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Biomedical subjects

S A Williams

Publications and source records attributed to S A Williams.

At least 19 recordsLinked to original sources
PubMed2004

A comparison of polyethylene wear rates between cemented and cementless cups. A prospective, randomised trial.

We selected randomly a consecutive series of 162 patients requiring hip replacement to receive either a cementless, hemispherical, modular, titanium acetabular cup or a cemented, all-polyethylene cup. These replacements were performed by two surgeons in four general hospitals. The same surgical technique was used and a 26 mm metal-head femoral component was used in every case. After exclusions, 115 hips were studied for differences in rates of wear and osteolysis. The mean clinical follow-up was eight years and the mean radiological follow-up, 6.5 years. The cementless cups wore at a mean rate of 0.15 mm per year and the cemented cups at 0.07 mm per year. This difference was significant (p < 0.0001). Our findings in this mid-term study suggest that cementless cups wear more than cemented cups.

Acetabulum↗
PubMed2003

Patterns of spatial genetic structuring in a hydropsychid caddisfly (Cheumatopsyche sp. AV1) from southeastern Australia.

We assessed levels of mitochondrial genetic spatial structuring in the hydropsychid caddisfly Cheumatopsyche sp. AV1 in southeastern New South Wales, Australia. No significant spatial structuring was detected within or between catchments using analysis of molecular variance, and nested clade contingency analysis suggested no strong relationship between haplotypes and geographical location, at any clade level. However, tests for association among haplotypes incorporating geographical distance in the nested clade analysis, revealed patterns of historical range expansion and recent restricted gene flow. Most likely, population fragmentation preceded range expansion, although subsequent recontact and gene flow among the previously sundered populations has apparently obscured the geographical signature of the former fragmentation. Taken together, our analyses suggest that a number of populations fragmented during the Pleistocene evolved in isolation for a time and subsequently expanded into secondary contact. Since expansion, there has apparently been substantial (albeit somewhat restricted) dispersal and gene flow of adult female Cheumatopsyche sp. AV1, throughout the study area.

Analysis of Variance↗
PubMed2002

Quantification of PCR amplification products of Brugia HhaI repeat DNA using a semiautomated Q-PCR system.

The sensitive, rapid and species-specific diagnosis of Brugia infections in humans or animal models is important in determining the level of parasitemia and the efficacy of chemotherapy or vaccinations. The HhaI family of highly repeated DNA sequences from Brugia have been useful in polymerase chain reaction (PCR)-based diagnosis of brugian filarial infections in blood samples and in mosquitoes. A PCR assay was developed using a biotinylated primer, a non-biotinylated primer and a species-specific chemiluminescent probe [tris[2,2'bipyridine] ruthenium (II) chelate, TBR] to detect PCR amplified Hhal family repeats. Individual blood samples from jirds infected with Brugia malayi or B. pahangi and with different levels of microfilaremia were tested in this assay. Known concentrations of Brugia DNA and DNA from the blood of uninfected control jirds were used as positive and negative controls, respectively. The PCR products generated by this method were analyzed using a semi-automated quantitative (Q)-PCR system. The levels of parasite DNA can be calculated from the luminosity units generated. Significant amounts of parasite DNA were detected in blood samples from infected jirds, and these values were correlated with the levels of microfilaremia. In contrast, reductions in circulating microfilaria following treatment with ivermectin correlated with low levels of measurable DNA. Using this system, we were also able to detect HhaI repeat DNA in the spleens of B. pahangi- infected jirds at 56 days post-infection when circulating microfilariae were not readily detectable. The results indicate that the species-specific Hhal Q-PCR detection and quantification method is rapid and sensitive, is useful in the detection of Brugia DNA in blood and other tissues and is suited for use in clinical settings because it does not require radioactive isotopes and gel-based protocols.

Animals↗
PubMed2002

Development and standardization of a rapid, PCR-based method for the detection of Wuchereria bancrofti in mosquitoes, for xenomonitoring the human prevalence of bancroftian filariasis.

PCR has recently been studied as a promising tool for monitoring the progress of efforts to eliminate lymphatic filariasis. PCR can be used to test concurrently at least 30 pools, with as many as 40 mosquitoes in each pool, for the presence of filarial larvae. The SspI PCR assay for the detection of Wuchereria bancrofti DNA in pools of mosquitoes has been used since 1994 in a variety of laboratories worldwide. During that time, the original assay has been modified in these different laboratories and no standardized assay currently exists. In an effort to standardize and improve the assay, a meeting was held on 15-16 November 2001, at Emory University in Atlanta, with representatives from most of the laboratories currently using the assay. The first round of testing was designed to test the four most promising methods for DNA extraction from pools of mosquitoes. Two of the four methods stood out as clearly the best and these will be now optimised and evaluated in two further rounds of testing.

Animals↗
PubMed2002

Xenomonitoring of Culex quinquefasciatus mosquitoes as a guide for detecting the presence or absence of lymphatic filariasis: a preliminary protocol for mosquito sampling.

A protocol for the collection of resting, blood-engorged Culex quinquefasciatus Say and their examination for microfilariae has been developed as a way of detecting whether lymphatic filariasis (LF) occurs in a particular locality. The protocol was first implemented in a pilot study in Trinidad, West Indies. For gathering prevalence data, such xenomonitoring is a suitable alternative to the use of human bait, which is ethically questionable. The resting mosquitoes were collected, either indoors or outdoors, using electrical and mouth aspirators. A 'cocoeya broom', made from a bunch of the midribs of coconut-palm leaves, was found to be useful in flushing out the mosquitoes resting in hard-to-reach areas within bedrooms. The rationale behind the strategy and the five-step methodology, of householder notification, mapping, preparation of equipment, mosquito collecting and laboratory processing, are described. Data from the pilot study indicate that this xenomonitoring protocol may be applicable worldwide, albeit with modifications to take account of variations in the vector species involved and their ecology and resting behaviour.

Animals↗
PubMed2001

Moderate alcohol consumption and risk of heart failure among older persons.

CONTEXT: Heavy consumption of alcohol can lead to heart failure, but the relationship between moderate alcohol consumption and risk of heart failure is largely unknown. OBJECTIVE: To determine whether moderate alcohol consumption predicts heart failure risk among older persons, independent of the association of moderate alcohol consumption with lower risk of myocardial infarction (MI). DESIGN: Prospective cohort study conducted from 1982 through 1996, with a maximum follow-up of 14 years. SETTING AND PARTICIPANTS: Population-based sample of 2235 noninstitutionalized elderly persons (mean age, 73.7 years; 41.2% male; 21.3% nonwhite) residing in New Haven, Conn, who were free of heart failure at baseline. Persons who reported alcohol consumption of more than 70 oz in the month prior to baseline were excluded. MAIN OUTCOME MEASURE: Time to first fatal or nonfatal heart failure event, according to the amount of alcohol consumed in the month prior to baseline. RESULTS: Increasing alcohol consumption in the moderate range was associated with decreasing heart failure rates. For persons consuming no alcohol (50.0%), 1 to 20 oz (40.2%), and 21 to 70 oz (9.8%) in the month prior to baseline, crude heart failure rates per 1000 years of follow-up were 16.1, 12.2, and 9.2, respectively. After adjustment for age, sex, race, education, angina, history of MI and diabetes, MI during follow-up, hypertension, pulse pressure, body mass index, and current smoking, the relative risks of heart failure for those consuming no alcohol, 1 to 20 oz, and 21 to 70 oz in the month prior to baseline were 1.00 (referent), 0.79 (95% confidence interval [CI], 0.60-1.02), and 0.53 (95% CI, 0.32-0.88) (P for trend =.02). CONCLUSIONS: Increasing levels of moderate alcohol consumption are associated with a decreasing risk of heart failure among older persons. This association is independent of a number of confounding factors and does not appear to be entirely mediated by a reduction in MI risk.

Aged↗
PubMed2001

SfiI endonuclease activity is strongly influenced by the non-specific sequence in the middle of its recognition site.

The SfiI endonuclease cleaves DNA at the sequence GGCCNNNN NGGCC, where N is any base and downward arrow is the point of cleavage. Proteins that recognise discontinuous sequences in DNA can be affected by the unspecified sequence between the specified base pairs of the target site. To examine whether this applies to SFII, a series of DNA duplexes were made with identical sequences apart from discrete variations in the 5 bp spacer. The rates at which SFII cleaved each duplex were measured under steady-state conditions: the steady-state rates were determined by the DNA cleavage step in the reaction pathway. SFII cleaved some of these substrates at faster rates than other substrates. For example, the change in spacer sequence from AACAA to AAACA caused a 70-fold increase in reaction rate. In general, the extrapolated values for k(cat) and K(m) were both higher on substrates with inflexible spacers than those with flexible structures. The dinucleotide at the site of cleavage was largely immaterial. SFII activity is thus highly dependent on conformational variations in the spacer DNA.

Base Sequence↗
PubMed2001

Post-operative recovery after inguinal herniotomy in ex-premature infants: comparison between sevoflurane and spinal anaesthesia.

We prospectively studied the post-operative recovery profile of 28 ex-premature infants undergoing inguinal herniotomy. All infants had a post-conceptual age of less than 46 weeks at the time of surgery and were randomized to receive either sevoflurane (group 1, 14 patients) or spinal anaesthesia (group 2, 14 patients). All patients received supplemental caudal analgesia before skin incision. Cardiorespiratory function was continuously recorded in all patients before and after surgery. A blinded observer analysed each paired recording for predefined episodes of apnoea, hypoxaemia or bradycardia and the reports were used to compare the two groups. Spinal anaesthesia was attempted unsuccessfully in four patients in group 2. Five patients in group 1 demonstrated an 'excess' number of episodes (median 4, range 3-12) of clinically silent post-operative cardiorespiratory complications. ('Excess' in our study was defined as a 3-fold or greater increase in the number of post-operative episodes of bradycardia or apnoea relative to pre-operative occurrence). Three of these patients had pre-existing abnormal respiratory function and accounted for 80% of the episodes (26/32) of post-operative bradycardia and all five episodes of post-operative apnoea identified. All episodes of bradycardia and apnoea were temporally unrelated. None of the remaining patients in group 2 demonstrated an unacceptable number of post-operative cardiorespiratory complications. Our limited study suggests that general anaesthesia with an inhalational agent such as sevoflurane may induce or unmask abnormalities of cardiopulmonary function in predisposed infants. Spinal anaesthesia may be preferable but it is potentially stressful for the infant and associated with a clinically significant failure rate.

Anesthesia, Spinal↗
PubMed2001

Detection of Brugia malayi in laboratory and wild-caught Mansonioides mosquitoes (Diptera: Culicidae) using Hha I PCR assay.

An Hha 1 based polymerase chain reaction (PCR) assay developed for the detection of Brugia malayi, the causative agent of Brugian lymphatic filariasis, was evaluated for its sensitivity in the laboratory and for its usefulness in measuring changes in transmission of the disease in the field. Laboratory studies showed that the new assay was highly sensitive in comparison with the standard dissection and microscopy technique. The assay can detect as little as 4 pg of parasite DNA or a single microfilaria in pools of up to 100 mosquitoes. The optimum pool size for convenience was found to be 50 mosquitoes per pool. The efficacy of PCR assay was evaluated in filariasis control programmes in operation in endemic areas of Kerala State, South India. The infection rates obtained by the Hha I PCR assay and the conventional dissection and microscopy technique were 1.2% and 1.7% respectively in operational areas and 8.3% and 4.4% respectively, in check areas, which were not significantly different (P < 0.05). Thus, the Hha I PCR assay was found to be as sensitive as the conventional technique and hence it can be used as a new epidemiological tool for assessing parasite infection in field-collected mosquitoes.

Aedes↗
PubMed2001

Effect of nutritional supplementation on quantities of glucose transporters 1 and 4 in sheep granulosa and theca cells.

The stimulatory effect of nutritional supplementation on ovarian activity in sheep has been linked to an increase in glucose availability that, with insulin, directly decreases follicular steroidogenesis. Glucose uptake occurs by glucose transporters, but it is not known which glucose transporters are present in the sheep ovary or whether they are affected by nutritional stimulation. The aim of this study was to determine whether widely distributed glucose transporter 1 (GLUT1) or insulin-responsive GLUT4 are present in the granulosa or theca cells of sheep ovarian follicles, and whether their concentrations are affected by nutritional stimulation. Merino ewes (n = 49-51 per group) were stimulated nutritionally for 5 days before luteolysis with lupin grain or with one of two regimens of a glucogenic mixture, administered orally, which increases blood glucose concentrations towards the upper end of the normal range. Water was used as a control. Ovaries (n = 3 per group) were dissected and the granulosa cells and thecal shell from individual follicles were examined for glucose transporters using western blotting. GLUT1 concentration was 7-18 times higher in the granulosa than in the theca cells. GLUT4 was detected at a similar concentration in both types of cell. Nutritional treatment had no effect on the concentration of GLUT1 or GLUT4 in either tissue, and did not increase ovulation rate, despite increased concentrations of glucose and insulin. Concentrations of glucose transporters were not correlated with follicular concentrations of oestradiol or androstenedione. The presence of GLUT1 and GLUT4 in the granulosa and theca of sheep follicles indicates that the transporters have a role within the ovary in the modulation of follicular function.

Animal Feed↗
PubMed2000

The filarial genome project: analysis of the nuclear, mitochondrial and endosymbiont genomes of Brugia malayi.

The Filarial Genome Project (FGP) was initiated in 1994 under the auspices of the World Health Organisation. Brugia malayi was chosen as the model organism due to the availability of all life cycle stages for the construction of cDNA libraries. To date, over 20000 cDNA clones have been partially sequenced and submitted to the EST database (dbEST). These ESTs define approximately 7000 new Brugia genes. Analysis of the EST dataset provides useful information on the expression pattern of the most abundantly expressed Brugia genes. Some highly expressed genes have been identified that are expressed in all stages of the parasite's life cycle, while other highly expressed genes appear to be stage-specific. To elucidate the structure of the Brugia genome and to provide a basis for comparison to the Caenorhabditis elegans genome, the FGP is also constructing a physical map of the Brugia chromosomes and is sequencing genomic BAC clones. In addition to the nuclear genome, B. malayi possesses two other genomes: the mitochondrial genome and the genome of a bacterial endosymbiont. Eighty percent of the mitochondrial genome of B. malayi has been sequenced and is being compared to mitochondrial sequences of other nematodes. The bacterial endosymbiont genome found in B. malayi is closely related to the Wolbachia group of rickettsia-like bacteria that infects many insect species. A set of overlapping BAC clones is being assembled to cover the entire bacterial genome. Currently, half of the bacterial genome has been assembled into four contigs. A consortium has been established to sequence the entire genome of the Brugia endosymbiont. The sequence and mapping data provided by the FGP is being utilised by the nematode research community to develop a better understanding of the biology of filarial parasites and to identify new vaccine candidates and drug targets to aid the elimination of human filariasis.

Animals↗
PubMed2000

The genomes of Onchocerca volvulus.

Onchocerca volvulus, the filarial parasite that causes onchocerciasis or river blindness, contains three distinct genomes. These include the nuclear genome, the mitochondrial genome and the genome of an intracellular endosymbiont of the genus Wolbachia. The nuclear genome is roughly 1.5x10(8) bp in size, and is arranged on four chromosome pairs. Analysis of expressed sequence tags from different life-cycle stages has resulted in the identification of transcripts from roughly 4000 O. volvulus genes. Several of these transcripts are highly abundant, including those encoding collagen and cuticular proteins. Analysis of several gene sequences from O. volvulus suggests that the nuclear genes of O. volvulus are relatively compact and are interrupted relatively frequently by small introns. The intron-exon boundaries of these genes generally follow the GU-AG rule characteristic of the splice donor and acceptors of other vertebrate organisms. The nuclear genome also contains at least one repeated sequence family of a 150 bp repeat which is arranged in tandem arrays and appears subject to concerted evolution. The mitochondrial genome of O. volvulus is remarkably compact, only 13747 bp in size. Consistent with the small size of the genome, four gene pairs overlap, eight contain no intergenic regions and the remaining gene pairs are separated by small intergenic domains ranging from 1 to 46 bp. The protein-coding genes of the O. volvulus mitochondrial genome exhibit a striking codon bias, with 15/20 amino acids having a single codon preference greater than 70%. Intraspecific variation in both the nuclear and mitochondrial genomes appears to be quite limited, consistent with the hypothesis that O. volvulus has suffered a genetic bottleneck in the recent past.

Animals↗
PubMed2000

Identification of potential vaccine and drug target candidates by expressed sequence tag analysis and immunoscreening of Onchocerca volvulus larval cDNA libraries.

The search for appropriate vaccine candidates and drug targets against onchocerciasis has so far been confronted with several limitations due to the unavailability of biological material, appropriate molecular resources, and knowledge of the parasite biology. To identify targets for vaccine or chemotherapy development we have undertaken two approaches. First, cDNA expression libraries were constructed from life cycle stages that are critical for establishment of Onchocerca volvulus infection, the third-stage larvae (L3) and the molting L3. A gene discovery effort was then initiated by random expressed sequence tag analysis of 5,506 cDNA clones. Cluster analyses showed that many of the transcripts were up-regulated and/or stage specific in either one or both of the cDNA libraries when compared to the microfilariae, L2, and both adult stages of the parasite. Homology searches against the GenBank database facilitated the identification of several genes of interest, such as proteinases, proteinase inhibitors, antioxidant or detoxification enzymes, and neurotransmitter receptors, as well as structural and housekeeping genes. Other O. volvulus genes showed homology only to predicted genes from the free-living nematode Caenorhabditis elegans or were entirely novel. Some of the novel proteins contain potential secretory leaders. Secondly, by immunoscreening the molting L3 cDNA library with a pool of human sera from putatively immune individuals, we identified six novel immunogenic proteins that otherwise would not have been identified as potential vaccinogens using the gene discovery effort. This study lays a solid foundation for a better understanding of the biology of O. volvulus as well as for the identification of novel targets for filaricidal agents and/or vaccines against onchocerciasis based on immunological and rational hypothesis-driven research.

Animals↗
PubMed2000

Detection of DNA of nocturnally periodic Brugia malayi in night and day blood samples by a polymerase chain reaction-ELISA-based method using an internal control DNA.

An internal control was used in a polymerase chain reaction (PCR)-ELISA-based technique to detect the Hha I repeat of the filarial parasite Brugia malayi. A single microfilaria added to 200 microl of blood was reliably detected. The assay was evaluated on field samples from persons living in an area endemic for Anopheles-transmitted, nocturnally periodic B. malayi in central Sulawesi, Indonesia. Examination of night blood of 138 individuals for the presence of microfilariae by filtration revealed 44 microfilaria carriers. All microfilaria carriers were also positive in the PCR-ELISA and, in addition, 14 more samples were proven to contain parasite DNA. The sensitivity of both methods was compared on night and on day blood samples collected from 113 persons. Whereas 37 microfilaria carriers were identified by filtration of night blood, no microfilariae were observed in the corresponding day blood samples. The PCR-ELISA result was positive in all 37 night blood samples of microfilaria carriers and in an additional 13 night blood samples without microfilariae. Parasite DNA was detected in 31 day blood samples of microfilaria carriers and in 3 day blood samples of amicrofilaremic persons. Assuming a sensitivity of the PCR-ELISA on night blood of 100%, the sensitivity of night blood filtration is 74% and that of the PCR-ELISA on day blood is 68%. These data suggest that the described PCR-ELISA method is capable of detecting infections with nocturnally periodic B. malayi in day blood samples. Therefore, this method may facilitate both the identification of endemic areas and the monitoring of control programs.

Adult↗
PubMed2000

Application of a polymerase chain reaction-ELISA to detect Wuchereria bancrofti in pools of wild-caught Anopheles punctulatus in a filariasis control area in Papua New Guinea.

Chemotherapy-based eradication programs are aimed at stopping transmission of Wuchereria bancrofti by its obligatory mosquito vector. This study compares one year post-treatment W. bancrofti infection rates of Anopheles punctulatus, the main vector of lymphatic filariasis in Papua New Guinea, using traditional dissection techniques and a polymerase chain reaction (PCR)-based ELISA of a parasite-specific Ssp I repeat. A total of 633 mosquitoes in 35 batches were dissected. Six batches contained W. bancrofti-infected mosquitoes, giving a minimum infection rate of 0.9%. This value was not different than the actual infection rate, which was 9 (1.4%) of 633 mosquitoes (P = 0.48). The DNA was extracted from 47 pools containing a mean of 13.2 mosquitoes per pool. A total of 621 mosquitoes were processed for the PCR-ELISA, including 486 caught by human bait and 135 by light trap, which included both dead and live mosquitoes. Of 23 pools of alcohol-preserved human-bait mosquitoes, seven were positive by the PCR-ELISA, giving an infection rate identical to that obtained by dissection of individual mosquitoes (1.4%). The minimum infection rates for pools of light-trap mosquitoes found dead and alive were 2.7% (2 of 74) and 4.9% (3 of 61), respectively. These values did not differ from each other (P = 0.84), but the overall infection rate of light-trap mosquitoes was greater than that of mosquitoes captured by human bait (3.7% versus 1.4%; P = 0.09). These data indicate that the PCR-ELISA of a W. bancrofti Ssp I repeat using pools of mosquitoes is comparable to traditional dissection techniques for monitoring transmission intensity following introduction of mass chemotherapy. This approach may also be useful for rapid and cost-effective assessment of transmission in endemic areas where the frequency of overt lymphatic pathology is low.

Animals↗
PubMed1999

Cumulative effect of anatomical risk factors for schizophrenia: an MRI study.

BACKGROUND: Although schizophrenic and control subjects differ on a variety of neuroanatomical measures, the specificity and sensitivity of any one measure for differentiating between groups are low. This study investigated the cumulative effect of deviant brain structure on diagnosis. METHODS: Hemisphere and third ventricle volume and the normalized (Talairach) location of three association cortex sulcal landmarks were measured on high-resolution MRI scans in 37 male patients with schizophrenia and 33 male control subjects matched on age, handedness, and parental socioeconomic status. RESULTS: While there were few group differences on individual anatomical measures, the 10 variables reliably discriminated between the two groups when used in concert in a discriminant function analysis (F[10.59] = 3.6, p < .0009) with 77% of the subjects correctly classified. Five of the measures (left posterior cingulate, left inferior frontal sulcus, right sylvian fissure, and left and right halves of the third ventricle) correlated significantly with the discriminant function (p < .005). CONCLUSIONS: This is the first study to demonstrate that schizophrenics can be distinguished from matched controls on the basis of brain anatomy alone. The risk of schizophrenia may depend on the total amount of neural deviance, rather than on anomalies in a single structure or circuit.

Adolescent↗