bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bacterial genotyping by 16S rRNA mass cataloging
Authors: Jackson George W , McNichols Roger J , Fox George E , Willson Richard C 
Published: June 2006

AbstractBackgroundIt has recently been demonstrated that organism identifications can be recovered from mass spectra using various methods including base-specific fragmentation of nucleic acids. Because mass spectrometry is extremely rapid and widely available such techniques offer significant advantages in some applications. A key element in favor of mass spectrometric analysis of RNA fragmentation patterns is that a reference database for analysis of the results can be generated from sequence information. In contrast to hybridization approaches, the genetic affinity of any unknown isolate can in principle be determined within the context of all previously sequenced 16S rRNAs without prior knowledge of what the organism is. In contrast to the original RNase T1cataloging method, when digestion products are analyzed by mass spectrometry, products with the same base composition cannot be distinguished. Hence, it is possible that organisms that are not closely related (having different underlying sequences) might be falsely identified by mass spectralcoincidence. We present a convenient spectral coincidence function for expressing the degree of similarity (or distance) between any two mass-spectra. Trees constructed using this function are consistent with those produced by direct comparison of primary sequences, demonstrating that the inherent degeneracy in mass spectrometric analysis of RNA fragments does not preclude correct organism identification.ResultsNeighbor-joining trees for important bacterial pathogens were generated using distances based on mass spectrometric observables and the spectral coincidence function. These trees demonstrate that most pathogens will be readily distinguished using mass spectrometric analyses of RNA digestion products. A more detailed, genus-level analysis of pathogens and near relatives was also performed, and it was found that assignments of genetic affinity were consistent with those obtained by direct sequence comparisons. Finally, typical values of the coincidence between organisms were also examined with regard to phylogenetic level and sequence variability.ConclusionCluster analysis based on comparison of mass spectrometric observables using the spectral coincidence function is an extremely useful tool for determining the genetic affinity of an unknown bacterium. Additionally, fragmentation patterns can determine within hours if an unknown isolate is potentially a known pathogen among thousands of possible organisms, and if so, which one.
Prevalence and predictors of tuberculin skin positivity in Hellenic Army recruits
Authors: German Vasilios , Giannakos Georgios , Kopterides Petros , Falagas Matthew E 
Published: June 2006

Abstract

Background
Tuberculosis (TB) remains one of the leading causes of death among infectious diseases worldwide. Despite its low incidence rates in countries of Western Europe and North America, the resurgence of TB in Eastern Europe and the increased immigration from high-incidence countries imply that extreme vigilance is required in order to detect early, treat, and isolate all new cases. In this study, we analyzed the prevalence and predictors of tuberculin skin testing positivity in Hellenic Army recruits.

Methods
The study population consisted of 953 Greek military recruits enlisted inthe Army during the period from November 2005 toFebruary 2006. Tuberculin skin testing was performed on all study subjects upon enrollment, according to the routine procedures. A tuberculin skin test reaction size >15 mm was considered positive for all study participants. Epidemiological data regarding age, repatriation status, geographic area of residence, smoking habits, and parental occupation were collected by means of personal interviews. In addition, body weight, height, and body mass index were measured.

Results
The mean age of the studied subjects (± SD) was 23.5 (± 6.4) years. The overall prevalence of tuberculin positivity was 3.9% (37/953), and bivariable analysis showed that it was associated with lower weight (p = 0.047) and repatriation status (p < 0.001). Tuberculin skin testing was positive in 2.6% of natives (24/900) and 24.5% of repatriates (13/53). A backward, stepwise multivariable logistic regression model showed that only repatriation status was independently associated with tuberculin positivity (p < 0.001; odds ratio [OR]: 14.1; 95% confidence interval [CI]: 6.5–30.3).

Conclusion
While the incidence of tuberculosis in the native Greek population is low, and comparable to other Western European countries, the extremely high tuberculin positivity in repatriated persons underscores the importance of actively screening for TB in order to promptly identify, isolate, and treat cases of active and latent infection.
How much time do health services spend on antenatal care? Implications for the introduction of the focused antenatal care model in Tanzania
Authors: von Both Claudia , Fleβa Steffen , Makuwani Ahmad , Mpembeni Rose , Jahn Albrecht 
Published: June 2006

Abstract

Background
Antenatal care (ANC) is a widely used strategy to improve the health of pregnant women and to encourage skilled care during childbirth. In 2002, the Ministry of Health of the United Republic of Tanzania developed a national adaptation plan based on the new model of the World Health Organisation (WHO). In this study we assess the time health workers currently spent on providing ANC services and compare it to the requirements anticipated for the new ANC model in order to identify the implications of Focused ANC on health care providers' workload.

Methods
Health workers in four dispensaries in Mtwara Urban District, Southern Tanzania, were observed while providing routine ANC. The time used for the overall activity as well as for the different, specific components of 71 ANC service provisions was measured in detail; 28 of these were first visits and 43 revisits. Standard time requirements for the provision of focused ANC were assessed through simulated consultations based on the new guidelines.

Results
The average time health workers currently spend for providing ANC service to a first visit client was found to be 15 minutes; the provision of ANC according to the focused ANC model was assessed to be 46 minutes. For a revisiting client the difference between current practise and the anticipated standard of the new model was 27 minutes (9 vs. 36 min.). The major discrepancy between the two procedures was related to counselling. On average a first visit client was counselled for 1:30 minutes, while counselling in revisiting clients did hardly take place at all. The simulation of focused ANC revealed that proper counselling would take about 15 minutes per visit.

Conclusion
While the introduction of focused ANC has the potential to improve the health of pregnant women and to raise the number of births attended by skilled staff in Tanzania, it may need additional investment in human resources. The generally anticipated saving effect of the new model through the reduction of routine consultations may not materialise because the number of consultations is already low in Tanzania with a median of only 4 visits per pregnancy. Special attention needs to be given to counselling attitudes and skills during the training for Focused ANC as this component is identified as the major difference between old practise and the new model. Our estimated requirement of 46 minutes per first visit consultation matches well with the WHO estimate of 40 minutes.
TUCAN/CARDINAL/CARD8 and apoptosis resistance in non-small cell lung cancer cells
Authors: Checinska Agnieszka , Giaccone Giuseppe , Hoogeland Bas SJ , Ferreira Carlos G , Rodriguez Jose A , Kruyt Frank AE 
Published: June 2006

Abstract

Background
Activation of caspase-9 in response to treatment with cytotoxic drugs is inhibited in NSCLC cells, which may contribute to the clinical resistance to chemotherapy shown in this type of tumor. The aim of the present study was to investigate the mechanism of caspase-9 inhibition, with a focus on a possible role of TUCAN as caspase-9 inhibitor and a determinant of chemosensitivity in NSCLC cells.

Methods
Caspase-9 processing and activation were investigated by Western blot and by measuring the cleavage of the fluorogenic substrate LEHD-AFC. Proteins interaction assays, and RNA interference in combination with cell viability and apoptosis assays were used to investigate the involvement of TUCAN in inhibition of caspase-9 and chemosensitivity NSCLC.

Results
Analysis of the components of the caspase-9 activation pathway in a panel of NSCLC and SCLC cells revealed no intrinsic defects. In fact, exogenously added cytochrome c and dATP triggered procaspase-9 cleavage and activation in lung cancer cell lysates, suggesting the presence of an inhibitor. The reported inhibitor of caspase-9, TUCAN, was exclusively expressed in NSCLC cells. However, interactions between TUCAN and procaspase-9 could not be demonstrated by any of the assays used. Furthermore, RNA interference-mediated down-regulation of TUCAN did not restore cisplatin-induced caspase-9 activation or affect cisplatin sensitivity in NSCLC cells.

Conclusion
These results indicate that procaspase-9 is functional and can undergo activation and full processing in lung cancer cell extracts in the presence of additional cytochrome c/dATP. However, the inhibitory protein TUCAN does not play a role in inhibition of procaspase-9 and in determining the sensitivity to cisplatin in NSCLC.
Randomised controlled trial of welfare rights advice accessed via primary health care: pilot study [ISRCTN61522618]
Authors: Mackintosh Joan , White Martin , Howel Denise , Chadwick Tom , Moffatt Suzanne , Deverill Mark , Sandell Adam 
Published: June 2006

Abstract

Background
Little research has directly evaluated the impact of increasing financial or material resources on health. One way of assessing this lies with assisting people to obtain full welfare benefit entitlements. In 2000–1, 2.3 million pensioners were living in poverty in the UK and estimates suggest that around one million do not claim the financial support to which they are entitled. The effectiveness of welfare rights advice services delivered via primary health care to promote health and reduce health inequalities is unknown.

Methods
The main objectives of this study were to assess the feasibility and acceptability of a randomised controlled trial of welfare rights advice in a community setting and identify appropriate health and social outcome measures in order to plan a definitive trial.
This was a single blind, community-based, pilot randomised controlled trial. 126 men and women aged 60 years and over, recruited from 4 general practices in Newcastle upon Tyne, UK, participated. The intervention comprised a structured welfare rights assessment followed by active assistance with welfare benefit claims over the following 24 months. The control group received the intervention after a six month delay. A range of socio-economic, health, behavioural and psycho-social outcomes were measured.

Results
126 out of 400 people invited agreed to participate and 109 were followed up at 24 months. Both the intervention and research procedures were feasible and acceptable to participants and professionals involved. 68 (58%) of all participants received a welfare benefit award (31 financial, 16 non-financial and 21 both). Median time to receipt of benefits from initial assessment was 14 (range 1 to 78) weeks and median financial award was £55 (€81, $98) per household per week. There was little evidence of health-related differences between groups or over time, which could be due to limitations of the study design.

Conclusion
Modification of the study design, including selection of study participants, timing of interventions and length of follow up are recommended for a definitive trial. More appropriate health and psycho-social outcome measures relevant to the elderly population should be sought, particularly focussing on those issues highlighted in the accompanying qualitative study.
Antimicrobial and toxicological evaluation of the leaves of Baissea axillaries Hua used in the management of HIV/AIDS patients
Authors: Abere Tavs A , Agoreyo Freddy O 
Published: June 2006

Abstract

Background
Persistent diarrhea is a common endemic disease with high incidence among the Africans including Nigerians. It also represents a frequent opportunistic disease in people living with HIV. Diarrhea represents one of the most distressful and persistent symptoms of HIV/AIDS, which may or may not be accompanied by an infection. The leaves decoction of Baissea axillaries Hua (Apocynaceae) is used by traditional herbalists in Edo state, Nigeria for the management of people living with HIV/AIDS. Determination of its antimicrobial activity and toxicological profile will provide supportive scientific evidence in favour of its continuous usage.

Method
Chemical and chromatographic tests were employed in phytochemical investigations. Inhibitory activities of aqueous and ethanolic extracts against clinical strains of Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus and Streptococcus faecalis were compared with Togamycin (Spectinomycin). Our report includes minimum inhibitory concentration (MIC) against the test organisms. Toxicological evaluation was determined by administering 250 mg/kg and 500 mg/kg of extracts on male Wister rats for 14 days with normal saline as control. The kidneys, liver, heart and testis tissues were examined.

Results
Phytochemical studies revealed the presence of alkaloids, tannins, and cyanogenetic glycosides. The extracts inhibited the growth of Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus to varying extents, but only the ethanolic extract inhibited growth in Streptococcus faecalis. The LD50 of the extract in mice was above 5000 mg/kg body weight when administered intraperitoneally. Toxicological evaluation showed mere ballooning degeneration of the liver at 250 mg/kg while at 500 mg/kg there was tissue necrosis. The low and high doses showed ill-defined leydig cells in the testis and no remarkable changes in the heart and kidneys.

Conclusion
Extracts of Baissea axillaries have demonstrated antimicrobial activity against clinical strains of selected microorganisms. While there is toxicity at the dose of 500 mg/kg, the therapy shows potential for application in the treatment of diarrhoea associated with AIDS/HIV. Further studies of Baissea axillaries on diarrhoea and toxicity are necessary to evaluate its mechanism of action and to fully establish its safety profile.
Mode of inhibition of HIV-1 Integrase by a C-terminal domain-specific monoclonal antibody*
Authors: Ramcharan Joseph , Colleluori Diana M , Merkel George , Andrake Mark D , Skalka Anna Marie 
Published: June 2006

AbstractBackgroundTo further our understanding of the structure and function of HIV-1 integrase (IN) we developed and characterized a library of monoclonal antibodies (mAbs) directed against this protein. One of these antibodies, mAb33, which is specific for the C-terminal domain, was found to inhibit HIV-1 IN processing activityin vitro; a corresponding Fv fragment was able to inhibit HIV-1 integrationin vivo. Our subsequent studies, using heteronuclear nuclear magnetic resonance spectroscopy, identified six solvent accessible residues on the surface of the C-terminal domain that were immobilized upon binding of the antibody, which were proposed to comprise the epitope. Here we test this hypothesis by measuring the affinity of mAb33 to HIV-1 proteins that contain Ala substitutions in each of these positions. To gain additional insight into the mode of inhibition we also measured the DNA binding capacity and enzymatic activities of the Ala substituted proteins.ResultsWe found that Ala substitution of any one of five of the putative epitope residues, F223, R224, Y226, I267, and I268, caused a decrease in the affinity of the mAb33 for HIV-1 IN, confirming the prediction from NMR data. Although IN derivatives with Ala substitutions in or near the mAb33 epitope exhibited decreased enzymatic activity, none of the epitope substitutions compromised DNA binding to full length HIV-1 IN, as measured by surface plasmon resonance spectroscopy. Two of these derivatives, IN (I276A) and IN (I267A/I268A), exhibited both increased DNA binding affinity and uncharacteristic dissociation kinetics; these proteins also exhibited non-specific nuclease activity. Results from these investigations are discussed in the context of current models for how the C-terminal domain interacts with substrate DNA.ConclusionIt is unlikely that inhibition of HIV-1 IN activity by mAb33 is caused by direct interaction with residues that are essential for substrate binding. Rather our findings are most consistent with a model whereby mAb33 binding distorts or constrains the structure of the C-terminal domain and/or blocks substrate binding indirectly. The DNA binding properties and non-specific nuclease activity of the I267A derivatives suggest that the C-terminal domain of IN normally plays an important role in aligning the viral DNA end for proper processing.
Tumour necrosis factor-α stimulates HIV-1 replication in single-cycle infection of human term placental villi fragments in a time, viral dose and envelope dependent manner
Authors: Kfutwah Anfumbom KW , Mary Jean-Yves , Nicola Marie-Anne , Blaise-Boisseau Sandra , Barré-Sinoussi Françoise , Ayouba Ahidjo , Menu Elisabeth 
Published: June 2006

AbstractBackgroundThe placenta plays an important role in the control ofin uteroHIV-1 mother-to-child transmission (MTCT). Proinflammatory cytokines in the placental environment are particularly implicated in this control. We thus investigated the effect of TNF-α on HIV-1 expression in human placental tissuesin vitro.ResultsHuman placental chorionic villi fragments were infected with varying doses of luciferase reporter HIV-1 pseudotypes with the R5, X4-Env or the vesicular stomatitis virus protein G (VSV-G). Histocultures were then performed in the presence or absence of recombinant human TNF-α. Luciferase activity was measured at different time points in cell lysates or on whole fragments usingex vivoimaging systems.A significant increase in viral expression was detected in placental fragments infected with 0.2 ng of p24 antigen/fragment (P = 0.002) of VSV-G pseudotyped HIV-1 in the presence of TNF-α seen after 120 hours of culture. A time independent significant increase of viral expression by TNF-α was observed with higher doses of VSV-G pseudotyped HIV-1. When placental fragments were infected with R5-Env pseudotyped HIV-1, a low level of HIV expression at 168 hours of culture was detected for 3 of the 5 placentas tested, with no statistically significant enhancement by TNF-α. Infection with X4-Env pseudotyped HIV-1 did not lead to any detectable luciferase activity at any time point in the absence or in the presence of TNF-α.ConclusionTNF-α in the placental environment increases HIV-1 expression and could facilitate MTCT of HIV-1, particularly in an inflammatory context.
Trimellitic anhydride-conjugated serum albumin activates rat alveolar macrophages in vitro
Authors: Valstar Dingena L , Schijf Marcel A , Stelekati Erietta , Nijkamp Frans P , Bloksma Nanne , Henricks Paul AJ 
Published: June 2006

AbstractBackgroundOccupational exposure to airborne low molecular weight chemicals, like trimellitic anhydride (TMA), can result in occupational asthma. Alveolar macrophages (AMs) are among the first cells to encounter these inhaled compounds and were previously shown to influence TMA-induced asthma-like symptoms in the Brown Norway rat. TMA is a hapten that will bind to endogenous proteins upon entrance of the body. Therefore, in the present study we determined if TMA and TMA conjugated to serum albumin induced the production of the macrophage mediators nitric oxide (NO), tumour necrosis factor (TNF), and interleukin 6 (IL-6)in vitrousing the rat AM cell line NR8383 and primary AMs derived from TMA-sensitized and naïve Brown Norway rats.MethodsCells were incubated with different concentrations of TMA, TMA conjugated to bovine serum albumin (BSA), and BSA as a control for 24 h and the culture supernatant was analyzed for mediator content.ResultsTMA alone was not able to induce the production of mediators by NR8383 cells and primary AMs from sensitized and sham-treated rats. TMA-BSA, on the contrary, dose-dependently stimulated the production of NO, TNF, and IL-6 by NR8383 cells and of NO and TNF, but not IL-6, by primary AMs independent of sensitization.ConclusionResults suggest that although TMA is a highly reactive compound, conjugation to a suitable protein is necessary to induce mediator production by AMs. Furthermore, the observation that effects of TMA-BSA were independent of sensitization suggests involvement of an immunologically non-specific receptor. In the discussion it is argued that a macrophage scavenger receptor is a likely candidate.
Neutrophil apoptosis in rheumatoid arthritis is regulated by local oxygen tensions within joints
Authors: Cross Andrew , Barnes Theresa , Bucknall Roger C , Edwards Steven W , Moots Robert J 
Published: June 2006

Abstract
Neutrophils are normally short-lived cells and die by apoptosis, but when recruited into tissues, their apoptosis is delayed, and they survive for much longer time periods. In inflammatory diseases, such as rheumatoid arthritis (RA), this delayed apoptosis may lead to increased tissue damage and a failure of the inflammation to resolve. However, there are conflicting reports in the literature as to whether neutrophil apoptosis is delayed or accelerated in rheumatoid joints. In this report, we show that neutrophils isolated from the ynovial fluid (SF) of patients with RA show accelerated rates of apoptosis when incubated ex vivo and that SF, despite containing a variety of antiapoptotic cytokines, is proapoptotic. Paradoxically, levels of the key neutrophil survival protein Mcl-1 are elevated in freshly isolated SF neutrophils compared with matched peripheral blood samples from the same patients, indicating that delayed neutrophil apoptosis has been signaled in vivo as the cells enter the joints. However, when SF was added to neutrophils and incubated under hypoxia (1% O2), conditions known to exist in vivo within joints, the SF was antiapoptotic. These data reveal that the rheumatoid synovial joint contains a complex mixture of pro- and antiapoptotic factors and that the low, local oxygen tensions that exist within these joints can exert profound effects on neutrophil survival. These experiments also highlight the importance of performing in vitro experiments under laboratory conditions that closely mimic those that occur in vivo; otherwise, misleading conclusions may be drawn.