cytoreduction for recurrent ovarian carcinoma of LMP.

Methods

Patients with ovarian carcinoma of LMP at advanced stages experiencing disease recurrence and treated by secondary surgical cytoreduction at Fudan University Cancer Hospital were retrospectively reviewed.

Results

Sixteen patients with recurrent serous and mucinous ovarian LMP tumors who underwent secondary surgical cytoreduction were entered in this study. The median age was 46.5 years. The 5‐year survival in those with residual disease ≤1 cm after secondary surgical cytoreduction was 83%, compared to 26% in those with residual disease >1 cm (P = 0.01). Multivariate analysis suggested that extent of recurrent disease (solitary vs. multiple, relative risk [RR] =2.69, P < 0.01), and residual disease after secondary surgical cytoreduction (≤1 cm vs. >1 cm, RR = 2.56, P < 0.01) were determinants of survival.

Conclusions

For recurrent ovarian carcinomas of low malignant potential, prolonged survival was observed in patients with solitary recurrent disease and optimal secondary surgical outcome. J. Surg. Oncol. 2005;91:67–72. © 2005 Wiley‐Liss, Inc.
Quantitative measurements of alternating finger tapping in Parkinson's disease correlate with UPDRS motor disability and reveal the improvement in fine motor control from medication and deep brain stimulation
Authors: Taylor Tavares Ana Lisa , Jefferis Gregory S.X.E , Koop Mandy , Hill Bruce C. , Hastie Trevor , Heit Gary , Bronte‐Stewart Helen M.
Published: July 2005

The Unified Parkinson's Disease Rating Scale (UPDRS) is the primary outcome measure in most clinical trials of Parkinson's disease (PD) therapeutics. Each subscore of the motor section (UPDRS III) compresses a wide range of motor performance into a coarse‐grained scale from 0 to 4; the assessment of performance can also be subjective. Quantitative digitography (QDG) is an objective, quantitative assessment of digital motor control using a computer‐interfaced musical keyboard. In this study, we show that the kinematics of a repetitive alternating finger‐tapping (RAFT) task using QDG correlate with the UPDRS motor score, particularly with the bradykinesia subscore, in 33 patients with PD. We show that dopaminergic medication and an average of 9.5 months of bilateral subthalamic nucleus deep brain stimulation (B‐STN DBS) significantly improve UPDRS and QDG scores but may have different effects on certain kinematic parameters. This study substantiates the use of QDG to measure motor outcome in trials of PD therapeutics and shows that medication and B‐STN DBS both improve fine motor control. © 2005 Movement Disorder Society