bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeting Adenoviral Vectors by Using the Extracellular Domain of the Coxsackie-Adenovirus Receptor: Improved Potency via Trimerization
Authors: Kim Jin , Smith Theodore , Idamakanti Neeraja , Mulgrew Kathy , Kaloss Michele , Kylefjord Helen , Ryan Patricia C. , Kaleko Michael , Stevenson Susan C. 
Published: July 2002

ABSTRACT
Adenovirus binds to mammalian cells via interaction of fiber with the coxsackie-adenovirus receptor (CAR). Redirecting adenoviral vectors to enter target cells via new receptors has the advantage of increasing the efficiency of gene delivery and reducing nonspecific transduction of untargeted tissues. In an attempt to reach this goal, we have produced bifunctional molecules with soluble CAR (sCAR), which is the extracellular domain of CAR fused to peptide-targeting ligands. Two peptide-targeting ligands have been evaluated: a cyclic RGD peptide (cRGD) and the receptor-binding domain of apolipoprotein E (ApoE). Human diploid fibroblasts (HDF) are poorly transduced by adenovirus due to a lack of CAR on the surface. Addition of the sCAR-cRGD or sCAR-ApoE targeting protein to adenovirus redirected binding to the appropriate receptor on HDF. However, a large excess of the monomeric protein was needed for maximal transduction, indicating a suboptimal interaction. To improve interaction of sCAR with the fiber knob, an isoleucine GCN4 trimerization domain was introduced, and trimerization was verified by cross-linking analysis. Trimerized sCAR proteins were significantly better at interacting with fiber and inhibiting binding to HeLa cells. Trimeric sCAR proteins containing cRGD and ApoE were more efficient at transducing HDF in vitro than the monomeric proteins. In addition, the trimerized sCAR protein without targeting ligands efficiently blocked liver gene transfer in normal C57BL/6 mice. However, addition of either ligand failed to retarget the liver in vivo. One explanation may be the large complex size, which serves to decrease the bioavailability of the trimeric sCAR-adenovirus complexes. In summary, we have demonstrated that trimerization of sCAR proteins can significantly improve the potency of this targeting approach in altering vector tropism in vitro and allow the efficient blocking of liver gene transfer in vivo.
Ty3 Integrase Is Required for Initiation of Reverse Transcription
Authors: Nymark-McMahon M. Henrietta , Beliakova-Bethell Nadejda S. , Darlix Jean-Luc , Le Grice Stuart F. J. , Sandmeyer Suzanne B. 
Published: July 2002

ABSTRACT

The integrase (IN) encoded by the
Saccharomyces cerevisiae
retroviruslike element Ty3 has features found in retrovirus IN proteins including the catalytic triad, an amino-terminal zinc-binding motif, and a nuclear localization sequence. Mutations in the amino- and carboxyl-terminal domains of Ty3 IN cause reduced accumulation of full-length cDNA in the viruslike particles. We show that the reduction in cDNA is accompanied by reduced amounts of early intermediates such as minus-strand, strong-stop DNA. Expression of a capsid (CA)-IN fusion protein (CA-IN) complemented catalytic site and nuclear localization mutants, but not DNA mutants. However, expression of a fusion of CA, reverse transcriptase (RT), and IN (CA-RT-IN) complemented transposition of catalytic site and nuclear localization signal mutants, increased the amount of cDNA in some of the mutants, and complemented transposition of several mutants to low frequencies. Expression of a CA-RT-IN protein with a Ty3 IN catalytic site mutation did not complement transposition of either a Ty3 catalytic site mutant or a nuclear localization mutant but did increase the amount of cDNA in several mutants and complement at least one of the cDNA mutants for transposition. These in vivo data support a model in which independent IN domains can contribute to reverse transcription and integration. We conclude that during reverse transcription, the Ty3 IN domain interacts closely with the polymerase domain and may even constitute a domain within a heterodimeric RT. These studies also suggest that during integration the IN catalytic site and at least portions of the IN carboxyl-terminal domain act in
cis
.
Selective Targeting and Inducible Destruction of Human Cancer Cells by Retroviruses with Envelope Proteins Bearing Short Peptide Ligands
Authors: Gollan Timothy J. , Green Michael R. 
Published: July 2002

ABSTRACTIn the accompanying study, we show how retroviral tropism can be redirected by insertion of short peptide ligands at multiple locations in envelope. Here we use this approach to selectively target and destroy human cancer cells. Many cancer cells overexpress specific cell surface receptors. We have generated Moloney murine leukemia virus (MLV) envelope derivatives bearing short peptide ligands for gastrin-releasing protein (GRP) and human epidermal growth factor receptors. Pseudotyped viruses containing these chimeric envelope derivatives selectively transduce human cancer cell lines that overexpress the cognate receptor. A retrovirus targeting the GRP receptor can deliver the thymidine kinase gene to human melanoma and breast cancer cells, which are killed by the subsequent addition of ganciclovir. Collectively, our results demonstrate that short peptide ligands inserted at appropriate locations in MLV envelope can selectively target retroviruses to human cancer cells and deliver a therapeutically relevant gene.
Evidence for the aetiology of injuries in Australian football
Authors: Norton K , Schwerdt S , Lange K 
Published: July 2002

Objectives—To determine in Australian football (a) the influence of ground hardness and playing grade (level) on game speed and structure, and (b) player movement patterns throughout the game and across levels.Methods—The design consisted of several studies. Seventeen games played on grounds of different hardness in 2000 were used to determine game speed and structure. Four first grade and four second grade grand final games (1994, 1996, 1997, 1999) were used to determine the game speed and structure on the same ground but at different levels. Fifty one players (44 first grade and seven second grade) were used to measure movement patterns within games and across levels during the 2000 season.Results—There was a significant relation between ground hardness and game speed, which could lead to higher injury rates when the ground is harder. There was a 6.7% difference in game speed between the first and second grade levels reflecting differences in injury incidence. The first grade games were also characterised by a greater number of shorter, high intensity play periods and longer stop periods than the second grade games. Midfield players in the first grade games covered about 24% greater distance than their second grade counterparts, and there was a significant difference in their playing speeds.Conclusions—Over the past 40 years, the game speed in the top level of Australian football has approximately doubled. Over the same time, the number of collisions and the estimated injury incidence have also doubled. This study provides additional support to the suggestion that these variables are strongly linked. Factors such as ground hardness, playing level, and time during the game influence game speed and are therefore important in injury development in Australian football.
Sea level and acute responses to hypoxia: do they predict physiological responses and acute mountain sickness at altitude?
Authors: Grant S , MacLeod N , Kay J W , Watt M , Patel S , Paterson A , Peacock A 
Published: July 2002

Objectives: To compare a range of physiological responses to acute sea level hypoxia at simulated altitudes with the same physiological responses and acute mountain sickness (AMS) scores measured at altitude (similar to the simulated altitudes) during a 17 day trek in the Himalayas.Methods: Twenty men and women aged 18–54 years took part in the study. End tidal CO2tension (Petco2) and saturated oxygen (Sao2) were measured using a capnograph. Observations made at sea level and some simulated altitudes were compared with those in the Himalayas. Pairwise correlations were used to examine the correlation between variables and regression, with 95% prediction intervals providing information on how well one variable could be predicted from another for a given subject.Results: There was only a significant correlation for a few comparisons. The 95% prediction intervals for individual Sao2values at a range of simulated altitudes were fairly wide going from ± 4% to ± 5%. All of the correlations between laboratory and Himalayan Petco2values were not statistically significant. There was a significant correlation for the relation between Sao2and Petco2at sea level for the laboratory data (r=−0.51; p=0.05). For the Himalayan data, there were significant correlations at Namche Bazaar (3450 m; day 3) (r=−0.56; p=0.01) and Dingboche (4300 m; day 6) (r=−0.48; p=0.03). The correlation between Sao2and Petco2and AMS was generally poor.Conclusions: The results indicate that limited information can be gained on a subject's response to altitude by assessing physiological variables at sea level and a range of simulated altitudes before the subject carries out a trek at altitude.
Randomised controlled study of oral erythromycin for treatment of gastrointestinal dysmotility in preterm infants
Authors: Ng P C , So K W , Fung K S C , Lee C H , Fok T F , Wong E , Wong W , Cheung K L , Cheng A F B 
Published: July 2002

AIMTo evaluate the effectiveness of oral erythromycin as a prokinetic agent for the treatment of moderately severe gastrointestinal dysmotility in preterm very low birthweight infants.METHODSA prospective, double blind, randomised, placebo controlled study in a tertiary referral centre of a university teaching hospital was conducted on 56 preterm infants (< 1500 g) consecutively admitted to the neonatal unit. The infants were randomly allocated by minimisation to receive oral erythromycin (12.5 mg/kg, every six hours for 14 days) or an equivalent volume of placebo solution (normal saline) if they received less than half the total daily fluid intake or less than 75 ml/kg/day of milk feeds by the enteral route on day 14 of life. The times taken to establish half, three quarters, and full enteral feeding after the drug treatment were compared between the two groups. Potential adverse effects of oral erythromycin and complications associated with parenteral nutrition were assessed as secondary outcomes.RESULTSTwenty seven and 29 infants received oral erythromycin and placebo solution respectively. The times taken to establish half, three quarters, and full enteral feeding after the drug treatment were significantly shorter in the group receiving oral erythromycin than in those receiving the placebo (p < 0.05, p < 0.05 and p < 0.0001 respectively). There was also a trend suggesting that more infants with prolonged feed intolerance developed cholestatic jaundice in the placebo than in the oral erythromycin group (10v 5 infants). None of the infants receiving oral erythromycin developed cardiac dysrhythmia, pyloric stenosis, or septicaemia caused by multiresistant organisms.CONCLUSIONSOral erythromycin is effective in facilitating enteral feeding in preterm very low birthweight infants with moderately severe gastrointestinal dysmotility. Treated infants can achieve full enteral feeding 10 days earlier, and this may result in a substantial saving on hyperalimentation. However, until the safety of erythromycin has been confirmed in preterm infants, this treatment modality should remain experimental. Prophylactic or routine use of this medication for treatment of mild cases of gastrointestinal dysmotility is probably not warranted at this stage.
Inflammatory bowel disease and laterality: is left handedness a risk?
Authors: Morris D L , Montgomery S M , Galloway M L , Pounder R E , Wakefield A J 
Published: July 2002

BACKGROUNDLeft handedness has been associated with inflammatory bowel disease (IBD) and autoimmune diseases.AIMSTo determine whether left handedness is associated with IBD in two prospective national birth cohorts.METHODSSubjects with Crohn's disease (CD) and ulcerative colitis (UC) were identified from two national longitudinal birth cohorts at age 26 years (1970 British Cohort Study (BCS70), born in 1970) and age 33 years (National Child Development Study (NCDS), born in 1958). Laterality was determined at age 10 (BCS70) or seven (NCDS) years, based on hand preference for writing and foot preference for kicking a ball (BCS70 only). Multiple logistic regression was used to assess the relationship of handedness with CD, UC, and IBD in the cohorts combined and adjusted for sex.RESULTSBoth cohorts combined showed increased adjusted relative odds of 2.13 (95% confidence interval (CI) 0.97–4.65; p=0.059), 2.13 (95% CI 0.92–4.91; p=0. 077), and 2.13 (95% CI 1.20–3.78; p=0.010) for CD, UC, and IBD, respectively in left handers.CONCLUSIONSThe study suggests a link between IBD and left handedness which may be genetic and/or environmental in origin.
Cohort study of occupational risk factors of low back pain in construction workers
Authors: Latza Ute , Karmaus Wilfried , Stürmer Til , Steiner Markus , Neth Axel , Rehder Uwe 
Published: July 2002

OBJECTIVESTo identify work related risk factors of future low back pain (LBP) in a cohort of construction workers free of LBP at the start of follow up.METHODSThe Hamburg construction worker study comprises 571 male construction workers who have undergone two comprehensive interview and physical examination surveys. A cohort of 285 subjects without LBP at baseline was identified. After a follow up of 3 years, the 1 year prevalence of self reported LBP was determined in the 230 men followed up (80.7%). Prevalence ratios (PRs) with 95% confidence intervals (95% CIs) of LBP at follow up according to self reported work tasks of construction workers measured at baseline were estimated from Cox's regression models which were adjusted for age, and anthropometric measures.RESULTSAt follow up 71 out of 230 workers (30.9%) reported LBP during the preceding 12 months. Four work tasks (scaffolding, erecting roof structures, sawing wood, laying large sandstones) with an increased risk of 1 year prevalence of LBP at follow up were further evaluated. After further adjustment for occupation the relative risk was increased for workers who had reported ⩾2 hour/shifts laying large sandstones (PR=2.6; 95% CI 1.1 to 6.5). Work load of bricklayers was additionally estimated by an index on stone load (high exposure: PR=4.0; 95% CI 0.8 to 19.8), and an index for laying huge bricks/blocks (yes/no: PR=1.7; 95% CI 0.5 to 5.7).CONCLUSIONSThe results suggest that self reported differences in brick characteristics (size and type of stone) and temporal aspects of the work of bricklayers (average hours per shift laying specified stones) can predict the future prevalence of LBP. The data have to be interpreted with caution because multiple risk factors were tested.
Rheumatoid arthritis in workers exposed to silica in the pottery industry
Authors: Turner Susan , Cherry Nicola 
Published: July 2002

OBJECTIVETo investigate the relation between rheumatoid arthritis and occupational exposure to silica in pottery and related industries.METHODSMedical records of 8325 men and women born 1916–45 and employed in pottery, refractory material (aluminosilicate or silica), and sandstone industries were examined to identify cases of rheumatoid arthritis. Medical and employment histories were extracted for cases and matched referents. Indices of duration, cumulative exposure, and mean silica concentration were compiled. Conditional logistic regression was used to investigate the relation between rheumatoid arthritis and indices of exposure, having allowed for potential confounders of smoking, employment in the coal mining industry, and number of pregnancies.RESULTS58 Cases of rheumatoid arthritis (43 men, 15 women) were identified. Cases had significantly shorter duration of exposure than referents. There was no significant difference between cases and referents in mean silica concentration. Men who had worked in the coal mining industry were particularly at risk (odds ratio 5.36, 95% confidence interval 1.92 to 15.03).CONCLUSIONThere was no evidence of increased risk of developing rheumatoid arthritis after occupational exposure to silica at mean exposures within the current United Kingdom exposure limits.
Occupational seafood allergy: a review
Authors: Jeebhay M F , Robins T G , Lehrer S B , Lopata A L 
Published: July 2002

BACKGROUNDRecent years have seen increased levels of production and consumption of seafood, leading to more frequent reporting of allergic reactions in occupational and domestic settings. This review focuses on occupational allergy in the fishing and seafood processing industry.REVIEWWorkers involved in either manual or automated processing of crabs, prawns, mussels, fish, and fishmeal production are commonly exposed to various constituents of seafood. Aerosolisation of seafood and cooking fluid during processing are potential occupational situations that could result in sensitisation through inhalation. There is great variability of aerosol exposure within and among various jobs with reported allergen concentrations ranging from 0.001 to 5.061(μg/m3). Occupational dermal exposure occurs as a result of unprotected handling of seafood and its byproducts. Occupational allergies have been reported in workers exposed to arthropods (crustaceans), molluscs, pisces (bony fish) and other agents derived from seafood. The prevalence of occupational asthma ranges from 7% to 36%, and for occupational protein contact dermatitis, from 3% to 11%. These health outcomes are mainly due to high molecular weight proteins in seafood causing an IgE mediated response. Cross reactivity between various species within a major seafood grouping also occurs. Limited evidence from dose-response relations indicate that development of symptoms is related to duration or intensity of exposure. The evidence for atopy as a risk factor for occupational sensitisation and asthma is supportive, whereas evidence for cigarette smoking is limited. Disruption of the intact skin barrier seems to be an important added risk factor for occupational protein contact dermatitis.CONCLUSIONThe range of allergic disease associated with occupational exposure to crab is well characterised, whereas for other seafood agents the evidence is somewhat limited. There is a need for further epidemiological studies to better characterise this risk. More detailed characterisation of specific protein antigens in aerosols and associated establishment of dose-response relations for acute and chronic exposure to seafood; the respective roles of skin contact and inhalational exposure in allergic sensitisation and cross reactivity; and the contribution of host associated factors in the development of occupational seafood allergies are important areas for future research.
International business travel: impact on families and travellers
Authors: Espino C M , Sundstrom S M , Frick H L , Jacobs M , Peters M 
Published: July 2002

Objectives: Spouses and staff of the World Bank Group (WBG) were questioned about the impact of international business travel on families and travellers. Dependent variables were self reported stress, concern about the health of the traveller, and negative impact on the family. We hypothesised that several travel factors (independent variables) would be associated with these impacts. These travel factors had to do with the frequency, duration, and predictability of travel and its interference with family activities.Methods: Survey forms were developed and distributed to all spouses of travelling staff as well as a small sample of operational staff. Kendall's tau b correlation coefficients of response frequencies were computed with the data from scaled items. Written responses to open ended questions were categorised.Results: Response rates for spouses and staff were 24% and 36%, respectively. Half the spouse sample (n=533) and almost 75% of the staff sample (n=102) reported high or very high stress due to business travel. Self reported spouse stress was associated with six out of eight travel factors. Female spouses, those with children, and younger spouses reported greater stress. Self reported staff stress was significantly associated with four out of nine travel factors. Further insight into how business travel affects families and staff (including children's behavioural changes) and how families cope was gained through responses to written questions.Conclusions: The findings support the notion that lengthy and frequent travel and frequent changes in travel dates which affect family plans, all characteristic of WBG missions, negatively affects many spouses and children (particularly young children) and that the strain on families contributes significantly to the stress staff feel about their travel. Policies or management practices that take into consideration family activities and give staff greater leeway in controlling and refusing travel may help relieve stress.
Galactorrhoea and pituitary mass: a typical prolactinoma?
Authors: Brändle Michael , Schmid Christoph 
Published: July 2002

Abstract
A 21 year old woman presenting with galactorrhoea, hyperprolactinaemia, and a pituitary mass on magnetic resonance imaging (MRI) is described who was referred to us before planned pituitary surgery. Although a thorough history did not suggest hypothyroidism, laboratory studies revealed profound primary hypothyroidism. At that time, pituitary MRI showed homogeneous enlargement of the pituitary gland consistent with pituitary hyperplasia due to primary hypothyroidism. With thyroid hormone replacement therapy the galactorrhoea resolved, concentrations of prolactin and thyroid hormones returned to normal, and the pituitary shrunk to normal size within two months. This case illustrates that primary hypothyroidism can present only with galactorrhoea and pituitary mass, and should therefore be considered in the differential diagnosis of hyperprolactinaemia and pituitary enlargement.
Role of smoking in inflammatory bowel disease: implications for therapy
Authors: Thomas Gareth A O , Rhodes John , Green John T , Richardson Charles 
Published: July 2002

Abstract
The relationship between smoking and inflammatory bowel disease is now firmly established but remains a source of confusion among both patients and doctors. It is negatively associated with ulcerative colitis but positively associated with Crohn's disease. In addition, it has opposite influences on the clinical course of the two conditions with benefit in ulcerative colitis but a detrimental effect in Crohn's disease. These differences have been the subject of much interest and scrutiny with the hope that they may offer some insight into the pathogenesis of the two conditions and possibly lead to alternative therapeutic options. Nicotine is probably the principal active ingredient in smoking responsible for the association; trials have shown it to be of some benefit in ulcerative colitis, but further research is required to establish its therapeutic role, and the relevant mechanisms responsible for its action. In this article, we review the role of smoking in inflammatory bowel disease and its implication for therapy.