bluuebunny/crossref_metadata_2025_split huggingface dataset:
A significant proportion of HIV‐infected patients admitted to hospital have immunosuppression as a result of failure of highly active antiretroviral therapy
Authors: Manavi K , McMillan A 
Published: September 2004

ObjectivesTo investigate the immunological and virological features of patients on highly active antiretroviral therapy (HAART) admitted to a tertiary centre.MethodsA retrospective study was carried out on HIV‐infected patients on HAART admitted to the Regional Infectious Disease Unit in Edinburgh between June 2002 and July 2003.ResultsA total of 125 patients who had been on HAART for at least 6 months were admitted during the study period. The frequencies of hepatitis C virus (HCV) and hepatitis B virus (HBV) coinfection were 52% (78 of 150 patients) and 48% (72 of 150 patients), respectively (P>0.05 for comparison of frequencies of hepatitis B and C). Of patients who had been on HAART for atleast 6 months, 50% (63 of 125 patients) were immuno‐suppressed and had significantly higher bed‐days 6 (3–12) compared with those with CD4>200 cells/μL (P<0.002). Amongst immuno‐suppressed patients, 38% (24 of 63) had undetectable viral load after at least 6 months of therapy. Those patients were mostly (67%) intravenous drug users and had a significantly higher median age (43 years; range 38–47 years) than other patients (P<0.001).ConclusionsEarlier start of HAART and addition of interleukin (IL)‐2 to the treatment regimens of patients at risk of slow CD4 T‐cell count recovery may reduce the duration of their subsequent hospital admissions.
In vivo regulation of dopamine and noradrenaline release by alpha2A‐adrenoceptors in the mouse nucleus accumbens
Authors: Ihalainen Jouni A. , Tanila Heikki 
Published: September 2004

AbstractThe present study investigated the role of alpha2A‐adrenoceptor (α2A‐AR) subtype in the regulation of noradrenaline (NA) and dopamine (DA) release in the nucleus accumbens (NAc). The effect of locally infused and systemically injected α2‐AR agonist, dexmedetomidine (DMT), and α2‐AR antagonist, atipamezole, on NA and DA release was investigated in α2A‐AR knockout and control mice by using in vivo microdialysis. In addition, we compared the drug effects on DA and NA release in the NAc to their effect on locomotor activity. Baseline NA and DA concentrations did not differ between genotypes. Local infusion of DMT decreased, in a concentration‐dependent manner, NA, but not DA, levels in the control mice. However, systemic injection of DMT decreased both NA and DA levels in the control mice. In both cases DMT had no effects on transmitter release in α2A‐AR knockout mice. Our results suggest that α2‐ARs regulate the release of NA, but not DA, at the terminal level in the NAc. However, α2‐ARs regulate DA release in the NAc indirectly by their effect on DA neurones in the ventral tegmental area via an unknown mechanism. In both cases the regulation is mediated by α2A‐adrenoceptor subtype. Also the modulation of locomotor activity by α2‐AR agonist and antagonist seems to be mediated via α2A‐adrenoceptors.
Dicyclohexylphthalate causes hyperactivity in the rat concomitantly with impairment of tyrosine hydroxylase immunoreactivity
Authors: Ishido Masami , Masuo Yoshinori , Sayato‐Suzuki Junko , Oka Syuichi , Niki Etsuo , Morita Masatoshi 
Published: September 2004

AbstractEndocrine disruptors possibly exert effects on neuronal functions leading, in particular, to behavioural alterations. In this study, we examined the effects of dicyclohexylphthalate (DCHP), an endocrine disruptor, on rat behavioural and cellular responses. Single intracisternal administration of DCHP (0.87–87 nmol) into 5‐day‐old male Wistar rats caused significant hyperactivity at 4–5 weeks of age. It was about 1.4‐fold more active in the nocturnal phase after administration of 87 nmol of DCHP than control rats (p < 0.001). The response had a tendency to be dose‐dependent. Based on DNA macoarray analyses, DCHP down‐regulated the levels of gene expression of the dopamine D4 receptor at 4 weeks old in both the midbrain and the striatum, and the dopamine transporter in the midbrain at 8 weeks old 1.7‐ to 2‐fold. The gene expression of several subtypes of glutamate receptors was facilitated in the striatum at 4 weeks old and in the midbrain at 8 weeks old. Some normalization and/or compensatory changes seemed to occur in gene expression of GABA or glycine transmission. Furthermore, DCHP abolished immunoreactivity of tyrosine hydroxylase in the substantia nigra at 8 weeks of age, where TUNEL‐positive cells were seen. We conclude that DCHP affected the developing rat brain, resulting in hyperactivity, probably as a result of degeneration of mesencephalic tyrosine hydroxylase rather than alteration of the level of gene expression.
Biochemical characterization and immunohistochemical localization of urotensin II in the human brainstem and spinal cord
Authors: Chartrel Nicolas , Leprince Jérôme , Dujardin Cynthia , Chatenet David , Tollemer Hélène , Baroncini Marc , Balment Richard J. , Beauvillain Jean‐Claude , Vaudry Hubert 
Published: September 2004

AbstractThe human urotensin II (UII) precursor encompasses several potential cleavage sites and thus, processing of pro‐UII may generate various forms of mature UII including the peptides of 11 (UII11), 16 (UII16) and 19 (UII19) residues. Until now, the native form of human UII had not been characterized. Here, we show that the major UII peptide occurring in the human spinal cord corresponds to UII11. In contrast, neither the UII16 nor the UII19 forms could be detected. In 50% of the brainstem and in all the spinal cord extracts analysed, a second minor UII‐immunoreactive peptide was resolved. Immunohistochemical labelling of the cervical segment of the human spinal cord revealed that the UII‐immunoreactive material was confined to a subset of ventral horn motoneurones. These data provide the first evidence that in the human, the UII precursor, expressed in motoneurones, is processed at the tribasic KKR93 cleavage site to generate a mature form of UII of 11 amino acids. The absence of N‐terminally elongated forms of UII of 16 and 19 residues indicates that pro‐UII is not cleaved at the R85 or K88 monobasic sites. Finally, the minor UII‐immunoreactive peptide detected in several tissue extracts might correspond to an extended form of UII resulting from the processing of the UII precursor at the basic RK50 or RK66 doublets.
The 5‐HT2A receptor antagonist M100,907 prevents extracellular glutamate rising in response to NMDA receptor blockade in the mPFC
Authors: Ceglia Ilaria , Carli Mirjana , Baviera Marta , Renoldi Giuliano , Calcagno Eleonora , Invernizzi Roberto W. 
Published: September 2004

AbstractWe recently found that intracortical injection of the selective and competitive N‐methyl‐d‐aspartate (NMDA) receptor antagonist 3‐(R)‐2‐carboxypiperazin‐4‐propyl‐1‐phosphonic acid (CPP) impaired attentional performance in rats and blockade of 5‐hydroxytryptamine (5‐HT)2A receptors antagonized this effect. Here, we used the microdialysis technique in conscious rats to study the effect of CPP on extracellular glutamate (GLU) in the medial prefrontal cortex (mPFC) and the regulation of this effect by 5‐HT2A receptors. Intraperitoneal injection of 20 mg/kg CPP increased extracellular GLU in the mPFC (201% of basal levels) but had no effect on 5‐HT. Intracortical infusion of 100 µm CPP increased extracellular GLU (230% of basal values) and 5‐HT (150% of basal values) in the mPFC, whereas 30 µm had no significant effect. The effect of 100 µm CPP on extracellular GLU was abolished by tetrodotoxin, suggesting that neuronal activity is required. Subcutaneous injection of 40 µg/kg M100,907 completely antagonized the effect of 100 µm cpp on extracellular GLU, whereas 10 µg/kg caused only partial attenuation. Likewise, intracortical infusion of 0.1 µm M100,907 completely reversed the increase of extracellular GLU induced by CPP. These findings show that blockade of NMDA receptors in the mPFC is sufficient to increase extracellular GLU locally. The increase of cortical extracellular GLU may contribute to CPP‐induced cognitive deficits and blockade of 5‐HT2A receptors may provide a molecular mechanism for reversing these deficits caused by dysfunctional glutamatergic transmission in the mPFC.
Ubiquitin‐proteasome‐mediated CREB repressor degradation during induction of long‐term facilitation
Authors: Upadhya Sudarshan C. , Smith Thuy K. , Hegde Ashok N. 
Published: September 2004

AbstractLong‐term facilitation in Aplysia and other forms of long‐term memory in invertebrates and vertebrates require the gene expression cascade induced by cAMP‐responsive element binding protein (CREB). Normally, gene expression by CREB is inhibited by repressors. The molecular mechanisms by which the repression is relieved are not understood. Our results show that Aplysia CREB repressor is a substrate for degradation by the ubiquitin‐proteasome pathway. Treatment with the facilitatory neurotransmitter 5‐hydroxy tryptamine (5‐HT) leads to CREB repressor degradation in vivo and the degradation can be blocked by a specific proteasome inhibitor. Our biochemical studies show that attachment of ubiquitin molecules marks the CREB repressor for degradation by the proteasome. Protein kinase C (PKC) stimulates ubiquitination and degradation of the CREB repressor. Our results suggest that proteolytic removal of the CREB repressor is a potential mechanism for controlling gene expression by CREB. Without stimulation, gene expression is suppressed by the CREB repressor. Upon stimulation with 5‐HT, PKC is activated, causing enhancement in ubiquitination and degradation of the CREB repressor. Thus, regulation of proteolysis of the CREB repressor by PKC might be critical in determining whether or not CREB‐mediated gene expression goes forward during induction of long‐term facilitation.
Protein processing and releases of neuregulin‐1 are regulated in an activity‐dependent manner
Authors: Ozaki Miwako , Itoh Kouich , Miyakawa Yukie , Kishida Haruo , Hashikawa Tsutomu 
Published: September 2004

AbstractIdentification of the key molecules that bridge presynaptic neuronal events and long‐term modification of the postsynaptic process is an important challenge which will have to be met in order to further our understanding of the mechanisms for learning and memory. This study is focused on neuregulin‐1 (NRG‐1), a neurotrophic factor, that is known to regulate the development of various tissues and/or the life/death of cells through activation of the ErbB family receptor tyrosine kinases. It was discovered that the soluble form of NRG‐1 (sNRG‐1) is produced from the transmembrane form of NRG through proteolytic cleavage during electrical stimulation of either cultured cerebellar granule cells (GCs) or pontine nucleus neurons (PNs) that are presynaptic to GCs. sNRG‐1 was assayed by measuring the phosphorylation of both the ErbB receptors and cyclic AMP‐responsive element‐binding protein (CREB), and by means of antibodies to sNRG‐1. The cleavage and release of NRG‐1 depended on the frequency of electrical stimulation; the peak effect was at 50 Hz in both GCs and PNs. Activation of protein kinase C (PKC) mimicked this effect. The culture apparatus provided along with the mass‐electrical stimulation that was employed proved to be a powerful tool for combining neuronal electrical events and chemical events. We conclude from the results that, in mossy fibre (PN axon)‐GC synapses, electrical activity controls the proteolytic processing of NRG‐1 in a frequency‐dependent fashion and involves PKC. Furthermore, cleaved sNRG‐1 plays an important functional role in regulating transmission across these synapses.
Novel tetranucleotide microsatellite markers from the Del Norte salamander (Plethodon elongatus) with application to its sister species the Siskiyou Mountain salamander (P. stormi)
Authors: DEGROSS DOUGLAS J. , MEAD LOUISE S. , ARNOLD STEVAN J. 
Published: September 2004

AbstractEleven tetranucleotide microsatellite loci were developed for the Del Norte salamander (Plethodon elongatus). The loci were variably polymorphic, ranging from two to 20 alleles per locus, with expected heterozygosities ranging from 0.07 to 0.86. The loci also amplified in a congener, the Siskiyou Mountain salamander (P. stormi). The microsatellite loci will be used to assess the utility of highly polymorphic markers to assay within‐ and between‐species differentiation between these two closely related species.
Necrotising fasciitis: a new management algorithm based on clinical classification
Authors: Carter Paul S , Banwell Paul E 
Published: September 2004

AbstractNecrotising fasciitis is a rare infection of the subcutaneous tissues. If untreated, it is invariably fatal, and thus a high index of suspicion for the diagnosis is required. The disease's manifestation can range from a fulminant presentation to a subtle and insidious development. The priority in every case is to proceed to radical surgical debridement. On review of the literature and based on our clinical experience, we propose a new classification based on clinical presentation and suggest an algorithm to facilitate the management of this devastating condition. Increasing awareness should be given to the management of the large wounds resulting from the surgical debridement of necrotising fasciitis.
What is responsible for the carcinogenicity of PM2.5?
Authors: Harrison R M , Smith D J T , Kibble A J 
Published: September 2004

Aims:To test whether exposure to known chemical carcinogens in the atmosphere is capable of explaining the association between concentrations of PM2.5and lung cancer mortality observed in the extended ACS Cohort Study.1Methods:Taking account of possible cancer latency periods, lung cancer rates due to exposure to As, Cr(VI), Ni, and polycyclic aromatic hydrocarbons (PAHs) were calculated based on a review of historic measurements from the United States and the use of unit risk factors. The predicted rates were compared with rates of cancer attributable to PM2.5derived from data in the ACS study.1Results:Despite many uncertainties, the lung cancer rates predicted due to exposure to US urban concentrations of the carcinogenic substances arsenic, nickel, chromium, and PAHs measured in 1960 and earlier (and hence allowing for a latency period) were within the range predicted on the basis of the ACS Cohort Study due to exposure of PM2.5. There are, however, many caveats, most particularly that for the chemical carcinogens to be responsible for the effects attributed to PM2.5by Pope and colleagues,1the concentrations of chemical carcinogens at the time of relevant exposures would need to be correlated with the concentrations of PM2.5in US urban areas measured between 1979 and 2000 and used in the ACS study.Conclusions:While many uncertainties remain, it appears plausible that known chemical carcinogens are responsible for the lung cancers attributed to PM2.5exposure in the extended ACS Cohort Study. However, the possibility should not be ruled out that particulate matter is capable of causing lung cancer independent of the presence of known carcinogens.
Work related shoulder disorders: quantitative exposure-response relations with reference to arm posture
Authors: Svendsen S W , Bonde J P , Mathiassen S E , Stengaard-Pedersen K , Frich L H 
Published: September 2004

Aims:To determine quantitative exposure-response relations between work with highly elevated arms and supraspinatus tendinitis, shoulder pain with disability, and shoulder pain without disability.Methods:A cross sectional study was conducted in a historical cohort of 1886 males from three occupational groups. Exposure measurements were performed for four consecutive working days in a random sample of 72 currently employed subjects. Individual work histories were obtained by questionnaire and register data. Health status was ascertained by physical examination blinded towards exposure and symptoms. Data were analysed by generalised estimating equation and multiple logistic regression with adjustment for potential confounders.Results:For current upper arm elevation above 90°, a duration increment of 1% of the daily working hours was associated with odds ratios of 1.23 (95% CI 1.10 to 1.39) for supraspinatus tendinitis, 1.16 (95% CI 1.08 to 1.24) for shoulder pain with disability, and 1.08 (95% CI 1.04 to 1.13) for shoulder pain without disability. The outcomes were not related to duration of employment in one of the three trades.Conclusions:Quantitative exposure-response relations were established between current work with highly elevated arms and clinically verified shoulder disorders. Substantial long term cumulative effects were not shown. A potential for primary prevention was revealed.
A strategy for health surveillance in laboratory animal workers exposed to high molecular weight allergens
Authors: Meijer E , Grobbee D E , Heederik D 
Published: September 2004

Aims:To develop a health surveillance strategy with the use of diagnostic and prognostic prediction models to detect and predict occupational allergic diseases efficiently.Methods:Data from laboratory animal workers (n = 351) participating in an ongoing cohort study were used to develop diagnostic and prognostic models with logistic regression analyses. A diagnostic model was developed from questionnaire items, and exposure measurements to find predictors for the estimation of the probability of sensitisation to workplace allergens. With the resulting questionnaire model workers were divided into subgroups (high/low probability). A prognostic model was established in workers initially low sensitised using follow up data over a 2–3 year period. The accuracy of the models was evaluated by the concordance (c) statistic, and by comparison of the predicted and observed prevalence.Results:A diagnostic rule, containing five questionnaire items, identified workers with a high risk of sensitisation. These workers showed high rates of work related asthma, allergic symptoms, doctor’s visit, and absenteeism. A prognostic rule based on four questionnaire items predicted workers at high risk of near future sensitisation with high rates of future (allergic) respiratory symptoms, and asthmatic attacks.Conclusion:The risk of (future) sensitisation and the severity of laboratory animal allergy can be predicted accurately with diagnostic and prognostic prediction models based on questionnaire items. Workers with an increased risk of future sensitisation also showed serious allergic symptoms at follow up. Workers with a low risk have a low risk of becoming diseased in the future.
Impact of musculoskeletal co-morbidity of neck and upper extremities on healthcare utilisation and sickness absence for low back pain
Authors: IJzelenberg W , Burdorf A 
Published: September 2004

Aims:To describe the presence of musculoskeletal co-morbidity of the neck and upper extremities among industrial workers with low back pain, and to examine whether it has an impact on healthcare utilisation and sickness absence for low back pain.Methods:A self administered questionnaire was used to collect data from 505 industrial workers (response 86%).Results:The 12 month prevalence of low back pain was 50%. Among subjects with low back pain the 12 month prevalence of musculoskeletal co-morbidity of the neck and upper extremities was 68%. Among workers with low back pain, subjects with high pain intensity or disabling low back pain were more likely to have musculoskeletal co-morbidity. In comparison to the subjects who report back pain only, subjects with co-morbidity showed worse general health and health related quality of life. No impact of upper extremity co-morbidity was found on healthcare utilisation, and sickness absence due to low back pain.Conclusions:This study provides no evidence that musculoskeletal co-morbidity of the neck and upper extremities influences the choice to seek care or take sick leave due to low back pain among industrial manual workers. For occupational health practitioners the finding of a high co-morbidity is important to consider when implementing workplace interventions aimed at the reduction of specific musculoskeletal complaints, since the controls for one musculoskeletal complaint may impact adversely on another musculoskeletal complaint. Researchers who perform low back pain intervention studies using generic health measures, should take into account the impact of musculoskeletal co-morbidity on these measures.
Surveillance of noise exposure in the Danish workplace: a baseline survey
Authors: Kock S , Andersen T , Kolstad H A , Kofoed-Nielsen B , Wiesler F , Bonde J P 
Published: September 2004

Aims:To evaluate an epidemiological approach to a national noise hazard surveillance strategy, and report current exposure levels in the Danish workplace.Methods:A study base of 840 companies in 10 selected high risk industries in the largest county in Denmark was identified from a national register. Noise exposure was measured among manual workers recruited from a random sample of workplaces in each industry. For reference, financial companies and a sample of residents were investigated according to the same protocol. The A-weighted equivalent sound level (LAeq) for a full shift was measured by portable dosimeters worn by 830 workers employed at 91 workplaces (67% of 136 eligible companies).Results:The epidemiological design proved feasible and established a baseline for future noise surveillance. Substantial resources were needed to motivate workplaces to enlist and the final participation rate was less than optimal (66.9%). The LAeq (8)values in the selected industries were highly elevated (mean 83.7 dB(A) (95% CI 83.3 to 84.1) in comparison with residents and office workers (mean 69.9 dB(A), 95% CI 68.8 to 71.0). Some 50% of the workers were exposed to more than 85 dB(A) and some 20% to more than 90 dB(A) in several industries.Conclusion:Noise levels in Danish high risk industries remain high. A substantial proportion of workers are exposed to noise levels above the current threshold limit of 85 dB(A). Ongoing surveillance of noise exposure using full shift dosimetry of workers in random samples of workplaces most at risk to high noise levels may help reinforce preventive measures. Such a programme would benefit from compulsory workplace participation.