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Biomedical subjects

R Armstrong

Publications and source records attributed to R Armstrong.

At least 19 recordsLinked to original sources
PubMed2001

The physiological role and pharmacological potential of nitric oxide in neutrophil activation.

There is contention over whether human neutrophils produce physiologically significant levels of nitric oxide (NO) during inflammatory reactions. Nevertheless, regardless of its cell source, NO does exert regulatory effects on neutrophil function. Depending on experimental conditions, NO can either inhibit or enhance neutrophil activation, in both cases probably acting through cyclic GMP. The explanation for these apparently contradictory findings may be that the effect depends upon the concentration of NO: low concentrations of NO being stimulatory and high concentrations inhibitory. Nitrite, produced at high concentrations from NO during inflammation, can react with neutrophil myeloperoxidase-derived hypochlorous acid (HOCl) to form the active oxidant nitryl chloride, a species capable of nitrating tyrosine and tyrosyl residues on proteins. Whether nitryl chloride acts to limit or amplify the oxidant effects of myeloperoxidase is not yet clear, although formation of nitrotyrosine has been linked with nitration of phagocytosed bacteria. Clearly, a better understanding of the inflammatory effects of NO on neutrophils is needed before the therapeutic potential of NO donors or inhibitors in inflammation can be realised.

Animals↗
PubMed2000

A "dystrophic" variant of autosomal recessive myotonia congenita caused by novel mutations in the CLCN1 gene.

OBJECTIVES: To identify the disease-causing mutation and its molecular consequence for a clinically distinct type of myotonic myopathy. BACKGROUND: The authors encountered a unique myotonic disorder of early onset in a 37-year-old man and his 47-year-old sister. METHODS: After examining known loci of inherited myotonic disorders, the authors looked for mutations within the CLCN1 gene using single strand conformation polymorphism and direct sequencing. To investigate the disease mechanism, reverse transcriptase PCR analyses of total RNA were performed. RESULTS: In the proband and his affected sister, two novel mutations comprising a compound heterozygous state in the CLCN1 gene were identified: 1) a base (G) insertion in exon 7 generating a premature termination codon (fs289X) in the D5 domain, and 2) a C-to-T substitution in exon 23 resulting in a missense mutation (P932L). These mutations accompanied a clinical phenotype that is distinguishable from recessive myotonia congenita by progressive generalized muscle weakness, severe distal muscle atrophy, joint contractures, high serum creatine kinase levels, and conspicuous myopathic changes on muscle histopathology. Reverse transcriptase PCR analyses detected only the P932L mutant mRNA in skeletal muscle, suggesting that the fs289X mRNA is degraded rapidly. CONCLUSIONS: These data suggest that fs289X is a null mutation, rendering the patients with the compound heterozygous genotype of fs289X/P932L to exclusively express P932L homomeric channels that may have caused the "dystrophic" phenotype.

Adult↗
PubMed2000

Association of SWAP-70 with the B cell antigen receptor complex.

SWAP-70 is a component of an enzyme complex that recombines Ig switch regions in vitro. We report here the cloning of the human cDNA and its B lymphocyte-specific expression. Although its sequence contains three nuclear localization signals, in small resting B cells, SWAP-70 is mainly found in the cytoplasm. On stimulation, SWAP-70 translocates to the nucleus. In activated, class-switching B cell cultures, it is associated with membrane IgG, but not IgM. The membrane Ig association requires a functional pleckstrin homology domain and is controlled by the C terminus. We suggest that SWAP-70 is involved not only in nuclear events but also in signaling in B cell activation.

Amino Acid Sequence↗
PubMed2000

A field efficacy evaluation of emamectin benzoate for the control of sea lice on Atlantic salmon.

This study evaluated the efficacy of emamectin benzoate, 0.2% aquaculture premix, against sea lice on Atlantic salmon in eastern Canada. Salmon pens received either emamectin benzoate, orally, in feed at 50 micrograms/kg body weight/day for 7 consecutive days, or the same diet with no added medication. The site veterinarian had the option of administering a bath treatment with azamethiphos to any pen in the trial. The mean number of lice per fish was lower (P < 0.05) in the experimental group when measured 1, 3, 4, and 6 weeks after the start of medication. Treatment efficacy was 70%, 88%, 95%, and 61%, respectively. Three azamethiphos bath treatments were applied to each control pen during the trial, while the treatment pens received no bath treatment. No gravid female parasites were observed on any fish in the treatment group, while these life stages were observed on fish in the control group. Orally administered emamectin benzoate was palatable and highly effective for control of sea lice on salmon.

Administration, Oral↗
PubMed1999

The prevalence of asthma symptoms, bronchial hyperresponsiveness and atopy in New Zealand adults.

AIMS: To examine the prevalence of asthma symptoms, bronchial hyperresponsiveness (BHR) and atopy in a random population sample of New Zealand adults. METHODS: A random sample of 2004 adults, aged 20-44 years, in Hawkes Bay, Wellington and Christchurch, were selected from respondents to a one-page respiratory screening questionnaire and invited to take part in further testing. Subjects attending the testing centres' laboratories underwent a detailed respiratory symptom questionnaire, Phazet testing to eleven common allergens, blood samples for total and specific IgE, and measurement of bronchial hyperresponsiveness. Subjects who did not wish to participate were encouraged to complete the questionnaire by telephone. RESULTS: A participation rate of 67% (1257 of 1877 eligibles) was achieved. We found a high prevalence for all measures of asthma in the previous 12 months: wheezing was reported by 28.5%, waking with shortness of breath by 7.7%, a physician diagnosis of asthma by 15.9% and asthma medications were used by 8.5%. Bronchial hyperresponsiveness was found in 24.9%, atopy in 34.8% and elevated serum IgE levels in 30.5%. Asthma symptoms (in the past 12 months) and atopy decreased with increasing age, whereas bronchial hyperresponsiveness increased with age. Females reported higher prevalences of waking with coughing (45.9%), nasal allergies (43.5%) and skin allergies (48.8%) compared to males (30.5%, 31.9% and 37.0%, respectively). There were no significant regional differences. CONCLUSIONS: Asthma symptoms, bronchial hyperresponsiveness and atopy are all common in adult New Zealanders. Their prevalence is associated with age, gender and current smoking but there are no significant regional differences between Hawkes Bay, Wellington and Christchurch.

Adult↗
PubMed1999

Contact or immersion technique for axial length measurement?

PURPOSE: The purpose of the present study was to determine whether contact and immersion A-scan techniques produce comparable measures of the magnitude of eye axial length. METHOD: A prospective study in which 225 consecutive patients scheduled for cataract surgery in a private day surgery setting had axial lengths measured with an Alcon Ocuscan machine (Alcon Australia, Frenchs Forest, NSW, Australia) using both contact and immersion techniques. Twelve patients had both techniques repeated on a separate occasion. RESULTS: Measurements of eye axial length obtained by the immersion technique averaged 0.1 mm longer than those obtained by the contact technique. A difference in axial length values was confirmed in eyes subjected to repeated measurements. CONCLUSIONS: Both techniques give consistent results, but the difference between axial lengths measured by the two techniques has implications for choice of intra-ocular lens power.

Anthropometry↗
PubMed1998

Enhanced clearance of a multiple antibiotic resistant Staphylococcus aureus in rats treated with PGG-glucan is associated with increased leukocyte counts and increased neutrophil oxidative burst activity.

PGG-Glucan [Betafectin], a highly purified soluble beta-(1-6)-branched beta-(1 3)-linked glucan isolated from Saccharomyces cerevisiae, has broad in vitro and in vivo anti-infective activities unrelated to cytokine induction. Here we present in vivo results on the anti-infective activity of PGG-Glucan against a multiple antibiotic resistant Staphylococcus aureus. PGG-Glucan (0.25-4 mg/kg) was administered intramuscularly to male Wistar rats 48 h, 24 h, and 4 h before and 4 h after intraperitoneal implantation of a gelatin capsule containing 10(8)S. aureus colony forming units (CFU). Blood samples were collected at various times after challenge to determine CFU levels, leukocyte counts and neutrophil oxidative burst activity; serum TNF-alpha, and IL-1beta levels were also evaluated. The 0.25 mg/kg PGG-Glucan dose had no effect on reducing blood CFU levels; however, PGG-Glucan doses of 0.5 mg/kg, 1 mg/kg, 2 mg/kg or 4 mg/kg significantly reduced blood CFU levels by 48 h after challenge. Reduced CFU levels correlated with significantly elevated absolute monocyte counts, absolute neutrophil counts, and neutrophil oxidative burst activity in the absence of any effect on TNF-alpha or on IL-1beta levels. In additional studies, effects on mortality and blood CFU levels were evaluated in rats treated with ampicillin (an antibiotic to which the S. aureus was resistant), PGG-Glucan, or both agents. Mortality and blood CFU levels were reduced most in combination-treated rats compared to saline control rats or rats treated with either ampicillin alone or PGG-Glucan alone. We conclude that in vivo (1) PGG-Glucan can enhance clearance of an antibiotic resistant S. aureus, (2) that this clearance is accompanied by an increase in monocytes and neutrophils as well as a potentiation of neutrophil oxidative microbiocidal activity without alteration of the proinflammatory cytokine response, and (3) PGG-Glucan can enhance the effectiveness of traditional antibiotic treatment.

Absorption↗
PubMed1998

Healing bone using recombinant human bone morphogenetic protein 2 and copolymer.

Middiaphyseal 2.5-cm segmental defects in the right femurs of 12 sheep were stabilized with stainless steel plates and implanted with (1) 2 mg recombinant human bone morphogenetic protein 2 and poly[D,L-(lactide-co-glycolide)] bioerodible polymer with autologous blood (n = 7), (2) 4 mg recombinant human bone morphogenetic protein 2 and poly[D,L-(lactide-co-glycolide)] and blood (n = 3), or (3) poly[D,L-(lactide-co-glycolide)] and blood only (n = 2). Bone healing was evaluated for 1 year using clinical, radiographic, gross pathologic, and histologic techniques. Union occurred in three sheep in Group 1, two in Group 2, and none in Group 3. In the animals that healed, new bone first was visible radiographically between Weeks 2 and 6 after implantation; new bone mineral content equaled that of the intact femur not surgically treated by Week 16; recanalization of the medullary cavity approached completion at Week 52; and at necropsy the surgical treated femurs were rigidly healed, the poly[D,L-(lactide-co-glycolide)] was resorbed completely, and woven and lamellar bone bridged the defect site. In two Group 1 sheep euthanized at Weeks 2 and 6, polymer particles were permeated by occasional multinucleated giant cells. Some plasma cells, lymphocytes, and neutrophils were present locally. The poly[D,L-(lactide-co-glycolide)] tended to fragment during surgical implantation. Despite these observations, the recombinant human bone morphogenetic protein 2/poly[D,L-(lactide-co-glycolide)] implant was able to heal large segmental bone defects in this demanding model.

Animals↗
PubMed1997

Arteritis and increased intracellular calcium as a possible mechanism for tacrolimus-related cardiac toxicity in a pediatric transplant recipient.

We recently reported partially to wholly reversible hypertrophic cardiomyopathy, including severe hypertrophic obstructive cardiomyopathy, as a side effect in pediatric transplant recipients receiving tacrolimus immunosuppression. This seemed to be dose related. We describe a pediatric patient receiving tacrolimus who died 3 weeks after liver/bowel transplantation. Postmortem findings revealed arteritis of cardiac arteries and extensive calcification of cardiac tissue suggesting a possible mechanism of tacrolimus cardiac toxicity. This is consistent with recent reports of tacrolimus increasing calcium release into the sarcoplasmic reticulum of cardiac and striated muscle.

Arteritis↗
PubMed1997

Expression of human cathepsin K in Pichia pastoris and preliminary crystallographic studies of an inhibitor complex.

Cathepsin K is a cysteine protease of the papain family, which is predominantly expressed in osteoclasts, and is regarded as a key protease in bone remodeling. To facilitate structural studies of the protein, the wild-type sequence of the protease has been mutated so as to replace a potential N-glycosylation site. We have expressed the mutant human cathepsin K to 190 mg/5 L using the Pichia pastoris expression system. Cathepsin K was inactivated with the mechanism-based inhibitor, APC3328, and crystallized from magnesium formate. A 2.2 A X-ray data set has been collected on crystals belonging to space group P2(1)2(1)2(1), with a = 41.66 A, b = 51.41 A, and c = 107.72 A. There is most likely one molecule per asymmetric unit.

Cathepsin K↗