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Biomedical subjects

K E Williams

Publications and source records attributed to K E Williams.

At least 37 records · Page 2Linked to original sources
PubMed1996

Overexpression of p53 protein is an independent prognostic indicator in human endometrial carcinoma.

The important role of the p53 gene in tumour progression and cellular response to DNA damage has prompted investigation of the clinical significance of alterations to this gene. We examined both p53 overexpression and mutation of the gene in endometrial carcinoma in order to evaluate the prognostic significance of these changes. Of 122 endometrial carcinomas, 33 (27%) showed overexpression of p53 in the nucleus and 66 (54%) in the cytoplasm. Mutation in the p53 gene was found in 16 (13%) cases but showed no significant association with patient survival. Nuclear p53 overexpression was associated with poor survival (48% vs 80% alive in negative tumours 5 years post operatively, P < 0.001). In contrast, cytoplasmic p53 overexpression was associated with better survival (85% vs 55%, P < 0.001). When patients were separated into prognostic subgroups according to established clinical markers, these associations remained significant within most subgroups examined. In multivariate analysis adjusted for surgical stage, histological grade and type and vascular invasion, both nuclear p53 overexpression [hazard ratio 4.9 (95% CI 1.3-17.6). P = 0.016] and cytoplasmic overexpression [0.25 (0.06-0.98), P = 0.047] were independent prognostic factors. Immunohistochemical assessment of p53 overexpression in the nucleus and cytoplasm could provide useful prognostic information for the management of patients with endometrial cancer.

Biomarkers, Tumor↗
PubMed1996

Postural adjustments produced by moving visual (horizontal optokinetic) patterns.

The effects of horizontal optokinetic stimulation (HOKS) on postural sway were examined in 30 normal subjects aged 20 to 75 years. Fixed-platform posturography was evaluated with the eyes open and closed and during HOKS (20-100 degrees/sec) in the rightward and leftward directions. Forward-backward sway was greater in amplitude than lateral sway under all viewing conditions. Sway amplitude was greater with eyes closed than with eyes open. HOKS significantly enhanced sway amplitude in both directions; however, significant differences occurred only between velocity extremes. Compared to younger subjects, older subjects showed greater forward-backward sway with eyes closed and greater lateral sway during HOKS. HOKS produces a visual cue that conflicts with the other two sensory signals regulating posture (vestibular and proprioceptive systems). Such conflicting visual cues may contribute to serious postural instability and falls in the elderly. The addition of optokinetic stimuli to fixed-platform posturography may enhance its diagnostic value.

Adult↗
PubMed1995

Glycogen metabolism in the rat visceral yolk sac. 2. Activity of glycogen-degrading enzymes.

In an attempt to explain the previous observation of the rise and subsequent fall in glycogen content of the rat visceral yolk sac during the latter half of gestation, the activities of glycogen phosphorylase, glucose-6-phosphatase and lysosomal alpha-glucosidase were measured. Glycogen phosphorylase was found to be present in the yolk sac and, as in adult rat liver, was predominantly in the 'a' (active) form. The specific activity of the enzyme was lower than in adult rat liver, when expressed per mg tissue protein or per mg tissue wet weight, but similar when expressed per mg tissue glycogen. Phosphorylase activity in yolk sac was similar at 16.5 and 18.5 days of gestation. Glucose-6-phosphatase activity was not detectable in the yolk sac at either 15.5 or 18.5 days of gestation. Two lysosomal enzymes, acid alpha-glucosidase and N-acetyl-beta-hexosaminidase, were shown to be present in the yolk sac at higher specific activity than in adult liver. Alpha-Glucosidase activity in yolk sac was similar at 15.5 and 18.5 days of gestation. It is concluded that the net degradation of yolk sac glycogen initiated around 18.5 days of gestation does not serve to provide glucose for the fetus, and may indicate an increased demand for metabolic energy within the yolk sac itself.

Animals↗
PubMed1992

Growth of Babesia bigemina parasites in suspension cultures for vaccine production.

An Australian Babesia bigemina vaccine strain was maintained in suspension culture for 40 days. Parasite growth was compared using two tissue-culture flask sizes (25 and 75 cm2), four gas mixes (2%, 2.5%, 3% and 3.5% O2; 5% CO2; and the balance N2) and four packed blood cell (PCV) volumes (7%, 9%, 13% and 18%). The best continuous parasite yields were obtained from suspension cultures in 75-cm2 flasks at a PCV of 13% and gas mixtures of 2%-3% O2, 5% CO2 and the balance N2. Parasite yields per millilitre of culture medium were 3 times those obtained in microaerophilous stationary-phase cultures. The method has thus far been used for 6 months to produce the Australian requirements for live B. bigemina vaccine.

Animals↗
PubMed1992

Neonatal Campylobacter fetus meningitis: a report of an unusual case.

Campylobacter fetus is a rare cause of meningitis in the pediatric age group and, in particular, among neonates. The clinical presentation of campylobacter meningitis in high-risk neonates is not well-described. A review of campylobacter meningitis by Lee et al in 1985 reported nine cases occurring in neonates, of which only one case was caused by C. fetus. In the ensuing six years only three more confirmed cases of neonatal meningitis caused by C. fetus have been reported. We here report another confirmed case of C. fetus meningitis in a neonate.

Campylobacter Infections↗
PubMed1991

HLA DQ alpha typing of forensic specimens by amplification restriction fragment polymorphism (ARFP) analysis.

The alleles present at the HLA DQ alpha locus may be typed by either allele specific oligonucleotide (ASO) probing or by restriction mapping, referred to here as amplification restriction fragment polymorphism (ARFP) analysis. ASO typing relies upon hybridization principles, whereas ARFP typing relies upon restriction site analysis. Dot-blot ASO typings which are of doubtful interpretation may be directly checked by ARFP analysis. Aliquots of the PCR products amplified using the commercial Amplitype HLA DQ alpha system are digested with suitable restriction endonucleases. Electrophoresis, blotting and detection of biotin-labelled restriction fragments provides a sensitive and robust typing method suited to forensic analysis.

Alleles↗
PubMed1989

Congenital atresia of the orifice of the left coronary artery and its main stem.

A 13-year-old black male who died suddenly as a result of atresia of the left coronary ostium and left main coronary artery is presented. An association between this anomaly and supravalvar aortic stenosis is observed. The literature is reviewed and 14 similar cases are compared. Presentation of this anomaly is variable, as is survival and may be attributed to the development of an adequate collateral circulation.

Adolescent↗
PubMed1988

Inflammatory joint disease: a comparison of liposome scanning, bone scanning, and radiography.

Patients with rheumatoid arthritis, psoriatic arthritis, and osteoarthritis were assessed by clinical evaluation, radiography, and joint scintigraphy using technetium labelled methylene diphosphonate (MDP) and technetium labelled liposomes. Although both scanning techniques were more sensitive than radiographs in detecting joint disease, the liposomes scans were positive only in clinically active inflammatory disease. In patients with rheumatoid arthritis liposome scintigraphy was also able to discriminate between different grades of joint tenderness. In inactive inflammatory polyarthropathies, although the MDP bone scans continued to show increased activity, the liposome scans did not and were therefore a more accurate reflection of the clinical state. The increased uptake in the liposome scans may be due to incorporation of the liposomes into the phagocytic cells of the synovium. This scan may, therefore, by reflecting the activity of cells involved in the disease process, provide a useful way of assessing disease activity and progression.

Arthritis↗
PubMed1987

Synovial accumulation of technetium labelled liposomes in rheumatoid arthritis.

Technetium labelled, negatively charged, unilamellar liposomes were given by intravenous injection to patients with rheumatoid arthritis and the joints scanned 20-22 hours later. Positive scintigraphy was obtained in all six patients with active disease, and, with the exception of the small interphalangeal joints, all clinically involved joints could be visualised.

Arthritis, Rheumatoid↗
PubMed1987

Ethanol-induced inhibition of pinocytosis and proteolysis in rat yolk sac in vitro.

Pinocytic capture of 125I-labelled polyvinylpyrrolidone and of formaldehyde-denatured 125I-labelled bovine serum albumin by 17.5-day rat visceral yolk sacs incubated in vitro was rapidly and strongly inhibited by low concentrations (0.01 and 0.05%, v/v) of ethanol. The induced inhibition of pinocytosis was readily reversible, but a marked lag was observed before ethanol-exposed tissue regained its full proteolytic capacity towards the exogenous protein. These observations suggest that the acute administration of ethanol to a pregnant rat may give rise to concentrations of ethanol in the maternal blood and/or uterine fluid that induce dysfunction of the yolk sac. In late gestation such inhibition of yolk-sac function may interfere with the transfer of passive immunity across the yolk sac. If similar dysfunction is induced earlier in gestation, in the period before the chorioallantoic placenta is functional, this could cause a transient period of inhibition of histiotrophic nutrition that may be important to the pathogenic mechanism of action of ethanol as a teratogen.

Animals↗
PubMed1986

The cDNA and protein sequence of a phenobarbital-induced chicken cytochrome P-450.

Several cDNA clones complementary to a chicken phenobarbital-inducible cytochrome P-450 have been isolated and sequenced, representing the first non-mammalian eukaryotic cytochrome P-450 sequence to be analyzed. The cDNA clones hybridized to two mRNAs of 3.5 and 2.5 kilobases in length, but further analysis indicated that the clones were derived from the larger mRNA. The sequence contains a 5'-noncoding region of 39 nucleotides and an open reading frame of 1473 nucleotides. The remainder of the sequence is due to the 3'-noncoding region and poly(A) tail. The open reading frame encodes a protein of 491 amino acids with a molecular weight of 56,196. The chicken cytochrome P-450 shows an overall homology of 45-54% compared with the mammalian phenobarbital-induced cytochrome P-450s. The degree of homology is not uniform, with some short regions showing much greater levels of sequence conservation. In particular, the chicken cytochrome P-450 contains the conserved cysteinyl domain near the carboxyl terminus, found in all cytochrome P-450s and which is thought to be involved in heme binding. Using the chicken sequence, a more accurate estimate of the evolutionary rates of cytochrome P-450s has been made. It is suggested that the phenobarbital-, 3-methylcholanthrene, and pregnenolone 16 alpha-carbonitrile-induced cytochrome P-450 gene families diverged from a common ancestral gene 600 million years ago. Furthermore the phenobarbital-inducible gene apparently underwent gene duplication events at about the time of the divergence of the chicken and mammalian lineages. The results imply that most mammals should have at least four rather distantly related phenobarbital-inducible gene subfamilies.

Allylisopropylacetamide↗
PubMed1983

The fate of homologous 125I-labelled immunoglobulin G within rat visceral yolk sacs incubated in vitro.

When 125I-labelled rat IgG (immunoglobulin G) is incubated in vitro with visceral yolk sacs from 17.5-day-pregnant rats, the protein is readily degraded. The major radioactive digestion product that accumulates in the medium is [125I]iodo-L-tyrosine. When rotenone (10 microM) is also present in the incubation medium, the rate of digestion of IgG is inhibited to the same extent as the rate of pinocytosis of 125I-labelled polyvinylpyrrolidone. Proteolysis is likewise inhibited when either NH4Cl (30 mM) or leupeptin (30 micrograms/ml) is present in the medium. The above findings strongly suggest that the observed proteolysis occurs within lysosomes. Normally, yolk sacs that have been exposed in vitro to radiolabelled substrates release radioactivity slowly when the tissue is re-incubated, unless the substrate can be degraded within lysosomes and released in the form of low-molecular-weight hydrolysis products. However, in such experiments 125I-labelled rat IgG shows quite exceptional behaviour in being rapidly released in an apparently intact form (as well as being degraded). If an agent that inhibits pinocytosis (e.g. rotenone or 2,4-dinitrophenol) is present in the incubation medium during exposure of the tissue to 125I-labelled rat IgG, it abolishes release of macromolecular radioactivity on re-incubation of the tissue. Enhanced tissue accumulation of 125I-labelled rat IgG, induced by the presence of leupeptin in the medium during the uptake phase, resulted in no concomitant increase in the amount of 125I-labelled IgG released in macromolecular form on re-incubation of the tissue. These findings indicate that the observed rapid release of 125I-labelled IgG is unlikely to represent release from lysosomes and is more compatible with release from a separate class of vesicle that does not fuse with lysosomes.

2,4-Dinitrophenol↗
PubMed1983

Inter-observer variation in the histopathological reporting of Hodgkin's disease: an analysis of diagnostic subcomponents using kappa statistics.

Levels of agreement between nine pathologists on the Rye classification of Hodgkin's disease and on diagnostic subcomponents used in applying the classification, were analysed by kappa statistics. Pathologists experienced comparatively little difficulty in agreeing on the presence of nodules and lacunar cells and hence best agreement was achieved on the nodular sclerosis category. Poorer agreement levels on the lymphocytic predominance, mixed cellularity and lymphocytic depletion categories were explained mainly by problems in the assessment of numbers of lymphocytes and abnormal reticulum cells other than Reed-Sternberg cells. Identification of the Reed-Sternberg cell, although of paramount importance to a diagnosis of Hodgkin's disease, appeared to have no great practical relevance to use of the Rye classification in this series of cases.

Cell Count↗