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Biomedical subjects

W G Murrell

Publications and source records attributed to W G Murrell.

At least 19 recordsLinked to original sources

Isolation and characterisation of a chick cDNA encoding the RNA polymerase common subunit RPB6.

The RPB6 cDNA of chicken, encoding one of the small subunits common to all three nuclear DNA-dependent RNA polymerases, has been isolated from an expression cDNA library by screening with a differential display derived probe, representing a gene shown to be highly up-regulated in early heart development. The nucleotide sequence of the cDNA isolated predicts a protein sequence of 127 amino acids. This sequence shares 124 amino acids (98% homology) with the human RNA polymerase II subunit 14.4 kDa (RPB6) and hamster hRPB6 and 123 amino acids (97% homology) with Rattus norvegicus RNA polymerase II subunit RPB6. Other conserved motifs in this protein and potential functions of RPB6 are discussed.

Amino Acid Sequence↗

Immunological evidence for a bacterial toxin aetiology in sudden infant death syndrome.

Toxin-specific antibodies to clostridial, enterobacterial and staphylococcal toxins implicated in sudden infant death syndrome were studied in sera from sudden infant death syndrome infants and a comparison group of infants (babies with phenylketonuria). The results indicated a higher proportion of sera from sudden infant death syndrome infants contained IgA that bound to clostridial and enterobacterial toxins but a higher proportion of sera from the phenylketonuria comparison group contained IgA that bound staphylococcal toxins. The higher proportion of serum samples with IgG and IgM in the healthy comparison babies serum probably indicated immunity in this group of babies to these toxins. The effect of gender and age had a minimal effect on the incidence of these antibodies. The presence of toxin-specific antibodies in sudden infant death syndrome and the of comparison infants suggests that all infants are exposed to these toxins and most babies successfully overcome the toxic challenge. Some infants with predisposing risk factors (temperature change, smoking, infection, immune development, sleeping position, etc.) that could affect the baby's immune competency could succumb to these and possibly other toxins. This immunological evidence further strengthens the view that bacterial toxins are a significant cause of sudden infant death syndrome.

Age Distribution↗

The effect of enteric bacterial toxins on the catecholamine levels of the rabbit.

The rabbit catecholamine responses to bacterial toxins commonly found in Sudden Infant Death Syndrome (SIDS) victims were studied as part of a proposed animal model for SIDS. Six bacterial toxins commonly isolated from SIDS baby feces and a comparison endotoxin were injected intravenously (i.v.) and intraluminarily (i.l.) to determine their effects on catecholamine levels. I.v. injected toxins clearly altered catecholamine levels causing sharp rises in adrenaline and noradrenaline levels and at critical toxin concentrations sudden death ensued. Clostridium perfringens enterotoxin and alpha-toxin, Clostridium difficile enterotoxin (A) and cytotoxin (B), Escherichia coli STa toxin and staphylococcal enterotoxin B caused rises in catecholamine levels similar to that caused by E. coli endotoxin. Control rabbits showed very little or no obvious change in catecholamine levels. Clostridium difficile enterotoxin (A) and cytotoxin (B) injected i.v. exhibited synergy. Toxins injected into the duodenum, jejunum, ileum, cecum and large intestine caused behavioural changes ranging from reduced appetite and diarrhea to, in rare cases, death. Changes in the catecholamine levels of these animals however were not significantly different from those of the control animals. The results are discussed in relation to the possible effect of certain conditions (physiological, viral infections and environmental) which increase toxin permeability and allow absorption of these toxins, possibly resulting in sudden infant death.

Animals↗

FGF2 promotes neuronal differentiation in explant cultures of adult and embryonic mouse olfactory epithelium.

Neurogenesis in the adult olfactory epithelium is highly regulated in vivo. Little is known of the molecular signals which control this process, although contact with the olfactory bulb or with astrocytes has been implicated. Explants of mouse olfactory epithelium were grown in the presence or absence of several peptide growth factors. Basic fibroblast growth factor (FGF2) stimulated differentiation of sensory neurons in adult and embryonic olfactory epithelium. Other growth factors tested were ineffective. FGF2-stimulated neurons were born in vitro and expressed neurofilament, neural cell adhesion molecule, and beta-tubulin. The cells also expressed olfactory marker protein, a marker for mature olfactory sensory neurons in vivo. These bipolar neurons did not express glial fibrillary acidic protein or low-affinity nerve growth factor receptor. These results indicate that neither astrocytes nor olfactory bulb are necessary for differentiation of olfactory sensory neurons in vitro.

Animals↗

Chromatin structure and the expression of cardiac genes.

Actively transcribed genes are more susceptible to nuclease digestion, an observation suggested to reflect an altered state of chromatin organization. It has been hypothesized that exposure or sequestration of chromatin domains is a higher order gene regulatory mechanism. In order to test whether tissue lineage is organized by mechanisms at the level or chromatin structure, three cardiac phenotype-conferring genes (atrial natriuretic factor, myosin light chain-1-ventricular and alpha-tropomyosin) have been assessed for DNase 1 sensitivity in nuclei prepared from tissues of the developing guinea pig. These data have been related to the level of tissue mRNA expression of these genes to ascertain whether the exposed state of genes can occur when transcription is low or undetectable. Although this phenomenon was evident in some cases, the data were not consistent with mechanisms at the level of chromatin structure directing tissue type.

Aging↗

Is cardiorespiratory failure induced by bacterial toxins the cause of sudden infant death syndrome? Studies with an animal model (the rabbit).

Recent studies have implicated various toxigenic bacteria and their toxins in the aetiology of sudden infant death syndrome (SIDS). Therefore the effect of six bacterial toxins on the cardiorespiratory system of the rabbit was studied as a model for SIDS. The toxins' effect on the heart rate, arterial blood pressure, and breathing of anaesthetized rabbits was determined and their action compared to that of endotoxin. Intravenous injection of Clostridium perfringens enterotoxin and alpha-toxin, Staphylococcus enterotoxin B, Escherichia coli heat-stable toxin (STa), Clostridium difficile toxin A and B reduced heart rate, blood pressure, respiration and increased, slowed and prolonged thorax expansion, and at higher concentrations caused sudden death without visible stress or trauma. A combination of a low concentration of enterotoxins caused a greater reduction of these activities and sudden death. These effects were generally similar to those produced by endotoxin. In non-anaesthetized rabbits, the toxins slowed metabolism until death occurred without agitation, spasms, visible distress or prolonged illness. Intestinal production of these toxins by toxigenic strains, when conditions are suitable, and their systemic absorption, could therefore cause SIDS by an endotoxin-like shock mechanism.

Animals↗

On the ontogeny of cardiac gene transcripts.

As a prerequisite to investigating the specification and differentiation of cardiac tissue in vitro, the ontogeny of a number of putative cardiac-specific, and striated muscle-specific gene transcripts has been studied. The probes used include cDNAs of alpha-actins, myosin heavy chains, myosin light chains, alpha-tropomyosin, troponin-T and atrial natriuretic factor. The expression of these genes was monitored by Northern analysis of heart and various other tissues at three developmental ages, viz, adult, neonatal and mid-foetal. The aim of this exercise was to confirm the efficacy of a number of markers to represent a cardiac-specific subset of gene expression in our mammalian model, the guinea pig. Our results indicate predominantly cardiac expression for the mRNA transcripts of cardiac alpha-actin (c alpha-actin), cardiac myosin heavy chain-alpha (MHC alpha), cardiac myosin heavy chain-beta (MHC beta), myosin light chain-1A (MLC1A), myosin light chain-1V (MLC1V), alpha-tropomyosin (alpha TM), cardiac troponin-T (cTnT) and atrial natriuretic factor (ANF). Furthermore, cardiac-specific expression at the midfoetal time point was observed for five gene transcripts, MLC1V, MHC alpha, MHC beta, striated alpha TM and ANF. No genes were expressed exclusively in cardiac tissue; for example, expression of the genes for c alpha-actin, both cardiac MHCs, both MLCs, alpha TM and cTnT was evident in skeletal and vascular smooth muscles at some stages of development. An interesting difference between this species and those of previous studies was the minor contribution of skeletal alpha-actin to cardiac phenotype.(ABSTRACT TRUNCATED AT 250 WORDS)

Actins↗

Sudden infant death syndrome (SIDS): are common bacterial toxins responsible, and do they have a vaccine potential?

Despite extensive research, no unifying concept has satisfactorily explained the cause of the sudden infant death syndrome (SIDS). The details are briefly outlined of some of the evidence supporting the hypothesis that common bacterial toxins are important in the aetiology of SIDS. These bacterial toxins act as triggers to initiate a biochemical cascade resulting in death. Data from four research groups, each working independently, indicated that the bacteria Clostridium perfringens, Escherichia coli, Staphylococcus aureus, Streptococcus spp. and Enterococcus spp. were present in higher numbers in infants who had suffered SIDS than in control infants. Certainly more detailed studies need to be performed on the role of bacterial infections in infants. There are many implications arising from this work, particularly the use of vaccination as a means of reducing infections, and consequently the number of SIDS deaths.

Bacterial Toxins↗

Effect of ambient temperature on SIDS rate.

OBJECTIVE: To examine the relationship between ambient temperature and rate of sudden infant death syndrome (SIDS). SUBJECTS AND SETTING: All infants with SIDS occurring during 1980-1989 in the Sydney metropolitan area. RESULTS: The SIDS rate varied more than threefold over the months of the year and peaked at the minimum daily temperature in July. The rate was negatively linearly related to both the monthly mean minimum and maximum daily temperatures. Both relationships were highly significant (P < 0.001). CONCLUSION: The significant relationship between daily temperature and SIDS rate means either that daily temperature is an excellent indicator of the cold weather conditions that have a profound effect on the rate of SIDS or that temperature itself plays a direct role in the cause of SIDS.

Cold Temperature↗

Enterotoxigenic bacteria in the sudden infant death syndrome.

Faecal samples from 123 infants who died with sudden infant death syndrome (SIDS) and from a comparative group of 52 age-matched babies were analysed for toxigenic bacteria and their toxins. Serum samples from the SIDS infants were also analysed for these toxins. A significantly higher proportion of toxigenic bacteria and their toxins were found in faecal samples of SIDS babies than in samples from the comparative group. These toxins were also found in serum from the SIDS babies. Clostridium perfringens was found in 54 (45.4%) of 119 SIDS cases compared with 10 (19.6%) of 51 healthy babies (chi 2 = 10.1, p < 0.01); C. difficile in 33 (27.7%) of 119 SIDS cases compared with 8 (14.8%) of 54 healthy babies (chi 2 = 3.43ns, p < 0.1); Staphylococcus aureus in 12 (27.3%; 66.7% enterotoxigenic) of 44 SIDS cases compared with 12 (85.7%; non-enterotoxigenic) of 14 healthy babies (chi 2 = 14.9, p < 0.001); C. botulinum in 6 (5.0%) of 120 SIDS cases compared with 0 of 53 healthy babies (chi 2 = 2.74, p < 0.1). Campylobacter jejuni, Yersinia enterocolitica, Vibrio parahaemolyticus, salmonellae and Bacillus cereus were not detected. Heat-labile toxin, lethal to mice (HLML) was found in 32 (27.1%) of 118 SIDS faecal samples compared with 5 (10.6%) of 47 healthy babies (chi 2 = 5.24, p < 0.05); cytotoxins in 38 (30.9%) of 123 SIDS faecal samples compared with 0 of 21 of healthy babies (chi 2 = 8.8, p < 0.01) and 24 (27.6%) of 87 SIDS serum samples. C. perfringens enterotoxin was detected in 33 (34.4%) of 96 SIDS faecal extracts compared with 0 of 23 of healthy babies (chi 2 = 10.94, p < 0.001), and in 27 (24.5%) of 110 SIDS serum samples. C. perfringens alpha-toxin (presumptive) was detected in 14 (17.5%) of 80 SIDS faecal extracts compared with 0 of 17 from healthy babies (chi 2 = 3.5ns, p congruent to 0.05) and in 2 (2.3%) of 87 SIDS serum samples. C. difficile toxin was detected in four SIDS faecal samples and two serum samples. C. botulinum toxin was detected in only one of 120 SIDS faecal samples compared with none of 49 from healthy babies. Staphylococcal enterotoxins were detected in 8 (19.5%) of 41 SIDS faecal samples compared with 0 of 19 from healthy babies (chi 2 = 4.278, p < 0.05), and in 4 (10.8%) of 37 SIDS serum samples.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

An epidemiological survey of SIDS in the Sydney metropolitan area.

Records of 1049 cases of Sudden Infant Death Syndrome (SIDS) (100%) in the Sydney metropolitan area (SMA) from 1980 to 1989 were analysed in relation to ambient temperature, geographical distribution and socio-economic scale. The SIDS rate varied between eastern and western Sydney and between statistical subdivisions; it peaked sharply in July, coinciding with the monthly mean minimum daily temperature (MMMDT; 6.5 and 5.4 degrees C, respectively). The inverse linear relationship between the SIDS rate and the MMMDT for the regions and the subdivisions was highly significant (P < 0.001). The SIDS rate showed a significant inverse linear relationship to two socio-economic scales (allotment and house value) for 82 of the 87 suburbs (94%) of the SMA. Temperature, indicative of cold weather, was the major factor determining SIDS rates, and this, together with socio-economic factors, largely explains the observed geographical distribution of SIDS rates in the SMA.

Cold Temperature↗

A comparison of UV induced DNA photoproducts from isolated and non-isolated developing bacterial forespores.

UV-induced photoproduct formation has been compared in non-isolated and isolated developing forespores. We have found that levels of spore type photoproducts are greatly affected by mother cell DNA. We have also observed the presence of the photoproduct 6-4'-(pyrimidin-2'-one)-thymine in developing forespores. We conclude from these and other data in the literature that the degree of hydration around the forespore DNA is reduced by the presence of dipicolinic acid which influences photoproduct formation without causing a change in conformational state.

Bacillus megaterium↗

A method for the isolation of intact, viable forespores from Bacillus species using high pressure.

Large-scale preparation of Bacillus forespores was performed using nitrogen gas under high pressure to force an osmotically stable spheroplast suspension through a micrometer needle valve. Ninety-nine percent recovery of intact viable forespores at various stages of sporulation was achieved with a variety of Bacillus species. The isolated forespores are stable for up to 7 days when kept under nongerminating conditions.

Bacillus↗

Botulism in New South Wales, 1980-1981.

The isolation of Clostridium botulinum from the home environment of New South Wales patients with infant botulism is reported. Of the three cases of infant botulism type B, the bacteria were isolated from soil around the dwelling in one, and from tank rainwater in another. In one case with type A, the bacteria were present in the soil, vacuum-cleaner dust, and tank rainwater. The bacteria were not detected in the environment of two adult patients and a child with C. botulinum in their stools. The home location of the patients with infant botulism, and the frequency of isolation of the bacteria from rainwater, soil and vacuum-cleaner dust in Cobar, Nyngan, some Sydney suburbs, and at five pastoral homesteads suggest that infants in rural areas are more at risk than those in large metropolitan areas. The age of the infants with diagnosed botulism in New South Wales, compared with those reported in the United States data, strongly suggests that the disease is not being fully recognised in younger infants.

Aged↗

Type C botulism in young dogs.

A diffuse lower motor neurone paralysis developed in a 6-month-old male Australian cattle dog pup 4 days after it had eaten the carcase of a rotting duck in Centennial Park, Sydney. Two other dogs which ate smaller portions of the same carcase were less severely affected. Clostridium botulinum type C was isolated from and C. botulinum type C toxin was detected in faeces from the severely affected dog. The serum contained 25 LD50 of toxin/ml. The high C. botulinum count and toxin level in the faeces declined progressively during the ensuing weeks, but 114 days after ingesting the carcase C. botulinum type C was still present in faeces and a low toxin titre persisted. Soil, mud and water samples in the area of the duck ponds in the park contained C. botulinum type C spores. Spores and high toxin titres were also found in the intestine of the carcases of 2 birds in the area.

Animals↗

Scanning electron probe x-ray microanalysis of elemental distributions in freeze-dried cryosections of Bacillus coagulans spores.

High-resolution scanning electron probe X-ray microanalysis had been employed to examine elemental distributions in freeze-dried cryosections of Bacillus coagulans spores. Calcium, manganese, and phosphorus were concentrated in the protoplast and the coat. Iron was found in the coat but not in the protoplast, whereas the silicon seen on the coat of other spore species was absent. Sulfur was present in the coat, but was distributed over a broader area than the other elements, which suggested that phosphorus and the metal ions were located in the outer coat layer.

Bacillus↗