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Biomedical subjects

G Moore

Publications and source records attributed to G Moore.

At least 37 records · Page 2Linked to original sources
PubMed2000

Adjunctive salvage therapy with inhaled aminoglycosides for patients with persistent smear-positive pulmonary tuberculosis.

A proportion of patients with drug-resistant and drug-susceptible tuberculosis (TB) have sputum that is smear and culture positive for Mycobacterium tuberculosis for a prolonged period of time, despite conventional therapy. Among such patients with refractory TB, an unblinded, observational study was undertaken that used conventional TB therapy and adjunctive aerosol aminoglycosides. Patients with persistent smear- and culture-positive sputum for M. tuberculosis (despite > or =2 months of optimal systemic therapy) were selected for adjunctive treatment via inhalation with aminoglycosides, and microbiological responses were monitored. Thirteen of 19 patients converted to smear negativity during the study: 6 of 7 with drug-susceptible TB and 7 of 12 with drug-resistant TB. Among patients with drug-susceptible TB, the median time to sputum conversion was 23 days, a shorter time than for a population of historical control patients. Recurrent infection was not observed. Adjunctive aerosol aminoglycosides may expedite sterilization of sputum among certain patients with refractory TB and diminish the risk of transmission.

Administration, Inhalation↗
PubMed2000

Independent and combined analyses of sequences from all three genomic compartments converge on the root of flowering plant phylogeny.

Plant phylogenetic estimates are most likely to be reliable when congruent evidence is obtained independently from the mitochondrial, plastid, and nuclear genomes with all methods of analysis. Here, results are presented from separate and combined genomic analyses of new and previously published data, including six and nine genes (8, 911 bp and 12,010 bp, respectively) for different subsets of taxa that suggest Amborella + Nymphaeales (water lilies) are the first-branching angiosperm lineage. Before and after tree-independent noise reduction, most individual genomic compartments and methods of analysis estimated the Amborella + Nymphaeales basal topology with high support. Previous phylogenetic estimates placing Amborella alone as the first extant angiosperm branch may have been misled because of a series of specific problems with paralogy, suboptimal outgroups, long-branch taxa, and method dependence. Ancestral character state reconstructions differ between the two topologies and affect inferences about the features of early angiosperms.

Cycadopsida↗
PubMed2000

Polyploidy induces centromere association.

Many species exhibit polyploidy. The presence of more than one diploid set of similar chromosomes in polyploids can affect the assortment of homologous chromosomes, resulting in unbalanced gametes. Therefore, a mechanism is required to ensure the correct assortment and segregation of chromosomes for gamete formation. Ploidy has been shown to affect gene expression. We present in this study an example of a major effect on a phenotype induced by ploidy within the Triticeae. We demonstrate that centromeres associate early during anther development in polyploid species. In contrast, centromeres in diploid species only associate at the onset of meiotic prophase. We propose that this mechanism provides a potential route by which chromosomes can start to be sorted before meiosis in polyploids. This explains previous reports indicating that meiotic prophase is shorter in polyploids than in their diploid progenitors. Even artificial polyploids exhibit this phenotype, suggesting that the mechanism must be present in diploids, but only expressed in the presence of more than one diploid set of chromosomes.

Centromere↗
PubMed2000

Treatment of experimental allergic encephalomyelitis (EAE) induced by guinea pig myelin basic protein epitope 72-85 with a human MBP(87-99) analogue and effects of cyclic peptides.

Experimental autoimmune encephalomyelitis (EAE) is an inflammatory and demyelinating disease of the central nervous system and is an animal model of multiple sclerosis (MS). In the present report, a linear analogue and a series of cyclic semi-mimetic peptides were designed and synthesized based on the human myelin basic protein (MBP(87-99)) epitope (Val87-His-Phe-Phe-Lys-Asn-Ile-Val-Thr-Pro-Arg-Thr-Pro90) and on Copolymer I (a mixture of random polymers of Ala, Gln, Lys and Tyr used to treat MS). These analogues were designed looking for suppressors of EAE induced by guinea pig MBP(72-85) epitope (Gln-Lys-Ser-Gln-Arg-Ser-Gln-Asp-Glu-Asn-Pro-Val) in Lewis rats. The linear analogue [Arg91,Ala96]MBP(87-99), in which Arg substitutes Lys91 and Ala substitutes Pro96, was found to be a strong inhibitor which when administered to Lewis rats together with the encephalitogenic agonist MBP(72-85) completely prevented the induction of EAE. In contrast, three N- and C-termini amide-linked cyclic semi-mimetic peptides, [cyclo-Phe-Arg-Asn-Ile-Val-Thr-Ala-Acp (1), cyclo-Phe-Ala-Arg-Gln-Acp (2), cyclo-Tyr-Ala-Lys-Gln-Acp (3)] as well as a Lys side chain and C-terminous cyclic semi mimetic peptide cyclo(Lys, Acp)-Phe-Lys-Asn-Ile-Val-Thr-Ala-Acp (4) which contain segments of MBP(87-99) or are constituted from immunophoric residues of copolymer 1, were ineffective in inducing or inhibiting EAE in Lewis rats. However co-injection of cyclic analogues with MBP(72-85) delayed the onset of EAE indicating a modulatory effect on the EAE activity of MBP(72-85). These findings suggest that molecule length, size of cyclic moiety and backbone conformation are important elements for immunogenic activity. Moreover blockade of MBP(72-85) induced EAE by the unrelated peptide [Arg91,Ala56]MBP(87-99) could indicate that the mechanism of inhibition is not due to binding competition but rather due to the delivery of a negative signal by the antagonist which overcomes the agonist response possibly through the activation of antigen specific regulatory T cells.

Animals↗
PubMed2000

Failure to thrive in a population context: two contrasting studies of feeding and nutritional status.

Although failure to thrive (FTT) is generally thought to be a nutritional problem, dietary intake in children with FTT has been little researched. We describe two community-based studies of dietary intake and eating behaviour in FTT. The first study of ninety-seven children with FTT identified by population screening found that only a minority of case children were associated with neglect, organic illness or deprivation, even though dietary information suggested an underlying nutritional cause in the majority. Limited case-control data suggested significantly delayed weaning and less liking for food in general among the case children. The second study found diminished appetite, delayed progression onto solid foods and fewer foods eaten by forty-four children referred with FTT compared with forty-five controls, but was unable to detect a significant difference in energy intake, even allowing for varying body composition and other confounding variables. This study also revealed the bias introduced by recruiting case children by referral rather than screening, and that despite rigorous matching procedures the controls were not representative of the general population. These studies suggest a wide range of differences in eating behaviour and feeding patterns between children with FTT and controls, but suggest that measurements of nutrient totals may not be robust. Studies of FTT based on referred children can be misleading, as can comparison with controls, unless allowance can be made for important confounding social variables.

Diet↗
PubMed2000

Functional importance of connective tissue repair during the development of experimental abdominal aortic aneurysms.

BACKGROUND: Abdominal aortic aneurysms (AAAs) involve an unfavorable balance between the destruction and the repair of connective tissue proteins. The purpose of this study was to assess the functional importance of connective tissue repair during experimental aneurysmal degeneration. METHODS: Male Wistar rats (n = 70) underwent transient intraluminal perfusion of the abdominal aorta with porcine pancreatic elastase. In Study I, the aortic diameter was measured before elastase perfusion and at days 0, 2, 7, and 14 (n = 6 rats at each interval). Aortic wall concentrations of desmosine (Des) and hydroxyproline (OHP) were measured at each interval, and the expression of tropoelastin (TE), alpha1(I) procollagen (PC), and lysyl oxidase genes was evaluated by reverse transcription-polymerase chain reaction. In Study II, 22 rats were treated with beta-aminopropionitrile (BAPN) to block connective tissue repair. In Study III (n = 30), rats were treated with doxycycline, a matrix metalloproteinase inhibitor, beginning 7 days after elastase perfusion. RESULTS: AAAs consistently developed between 7 and 14 days after elastase perfusion. Aortic wall Des concentration decreased markedly during aneurysm development, reaching 3% of normal by day 14 (377 +/- 22 pmol of Des/sample on day 0 vs 9 +/- 1 pmol of Des/sample on day 14; P <.05). Aortic wall OHP decreased to only 68% of normal at the same interval (121 +/- 10 nmol of OHP/sample on day 0 vs 82 +/- 14 nmol of OHP/sample on day 14; P <.05). TE and PC expression was undetectable in healthy aorta, but they both increased by day 7 (P <.05); while TE expression decreased again by day 14, PC continued to rise. Lysyl oxidase expression progressively decreased at all intervals after elastase perfusion. Treatment with beta-aminoproprionitrile resulted in acute aortic dissection in 81% of the rats (50% mortality). These early deaths occurred between days 3 and 6, coinciding with aortic infiltration by proteinase-secreting inflammatory cells. Delayed treatment with doxycycline suppressed the progression of aneurysmal dilatation between days 7 and 21 (P <.05 vs untreated controls). CONCLUSIONS: The development of elastase-induced AAAs is accompanied by an active process of connective tissue repair. While this reparative process is necessary to stabilize the developing aneurysm wall, it is insufficient to prevent aneurysm progression. In contrast, reducing the proteolytic destruction of connective tissue proteins promotes stabilization of the aneurysmal aorta.

Aminopropionitrile↗
PubMed2000

Effect of creatine loading on neuromuscular fatigue threshold.

The purpose of this investigation was to determine the effect of creatine (Cr) loading on the onset of neuromuscular fatigue by monitoring electromyographic fatigue curves from the vastus lateralis muscle using the physical working capacity at the fatigue threshold (PWC(FT)) test. Using a double-blind random design, 15 women athletes [mean age 19.0 +/- 2.0 (SD) yr] from the university crew team received a placebo (n = 8; 20 g glucose) or Cr (n = 7; 5 g Cr monohydrate + 20 g glucose) four times per day for 5 consecutive days. Analysis of covariance was used to analyze the data (covaried for presupplementation PWC(FT) values). The adjusted mean postsupplementation PWC(FT) value for the Cr group (mean = 186 W) was significantly (P < 0.05) higher than that of the placebo group (mean = 155 W). These findings suggest that Cr loading may delay the onset of neuromuscular fatigue.

Adolescent↗
PubMed2000

Rapid genetic diagnosis in neonatal pulmonary artery thrombosis caused by homozygous antithrombin Budapest 3.

We report a case of spontaneous left pulmonary artery thrombosis in a 3-day-old male neonate. The presentation of heparin resistance and thrombosis raised the possibility of a type II heparin binding site antithrombin deficiency. A continuous infusion of antithrombin concentrate was used successfully, following failure of plasma, to correct the heparin resistance. Rapid genetic analysis allowed sequencing of the antithrombin gene within 5 working days. This showed the infant to be homozygous for the substitution of C to T at nucleotide 2759. This base change causes mutation of the native leucine at codon 99 to a phenylalanine. This antithrombin variant has been previously reported (antithrombin Budapest 3) and results in reduced binding of heparin to antithrombin. Such a molecular diagnostic approach is feasible and warranted in such cases of neonatal thrombosis because of the diagnostic difficulties encountered.

Antithrombin III Deficiency↗
PubMed2000

Bactericidal properties of ozone and its potential application as a terminal disinfectant.

The efficacy of ozone as a terminal disinfectant was evaluated under laboratory conditions. Different microorganisms of importance to the food industry were inoculated onto stainless steel squares and incubated at various temperatures and relative humidities for up to 4 h. Survival of microorganisms from these controls was compared with identically incubated squares exposed to ozone. Exposure of the contaminated surfaces to ozone (2 ppm for 4 h) resulted in a reduction in microbial viability that ranged, depending on organism type, from 7.56 to 2.41 log values. For all the microorganisms tested, this loss in viability was significantly greater (P < 0.05) than that observed in the absence of ozone. Gram-negative bacteria were more sensitive to ozone than gram-positive organisms; bacteria were more sensitive than the yeast strain tested. Exposure to ozone (2 ppm for 4 h) in the presence of ultra-high temperature (UHT) milk resulted in a reduction in bacterial viability that ranged from 5.64 to 1.65 log values. In most cases, this reduction was significantly less (P < 0.05) than that achieved in the absence of organic material, although still significantly greater (P < 0.05) than that observed in the absence of ozone. The presence of a meat-based broth reduced the effectiveness of ozone to a greater extent, although the number of surviving gram-negative organisms was still significantly less (P < 0.05) than in the absence of ozone. Less than 1 log unit of yeast cells was destroyed when exposed to ozone in the presence of UHT milk or meat-based broth. Results of this investigation suggest that if applied after adequate cleaning ozone could be used as an effective disinfectant.

Animals↗
PubMed1999

Role of mitochondrial membrane permeability transition in p-hydroxybenzoate ester-induced cytotoxicity in rat hepatocytes.

The relationship between mitochondrial membrane permeability transition (MPT) and the toxic effects of the alkyl esters of p-hydroxybenzoic acid (parabens) has been studied in mitochondria and hepatocytes isolated from rat liver. MPT has been proposed as a common final pathway in acute cell death through mitochondrial dysfunction. In isolated mitochondria, propyl-paraben (0.1 to 0.5 mM) in the presence of Ca2+ (50 microM) elicited a concentration-dependent induction of mitochondrial swelling dependent on MPT. This was prevented by pretreatment with a specific inhibitor of MPT, cyclosporin A (0.2 microM). For the other parabens tested, the induction of MPT depended on the relative elongation of alkyl side-chains in their molecular structure and was associated with the partition coefficients. In contrast, the induction caused by p-hydroxybenzoic acid was more potent than that of methyl- or ethyl-paraben. The pretreatment of freshly isolated hepatocytes with cyclosporin A (5 microM) and trifluoperazine (10 microM), which inhibit MPT in a synergistic manner, partially but not completely prevented propyl-paraben (1 mM; plus diazinon, 100 microM)-induced cell death, ATP loss, and decreased mitochondrial membrane potential. These results suggest that the onset of paraben-induced cytotoxicity is linked to mitochondrial failure dependent upon induction of MPT accompanied by the mitochondrial depolarization and depletion of cellular ATP through uncoupling of oxidative phosphorylation.

Animals↗
PubMed1999

Suppression of experimental abdominal aortic aneurysms by systemic treatment with a hydroxamate-based matrix metalloproteinase inhibitor (RS 132908).

BACKGROUND: Abdominal aortic aneurysms (AAAs) are associated with chronic inflammation, disruption of medial elastin, and increased local production of elastolytic matrix metalloproteinases (MMPs). The purpose of this study was to investigate how treatment with a hydroxamate-based MMP antagonist (RS 132908) might affect the development of experimental AAAs. METHODS: Male Wistar rats underwent intraluminal perfusion of the abdominal aorta with 50 units of porcine pancreatic elastase followed by treatment for 14 days with RS 132908 (100 mg/kg/day subcutaneously; n = 8) or with vehicle alone (n = 6). The external aortic diameter (AD) was measured in millimeters before elastase perfusion and at death, with AAA defined as an increase in AD (DeltaAD) of at least 100%. Aortic wall elastin and collagen concentrations were measured with assays for desmosine and hydroxyproline, and fixed aortic tissues were examined by light microscopy. RESULTS: AAAs developed in all vehicle-treated rats, with a mean AD (+/- SE) that increased from 1.60 +/- 0.03 mm before perfusion to 5.98 +/- 1.02 mm on day 14 (DeltaAD = 276.4 +/- 67.7%). AAAs developed in only five of eight animals (62.5%) after MMP inhibition, with a mean AD that increased from 1.56 +/- 0.05 mm to 3.59 +/- 0.34 mm (DeltaAD = 128.1 +/- 18.7%; P <.05, vs vehicle). The overall inhibition of aortic dilatation attributable to RS 132908 was 53.6 +/- 6.8%. Aortic wall desmosine fell by 85.4% in the vehicle-treated rats (1210.6 +/- 87.8 pmol/sample to 176.7 +/- 33.4 pmol/sample; P <.05) but only by 65.6% in the animals treated with RS 312908 (416.2 +/- 120.5 pmol/sample). In contrast, hydroxyproline was not significantly affected by either elastase perfusion or drug treatment. Microscopic examination revealed the preservation of pericellular elastin and a greater degree of fibrocollagenous wall thickening after MMP inhibition, with no detectable difference in the extent of inflammation. CONCLUSIONS: Systemic MMP inhibition suppresses aneurysmal dilatation in the elastase-induced rodent model of AAA. Consistent with its direct inhibitory effect on various MMPs, RS 132908 promotes the preservation of aortic elastin and appears to enhance a profibrotic response within the aortic wall. Hydroxamate-based MMP antagonists may therefore be useful in the development of pharmacologic approaches to the suppression of AAAs.

Animals↗
PubMed1999

Design and synthesis of thrombin receptor-derived nonpeptide mimetics utilizing a piperazine scaffold.

Focal thrombus formation and vasoconstriction serve to defend vessels when vascular damage occurs, but may be detrimental when an atherosclerotic plaque is disrupted. Recently, the identification of the platelet thrombin receptor opened a new area in the development of agents that may selectively inhibit the effects of thrombin on cells, without affecting fibrin formation. In this regard, we have synthesized a number of 1,4-disubstituted piperazines which are designed to be analogues of thrombin receptor activating peptides (TRAP) and carry the pharmacophoric features of Phe and Arg residues present in the active pentapeptide SFLLR. These compounds were tested in the rat aorta relaxation assay and in platelet aggregation studies and their biological activity was consistent with a direct action on thrombin receptor. Furthermore, the structure activity relationships confirmed the importance of Phe and Arg for receptor activation and the molecular modeling revealed an intriguing relationship between their amphipathic similarity with SFLLR and their biological activity.

Animals↗
PubMed1999

Heterozygous factor XI deficiency associated with three novel mutations.

To determine the utility of single-stranded conformation polymorphism (SSCP) analysis for screening mutations in the factor XI (fXI) gene, we investigated three patients with heterozygous factor XI deficiency. DNA sequence analysis confirmed three novel mutations; a CGC --> TGC (Arg308Cys) mutation in exon 9, a GCT-->GTT (Ala412Val) mutation in exon 11 and an AGC --> AGA (Ser576Arg) mutation in exon 15. We postulated on the structural implications of these missense mutations. Our results demonstrated that genotypic analysis is a useful tool for conclusive differentiation between heterozygous factor XI deficiency and normal subjects.

Factor XI Deficiency↗
PubMed1999

Health screening for people with learning disabilities by a community learning disability nursing service in Northern Ireland.

Over the last 30 years there has been a considerable increase in the life expectancy of people with learning disabilities. This has resulted in changing patterns of morbidity and mortality and an increasing recognition of the health needs of people with learning disabilities. Major strides forward have been made in the reduction of preventable illnesses among the general population. However, among people with learning disabilities such illnesses have received only limited health promotion attention until recently. In the last decade major gaps have been identified in the ability of current primary health services to respond to the needs of people with learning disabilities. The need to respond effectively to this situation has been identified as a priority by the current United Kingdom Government. Following an overview of the literature in relation to the changing health profile of people with learning disabilities and the need for health screening, consideration is given to some of the key difficulties which may be encountered when attempting to utilize current primary health services. The analysis of data derived from the health screening of 373 people with learning disabilities by a community nursing service in Down and Lisburn Health and Social Services Trust reveals the need for further action in relation to cardiovascular status, sensory deficits, mobility and aspects of sexual health.

Activities of Daily Living↗
PubMed1999

The development of meat-eating habits during childhood in Australia.

The development of meat-eating habits of 999 Australian children between 1 and 16 years of age stratified across socioeconomic groups, was determined using a 4-day diary and measurement procedures to document intake. The results indicated that a stable pattern of meat-eating behaviour, as regards the frequency and type of meat eaten was established during the period 1-4 years of age and remained until 10-12 years for males and until at least 14-16 years for females. In contrast, the amount of meat consumed increased with age, the greatest increases occurring with adolescent males who ate the largest amounts of beef, chicken and pork. It is suggested that the early establishment of meat-eating habits may reflect a more general effect that may occur with other types of food.

Adolescent↗