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R Anderson

Publications and source records attributed to R Anderson.

At least 235 records · Page 13Linked to original sources
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↗
PubMed1996

Maternal beta-catenin establishes a 'dorsal signal' in early Xenopus embryos.

In previous work, we demonstrated that maternally encoded beta-catenin, the vertebrate homolog of armadillo, is required for formation of dorsal axial structures in early Xenopus embryos (Heasman, J., Crawford, A., Goldstone, K., Garner-Hamrick, P., Gumbiner, B., Kintner, C., Yoshida-Noro, C. and Wylie, C. (1994). Cell 79, 791-803). Here we investigated, firstly, the role(s) of beta-catenin in spatial terms, in different regions of the embryo, by injecting beta-catenin mRNA into individual blastomeres of beta-catenin-depleted embryos at the 32 cell stage. The results indicate that beta-catenin can rescue the dorsal axial structures in a non-cell-autonomous way and without changing the fates of the injected cells. This suggests that cells overexpressing beta-catenin send a 'dorsal signal' to other cells. This was confirmed by showing that beta-catenin overexpressing animal caps did not cause wild-type caps to form mesoderm, but did cause isolated beta-catenin-deficient marginal zones to form dorsal mesoderm. Furthermore beta-catenin-deficient vegetal masses treated with overexpressing caps regained their ability to act as Nieuwkoop Centers. Secondly, we studied the temporal activity of beta-catenin. We showed that zygotic transcription of beta-catenin starts after the midblastula transition (MBT), but does not rescue dorsal axial structures. We further demonstrated that the vegetal mass does not release a dorsal signal until after the onset of transcription, at the midblastula stage, suggesting that maternal beta-catenin protein is required at or before this time. Thirdly we investigated where, in relationship to other gene products known to be active in axis formation, beta-catenin is placed. We find that BVg1, bFGF, tBR (the truncated form of BMP2/4R), siamois and noggin activities are all downstream of beta-catenin, as shown by the fact that injection of their mRNAs rescues the effect of depleting maternally encoded beta-catenin. Interference with the action of glycogen synthase kinase (GSK), a vertebrate homolog of the Drosophila gene product, zeste white 3 kinase, does not rescue the effect, suggesting that it is upstream.

Animals↗
PubMed1996

Health effects of passive smoking in adolescent children.

OBJECTIVE AND DESIGN: To study the effects of passive smoking on health in adolescent schoolchildren by questionnaire, spirometry and laboratory investigations. SETTING: Two schools in the Vanderbijlpark area. PARTICIPANTS: Seven hundred and twenty-six high-school children of average age 16 years. OUTCOME MEASURES: Lung function, serological abnormality or historical (i.e. questionnaire) evidence of ill health. RESULTS: The prevalence of respiratory illness before and after 2 years, respiratory symptoms, earache over the past year, low birth weight and learning difficulties were found to be significantly increased in the children exposed to parenteral smoke in the home, especially those exposed to maternal smoking. Spirometric and laboratory parameters, however, were not affected by passive smoking.

Adolescent↗