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Biomedical subjects

A Potter

Publications and source records attributed to A Potter.

At least 55 records · Page 3Linked to original sources

Oncogene expression in primary myelodysplasia: correlation with haematological, karyotypic, and clinical progression.

AIMS: To see if the relative expressions of proto-oncogenes that are increased in acute myeloid leukaemia are raised in patients with myelodysplastic syndromes (MDS), and to see if they increase with progression to leukaemia. To note if there is a correlation between morphology, karyotype, and these proto-oncogene expressions and if any one proto-oncogene can predict prognosis. METHOD: Bone marrow from 130 patients was analysed at six monthly intervals over two years for relative mRNA expression of seven oncogenes, karyotype, and morphology. The technique used slot blot hybridisation and densitometric analysis. The results were compared with 14 surgical controls and 30 people with vitamin deficiency anaemia. RESULTS: Six of seven oncogenes showed increased expression which progressed with time, but did not correlate with morphological or karyotypic changes. Expression of four of the seven oncogenes was increased in megaloblastic and iron deficiency anaemia. C-mos showed differences among the five morphological subgroups; it correlated with abnormal location (p = 0.025) and seemed to influence prognosis. CONCLUSION: Increased proto-oncogenes reflect the overall marrow perturbation in MDS. C-mos may reflect persistence of monocyte pathway which confirms marrow stability.

Aged↗

Secondary in vitro B lymphocyte (antibody) response to microbial antigens: use in appraisal of vaccine immunogenicity and cytokine immunoregulation.

In order to perform preliminary evaluations of subunit vaccine candidates before extensive trials in large food-producing animals, an in vitro B-lymphocyte response assay, based on the principles of an ELISA, was established. The assay was developed in detail for the porcine system using antigens from the Gram-negative bacterium Actinobacillus pleuropneumoniae, but is shown to be applicable to other species and antigens, including viral components. It is further shown that B-cell activity in the assay is dependent on T-helper cells as well as macrophages and/or their secretory products. Thus, in addition to providing a tool for evaluation of T and B memory cell activity, the system also lends itself to dissection of T-B cell collaboration and the regulatory functions of interleukins in secondary (in vitro) antibody responses.

Actinobacillus↗

Response of cerebral blood volume to changes in arterial carbon dioxide tension in preterm and term infants.

The response of cerebral blood volume (CBVR) to a small induced change in arterial carbon dioxide tension was studied by near-infrared spectroscopy in 17 newborn infants born from 26 wk of gestation to term. All 17 infants were undergoing mechanical ventilation but had apparently normal brains. The CBVR per kPa change in arterial carbon dioxide tension within the range 3.9 to 9.6 kPa was calculated from the change in total cerebral Hb concentration ([TCHb]) using the equation: delta CBV = delta [TCHb] x 0.89/[H] where [H] is the large vessel Hb concentration. A least-squares regression line with 95% confidence limits was derived for CBVR against gestational age. A highly significant linear increase in CBVR was found: mean CBVR from the regression increased from 0.07 mL.100 g-1.kPa-1 at 26 wk to 0.51 mL.100 g-1.kPa-1 at 40 wk.

Arteries↗

Effects of indomethacin on cerebral haemodynamics in very preterm infants.

Near infrared spectroscopy was used to investigate the effects of intravenously administered indomethacin (0.1-0.2 mg/kg) on cerebral haemodynamics and oxygen delivery in 13 very preterm infants treated for patent ductus arteriosus. 7 infants received indomethacin by rapid injection (30 s) and 6 by slow infusion (20-30 min). In all the infants cerebral blood flow, oxygen delivery, blood volume, and the reactivity of blood volume to changes in arterial carbon dioxide tension fell sharply after indomethacin. There were no differences in the effects of rapid and slow infusion. These falls in cerebral oxygen delivery and the disruption of cerebrovascular control might compromise cellular oxygen availability, particularly in regions of the brain where the arterial supply is precarious. Care should be taken to ensure that oxygen delivery is optimum before the administration of indomethacin to preterm infants.

Blood Gas Monitoring, Transcutaneous↗

Time and temperature dependence of granulocyte damage by leucotoxic supernatants from Pasteurella haemolytica A1.

Bacterial exotoxins may contribute to the pathogenic potential of micro-organisms through interactions with cells of the host defence system as well as by directly damaging host tissue. The present studies were designed to explore mechanisms of interaction between bovine granulocytes and the leucotoxin produced by Pasteurella haemolytica, a major cause of bovine respiratory disease. Leucotoxin-containing supernatant from P. haemolytica A1 caused rapid cell death in isolated bovine granulocytes that was close to half-maximal by 5 min and nearly 90% complete after 30 min at 37 degrees C. Maintaining granulocytes at ice-water temperature markedly attenuated or prevented the toxic effect; furthermore, if exposed to supernatants at ice-water temperature and then washed, most cells remained viable even after rewarming to room temperature. However, even a very brief exposure (about 5 s) at 37 degrees C led to extensive cell death even after immediate cold dilution and washing. Granule enzymes such as arylsulphatase were released far more slowly than cytosol contents. Leucotoxin purified by column chromatography showed temperature dependence and divergence between cytosol and granule marker release similar to those observed with the crude supernatant preparation. These findings indicate that irreversible interaction between P. haemolytica leucotoxin and bovine granulocytes is initiated very rapidly at 37 degrees C but markedly impeded at low temperature, while granule enzyme release follows cytosol marker release over a much longer period. The results suggest either a requirement for target cell metabolic activity to initiate toxin effects or a temperature-dependent receptor conformation, with granule enzyme release following as a secondary consequence of granulocyte death.

Animals↗

Interleukin-2 induces a rapid increase in ornithine decarboxylase mRNA in a cloned murine T lymphocytic cell line.

We recently observed a 25-fold increase in the activity of ornithine decarboxylase (ODC) 6 h after treatment of G1-synchronized CTLL-2 cells with interleukin-2 (IL-2). Here we show that the ODC mRNA content increased in parallel with the ODC activity during the first hours of stimulation with IL-2, resulting in a 25-fold increase at 6 h. Between 6 and 24 h the ODC mRNA content continued to increase steadily up to 50-fold, even after the ODC activity had returned to low basal levels. In the case of density-arrested CTLL-2 cells deprived of IL-2 for 16 h, the IL-2-mediated increase in ODC mRNA was 2-fold at 1 h and 5-fold at 8 h, irrespective of the capability of the cells to resume their cycle. There was no marked increase in the rate of transcription of the ODC gene, at least during the first 2 h of stimulation with IL-2. These findings suggest that the regulation of the ODC activity by IL-2 is a primary event in IL-2-induced cell proliferation and occurs at the post-transcriptional level, possibly by stabilizing the ODC mRNA and affecting the efficiency of translation of the messenger.

Animals↗

Interleukin-2 regulates the activity of ornithine decarboxylase in a cloned murine T lymphocytic cell line: evidence for a protein kinase C-dependent pathway.

The role of protein kinase C (PKC) in the regulation of ornithine decarboxylase (ODC) activity during interleukin-2 (IL-2)-dependent cell growth was investigated. A large biphasic increase in the activity of ODC was observed after treatment of IL-2-deprived CTLL-2 cells with recombinant human IL-2 (rec IL-2). The PKC activators phorbol 12-myristate 13-acetate (PMA) and 4 beta-phorbol 12,13-didecanoate (4 beta-PDD), but not the inactive analog 4 alpha-PDD, induced ODC activity in exponentially growing cultures. Unlike IL-2, however, phorbol esters were poor inducers of IL-2-depleted cultures. H-7, a potent inhibitor of PKC and cyclic nucleotide-dependent protein kinases (CN-PK), suppressed the IL-2-induced ODC activity, while HA1004, a more potent inhibitor of CN-PK than of PKC, had opposite effects depending on its concentration. The results suggest that activation of PKC is involved in but is not the sole mechanism for the induction of ODC by rec IL-2. At concentrations which suppressed the induction of ODC activity by IL-2, H-7 inhibited DNA synthesis and HA1004 did not.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Characterization of a streptomycin-sulfonamide resistance plasmid from Actinobacillus pleuropneumoniae.

An Actinobacillus pleuropneumoniae strain contained a plasmid (pHD8.1) conferring resistance to streptomycin and sulfonamide. Restriction endonuclease mapping and DNA-DNA hybridization showed that pHD8.1 is related to RSF1010 from Salmonella panama, which also confers resistance to streptomycin and sulfonamide, and to pHD148 from Haemophilus ducreyi, which confers resistance only to sulfonamide.

Actinobacillus↗

Markers of differentiated B cell leukaemia: CD22 antibodies and FMC7 react with different molecules.

FMC7, a monoclonal antibody used extensively to characterize B cell leukaemias of differentiated phenotype (prolymphocytic, hairy cell, and similar leukaemias) was compared directly with antibodies of the CD22 cluster, which also react with B cells at a late stage in differentiation. Detailed comparison shows that the reaction spectrum, though similar, is not identical. Differences were particularly prominent in chronic lymphocytic leukaemia (CLL) and non-Hodgkin's lymphoma (NHL). Binding studies show that the antibodies react with different antigenic determinants, and immunochemical studies show that they react with different molecules. The FMC7 antigen, not previously characterized, was shown to be a protein of apparent molecular weight 105,000, by immunoblotting after electrophoresis of membrane extracts.

Antibodies, Monoclonal↗

Evaluation of a monoclonal IgM antibody for purging of bone marrow for autologous transplantation.

A monoclonal antibody of the IgM class, reacting with the CD9 (p24) antigen is described. The antibody (FMC27) is cytotoxic against cells of the common type of acute lymphoblastic leukaemia (c-ALL), giving killing at higher dilutions than an IgG antibody (FMC8) against the same antigen. FMC27 and FMC8 recognise different epitopes, and FMC27 may thus be used in a cocktail together with FMC8 and an antibody against the c-ALL antigen, WM21. Furthermore, the IgM antibody can be coated directly onto magnetic microparticles for magnetic purging, unlike the IgG antibody which must be used in a two-layer procedure.

Antibodies, Monoclonal↗

The purification of mouse monoclonal antibodies from ascitic fluid.

A method is described for the purification of monoclonal antibody from mouse ascitic fluid. The fluid is clarified and the lipid removed using silicon dioxide powder, before the immunoglobulin is precipitated using polyethylene glycol. The method provides IgM antibody in high yield and good purity. In the case of IgG antibodies the purity is 30-40% after PEG precipitation and the yield is high. The enriched IgG is adequate for many purposes and is suitable for further purification on an ion exchange column.

Animals↗

Lupus-like nephritis heralding the definitive manifestation of systemic lupus erythematosus.

Four patients presented with the nephrotic syndrome. The histological appearances on renal biopsy were in three characteristic and in one suggestive of lupus nephritis. These patients did not initially have other clinical features of SLE, but three had a positive ANA and one a raised DNA titre. Remission occurred in two patients, in one spontaneously and in another following corticosteroid therapy, but two developed renal failure. During follow-up all developed elevated DNA binding levels and arthralgia or lymphopenia. The ARA classification criteria for lupus were only fulfilled at this late stage.

Adult↗

Identification of patients at high risk for complications of intraaortic balloon counterpulsation: a multivariate risk factor analysis.

Risk factors for vascular complications of intraaortic balloon (IAB) counterpulsation were evaluated in 206 consecutive patients. The approach was percutaneous in 105 patients and surgical cutdown in 101. Vascular complications occurred in 42 patients, and of these 21 required surgery. Multivariate analysis demonstrated the following major risk factors for vascular complications: preexisting peripheral vascular disease (PVD) defined as a history of claudication, femoral bruit or absent pedal pulse (p less than 0.01); and the use of the percutaneous approach (p = 0.02). Evidence of PVD was particularly predictive of major vascular complications requiring surgery (p less than 0.01). In patients with evidence of previous PVD, the risk for a major vascular complication was 31% with the percutaneous, and 16% with the surgical cutdown approach. Without PVD, the risk for a major vascular complication was 4 times higher in women (15%) than in men (3.5%), but in the presence of PVD gender had no significant effect (p = 0.03). Age, duration of IAB counterpulsation and indication for insertion were not significant risk factors. It is concluded that (1) without previous PVD, women are at greater risk than men for major vascular complications (due to smaller arterial size); and (2) evidence of previous PVD identifies patients at high risk for major vascular complications with IAB counterpulsation, particularly by way of the percutaneous approach.

Assisted Circulation↗

Comparison of intravenous nitroglycerin and sodium nitroprusside for treatment of acute hypertension developing after coronary artery bypass surgery.

The present study was designed to test the hypothesis that i.v. nitroglycerin is as effective as sodium nitroprusside for managing acute hypertension early after coronary artery bypass surgery. Seventeen patients received both nitroglycerin and nitroprusside in a randomized crossover protocol. Infusion rates were increased stepwise to lower mean arterial pressures comparably with each drug. In 14 of 17 patients, similar infusion rates of the two vasodilators resulted in equal lowering of both blood pressure and systemic vascular resistance. In the remaining three patients, very high infusion rates of nitroglycerin were required and achieved only 20-50% of nitroprusside's response in two of three. Hemodynamic responses to the two vasodilators were similar, except that nitroglycerin increased cardiac output more than nitroprusside did. In contrast, pulmonary gas exchange responses differed in that nitroglycerin improved intrapulmonary shunting, while nitroprusside worsened it. Similarly, nitroglycerin resulted in a significantly smaller increase in the alveolar arterial oxygen gradient than did nitroprusside. These results suggest that in the majority of patients, i.v. nitroglycerin was as effective as nitroprusside in controlling acute hypertension after coronary artery bypass surgery. In addition, nitroglycerin appeared to have more favorable effects on pulmonary gas exchange. Because nitroglycerin has more beneficial effects on intercoronary collateral blood flow in the setting of regional ischemia, it may be preferable to nitroprusside in patients with ischemic heart disease.

Blood Pressure↗

The school nurse.

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School Nursing↗