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Biomedical subjects

K Williams

Publications and source records attributed to K Williams.

At least 163 records · Page 9Linked to original sources
PubMed1998

Rapid method for fluorescent in situ ribosomal RNA labelling of Cryptosporidium parvum.

A method for fluorescence in situ hybridization (FISH) is described that requires less than 1 h duration. Oocysts were resuspended in 50% ethanol and incubated at 80 degrees C for 10 min for simultaneous fixation and permeabilization. Samples were than incubated with the oligonucleotide probe at 48 degrees C for more than 30 min. The rRNA binding specificity of the optimized protocol was confirmed. FISH was found to be valuable as a second label for oocysts presumptively identified immunofluorescently, but required more than an order of magnitude signal amplification for independent use. The number of oligonucleotide probes bound per oocyst was compared with the copy number of 18S rRNA molecules per oocyst to provide a measure of the labelling efficiency of the FISH method. Hybridization kinetics were also analysed. These data indicate that significant further increases in the brightness of FISH-labelled oocysts cannot be achieved by further optimization of the pre-treatment and hybridization conditions.

Animals↗
PubMed1998

Changes in throwing by older adults: a longitudinal investigation.

This investigation examined change in a motor pattern requiring multisegmented coordination in older adults. The overarm throw was observed longitudinally in 8 elderly individuals over 7 years. Data were evaluated using Roberton's (Roberton & Halverson, 1984) movement components. Contrasting the assumed pattern of aging, only small declines in movement form were observed. Individual cases revealed additional, noncategorizable declines within component categories, including slower movement speed and decreased range of motion. Increased trial-to-trial variability also was associated with change. These changes suggested that elderly participants coordinated their movements in a manner similar to younger participants but controlled them differently. The small changes observed in this investigation suggest that performance, at least for some skills, is more stable than traditionally assumed.

Aged↗
PubMed1998

Clinical trials of antibacterial agents: a practical guide to design and analysis. Statisticians in the Pharmaceutical Industry Working Party.

Guidelines on the conduct of clinical trials of antibacterial agents produced by the US Food and Drug Administration, the British Society for Antimicrobial Chemotherapy, the Infectious Diseases Society of America and a European Working Party have been reviewed. Although very informative, these guidelines provide limited practical guidance on the design and statistical aspects of phase III studies of antimicrobial agents. This paper describes the differences between antibacterial trials and clinical studies in other therapeutic areas with regard to subjective endpoints, dual clinical and bacteriological endpoints, frequent protocol violations and difficulty of using placebo controls. The importance of a detailed protocol and planned analysis strategy is emphasized. The choice of comparator agents, practical issues with the blinding of trial materials and the documentation of patients excluded from study entry are discussed. The use of different patient groups and different endpoints in analyses are described. The principles of equivalence and their application to trials of antibacterial agents are discussed, together with an approach to calculating sample size. A variety of statistical analyses of results are compared for different situations indicating some of the problems that can arise. Different methods of presentation of study data are included with emphasis on regulatory submissions rather than scientific publications. Some graphical presentations are recommended and issues regarding data across different studies are discussed.

Anti-Infective Agents↗
PubMed1998

Expression of extracellular superoxide dismutase in the human male reproductive tract, detected using antisera raised against a recombinant protein.

Mammalian spermatozoa are particularly susceptible to the deleterious effects of reactive oxygen species and lipid peroxidation, which ultimately lead to impaired fertility. A number of enzymes are present in the male reproductive tract which may play a role in preventing oxidative damage; in particular, the epididymis is the site of synthesis and secretion of large amounts of extracellular superoxide dismutase (eSOD). In order to study the distribution of eSOD in the male reproductive tract, and distinguish it from other related superoxide dismutase isoenzymes (e.g. cytosolic SOD), polyclonal antisera have been raised against a recombinant human eSOD fusion protein, expressed in bacterial cells. This protein was expressed from a synthetic gene fragment, using preferred Escherichia coli codons, designed to overcome the problems associated with the high guanine+cytosine content of the natural human eSOD transcript. Using this antiserum, eSOD can be readily detected in a range of human reproductive tissues as well as in human seminal plasma. However, the presence of similar levels of eSOD in the seminal plasma of vasectomized men (probably of prostatic origin) precludes its use as a simple diagnostic indicator of eSOD activity levels in the epididymis.

Amino Acid Sequence↗
PubMed1998

Expression of extracellular glutathione peroxidase type 5 (GPX5) in the rat male reproductive tract.

The mammalian epididymis is the site of expression and secretion of an abundant, tissue-specific, androgen-regulated, selenium-independent, glutathione peroxidase isoenzyme (GPX5), which has been proposed to play a role in protecting the membranes of spermatozoa from the damaging effects of lipid peroxidation and/or preventing premature acrosome reaction. Using a combination of reverse transcription-polymerase chain reaction, Northern blot analysis and Western blotting, we now describe in detail the developmental expression of GPX5 transcripts and protein in the rat epididymis and characterize the association of rat GPX5 with the sperm plasma membrane.

Animals↗
PubMed1998

Genetic characterization of RRS1, a recessive locus in Arabidopsis thaliana that confers resistance to the bacterial soilborne pathogen Ralstonia solanacearum.

The soilborne, vascular pathogen Ralstonia solanacearum, the causative agent of bacterial wilt, was shown to infect a range of Arabidopsis thaliana accessions. The pathogen was capable of infecting the Col-5 accession in an hrp-dependent manner, following root inoculation. Elevated bacterial population levels were found in leaves of Col-5, 4 to 5 days after root inoculation by the GMI1000 strain. Bacteria were found predominantly in the xylem vessels and spread systematically throughout the plant. The Nd-1 accession of A. thaliana was resistant to the GMI1000 strain of R. solanacearum. Bacterial concentrations detected in leaves of Nd-1, inoculated with an hrp+ strain of R. solanacearum, were only slightly higher than those detected in the susceptible accession, Col-5, following inoculation with a strain whose hrp gene cluster was deleted. Leaf inoculation of the GMI1000 strain on the resistant accession Nd-1 induced the formation of lesions in the older leaves of the rosette whereas the same strain of R. solanacearum provoked complete wilting of Col-5. Resistance to strain GMI1000 of R. solanacearum segregated as a simply inherited recessive trait in a genetic cross between Col-5 and Nd-1. F9 recombinant inbred lines generated between these two accessions were used to map a locus, RRS1, that was the major determinant of resistance between restriction fragment length polymorphism markers mi83 and mi61 on chromosome V. This region of the A. thaliana genome is known to contain many other pathogen recognition capabilities.

Arabidopsis↗
PubMed1998

The impact of diagnostic labelling in population-based research into cerebral palsy.

This study explores and quantifies the impact on the estimation of prevalence rates and aetiological hypotheses of inclusion and exclusion of different diagnostic labels and types of cerebral palsy (CP). The study was based on data from a CP register which had been established in the English North East Thames Regional Health Authority (NETRHA). As a deliberate policy, no definition of CP was given to notifiers and no inclusion or exclusion criteria were specified. Clinical information, including known malformations, genetic disorders, and features that made the diagnosis doubtful, was requested. Rates and relative risks for different inclusion and exclusion criteria were calculated. The crude rate of CP as defined above was 1.6/1000 (95%CI 1.5, 1.7). Exclusion of all cases with a known or potentially causal association reduced this rate to 1.2/1000 (95%CI 1.0, 1.3). Comparison with an intensively investigated sample from Germany and Sweden showed that more of the same causal associations (or diagnostic labels) were found, particularly where MRI studies had been carried out. Future comparative studies in CP will need to be very precise in specifying inclusions and exclusions and in estimating the effects they will have on monitoring trends over time and aetiological hypotheses.

Cerebral Palsy↗
PubMed1998

Prospective investigation of cryptic outbreaks of Salmonella agona salmonellosis.

The number of Salmonella agona isolates reported annually in Texas from 1992 through 1994 ranged from 14 to 21. An increase in incidence of S. agona infections was noted in the fall of 1995. Pulsed-field gel electrophoresis (PFGE) analysis identified prospectively two possible cryptic outbreaks caused by an indistinguishable strain which was isolated from 18 of 59 patients who were culture positive from March through December 1995. These 18 patients had onset of illness from 20 May through 3 October 1995. Eight individuals resided in the Austin area, eight resided in San Antonio, and two resided in Houston; none had attended a common social gathering or owned common pets. Six patients in San Antonio and one patient from Houston recalled eating food items from the same Mexican food restaurant in San Antonio. S. agona organisms with the same PFGE profile were isolated from machacado, an air-dried, raw beef product prepared at the restaurant. The machacado had been shredded in a kitchen blender which was the probable source for cross-contamination of other food items. Five patients in Austin reported eating at a popular Mexican food restaurant in Austin. Improperly prepared machacado also may have been served at the Austin restaurant; however, sufficient quantities of machacado were not available for analysis. PFGE was essential in determining whether the cases constituted outbreaks and was invaluable in guiding the epidemiological investigation.

Demography↗
PubMed1998

Substitution of ras for the herpesvirus saimiri STP oncogene in lymphocyte transformation.

STP-C488 (STP of herpesvirus saimiri [HVS] group C strain 488 [C488]) is the only virus-encoded protein found to associate with cellular ras and activate ras signal transduction pathways. To investigate an important role for ras signal transduction in STP-dependent growth transformation, we constructed recombinant strains of HVS C488 in which the STP-C488 oncogene was replaced with cellular normal ras (c-ras) or viral oncogenic ras (v-ras). Recombinant HVS deltaSTP/v-ras immortalized primary common marmoset T lymphocytes to interleukin-2-independent growth as efficiently as wild-type HVS C488 (wt HVS), while recombinant HVS deltaSTP/c-ras did so with low efficiency. Whereas wt HVS immortalized CD4- CD8+ single-positive T lymphocytes, HVS deltaSTP/c-ras- and HVS deltaSTP/v-ras-immortalized cells were principally CD4+ CD8+ double-positive T lymphocytes. In addition, HVS deltaSTP/v-ras-immortalized T cells showed a high level of ras expression and exhibited an adherent macrophage-like morphology. These phenotypes were likely caused by the drastic activation of AP-1 transcriptional factor activity. Finally, HVS deltaSTP/v-ras and HVS deltaSTP/c-ras each induced lymphoma in one of two common marmosets, although onset of disease was more rapid with the v-ras virus. These results demonstrate that ras can substitute for the STP oncogene of HVS C488 to allow immortalized growth of primary lymphoid cells and that an activated form of ras does so more efficiently than the normal cellular form of ras.

Animals↗
PubMed1998

Kawasaki disease in Australia, 1993-95.

AIM: To describe the epidemiology, management, and rate of cardiac sequelae of Kawasaki disease in Australia. DESIGN: Cases were notified to the Australian Paediatric Surveillance Unit, an active national surveillance scheme, from May 1993 to June 1995. RESULTS: 139 cases of Kawasaki disease were confirmed. In 1994, the annual incidence was 3.7/100,000 children < 5 years old. Sixteen children were not admitted to hospital. Coronary artery abnormalities were reported in 35 (25%) children. Two patients were diagnosed at postmortem examination. Sixty six per cent of patients were diagnosed within 10 days of onset and 81% of these received intravenous gammaglobulin within 10 days. Forty five of the notified children did not fulfil the study criteria because of streptococcal infection or insufficient clinical criteria. One child with streptococcal infection had coronary artery dilatation. CONCLUSION: Diagnosis of Kawasaki disease was delayed beyond 10 days in one third of patients, and almost 20% of children who could have received gammaglobulin within 10 days did not. The distinction between Kawasaki disease, streptococcal infection, and other possible diagnoses is problematic in some children.

Adolescent↗
PubMed1998

Economic analysis of fluconazole versus amphotericin B for the treatment of candidemia in non-neutropenic patients.

Fluconazole (FLU) is an alternative to amphotericin B (AMB) for the treatment of candidemia in non-neutropenic patients. This agent has similar clinical efficacy but significantly reduced adverse effects compared with AMB. Using the database from a Canadian randomised multicentre comparative trial of FLU versus AMB in the treatment of non-neutropenic patients with candidemia, an economic analysis of antifungal therapy was conducted from a Canadian hospital perspective. Patient records were examined for information containing hospital resource consumption. This included the costs for primary intravenous therapy with either AMB or FLU, laboratory tests, patient clinical monitoring and adverse effects management. The robustness of the baseline results were then tested by a comprehensive sensitivity analysis. The mean duration of therapy in the AMB and FLU arms was 17.1 and 23.7 days, respectively (p < 0.001). Assuming that all of the FLU was administered intravenously, the outcomes of the baseline economic analysis revealed that the treatment cost for patients randomized to receive FLU was approximately 50% higher than that for patients treated with AMB [AMB: $Can2370 vs FLU: $Can3578; p = 0.001 ($Can = Canadian dollars)]. In the sensitivity analysis, substitution to oral FLU after 7 days of intravenous therapy produced economic differences that were no longer statistically significant (AMB: $Can2370 vs FLU: $Can2705; p = 0.10). These results suggest that the FLU administration regimen used in the Canadian randomized trial for the treatment of candidemia in non-neutropenic patients may result in increased hospital costs compared with AMB. However, comparable expenditures could be realized if FLU is administered intravenously for the first 7 days and then orally in patients whose condition allows for reliable oral therapy.

Adult↗
PubMed1998

Multidimensional correlates of falls in older women.

Older women who had fallen within the last year (n = 63) were compared with those who had not fallen (n = 67) on several psychological and motor measures. Both fallers and nonfallers demonstrated high levels of functioning. Discriminant analysis results indicated that a combination of variables, including physical activity and both psychological (general well-being, self-efficacy) and motor (functional reach, mobility) measures differentiated fallers and nonfallers. Results suggest that falling is a multidimensional phenomenon, that small declines on multiple factors may increase risk of falls, and that multifaceted interventions may help maintain high levels of functioning and prevent declines often associated with increased age.

Accidental Falls↗
PubMed1998

The selectivity filter of the N-methyl-D-aspartate receptor: a tryptophan residue controls block and permeation of Mg2+.

A hallmark feature of N-methyl-D-aspartate (NMDA) receptors is their voltage-dependent block by extracellular Mg2+. The structural basis for Mg2+ block is not fully understood. Although asparagine residues in the pore-forming M2 regions of NR1 and NR2 subunits influence Mg2+ block, it has been speculated that additional residues are likely to be involved. Here, we report the unexpected finding that a tryptophan residue in the M2 region of NR2 subunits controls Mg2+ block. An NR2B(W607L) mutation abolished block and greatly increased permeation of extracellular Mg2+. A similar effect was seen with a mutation at the equivalent residue in NR2A but not with mutations at the equivalent residue or adjacent residues in NR1. In NR2B, mutations that changed NR2B(W607) to asparagine (W607N) or alanine (W607A) also greatly reduced Mg2+ block, whereas mutations that changed W607 to the aromatic residues tyrosine (W607Y) or phenylalanine (W607F) had little or no effect on Mg2+ block. Furthermore, the W607L, W607N, and W607A mutants, but not the W607Y and W607F mutants, decreased Ba2+ permeability of NMDA channels. Thus, residue NR2B(W607) may be involved in binding of divalent cations, in particular Mg2+, through a cation-pi interaction with the electron-rich aromatic ring of the tryptophan. We previously suggested that NR2B(W607) may contribute to the narrow constriction of the NMDA channel. A model is now proposed in which the M2 loop of NR2B is folded in such a way that NR2B(W607) is positioned at the narrow constriction, at a level similar to NR2B(N616) and NR1(N616), with these three residues forming a binding site for Mg2+.

Amino Acid Sequence↗
PubMed1998

Geriatric education in dental hygiene programs.

This study examined the current status of geriatric curricula in dental hygiene programs in both the United States and Canada and was comprised of a twenty-six-item survey sent to dental hygiene programs. Responses (82 percent) revealed didactic requirements in 89 percent of programs and clinical requirements in 54.2 percent of programs surveyed. Mean didactic clock hours were ten (+/- 8.2), while clinical clock hours were 21.8 (+/- 27.5). Specific geriatric courses were found in only 18.8 percent of programs, while 81.2 percent integrated geriatrics with other coursework. Both clinical (98.8 percent) and didactic courses (81.5 percent) were taught primarily by dental hygiene faculty. Clinical experiences were primarily provided at extramural sites (79 percent). Half of schools surveyed (49.5 percent) felt their geriatric curriculum was less than optimal. The authors conclude that current levels of geriatric dental hygiene education may not meet the increasing demands of this growing population.

Aged↗