bluuebunny/crossref_metadata_2025 huggingface dataset:
Phenoxaphosphino‐Modified Xantphos‐Type Ligands in the Rhodium‐Catalysed Hydroformylation of Internal and Terminal Alkenes
Authors: Bronger Raymond P. J. , Bermon Jochem P. , Herwig Jürgen , Kamer Paul C. J. , van Leeuwen Piet W. N. M.
Published: July 2004

The solubility of the modifying ligand is an important parameter for the efficiency of a rhodium‐catalysed hydroformylation system. A facile synthetic procedure for the preparation of well‐defined xanthene‐type ligands was developed in order to study the influence of alkyl substituents at the 2‐, and 7‐positions of the 9,9‐dimethylxanthene backbone and at the 2‐, and 8‐positions of the phenoxaphosphino moiety of ligands 1–16 on solubility in toluene and the influence of these substituents on the performance of the ligands in the rhodium‐catalysed hydroformylation. An increase in solubility from 2.3 mmol⋅L−1 to >495 mmol⋅L−1 was observed from the least soluble to the most soluble ligand. A solubility of at least 58 mmol⋅L−1 was estimated to be sufficient for a large‐scale application of these ligands in hydroformylation. Highly active and selective catalysts for the rhodium‐catalysed hydroformylation of 1‐octene and trans‐2‐octene to nonanal, and for the hydroformylation of 2‐pentene to hexanal were obtained by employing these ligands. Average rates of >1600 (mol aldehyde) × (mol Rh)−1×h−1 {conditions: p(CO/H2) = 20 bar, T = 353 K, [Rh] = 1 mM, [alkene] = 637 mM} and excellent regio‐selectivities of up to 99% toward the linear product were obtained when 1‐octene was used as substrate. For internal olefins average rates of >145 (mol aldehyde)×(mol Rh)−1×h−1 {p(CO/H2) = 3.6–10 bar, T = 393 K, [Rh] = 1 mM, [alkene] = 640–928 mM} and high regio‐selectivities up to 91% toward the linear product were obtained.
Highly Enantioselective Synthesis of Secondary Alcohols using Triphenylborane
Authors: Rudolph Jens , Schmidt Frank , Bolm Carsten
Published: July 2004

Asymmetric phenyl transfer reactions with triphenylborane as aryl source and a ferrocene‐based catalyst give secondary alcohols in high yields and excellent enantioselectivities.
Second‐Generation Paracyclophane Imine Ligands for the Dialkylzinc Addition to Aldehydes. Optimization of the Branched Side Chain leads to Improvement for Aliphatic Aldehydes
Authors: Höfener Sebastian , Lauterwasser Frank , Bräse Stefan
Published: July 2004

Two novel diastereomeric [2.2]paracyclophane ketimine ligands (SP,S)‐2 and (RP,S)‐2, which unite a planar chiral element and a central chiral element, were used towards the enantioselective diethylzinc addition onto aliphatic aldehydes. These improved second‐generation ligands, which are stable in air and water and are easy to obtain, showed significant improvements with respect to the ligands that were previously used.
Smoking is an occupational hazard
Authors: Howard John
Published: July 2004

Background

Even though the prevalence of tobacco smoking has declined in the general population and among white‐collar workers, the prevalence of tobacco smoking among blue‐collar workers remains unacceptably high. Blue‐collar workers experience greater exposure to workplace toxins which can add to, or even multiply, their risk of adverse health effects from tobacco smoking. Among blue‐collar workers, workers in the restaurant, bar, and gaming industries are exposed to much higher levels of environmental tobacco smoke (ETS) than are office workers, and are at increased risk of cancer and cardiovascular diseases even if they are non‐smokers themselves.

Methods

The literature on health risks, and the disparity between white and blue collar workers in smoking prevalence, and the literature on various tobacco control strategies provide the sources on which this review is based.

Conclusions

Over the past 20 years, the accumulating scientific evidence about smoking as an occupational hazard has prompted the implementation of various educational, economic, and legal tobacco control strategies. Am. J. Ind. Med. 46:161–169, 2004. Published 2004 Wiley‐Liss, Inc.
Efficacy of tobacco dependence treatment in the context of a “smoke‐free grounds” worksite policy: A case study
Authors: Osinubi Omowunmi Y.O. , Sinha Sharmila , Rovner Elisheva , Perez‐Lugo Marla , Jain Neetu J. , Demissie Kitaw , Goldman Maurice
Published: July 2004

Background

Smoking restrictions provide opportunities to modify smoking behavior. A large insurance company implemented a smoke‐free grounds policy at two of their office complexes in January, 2000.

Methods

This cohort study evaluated the impact of the smoke‐free grounds policy on abstinence among 128 employees who participated in a tobacco dependence treatment program.

Results

The overall quit rate at 6 months was 44.5%. The larger complex showed a trend for higher quit rates compared to the smaller complex (46.5 vs. 28.6%). Post‐ban participants had higher quit rates than pre‐ban participants (52.4 vs. 43.0%). The probability of abstinence at 6 months follow‐up was higher for post‐ban compared to pre‐ban participants (P = 0.03). Post‐ban participants were 80% less likely to relapse than pre‐ban participants. Non‐quitters decreased their consumption by 6.6 cigarettes/day (39.1% decrease).

Conclusions

A “smoke‐free grounds” policy encourages abstinence and may play a significant role in harm reduction among continuing tobacco users. Am. J. Ind. Med. 46:180–187, 2004. © 2004 Wiley‐Liss, Inc.
Evaluation of the reliability and validity of the University of South Florida Environmental Assessment Questionnaire
Authors: Haight Robert R. , Vuskovich Matthew A. , Brooks Stuart M. , Berish Thomas S.
Published: July 2004

Background

The National Institute for Occupational Safety and Health's (NIOSH) National Occupational Research Agenda (NORA), identified “exposure assessment methods” as a priority area for research in occupational medicine.

Methods

The University of South Florida Environmental Assessment Questionnaire (EAQ) describes exposures from the workers point of view. The questionnaire was distributed to a sample of workers drawn from a population of over 3,000 workers employed by a Florida food processing plant. The analysis of the validity was based on 211 subjects and the analysis of the reliability was based on 44 subjects.

Results

For the category scores, the sensitivities ranged from 0.67 to 1.0, the specificities ranged from 0.52 to 0.83, the positive predictive values ranged from 0.60 to 1.0, and the negative predictive values ranged from 0.55 to 1.0. All of the weighted kappas for the subcategories were above zero. The Spearman rank‐order coefficients were above 0.5 for all of the exposure categories except the mold, plant, and animal exposure category which was 0.49. The correlation coefficient for the questionnaire as a whole was 0.85.

Conclusions

This study showed the EAQ as a whole to be reliable and valid. Gathering valid occupational exposure information with this method was both feasible and economical. Am. J. Ind. Med. 46:142–150, 2004. © 2004 Wiley‐Liss, Inc.
Reducing occupation‐based disparities related to tobacco: Roles for occupational health and organized labor
Authors: Barbeau Elizabeth M. , McLellan Deborah , Levenstein Charles , DeLaurier Gregory F. , Kelder Graham , Sorensen Glorian
Published: July 2004

Background

Persistent and growing occupation‐based disparities related to tobacco pose a serious public health challenge. Tobacco exacts a disproportionate toll on individuals employed in working class occupations, due to higher prevalence of smoking and exposure to secondhand smoke among these workers compared to others.

Methods

We provide an overview of recent advances that may help to reduce these disparities, including research findings on a successful social contextual intervention model that integrates smoking cessation and occupational health and safety, and a new national effort to link labor unions and tobacco control organizations around their shared interest in reducing tobacco's threat to workers' health.

Conclusions

Implications of these efforts for future research and action are discussed. Am. J. Ind. Med. 46:170–179, 2004. © 2004 Wiley‐Liss, Inc.
The New York City Smoke‐Free Air Act: Second‐hand smoke as a worker health and safety issue
Authors: Chang Christina , Leighton Jessica , Mostashari Farzad , McCord Colin , Frieden Thomas R.
Published: July 2004

Background

Despite the provisions of a Smoke‐Free Air Act (SFAA) enacted in 1995, more than 415,000 non‐smoking New York City workers reported exposure to second‐hand smoke in the workplace all or most of the time in 2002. Continued exposure to second‐hand smoke in New York City prompted a renewed debate about a broader smoke‐free air law.

Methods

The approach taken by the New York City Department of Health and Mental Hygiene to make the case for workplace protection from second‐hand smoke, counter the opposition's arguments, and ultimately win the support of policymakers and the public for comprehensive smoke‐free workplace legislation is described.

Results

On December 30, 2002, New York City's Mayor signed the SFAA of 2002 into law, making virtually all workplaces, including restaurants and bars, smoke‐free.

Conclusions

Proponents for a stronger law prevailed by defining greater protection from second‐hand smoke as a matter of worker health and safety. Efforts to enact smoke‐free workplace laws will inevitably encounter strong opposition, with the most common argument being that smoke‐free measures will harm businesses. These challenges, however, can be effectively countered and public support for these measures is likely to increase over time by focusing the debate on worker protection from second‐hand smoke exposure on the job. Am. J. Ind. Med. 46:188–195, 2004. © 2004 Wiley‐Liss, Inc.
Predictors of smoke‐free workplaces by employee characteristics: Who is left unprotected?
Authors: Delnevo Cristine D. , Hrywna Mary , Jane Lewis M.
Published: July 2004

Background

Over the last decade, there has been steady progress in the adoption of workplace smoking policies in the United States. However, the benefits of a smoke‐free workplace are not distributed equally among the workforce.

Methods

Data from 44,357 adults who reported that they work indoors were derived from an optional tobacco module on the 2001 Behavioral Risk Factor Surveillance System (BRFSS), administered by 25 states. Logistic regression was utilized to examine factors associated with the absence of a smoke‐free workplace policy.

Results

Overall, 70.9% of respondents reported working under a smoke‐free workplace policy. The likelihood of being protected by a smoke‐free workplace policy was significantly lower among workers who were younger, male, non‐white, engaged in heavy labor, earned less than $50,000 annually, had a high school education or less, smoked everyday, or worked in the South or Midwest.

Conclusions

There remain considerable gaps in smoke‐free workplace policy coverage. Am. J. Ind. Med. 46:196–202, 2004. © 2004 Wiley‐Liss, Inc.
Airflow obstruction attributable to work in industry and occupation among U.S. race/ethnic groups: A study of NHANES III data
Authors: Hnizdo Eva , Sullivan Patricia A. , Bang Ki Moon , Wagner Gregory
Published: July 2004

Objectives

To estimate the fraction of airflow obstruction attributable to workplace exposure by U.S. race/ethnic group.

Methods

U.S. population‐based third National Health and Nutrition Examination Survey (NHANES III) data on 4,086 Caucasians, 2,774 African‐Americans, and 2,568 Mexican‐Americans, aged 30–75, were studied. Airflow obstruction was defined as FEV1/FVC<75% and FEV1<80% predicted. Weighted prevalence, and prevalence odds ratios (OR) adjusted for the effect of age, smoking status, pack‐years, body mass index, education, and socio‐economic status were estimated using SUDAAN software.

Results

Industries with the most cases of airflow obstruction attributable to workplace exposure include: armed forces; rubber, plastics, and leather manufacturing; utilities; textile mill manufacturing; health care; food products manufacturing; sales; construction; and agriculture. The fraction of cases with airflow obstruction associated with work in industry varied by race/ethnic group and was estimated as 22.2% (95% CI 9.1–33.4) among Caucasians, 23.4% (95% CI 2.2–40.0) among African‐Americans, and 49.6% (32.1–62.6) among Mexican‐Americans.

Conclusions

This study found differences in the fraction of airflow obstruction cases associated with employment pattern among major U.S. race/ethnic population groups. Am. J. Ind. Med. 46:126–135, 2004. Published 2004 Wiley‐Liss, Inc.
Lack of modulating influence of GSTM1 and GSTT1 polymorphisms on urinary biomonitoring markers in coke‐oven workers
Authors: Wu Ming‐Tsang , Pan Chih‐Hong , Chen Ching‐Yi , Chen Chiou‐Jong , Huang Li‐Hung , Tsai Li‐Yu , Huang Chia‐Tsuan , Ho Chi‐Kung
Published: July 2004

Background

Coke‐oven workers (COWs) are occupationally exposed to high concentrations of polycyclic aromatic hydrocarbons (PAHs). Urinary 8‐hydroxy‐2‐deoxyguanosine (8‐OH‐dG) and 1‐hydroxypyrene (1‐OHP) are biological markers of oxidative DNA damage and PAHs metabolism, respectively. In this study, we investigated whether polymorphisms of glutathione S‐transferase (GSTM1 and GSTT1) can modulate the relationship between urinary 8‐OH‐dG and 1‐OHP concentrations among the COWs.

Methods

This was a cross‐sectional study. Between February and November of 2001, 53 topside‐oven and 130 side‐oven workers with the presence of GSTM1 and GSTT1 genotypes were investigated.

Results

Urinary 1‐OHP and 8‐OH‐dG concentrations (mean ± SD) in the topside‐oven workers with the presence of GSTM1 were 107.2 ± 107.9 and 15.3 ± 9.7 ng/ml, respectively, which were not significantly different from those in the absence of GSTM1 (84.1 ± 104.5 and 12.8 ± 14.1 ng/ml). The similar insignificant results were also noted in the sideoven workers. For GSTT1 polymorphism, the results remained insignificant. In contrast, individual excretion of urinary 8‐OH‐dG and 1‐OHP concentrations were still highly correlated (Spearman correlation coefficients: r = 0.43, P < 0.0001, n = 183).

Conclusions

GST may not play a role in the regulation of metabolism of urinary biological markers in COWs. Am. J. Ind. Med. 46:112–119, 2004. © 2004 Wiley‐Liss, Inc.
Impairment of cell and plasma redox state in subjects professionally exposed to chromium
Authors: Mattia Giancarlo De , Bravi Maria Cristina , Laurenti Oriana , Luca Orietta De , Palmeri Alessandro , Sabatucci Antonio , Mendico Gino , Ghiselli Andrea
Published: July 2004

Background

Chromium (Cr) is widely used in chemical, tannery, building, and metal industries. More recently, it has been demonstrated that Cr induces oxidative stress in mouse brain. Nevertheless very few data exist on in vivo oxidative damage in humans exposed to Cr.

Methods

Changes in antioxidant parameters both in plasma (acid ascorbic redox state and total antioxidant capacity) and in red blood cells (glutathione (GSH) redox state) of 40 subjects (age 37.65 ± 7.46; M/F 20/20) professionally exposed to Cr who were recruited from metal, chemistry, and building industries were evaluated. We also evaluated the levels of lipoperoxidation (thiobarbituric acid‐reactive material, TBA‐RM) and thiol levels in plasma to assess the extent of oxidative stress state. To evaluate Cr exposure rate, we measured urinary‐chromium (U‐Cr) by an electrothermic atomization‐atomic absorption spectrometry (ETA‐AAS) method.

Results

In this study, we found that Cr exposure induced a decrease both in GSH (P < 0.0005) and GSH/oxidized glutathione (GSSG) ratio (P < 0.0001) in red blood cells from workers with respect to control subjects. Furthermore, we also demonstrated a significant decrease of plasma acid ascorbic levels (45.7 ± 14.9 vs. 53.5 ± 16.5 μmol/L; P < 0.05) and in total plasma antioxidant capacity (1,126.3 ± 212.2 vs. 1,266.9 ± 207.8 μmol/L; P < 0.05) in subjects exposed to Cr. No difference was found with regard to TBA‐RM and thiol levels.

Conclusions

This study demonstrated that in humans, an oxidative stress occurs for Cr exposures as low as those considered safe. This oxidative stress appears to be able to affect intracellular and plasmatic antioxidant defense. Am. J. Ind. Med. 46:120–125, 2004. © 2004 Wiley‐Liss, Inc.
The association between HLA‐DPB1Glu69 and chronic beryllium disease and beryllium sensitization
Authors: McCanlies Erin C. , Ensey James S. , Schuler Christine R. , Kreiss Kathleen , Weston Ainsley
Published: July 2004

Background

Several case‐control studies have found an association between chronic beryllium disease (CBD) and HLA‐DPB1 gene variants. However, the relationship between HLA‐DPB1 and beryllium sensitization, and whether the presence of one or two HLA‐DPB1Glu69 alleles is differentially associated with CBD and beryllium sensitization have not been completely resolved.

Methods

Restriction fragment length polymorphism (RFLP) analysis was used to address these questions in a large population‐based cohort consisting of 884 beryllium workers (90 with CBD, 64 beryllium sensitized).

Results

HLA‐DPB1Glu69 was associated with both CBD (OR = 9.4; 95% CI = 5.4, 16.6) and sensitization (OR = 3.3, 95% CI = 1.9, 5.9). Further, workers with CBD and sensitization were more likely to be homozygous HLA‐DPB1Glu69 compared to workers without disease or sensitization (P < 0.001).

Conclusions

Follow‐up of this cohort, scrutiny of HLA‐DPB1 haplotypes, and evaluation of gene–environment and gene–gene interactions will be important for fully understanding the immunogenetic nature of this occupational disease. Am. J. Ind. Med. 46:95–103, 2004. Published 2004 Wiley‐Liss, Inc.
Self‐reported dermatitis and skin cancer in California farm operators
Authors: Susitaival Päivikki , Beckman Robin , Samuels Steven J. , Schenker Marc B.
Published: July 2004

Background

High rates of skin diseases and higher non‐melanoma skin cancer rates have been reported in farmers.

Methods

Self‐report of dermatitis and skin cancer was among the information collected from 1947 California farm operators, mostly men, in a telephone survey. The majority of the farmers cultivated fruits, nuts, or other field crops.

Results

Dermatitis was reported by 8.9% of men and 15.8% of women during the previous 12 months. In a logistic regression model, female gender (OR 2.0, 95% confidence interval 1.3–3.0) and respiratory atopy (OR 1.4, 1.01–1.90) were the only significant independent risk factors for reported dermatosis. There was significantly less reporting of skin cancer among field farmers when compared to others. Regular sunscreen use was reported significantly more often by women (42%) as compared to men (11%).

Conclusions

More in‐depth studies are needed to get information on the role of agrochemicals as risk factors for dermatitis and skin cancer. Am. J. Ind. Med. 46:136–141, 2004. © 2004 Wiley‐Liss, Inc.
Spray‐painting and chronic airways obstruction
Authors: Glindmeyer Henry W. , Lefante John J. , Rando Roy J. , Freyder Laurie , Hnizdo Eva , Jones Robert N.
Published: July 2004

Background

The aim was to investigate the respiratory response of HDI‐based paint aerosol within the context of the protection afforded by current exposure guidelines.

Methods

A cross‐sectional study of 240 painters spraying polyurethane enamels was undertaken at four aircraft maintenance plants. Questionnaire and spirometric data were related to gravimetric measures of cumulative total and respirable paint aerosol (TPA and RPA) and estimated isocyanate in total and respirable aerosols (TIA and RIA).

Results

Average cumulative exposures in mg/m3‐years ± SD were 159.0 ± 115.2 TPA, 19.1 ± 13.8 RPA, 15.8 ± 11.5 TIA, and 1.9 ± 1.4 RIA. After adjusting for smoking and asthma symptoms, higher exposures were associated with statistically significant reduction in expiratory flowrates. Significant smoking‐related reductions were also observed, without exposure interactions.

Conclusions

These results suggest important respiratory effects from exposures to spray paint aerosols at levels generally in compliance with existing standards for otherwise unregulated particulates and for the isocyanate component of the paint. Am. J. Ind. Med. 46:104–111, 2004. © 2004 Wiley‐Liss, Inc.
Spondylometaphyseal dysplasia with cone‐rod dystrophy
Authors: Walters Brent A. , Raff Michael L. , Hoeve James Ver , Tesser Rachel , Langer Leonard O. , France Thomas D. , Glass Ian A. , Pauli Richard M.
Published: July 2004

The co‐occurrence of ophthalmologic abnormality and intrinsic skeletal dysplasia is uncommon. We describe eight instances of a unique form of spondylometaphyseal dysplasia (SMD) associated with cone‐rod dystrophy (although documentation is insufficient to be certain of that diagnosis in some). This is a new, syndromic form of SMD for which there is evidence for autosomal recessive transmission. Recognition of the specific bony features described here should precipitate comprehensive ophthalmologic assessment, since vision impairment becomes significantly disabling with age. © 2004 Wiley‐Liss, Inc.
Congenital glaucoma and brain stem atrophy as features of Aicardi–Goutières syndrome
Authors: Crow Yanick J. , Massey R.F. , Innes J.R. , Pairaudeau P.W. , Rowland Hill C.A. , Woods C.G. , Ali M. , Livingston J.H. , Lebon P. , Nischall K. , McEntagart M. , Hindocha N. , Winter R.M.
Published: July 2004

We report on three children from two families with Aicardi–Goutières syndrome. All three had congenital glaucoma. Additionally, neuroimaging demonstrated significant brain stem atrophy in the affected sib‐pair. These features have not been previously described in Aicardi–Goutières syndrome and expand the phenotypic spectrum. © 2004 Wiley‐Liss, Inc.
Idiopathic hyposmia as a preclinical sign of Parkinson's disease
Authors: Ponsen Mirthe M. , Stoffers Diederick , Booij Jan , van Eck‐Smit Berthe L. F. , Wolters Erik Ch. , Berendse Henk W.
Published: July 2004

Olfactory dysfunction is an early and common symptom in Parkinson's disease (PD). In an effort to determine whether otherwise unexplained (idiopathic) olfactory dysfunction is associated with an increased risk of developing PD, we designed a prospective study in a cohort of 361 asymptomatic relatives (parents, siblings, or children) of PD patients. A combination of olfactory detection, identification, and discrimination tasks was used to select groups of hyposmic (n = 40) and normosmic (n = 38) individuals for a 2‐year clinical follow‐up evaluation and sequential single‐photon emission computed tomography (SPECT), using [123I]β‐CIT as a dopamine transporter ligand, to assess nigrostriatal dopaminergic function at baseline and 2 years from baseline. A validated questionnaire, sensitive to the presence of parkinsonism, was used in the follow‐up of the remaining 283 relatives. Two years from baseline, 10% of the individuals with idiopathic hyposmia, who also had strongly reduced [123I]β‐CIT binding at baseline, had developed clinical PD as opposed to none of the other relatives in the cohort. In the remaining nonparkinsonian hyposmic relatives, the average rate of decline in dopamine transporter binding was significantly higher than in the normosmic relatives. These results indicate that idiopathic olfactory dysfunction is associated with an increased risk of developing PD of at least 10%. Ann Neurol 2004
Influence of somatosensory input on motor function in patients with chronic stroke
Authors: Floel Agnes , Nagorsen Ulrike , Werhahn Konrad J. , Ravindran Shashi , Birbaumer Niels , Knecht Stefan , Cohen Leonardo G.
Published: July 2004

In healthy volunteers, reduction of somatosensory input from one hand leads to rapid performance improvements in the other hand. Thus, it is possible that reduction of somatosensory input from the healthy hand can influence motor function in the paretic hand of chronic stroke patients with unilateral hand weakness. To test this hypothesis, we had 13 chronic stroke patients perform motor tasks with the paretic hand and arm during cutaneous anesthesia of the healthy hand and healthy foot in separate sessions. Performance of a finger tapping task, but not a wrist flexion task, improved significantly with anesthesia of the hand, but not the foot. This effect progressed with the duration of anesthesia and correlated with baseline motor function. We conclude that cutaneous anesthesia of the healthy hand elicits transient site‐specific improvements in motor performance of the moderately paretic hand in patients with chronic stroke, consistent with interhemispheric competition models of sensorimotor processing. Ann Neurol 2004;56:206–212
An anti‐ganglioside antibody‐secreting hybridoma induces neuropathy in mice
Authors: Sheikh Kazim A. , Zhang Gang , Gong Yanpin , Schnaar Ronald L. , Griffin John W.
Published: July 2004

Immune responses against gangliosides are strongly implicated in the pathogenesis of some variants of Guillain–Barré syndrome (GBS). For example, IgG antibodies against GM1, GD1a, and related gangliosides are frequently present in patients with post‐Campylobacter acute motor axonal neuropathy (AMAN) variant of GBS, and immunization of rabbits with GM1 has produced a model of AMAN. However, the role of anti‐ganglioside antibodies in GBS continues to be debated because of lack of a passive transfer model. We recently have raised several monoclonal IgG anti‐ganglioside antibodies. We passively transfer these antibodies by intraperitoneal hybridoma implantation and by systemic administration of purified anti‐ganglioside antibodies in mice. Approximately half the animals implanted with an intraperitoneal clone of anti‐ganglioside antibody‐secreting hybridoma developed a patchy, predominantly axonal neuropathy affecting a small proportion of nerve fibers. In contrast to hybridoma implantation, passive transfer with systemically administered anti‐ganglioside antibodies did not cause nerve fiber degeneration despite high titre circulating antibodies. Blood–nerve barrier studies indicate that animals implanted with hybridoma had leaky blood–nerve barrier compared to mice that received systemically administered anti‐ganglioside antibodies. Our findings suggest that in addition to circulating antibodies, factors such as antibody accessibility and nerve fiber resistance to antibody‐mediated injury play a role in the development of neuropathy. Ann Neurol 2004;56:228–239
Microstructural white matter changes in carriers of the DYT1 gene mutation
Authors: Carbon Maren , Kingsley Peter B. , Su Sherwin , Smith Gwenn S. , Spetsieris Phoebe , Bressman Susan , Eidelberg David
Published: July 2004

We tested the hypothesis that the DYT1 genotype is associated with a disorder of anatomical connectivity involving primarily the sensorimotor cortex. We used diffusion tensor magnetic resonance imaging (DTI) to assess the microstructure of white matter pathways in mutation carriers and control subjects. Fractional anisotropy (FA), a measure of axonal integrity and coherence, was reduced (p < 0.005) in the subgyral white matter of the sensorimotor cortex of DYT1 carriers. Abnormal anatomical connectivity of the supplementary motor area may contribute to the susceptibility of DYT1 carriers to develop clinical manifestations of dystonia. Ann Neurol 2004
The factor V G1691A mutation is a risk for porencephaly: A case–control study
Authors: Debus Otfried M. , Kosch Andrea , Sträter Ronald , Rossi Rainer , Nowak‐Göttl Ulrike
Published: July 2004

This study was initiated to investigate prothrombotic risk factors in children with porencephaly. 76 porencephalic and 76 healthy infants were investigated for factor V (FV) G1691A mutation, factor II G20210A variant, methylenetetrahydrofolate reductase (MTHFR) C677T genotype, lipoprotein (a), protein C, protein S, and antithrombin. Only the FV mutation (p = 0.005) and combinations of two or three different risk factors (p = 0.003) were significantly associated with porencephaly. These data give evidence that the FV G1691A mutation and a combination of prothromboic factors play a major role in the development of childhood porencephaly. Ann Neurol 2004.
Functional significance of S6K overexpression in meningioma progression
Authors: Surace Ezequiel I. , Lusis Eriks , Haipek Carrie A. , Gutmann David H.
Published: July 2004

One common genetic change in anaplastic meningiomas is amplification of chromosome 17q23 containing the S6 kinase (S6K) gene. We show, for the first time to our knowledge, increasedS6KmRNA expression in anaplastic meningiomas compared with benign tumors. To evaluateS6Kas a candidate meningioma progression gene, we generated IOMM‐Lee human meningioma cell lines overexpressing S6K. Whereas no effect of S6K overexpression on meningioma cell growth, motility, or adhesion was observed in vitro, S6K overexpression resulted in increased tumor size in vivo. Collectively, these results suggest that S6K is functionally important for meningioma progression and may represent a target for future meningioma therapy. Ann Neurol 2004
Polycystins and mechanosensation in renal and nodal cilia
Authors: Nauli Surya M. , Zhou Jing
Published: July 2004

The external surfaces of the human body, as well as its internal organs, constantly experience different kinds of mechanical stimulations. For example, tubular epithelial cells of the kidney are continuously exposed to a variety of mechanical forces, such as fluid flow shear stress within the lumen of th nephron. The majority of epithelial cells along the nephron, except intercalated cells, possess a primary cilium, an organelle projecting from the cell's apical surface into the luminal space. Despite its discovery over 100 years ago, the primary cilium's function continued to elude researchers for many decades. However, recent studies indicate that renal cilia have a sensory function. Studies on polycystic kidney disease (PKD) have identified many of the molecular players, which should help solve the mystery of how the renal cilium senses fluid flow. In this review, we will summarize the recent breakthroughs in PKD research and discuss the role(s) of th polycystin signaling complex in mediating mechanosensory function by the primary cilium of renal epithelium as well as of the embryonic node. BioEssays 26:844–856, 2004. © 2004 Wiley Periodicals, Inc.
Serial analysis of gene expression (SAGE): unraveling the bioinformatics tools
Authors: Tuteja Renu , Tuteja Narendra
Published: July 2004

Serial analysis of gene expression (SAGE) is a powerful technique that can be used for global analysis of gene expression. Its chief advantage over other methods is that it does not require prior knowledge of the genes of interest and provides qualitative and quantitative data of potentially every transcribed sequence in a particular cell or tissue type. This is a technique of expression profiling, which permits simultaneous, comparative and quantitative analysis of gene‐specific, 9‐ to 13‐basepair sequences. These short sequences, called SAGE tags, are linked together for efficient sequencing. The sequencing data are then analyzed to identify each gene expressed in the cell and the levels at which each gene is expressed. The main benefit of SAGE includes the digital output and the identification of novel genes. In this review, we present an outline of the method, various bioinformatics methods for data analysis and general applications of this important technology. BioEssays 26:916–922, 2004. © 2004 Wiley Periodicals, Inc.
The redox regulation of intermediary metabolism by a superoxide–aconitase rheostat
Authors: Armstrong Jeffrey S. , Whiteman Matthew , Yang Hongyuan , Jones Dean P.
Published: July 2004

In this article, we discuss a hypothesis to explain the preferential synthesis of the superoxide sensitive form of aconitase in mitochondria and the phenotype observed in manganese superoxide dismutase mutant mice, which show a gross over accumulation of stored fat in liver. The model proposes that intermediary metabolism is redox regulated by mitochondrial superoxide generated during mitochondrial respiration. This regulates the level of reducing equivalents (NADH) entering the electron transport chain (ETC) through the reversible inactivation of mitochondrial aconitase. This control mechanism has a dual function; firstly, it regulates levels of superoxide generated by the ETC and, secondly, it fine‐tunes metabolism by channeling citrate either for the production of NADH for energy metabolism or diverting it for the synthesis of fats. In this setting, the mitochondrial redox state influences metabolic decisions via a superoxide–aconitase rheostat. BioEssays 26:894–900, 2004. © 2004 Wiley Periodicals, Inc.
Functional genomics studied by proteomics
Authors: Honoré Bent , Østergaard Morten , Vorum Henrik
Published: July 2004

The human genome contains about 30,000 genes, each creating several transcripts per gene. Transcript structures and expression are studied by high‐throughput transcriptomic techniques using microarrays. Generally, transcripts are not directly operating molecules, but are translated into functional proteins, post‐translationally modified by proteolysis, glycosylation, phosphorylation, etc., sometimes with great functional impact. Proteins need to be analyzed by proteomic techniques, less suited for high‐throughput. Two‐dimensional polyacrylamide gel electrophoresis (2D‐PAGE), separating thousands of proteins has developed slowly over the past quarter of a century. This technique is now quite reproducible and suitable for differential proteomics, comparing normal and diseased cells/tissues revealing differentially regulated proteins. 2D‐PAGE is combined with protein‐identification methods, currently mass spectrometry (MS), which has been significantly improved over the last decade. Other proteomic techniques studying protein–protein interactions are now either established or still being developed, such as peptide or protein arrays, phage display, and the yeast two‐hybrid system. The strengths and weaknesses of these techniques are discussed. BioEssays 26:901–915, 2004. © 2004 Wiley Periodicals, Inc.
Opposing FGF and retinoid pathways: a signalling switch that controls differentiation and patterning onset in the extending vertebrate body axis
Authors: del Corral Ruth Diez , Storey Kate G.
Published: July 2004

Construction of the trunk/caudal region of the vertebrate embryo involves a set of distinct molecules and processes whose relationships are just coming into focus. In addition to the subdivision of the embryo into head and trunk domains, this “caudalisation” process requires the establishment and maintenance of a stem zone. This sequentially generates caudal tissues over a long period which then undergo differentiation and patterning in the extending body axis. Here we review recent studies that show that changes in the signalling properties of the paraxial mesoderm act as a switch that controls onset of differentiation and pattern in the spinal cord. These findings identify distinct roles for different caudalising factors; in particular, Fibroblast Growth Factor (FGF) inhibits differentiation in the caudal stem zone, while Retinoic acid (RA) provided rostrally by somitic mesoderm is required for neuronal differentiation and establishment of ventral neural pattern. Furthermore, the mutual opposition of FGF and RA pathways controls not only neural differentiation but also mesoderm segmentation and might also underlie the progressive assignment of rostrocaudal identity by regulating Hox gene availability and activation. BioEssays 26:857–869, 2004. © 2004 Wiley Periodicals, Inc.
The ins and outs of lysophosphatidic acid signaling
Authors: Moolenaar Wouter H. , van Meeteren Laurens A. , Giepmans Ben N.G.
Published: July 2004

Lysophosphatidic acid (LPA) is a lipid mediator with a wide variety of biological actions, particularly as an inducer of cell proliferation, migration and survival. LPA binds to specific G‐protein‐coupled receptors and thereby activates multiple signal transduction pathways, including those initiated by the small GTPases Ras, Rho, and Rac. LPA signaling has been implicated in such diverse processes as wound healing, brain development, vascular remodeling and tumor progression. Knowledge of precisely how and where LPA is produced has long proved elusive. Excitingly, it has recently been discovered that LPA is generated from precursors by ‘autotaxin’, a once enigmatic exo‐phosphodiesterase implicated in tumor cell motility. Exogenous phospholipases D can also produce LPA, which may contribute to their toxicity. Here we review recent progress in our understanding of LPA bioactivity, signaling and synthesis. BioEssays 26:870–881, 2004. © 2004 Wiley Periodicals, Inc.
Coming to our senses
Authors: Treisman Jessica E.
Published: July 2004

Sensory organs are specialized to receive different kinds of input from the outside world. However, common features of their development suggest that they could have a shared evolutionary origin. In a recent paper, Niwa et al.1 show that three Drosophila adult sensory organs all rely on the spatial signals Decapentaplegic and Wingless to specify their position, and the temporal signal ecdysone to initiate their development. The proneural gene atonal is an important site for integration of these regulatory inputs. These results suggest the existence of a primitive sensory organ precursor, which would differentiate according to the identity of its segment of origin. The authors argue that the eyeless gene controls eye disc identity, indirectly producing an eye from the sensory organ precursor within this disc. BioEssays 26:825–828, 2004. © 2004 Wiley Periodicals, Inc.
Mouse‐centric comparative transcriptomics of protein coding and non‐coding RNAs
Authors: Suzuki Masanori , Hayashizaki Yoshihide
Published: July 2004

The largest transcriptome reported so far comprises 60,770 mouse full‐length cDNA clones, and is an effective reference data set for comparative transcriptomics. The number of mouse cDNAs identified greatly exceeds the number of genes predicted from the sequenced human and mouse genomes. This is largely because of extensive alternative splicing and the presence of many non‐coding RNAs (ncRNAs), which are difficult to predict from genomic sequences. Notably, ncRNAs are a major component of the transcriptomes of higher organisms, and many sense–antisense pairs have been identified. The ncRNAs function in a range of regulatory mechanisms for gene expression and other biological processes. They might also have contributed to the increased functional diversification of genomes during evolution. In this review, we discuss aspects of the transcriptome of various organisms in relation to the mouse data, in order to shed light on the regulatory mechanisms and physiological significance of these abundant RNAs. BioEssays 26:833–843, 2004. © 2004 Wiley Periodicals, Inc.
The PARP superfamily
Authors: Amé Jean‐Christophe , Spenlehauer Catherine , de Murcia Gilbert
Published: July 2004

Poly(ADP‐ribosyl)ation is an immediate DNA‐damage‐dependent post‐translational modification of histones and other nuclear proteins that contributes to the survival of injured proliferating cells. Poly(ADP‐ribose) polymerases (PARPs) now constitute a large family of 18 proteins, encoded by different genes and displaying a conserved catalytic domain in which PARP‐1 (113 kDa), the founding member, and PARP‐2 (62 kDa) are so far the sole enzymes whose catalytic activity has been shown to be immediately stimulated by DNA strand breaks. A large repertoire of sequences encoding novel PARPs now extends considerably the field of poly(ADP‐ribosyl)ation reactions to various aspects of the cell biology including cell proliferation and cell death. Some of these new members interact with each other, share common partners and common subcellular localizations suggesting possible fine tuning in the regulation of this post‐translational modification of proteins. This review summarizes our present knowledge of this emerging superfamily, which might ultimately improve pharmacological strategies to enhance both antitumor efficacy and the treatment of a number of inflammatory and neurodegenerative disorders. A provisional nomenclature is proposed. BioEssays 26:882–893, 2004. © 2004 Wiley Periodicals, Inc.
Renewed debate over postnatal oogenesis in the mammalian ovary
Authors: Greenfeld Chuck , Flaws Jodi A.
Published: July 2004

The central dogma of female reproductive biology has long held that oogenesis ceases prior to birth in mammals. During the first half of the last century, there was much debate about whether this was the case or whether oogenesis continued in the postnatal ovary. A report in 1951 effectively put an end to this debate and laid the foundation for the dogma. A new paper by Johnson et al. (2004)1 resurrects the debate over whether postnatal oogenesis occurs in the mammalian ovary. If confirmed, this would have tremendous impact on issues related to female fertility and reproductive longevity. BioEssays 26:829–832, 2004. © 2004 Wiley Periodicals, Inc.
A new HPLC method for serum neopterin measurement and relationships with plasma thiols levels in healthy subjects
Authors: Carru Ciriaco , Zinellu Angelo , Sotgia Salvatore , Serra Roberta , Usai Maria Franca , Pintus Gian Franco , Pes Giovanni Mario , Deiana Luca
Published: July 2004

Neopterin, a pyrazinopyrimidine compound, serves as a marker of cellular immune system activation, and it can be used as a prognostic predictor for certain types of diseases. We propose a new simple HPLC method to measure serum neopterin with highly sensitive ﬂuorimetric detection. After TCA serum protein precipitation, the supernatant was diluted ﬁve times, injected into a C18 reversed‐phase column and eluted at a ﬂow rate of 1.5 mL/min by an isocratic water–acetonitrile (99:1) mobile phase. The natural ﬂuorescence of the molecule was detected at excitation wavelength 353 nm and emission 438 nm. In these conditions the neopterin retention time was about 4 min. Our proposed method was compared with a validated chromatographic separation, and the obtained data of the serum neopterin from 35 healthy volunteers were analysed by Passing–Bablok regression and Bland–Altman test. Neopterin measurement in healthy subjects was also employed to investigate on its potential relationships with plasma thiols levels. Copyright © 2004 John Wiley & Sons, Ltd.
Isoform‐speciﬁc quantiﬁcation of endothelins in HUVEC culture supernatants by on‐line high‐performance liquid chromatography/electrospray mass spectrometry
Authors: Carrascal Montserrat , Schneider Klaus , Peralta Carmen , Escolar Gines , Gelpi Emilio , Abian Joaquin
Published: July 2004

A method for the quantitative analysis of endothelin peptides in human umbilical vein endothelial cell (HUVEC) culture supernatants is reported. The analysis is isoform‐speciﬁc and employs solid‐phase extraction and subsequent HPLC fractionation followed by HPLC‐ESIMS analysis.

The peptide vasoactive‐intestinal‐contractor (VIC) was used as internal standard for the HPLC‐ESIMS analysis. Linearity of calibration curves was from 50 fmol to 25 pmol. The limit of detection of the HPLC‐ESIMS step using a buffer matrix was estimated at 50 fmol (S/N > 3). The overall limit of detection for supernatants of HUVEC was 500 fmol/mL.

In HUVEC culture supernatants only ions of endothelin‐1 (ET1) were observed. Basal levels were determined to be 1.8 ± 0.3 pmol/mL. Quantitative results obtained for ET1 were in agreement with those obtained by using a standard addition method and by an ELISA method. Copyright © 2004 John Wiley & Sons, Ltd.
A more sensitive MS detector does not obviously lead to a more sensitive assay: experiences with ES‐285
Authors: Stokvis Ellen , Rosing Hilde , López‐Lázaro Luis , Schellens Jan H. M. , Beijnen Jos H.
Published: July 2004

In this paper the transfer of an existing method for the quantitative determination of the anticancer agent ES‐285 in human plasma using liquid chromatography tandem mass spectrometry on an API 365 to an API 3000 mass spectrometer is described. The transfer appeared not to be straightforward. Problems arose resulting from carry‐over and interferences. In addition, due to the expansion of the calibration range, data ought to be weighted with a different factor to increase the accuracy of the lower concentrations. After ﬁnding appropriate solutions for these problems, the lower limit of quantitation could be lowered from 10 to 1 ng/mL for ES‐285 in human plasma. The usefulness and necessity of the modiﬁed assay was demonstrated by analysis of plasma samples from a patient receiving a low dosage of the drug. Copyright © 2004 John Wiley & Sons, Ltd.
Cubane‐Type Mo3CoS4 Molecular Clusters with Three Different Metal Electron Populations: Structure, Reactivity and Their Use in the Synthesis of Hybrid Charge‐Transfer Salts
Authors: Feliz Marta , Llusar Rosa , Uriel Santiago , Vicent Cristian , Coronado Eugenio , Gómez‐García Carlos J.
Published: July 2004

Heterodimetallic cubane‐type complexes coordinated to diphosphanes [Mo3CoS4(dmpe)3Cl4]+ ([1]+) (dmpe=1,2‐bis(dimethylphosphanyl)ethane), [Mo3CoS4(dmpe)3Cl4] (1) and [Mo3CoS4(dmpe)3Cl3(CO)] (2) with 14, 15 and 16 metal electrons, respectively, have been prepared from the [Mo3S4(dmpe)3Cl3]+ trinuclear precursor using [Co2(CO)8] or CoCl2 as cobalt source. Cluster complexes [1]+ and 1 are easily interconverted chemically and electrochemically. The CoCl distance increases upon electron addition and substitution of the chlorine atom coordinated to cobalt with CO only takes place in presence of a reducing agent to give complex 2. Structural changes in the intermetallic distances agree with the entering electrons occupying an orbital which is basically MoMo non‐bonding and slightly MoCo bonding. Magnetic susceptibility measurements for [1]+ and 1 are consistent with the presence of two and one unpaired electrons, respectively and therefore with an “e” character for the HOMO orbital. Oxidation of 1 with TCNQ results in the formation of a charge transfer salt formulated as [1]+[TCNQ]− with alternate layers of paramagnetic cluster cations and also paramagnetic organic anions. There is no magnetic interaction between layers and the thermal variation of the magnetic susceptibility has been modelled as a S=${{ 1/2 }}$ TCNQ antiferromagnetic chain plus a S=1 cluster monomer with zero field splitting.
Theoretical Study of the Electrocyclic Ring Closure of Hydroxypentadienyl Cations
Authors: Nieto Faza Olalla , Silva López Carlos , Álvarez Rosana , de Lera Ángel R.
Published: July 2004

At the 6‐311G* level of theory, DFT methods predict that the rearrangement of 1,4‐dihydroxy‐5‐methylpentadienyl cation 1 (R = Me) to protonated trans‐3‐hydroxy‐2‐methylcyclopent‐4‐en‐1‐one 2, an intermediate step in the Piancatelli reaction or rearrangement of furfuryl carbinols to trans‐2‐alkyl(aryl)‐3‐hydroxycyclopent‐4‐en‐1‐one, is a concerted electrocyclic process. Energetic, magnetic, and stereochemical criteria are consistent with a conrotatory electrocyclic ring closure of the most stable out,out‐1 isomer to afford trans‐2. Although the out,in‐1 isomer is thermodynamically destabilized by 6.84 kcal mol−1, the activation energy for its cyclization is slightly lower (5.29 kcal mol−1 versus 5.95 kcal mol−1). The cyclization of the isomers of 1 with the C1‐hydroxy group inwards showed considerably higher activation energies than their outwards counterparts. in,out‐1, although close in energy to out,out‐1 (difference of 1.57 kcal mol−1) required about 10 kcal mol−1 more to reach the corresponding transition structure. The value measured for the activation energy of in,in‐1 (17.32 kcal mol−1) eliminates the alternative conrotatory electrocyclization of this isomer to provide trans‐2. Geometric scrambling by isomerization of the terminal C1C2 bond of 1 is also unlikely to compete with electrocyclization. The possibility to interpret the 1→2 reaction as a nonpericyclic cationic cyclization was also examined through NBO analysis, and the study of bond lengths and atomic charges. It was found that the 1→2 concerted rearrangement benefits from charge separation at the cyclization termini, an effect not observed in related concerted electrocyclic processes, such as the classical Nazarov reaction 3→4 or the cyclization of the isomeric 2‐hydroxypentadienyl cation 5.