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1.
JMIR Mhealth Uhealth ; 8(6): e16343, 2020 06 03.
Article in English | MEDLINE | ID: mdl-32490844

ABSTRACT

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a major health problem and an economic burden globally. There is growing interest in how electronic health (eHealth) can be used to provide efficient health care. Telemonitoring, where the patient's health-related data is transmitted to a health care provider, can be used to detect early signs of exacerbations. A successful implementation of telemonitoring systems into clinical practice requires in-depth knowledge of the users' preferences. OBJECTIVE: The aim of this study was to explore perceptions of the use of a home telemonitoring system among patients with COPD. METHODS: Semistructured individual interviews were carried out with 8 women and 5 men who were participants in a project aimed at developing and evaluating a telemonitoring system. The web-based telemonitoring system measured pulmonary function, subjective symptoms, and oxygen saturation. Participants were interviewed after having used the system for 2-4 months. Interview transcripts were analyzed with qualitative content analysis. RESULTS: The analysis resulted in the theme A transition toward increased control and security and four categories: using with (in)security, affecting technical concern or confidence, providing easy access to health care, and increasing control over the disease. The participants reported various perceptions of using the telemonitoring system. They expressed initial feelings of insecurity, both in terms of operating the system and in terms of their disease. However, the practical management of the telemonitoring system became easier with time; the participants gradually gained confidence and improved their self-management. New technology was perceived as an important complement to existing health care, but the importance of maintaining a human contact in real life or through the telemonitoring system was emphasized. CONCLUSIONS: This study captured a transition among the participants from being insecure and experiencing technical concerns to acquiring technical confidence and improving disease management. Telemonitoring can be a valuable complement to health care, leading to increased self-knowledge, a sense of security, and improved self-management. Suggestions to improve the further development and implementation of telemonitoring systems include better patient education and the involvement of end users in the technical development process. Additional research is needed, particularly in the design of user-friendly systems, as well as in developing tools to predict which patients are most likely to find the equipment useful, as this may result in increased empowerment, improved quality of life, reduced costs, and a contribution to equity in health.


Subject(s)
Pulmonary Disease, Chronic Obstructive , Aged , Female , Humans , Male , Perception , Pulmonary Disease, Chronic Obstructive/diagnosis , Pulmonary Disease, Chronic Obstructive/therapy , Qualitative Research , Quality of Life , Self-Management
2.
BMC Med Inform Decis Mak ; 20(1): 87, 2020 05 12.
Article in English | MEDLINE | ID: mdl-32398161

ABSTRACT

BACKGROUND: Many telehealth systems have been designed to identify signs of exacerbations in patients with chronic obstructive pulmonary disease (COPD), but few previous studies have reported the nature of recorded lung function data and what variations to expect in this group of individuals. The aim of the study was to evaluate the nature of individual diurnal, day-to-day and long-term variation in important prognostic markers of COPD exacerbations by employing a telehealth system developed in-house. METHODS: Eight women and five men with COPD performed measurements (spirometry, pulse oximetry and the COPD assessment test (CAT)) three times per week for 4-6 months using the telehealth system. Short-term and long-term individual variations were assessed using the relative density and weekly means respectively. Quality of the spirometry measurements (forced expiratory volume in one second (FEV1) and inspiratory capacity (IC)) was assessed employing the criteria of American Thoracic Society (ATS)/European Respiratory Society (ERS) guidelines. RESULTS: Close to 1100 measurements of both FEV1 and IC were performed during a total of 240 patient weeks. The two standard deviation ranges for intra-individual short-term variation were approximately ±210 mL and ± 350 mL for FEV1 and IC respectively. In long-term, spirometry values increased and decreased without notable changes in symptoms as reported by CAT, although it was unusual with a decrease of more than 50 mL per measurement of FEV1 between three consecutive measurement days. No exacerbation occurred. There was a moderate to strong positive correlation between FEV1 and IC, but weak or absent correlation with the other prognostic markers in the majority of the participants. CONCLUSIONS: Although FEV1 and IC varied within a noticeable range, no corresponding change in symptoms occurred. Therefore, this study reveals important and, to our knowledge, previously not reported information about short and long-term variability in prognostic markers in stable patients with COPD. The present data are of significance when defining criteria for detecting exacerbations using telehealth strategies.


Subject(s)
Pulmonary Disease, Chronic Obstructive , Telemedicine , Aged , Disease Progression , Female , Humans , Lung , Male , Middle Aged , Patients , Spirometry
3.
Am J Trop Med Hyg ; 103(1): 120-131, 2020 07.
Article in English | MEDLINE | ID: mdl-32394883

ABSTRACT

The incidence and geographical distribution of dengue fever has increased in recent decades. The actual disease burden is unknown owing to frequent underreporting and misclassification of cases. A well-functioning system for diagnosing, treating, and reporting cases is of prime importance as disease statistics is the foundation for decisions aiming to control the disease. This study aimed to explore the hospital-based disease surveillance system in Yogyakarta, a dengue-endemic region on Java, Indonesia. Semi-structured interviews were performed with 16 informants from four hospitals, including five general practitioners, three internists, four pediatricians, and four administrative staff working with administration relating to dengue diagnostics and reporting. Data were analyzed using content analysis. A theme arose from the analysis "Dengue surveillance stands and falls by the rigor of the health system." The theme, and underlying categories and subcategories, describes a surveillance system that in the best-case scenario works well and is likely to produce reliable dengue case data. However, there is a lack of synchronization between regulations and guidelines in different hospitals and some friction between regulatory bodies and the care provider. Knowledge among the staff appears to vary, and many clinical and financial decisions are made rather arbitrarily, which ultimately might lead to unequal health service delivery. In conclusion, the dengue surveillance system under study could improve further, particularly by ensuring that all regulations and recommended procedures are standardized and that all staff are given the best opportunity to stay updated on dengue-related matters, clinical as well as regulatory, on a regular basis.


Subject(s)
Dengue Virus/pathogenicity , Dengue/epidemiology , Epidemiological Monitoring , Health Knowledge, Attitudes, Practice , Adult , Dengue/diagnosis , Dengue/virology , Disease Notification/statistics & numerical data , Female , Hospitals , Humans , Incidence , Indonesia/epidemiology , Male , Practice Guidelines as Topic , Qualitative Research , Surveys and Questionnaires
4.
Article in English | MEDLINE | ID: mdl-30897770

ABSTRACT

Effort to control dengue transmission requires community participation to ensure its sustainability. We carried out a knowledge attitude and practice (KAP) survey of dengue prevention to inform the design of a vector control intervention. A cross-sectional survey was conducted in June⁻August 2014 among 521 households in two villages of Yogyakarta, Indonesia. Demographic characteristics and KAP questions were asked using a self-managed questionnaire. Knowledge, attitudes and practice scores were summarized for the population according to sex, age, occupation and education. The average knowledge score was rather poor-3.7 out of 8-although both attitude and practice scores were good: 25.5 out of 32 and 9.2 out of 11 respectively. The best knowledge within the different groups were found among women, the age group 30⁻44 years, people with a university degree and government employees. Best practice scores were found among retired people and housewives. There were several significant gaps in knowledge with respect to basic dengue symptoms, preventive practices and biting and breeding habits of the Aedes mosquito. In contrast, people's practices were considered good, although many respondents failed to recognize outdoor containers as mosquito breeding sites. Accordingly, we developed a vector control card to support people's container cleaning practices. The card was assessed for eight consecutive weeks in 2015, with pre-post larvae positive houses and containers as primary outcome measures. The use of control cards reached a low engagement of the community. Despite ongoing campaigns aiming to engage the community in dengue prevention, knowledge levels were meagre and adherence to taught routines poor in many societal groups. To increase motivation levels, bottom-up strategies are needed to involve all community members in dengue control, not only those that already comply with best practices.


Subject(s)
Community Participation/methods , Dengue/prevention & control , Health Knowledge, Attitudes, Practice , Mosquito Control/methods , Mosquito Vectors/growth & development , Adolescent , Adult , Age Factors , Animals , Cross-Sectional Studies , Dengue/epidemiology , Female , Humans , Indonesia/epidemiology , Male , Middle Aged , Power, Psychological , Sex Factors , Socioeconomic Factors , Young Adult
5.
JMIR Hum Factors ; 5(4): e10801, 2018 Oct 26.
Article in English | MEDLINE | ID: mdl-30368440

ABSTRACT

BACKGROUND: New strategies are urgently needed to support self-management for people with chronic obstructive pulmonary disease (COPD) in primary care. The use of electronic health (eHealth) solutions is promising. However, there is a lack of knowledge about how such eHealth tools should be designed in order to be perceived as relevant and useful and meet the needs and expectations of the health professionals as well as people with COPD and their relatives. OBJECTIVE: The objective of this study was to explore the aspects of an eHealth tool design and content that make it relevant and useful for supporting COPD-related self-management strategies from the perspective of health care professionals, people with COPD and their relatives, and external researchers. METHODS: Data were collected during the development of an eHealth tool. A cocreation process was carried out with participants from two primary care units in northern Sweden and external researchers. Individual interviews were performed with health care professionals (n=13) as well as people with COPD (n=6) and their relatives (n=2), and focus group discussions (n=9) were held with all groups of participants. Data were analyzed using qualitative content analysis. RESULTS: The overarching theme, reinforcing existing support structures, reflects participant views that the eHealth tool needs to be directly applicable and create a sense of commitment in users. Moreover, participants felt that the tool needs to fit with existing routines and contexts and preferably should not challenge existing hierarchies between health care professionals and people with COPD. Important content for health care professionals and people with COPD included knowledge about self-management strategies. Videos were regarded as the most effective method for communicating such knowledge. CONCLUSIONS: The cocreation in the development process enables participant perspectives and priorities to be built into the eHealth tool. This is assumed to contribute to a tool that is useful and relevant and, therefore, adopted into clinical practice and everyday life. Findings from this study can inform the development of eHealth tools for people with COPD in other contexts, as well as the development of eHealth tools for self-management support of other chronic diseases.

6.
BMC Health Serv Res ; 17(1): 467, 2017 07 10.
Article in English | MEDLINE | ID: mdl-28693473

ABSTRACT

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a public health problem. Interprofessional collaboration and health promotion interventions such as exercise training, education, and behaviour change are cost effective, have a good effect on health status, and are recommended in COPD treatment guidelines. There is a gap between the guidelines and the healthcare available to people with COPD. The aim of this study was to increase the understanding of what shapes the provision of primary care services to people with COPD and what healthcare is offered to them from the perspective of healthcare professionals and managers. METHODS: The study was conducted in primary care in a Swedish county council during January to June 2015. A qualitatively driven mixed methods design was applied. Qualitative and quantitative findings were merged into a joint analysis. Interviews for the qualitative component were performed with healthcare professionals (n = 14) from two primary care centres and analysed with qualitative content analysis. Two questionnaires were used for the quantitative component; one was answered by senior managers or COPD nurses at primary care centres (n = 26) in the county council and the other was answered by healthcare professionals (n = 18) at two primary care centres. The questionnaire data were analysed with descriptive statistics. RESULTS: The analysis gave rise to the overarching theme building COPD care on shaky ground. This represents professionals driven to build a supportive COPD care on 'shaky' organisational ground in a fragmented and non-compliant healthcare organisation. The shaky ground is further represented by uninformed patients with a complex disease, which is surrounded with shame. The professionals are autonomous and pragmatic, used to taking responsibility for their work, and with limited involvement of the management. They wish to provide high quality COPD care with interprofessional collaboration, but they lack competence and are hindered by inadequate routines and lack of resources. CONCLUSIONS: There is a gap between COPD treatment guidelines and the healthcare that is provided in primary care. To facilitate implementation of the guidelines several actions are needed, such as further training for professionals, additional resources, and improved organisational structure for interprofessional collaboration and patient education.


Subject(s)
Health Personnel/psychology , Primary Health Care , Pulmonary Disease, Chronic Obstructive/therapy , Adult , Communication , Cost-Benefit Analysis , Delivery of Health Care/organization & administration , Female , Health Knowledge, Attitudes, Practice , Humans , Interviews as Topic , Male , Middle Aged , Qualitative Research , Quality of Health Care , Surveys and Questionnaires , Sweden
7.
PLoS One ; 11(3): e0152688, 2016.
Article in English | MEDLINE | ID: mdl-27031524

ABSTRACT

Research is needed to create early warnings of dengue outbreaks to inform stakeholders and control the disease. This analysis composes of a comparative set of prediction models including only meteorological variables; only lag variables of disease surveillance; as well as combinations of meteorological and lag disease surveillance variables. Generalized linear regression models were used to fit relationships between the predictor variables and the dengue surveillance data as outcome variable on the basis of data from 2001 to 2010. Data from 2011 to 2013 were used for external validation purposed of prediction accuracy of the model. Model fit were evaluated based on prediction performance in terms of detecting epidemics, and for number of predicted cases according to RMSE and SRMSE, as well as AIC. An optimal combination of meteorology and autoregressive lag terms of dengue counts in the past were identified best in predicting dengue incidence and the occurrence of dengue epidemics. Past data on disease surveillance, as predictor alone, visually gave reasonably accurate results for outbreak periods, but not for non-outbreaks periods. A combination of surveillance and meteorological data including lag patterns up to a few years in the past showed most predictive of dengue incidence and occurrence in Yogyakarta, Indonesia. The external validation showed poorer results than the internal validation, but still showed skill in detecting outbreaks up to two months ahead. Prior studies support the fact that past meteorology and surveillance data can be predictive of dengue. However, to a less extent has prior research shown how the longer-term past disease incidence data, up to years, can play a role in predicting outbreaks in the coming years, possibly indicating cross-immunity status of the population.


Subject(s)
Dengue/epidemiology , Meteorological Concepts , Climate , Dengue/diagnosis , Dengue/transmission , Dengue Virus/isolation & purification , Disease Outbreaks , Humans , Humidity , Incidence , Indonesia/epidemiology , Linear Models , Models, Biological , Models, Statistical , Rain , Temperature
8.
J Adv Nurs ; 71(8): 1883-91, 2015 Aug.
Article in English | MEDLINE | ID: mdl-25810044

ABSTRACT

AIM: The aim of this study was to explore nurses' perceptions of climate and environmental issues and examine how nurses perceive their role in contributing to the process of sustainable development. BACKGROUND: Climate change and its implications for human health represent an increasingly important issue for the healthcare sector. According to the International Council of Nurses Code of Ethics, nurses have a responsibility to be involved and support climate change mitigation and adaptation to protect human health. DESIGN: This is a descriptive, explorative qualitative study. METHODS: Nurses (n = 18) were recruited from hospitals, primary care and emergency medical services; eight participated in semi-structured, in-depth individual interviews and 10 participated in two focus groups. Data were collected from April-October 2013 in Sweden; interviews were transcribed verbatim and analysed using content analysis. RESULTS: Two main themes were identified from the interviews: (i) an incongruence between climate and environmental issues and nurses' daily work; and (ii) public health work is regarded as a health co-benefit of climate change mitigation. While being green is not the primary task in a lifesaving, hectic and economically challenging context, nurses' perceived their profession as entailing responsibility, opportunities and a sense of individual commitment to influence the environment in a positive direction. CONCLUSIONS: This study argues there is a need for increased awareness of issues and methods that are crucial for the healthcare sector to respond to climate change. Efforts to develop interventions should explore how nurses should be able to contribute to the healthcare sector's preparedness for and contributions to sustainable development.


Subject(s)
Climate Change , Nursing Staff/psychology , Humans , Qualitative Research , Sweden
9.
Respir Med ; 109(1): 11-26, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25464906

ABSTRACT

BACKGROUND: Only a minority of patients with chronic obstructive pulmonary disease (COPD) have access to pulmonary rehabilitation (PR). Home-based solutions such as telehealthcare, have been used in efforts to make PR more available. The aim of this systematic review was to investigate the effects of telehealthcare on physical activity level, physical capacity and dyspnea in patients with COPD, and to describe the interventions used. METHODS: Randomized controlled trials were identified through database searches, reference lists and included authors. Articles were reviewed based on eligibility criteria by three authors. Risk of bias was assessed by two authors. Standardized mean differences (SMD) or mean differences (MD) with 95% CI were calculated. Forest plots were used to present data visually. RESULTS: Nine studies (982 patients) were included. For physical activity level, there was a significant effect favoring telehealthcare (MD, 64.7 min; 95% CI, 54.4-74.9). No difference between groups was found for physical capacity (MD, -1.3 m; 95% CI, -8.1-5.5) and dyspnea (SMD, 0.088; 95% CI, -0.056-0.233). Telehealthcare was promoted through phone calls, websites or mobile phones, often combined with education and/or exercise training. Comparators were ordinary care, exercise training and/or education. CONCLUSIONS: The use of telehealthcare may lead to improvements in physical activity level, although the results should be interpreted with caution given the heterogeneity in studies. This is an important area of research and further studies of the effect of telehealthcare for patients with COPD would be beneficial. REGISTRATION: In PROSPERO 2012: CRD42012003294. STUDY PROTOCOL: http://www.crd.york.ac.uk/PROSPEROFILES/3294_PROTOCOL_20121016.pdf.


Subject(s)
Dyspnea/rehabilitation , Pulmonary Disease, Chronic Obstructive/rehabilitation , Telerehabilitation/methods , Dyspnea/etiology , Dyspnea/physiopathology , Humans , Motor Activity/physiology , Pulmonary Disease, Chronic Obstructive/complications , Pulmonary Disease, Chronic Obstructive/physiopathology , Treatment Outcome
10.
PLoS One ; 9(9): e105040, 2014.
Article in English | MEDLINE | ID: mdl-25188322

ABSTRACT

BACKGROUND: The healthcare sector is a significant contributor to global carbon emissions, in part due to extensive travelling by patients and health workers. OBJECTIVES: To evaluate the potential of telemedicine services based on videoconferencing technology to reduce travelling and thus carbon emissions in the healthcare sector. METHODS: A life cycle inventory was performed to evaluate the carbon reduction potential of telemedicine activities beyond a reduction in travel related emissions. The study included two rehabilitation units at Umeå University Hospital in Sweden. Carbon emissions generated during telemedicine appointments were compared with care-as-usual scenarios. Upper and lower bound emissions scenarios were created based on different teleconferencing solutions and thresholds for when telemedicine becomes favorable were estimated. Sensitivity analyses were performed to pinpoint the most important contributors to emissions for different set-ups and use cases. RESULTS: Replacing physical visits with telemedicine appointments resulted in a significant 40-70 times decrease in carbon emissions. Factors such as meeting duration, bandwidth and use rates influence emissions to various extents. According to the lower bound scenario, telemedicine becomes a greener choice at a distance of a few kilometers when the alternative is transport by car. CONCLUSIONS: Telemedicine is a potent carbon reduction strategy in the health sector. But to contribute significantly to climate change mitigation, a paradigm shift might be required where telemedicine is regarded as an essential component of ordinary health care activities and not only considered to be a service to the few who lack access to care due to geography, isolation or other constraints.


Subject(s)
Carbon Footprint , Health Care Sector , Telemedicine , Carbon Footprint/economics , Carbon Footprint/statistics & numerical data , Climate Change/economics , Cost-Benefit Analysis , Delivery of Health Care/economics , Health Care Sector/economics , Hospitals, University , Humans , Sweden , Telemedicine/economics , Travel/economics , Videoconferencing/economics
11.
Stud Health Technol Inform ; 192: 585-8, 2013.
Article in English | MEDLINE | ID: mdl-23920623

ABSTRACT

Dengue fever is a major problem in many developing countries, including Indonesia. Laboratory examination is used to diagnose dengue infection and to monitor disease progression. Hematology tests, such as platelet count, are also used for timely recognition of the development of severe dengue. In primary health care centers platelet counting is typically performed manually, which is labor intensive and requires an experienced laboratory technician. To address this challenge, we have developed an automatic platelet counter for primary health care and resource-poor settings. The technology is based on a conventional microscope equipped with a digital camera linked to a personal computer, which can capture and analyze microscope images of blood samples. To evaluate the accuracy of the technology, it was compared to platelet counts performed manual by an experienced laboratory technician. Statistical analysis shows no difference between the techniques with a kappa coefficient of 0.6. This method is judged to have great potential as a tool to help primary health centers and other facilities with limited resources to deal with the burden of dengue.


Subject(s)
Blood Platelets/pathology , Dengue/blood , Dengue/diagnosis , Diagnosis, Computer-Assisted/methods , Image Interpretation, Computer-Assisted/methods , Microscopy/methods , Platelet Count/methods , Artificial Intelligence , Cells, Cultured , Dengue/pathology , Diagnosis, Computer-Assisted/instrumentation , Equipment Design , Equipment Failure Analysis , Humans , Image Interpretation, Computer-Assisted/instrumentation , Indonesia , Microscopy/instrumentation , Pattern Recognition, Automated/methods , Platelet Count/instrumentation , Primary Health Care/methods , Reproducibility of Results , Sensitivity and Specificity , Software
12.
Article in English | MEDLINE | ID: mdl-22679398

ABSTRACT

Climate change is one of today's most pressing global issues. Policies to guide mitigation and adaptation are needed to avoid the devastating impacts of climate change. The health sector is a significant contributor to greenhouse gas emissions in developed countries, and its climate impact in low-income countries is growing steadily. This paper reviews and discusses the literature regarding health sector mitigation potential, known and hypothetical co-benefits, and the potential of health information technology, such as eHealth, in climate change mitigation and adaptation. The promising role of eHealth as an adaptation strategy to reduce societal vulnerability to climate change, and the link's between mitigation and adaptation, are also discussed. The topic of environmental eHealth has gained little attention to date, despite its potential to contribute to more sustainable and green health care. A growing number of local and global initiatives on 'green information and communication technology (ICT)' are now mentioning eHealth as a promising technology with the potential to reduce emission rates from ICT use. However, the embracing of eHealth is slow because of limitations in technological infrastructure, capacity and political will. Further research on potential emissions reductions and co-benefits with green ICT, in terms of health outcomes and economic effectiveness, would be valuable to guide development and implementation of eHealth in health sector mitigation and adaptation policies.


Subject(s)
Climate Change , Delivery of Health Care/organization & administration , Telemedicine/organization & administration , Conservation of Natural Resources , Health Policy , Humans , Medical Informatics
13.
Biochem Biophys Res Commun ; 418(4): 731-5, 2012 Feb 24.
Article in English | MEDLINE | ID: mdl-22305717

ABSTRACT

Cholera is a disease which shows a clear blood group profile, with blood group O individuals experiencing the most severe symptoms. For a long time, the cholera toxin has been suspected to be the main culprit of this blood group dependence. Here, we show that both El Tor and classical cholera toxin B-pentamers do indeed bind blood group determinants (with equal affinities), using Surface Plasmon Resonance and NMR spectroscopy. Together with previous structural data, this confirms our earlier hypothesis as to the molecular basis of cholera blood group dependence, with an interesting twist: the shorter blood group H-determinant characteristic of blood group O individuals binds with similar binding affinity compared to the A-determinant, however, with different kinetics.


Subject(s)
Blood Group Antigens/chemistry , Cholera Toxin/chemistry , Binding Sites , Humans , Nuclear Magnetic Resonance, Biomolecular , Protein Conformation , Surface Plasmon Resonance
14.
J Mol Biol ; 406(3): 387-402, 2011 Feb 25.
Article in English | MEDLINE | ID: mdl-21168418

ABSTRACT

Cholera toxin (CT) and Escherichia coli heat-labile enterotoxin (LT) are structurally and functionally related and share the same primary receptor, the GM1 ganglioside. Despite their extensive similarities, these two toxins exhibit distinct ligand specificities, with LT being more promiscuous than CT. Here, we have attempted to rationalize the broader binding specificity of LT and the subtle differences between the binding characteristics of LTs from human and porcine origins (mediated by their B subunit pentamers, hLTB and pLTB, respectively). The analysis is based on two crystal structures of pLTB in complexes with the pentasaccharide of its primary ligand, GM1, and with neolactotetraose, the carbohydrate determinant of a typical secondary ligand of LTs, respectively. Important molecular determinants underlying the different binding specificities of LTB and CTB are found to be contributed by Ser95, Tyr18 and Thr4 (or Ser4 of hLTB), which together prestabilize the binding site by positioning Lys91, Glu51 and the adjacent loop region (50-61) containing Ile58 for ligand binding. Glu7 and Ala1 may also play an important role. Many of these residues are closely connected with a recently identified second binding site, and there appears to be cross-talk between the two sites. Binding to N-acetyllactosamine-terminated receptors is further augmented by Arg13 (present in pLT and some hLT variants), as previously predicted.


Subject(s)
Bacterial Toxins/chemistry , Cholera Toxin/chemistry , Enterotoxins/chemistry , Escherichia coli Proteins/chemistry , Amino Acid Sequence , Amino Sugars , Animals , Bacterial Toxins/metabolism , Binding Sites , Cholera Toxin/metabolism , Crystallography, X-Ray , Enterotoxins/metabolism , Escherichia coli , Escherichia coli Proteins/metabolism , G(M1) Ganglioside/metabolism , Humans , Ligands , Models, Molecular , Molecular Sequence Data , Protein Binding , Species Specificity , Swine
15.
FEBS Lett ; 584(12): 2548-55, 2010 Jun 18.
Article in English | MEDLINE | ID: mdl-20417206

ABSTRACT

Climate change has the potential to increase the threat of water-borne diseases, through rises in temperature and sea-level, and precipitation variability. Cholera poses a particular threat, and the need to develop better intervention tools is imminent. Cholera infections are particularly severe for blood group O individuals, who are less protected by the current vaccines. Here we derive a hypothesis as to the molecular origins of blood-group dependence of this disease, based on relevant epidemiological, clinical and molecular data, and give suggestions on how to plan prevention strategies, and develop novel and improved pharmaceuticals.


Subject(s)
Blood Group Antigens , Cholera/blood , ABO Blood-Group System/chemistry , Cholera/etiology , Cholera/prevention & control , Cholera Toxin/chemistry , Cholera Toxin/toxicity , Climate Change , Humans , Models, Biological , Models, Molecular
16.
J Mol Biol ; 371(3): 754-64, 2007 Aug 17.
Article in English | MEDLINE | ID: mdl-17586525

ABSTRACT

In a number of bacterial infections, such as Helicobacter pylori, Campylobacter jejuni and Vibrio cholerae infections, a correlation between the severity of disease and blood group phenotype of infected individuals has been observed. In the present investigation, we have studied the molecular basis of this effect for enterotoxigenic Escherichia coli (ETEC) infections. ETEC are non-invasive bacteria, which act through second messenger pathways to cause diarrhea. It has been suggested that the major virulence factor of ETEC from human isolates, i.e. the human heat-labile enterotoxin (hLT), recognizes certain blood group epitopes, although the molecular basis of blood group antigen recognition is unknown. The 2.5 A crystal structure of the receptor-binding B-subunit of hLT in complex with the blood group A antigen analog GalNAcalpha3(Fucalpha2)Galbeta4(Fucalpha3)Glcbeta provides evidence of a previously unknown binding site in the native toxin. The structure reveals the molecular interactions underlying blood group antigen recognition and suggests how this protein can discriminate between different blood group epitopes. These results support the previously debated role of hLT in the blood group dependence of ETEC infections. Similar observations regarding the closely related cholera toxin in V. cholera infections are also discussed.


Subject(s)
Bacterial Toxins/metabolism , Blood Group Antigens/metabolism , Enterotoxins/metabolism , Escherichia coli Proteins/metabolism , Escherichia coli/metabolism , Hot Temperature , Amino Acid Sequence , Bacterial Toxins/chemistry , Binding Sites , Carbohydrate Metabolism , Crystallography, X-Ray , Enterotoxins/chemistry , Escherichia coli Proteins/chemistry , Humans , Models, Molecular , Molecular Sequence Data , Protein Binding , Sequence Alignment , Surface Properties
17.
J Mol Biol ; 369(3): 710-21, 2007 Jun 08.
Article in English | MEDLINE | ID: mdl-17442345

ABSTRACT

MOA, a lectin from the mushroom Marasmius oreades, is one of the few reagents that specifically agglutinate blood group B erythrocytes. Further, it is the only lectin known to have exclusive specificity for Galalpha(1,3)Gal-containing sugar epitopes, which are antigens that pose a severe barrier to animal-to-human organ transplantation. We describe here the structure of MOA at 2.4 A resolution, in complex with the linear trisaccharide Galalpha(1,3)Galbeta(1,4)GlcNAc. The structure is dimeric, with two distinct domains per protomer: the N-terminal lectin module adopts a ricinB/beta-trefoil fold and contains three putative carbohydrate-binding sites, while the C-terminal domain serves as a dimerization interface. This latter domain, which has an unknown function, reveals a novel fold with intriguing conservation of an active site cleft. A number of indications suggest that MOA may have an enzymatic function in addition to the sugar-binding properties.


Subject(s)
Agaricales/metabolism , Carbohydrates/chemistry , Epitopes/chemistry , Lectins/chemistry , Proteins/chemistry , Amino Acid Sequence , Crystallography, X-Ray , Dimerization , Models, Molecular , Molecular Conformation , Molecular Sequence Data , Protein Conformation , Protein Structure, Tertiary , Ricin/chemistry , Transplantation, Heterologous
18.
Acta Crystallogr D Biol Crystallogr ; 60(Pt 11): 2038-9, 2004 Nov.
Article in English | MEDLINE | ID: mdl-15502320

ABSTRACT

The Marasmius oreades agglutinin (MOA) recognizes blood group B oligosaccharides. This mushroom lectin belongs to the ricin superfamily and is currently the only lectin known with exclusive specificity for Galalpha1,3Gal-structures, as occur in the subterminally fucosylated blood group B epitope Galalpha1,3(Fucalpha1,2)Galbeta1,4GlcNAc (MOA's preferred ligand) or without fucosylation in the xenotransplantation epitope. MOA has been co-crystallized with the linear blood group B trisaccharide Galalpha1,3Galbeta1,4GlcNAc using the hanging-drop vapour-diffusion technique at room temperature. MOA crystals were grown in the presence of ammonium formate and HEPES buffer. A 3.0 A data set has been collected. Preliminary analysis of the X-ray data is consistent with space group P3(1) or P3(2) and unit-cell parameters a = b = 105, c = 113 A, with two dimers per asymmetric unit.


Subject(s)
Agaricales/chemistry , Lectins/chemistry , Crystallization , Crystallography, X-Ray
19.
Structure ; 12(9): 1655-67, 2004 Sep.
Article in English | MEDLINE | ID: mdl-15341730

ABSTRACT

A hybrid between the B subunits of cholera toxin and Escherichia coli heat-labile enterotoxin has been described, which exhibits a novel binding specificity to blood group A and B type 2 determinants. In the present investigation, we have determined the crystal structure of this protein hybrid, termed LCTBK, in complex with the blood group A pentasaccharide GalNAcalpha3(Fucalpha2)Galbeta4(Fucalpha3)GlcNAcbeta, confirming not only the novel binding specificity but also a distinct new oligosaccharide binding site. Binding studies revealed that the new specificity can be ascribed to a single mutation (S4N) introduced into the sequence of Escherichia coli heat-labile enterotoxin. At a resolution of 1.9 A, the new binding site is resolved in excellent detail. Main features include a complex network of water molecules, which is well preserved by the parent toxins, and an unexpectedly modest contribution to binding by the critical residue Asn4, which interacts with the ligand only via a single water molecule.


Subject(s)
Bacterial Toxins/chemistry , Cholera Toxin/chemistry , Enterotoxins/chemistry , Escherichia coli Proteins/chemistry , Protein Structure, Tertiary , Protein Subunits/chemistry , Recombinant Fusion Proteins/chemistry , Asparagine/metabolism , Bacterial Toxins/genetics , Bacterial Toxins/metabolism , Binding Sites , Blood Group Antigens/metabolism , Cholera Toxin/genetics , Cholera Toxin/metabolism , Crystallography, X-Ray , Drug Design , Enterotoxins/genetics , Enterotoxins/metabolism , Escherichia coli Proteins/genetics , Escherichia coli Proteins/metabolism , Glycosphingolipids/chemistry , Glycosphingolipids/metabolism , Humans , Models, Molecular , Molecular Sequence Data , Molecular Structure , Oligosaccharides/chemistry , Oligosaccharides/metabolism , Protein Binding , Protein Subunits/genetics , Protein Subunits/metabolism , Recombinant Fusion Proteins/genetics , Recombinant Fusion Proteins/metabolism , Water/chemistry
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