bluuebunny/crossref_metadata_2025 huggingface dataset:
Oral manifestations of adverse drug reactions: guidelines
Authors: Femiano F , Lanza A , Buonaiuto C , Gombos F , Rullo R , Festa V , Cirillo N
Published: March 2008

Background  Adverse drug reactions are noxious and unintended responses to a medicinal product.

Many drugs have the potential to induce adverse reactions in the mouth. The extent of such reactions is unknown; however, because a lot of them are asymptomatic, many are believed to go unnoticed. Adverse oral drug reactions are responsible for oral lesions and manifestations that can mime local or systemic disease.

Their pathogenesis, especially of the mucosal reactions, is largely unknown and appears to involve complex interactions between the drug in question, other medications, the patient's underlying disease, genetics and lifestyle factors.

Aim  In this study, we have listed the principal signs and symptoms of oral and perioral adverse drug reactions and the responsible drugs. Diagnosis for adverse drug reaction is not easy given also the limited utility of laboratory tests. The association between a drug and an adverse drug reaction is mostly based on the disappearance of the reactions following discontinuance of the offending drug.

Sometimes, it is useful to perform rechallenge tests reintroducing the drug to establish cause and effect.

Conclusions  Knowledge of adverse drug‐induced oral effects helps health professionals to better diagnose oral disease, administer drugs and improve patient compliance during drug therapy and may foster a more rational use of drugs.
Diffusion of efficacious interventions for children and adolescents with mental health problems
Authors: Graeff‐Martins Ana Soledade , Flament Martine F. , Fayyad John , Tyano Sam , Jensen Peter , Rohde Luis Augusto
Published: March 2008

Background:  Child and adolescent mental health problems are prevalent and require adequate interventions. Despite several evidence‐based interventions for these problems described in the literature, few studies addressed strategies to diffuse efficacious interventions for child mental disorders especially in developing countries.

Methods:  An extensive but not systematic review of the literature was performed aiming to identify evidence‐based interventions for children and adolescents with mental disorders, professionals to target in disseminating these interventions, and the available strategies to diffuse information.

Results:  Substantial evidence‐based information is available to guide preventive, psychosocial and psychopharmacological interventions. The effectiveness of treatments in real‐world settings and the cost‐effectiveness of interventions are rarely tested. Professionals at different levels (teachers, school counselors, social workers, general practitioners, pediatricians, child psychologists and psychiatrists) should be targeted in diffusing efficacious interventions for child mental health problems worldwide. Telepsychiatry and the internet seem to be the most promising strategies to diffuse knowledge with lower costs.

Conclusions:  Medical and allied professionals must incorporate child and adolescent mental health issues in their under‐ and postgraduate curricula, and be better prepared to critically evaluate available information. Professionals need to disseminate evidence‐based programs to guide parents and teachers in developing countries to deal with child and adolescent difficulties. Countries need to explore internet solutions for dissemination of medical information.
Models of intrapartum care and women’s trade‐offs in remote and rural Scotland: a mixed‐methods study
Authors: Pitchforth E , Watson V , Tucker J , Ryan M , Van Teijlingen E , Farmer J , Ireland J , Thomson E , Kiger A , Bryers H
Published: March 2008

Objective  To explore women’s preferences for, and trade‐offs between, key attributes of intrapartum care models.

Design  Mixed‐methods study using discrete choice experiments (DCEs) and focus groups.

Setting  The North of Scotland.

Population  Women from the catchment areas of eight rural maternity units in the North of Scotland.

Methods  Based on current policy, ‘model of care’ and ‘time travelled’ were selected as key attributes of intrapartum care in remote and rural settings. A DCE questionnaire explored women’s preferences for and trade‐offs between these attributes. Focus groups validated the DCE attributes and provided valuable information about the drivers of women’s preferences for place of delivery.

Main outcome measures  Preferences for attributes of intrapartum care.

Results  Eight focus groups were conducted, and 877 eligible women completed the questionnaire. Overall, the DCE results found women preferred delivery in a unit to home birth and consultant‐led care (CLC) to midwife‐managed care (MMC). Women preferring CLC associated it with covering every eventuality and increased safety. Although women preferred shorter travel times, trade‐offs indicated a willingness to travel for approximately 2 hours to get one’s preferred choice. Focus group findings and subgroup DCE analysis showed heterogeneity of preferences related to experience, risk status, geographic location, perception of care and family circumstances.

Conclusions  In contrast to service redesign offering local midwife‐managed intrapartum care, most rural women in our study expressed a preference to give birth in hospital and have CLC because they felt safer. Women were willing to travel for this but within limits. Qualitative results showed that women’s preferences were influenced by their home and family context, beliefs and previous pregnancy experiences. Challenges for service redesign are to provide comprehensive obstetric services within acceptable travel time, while responding to the heterogeneity of women’s preferences.
Outcome of anaemic monochorionic single survivors following early intrauterine rescue transfusion in cases of feto‐fetal transfusion syndrome
Authors: Quarello E , Stirnemann J , Nassar M , Nasr B , Bernard J‐P , Leleu‐Huard F , Ville Y
Published: March 2008

Objective  To evaluate the outcome of severely anaemic monochorionic (MC) twins surviving the death of their co‐twin following early intrauterine rescue transfusion in cases of feto‐fetal transfusion syndrome (FFTS).

Study design  We reviewed all MC pregnancies complicated with FFTS following primary management, in which a single intrauterine fetal death (IUFD) was diagnosed with certainty within 24 hours between January 1999 and December 2006. We included MC survivors who presented ultrasound or Doppler features of fetal anaemia following the death of their co‐twin. Intrauterine transfusion (IUT) was given to all survivors who were anaemic.

Results  Nineteen MC twin pregnancies presented a single intrauterine death (IUD) associated with an anaemic co‐twin. Median gestational age at IUD was 23 [20–28] weeks. The median interval between IUD and IUT was 12 [8–24] hours. There were 58% (11/19) healthy survivors. Perinatal death rate was 26% (5/19) including 16% (3/19) intrauterine and 10% (2/19) neonatal deaths. Abnormal prenatal cerebral findings developed in 21% (4/19) cases, always within 1 month after the death of the co‐twin. Considering occlusive techniques and other management separately, there were 64% (7/11) and 50% (4/8) healthy survivors, respectively, and perinatal death occurred in 36% (4/11) and 12.5% (1/8) of fetuses, respectively. Prenatal fetal cerebral lesions developed in 9% (1/11) of cases following occlusive techniques and in 37.5% (3/8) of fetuses when managed differently. The median gestational age at delivery in the survivors was 31 [25–38] weeks.

Conclusion  In cases of FFTS with single anaemic survivors, early IUT could be offered following extensive counselling and close follow up.
An estimation of intrapartum‐related perinatal mortality rates for booked home births in England and Wales between 1994 and 2003
Authors: Mori R , Dougherty M , Whittle M
Published: March 2008

Objective  The objective of this study was to obtain the best estimate of intrapartum‐related perinatal mortality (IPPM) rates for booked home births.

Design  A population‐based cross‐sectional study.

Setting  England and Wales.

Subjects  All births in England and Wales, including home births (intended or unintended) occurring between 1994 and 2003.

Methods  All IPPM data were derived from the Confidential Enquiry into Maternal and Child Health. Denominators were derived by using unintended home births and transfer rates from home to hospital, from previous studies, with sensitivity analyses. IPPM rates were calculated for the three following subgroups: (a) the completed home birth group, (b) the transferred group and (c) the unintended home birth group.

Outcome  IPPM rate.

Results  The overall IPPM rate for England and Wales improved between 1994 and 2003. However, data to obtain a precise estimate of IPPM rate for booked home birth were not available. The average IPPM rate for all births in the study period was 0.79 per 1000 births (95% CI 0.77–0.81), and the estimated IPPM rate for booked home births was 1.28 or 0.74 per 1000 births, depending on the method of calculation (range 0.49–1.47). The IPPM rates for the completed home birth group appeared to be lower throughout the study period compared with the unintended home birth groups. Those women who had booked for a home birth, but later needed to transfer their care for a hospital birth, appeared to have the highest risk of IPPM in the study period.

Conclusions  The results of this study need to be interpreted with caution due to inconsistencies occurring in the recorded data. However, the data do highlight two important features. First, they suggest that IPPM rates for home births do not appear to have improved over the study period examined, even though rates did so overall. Second, although the women who booked for home births and had their babies at home seemed to have a generally low IPPM rate, those who required their care to be transferred to hospital did not. Women who book for home births should be offered comprehensive evidence‐based information about the potential benefits, risks and uncertainties associated with their choice of birthplace by the healthcare professional responsible for supporting their decision. It is of considerable concern that the data recorded nationally in England and Wales do not provide accurate information about when and why a transfer from home to hospital booking occurs and about their outcomes.
Establishment of reference range for thyroid hormones in normal pregnant Indian women
Authors: Marwaha RK , Chopra S , Gopalakrishnan S , Sharma B , Kanwar RS , Sastry A , Singh S
Published: March 2008

Background  Interpretation of thyroid function tests during pregnancy needs trimester‐related reference intervals from pregnant populations with minimal risk for thyroid dysfunction. While India has become iodine sufficient after two decades of salt iodisation, there is no normative data for thyroid function from healthy pregnant women of this country.

Aims and objectives  To determine trimester‐specific reference ranges for free triiodothyronine (FT3), free thyroxine (FT4) and thyrotropin (TSH) from healthy pregnant Indian women.

Design  Cross‐sectional study in a reference population of pregnant women.

Setting  Primary care level obstetric department in India.

Population  Women with uncomplicated pregnancy in any trimester.

Methods  Five hundred and forty‐one apparently healthy pregnant women with uncomplicated single intrauterine gestations reporting to the Armed Forces Clinic in any trimester were consecutively recruited. Clinical examination, thyroid ultrasound for echogenicity and nodularity and estimation of FT3, FT4, TSH and antithyroid antibodies (antithyroperoxidase [anti‐TPO] and antithyroglobulin [anti‐Tg]) using electrochemiluminescence technique were carried out. From this entire sample, a disease‐ and risk‐free reference population was obtained by excluding those with any known factor that could affect thyroid function or those who were being treated for thyroid dysfunction.

Main outcome measure  None.

Results  Of the 541 consecutive pregnant women in different trimesters enrolled for the study, 210 women were excluded. The composition of reference population comprising 331 women was 107 in first trimester, 137 in second trimester and 87 in third trimester. The 5th and 95th percentiles values were used to determine the reference ranges for FT3, FT4 and TSH. The trimester‐wise values in the first, second and third trimesters were: FT3 (1.92–5.86, 3.2–5.73 and 3.3–5.18 pM/l), FT4 (12–19.45, 9.48–19.58 and 11.32–17.7 pM/l) and TSH (0.6–5.0, 0.44–5.78 and 0.74–5.7 iu/ml), respectively. Analysis of mean, median values for FT3, FT4 and TSH between each trimester showed no significant difference in FT3 and TSH values (95% CI). However, FT4 showed significant variation between trimesters with values decreasing with advancing gestational age (P value: first versus second = 0.015, first versus third = 0.003 and second versus third = not significant). Women with antibody positivity and hypoechogenicity of thyroid gland had significantly higher TSH values when compared with women with antibody negativity and normoechogenicity.

Conclusions  Reference ranges of FT3, FT4 and TSH have been established for pregnant Indian women using 5th and 95th percentiles.
Kynurenine pathway metabolism in human blood–brain–barrier cells: implications for immune tolerance & neurotoxicity
Authors: Owe‐Young Robert , Webster Nicole L. , Mukhtar Muhammad , Pomerantz Roger J. , Smythe George , Walker David , Armati Patricia J. , Crowe Suzanne M. , Brew Bruce J.
Published: March 2008

The catabolic pathway of l‐tryptophan (l‐trp), known as the kynurenine pathway (KP), has been implicated in the pathogenesis of a wide range of brain diseases through its ability to lead to immune tolerance and neurotoxicity. As endothelial cells (ECs) and pericytes of the blood–brain–barrier (BBB) are among the first brain‐associated cells that a blood‐borne pathogen would encounter, we sought to determine their expression of the KP. Using RT‐PCR and HPLC/GC‐MS, we show that BBB ECs and pericytes constitutively express components of the KP. BBB ECs constitutively synthesized kynurenic acid, and after immune activation, kynurenine (KYN), which is secreted basolaterally. BBB pericytes produced small amounts of picolinic acid and after immune activation, KYN. These results have significant implications for the pathogenesis of inflammatory brain diseases in general, particularly human immunodeficiency virus (HIV)‐related brain disease. Kynurenine pathway activation at the BBB results in local immune tolerance and neurotoxicity: the basolateral secretion of excess KYN can be further metabolized by perivascular macrophages and microglia with synthesis of quinolinic acid. The results point to a mechanism whereby a systemic inflammatory signal can be transduced across an intact BBB to cause local neurotoxicity.
The co‐evolution of phytoplankton and trace element cycles in the oceans
Authors: MOREL FRANÇOIS M. M.
Published: March 2008

The composition of the oceans and of its biota have influenced each other through Earth's history. Of all the biologically essential elements, nitrogen is the only one whose seawater concentration is clearly controlled biologically; this is presumably the main reason why the stoichiometry of nitrogen (defined as its mol ratio to phosphorus), but not that of the trace nutrients manganese, iron, cobalt, nickel, copper, zinc and cadmium, is the same in seawater and in the plankton. Like the major nutrients, the trace nutrients are depleted in surface seawater as a result of quasi‐complete utilization by the biota. This is made possible in part by the ability of marine phytoplankton to replace one trace metal by another in various biochemical functions. This replacement also results in an equalization of the availability of most essential trace metals in surface seawater. The difference in the stoichiometric composition of the plankton and of deep seawater, which is the dominant source of new nutrients to the surface, indicates that some nutrients are likely recycled with different efficiencies in the photic zone. The difference in the composition of the ocean and its biota provides insight into the coupling of biochemistry and biogeochemistry in seawater.
Genetic and Environmental Influences on the Rate of Progression to Alcohol Dependence in Young Women
Authors: Sartor Carolyn E. , Agrawal Arpana , Lynskey Michael T. , Bucholz Kathleen K. , Heath Andrew C.
Published: March 2008

Background:  The development of alcohol dependence (AD) involves transitions through multiple stages of drinking behaviors and is shaped by both heritable and environmental influences. We attempted to capture this dynamic process by characterizing genetic and environmental contributions to the rate at which women progressed through 3 significant transitions along the pathway to AD: nonuse to initiation, initiation to onset of first alcohol‐related problem, and first problem to onset of AD.

Methods:  The sample consisted of 3,546 female twins from the Missouri Adolescent Female Twin Study. Participants ranged in age from 18 to 29 years. Retrospective reports of alcohol use histories were collected by telephone diagnostic interview and transition times between drinking milestones were coded ordinally. Standard genetic analyses were conducted in Mx to derive a trivariate model that provided estimates of genetic and environmental influences that were common as well as specific to the 3 transition times.

Results:  Heritable influences were found for rate of progression across all 3 transitions, accounting for 30 to 47% of the variance in transition times. Shared environmental contributions were evident only in rate of progression from nonuse to initiation (i.e., age at first drink). Heritable contributions to the rate of movement through successive drinking milestones were attributable to a common factor, whereas environmental influences were transition‐specific.

Conclusions:  The current study is unique in its use of a genetically informative design to document the rate of movement between drinking milestones in a female sample and to examine genetic contributions to multiple transition times over the course of AD development. Results indicate that an earlier report of heritability for males in rate of progression from regular drinking to AD generalizes to women and to other alcohol stage transitions. Findings also suggest the need to consider stage‐specific environmental contributions to alcohol outcomes in developing interventions.
Association of ADH and ALDH Genes With Alcohol Dependence in the Irish Affected Sib Pair Study of Alcohol Dependence (IASPSAD) Sample
Authors: Kuo Po‐Hsiu , Kalsi Gursharan , Prescott Carol A. , Hodgkinson Colin A. , Goldman David , Van Den Oord Edwin J. , Alexander Jeffry , Jiang Cizhong , Sullivan Patrick F. , Patterson Diana G. , Walsh Dermot , Kendler Kenneth S. , Riley Brien P.
Published: March 2008

Background:  The genes coding for ethanol metabolism enzymes [alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH)] have been widely studied for their influence on the risk to develop alcohol dependence (AD). However, the relation between polymorphisms of these metabolism genes and AD in Caucasian subjects has not been clearly established. The present study examined evidence for the association of alcohol metabolism genes with AD in the Irish Affected Sib Pair Study of alcohol dependence.

Methods:  We conducted a case–control association study with 575 independent subjects who met Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, AD diagnosis and 530 controls. A total of 77 single nucleotide polymorphisms (SNPs) in the seven ADH (ADH1‐7) and two ALDH genes (ALDH1A1 and ALDH2) were genotyped using the Illumina GoldenGate protocols. Several statistical procedures were implemented to control for false discoveries.

Results:  All markers with minor allele frequency greater than 0.01 were in Hardy–Weinberg equilibrium. Numerous SNPs in ADH genes showed association with AD, including one marker in the coding region of ADH1C (rs1693482 in exon6, Ile271Gln). Haplotypic association was observed in the ADH5 and ADH1C genes, and in a long haplotype block formed by the ADH1A and ADH1B loci. We detected two significant interactions between pairs of markers in intron 6 of ADH6 and intron 12 of ALDH2 (p = 5 × 10−5), and 5′ of both ADH4 and ADH1A (p = 2 × 10−4).

Conclusion:  We found evidence for the association of several ADH genes with AD in a sample of Western European origin. The significant interaction effects between markers in ADH and ALDH genes suggest possible epistatic roles between alcohol metabolic enzymes in the risk for AD.
Liver dysfunction after chemotherapy in lymphoma patients infected with hepatitis C
Authors: Dizdar Omer , Tapan Umit , Aksoy Sercan , Harputluoglu Hakan , Kilickap Saadettin , Barista Ibrahim
Published: March 2008

Reactivation of hepatitis B virus (HBV) infection in asymptomatic hepatitis B surface antigen carriers undergoing chemotherapy or immunosuppressive therapy is a well‐documented complication. However, data on the consequence of chemotherapy on the course of hepatitis C virus (HCV) infection in HCV(+) patients have been controversial. Here, we review the current knowledge about the complications related to HCV in lymphoma patients receiving chemotherapy/immunosuppressive therapy. Although less frequent than HBV, these complications occur in a subset of patients with mortality rates up to 45%. Therefore, baseline screening for HBV and HCV before initiation of chemotherapy is crucial. High‐risk patients having chronic active hepatitis, high baseline HCV viral load, HBV co‐infection and receiving cytotoxic drugs, corticosteroids and rituximab (particularly if combined) should be closely monitored for serum transaminase, bilirubin and HCV RNA levels.
The silver locus product (Silv/gp100/Pmel17) as a new tool for the analysis of melanosome transfer in human melanocyte–keratinocyte co‐culture
Authors: Singh Suman K. , Nizard Carine , Kurfurst Robin , Bonte Frederic , Schnebert Sylvianne , Tobin Desmond J.
Published: March 2008

Abstract:  Melanosomes are melanocyte‐specific lysosome‐related organelles that are transferred to keratinocytes of the epidermis and anagen hair bulb. Transferred melanin forms supra‐nuclear caps that protect epidermal keratinocytes against UV irradiation. The mechanism(s) responsible for melanosome transfer into keratinocytes and their subsequent intra‐keratinocyte distribution has long remained one of the most enigmatic of heterotypic cell interactions. Although there have been many attempts to study this process, significant progress has been hindered by the absence of an adequate in vitro model. During our ongoing study of melanocyte–keratinocyte interactions in skin and hair follicle, we have developed a novel in vitro assay that exploits the specificity of Silv/Pmel17/gp100 expression for melanosome/melanin granules. Using matched cultures of keratinocytes and melanocytes isolated from normal healthy epidermis together with double immunofluorescence, we have determined that gp100 is a surprisingly useful tracker of transferred melanin. Moreover, transferred gp100 stained melanin granules emit a bright fluorescence signal, facilitating ready quantification of melanin transfer levels between melanocytes and keratinocytes. This quantitative approach was validated using known inducers and inhibitors of the melanocyte phenotype. This assay further confirmed that cytophagocytosis of melanocyte components (e.g. dendrite tips) by keratinocytes is one route for melanin incorporation into keratinocytes. Lastly, a role for the recently proposed filopodium as a direct conduit for melanin transfer was substantiated using this novel approach. In conclusion, this assay promises to significantly aid our investigations of the molecular basis of melanosome transfer and offers a new tool for the clinical evaluation of melanocyte modulators.
High‐Resolution 3D Quantitative Analysis of Caveolar Ultrastructure and Caveola–Cytoskeleton Interactions
Authors: Richter Tobias , Floetenmeyer Matthias , Ferguson Charles , Galea Janette , Goh Jaclyn , Lindsay Margaret R. , Morgan Garry P. , Marsh Brad J. , Parton Robert G.
Published: March 2008

Caveolae are characteristic invaginations of the mammalian plasma membrane (PM) implicated in lipid regulation, signal transduction and endocytosis. We have employed electron microscope tomography (ET) to quantify caveolae structure–function relationships in three‐dimension (3D) at high resolution both in conventionally fixed and in fast‐frozen/freeze‐substituted (intact) cells as well as immunolabelled PM lawns. Our findings provide a detailed quantitative comparison of the average caveola dimensions for different cell types including tissue endothelial cells and cultured 3T3‐L1 adipocytes. These studies revealed the presence of a spiked caveolar coat and a wide caveolar neck open to the extracellular milieu that is sensitive to conventional fixation; the neck region appeared to form a specialized microdomain with associated cytoplasmic material. In endothelial cells in situ in pancreatic islets of Langerhans, the diaphragm spanning the caveolar opening was clearly resolved by ET, and the involuted 3D topology of the cell surface mapped to measure the contribution of caveolar membranes to local increases in the surface area of the PM. The complexity of connections among caveolae and to the actin cytoskeleton and microtubules suggests that individual caveolae may be interconnected through a complex filamentous network to form a single functional unit.
Neonatal testicular torsion – a lost cause?
Authors: Mathews John Cheri , Kooner Gagan , Mathew Deepa E , Ahmed Shiban , Kenny Simon E
Published: March 2008

Twenty‐four neonates presented with signs of testicular ischaemia over a 13‐year period. They had a mean birth weight of 3.706 kg. The right testicle was affected in 13, the left in 9 and there was bilateral torsion in 2 babies. Two babies had no twist in the cord, but the testicles were nonviable macroscopically and microscopically. Twenty‐one babies had primary exploration revealing necrotic testes in all patients and they underwent orchidectomies. The other three babies had conservative management and the affected testes had atrophied on follow‐up. Sixteen babies had contralateral orchidopexy. Doppler ultrasound scans were reported as normal in 2 of 13 babies who had scans. No testes were salvaged following surgery.

Conclusion: The incidence of testicular torsion in the neonatal period was calculated as 6.1 per 100 000 live births. No testis was salvaged following surgery in our series of 24 patients. This dismal outcome underlines that immediate surgical exploration, although commonly performed, rarely saves torted testes.
Modulation of amyloid‐β aggregation and toxicity by inosose stereoisomers
Authors: Nitz Mark , Fenili Daniela , Darabie Audrey A. , Wu Ling , Cousins Julian E. , McLaurin JoAnne
Published: March 2008

Amyloid‐β (Aβ) aggregation and amyloid formation are key pathological features of Alzheimer’s disease, and are considered to be two of the major contributing factors to neurodegeneration and dementia. Identification of small molecule inhibitors that are orally available, have low toxicity and high central nervous system bioavailability is one approach to the potential development of a disease‐modifying treatment for Alzheimer’s disease. We have previously identified inositol stereoisomers as exhibiting stereospecific inhibition of Aβ aggregation and toxicity in vitro and in vivo. We report here the effects of inosose versus inositol stereoisomers on Aβ fibrillogenesis as determined using CD and fluorescence spectroscopy and negative‐stain electron microscopy. The inososes differ from inositols by the oxidation of one of the hydroxyl groups to a ketone. These molecules help in the further elucidation of the structure–activity relationships of inositol–Aβ interactions and identify both allo‐inositol and epi‐2‐inosose as in vitro inhibitors of Aβ aggregation.
Epigenetics: the study of embryonic stem cells by restriction landmark genomic scanning
Authors: Hattori Naka , Shiota Kunio
Published: March 2008

During mammalian development, it is essential that the proper epigenetic state is established across the entire genome in each differentiated cell. To date, little is known about the mechanism for establishing epigenetic modifications of individual genes during the course of cellular differentiation. Genome‐wide DNA methylation analysis of embryonic stem cells by restriction landmark genomic scanning provides information about cell type‐ and tissue‐specific DNA methylation profiles at tissue‐specific methylated regions associated with developmental processes. It also sheds light on DNA methylation alterations following fetal exposure to chemical agents. In addition, analysis of embryonic stem cells deficient in epigenetic regulators will contribute to revealing the mechanism for establishing DNA methylation profiles and the interplay between DNA methylation and other epigenetic modifications.
The amyloplast proteome of potato tuber
Authors: Stensballe Allan , Hald Simon , Bauw Guy , Blennow Andreas , Welinder Karen G.
Published: March 2008

Potato (Solanum tuberosum) is the fourth largest crop worldwide in yield, and cv. Kuras is the major starch potato of northern Europe. Storage starch is packed densely in tuber amyloplasts, which become starch granules. Amyloplasts of soil‐grown mini‐tubers and agar‐grown micro‐tubers of cv. Kuras were purified. The mini‐tuber amyloplast preparation was enriched 10–20‐fold and the micro‐tuber amyloplast approximately fivefold over comparative total protein extracts. Proteins separated by SDS–PAGE were digested with trypsin, analysed by mass spectrometry and identified by mascot software searches against an in‐house potato protein database and the NCBI non‐redundant plant database. The differential growth conditions for mini‐ and micro‐tubers gave rise to rather different protein profiles, but the major starch granule‐bound proteins were identical for both and dominated by granule‐bound starch synthase I, starch synthase II and α‐glucan water dikinase. Soluble proteins were dominated by starch phosphorylase L‐1, other large proteins of the classes ‘starch and sucrose metabolism’, ‘pentose phosphate pathway’, ‘glycolysis’, ‘amino acid metabolism’, and other proteins such as plastid chaperonins. The majority of the identified proteins had a predicted plastid transit peptide, supporting their presence in the amyloplast. However, several highly expressed proteins had no transit peptide, such as starch phosphorylase H, or had a predicted mitochondrial location. Intriguingly, all polyphenol oxidases, a family of enolases, one transketolase, sulfite reductase, deoxynucloside kinase‐like and dihydroxy‐acid dehydrase had twin‐arginine translocation motifs, and a homologue to dihydrolipoamide dehydrogenase had a Sec (secretory) motif; these motifs usually target thylakoid‐like structures.
Interaction and functional association of protein disulfide isomerase with αVβ3 integrin on endothelial cells
Authors: Swiatkowska Maria , Szymański Jacek , Padula Gianluca , Cierniewski Czeslaw S.
Published: March 2008

Adhesive properties of endothelial cells are influenced by the thioldisulfide balance. However, the molecular mechanism of this effect is unclear, although recent observations indicate that integrin receptors may be direct targets for redox modulation. The purpose of this study was to examine whether protein disulfide isomerase (PDI) is directly involved in this process. As manganese ions are known to affect the thioldisulfide balance and activate integrins to maximal affinity, we searched for PDI interactions with integrins, particularly with αVβ3, in Mn2+‐treated endothelial cells. By employing confocal microscopy, flow cytometry and coimmunoprecipitation experiments, we showed that exposure of endothelial cells to Mn2+ resulted in: (a) the appearance of surface protein thiol groups, which can be found in PDI and αVβ3, and both proteins colocalizing on the cellular surface; and (b) the formation of the PDI–αVβ3 complex, which dissociates upon reduction. In addition, PDI in a complex with αVβ3 induces conversion of the integrin to the ligand‐competent high‐affinity state, as evidenced by increased binding of vitronectin. The membrane‐impermeable sulfhydryl blockers 3‐N‐maleimidylpropionyl biocytin 3‐N‐maleimidylpropionyl biocytin and p‐chloromercuriphenyl sulfonate, as well as the PDI inhibitors bacitracin, MA3 018, and MA3 019, abolished the binding of vitronectin and LM609 to endothelial cells that is activated by Mn2+. Consistently, LM609 almost completely blocked binding of vitronectin to such cells. The formation of the PDI–αVβ3 stoichiometric complex was further demonstrated by surface plasmon resonance analysis, which showed that the initial reversible binding of PDI becomes irreversible in the presence of Mn2+, probably mediated by disulfide bonds. Thus, we show that Mn2+ simultaneously modulates the thiol isomerase activity of PDI that is bound to αVβ3 and induces its transition to the ligand‐competent state, suggesting an alternative mechanism of integrin regulation.
Tracing Ground Water Input to Base Flow Using Sulfate (S, O) Isotopes
Authors: Gu Ailiang , Gray Floyd , Eastoe Christopher J. , Norman Laura M. , Duarte Oscar , Long Austin
Published: March 2008

Sulfate (S and O) isotopes used in conjunction with sulfate concentration provide a tracer for ground water contributions to base flow. They are particularly useful in areas where rock sources of contrasting S isotope character are juxtaposed, where water chemistry or H and O isotopes fail to distinguish water sources, and in arid areas where rain water contributions to base flow are minimal. Sonoita Creek basin in southern Arizona, where evaporite and igneous sources of sulfur are commonly juxtaposed, serves as an example. Base flow in Sonoita Creek is a mixture of three ground water sources: A, basin ground water with sulfate resembling that from Permian evaporite; B, ground water from the Patagonia Mountains; and C, ground water associated with Temporal Gulch. B and C contain sulfate like that of acid rock drainage in the region but differ in sulfate content. Source A contributes 50% to 70%, with the remainder equally divided between B and C during the base flow seasons. The proportion of B generally increases downstream. The proportion of A is greatest under drought conditions.
Quantum Mechanical/Molecular Mechanical Studies on Spectral Tuning Mechanisms of Visual Pigments and Other Photoactive Proteins†
Authors: Altun Ahmet , Yokoyama Shozo , Morokuma Keiji
Published: March 2008

The protein environments surrounding the retinal tune electronic absorption maximum from 350 to 630 nm. Hybrid quantum mechanical/molecular mechanical (QM/MM) methods can be used in calculating excitation energies of retinal in its native protein environments and in studying the molecular basis of spectral tuning. We hereby review recent QM/MM results on the phototransduction of bovine rhodopsin, bacteriorhodopsin, sensory rhodopsin II, nonretinal photoactive yellow protein and their mutants.
Melanosomal Damage in Normal Human Melanocytes Induced by UVB and Metal Uptake—A Basis for the Pro‐oxidant State of Melanoma†
Authors: Gidanian Shirley , Mentelle Mallory , Meyskens Frank L. , Farmer Patrick J.
Published: March 2008

Melanins are ubiquitous catecholic pigments, formed in organelles called melanosomes within melanocytes, the function of which is to protect skin against harmful effects of UV radiation. Melanosomes within melanoma cells are characteristically abnormal, with fragmented melanin and disrupted membranes. We hypothesize that the disruption of melanosomal melanin might be an early event in the etiology and progression of melanoma, leading to increased oxidative stress and mutation. In this report, we examine the effect of a combination of UV treatment and metal ion exposure on melanosomes within melanocytes, as well as their ability to act as pro‐oxidants in ex situ experiments, and assay the effects of this treatment on viability and cell cycle progression. UVB exposure causes morphologic changes of the cells and bleaching of melanosomes in normal melanocytes, both significantly enhanced in Cu(II) and Cd(II)‐treated cells, as observed by microscopy. The promoted bleaching by Cu(II) is due to its ability to redox cycle under oxidative conditions, generating reactive oxygen species; verified by the observed enhancement of hydroxyl radical generation when isolated melanosomes were treated with both Cu(II) ions and UVB, as assayed by DNA clipping. Single‐dose UVB/Cu treatment does not greatly affect cell viability or cell cycle progression in heavily pigmented cells, but did so in an amelanotic early stage melanoma cell line.
Salamander Blue‐sensitive Cones Lost During Metamorphosis†
Authors: Chen Ying , Znoiko Sergey , DeGrip Willem J. , Crouch Rosalie K. , Ma Jian‐xing
Published: March 2008

The tiger salamander lives in shallow water with bright light in the aquatic phase, and in dim tunnels or caves in the terrestrial phase. In the aquatic phase, there are five types of photoreceptors—two types of rods and three types of cones. Our previous studies showed that the green rods and blue‐sensitive cones contain the same visual pigment and have the same absorbance spectra; however, the green rods have a larger photon‐catch area and thus have higher light sensitivity than the blue‐sensitive cones. Here we show that after metamorphosis, the terrestrial salamander looses the blue‐sensitive cones, while the density of the green rods increases. Moreover, the size of the green rod outer segments is increased in the terrestrial phase, compared to that in the aquatic phase. This switch from the blue‐sensitive cones to the green rods may represent an adaptation to the dim light environment of the terrestrial phase.
Oxygen Dependence of Two‐photon Activation of Zinc and Copper Phthalocyanine Tetrasulfonate in Jurkat Cells
Authors: Mir Youssef , Van Lier Johan E. , Paquette Benoit , Houde Daniel
Published: March 2008

Photodynamic therapy (PDT), the use of light‐activated drugs, is a promising treatment of cancer as well as several nonmalignant conditions. However, the efficacy of one‐photon (1‐γ) PDT is limited by hypoxia, which can prevent the production of the cytotoxic singlet oxygen (1O2) species, leading to tumor resistance to PDT. To solve this problem, we propose an irradiation protocol based on a simultaneous, two‐photon (2‐γ) excitation of the photosensitizer (Ps). Excitation of the Ps triplet state leads to an upper excited triplet state Tn with distinct photochemical properties, which could inflict biologic damage independent of the presence of molecular oxygen. To determine the potential of a 2‐γ excitation process, Jurkat cells were incubated with zinc or copper phthalocyanine tetrasulfonate (ZnPcS4 or CuPcS4). ZnPcS4 is a potent 1O2 generator in 1‐γ PDT, while CuPcS4 is inactive under these conditions. Jurkat cells incubated with either ZnPcS4 or CuPcS4 were exposed to a 670 nm continuous laser (1‐γ PDT), 532 nm pulsed‐laser light (2‐γ PDT), or a combination of 532 and 670 nm (2‐γ PDT). The efficacy of ZnPcS4 to photoinactivate the Jurkat cells decreased as the concentration of oxygen decreased for both the 1‐γ and 2‐γ protocols. In the case of CuPcS4, cell phototoxicity was measured only following 2‐γ irradiation, and its efficacy also decreased at a lower oxygen concentration. Our results suggest that for CuPcS4 the Tn excited state can be populated after 2‐γ irradiation at 532 nm or the combination of 532 and 670 nm light. Dependency of phototoxicity upon aerobic conditions for both 1‐γ and 2‐γ PDT suggests that reactive oxygen species play an important role in 1‐γ and 2‐γ PDT.
The Length of Esterifying Alcohol Affects the Aggregation Properties of Chlorosomal Bacteriochlorophylls
Authors: Zupcanova Anita , Arellano Juan B. , Bina David , Kopecky Jiri , Psencik Jakub , Vacha Frantisek
Published: March 2008

Chlorosomes, the main light‐harvesting complexes of green photosynthetic bacteria, contain bacteriochlorophyll (BChl) molecules in the form of self‐assembling aggregates. To study the role of esterifying alcohols in BChl aggregation we have prepared a series of bacteriochlorophyllide c (BChlide c) derivatives differing in the length of the esterifying alcohol (C1, C4, C8 and C12). Their aggregation behavior was studied both in polar (aqueous buffer) and nonpolar (hexane) environments and the esterifying alcohols were found to play an essential role. In aqueous buffer, hydrophobic interactions among esterifying alcohols drive BChlide c derivatives with longer chains into the formation of dimers, while this interaction is weak for BChlides with shorter esterifying alcohols and they remain mainly as monomers. All studied BChlide c derivatives form aggregates in hexane, but the process slows down with longer esterifying alcohols due to competing hydrophobic interactions with hexane molecules. In addition, the effect of the length of the solvent molecules (n‐alkanes) was explored for BChl c aggregation. With an increasing length of n‐alkane molecules, the hydrophobic interaction with the farnesyl chain becomes stronger, leading to a slower aggregation rate. The results show that the hydrophobic interaction is the driving force for the aggregation in an aqueous environment, while in nonpolar solvents it is the hydrophilic interaction.
Aristotle and Earthquake Data: A Historical Note
Authors: Missiakoulis Spyros
Published: March 2008

The earliest known written work on earthquake theory was written by Aristotle (c. 330 B.C.). Aristotle had collected a lot of earthquake data and therefore we assume (or rather speculate) he had to organize, to classify and to summarize them in order to use and describe them in his work. With respect to the history of Statistics, the Aristotelian text on earthquake theory is probably the earliest written application of statistical tables on collected data.
Investigating the Fate and Transport of Escherichia coli in the Charles River, Boston, Using High‐Resolution Observation and Modeling1
Authors: Hellweger Ferdi L. , Masopust Petr
Published: March 2008

Abstract:  The processes affecting the fate and transport of Escherichia coli in surface waters were investigated using high‐resolution observation and modeling. The concentration patterns in Boston’s Charles River were observed during four sampling events with a total of 757 samples, including two spatial surveys with two along‐river (1,500 m length) and three across‐river (600 m length) transects at approximately 25‐m intervals, and two temporal surveys at a fixed location (Community Boating) over seven days at hourly intervals. The data reveal significant spatial and temporal structure at scales not resolved by typical monitoring programs. A mechanistic, time‐variable, three‐dimensional coupled hydrodynamic and water quality model was developed using the ECOMSED and RCA modeling frameworks. The computational grid consists of 3,066 grid cells with average length dimension of 25 m. Forcing functions include upstream and downstream boundary conditions, Stony Brook, and Muddy River (major tributaries) combined sewer overflow (CSO) and non‐CSO discharge and wind. The model generally reproduces the observed spatial and temporal patterns. This includes the presence and absence of a plume in the study area under similar loading, but different hydrodynamic conditions caused by operation of the New Charles River Dam (downstream) and wind. The model also correctly predicts an episode of high concentrations at the time‐series station following seven days of no rainfall. The model has an overall root mean square error (RMSE) of 250 CFU/100 ml and an error rate (above or below the USEPA‐recommended single sample criteria value of 235 CFU/100 ml) of 9.4%. At the time series station, the model has an RMSE of 370 CFU/100 ml and an error rate of 15%.
Dental Health Services Utilization and Associated Factors in Children 6 to 12 Years Old in a Low‐Income Country
Authors: Medina‐Solis Carlo Eduardo , Maupomé Gerardo , Del Socorro Herrera Miriam , Pérez‐Núñez Ricardo , Ávila‐Burgos Leticia , Lamadrid‐Figueroa Hector
Published: March 2008

Objective: To determine the factors associated with the dental health services utilization among children ages 6 to 12 in León, Nicaragua.

Material and Methods: A cross‐sectional study was carried out in 1,400 schoolchildren. Using a questionnaire, we determined information related to utilization and independent variables in the previous year. Oral health needs were established by means of a dental examination. To identify the independent variables associated with dental health services utilization, two types of multivariate regression models were used, according to the measurement scale of the outcome variable: a) frequency of utilization as (0) none, (1) one, and (2) two or more, analyzed with the ordered logistic regression and b) the type of service utilized as (0) none, (1) preventive services, (2) curative services, and (3) both services, analyzed with the multinomial logistic regression.

Results: The proportion of children who received at least one dental service in the 12 months prior to the study was 27.7 percent. The variables associated with utilization in the two models were older age, female sex, more frequent toothbrushing, positive attitude of the mother toward the child's oral health, higher socioeconomic level, and higher oral health needs.

Conclusion: Various predisposing, enabling, and oral health needs variables were associated with higher dental health services utilization. As in prior reports elsewhere, these results from Nicaragua confirmed that utilization inequalities exist between socioeconomic groups. The multinomial logistic regression model evidenced the association of different variables depending on the type of service used.
Rural and Urban Disparities in Caries Prevalence in Children with Unmet Dental Needs: The New England Children's Amalgam Trial
Authors: Maserejian Nancy Nairi , Tavares Mary A. , Hayes Catherine , Soncini Jennifer A. , Trachtenberg Felicia L.
Published: March 2008

Objectives: To compare the prevalence of caries between rural and urban children with unmet dental health needs who participated in the New England Children's Amalgam Trial.

Methods: Baseline tooth and surface caries were clinically assessed in children from rural Maine (n = 243) and urban Boston (n = 291), who were aged 6 to 10 years, with two or more posterior carious teeth and no previous amalgam restorations. Statistical analyses used negative binomial models for primary dentition caries and zero‐inflated models for permanent dentition caries.

Results: Urban children had a higher mean number of carious primary surfaces (8.5 versus 7.4) and teeth (4.5 versus 3.9) than rural children. The difference remained statistically significant after adjusting for sociodemographic factors and toothbrushing frequency. In permanent dentition, urban children were approximately three times as likely to have any carious surfaces or teeth. However, rural/urban dwelling was not statistically significant in the linear analysis of caries prevalence among children with any permanent dentition caries. Covariates that were statistically significant in all models were age and number of teeth. Toothbrushing frequency was also important for permanent teeth.

Conclusions: Within this population of New England children with unmet oral health needs, significant differences were apparent between rural and urban children in the extent of untreated dental decay. Results indicate that families who agree to participate in programs offering reduced cost or free dental care may present with varying amounts of dental need based on geographic location.