How to deal with medically unknown symptoms.
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Biomedical subjects
Publications and source records attributed to T Williams.
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The Pacific bonito, Sarda chiliensis, is anatomically intermediate between mackerel and tuna. The specialisations exhibited by tuna are present in the bonito, but to a lesser degree. Slow-twitch muscle strain and activity patterns were determined during steady swimming (tailbeat frequency 1.2-3.2 Hz) at four locations on the body of Sarda chiliensis using sonomicrometry and electromyography. Both strain and the phase of electromygraphic activity were independent of tailbeat frequency. The strain of superficial slow-twitch muscle increased from +/-3.1 % l(0) at 0.35FL to +/-5.8 % l(0) at 0.65FL, where l(0) is muscle resting length and FL is the body length from snout to tail fork. Between 0.35 and 0.65FL, there was a negative phase shift of 16 degrees in the onset of electromygraphic activity in superficial slow-twitch muscle relative to the strain cycle. Muscle activity patterns are comparable with those of tuna. At 0.58FL, the onset of activity in deep slow-twitch muscle was approximately synchronous with the onset of activity in superficial muscle in the same myotome at 0.65FL. The distribution of slow-twitch muscle along the body of Sarda chiliensis and four additional fish species, Anguilla anguilla, Oncorhynchus mykiss, Scomber scombrus and Thunnus albacares, was also measured. Slow-twitch muscle appears to become more concentrated at approximately 0.5FL as swimming kinematics become more thunniform.
As interest in telemedicine grows, many of its proponents and vendors increasingly suggest that it is now time to move to full-scale implementation of telemedicine services in a variety of contexts throughout the world, and question the need for further evidence of its utility and cost-effectiveness. We have reviewed the published literature relating to cost-effectiveness studies in telemedicine and have identified some important weaknesses. Ten recommendations regarding the design of economic evaluations of telemedicine are suggested.
The predatory bug Orius majusculus (Reuter) was reared on 2 different diets during the nymphal stages. The 1st group was exclusively offered eggs of Ephestia kuehniella Zeller (Lepidoptera: Pyralidae), a standard diet for O. majusculus production. The 2nd group was exclusively offered 4th instars of the pea aphid, Acyrtosiphon pisum (Harris). Subsequently, adult predatory behavior in experimental arenas containing A. pisium was recorded using 2 video cameras. One camera permitted observation of the predator's contact with the prey, where the 2nd camera viewed the arena from above to record the path taken by O. majusculus adults before and after contact with prey. When O. majusculus were reared on aphids, adult bugs successfully located and consumed 55% of experimental prey and continued prey search behavior after each aphid meal. O. majusculus adults that had no experience of aphid predation as nymphs, did not prey on aphids in the experimental arena. The mean walking speed of this group of predators increased from 5.9 +/- 1.2 mm/s to 9.8 +/- 0.7 mm/s after contact or detection of prey, indicating that predators rapidly moved away from unfamiliar prey. Moreover, for egg-reared O. majusculus, all contacts between aphid and predator were lateral, along the side of the prey and were effectively repelled by an aphid kicking response. In contrast, 83% of attacks by aphid-reared O. majusculus were directed at the head or posterior abdomen for which the prey could not defend themselves adequately. When egg-reared O. majusculus were exposed to novel aphid prey for 1-8 d, the frequency of aphid attack increased significantly. We conclude that the standard diet used for rearing O. majusculus may adversely affect the efficiency of this predator as an agent of biological control.
A flurry of software development, much of it web-based, offers alternatives for agencies to address PPS requirements, streamline operations, and improve agency performance. PPS changes everything--dramatically altering the home care community's financial incentives and focusing attention on technologies that will enable agencies to succeed in this new environment.
UNLABELLED: Bronchiolitis Obliterans Syndrome (BOS) remains a major cause of long term morbidity and mortality in lung transplantation, and occurs despite significant immunosuppression. Airway inflammation is thought to precede the development of BOS. OBJECTIVES: To examine the effect of inhaled corticosteroids on airway inflammation and the development of BOS in lung transplant recipients. METHODS: 30 patients were recruited and randomised in a double blind fashion to receive either 750 micrograms Fluticasone propionate (FP) twice daily or an identical appearing placebo for 3 months. BAL cell counts and differentials were performed at time 0 and after 3 months treatment. Lung function was assessed at each time point using spirometry. RESULTS: 24 patients were felt to be stable and free from infection at both time points and thus included in the analysis. There was a significant reduction in total cell count in BAL fluid after treatment with 3 months FP compared to 3 months placebo, however no change in cell differentials nor lung function was found. DISCUSSION: Despite a reduction in total cell numbers in BAL fluid, lung function was not altered over the 3 months of treatment. It may be that longer treatment is required to see an effect.
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The treatment of Epstein-Barr virus (EBV)-associated lymphoproliferative disease (PTLD) in EBV seronegative solid organ transplant recipients who acquire their EBV infection after engraftment poses a considerable challenge because of underlying immunosuppression that inhibits the virus-specific cytotoxic T cell (CTL) response in vivo. We have developed a protocol for activating autologous EBV-specific CTL lines from these patients and show their potential use for immunotherapy against PTLD in solid organ transplant patients. Peripheral blood mononuclear cells from a panel of solid organ transplant recipients with and without active PTLD were used to assess EBV-specific memory CTL responses. The activation protocol involved cocultivation of peripheral blood mononuclear cells with an autologous lymphoblastoid cell line under conditions that favored expansion of virus-specific CTL and hindered the proliferation of allospecific T cells. These CTL consistently showed (i) strong EBV-specificity, including reactivity through defined epitopes in spite of concurrent immunosuppressive therapy, and (ii) no alloreactivity toward donor alloantigens. More importantly, adoptive transfer of these autologous CTLs into a single patient with active PTLD was coincident with a very significant regression of the PTLD. These results demonstrate that a potent EBV-specific memory response can be expanded from solid organ recipients who have acquired their primary EBV infection under high levels of immunosuppressive therapy and that these T cells may have therapeutic potential against PTLD.
The AP-2 family of transcription factors are defined by the presence of a novel DNA binding domain, termed a 'basic helix-span-helix' motif. The AP-2 genes regulate important aspects of vertebrate embryogenesis and have also been linked to the control of cell proliferation and tumorigenesis, but the cellular targets that the AP-2 proteins control are largely undefined. In particular, since only a limited number of sequences have previously been utilized to define the nature of the AP-2 binding site, the range of DNA sequences recognized by the AP-2 proteins remains unknown. We have therefore utilized a SELEX analysis to identify multiple new AP-2[alpha] binding sites. Moreover, we have devised a novel missing phosphate and nucleotide competition analysis to characterize the residues in the binding site required for AP-2[alpha] protein:DNA contact. These studies suggest that the AP-2[alpha] protein:DNA complex is flexible and indicate that AP-2[alpha] can bind three related sequence motifs: GCC N3 GGC, GCC N4 GGC and GCC N3/4 GGG. The availability of these more refined consensus sequences should assist in the identification of target genes for this critical transcription factor.
This article describes the calibration of a spectroscopic scanning instrument for the measurement of selected contaminants in a complex biological process stream. Its use is for the monitoring of a process in which contaminants are to be removed selectively by flocculation from yeast cell homogenate. The main contaminants are cell debris, protein, and RNA. A low-cost instrument has been developed for sensitivity in the region of the NIR spectrum (from 1900 to 2500 nm) where preliminary work found NIR signatures from cell debris, protein, and RNA. Calibration models have been derived using a multivariate method for concentrations of these contaminants, such as would be found after the flocculation process. Two strategies were compared for calibrating the NIR instrument. In one case, samples were prepared by adding materials representative of the contaminants to clarified yeast homogenate so the contaminant levels were well known but outside the range of interest. In the other case, where samples were like those from the process stream after flocculation and floc removal, there was uncertainty of analysis of contaminant level, but the calibration was in the range of interest. Calibration using process stream samples gave results close to those derived from traditional assays. When the calibration models were used to predict the contaminant concentrations in previously unseen samples, the correlation coefficients between measurements and predictions were above 90% in all cases but one. The prediction errors were similar to the errors in the traditional assays.
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AP-2 transcription factors are a family of retinoic acid-responsive genes, which are involved in complex morphogenetic processes. In the current study, we determine the requirement for AP-2alpha in early morphogenesis of the eye by examining the nature of the ocular defects in AP-2alpha null and chimeric mice. AP-2alpha null embryos exhibited ocular phenotypes ranging from a complete lack of eyes (anophthalmia) to defects in the developing lens involving a persistent adhesion of the lens to the overlying surface ectoderm. Two genes involved in lens development and differentiation, Pax6 and MIP26 were also misexpressed. AP-2alpha mutants also exhibited defects in the optic cup consisting of transdifferentiation of the dorsal retinal pigmented epithelium into neural retina and the absence of a defined ganglion cell layer. Newly generated chimeric embryos consisting of a population of AP-2alpha-/- and AP-2alpha+/+ cells exhibit ocular defects similar to those seen in the knockout embryos. Immunolocalization of AP-2 proteins (alpha, beta, and gamma) to the normal developing eye revealed both unique and overlapping expression patterns, with AP-2alpha expressed in a number of the ocular tissues that exhibited defects in the mutants, including the developing lens where AP-2alpha is uniquely expressed. Together these findings demonstrate a requirement for AP-2alpha in early morphogenesis of the eye.
An association between obsessive compulsive disorder and eating disorders has often been reported in the literature. It has been suggested that the association may be accounted for by depression, starvation or family factors but the literature remains inconclusive. In this study self-report scales were used to measure eating attitudes, obsessional symptoms, depressive symptoms and family functioning in an eating disordered group, a psychiatric control group and in the parents of both groups. The eating disordered group scored significantly higher than controls on the Maudsley Obsessive Compulsive Inventory and the Leyton Obsessional Inventory but not on the Childhood Depression Inventory. The differences were not correlated with Quetelet's Body Mass Index. Both groups of parents scored within the normal range for all scales. The high obsessional scores in the anorexic group seem to be due to high scoring on items relating to perfectionism. The role of perfectionism as a risk factor for the development of eating disorders and OCD is discussed.
A multicentre, prospective, randomized, double-blind, parallel group study was undertaken to compare the efficacy and tolerability of topical terbinafine with topical clotrimazole in the treatment of interdigital tinea pedis. Patients were randomized to receive either terbinafine 1% cream twice daily for 1 week, followed by a similar placebo cream for 5 weeks, or clotrimazole 1% cream twice daily for 4 weeks. Outcome measures were: (i) mycological cure (negative culture); (ii) effective treatment (negative culture plus a symptom score of 2 or less out of a maximum score of 18); and (iii) complete cure (negative culture and a symptom score of 0); measured at 1, 4, 8 and 12 weeks after the commencement of the study. One hundred and four of the 217 patients randomized had a culture-confirmed dermatophyte infection at baseline. In these patients, 84.6% in the terbinafine group were culture negative after 1 week, compared with only 55.8% in the clotrimazole group. Both agents were well tolerated. The study showed that terbinafine achieves mycological cure more rapidly than clotrimazole. This may result in improved compliance and better control over transmission of infection.
The current study describes toxic effects of the Bacillus thuringiensis beta-exotoxin toward 3rd instars of 3 fruit fly species: Anastrepha ludens (Loew), A. obliqua (Macquart), and A. serpentina (Wiedemann). The beta-exotoxin was highly toxic to all 3 species tested, with LC50 values calculated as 0.641, 0.512, and 0.408 microgram/cm2 of filter paper used to expose the larvae, for A. ludens, A. obliqua, and A. serpentina, respectively. Exposure to beta-exotoxin was associated with an increase in the incidence of deformed pupae. The adult survivors from beta-exotoxin treatments showed no negative effects in terms of their longevity, fecundity, or egg eclosion (fertility). We conclude that the beta-exotoxin may have potential as a control agent for fruit fly pests.
Spodoptera frugiperda (J. E. Smith) (Lepidoptera: Noctuidae) is the principal pest of maize in tropical and subtropical regions of the Americas. Larvae of this species are susceptible to a nucleopolyhedrovirus (NPV) which has attracted interest as a potential biocontrol agent. Four strains of NPV isolated from infected S. frugiperda larvae in the United States, Nicaragua, and Argentina were subjected to a structural, genetic, and biological comparison to select a candidate isolate for use in biocontrol experiments in Mexico and Honduras. All isolates had an occlusion body polyhedrin protein of 32 kDa, but the virions of each isolate differed subtly in the pattern and abundance of certain structural polypeptides revealed by SDS-PAGE analysis. Restriction endonuclease analysis of viral DNA confirmed that these isolates were strains of a single virus species but showed that they were not genetically homogeneous; each isolate could be differentiated from the others using common restriction enzymes. Droplet feeding bioassays indicated that an isolate from Nicaragua (Sf-NIC) and an isolate from the United States (Sf-US) had the highest infectivity when tested against 2nd instars originating from a Honduran S. frugiperda colony. No significant differences were detected in the speed of kill of Sf-NIC (102.7 h), Sf-US (102.3 h) and Sf-AR (103.4 h), whereas that of Sf-2 (97.3 h) was significantly shorter. Additional bioassays of the Sf-NIC isolate against 2nd to 6th instars demonstrated that LC50 values increased with larval stage from 2.03 x 10(5) OBs/ml for 2nd instars to 1.84 x 10(8) OBs/ml for 5th instars. The concentration required to elicit a lethal infection of 6th instars was so high that a reliable estimate of LC50 could not be obtained. The mean time to death for each stage challenged with the Sf-NIC isolate increased with instar from an average of 102.7 h in 2nd instars to 136.9 h in 5th instars.
General practice computers have been widely used in the United Kingdom for the last 10 years and there are over 30 different systems currently available. The commercially available databases are based on two of the most widely used systems--VAMP Medical and Meditel. These databases provide both longitudinal and cross-sectional data on between 1.8 and 4 million patients. Despite their availability only limited use has been made of them for epidemiological and health service research purposes. They are a unique source of population-based information and deserve to be better recognized. The advantages of general practice databases include the fact that they are population based with excellent prescribing data linked to diagnosis, age and gender. The problems are that their primary purpose is patient care and the database population is constantly changing, as well as the usual problems of bias and confounding that occur in any observational studies. The barriers to the use of general practice databases include the cost of access, the size of the databases and that they are not structured in a way that easily allows analysis. Proper utilization of these databases requires powerful computers, staff proficient in writing computer programs to facilitate analysis and epidemiologists skilled in their use. If these structural problems are overcome then the databases are an invaluable source of data for epidemiological studies.
Translation elongation factor 1beta (EF-1beta) is a member of the family of guanine nucleotide exchange factors, proteins whose activities are important for the regulation of G proteins critical to many cellular processes. EF-1beta is a highly conserved protein that catalyzes the exchange of bound GDP for GTP on EF-1alpha, a required step to ensure continued protein synthesis. In this work, we demonstrate that the highly conserved C-terminal region of Saccharomyces cerevisiae EF-1beta is sufficient for normal cell growth. This region of yeast and metazoan EF-1beta and the metazoan EF-1beta-like protein EF-1delta is highly conserved. Human EF-1beta, but not human EF-1delta, is functional in place of yeast EF-1beta, even though both EF-1beta and EF-1delta have previously been shown to have guanine nucleotide exchange activity in vitro. Based on the sequence and functional homology, mutagenesis of two C-terminal residues identical in all EF-1beta protein sequences was performed, resulting in mutants with growth defects and sensitivity to translation inhibitors. These mutants also enhance translational fidelity at nonsense codons, which correlates with a reduction in total protein synthesis. These results indicate the critical function of EF-1beta in regulating EF-1alpha activity, cell growth, translation rates, and translational fidelity.