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R Anderson

Publications and source records attributed to R Anderson.

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

Membrane stabilizing, anti-oxidative interactions of propranolol and dexpropranolol with neutrophils.

We have investigated the effects of the beta-adrenoreceptor-blocking agent, propranolol (9-300 microM) on several pro-inflammatory activities of human neutrophils in vitro. Superoxide production by calcium ionophore (A23187)-activated neutrophils was particularly sensitive to inhibition by low concentrations (9-18.7 microM) of this drug. However, inhibition of superoxide generation by neutrophils activated with phorbol myristate acetate (PMA), opsonized zymosan (OZ), and arachidonate (AA) only occurred with higher concentrations of propranolol, and coincided with decreased intracellular calcium fluxes, phospholipase A2 (PLA2) activity and synthesis of platelet-activating factor (PAF). Propranolol possessed neither cytotoxic nor superoxide-scavenging properties but, using a haemolytic assay of membrane-stabilizing activity, this agent neutralized the membrane-disruptive effects of the bioactive phospholipids, lysophosphatidylcholine (LPC), PAF, and lysoPAF(LPAF). A mechanistic relationship between the anti-oxidative and membrane-stabilizing properties of propranolol was suggested by the observation that pretreatment of neutrophils with LPC or PAF eliminated the inhibitory effects of the drug on superoxide generation by PMA-activated neutrophils. Dexpropranolol, a stereoisomer with minimal beta-blocking activity, and propranolol were equally effective with respect to their membrane-stabilizing and anti-oxidative interactions with neutrophils, but several other beta-blocking agents (atenolol, metoprolol, sotalol, and timolol) did not possess these activities. Inhibition of oxidant generation is, therefore, not a common property of beta-blocking agents and, in the case of propranolol, appears to occur as a consequence of membrane-stabilization rather than by beta-receptor-directed effects.

Acridines↗
PubMed1996

FGF-2 influences cell movements and gene expression during limb development.

FGF-2 is proposed to be an important ectodermal signal directing limb outgrowth and patterning. Consistent with this hypothesis we show that ectopic application of FGF-2 can maintain the apical ectodermal ridge (AER)-dependent expression of Sonic hedgehog (Shh), and AER-dependent zone of polarizing activity (ZPA) signaling. We also find that ectopic FGF-2 applied to the posterior wing bud caused a dramatic change in the morphology of the limb bud, and results in limbs that display a reduction in the length of individual skeletal elements and loss of digits. Associated with these morphological changes was an FGF-2-stimulated expansion and bifurcation of the expression domains of two posteriorly expressed genes, Shh and HoxD13. Applying FGF-2 at a central or anterior location in the limb bud did not alter the Shh expression domain or cause digit loss. To test whether ectopic application of FGF-2 into the posterior limb bud was influencing the movement of limb bud cells, we used the lipophilic dye DiI to map the behavior of posterior cells in response to FGF-2. In response to FGF-2 posterior limb bud cells move in both a proximal and a distal direction, causing the initially labeled cell population to bifurcate into two distinct domains. Our data suggest that FGF-2 is influencing limb outgrowth by modifying cell movements and subsequent position-specific cell-cell interactions that are important for limb morphogenesis.

Animals↗
PubMed1996

Membrane-stabilizing, anti-inflammatory interactions of macrolides with human neutrophils.

The effects of the macrolide antimicrobial agents azithromycin, clarithromycin, erythromycin and roxithromycin on the prooxidative activity of stimulated human neutrophils have been investigated in vitro. Superoxide generation by activated neutrophils was measured by lucigenin-enhanced chemiluminescence. At the concentrations used (2.5-80 micrograms/ml) none of the test agents was cytotoxic, nor did they possess superoxide-scavenging properties. Treatment of neutrophils with all 4 macrolides was accompanied by dose-related inhibition of superoxide production by cells activated with FMLP or the calcium ionophore (A23187), while the responses activated by phorbol myristate acetate (PMA) or opsonized zymosan were minimally affected. The anti-oxidative interactions of roxithromycin with FMLP-activated neutrophils were neutralized by pretreatment of the cells with low, non-cytotoxic concentrations (0.5 microgram/ml) of the prooxidative, proinflammatory bioactive phospholipids, lysophosphatidylcholine (LPC), platelet-activating factor (PAF) and lyso-PAF (LPAF). Using an assay of membrane-stabilizing activity, the macrolides antagonized the membrane-disruptive effects of LPC, PAF and LPAF, without affecting enzymes involved in their synthesis. These membrane-stabilizing interactions of macrolides with neutrophils may counteract the proinflammatory, prooxidative activity of several bioactive lipids which have been implicated in the pathogenesis of bronchial asthma.

Adult↗
PubMed1996

Increased levels of autoantibodies to cardiolipin and oxidised low density lipoprotein are inversely associated with plasma vitamin C status in cigarette smokers.

In this study we have measured circulating levels of autoantibodies to cardiolipin and oxidised low-density lipoprotein (ox-LDL) and correlated these with plasma concentrations of the anti-oxidant nutrients vitamin C, vitamin E and beta-carotene, in a group (79) of asymptomatic, male cigarette smokers and in non-smoking control subjects. Cigarette smoking, a well-known risk factor for development of atherosclerosis, was found to be associated with moderately elevated levels of autoantibodies to both cardiolipin and ox-LDL. Increased levels of these autoantibodies were most evident in the older smokers (> 30 years) and were significantly and inversely correlated with plasma vitamin C, but not with vitamin E or beta-carotene. Absorption studies designed to investigate the specificity of these autoantibodies demonstrated a high degree of cross-reactivity of cardiolipin antibodies with ox-LDL, while antibodies to the oxidatively modified lipoprotein tended to be specific for this antigen. These findings suggest that cigarette smoking promotes formation of autoantibodies to both cardiolipin and ox-LDL and that these may be involved in the initiation and/or perpetuation of atherosclerosis. Dietary intake of vitamin C may be a determinant of susceptibility to development of this cardiovascular disorder.

Adult↗
PubMed1996

Morphologic changes in offspring of female mice exposed to ethanol before conception.

OBJECTIVE: Our purpose was to evaluate the mutagenic effects of preconceptional ethanol exposure by use of the mouse model. STUDY DESIGN: Fifty-three adult female CF-1 mice were divided into one of five groups with or without an ethanol diet for 28 days. Mice were then superovulated and mated. On day 14 of gestation all mice were killed and fetuses removed and examined for abnormalities. RESULTS: The mutation index for the study and mutagen groups was similar (48% vs 41%). The percentage of any anatomic abnormality in any treatment group were between 50% and 100%. Anomalies of the abdominal wall were most commonly seen in the mutagenic groups. CONCLUSIONS: Chronic ethanol exposure in the female mouse before conception yields anatomic abnormalities in the offspring. These mutagenic effects may be variable in that they may result in a dominant lethal mutation or a delayed interference with organogenesis. Ethanol consumption, whether before or after conception, poses an unfavorable outcome in the offspring produced.

Abnormalities, Drug-Induced↗
PubMed1996

Delivery of the Pertactin/P.69 polypeptide of Bordetella pertussis using an attenuated Salmonella typhimurium vaccine strain: expression levels and immune response.

Pertactin/P.69, a surface-associated polypeptide antigen of Bordetella pertussis, was expressed in a Salmonella typhimurium aroA aroD vaccine strain, BRD509, using different expression systems, and the immune response in mice against these constructs was compared. Initially, Pertactin/P.69 was expressed on the surface of BRD509 from a single copy of the gene encoding the antigen localized on the Salmonella chromosome. As previously shown, secretory and humoral antibody responses could not be detected following multiple immunization with this strain (BRD640). However, a strong anti-Pertactin/P.69 proliferative response was observed in murine splenocytes following a single oral dose with BRD640. The stimulated splenocytes secreted interferon-gamma but not interleukin-5, indicating that BRD640 induced a Th1 type T-helper response against Pertactin/P.69. We wished to construct a vaccine strain that might induce secretory and humoral responses against Pertactin/P.69 as well as a cell-mediated immune response. Consequently, Pertactin/P.69 was expressed at high levels in the cytoplasm of BRD509 under the control of the inducible nirB promoter from a ColE1-based replicon. Anti-Pertactin/P.69 immune responses were not observed following immunization of BALB/c mice with this strain (BRD975). Priming of the immune system against Pertactin/P.69 was, however, observed following oral immunization with BRD975 and boosting subcutaneously with purified Pertactin/P.69 antigen. The major anti-Pertactin/P.69 IgG subclass detected in boosted mice was IgG2a; thus, as BRD640, BRD975 appeared to induce a Th1 type T-helper response against Pertactin/P.69.

Animals↗
PubMed1996

Bonesetters and curers in a Mexican community: conceptual models, status, and gender.

In the indigenous Mexican village of Hueyapan, there is a clear contrast between the supernatural beliefs curers use to explain illness and the naturalistic assumptions made by this community's bonesetters. In addition to employing different conceptual models, the two types of healers differ with respect to their manner of recruitment, training, types of illnesses treated, social status, and gender. These differences add up to a seeming enigma: in a community where men largely control political, economic, and religious affairs, the higher status role of curer is undertaken most frequently by women and the lower status specialty of bonesetter by men. Hueyapan's health care system becomes less problematical, however, when it is recognized that recruitment to the bonesetter and curer roles is shaped by pragmatic considerations of role continuity and compatibility independent of the social status of these two occupations.

Female↗
PubMed1996

The riminophenazines, clofazimine and B669, inhibit potassium transport in gram-positive bacteria by a lysophospholipid-dependent mechanism.

The effects of the riminophenazine antimicrobial agents clofazimine and B669 as well as those of lysophosphatidylcholine (LPC), on microbial K(+)-transporting systems were investigated in a range of Gram-positive and Gram-negative bacteria using 42K and 86Rubidium (86Rb) as tracers. Exposing the Gram-positive bacteria to 0.1-10 mg/L of the drugs resulted in a dose-related inhibition of uptake of both radiolabelled cations due primarily to the inhibition of their influx which was prevented by pretreating the microorganisms with 25 mg/L alpha-tocopherol (vitamin E) which forms a complex with lysophospholipids. In contrast, Gram-negative bacteria were resistant to riminophenazine-mediated inhibition of K(+)-transport, with only one of four well-characterised K(+)-transport system mutants of Escherichia coli, namely Kup, being affected by the antimicrobial agents. The selective antimicrobial activity of riminophenazines against Gram-positive bacteria is probably achieved by lysophospholipid-mediated inactivation of K(+)-transport, while Gram-negative microorganisms possess several K(+)-transport systems which are either inaccessible and/or insensitive to lysophospholipids. Thus, K(+)-transport systems may represent novel targets for antimicrobial agents.

Adenosine Triphosphate↗
PubMed1996

Anti-inflammatory, membrane-stabilizing interactions of salmeterol with human neutrophils in vitro.

1. We have investigated the effects of salmeterol (0.3-50 microM) on several pro-inflammatory activities of human neutrophils in vitro. 2. Oxidant production by FMLP- and calcium ionophore (A23187)-activated neutrophils was particularly sensitive to inhibition by low concentrations (0.3-3 microM) of salmeterol, while the responses of phorbol myristate acetate- and opsonised zymosan-stimulated cells were affected only by higher concentrations (3-50 microM) of the drug. At these concentrations salmeterol is not cytotoxic, nor does it act as a scavenger of superoxide. 3. These anti-oxidative interactions of salmeterol with neutrophils were insensitive to propranolol but could be eliminated by washing the cells, or by pretreatment with low concentrations (1-2 microM) of the pro-oxidative, membrane-destabilizing phospholipids, lysophosphatidylcholine (LPC), platelet activating factor (PAF) and lysoPAF (LPAF). 4. At concentrations of 6.25-50 microM salmeterol interfered with several other activities of stimulated neutrophils, including intracellular calcium fluxes, phospholipase A2 activity and synthesis of PAF. 5. In an assay of membrane-stabilizing activity, salmeterol (25 and 50 microM) neutralized the haemolytic action of LPC, PAF and LPAF. 6. Of the other commonly used beta 2-adrenoceptor agonists, fenoterol, and formoterol, but not salbutamol, caused moderate inhibition of neutrophil oxidant generation by a superoxide-scavenging mechanism. However, unlike salmeterol, these agents possessed only weak membrane stabilizing properties. 7. We conclude that salmeterol antagonizes the pro-inflammatory, pro-oxidative activity of several bioactive lipids implicated in the pathogenesis of bronchial asthma, by a mechanism related to the membrane-stabilizing, rather than to the beta 2-agonist properties of this agent.

Adenosine Triphosphate↗
PubMed1996

Immune response in mice following immunization with DNA encoding fragment C of tetanus toxin.

Tetanus toxin is a potent neurotoxin synthesized by Clostridium tetani. Immunization with fragment C protein, the nontoxic C-terminal domain of tetanus toxin, will protect mice against lethal challenge with tetanus toxin. A synthetic gene encoding fragment C (tetC) had previously been shown to express high levels of fragment C in Saccharomyces cerevisiae. A plasmid, pcDNA3/tetC, which encodes the synthetic tetC gene expressed under the control of the human cytomegalovirus major intermediate-early promoter/enhancer region, was constructed. Expression of fragment C was observed in eukaryotic cells growing in vitro following transfection with pcDNA3/tetC. The immune response induced by intramuscular immunization with pure pcDNA3/tetC DNA was evaluated in a murine model. Anti-fragment C serum immunoglobulin and proliferative responses in splenocytes were observed in BALB/c mice following two immunizations with pcDNA3/tetC. The major immunoglobulin G subclass that recognized fragment C was immunoglobulin G2a, and the stimulated splenocytes secreted high levels of gamma interferon. Immunity to tetanus is dependent on the presence of neutralizing serum antibodies against tetanus toxin. Sufficient anti-fragment C serum immunoglobulins were induced by DNA-mediated immunization to protect mice against lethal challenge with tetanus toxin.

Animals↗
PubMed1996

Community acquired pneumonia: aetiology and usefulness of severity criteria on admission.

BACKGROUND: Community acquired pneumonia remains an important cause of hospital admission and carries an appreciable mortality. Criteria for the assessment of severity during admission have been developed by the British Thoracic Society (BTS). A study was performed to determine the sensitivity and specificity of a severity rule based on a modification of the BTS prognostic rules applied on admission, to compare severity as assessed by medical staff with the modified rule, and to determine the microbiological cause of community acquired pneumonia in Christchurch. METHODS: A 12 month study of all adults admitted to Christchurch Hospital with community acquired pneumonia was undertaken. Three hundred and sixteen consecutive patients with suspected community acquired pneumonia were screened for inclusion. Variables obtained from the history, examination, investigations, and initial treatment were examined for association with mortality. RESULTS: Two hundred and fifty five patients met the inclusion criteria. Their mean age was 58 years (range 18-97). A microbiological diagnosis was made in 181 cases (71%), Streptococcus pneumonia (39%), Mycoplasma pneumoniae (16%), Legionella species (11%), and Haemophilus influenzae (11%) being the most commonly identified organisms. Patients had a 36-fold increased risk of death if any two of the following were present on admission: respiratory rate > or = 30/min, diastolic BP < or = 60 mm Hg, urea > 7 mmol/l, or confusion. The severity rule identified 19 of the 20 patients who died and six of eight patients admitted to the intensive care unit as having life threatening community acquired pneumonia. The sensitivity of the modified rule for predicting death was 0.95 and the specificity 0.71. In 47 cases (21%) the clinical team appeared to underestimate the severity of the illness. CONCLUSIONS: The organisms responsible for community acquired pneumonia in Christchurch are similar to those reported from other centres except for Legionella species which were more common than in most studies. The modification of the BTS prognostic rules applied as a severity indicator at admission performed well and could be incorporated into management guidelines.

Adolescent↗
PubMed1996

A two-year follow-up on the effects of a smoking ban in an inpatient psychiatric service.

The effects of prohibiting cigarette smoking on the behavior of patients on a 25-bed psychiatric inpatient unit were assessed immediately after implementation of a smoking ban and two years later. No major behavioral disruptions were observed after the ban. The number of calls for security assistance, physical assaults, instances of leather restraints and of seclusions, and discharges against medical advice did not increase significantly immediately after the restriction on smoking or two years later. Significantly more verbal assaults and prescribing of p.r.n. medications for anxiety occurred immediately after the ban but not two years later.

Adolescent↗