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Biomedical subjects

R Wall

Publications and source records attributed to R Wall.

At least 37 records · Page 2Linked to original sources

Temporary articulating methylmethacrylate antibiotic spacer (TAMMAS). A new method of intraoperative manufacturing of a custom articulating spacer.

A temporary articulating antibiotic-impregnated cement spacer for use during the first stage of a two-stage revision of a total knee replacement that had failed because of infection was developed by one of us (W.M.G.). It is simply a knee prosthesis made of methylmethacrylate and antibiotics that is manufactured intraoperatively with use of instruments, medications, and supplies that are already available at most hospitals. This construct allows for motion of the knee during treatment of the infection, thereby reducing the risk of loss of motion after subsequent revision. The technique has been successfully utilized in five patients since 1999 and has now become our standard treatment method.

Anti-Bacterial Agents↗

The use of entomopathogenic fungi for the control of parasitic mites, Psoroptes spp.

In vitro trials were carried out to evaluate the potential of fungal pathogens as biological control agents of parasitic mites, Psoroptes ovis (Hering) (Acari: Psoroptidae) from rabbit hosts (synonym: Psoroptes cuniculi). The fungus Hirsutella thompsonii Fisher showed no pathogenicity. Metarhizium anisopoliae (Metschinkoff), however, showed a high level of pathogenicity; 3 days after exposure to fungal conidia all mites were dead and 6 days after exposure 60% of the dead adult females, 10% of the dead adult males and 30% of the dead female nymphs had fungal hyphae protruding from their cuticular surface. There was a significant effect of conidial concentration on the number of mite cadavers that displayed fungal infection. Exposure to between 1x10(4) and 1x10(6) conidiaml(-1) resulted in 2-25% of the mites being infected. Mean infection levels were highest, 71%, when the mites were exposed to 1x10(7) conidiaml(-1). Similarly, there was a significant effect of conidial concentration on the time taken for the mites to reach 50% levels of mortality (LT(50)) The mean LT(50) value was approximately 2.7 days, when the mites were exposed to a solution of 1x10(7) and 1x10(8) conidiaml(-1) which was significantly shorter than controls exposed to 0.03% Tween-80 solution only. There was no significant effect of passaging the fungus, either once or twice, through the host on the subsequent infectivity of M. anisopliae. The potential for use of entornopathogenic fungi for the control of parasitic mites, particularly in relation to sheep, is discussed.

Animals↗

Aberrant B cell receptor signaling from B29 (Igbeta, CD79b) gene mutations of chronic lymphocytic leukemia B cells.

Chronic lymphocytic leukemia (CLL) B cells characteristically exhibit low or undetectable surface B cell receptor (BCR) and diminished responses to BCR-mediated signaling. These features suggest that CLL cells may have sustained mutations affecting one or more of the BCR proteins required for receptor surface assembly and signal transduction. Loss of expression and mutations in the critical BCR protein B29 (Igbeta, CD79b), are prevalent in CLL and could produce the hallmark features of these leukemic B cells. Because patient CLL cells are intractable to manipulation, we developed a model system to analyze B29 mutations. Jurkat T cells stably expressing micro, kappa, and mb1 efficiently assembled a functional BCR when infected with recombinant vaccinia virus bearing wild-type B29. In contrast, a B29 CLL mutant protein truncated in the transmembrane domain did not associate with mu or mb1 at the cell surface. Another B29 CLL mutant lacking the C-terminal immunoreceptor tyrosine activation motif tyrosine and distal residues brought the receptor to the surface as well as wild-type B29 but showed significant impairment in anti-IgM-stimulated signaling events including mitogen-activated protein kinase activation. These findings demonstrate that B29 mutations previously identified in CLL patients can affect BCR-dependent signaling and may contribute to the unresponsive B cell phenotype in CLL. Finally, the features of the B29 mutations in CLL predict that they may be generated by somatic hypermutation.

Antigens, CD↗

In vitro insecticidal effects of fipronil and beta-cyfluthrin on larvae of the blowfly Lucilia sericata.

The insecticidal effects of the phenylpyrazole, fipronil, and a pyrethroid, beta-cyfluthrin, on larvae of the blowfly Lucilia sericata were determined in laboratory assays. When first stage larvae of L. sericata were reared on homogenized pig liver which had been treated with known amounts of test compounds, both fipronil and beta-cyfluthrin induced significant levels of mortality compared to acetone and water controls. However, fipronil was approximately 10 times more toxic than beta-cyfluthrin to L. sericata larvae following ingestion. Beta-cyfluthrin had little effect on mortality until concentrations of approximately 0.5 ppm were reached. In contrast, fipronil effected L. sericata mortality at a concentration of 0.05 ppm and 100% mortality was reached by 0.5 ppm. The lethal concentration (LC50) value for beta-cyfluthrin was 1.56 ppm as compared to 0.14 ppm for fipronil. Following contact of first and third stage larvae with cloth impregnated with known amounts of test compound, the mortality profiles of fipronil and beta-cyfluthrin were similar. At short contact times, the LC50 values for fipronil were lower than those for beta-cyfluthrin. However, at the highest contact time evaluated for the first stage larvae, 300 s, there was a reversal in this trend. The results suggest that the phenylpyrazole fipronil may represent a new potential insecticide for development against blowfly strike of sheep.

Administration, Topical↗

An upstream Oct-1- and Oct-2-binding silencer governs B29 (Ig beta) gene expression.

The B cell-specific B29 (Igbeta) gene is activated in the earliest B cell precursors and is expressed throughout B cell development. Tissue-specific expression of the murine B29 gene is controlled by a B cell-specific promoter whose activity is governed by a cassette of upstream transcriptional silencers. This study describes a potent new silencer that is located 5' of the previously identified B29 silencer elements, FROG and TOAD. Like these known elements, the new B29 silencer is not restricted to the B29 promoter. Nuclear proteins from all cell lines tested interacted with this A+T-rich sequence, which closely resembled a noncanonical octamer binding motif and also conformed to the consensus sequence for nuclear matrix attachment regions. Interaction of Oct-1 and Oct-2 with the B29 A+T-rich sequence was confirmed using octamer-specific Abs. Oct-1/Oct-2 binding was required for the inhibitory activity of this sequence because mutations that blocked Oct-1/Oct-2 binding also eliminated inhibition of the B29 promoter. This B29 A+T-rich sequence specifically interacted with isolated nuclear matrix proteins in vitro, suggesting that it may also function as a matrix attachment region element. Maintenance of the level of B29 gene expression through the interaction of the minimal promoter and the upstream silencer elements FROG, TOAD, and the A+T-rich Oct-1/Oct-2 binding motif may be essential for normal B cell development and/or function.

5' Untranslated Regions↗

Social costs of untreated opioid dependence.

Using cost-of-illness methodology applied to a comprehensive survey of 114 daily opiate users not currently in or seeking treatment for their addiction, we estimated the 1996 social costs of untreated opioid dependence in Toronto (Ontario, Canada). The survey collected data on social and demographic characteristics, drug use history, physical and mental health status, the use of health care and substance treatment services, drug use modality and sex-related risks of infectious diseases, sources of income, as well as criminality and involvement with the law enforcement system. The annual social cost generated by this sample, calculated at Canadian $5.086 million, is explained mostly by crime victimization (44.6%) and law enforcement (42.4%), followed by productivity losses (7.0%) and the utilization of health care (6.1%). Applying the $13,100 cost to the estimated 8,000 to 13,000 users and 2.456 million residents living in Toronto yields a range of social cost between $43 and $69 per capita.

Cost of Illness↗

An essential octamer motif in the mb-1 (Igalpha) promoter.

The mb-1 (Igalpha) gene is B cell-specific and expressed throughout B cell maturation. In combination with B29 (Igbeta) and surface immunoglobulin mb-1 comprises the B cell receptor complex (BCR). The murine mb-1 promoter has been characterized to depend on the trans-acting transcription factors; Sp1, ets, lkaros, and EBF for full promoter activity. These trans-acting factors are also involved in the regulation of mb-1's closely related heterodimeric partner, B29. However, octamer transcription factors 1 and 2 (Oct-1 and Oct-2) are also necessary for full B29 promoter activity while they are not known to be required for mb-1 promoter activity. Here, we show that the octamer transcription factors bind a degenerate octamer consensus sequence within the mb-1 promoter. Like B29, the mb-1 octamer-binding, motif interacted with both ubiquitously expressed Oct-1 and the B cell-specific Oct-2 transcription factors. Furthermore, the interaction of Oct-1 and Oct-2 contributed to the regulation of the mb-1 promoter as site-directed mutations within the octamer motif substantially reduced its activity. These data confirm that octamer factor interactions and function contribute to the full transcriptional activity of the mb-1 promoter.

Animals↗

Clusters of new tuberculosis cases in North-west London: a survey from three hospitals based on IS6110 RFLP typing.

OBJECTIVES: The relative contributions of reactivation of latent infection and clusters of new infections to the overall incidence of tuberculosis in the U.K. is unknown. A study was carried out in North-West London to determine the feasibility of IS6110 RFLP strain typing as a tool to investigate the relative contributions of these two sources. METHODS: All available isolates of M. tuberculosis from specimens collected over a calendar year at three participating hospitals were typed by RFLP using an IS6110 probe. Isolates exhibiting a single band pattern were subject to further typing using an oligonucleotide direct repeat probe. Demographic and clinical information on cases was obtained from the National Survey of Tuberculosis Notifications in England and Wales and further information sought on clustered cases as identified by RFLP typing. RESULTS: Twenty-seven (23%) of the 118 cases had shared IS6110 RFLP patterns. Strains from nine cases had single band patterns, but these were all distinguishable from each other when subjected to further typing by direct repeat probe. The remaining 18 cases belonged to eight clusters. Epidemiological links were established between all the patients in each cluster. The likelihood of being in a cluster was increased in cases with pulmonary smear-positive disease. It was lower in cases of Indian Sub-continent ethnic origin. For 10 of the 18 clustered cases epidemiological links had not been established by conventional contact tracing. CONCLUSIONS: Investigation of the relative contributions of reactivation of latent infection and new infection is feasible in a UJK population, using IS6110 RFLP typing of M. tuberculosis isolates and epidemiological enquiries. This study in London identified clustered, presumably new cases, the majority of whom had not been linked epidemiologically. Comprehensive IS6110 RFLP typing of UK isolates would probably identify many clusters of incident tubercular infection.

Adolescent↗

Life-cycle stage morphology of Psoroptes mange mites.

Detailed life-cycle stage descriptions for the ectoparasitic mite Psoroptes ovis (Hering) (Acari: Psoroptidae) from rabbit hosts (syn. Psoroptes cuniculi) are presented. The results resolve a number of contradictions in the literature relating to the recognition of the life cycle stages of these mites. This study supports the view that there are two distinct male nymphal stages, both lacking dorsoposterior tubercles. The male tritonymph is significantly larger than the protonymph and has five pairs of metapodosomal setae rather than three. In addition, male tritonymphs have two pairs of cuticular pits on the central metapodosoma rather than the single pair of the protonymph. The results also show that the female protonymph can be distinguished from the male nymphal stages and the female tritonymph. Both female nymphal stages possess dorsoposterior tubercles, but the protonymph is significantly smaller than the tritonymph. In addition, the protonymph possesses three pairs of metapodosomal setae rather than five, one pair of cuticular pits rather than two, and a pulvillus on leg IV which is absent in the female tritonymph. The presence of dorsoposterior tubercles enables the female nymphs to be distinguished easily from the males. By contrast, distinguishing between the nymphal stages of the same sex relies on the identification of both the number of metapodosomal setae and cuticular pits. These descriptions are used to produce a key, which allows the various stages of both sexes to be distinguished.

Animals↗

Compliance with advice to boil drinking water during an outbreak of cryptosporidiosis. Outbreak Investigation Team.

All 2000 employees of a hospital in an area of the North Thames region where 300,000 households were advised to boil tap water before consumption during a large outbreak of cryptosporidiosis were surveyed about compliance with and adverse events linked to the boil water notice. Eighty-five per cent (408/479) of respondents who lived in the boil water area said that they used boiled water while the notice was in place, 72% (347) used bottled water, and 12% (59) did not continue to boil water for the whole 16 days. Although 88% believed that they were following the advice, 20% washed food that would be eaten raw in unboiled tap water and 57% used it to clean their teeth. If a boil water notice is applied for more than a few days it may be helpful to issue a detailed follow up letter.

Cryptosporidiosis↗

TCL1 oncogene expression in AIDS-related lymphomas and lymphoid tissues.

AIDS-related non-Hodgkin's lymphoma (AIDS NHL) comprises a diverse and heterogeneous group of high-grade B cell tumors. Certain classes of AIDS NHL are associated with alterations in oncogenes or tumor-suppressor genes or infections by oncogenic herpesviruses. However, the clinically significant class of AIDS NHL designated immunoblastic lymphoma plasmacytoid (AIDS IBLP) lacks any consistent genetic alterations. We identified the TCL1 oncogene from a set of AIDS IBLP-associated cDNA fragments generated by subtractive hybridization with non-AIDS IBLP. Aberrant TCL1 expression has been implicated in T cell leukemia/lymphoma development, and its expression also has been seen in many established B cell tumor lines. However, TCL1 expression has not been reported in AIDS NHL. We find that TCL1 is expressed in the majority of AIDS IBLP tumors examined. TCL1 protein expression is restricted to tumor cells in AIDS IBLP tissue samples analyzed with immunohistochemical staining. Hyperplastic lymph node and tonsil also exhibit strong TCL1 protein expression in mantle zone B cells and in rare interfollicular zone cells, whereas follicle-center B cells (centroblasts and centrocytes) show weaker expression. These results establish TCL1 as the most prevalent of all of the surveyed oncogenes associated with AIDS IBLP. They also indicate that abundant TCL1 expression in quiescent mantle zone B cells is down-regulated in activated germinal center follicular B cells in parallel to the known expression pattern of BCL-2. High-level expression in nonproliferating B cells suggests that TCL1 may function in protecting naïve preactivated B cells from apoptosis.

B-Lymphocytes↗

Sheep scab outbreaks in Great Britain between 1973 and 1992: spatial and temporal patterns.

In January 1973, the mange mite Psoroptes ovis was found in a sheep flock in Lancashire, UK after a 20 year period of eradication. Over the next 20 years, a total of 1480 flock outbreaks were reported, until June 1992 when the control of sheep scab was deregulated. The spatial and temporal patterns of the number of outbreaks in each month over this period were analysed using time series methods, a geographical information system (GIS) and second order approaches to the exploration of space-time interaction (K-function analysis). The monthly time series displays clear evidence of seasonal cyclicity, with most outbreaks being reported in the winter months. After removal of the summer compulsory dip in 1988 however, there is evidence of a change in the seasonal pattern, with more cases being reported in the autumn months. There is also evidence of a contribution from a sinusoidal wave with a period of 8 years, which roughly corresponds to the major changes in the national control policy. The spatial pattern also appears to expand and contract on a roughly 4 year cycle, again reflecting the oscillating periods of success and failure. Examination of the spatial and temporal pattern revealed strong evidence of space-time clustering (p < 0.001) and a major contribution to the pattern from very local (< 12 km) spread within 5 months of an arbitrary outbreak.

Animals↗

Simulation analysis of the population dynamics of the mite, Psoroptes ovis, infesting sheep.

The pattern of population growth of the ectoparasitic mite, Psoroptes ovis (Acari: Psoroptidae), on its ovine host is considered through the development of a Leslie matrix-based, simulation model. The model is parameterised using experimental data in conjunction with reanalysis of published data. The model shows that on sheep P. ovis populations grow at a rate of approximately 11% per day and the population doubles every 6.3 days. Additional rates of adult mortality, in excess of 50% per day, need to be imposed to prevent population growth. The predictions of the model are tested by comparison of the expected numbers of mites with the numbers recorded in lesions either on naturally infested sheep where the date of infestation can be estimated or on one artificially infested animal, where the initial number of mites and date of infestation are known precisely. In both cases the observed number of mites in lesions relate closely to the numbers expected from the simulations. The model simulations do not support the concept of a 'lag' phase as distinct from the 'growth' phase in the changing pattern of mite abundance on an infested sheep and suggests that the observed pattern of growth is a natural function of an exponential increase in numbers. The development of such models and their use in explaining the demographic processes which drive mite population dynamics are discussed.

Animals↗

The effects of temperature and humidity on the off-host survival of Psoroptes ovis and Psoroptes cuniculi.

The effects of both temperature and humidity on the survival of the mites Psoroptes ovis and Psoroptes cuniculi were considered in laboratory assays. When P. ovis and P. cuniculi were maintained at 95% humidity, maximum survival decreased linearly with increasing temperature, from approximately 15 days at 9 degrees C to 5 days at 30 degrees C. There was no significant difference between P. ovis and P. cuniculi in the effects of temperature on maximum survival. Adult male P. ovis and P. cuniculi had lower mean maximum survival than any of the other life cycle stages. There was a small but significant effect of humidity on survival for P. cuniculi; LT50 values were greater at 75-85% r.h. than at 55-65% r.h. The influence of off-host survival and the infestation of naive sheep from mites in the environment on the epidemiology of sheep scab are discussed.

Animals↗

Within-flock transmission of sheep scab in naive sheep housed with single infested sheep.

The within flock transmission of sheep scab was studied in two trials, which lasted 14 and 12 weeks, respectively. A total of 40 non-infested, scab-naive sheep were divided into six groups of between 6 and 20 individuals. Each group was subsequently housed with a single infested index case, carrying scab lesions of different ages. The groups of sheep in both trials were video recorded continuously and all the sheep were individually examined on a weekly basis. The occurrence of transmission was measured in two ways: first, by the detection of early scab lesions during clinical examination and, second, by an increase in the rubbing of individual sheep as noted from the analysis of the video recordings. These two methods complemented each other in predicting the week on which transmission occurred. Overall, transmission was detected in 34 of the 40 scab-naive sheep. Transmission was shown to occur at about the time when the population of adult mites in lesions on index cases reached their peak numbers. The highest number of mites at this time, however, differed markedly between index sheep. There was no obvious relationship between the incidence of transmission and the time index sheep spent rubbing each day or other index sheep variables, including the age of the lesion or the time since the introduction to the scab free sheep.

Animals↗

The effects of oviposition aggregation on the incidence of sheep blowfly strike.

The distribution of a parasite population within its natural host population can have a significant influence on the dynamics of both the host and parasite populations. The majority of parasite species are typically distributed in an aggregated manner within the host population, leaving most hosts lightly infected and a few hosts supporting very large parasite burdens. This paper presents a consideration of the effects of aggregation on the incidence of ovine cutaneous myiasis caused by the sheep blowfly, Lucilia sericata (Meigen). Using simulation analysis, the mechanisms causing larval aggregation are included in the model, allowing the consequences for control to be investigated. By explicitly incorporating host susceptibility, it becomes apparent that early in the season, strategies targeting the blowfly population may prove more effective in suppressing strike levels, whereas later in the season, treatment of the sheep population may be more beneficial. The analysis also shows that the greater the degree of aggregation, the fewer sheep that become struck and, hence, suggests that increasing the heterogeneity in susceptibility amongst a flock of sheep restricts strikes to relatively few sheep. Providing the highly-susceptible sheep could be identified, concentrating strikes on a low number of sheep would allow fewer sheep to be treated, leading to a more efficient means of controlling the blowfly population and suppressing strike.

Animals↗