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Biomedical subjects

P Dobson

Publications and source records attributed to P Dobson.

At least 37 records · Page 2Linked to original sources
PubMed1986

Arthroscopic synovectomy: a prospective study.

Seven patients undergoing arthroscopic synovectomy for painful knee joint synovitis with marked synovial swelling were assessed preoperatively and up to 24 months postoperatively. Six patients had rheumatoid arthritis and one psoriatic arthritis. Patients were assessed for overall disease activity and indices of synovitis and function of the knees. There was minimal or no loss of function in the operated knee at one month. Subsequent improvement was reflected in reduction of pain on walking, pain on using steps, and swelling of the knee, with improvement occurring up to 6 months and maintained at 24 months. No sustained loss of movement was observed in the operated knee and all patients had improvement in knee flexion at 24 months. Patients universally regarded the procedure as worthwhile. These results highlight the lesser morbidity of arthroscopic synovectomy compared to that known to be associated with open synovectomy. Further study is required to evaluate the longterm value of this procedure.

Adult↗
PubMed1984

Discriminative effect of gamma-glutamyl transpeptidase inhibitors on metabolism of leukotriene C4 in peritoneal cells.

Leukotrienes are naturally-occurring metabolites of arachidonic acid that are formed via the 5-lipoxygenase pathway in several tissues. Rat peritoneal cells (RPC) can produce leukotrienes C4, D4 and E4 (LTC4, LTD4 and LTE4) in response to stimulation with the calcium ionophore A23187 (1,2). The mechanism of enzymatic conversion of LTC4 to LTD4 is presumed to be via the action of gamma-glutamyl transpeptidase (gamma-GTPase, Figure 1) and has been demonstrated with purified enzymes from rat and porcine kidneys (3-6). We report that RPC contain gamma-GTPase-like activity that catalyzes the liberation of p-Nitroaniline (p-NA) from the chromophoric substrate gamma-glutamyl-p-nitroanilide (gamma-GpNA) in the presence of the acceptor molecules glycylglycine and L-cysteine. Furthermore, we demonstrate that under similar conditions, this preparation catalyzes the conversion of LTC4 to LTD4. Activity with gamma-GpNA is inhibited by D,L-gamma-glutamyl(o-carboxy)-phenylhydrazide (GOP) and serine-borate complex, (competitive inhibitors of kidney gamma-GTPase), and 6-diazo-5-oxo-L-norleucine (DON) and o-diazo-acetyl-L-serine (AZA), (irreversible inhibitors of kidney gamma-GTPase). In contrast, conversion of both endogenously-generated or exogenous LTC4 into LTD4 by RPC is inhibited only by serine-borate complex. These results suggest that RPC contain at least two distinct forms of gamma-GTPase; one capable of recognizing gamma-GpNA and susceptible to inhibition by all four compounds, and a second form utilizing also LTC4 as substrate, and is not inhibited by high concentrations of several "classic" gamma-GTPase inhibitors.

Aniline Compounds↗
PubMed1984

A radioimmunoassay for the histamine H2-antagonist, tiotidine.

A specific and sensitive radioimmunoassay (RIA) for the histamine H2-antagonist, tiotidine, has been developed. The assay is based upon competition of tiotidine with [3H]-tiotidine for antibody (Ab) obtained from immunized rabbits. The immunogen used was a glutaraldehyde coupled conjugate of the tiotidine derivative (ICI 147,655) and bovine serum albumin (BSA). Displacement of [3H]-tiotidine by unlabeled tiotidine was competitive over a concentration range of 10-1000 fmol. The Ab was 100-fold less sensitive to the pharmacologically inactive metabolite of tiotidine (ICI 129,585) and did not cross-react with histamine, cimetidine or phenylguanidine. In dogs given an i.v dose of tiotidine, plasma levels of the antagonist, as measured by the RIA, were correlated with inhibition of histamine-induced gastric acid secretion. Tiotidine (0.3 or 0.6 mumol kg-1) caused a dose-dependent and transient decrease in acid secretion at plasma concentrations of 10(-6) to 10(-8) M. Other potential analytical and research uses of H2-antagonist radioimmunoassays are discussed.

Animals↗
PubMed1984

A radiochemical assay for detection of leukotriene B4 production from isolated cells.

A radiochemical procedure for quantitating the effect of inhibitors of leukotriene B4 (LTB4) biosynthesis is described. Rat peritoneal cells were labeled with 3H-arachidonic acid and stimulated with the calcium ionophore A23187. 3H-LTB4 was isolated by processing on C18-Sep Pak cartridges followed by reverse-phase high pressure liquid chromatography (HPLC). The identity of this product, as well as other arachidonic acid metabolites, was verified by using silicic acid column chromatography followed by straight-phase HPLC and thin layer chromatography. Using this assay, LTB4 release by ionophore A23187 has been shown to be both time- and concentration-dependent. Indomethacin enhanced, while NDGA and ETYA inhibited, the A23187-induced production of LTB4. This procedure is both simple and direct and is capable of assessing the ability of novel compounds to alter LTB4 production.

5,8,11,14-Eicosatetraynoic Acid↗
PubMed1984

Pharmacological and biochemical evidence for metabolism of peptide leukotrienes by guinea-pig airway smooth muscle in vitro.

It has been demonstrated that leukotriene (LT)C4 is metabolized to LTD4 via the action of the enzyme gamma-glutamyl transpeptidase. LTD4 is, in turn, converted by the enzyme aminopeptidase to LTE4. In the present study, the pharmacological effects of the aminopeptidase inhibitor, L-cysteine and the gamma-glutamyl transpeptidase inhibitor, L-serine borate, on peptide LT concentration-response curves were evaluated in isolated guinea-pig trachea. L-Cysteine (3 mM) enhanced the contractile activity of both LTC4 and LTD4. L-Serine borate (45 mM) enhanced the contractile activity of LTC4 without altering the response to LTD4. In contrast, neither L-cysteine nor L-serine borate consistently altered the concentration-response curves to LTE4, histamine or carbachol, which rules out a nonspecific effect of these inhibitors on airway smooth muscle. In the absence of enzyme inhibitors the peptide LTs were equipotent; whereas in their presence the relative order of potency was LTC4 = LTD4 greater than LTE4. Incubation of isolated guinea-pig trachea with [3H]LTC4 resulted in the formation of [3H]LTD4 and [3H]LTE4 with a proportional decrease in [3H]LTC4. The bioconversion of [3H]LTC4 was blocked by L-serine borate in a concentration-related manner (IC50 = 3.4 +/- 0.5 mM, mean +/- S.E.M., n = 3) and the formation of LTE4 was blocked by L-cysteine (10 mM). The results suggest that LTC4 is converted to LTD4 and subsequently to LTE4 by isolated guinea-pig trachea. The potency of LTC4 and LTD4 is increased when their transformation to LTE4 is prevented.

Aminopeptidases↗
PubMed1983

Determination of SRS-A release from guinea-pig lungs by a radioimmunoassay.

A sensitive radioimmunoassay for leukotrienes (LTs) has been developed. Rabbits were immunized with a conjugate of LTD4 and bovine serum albumin, prepared by using 1,5-difluoro-2,4-dinitrobenzene as the coupling agent. The assay can detect 0.045 pmol LTD4 at a final plasma dilution of 1:72. 50% displacement of bound 3H-LTD4 was obtained with 0.43 +/- 0.03 pmol LTD4. LTC4, LTE4 and LTF4 cross-react 159%, 57% and 85%, respectively, whereas LTB4, 5-HETE and prostaglandins did not. The assay was validated by measuring the antigen-induced release of LTs from sensitized guinea-pig chopped lungs. High correlation (0.9434, p less than 0.05) was found when LTs were simultaneously determined by this assay and a bioassay on guinea pig ileum.

Animals↗
PubMed1983

Development of a sensitive method for measurement of leukotriene production by isolated cells.

Washed rat peritoneal cells (RPC) rapidly and efficiently incorporated exogenous [3H]-arachidonic acid (AA). Exposure of labeled RPC to the calcium ionophore A23187 induced production of [3H]-leukotriene C4, D4 and E4 (LTC4, LTD4 and LTE4) and [3H]-prostaglandins (PGs). The radiolabeled lipoxygenase metabolites were isolated by a combination of organic extraction, silicic acid chromatography and reverse-phase high pressure liquid chromatography (RP-HPLC). Authentic leukotrienes (LT) were used to identify the biologically-synthesized products on RP-HPLC and to calculate recovery. The endogenously generated LT were also characterized by their ability to contract guinea-pig ileum and their susceptibility to soybean lipoxygenase. A23187 induced a bell-shaped concentration-dependent release of [3H]-LT which peaked at 1 X 10(-6)M ionophore. Kinetic studies revealed that ionophore stimulated the formation of mainly [3H]-LTE4 with only transient accumulation of [3H]-LTC4 and D4. In the presence of cysteine, however, production of [3H]-LTE4 was abolished with a subsequent accumulation of [3H]-LTD4. Non-steroidal antiinflammatory drugs (NSAID) moderately enhanced A23187-induced [3H]-LT production, whereas phospholipase and lipoxygenase inhibitors inhibited. The method is sensitive, reliable, and efficient for measurement of small quantities of LT produced from isolated cells.

Animals↗
PubMed1980

Inhibition of acyltransferase in lymphocytes by concanavalin A.

The effects of concanavalin A and succinylated concanavalin A on the transformation of mouse splenic lymphocytes, and on early biochemical events in the transformation, were compared. 1. The transformation of lymphocytes is biphasic with respect to concanavalin A concentration with optimal activation at about 1 microgram/ml. Activation by succinyl concanavalin A is not biphasic over a range of lectin concentration of 1--16 microgram/ml. 2. In intact lymphocytes cultured for 4 h, the enzyme Acyl-CoA:1-acylglycero-3-phosphocholine O-acyltransferase (EC 2.3.1.23) was not activated by concanavalin A but was inhibited at all concentrations tested, and was about 60% inhibited at 16 micrograms concanavalin A per ml. Succinyl concanavalin A gave little or no inhibition at similar concentrations. 3. Lymphocytes become committed to divide while their acyltransferase activities are markedly inhibited by concanavalin A. 4. The inhibition of acyltransferase by concanavalin A can be lifted by displacing the lectin from the cells by alpha-methylmannoside. Lowered enzyme activity is not caused by cell agglutination or by direct cross-linking of lectin receptors. It is unlikely that the inhibition of acyltransferase is due to indirect cross-linking via the cytoskeleton since colchicine did not reverse the inhibition. 5. The inhibition of acyltransferase and the reduced stimulation of transformation by higher levels of concanavalin A appear to be due to hydrophobic interaction of the lectin with the plasma membrane, as shown by liposome aggregation studies.

1-Acylglycerophosphocholine O-Acyltransferase↗
PubMed1979

Immunological specificity of natural opsonins and their role in the cross-reactivity between Staphylococcus aureus Mardi and Escherichia coli 101.

The immunochemical specificity of the observed cross-reactivity between Escherichia coli strain 101 and Staphylococcus aureus strain Mardi was examined. The cross-reactivity was shown to be dependent upon mucopeptide antibodies which are present in normal and immune sera. Although both organisms contained surface antigens with immunodominant glucuronic acid residues, in vitro phagocytosis studies indicated that antibodies directed against these antigens were not significantly involved in the opsonization process. Rather, antibodies with mucopeptide specificity were shown to be involved in the in vitro phagocytosis of these organisms by polymorphonuclear leukocytes. The mucopeptide antibodies, which were found in both nonimmune and immune sera, were shown to be effective in opsonizing both the S. aureus strain and the E. coli strain. The ubiquitous distribution of E. coli strains containing mucopeptide antigens common to most bacteria suggests that these organisms may be responsible for the wide prevalence of natural staphylococcal opsonins with mucopeptide specificity in normal sera.

Antibodies, Bacterial↗
PubMedDate not supplied

The status of HIV/AIDS nursing in Australia: a specialty in decline?

Since the introduction of highly active antiretroviral therapy (HAART), occasions of service for patients with HIV/AIDS have altered drastically. HIV/AIDS nurses perceived that this change in activity had caused an exodus from the specialty by experienced nurses, and those that remained were rapidly deskilling. A survey of nurses working in HIV/AIDS in Australia and New Zealand was conducted to assess the impact of HAART on nursing skills and retention. More than 72% of respondents reported that they had lost some or many clinical HIV/AIDS nursing skills. About 37% of nurses reported that they were losing confidence in their knowledge of the management of opportunistic infections and cancers. About 27% reported larger numbers of nurses leaving their specialty area than in previous years. To enable nurses to respond rapidly to a potential decline in the effectiveness of HAART, this loss in skills and knowledge must be addressed.

Attitude of Health Personnel↗