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Biomedical subjects

J A Williamson

Publications and source records attributed to J A Williamson.

At least 19 recordsLinked to original sources
PubMed1998

The rfb genes in Azotobacter vinelandii are arranged in a rfbFGC gene cluster: a significant deviation to the arrangement of the rfb genes in Enterobacteriaceae.

We report the identification of rfbF and rfbC located adjacent to the previously identified rfbG (Gavini et. al. Biochem. Biophys. Res. Commun. 1997, 240, 153-161) from the non-symbiotic, non-pathogenic soil bacterium Azotobacter vinelandii. The rfbF open reading frame encodes a putative polypeptide of 256 amino acids. This polypeptide shares a homology of 74% with the RfbF of Synechocystis sp. and a 70% homology with the AscA of Yersinia pseudotuberculosis which function as alpha-D-glucose-1-phosphate cytidylyltransferases in the biosynthesis of the O-antigen. The rfbC encodes a putative polypeptide of 186 amino acids. It shows strongest homology to the RfbC of Synechocystis sp. (64%) and Salmonella typhimurium (40%). RfbC functions as a dTDP-4-Dehydrorhamnose 3,5-Epimerase. The genes identified here have a low G + C content (approximately 56%) as compared to the A. vinelandii chromosome (approximately 63%) which is characteristic of the rfb clusters identified in other bacteria and may be indicative of the acquisition of the rfb genes by interspecific gene transfer. Despite the high level of sequence conservation, the organization of the rfb genes in A. vinelandii deviates from the arrangement of the most thoroughly studied rfb gene clusters of Enterobacteriaceae.

Amino Acid Sequence↗
PubMed1998

Autonomic neurotoxicity of jellyfish and marine animal venoms.

Venoms and poisons of jellyfish and other marine animals can induce damage to the human nervous and circulatory systems. Clues to the pathogenesis and clinical manifestations of these lesions can be obtained from data of human envenomations and animal experimentation. Because many investigators are unaware that marine animal venoms have autonomic actions, this paper aims to elucidate the broad antagonistic or toxic effects these compounds have on the autonomic nervous system. Marine venoms can affect ion transport of particularly sodium and calcium, induce channels or pores in neural and muscular cellular membranes, alter intracellular membranes of organelles and release mediators of inflammation. The box jellyfish, particularly Chironex fleckeri, in the Indo-Pacific region, is the world's most venomous marine animal and is responsible for autonomic disorders in patients. The symptoms induced by these venoms are vasospasm, cardiac irregularities, peripheral neuropathy, aphonia, ophthalmic abnormalities and parasympathetic dysautonomia. Cases of Irukandji syndrome, caused by the jellyfish Carukia barnesi, have symptoms that mimic excessive catecholamine release. Coelenterate venoms can also target the myocardium, Purkinje fiber, A-V node or aortic ring. Actions on nerves, as well as skeletal, smooth or cardiac muscle occur. Recent studies indicate that the hepatic P-450 enzyme family may be injured by these compounds. The multiplicity of these venom activities means that a thorough understanding of the sting pathogenesis will be essential in devising effective therapies.

Animals↗
PubMed1998

The role of endothelial nitric oxide synthase expression in the development of pulmonary hypertension in chronically hypoxic infant swine.

OBJECTIVE: Our goal was to determine the role of pulmonary endothelial nitric oxide synthase expression in the development of pulmonary hypertension in infants with congenital cyanotic heart disease. METHODS: Two groups of 4-week-old piglets were studied. In one group, the piglets were raised in an environment of 10% oxygen from 2 days of age (cyanotic, n = 6), and in the other group the piglets were raised at room air (control, n = 5). Pulmonary hemodynamics were measured in vivo for each animal, and peripheral lung biopsy specimens were obtained for Western blot analysis with the use of antiendothelial nitric oxide synthase antibody and for activity analysis with the use of the tritiated L-arginine assay. RESULTS: The piglets in the chronically hypoxic group had significant increases in mean pulmonary arterial pressure (44.0 +/- 3.8 mm Hg vs 14.8 +/- 1.2 mm Hg in controls, p = 0.0007) and pulmonary vascular resistance (7272.0 +/- 871.1 dyne x cm x sec(-5) vs 1844.5 +/- 271.2 dyne x cm x sec(-5) in controls, p = 0.002). These changes in the pulmonary hemodynamics of the hypoxic piglets were accompanied by a twofold increase in the expression of pulmonary endothelial nitric oxide synthase (p = 0.0043) but no corresponding increase in nitric oxide synthase activity. CONCLUSIONS: Raising infant piglets in an environment of 10% oxygen for 4 weeks results in significant pulmonary arterial hypertension accompanied by increased expression of nitric oxide synthase within the lung endothelium. Furthermore, the increased levels of nitric oxide synthase within the lungs of the hypoxic swine were not accompanied by a proportional increase in enzyme activity. These findings suggest that the development of pulmonary hypertension in infants with congenital cyanotic disease is not due to decreased expression of endothelial nitric oxide synthase, but instead may be related to a decreased ability of the enzyme to produce sufficient nitric oxide.

Animals↗
PubMed1997

Identification and mutational analysis of rfbG, the gene encoding CDP-D-glucose-4,6-dehydratase, isolated from free living soil bacterium Azotobacter vinelandii.

We have identified the rfbG from a non-symbiotic and non-pathogenic soil bacterium, Azotobacter vinelandii. The nucleotide sequence analysis of the rfbG revealed an open reading frame that encodes a peptide of 360 amino acids. This deduced peptide shares 57% homology with the RfbG of Synechocystis and 47% homology with the RfbG of Yersinia pseudotuberculosis. The previously identified short-chain dehydrogenases/reductases family signature sequence is conserved in the sequence of the RfbG of A. vinelandii. Southern blotting analysis of A. vinelandii chromosome by probed with 1.1 kb PstI DNA fragment corresponding to rfbG revealed that it is present as single copy on A. vinelandii chromosome. Disrupting the rfbG present on the chromosome of A. vinelandii, by insertion of kanamycin resistance marker via homologous recombination, resulted in drastic changes in the growth characteristics. The rfbG-negative A. vinelandii grown in liquid medium exhibited agglutination that is characteristic of rfb- mutants of other bacteria, suggesting that we have cloned the functional copy of the rfbG of A. vinelandii.

Amino Acid Sequence↗
PubMed1997

A Queensland family with ciguatera after eating coral trout.

Ciguatera (poisoning caused by eating fish contaminated with algal toxins) is usually diagnosed clinically. We describe a Queensland family of four (including a pregnant woman) with ciguatera, confirmed by bioassay of the implicated fish for ciguatoxin. All four recovered, illustrating the effectiveness of treatment with intravenous mannitol. At birth, the infant appeared to suffer no adverse effects attributable to ciguatera; to our knowledge, this is the first report of the effect of severe ciguatera in the first trimester of pregnancy.

Adult↗
PubMed1996

Chromosomal localisation of the human envoplakin gene (EVPL) to the region of the tylosis oesophageal cancer gene (TOCG) on 17q25.

Envoplakin is a membrane-associated precursor of the epidermal cornified envelope. Envoplakin is homologous to desmoplakin I and desmoplakin II (DPI/II), bullous pemphigoid antigen 1 (BPAG1), and plectin and is proposed to link desmosomes and keratin filaments to the cornified envelope. We describe the isolation of cosmids and yeast artificial chromosomes containing the complete human envoplakin gene (EVPL) and show, by analysis of somatic cell hybrids and chromosomal in situ hybridisation, that the envoplakin gene, unlike the genes encoding BPAG1 and DPI/II, maps to 17q25 and is physically linked to D17S1603. This sequence-tagged site segregates with the autosomal dominant human disease focal nonepidermolytic palmoplantar keratosis (NEPKK; "tylosis"), which is associated with an increased risk of oesophageal cancer. The chromosomal localisation of the envoplakin gene, the homology of the encoded protein to keratin-binding proteins, and its expression in epidermal and oesophageal keratinocytes all raise the possibility that loss of envoplakin function could be responsible for this form of palmoplantar keratoderma.

Chromosome Mapping↗
PubMed1996

Chromosomal mapping of the human and mouse homologues of two new members of the AP-2 family of transcription factors.

The AP-2 transcription factor has been shown to play an important role in the development of tissues of ectodermal origin and has also been implicated in mammary oncogenesis. It has recently been found that AP-2 is encoded by a family of related genes, AP-2alpha, AP-2beta, and AP-2gamma. As a further step in understanding the role each of these genes has in development, we have used fluorescence in situ hybridization to map the chromosomal locations of the mouse and human homologues of the newly isolated AP-2beta and AP-2gamma genes. Tcfap2b and Tcfap2c map to mouse chromosomes 1A2-4 and 2H3-4, respectively, while TFAP2B and TFAP2C map to human chromosomes 6p12 and 20q13.2, the latter being a region that is frequently amplified in breast carcinoma.

Animals↗
PubMed1996

Polyclonal origin of colonic adenomas in an XO/XY patient with FAP.

It is widely accepted that tumors are monoclonal in origin, arising from a mutation or series of mutations in a single cell and its descendants. The clonal origin of colonic adenomas and uninvolved intestinal mucosa from an XO/XY mosaic individual with familial adenomatous polyposis (FAP) was examined directly by in situ hybridization with Y chromosome probes. In this patient, the crypts of the small and large intestine were clonal, but at least 76 percent of the microadenomas were polyclonal in origin.

Adenomatous Polyposis Coli↗
PubMed1995

Guess LOD approach: sufficient conditions for robustness.

Analysis of genetic linkage between a disease and a marker locus requires specifying a genetic model describing both the inheritance pattern and the gene frequencies of the marker and trait loci. Misspecification of the genetic model is likely for etiologically complex diseases. In previous work we have shown through analytic studies that misspecifying the genetic model for disease inheritance does not lead to excess false-positive evidence for genetic linkage provided the genetic marker alleles of all pedigree members are known, or can be inferred without bias from the data. Here, under various selection or ascertainment schemes we extend these previous results to situations in which the genetic model for the marker locus may be incorrect. We provide sufficient conditions for the asymptotic unbiased estimation of the recombination fraction under the null hypothesis of no linkage, and also conditions for the limiting distribution of the likelihood ratio test for no linkage to be chi-squared. Through simulation studies we document some situations under which asymptotic bias can result when the genetic model is misspecified. Among those situations under which an excess of false-positive evidence for genetic linkage can be generated, the most common is failure to provide accurate estimates of the marker allele frequencies. We show that in most cases false-positive evidence for genetic linkage is unlikely to result solely from the misspecification of the genetic model for disease or trait inheritance.

Genetic Linkage↗
PubMed1993

First aid treatment of jellyfish stings in Australia. Response to a newly differentiated species.

Vinegar has been shown to inhibit neomatocyst discharge in Chironex fleckeri, the deadly north Australian box-jellyfish, and application of vinegar has become accepted first aid, not only for box-jellyfish stings, but also for stings by other Australian jellyfish. However, in a newly differentiated species of Physalia in Australian waters, which causes severe envenomation, vinegar was found to cause discharge in up to 30% of neomatocysts. In treating these stings, the use of vinegar is not recommended as it may increase envenomation. Stings from the single-tentacled Physalia utriculus (the "bluebottle") are not severe, tentacles with unfired nematocysts rarely adhere to the victim's skin and vinegar dousing is not required. Vinegar treatment is therefore an unnecessary step in the first aid management of any Physalia sting but remains an essential first aid treatment for all cubozoan (box) jellyfish tested to date.

Acetates↗
PubMed1993

Path analysis and sib-pair linkage.

When the distance between linked loci is expressed in terms of the correlation between the identity-by-descent (idb) values of the loci, then a path model may be used to order loci with data on sib-pairs and their parents. The relationship between the recombination fraction and the correlation coefficient is developed and a method for fitting a covariance matrix predicted by a specific ordering of loci to an observed covariance matrix is proposed.

Epidemiologic Methods↗
PubMed1993

Plasma catecholamine levels during exposure to an environment of hyperbaric oxygen.

Plasma catecholamine levels were measured before, during and after hyperbaric oxygen therapy in nine subjects. Adrenaline levels were elevated immediately prior to hyperbaric oxygen therapy, but then fell and stabilized once treatment commenced. No significant fluctuations in plasma dopamine or noradrenaline levels were noted during the treatment period. This study does not support the premise that there is a suppression of endogenous plasma catecholamine levels during hyperbaric oxygen as has been previously reported. The observed initial increase in adrenaline can be attributed to stress/anxiety and the subsequent decline in this stress, rather than the result of the hyperbaric oxygen treatment itself.

Adult↗
PubMed1993

The Australian Incident Monitoring Study. Errors, incidents and accidents in anaesthetic practice.

Human error is a pervasive and normal part of everyday life and is of interest to the anaesthetist because errors may lead to accidents. Definitions of, and the relationships between, errors, incidents and accidents are provided as the basis to this introduction to the psychology of human error in the context of the work of the anaesthetist. Examples are drawn from the Australian Incident Monitoring Study (AIMS). An argument is put forward for the use of contemporaneous incident reporting (eliciting relevant contextual information as well as details of use to cognitive psychologists), rather than the use of accident investigation after the event (with the inherent problems of scant information, altered perception and outcome bias). A classification of errors is provided. "Active" errors may be classified into knowledge-based, rule-based, skill-based and technical errors. Different strategies are required for the prevention of each type and it may now be useful to place more emphasis in anaesthetic practice on categories to which little attention has been directed in the past. "Latent" errors make an enormous contribution to problems in anaesthesia and several categories are discussed (e.g. environment, physiological state, equipment, work practices, personnel training, social and cultural factors). An approach is provided for the prevention and management of errors, incidents and accidents which allows clinical problems to be categorized, the relative importance of various contributing factors to be established, and appropriate preventative strategies to be devised and implemented on the basis of priorities determined from the AIMS data. Accidents cannot be abolished; however, an understanding of the factors underlying them can lead to the rational direction of resources and effort to prevent them and minimise their effects.

Accident Prevention↗
PubMed1993

The Australian Incident Monitoring Study: an analysis of 2000 incident reports.

The Australian Patient Safety Foundation was formed in 1987; it was decided to set up and co-ordinate the Australian Incident Monitoring Study as a function of this Foundation; 90 hospitals and practices joined the study. Participating anaesthetists were invited to report, on an anonymous and voluntary basis, any unintended incident which reduced, or could have reduced, the safety margin for a patient. Any incident could be reported, not only those which were deemed "preventable" or were thought to involve human error. The Mark I AIMS form was developed which incorporated features and concepts from several other studies. All the incidents in this symposium were reported using this form, which contains general instructions to the reporter, key words and space for a narrative of the incident, structured sections for what happened (with subsections for circuitry incidents, circuitry involved, equipment involved, pharmacological incidents and airway incidents), why it happened (with subsections for factors contributing to the incident, factors minimising the incident and suggested corrective strategies), the type of anaesthesia and procedure, monitors in use, when and where the incident happened, the experience of the personnel involved, patient age and a classification of patient outcome. Enrollment, reporting and data-handling procedures are described. Data on patient outcome are presented; this is correlated with the stages at which the incident occurred and with the ASA status of the patients. The locations at which the incidents occurred and the types of procedures, the sets of incidents analysed in detail and a breakdown of the incidents due to drugs are also presented.(ABSTRACT TRUNCATED AT 250 WORDS)

Accidents↗
PubMed1993

The Australian Incident Monitoring Study. Which monitor? An analysis of 2000 incident reports.

The role of monitors in patients undergoing general anaesthesia was studied by analysing the first 2000 incidents reported to the Australian Incident Monitoring Study; 1256 (63%) were considered applicable to this study. In 52% of these a monitor detected the incident first; oximetry (27%) and capnography (24%) detected over half of the monitor detected incidents, the electrocardiograph 19%, blood pressure monitors 12%, a low pressure (circuit) alarm 8%, and the oxygen analyser 4%. Of the other monitors used, 5 first detected 1-2% of incidents, and the remaining 8 less than 0.5% each. The oximeter would have detected over 40% of the monitor detected incidents had its more informative modulated pulse tone always been relied upon instead of the "bleep" of the ECG. A theoretical analysis was then carried out to determine which of an array of 17 monitors would reliably have detected each incident had each monitor been used on its own and had the incident been allowed to evolve. To facilitate "scoring" of monitors, the incidents were categorized empirically into 60 clinical situations; 40% of applicable incidents were accounted for by only 5 clinical situations, 60% by 10 and nearly 80% by 20. 98% were accounted for by the 60 situations. A pulse oximeter, used on its own, would theoretically have detected 82% of applicable incidents (nearly 60% before any potential for organ damage). These figures for capnography are 55% and 43% and for oximetry and capnography combined are 88% and 65%, respectively. With the addition of blood pressure monitoring these become 93% and 65%, and of an oxygen analyser, 95 and 67%. Other monitors, including the ECG, each increase the yield by by less than 0.5%. The international monitoring recommendations and those of the Australian and New Zealand College of Anaesthetists are thoroughly vindicated by the patterns revealed in this study. The priority sequence of monitor acquisition for those with limited resources should be stethoscope, sphygmomanometer, oxygen analyser if nitrous oxide is to be used, pulse oximeter, capnograph, high pressure alarm, and, if patients are to be mechanically ventilated, a low pressure alarm (or spirometer with alarm); an ECG, a defibrillator, a spirometer and a thermometer should be available.

Accidents↗