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Biomedical subjects

A J Lawrence

Publications and source records attributed to A J Lawrence.

At least 109 records · Page 6Linked to original sources
PubMed1994

Dispersive locomotion of human neutrophils in response to a steroid-induced factor from monocytes.

A monocyte-derived factor that stimulates the locomotion of human neutrophils on an albumin-coated glass surface has been prepared from the culture supernatant of dexamethasone-treated human monocytes and called STMS (steroid-treated monocyte supernatant). A modified cell tracking program has been developed and the parameters of locomotion determined by the analysis of Gail and Boone for cells moving in a persistent random walk. Cells moving in uniform concentrations of STMS, interleukin-8 (IL-8) and N-formyl-methionyl-leucyl-phenylalanine (fMLP) chosen to give a sub-maximal speed of locomotion show persistent, random and constrained random diffusion, respectively, with augmented diffusion coefficients of 0.8 +/- 0.1, 0.14 +/- 0.02 and 0.12 +/- 0.03 microns 2 per second for STMS, IL-8 and fMLP, respectively. The augmented diffusion coefficient and the underlying persistence are therefore sensitive quantitative assay parameters for STMS activity and the qualitative characteristics of locomotion allow STMS activity to be distinguished from that of all other factors tested. The contribution of lowered adhesion to locomotion was examined in a novel tilt-assay, which demonstrated that cells in the presence of STMS, but not other factors, moved down slope with significantly increased speed while maintaining contact with the substratum. The results were interpreted in terms of the bipolar form of STMS-treated cells, contrasting with multipolar forms in response to other agents. This together with low adhesiveness plus an inherent tendency of a single locomotor focus to continue motion in its original direction has been used to explain the difference between response to STMS and other factors.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Adhesion↗
PubMed1994

Workforce predictions: a situational analysis and critique of the World Health Organisation model.

The FDI/WHO JWG6 Computer Program is a needs-based, demand-weighted method of workforce prediction. Using this program and recent Victorian epidemiological data the objectives of the investigation were: to calculate the current state of community need for dental services and personnel in the State of Victoria; to forecast community service and personnel needs for the years 2000 and 2020; and to report qualitatively on the program's value as a workforce planning tool. High, low and moderate estimates of workforce requirements for the year 1988 were obtained by modifying certain variables related to needs/demands. The moderate estimate was used to calculate the number of operators needed within the population, and this demonstrated a required operator to population ratio of 1:2,019. Results for the year 2000 predicted the operator to population ratio required in Victoria will be 1:1,988 and for the year 2020, 1:2,165. Conclusions concerning the WHO program are firstly that it suggests a present under-supply of oral health care providers which is likely to increase by the year 2020 and secondly that it is a useful tool for workforce planning and monitoring.

Adolescent↗
PubMed1993

Nitric oxide increases interstitial excitatory amino acid release in the rat dorsomedial medulla oblongata.

In vivo microdialysis was employed to measure release of the neuroactive amino acids L-glutamate (Glu) and L-aspartate (Asp) in the dorsomedial medulla oblongata of the anaesthetised rat. Basal levels of endogenous extracellular Glu and Asp were increased over 5-fold and 3-fold, respectively, following perfusion with a depolarising stimulus of KCl. Intracerebral administration of the nitric oxide (NO) donor S-nitroso-N-acetylpenicillamine (SNAP, 30 microM) caused a 5-fold increase in extracellular Asp and a 2-fold increase in extracellular Glu, which was blocked by Methylene blue. These data suggest that NO, acting through guanylate cyclase, can affect excitatory amino acid neurotransmission in the dorsomedial medulla oblongata.

Amino Acids↗
PubMed1993

Purification and activation of phospholipase A2 isoforms from Naja mossambica mossambica (spitting cobra) venom.

Isoforms of phospholipase A2 (PLA2) from the venom of Naja mossambica mossambica (the spitting cobra) were purified by a combination of gel filtration on Bio-gel P-30 and ion exchange chromatography on DE-52 Cellulose and the purification followed by three types of polyacrylamide gel electrophoresis. SDS PAGE failed to resolve the active band into separate isoforms. Acid/urea PAGE, resolved the peptides and major protein components of the venom and was able to separate two PLA2 bands in the whole venom. Alkali/urea PAGE resolved four PLA2 bands in whole venom, but could resolve six distinct purified PLA2 species. Of the known isoforms, the acidic form (CM-1) was purified to homogeneity. The basic non-toxic isoform (CM-II) was shown to migrate as a close doublet of PLA2 isoforms. A novel minor purified isoform was identified with mobility intermediate between CM-I and the basic non-toxic isoform CM-II. CM-III was shown to contain a minor PLA2 contaminant. The analysis was facilitated by the fact that all of the isoforms could be eluted from the gels with > 60% recovery of activity. The venom therefore contains at least six isoforms of PLA2 which differ largely by their content of acidic acids. Oleoyl imidazolide treatment increased the haemolytic activity of all but the toxic PLA2 isoform in Naja mossambica mossambica, but partially inhibited the catalytic activity of acidic, toxic and newly purified isoforms whilst partially activating the non-toxic isoform.

Amino Acid Sequence↗
PubMed1993

A factor released by monocytes in the presence of dexamethasone stimulates neutrophil locomotion.

1. Steroid-treated monocyte supernatants cause a dramatic increase in the speed of locomotion of human neutrophils and a significant decrease in their adhesion to protein-coated glass. In contrast, control monocyte supernatants have a smaller effect on the speed of locomotion, but cause a large increase in their adhesiveness. 2. This supernatant activity was produced equally well in the presence or absence of serum after 24 h culture at 37 degrees C with 10(-6) M dexamethasone. 3. The effect of the steroid-treated monocyte supernatants on the speed of locomotion of human peripheral blood neutrophils was not altered by rabbit polyclonal antisera against lipocortins 1-6. 4. Rabbit anti-interleukin-8 antibody which blocked the effect of IL-8 on the speed of locomotion of neutrophils did not antagonize the locomotion stimulating action of steroid-treated monocyte supernatants. 5. The exocellular release of this factor(s) by human mononuclear leucocytes suggests that it may be an in vivo mediator of the anti-inflammatory effect of glucocorticoids.

Annexins↗
PubMed1993

Liposome-encapsulated gentamicin treatment of Mycobacterium avium-Mycobacterium intracellulare complex bacteremia in AIDS patients.

TLC G-65, a liposome-encapsulated gentamicin, was given intravenously twice weekly for 4 weeks to AIDS patients with Mycobacterium avium-M. intracellulare complex (MAC) bacteremia at 1.7 mg of gentamicin per kg of body weight per infusion (4 patients), 3.4 mg/kg (10 patients), and 5.1 mg/kg (7 patients). MAC colony counts in blood fell by 75% or more in all three groups (P < 0.005). Drug resistance did not emerge during the study period. Transient renal insufficiency developed in one patient; no other adverse effects were detected. Liposome-encapsulated gentamicin is a potential therapy for MAC infections in AIDS patients.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Differential inhibition of hepatic morphine UDP-glucuronosyltransferases by metal ions.

The major metabolites of morphine, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G), possess significant pharmacological properties. Whilst both metabolites bind to mu-opioid binding sites, M6G is a potent agonist whereas M3G antagonizes some of the effects of morphine and M6G. An inter-species comparison of in vitro hepatic morphine processing was performed. The results showed that not all species were able to produce M6G whereas all those tested did produce M3G. Guinea-pig liver produced the greatest amounts of M6G and was therefore chosen as a model to study morphine glucuronidation in further detail. Inclusion of the detergent Brij 58 (0.33 mg/mg protein) and Mg2+ (15 mM) in the standard assay incubation gave optimal production of both M3G and M6G by guinea-pig liver homogenates. A number of metal ions were investigated for their ability to inhibit glucuronidation of morphine in both the 3- and 6-positions. Some metal ions, namely Cu+, Cu2+ and Cd2+, were able to inhibit the production of M3G without affecting glucuronidation at the 6-position. Taken together, these data provide further evidence for the existence of UDP-glucuronosyltransferase isoenzymes responsible for the metabolism of morphine. In addition these isoenzymes can be differentially modulated and therefore it is possible to alter the ratio of M3G:M6G formed during in vitro metabolic studies.

Animals↗
PubMed1992

Evidence for analgesia mediated by peripheral opioid receptors in inflamed synovial tissue.

Intra-articular morphine (5 mg in 25 ml) was administered to patients for post-operative analgesia following arthroscopic knee surgery. At various time intervals, 30 min to 4 h post morphine, venous blood samples were taken in order to determine plasma levels of morphine and its primary metabolites, morphine-3-glucuronide and morphine-6-glucuronide. Measurable amounts of morphine and morphine-3-glucuronide were found in the plasma of 7/10 patients whereas morphine-6-glucuronide was detected in only 2/10 patients. The plasma levels of morphine were lower than that regarded sufficient for post-operative analgesia in all but two patients, indicating a possibility of peripheral analgesia. In addition, synovial biopsy samples were assayed for the presence of opioid binding sites. Tissue samples from 11 different patients were analysed and 6/11 exhibited specific binding of [3H]naloxone, indicating the presence of opioid binding sites/receptors. The receptor type (i.e. mu-, delta- or k-) is at present unknown. Taken together, these data provide evidence that locally administered opiates can act on specific opioid receptors in the synovium to mediate analgesia.

Adult↗
PubMed1992

Attenuation of chemically induced defence response by 5-HT1 receptor agonists administered into the periaqueductal gray.

The ability of 5-HT1 receptor agonists to modulate a chemically induced defence response has been studied in Lister hooded rats. Microinjections of the excitatory amino acid D,L-homocysteic acid (DLH) in both rostral and caudal dorsal periaqueductal gray matter (PAG) caused explosive motor behaviour characteristic of defence. This behaviour was quantified in terms of response duration, arena revolutions and number of defensive jumps. Direct administration into the PAG of either 5-carboxamidotryptamine (5-CT) or 8-hydroxy-2-(di-n-propylamino) tetralin (8-OHDPAT) produced behaviours (decreased exploratory rearing, dose related onset of flat body posture) indicative of 5-HT1A receptor activation. Pretreatment with either 5-CT or 8-OHDPAT directly in the PAG caused a significant attenuation, and in some cases a complete abolition, of the DLH evoked response. These agonists share high affinity in vitro for the 5-HT1A receptor. Thus the results suggest that in vivo activation of 5-HT1A receptors mediates an antiaversive response with respect to defensive behaviour elicited by specific chemical stimulation of the dorsal PAG.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1992

Clostridium botulinum and sudden infant death syndrome: a 10 year prospective study.

It has been proposed that sudden and unexpected death in infants due to intestinal infection with Clostridium botulinum may mimic the clinicopathological features of sudden infant death syndrome. Between 3.3 and 3.8% of infants in some series have had this neurotoxin-producing bacterium isolated on faecal culture. Prospective screening of 248 infants presenting with the sudden infant death syndrome to the Adelaide Children's Hospital over a 10 year period from 1981 to 1990 was conducted. Faecal samples were obtained from both small and large intestines and cultured specifically for C. botulinum. No samples were positive. The results of this study suggest that routine post-mortem culture of faeces for C. botulinum has been of limited use within the South Australian infant population over the last decade, and that occult botulism has not been a significant factor in the causation of sudden death.

Botulism↗
PubMed1992

Terminal autoreceptor control of 5-hydroxytryptamine release as measured by in vivo microdialysis in the conscious guinea-pig.

In vivo microdialysis in the frontal cortex of the freely moving guinea-pig was used to measure extracellular 5-hydroxytryptamine (5-HT) and study terminal autoreceptor control of its release. The indoleamine levels were determined by HPLC with electrochemical detection. Release of extracellular 5-HT and, to a lesser extent, 5-hydroxyindoleacetic acid was sensitive to tetrodotoxin, confirming the neuronal origin of measured neurotransmitter levels. Both systemic and local administration of the 5-HT1 agonist 5-carboxamidotryptamine caused inhibition of extracellular 5-HT levels, confirming the regulatory role of the terminal, and possibly also the somatodendritic, 5-HT autoreceptor on neuronal 5-HT release. Levels of extracellular 5-hydroxyindoleacetic acid were not affected by 5-carboxamidotryptamine following either central or peripheral administration.

Animals↗
PubMed1992

Rapid detection of respiratory syncytial virus in nasopharyngeal aspirates by reverse transcription and polymerase chain reaction amplification.

A rapid method for detection of respiratory syncytial virus (RSV) in nasopharyngeal aspirates, involving a combination of reverse transcription and polymerase chain reaction amplification (RT-PCR), has been developed. The RT-PCR assay employs oligonucleotide primers specific for the region of the RSV genome which encodes the F1 subunit of the fusion (F) glycoprotein. Other respiratory viruses do not give a positive reaction. The RT-PCR assay was tested on 202 nasopharyngeal aspirates collected from children with clinical signs of respiratory infection, and the results from RT-PCR were compared with those obtained from virus culture and direct detection by enzyme immunoassay (EIA). RT-PCR results were positive in 118 of 125 samples from which RSV was cultured, as well as in 4 of 7 samples which were culture negative but EIA positive. RT-PCR results were negative in 68 of 70 culture-negative, EIA-negative samples, which included 11 samples from which other respiratory viruses were isolated. The speed, sensitivity (94.6%), and specificity (greater than 97%) of the RT-PCR assay suggest that this technique could be useful for rapid detection of RSV in clinical samples.

Base Sequence↗
PubMed1992

Intra-articular morphine for pain relief after knee arthroscopy.

We performed a randomised double-blind controlled study in patients undergoing elective knee arthroscopy to assess the effect of intra-articular morphine on postoperative pain relief. Patients in the study group (n = 10) received 5 mg of morphine in a 25 ml dilution intra-articularly while those in the control group (n = 10) received 25 ml of saline. Postoperative pain was assessed at intervals by a visual analogue scale and the requirement for supplementary analgesia was recorded. Those in the study group had significantly lower pain scores and required less systemic analgesics than those in the control group. Plasma profiles for morphine and its metabolites were assayed and showed that they were too low to produce effective analgesia. Evidence suggests that analgesia was mediated by local action within the joint.

Anesthesia Recovery Period↗
PubMed1990

Rapid activation of the non-toxic basic isoform of phospholipase A2 from Naja mossambica mossambica (spitting cobra) by long-chain fatty acylation.

Purified phospholipase A2 from Naja naja (common Indian cobra) venom, a basic non-toxic isoform and a toxic isoform from Naja mossambica mossambica venom were treated with an equimolar amount of oleoyl imidazolide, a known activator of bee venom phospholipase A2. The ability of the first two enzymes to induce erythrocyte lysis was strongly activated while hydrolysis of dioctanoyl phosphatidyl choline was only weakly activated. The toxic enzyme showed little change in either assay. The susceptible enzyme from Naja mossambica mossambica venom reacted very much more rapidly with oleoyl imidazolide than did the bee venom enzyme and oleic acid was shown to be a relatively weak antagonist. Activation had very little effect on the metal ion dependence of these enzymes. Although activation was a progressive response having the characteristics of a chemical reaction which could not be mimicked by free fatty acids, the adduct did not appear to be stable under acidic conditions. This evidence suggested that primary amino groups were not the target for acylation.

Acylation↗
PubMed1990

The selectivity of the opioid antagonist, naltrindole, for delta-opioid receptors.

In the mouse vas deferens, naltrindole gave pKB values of 9.7, 8.3, and 7.5 at the delta-, mu-, and kappa-sites and in binding assays, pIC50 values of 9.6, 7.8 and 7.2 at the same sites. The affinity of naltrindole for the delta binding site was increased in the presence of sodium ions and 5'-guanylylimidophosphate. Naltrindole is, thus, a potent opioid antagonist with marked selectivity for the delta-opioid receptor.

Animals↗
PubMed1990

Analysis of a repetitive DNA sequence from Bordetella pertussis and its application to the diagnosis of pertussis using the polymerase chain reaction.

A tandemly repeated 1,046-base-pair (bp) ClaI DNA fragment from Bordetella pertussis was cloned into Escherichia coli by using the vector pUC19. This fragment, when isolated, hybridized strongly to DNA from all 100 clinical isolates of B. pertussis tested. It was shown to have homology to single-copy sequences in Bordetella bronchiseptica but not Bordetella parapertussis and did not hybridize to lysate blots of a wide range of other bacteria, including members of the closely related genera Pasteurella, Alcaligenes, and Haemophilus. The 1,046-bp fragment was sequenced, and complementary synthetic oligonucleotides flanking a 153-bp region within the repeated element were used as primers for specific amplification of this region using the polymerase chain reaction (PCR). This procedure was then applied to the rapid (5-h) detection of B. pertussis in nasopharyngeal secretions collected from 332 children with suspected pertussis. The test yielded positive results in a total of 98 samples, compared with 66 for culture and 33 for direct immunofluorescence (IF). All of the IF-positive samples were PCR positive, as were 63 of the samples from which B. pertussis was eventually cultured. Two hundred thirty-one specimens which were negative by IF and culture were also negative in the PCR assay. However, 33 culture- and IF-negative specimens were positive by PCR assay. Several of these specimens were collected from close contacts of culture-proven pertussis patients, were follow-up specimens from such patients, or were from patients with serological evidence of pertussis and therefore may be true-rather than false-positives.

Base Sequence↗