Antibody levels to the class I and II epitopes of the M protein and myosin are related to group A streptococcal exposure in endemic populations

Rheumatic fever (RF)/rheumatic heart disease (RHD) and post-streptococcal glomerulonephritis are thought to be autoimmune diseases, and follow group A streptococcal (GAS) infection. Different GAS M types have been associated with rheumatogenicity or nephritogenicity and categorized into either of two distinct classes (I or II) based on amino acid sequences present within the repeat region ('C' repeats) of the M protein. Sera from ARF patients have previously been shown to contain elevated levels of antibodies to the class I-specific epitope and myosin with the class I-specific antibodies also being cross-reactive to myosin, suggesting a disease association. This study shows that immunoreactivity of the class I-specific peptide and myosin does not differ between controls and acute RF (ARF)/RHD in populations that are highly endemic for GAS, raising the possibility that the association is related to GAS exposure, not the presence of ARF/RHD. Peptide inhibition studies suggest that the class I epitope may be conformational and residue 10 of the peptide is critical for antibody binding. We demonstrate that correlation of antibody levels between the class I and II epitope is due to class II-specific antibodies recognizing a common epitope with class I which is contained within the sequence RDL-ASRE. Our results suggest that antibody prevalence to class I and II epitopes and myosin is associated with GAS exposure, and that antibodies to these epitopes are not an indicator of disease nor a pathogenic factor in endemic populations.

Protein targeting to the plasma membrane of adult skeletal muscle fiber: An organized mosaic of functional domains

The plasma membrane of differentiated skeletal muscle fibers comprises the sarcolemma, the transverse (T) tubule network, and the neuromuscular and muscle-tendon junctions. We analyzed the organization of these domains in relation to defined surface markers, beta -dystroglycan, dystrophin, and caveolin-3, These markers were shown to exhibit highly organized arrays along the length of the fiber. Caveolin-3 and beta -dystroglycan/dystrophin showed distinct, but to some extent overlapping, labeling patterns and both markers left transverse tubule openings clear. This labeling pattern revealed microdomains over the entire plasma membrane with the exception of the neuromuscular and muscle-tendon junctions which formed distinct demarcated macrodomains. Our results suggest that the entire plasma membrane of mature muscle comprises a mosaic of T tubule domains together with sareolemmal caveolae and beta -dystroglycan domains. The domains identified with these markers were examined with respect to targeting of viral proteins and other expressed domain-specific markers, We found that each marker protein was targeted to distinct microdomains, The macrodomains were intensely labeled with all our markers. Replacing the cytoplasmic tail of the vesicular stomatitis virus glycoprotein with that of CD4 resulted in retargeting from one domain to another. The domain-specific protein distribution at the muscle cell surface may be generated by targeting pathways requiring specific sorting information but this trafficking is different from the conventional apical-basolateral division. (C) 2001 Academic Press.

A cluster of melioidosis cases from an endemic region is clonal and is linked to the water supply using molecular typing of Burkholderia pseudomallei isolates

Nine cases of melioidosis with four deaths occurred over a 28-month period in members of a small remote Aboriginal community in the top end of the Northern Territory of Australia. Typing by pulsed-field gel electrophoresis showed isolates of Burkholderia pseudomallei from six of the cases to be clonal and also identical to an isolate from the community water supply, but not to soil isolates. The clonality of the isolates found in this cluster contrasts with the marked genetic diversity of human and environmental isolates found in this region which is hyperendemic for B. pseudomallei. It is possible that the clonal bacteria persisted and were propagated in biofilm in the water supply system. While the exact mode of transmission to humans and the reasons for cessation of the outbreak remain uncertain, contamination of the unchlorinated community water supply is a likely explanation.

Development of a fully quantitative approach to the interpretation of stress echocardiography using radial and longitudinal myocardial velocities

Background: Tissue Doppler may be used to quantify regional left ventricular function but is limited by segmental variation of longitudinal velocity from base to apex and free to septal walls. We sought to overcome this by developing a composite of longitudinal and radial velocities. Methods and Results. We examined 82 unselected patients undergoing a standard dobutamine echocardiogram. Longitudinal velocity was obtained in the basal and mid segments of each wall using tissue Doppler in the apical views. Radial velocities were derived in the same segments using an automated border detection system and centerline method with regional chords grouped according to segment location and temporally averaged. In 25 patients at low probability of coronary disease, the pattern of regional variation in longitudinal velocity (higher in the septum) was the opposite of radial velocity (higher in the free wall) and the combination was homogenous. In 57 patients undergoing angiography, velocity in abnormal segments was less than normal segments using longitudinal (6.0 +/- 3.6 vs 9.0 +/- 2.2 cm/s, P = .01) and radial velocity (6.0 +/- 4.0 vs 8.0 +/- 3.9 cm/s, P = .02). However, the composite velocity permitted better separation of abnormal and normal segments (13.3 +/- 5.6 vs 17.5 +/- 4.2 cm/s, P = .001). There was no significant difference between the accuracy of this quantitative approach and expert visual wall motion analysis (81% vs 84%, P = .56). Conclusion: Regional variation of uni-dimensional myocardial velocities necessitates site-specific normal ranges, probably because of different fiber directions. Combined analysis of longitudinal and radial velocities allows the derivation of a composite velocity, which is homogenous in all segments and may allow better separation of normal and abnormal myocardium.

Physiological responses to the menstrual cycle - Implications for the development of heat illness in female athletes

Fluctuations in estrogen and progesterone during the menstrual cycle can cause changes in body systems other than the reproductive system. For example, progesterone is involved in the regulation of fluid balance in the renal tubules and innervation of the diaphragm via the phrenic nerve. However, few significant changes in the responses of the cardiovascular and respiratory systems, blood lactate, bodyweight, performance and ratings of perceived exertion are evident across the cycle. Nevertheless, substantial evidence exists to suggest that increased progesterone levels during the luteal phase cause increases in both core and skin temperatures and alter the temperature at which sweating begins during exposure to both ambient and hot environments. As heat illness is characterised by a significant increase in body temperature, it is feasible that an additional increase in core temperature during the luteal phase could place females at an increased risk of developing heat illness during this time. In addition, it is often argued that physiological gender differences such as oxygen consumption, percentage body fat and surface area-to-mass ratio place females at a higher risk of heat illness than males. This review examines various physiological responses to heat exposure during the menstrual cycle at rest and during exercise, and considers whether such changes increase the risk of heat illness in female athletes during a particular phase of the menstrual cycle.

Longitudinal study of veterinarians from entry to the veterinary course to ten years after graduation: career paths

Objective To map out the career paths of veterinarians during their first 10 years after graduation, and to determine if this could have been predicted at entry to the veterinary course. Design Longitudinal study of students who started their course at The University of Queensland in 1985 and 1986, and who completed questionnaires in their first and fifth year as students, and in their second, sixth and eleventh year as veterinarians. Methods Data from 129 (96%) questionnaires completed during the eleventh year after graduation were coded numerically then analysed, together with data from previous questionnaires, with SAS System 7 for Windows 95. Results Ten years after they graduated, 80% were doing veterinary work, 60% were in private practice, 40% in small animal practice and 18% in mixed practice. The equivalent of 25% of the working time of all females was taken up by family duties. When part-time work was taken into account, veterinary work constituted the equivalent of 66% of the group working full-time. That 66% consisted of 52% on small animals, 7% on horses, 6% on cattle/sheep and 1% on pigs/poultry. Those who had grown up on farms with animals were twice as likely to be working with farm animals as were those from other backgrounds. Forecasts made on entry to the veterinary course were of no value in predicting who would remain in mixed practice. Conclusions Fewer than one-fifth of graduates were in mixed practice after 10 years, but the number was higher for those who grew up on farms with animals. Forecasts that may be made at interview before entry to the course were of little value in predicting the likelihood of remaining in mixed veterinary practice.

Longitudinal study of veterinarians from entry to the veterinary course to 10 years after graduation: attitudes to work, career and profession

Objective To describe the attitudes of veterinarians to their work, career and profession during the 10 years after graduation. Design Longitudinal study of students who started their course at The University of Queensland in 1985 and 1986, and who completed questionnaires in their first and fifth year as students, and after one, five and 10 years as veterinarians. Methods Data from 129 (96%) questionnaires completed after 10 years as a veterinarian were coded numerically then analysed, together with data from previous questionnaires, with SAS System 7 for Windows 95. Results After 10 years, almost all respondents were either very glad they had done the veterinary course (57%) or generally glad, though with some misgivings (37%). Despite this, only 55% would definitely become a veterinarian if they 'had to do it over again'. The responses for about one-third were different from those given five years earlier. The views of many were related to the level of support and encouragement received in their first job after graduation. There were 42% who were working less than half-time as veterinarians, and their main reasons were, in order, raising children, long hours of work, attitudes of bosses and clients, and poor pay. A majority was concerned about the ethics and competence of some colleagues, and almost all believed that consideration of costs must influence the type of treatment animals receive. Conclusions Most veterinarians were glad to have done the veterinary course, but for about one-quarter their career had not lived up to expectations and almost half would not do it again in another incarnation. Stress, hours of work, difficulties in balancing personal life with career and low income were important concerns for many. Low income may contribute to the low number of males entering the veterinary profession.

Isolation and characterisation of a novel rabbit sulfotransferase isoform belonging to the SULT1A subfamily

Sulfotransferases (SULTs) catalyse the sulfonation of both endogenous and exogenous compounds including hormones, catecholamines. drugs and xenobiotics. While in most occasions, sulfonation is a detoxication pathway. in the case of certain drugs and carcinogens. it leads to metabolic activation. Since, the rabbit has been extensively used for both pharmacological and toxicological studies, the purpose of this study was to further characterise the sulfotransferase system of this animal. In the present study, a novel sulfotransferase isoform (GenBank Accession no. AF360872) was isolated from a rabbit liver cDNA lambdaZAP 11 library. The full-length sequence of the clone was 1138 bp long and contained a coding region of 888 bp encoding a cytosolic protein of 295 amino acids (deduced molecular weight 34,193 Da). The amino acid sequence of this novel SULT isoform showed >70% identity with members of the SULT1A subfamily of sulfotransferases from other species. Upon expression of the encoded rabbit sulfotransferase in Escherchia coli (E. coli), it was shown that the enzyme was capable of sulfonating both p-nitrophenot (K-m and V-max values of 0.15 muM and 897.5 nmol/min/mg protein. respectively) and dopamine (K-m and V-max values of 175.3 muM and 151.1 nmol/min/mg protein, respectively). Based on the sequence data obtained and substrate specificity, this new rabbit sulfotransferase was named rabSULT1A1. Immunoblotting was used to demonstrate that rabSULT1A1 protein is expressed in liver, duodenum, jejunum, ileum, colon and recturm. (C) 2002 Elsevier Science Ltd. All rights reserved.

The morbidity of Guillain-Barré syndrome admitted to the intensive care unit

Patients with severe forms of Guillain-Barré syndrome (GBS) require intensive care. Specific treatment, catheterization, and devices may increase morbidity in the intensive care unit (ICU). To understand the spectrum of morbidity associated with ICU care, the authors studied 114 patients with GBS. Major morbidity occurred in 60% of patients. Complications were uncommon if ICU stay was less than 3 weeks. Respiratory complications such as pneumonia and tracheobronchitis occurred in half of the patients and were linked to mechanical ventilation. Systemic infection occurred in one-fifth of patients and was more frequent with increasing duration of ICU admission. Direct complications of treatment and invasive procedures occurred infrequently. Life-threatening complications such as gastrointestinal bleeding and pulmonary embolism were very uncommon. Pulmonary morbidity predominates in patients with severe GBS admitted to the ICU. Attention to management of mechanical ventilation and weaning is important to minimize this complication of GBS. Other causes of morbidity in a tertiary center ICU are uncommon.

Visual Biology of Hawaiian Coral Reef Fishes. III. Environmental Light and an Integrated Approach to the Ecology of Reef Fish Vision

In the previous two papers in this three-part series, we have examined visual pigments, ocular media transmission, and colors of the coral reef fish of Hawaii. This paper first details aspects of the light field and background colors at the microhabitat level on Hawaiian reefs and does so from the perspective and scale of fish living on the reef. Second, information from all three papers is combined in an attempt to examine trends in the visual ecology of reef inhabitants. Our goal is to begin to see fish the way they appear to other fish. Observations resulting from the combination of results in all three papers include the following. Yellow and blue colors on their own are strikingly well matched to backgrounds on the reef such as coral and bodies of horizontally viewed water. These colors, therefore, depending on context, may be important in camouflage as well as conspicuousness. The spectral characteristics of fish colors are correlated to the known spectral sensitivities in reef fish single cones and are tuned for maximum signal reliability when viewed against known backgrounds. The optimal positions of spectral sensitivity in a modeled dichromatic visual system are generally close to the sensitivities known for reef fish. Models also predict that both UV-sensitive and red-sensitive cone types are advantageous for a variety of tasks. UV-sensitive cones are known in some reef fish, red-sensitive cones have yet to be found. Labroid colors, which appear green or blue to us, may he matched to the far-red component of chlorophyll reflectance for camouflage. Red cave/hole dwelling reef fish are relatively poorly matched to the background they are often viewed against but this may be visually irrelevant. The model predicts that the task of distinguishing green algae from coral is optimized with a relatively long wavelength visual pigment pair. Herbivorous grazers whose visual pigments are known possess the longest sensitivities so far found. Labroid complex colors are highly contrasting complementary colors close up but combine, because of the spatial addition, which results from low visual resolution, at distance, to match background water colors remarkably well. Therefore, they are effective for simultaneous communication and camouflage.

Issues related to the wearing of fall-arrest harnesses in the construction industry

Work-related falls continues to be one of the leading causes of fatalities in the Australian construction industry, and the failure to use fall protection equipment, such as fall-arrest harnesses and arresting devices, has been found to be a contributing factor. In an attempt to gain an understanding of the issues surrounding the use of fallarrest harness systems by construction workers a study involving semi-structured interviews of 15 male construction workers was carried out at three construction sites. The majority of interviewees commented that there was discomfort in wearing a fall-arrest harness; that there were a number of problems when anchored via an arresting device; and that using a fall-arrest system reduced productivity. Most of the interviewees considered that they needed safety precautions against falls, and they expressed the view that workers’ attitudes towards safety depended critically upon their supervisors’ attitude towards safety. It was also found that workers were not trained in rescue procedures. Interviewees expressed concern that retrieval of a suspended worker may not be carried out in time to prevent the onset of suspension trauma. A number of issues were identified which require further research, such as, investigation into suspension trauma, harness and arresting device design, training provided to workers, and the provision for rescues.

Higher education of tourism in Spain and its adaptation to the European higher education area

The international tourism system has deeply undergone structural changes in the last decades which not remain outside the subsystem higher education in tourism, especially in the European case. This article has two objectives: firstly, describes the European higher education area and the objectives, skills and subjects taught in the main Spanish universities that offer higher education in tourism. On the other hand, in the light of knowledge that researchers' descriptive models, provide experience of the implementation of European credit and thorough a deeply review of the literature on the topic higher education in tourism, to propose strategies that will enable other tourism higher education systems approach to the European reality. These policy proposals are aimed at agents and elements from higher education in tourism subsystem and they specifically include: the institutions providing education in tourism, the curriculum, the teaching methods, teachers and students.

A multifactor approach to the social discount rate

This work focuses on the appraisal of public and environmental projects and, more specifically, on the calculation of the social discount rate (SDR) for this kind of very long-term investment projects. As a rule, we can state that the instantaneous discount rate must be equal to the hazard rate of the public good or to the mortality rate of the population that the project is intended to. The hazard can be due to technical failures of the system, but, in this paper, we are going to consider different independent variables that can cause the hazard. That is, we are going to consider a multivariate hazard rate. In our empirical application, the Spanish forest surface will be the system and the forest fire will be the fail that can be caused by several factors. The aim of this work is to integrate the different variables that produce the fail in the calculation of the SDR from a multivariate hazard rate approach.

A new cloning system based on the OprI lipoprotein for the production of recombinant bacterial cell wall-derived immunogenic formulations

The conjugation of antigens with ligands of pattern recognition receptors (PRR) is emerging as a promising strategy for the modulation of specific immunity. Here, we describe a new Escherichia coli system for the cloning and expression of heterologous antigens in fusion with the OprI lipoprotein, a TLR ligand from the Pseudomonas aeruginosa outer membrane (OM). Analysis of the OprI expressed by this system reveals a triacylated lipid moiety mainly composed by palmitic acid residues. By offering a tight regulation of expression and allowing for antigen purification by metal affinity chromatography, the new system circumvents the major drawbacks of former versions. In addition, the anchoring of OprI to the OM of the host cell is further explored for the production of novel recombinant bacterial cell wall-derived formulations (OM fragments and OM vesicles) with distinct potential for PRR activation. As an example, the African swine fever virus ORF A104R was cloned and the recombinant antigen was obtained in the three formulations. Overall, our results validate a new system suitable for the production of immunogenic formulations that can be used for the development of experimental vaccines and for studies on the modulation of acquired immunity.