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Biomedical subjects

A Graham

Publications and source records attributed to A Graham.

At least 55 records · Page 3Linked to original sources
PubMed2000

Are routine sensitivity test data suitable for the surveillance of resistance? Resistance rates amongst Escherichia coli from blood and CSF from 1991-1997, as assessed by routine and centralized testing.

Surveillance of antibiotic resistance can be undertaken by compilation of routine data or by central testing of isolates. Routine results can be obtained cheaply and in sufficient quantities for correlation with population and prescribing denominators but there is concern about their quality. As one of a series of ongoing studies to assess this quality, we compared the proportions of resistance amongst Escherichia coli from patients with bacteraemia or meningitis between 1991 and 1997 (i) as recorded in routine data reported to the PHLS and (ii) as found in tests performed at the PHLS Laboratory of Enteric Pathogens (LEP). These two data sets both showed an overall upward trend in the proportion of isolates resistant to ampicillin, trimethoprim, gentamicin and ciprofloxacin. The average annual percentage increase in resistance was estimated in separate logistic regression models, and 95% confidence intervals (CI) were determined. The annual percentage increases in the proportions of isolates reported resistant were similar in the two data sets for trimethoprim, gentamicin and ciprofloxacin but differed for ampicillin. The upward trends were statistically significant except for gentamicin resistance in the LEP data set, where the 95% CI straddled zero. The proportions of resistant isolates for each antibiotic in the two data sets each year were in poorer agreement than the trends; however, the 95% CI of the difference of proportions resistant between the routine and LEP data sets straddled zero in 4 or 5 of the 7 years studied. Some discrepancies might be explained by geographical bias in the sampling or by differences in definitions of resistance. Thus (i) the proportion of resistant isolates tested at LEP almost always fell within the ranges bounded by the highest and lowest proportions for individual Regional Health Authorities, as recorded in the routine data, and (ii) the fact that LEP consistently recorded less gentamicin resistance but more ciprofloxacin resistance than the routine could be explained by breakpoint differences. We conclude that routine susceptibility data for ampicillin, ciprofloxacin, gentamicin and trimethoprim appear sound for E. coli and might be suitable for correlation with other data, e.g. for prescribing.

Bacteremia↗
PubMed2000

Abnormalities of somite development in the absence of retinoic acid.

We describe the effects of an absence of retinoic acid (RA) on the development of somites in the quail embryo. RA was removed by generating vitamin A deficient quail embryos whereupon the resulting defects in the embryos can be analysed. The effect on the somites is threefold. Firstly, they are half the size of normal, but the total number of somites is the same as normal. There has therefore been some global regulation event. Secondly, by TUNEL staining and TEM we show that the lateral halves of all of the somites undergo apoptosis between stages 11 and 14. This effect is confined to the sclerotome of the somites. Thirdly, some of the genes involved in somite differentiation are down-regulated such as fgf-4, fgf-8, engrailed and myogenin whereas others we examined such as cek-8, Delta, follistatin and myf5 are not affected. These studies reveal remarkably specific effects of RA on developmental gene pathways in the embryo.

Animals↗
PubMed2000

Petrofilaments in palynological preparations.

Microscopic structures (petrofilaments) may develop during palynological laboratory processing procedures that are superficially similar to secondary wall thickenings and elaters. These filaments form from angular bodies that resemble fungal spores and resin bodies. The angular bodies are a type of hydrocarbon called asphaltene and extrude the filaments when compounds in the bodies react with solvents in the mounting medium. They may be misinterpreted as fossils and so are illustrated here for the first time in the published literature.

Journal Article↗
PubMed2000

Studies in Neotropical paleobotany. XIV. A palynoflora from the Middle Eocene Saramaguacan Formation of Cuba.

An assemblage of 46 fossil pollen and spore types is described from a core drilled through the middle Eocene Saramaguacán Formation, Camagüey Province, eastern Cuba. Many of the specimens represent unidentified or extinct taxa but several can be identified to family (Palmae, Bombacaceae, Gramineae, Moraceae, Myrtaceae) and some to genus (Pteris, Crudia, Lymingtonia?). The paleoclimate was warm-temperate to subtropical which is consistent with other floras in the region of comparable age and with the global paleotemperature curve. Older plate tectonic models show a variety of locations for proto-Cuba during Late Cretaceous and later times, including along the norther coast of South America. More recent models depict western and central Cuba as two separate parts until the Eocene, and eastern Cuba (joined to northern Hispaniola) docking to central Cuba also in the Eocene. All fragments are part of the North American Plate and none were directly connected with northern South America in late Mesozoic or Cenozoic time. The Saramaguacán flora supports this model because the assemblage is distinctly North American in affinities, with only one type (Retimonocolpites type 1) found elsewhere only in South America.

Journal Article↗
PubMed1999

Developmental evolution: this side of paradise.

It has long been appreciated that the evolution of snakes involved the loss of limbs and axis elongation, but their developmental basis has been obscure. It has now been shown that alterations in the deployment of Hox genes and an early block in the formation of hindlimb primordia underpin these modifications.

Animals↗
PubMed1999

Limb development: Farewell to arms.

Forelimbs and hindlimbs are, clearly, quite different, and it has long been appreciated that their differences are assigned early in development; the genetic basis of these differences has been more mysterious, however. Recent work has now shown that the homeobox gene Pitx1 imparts identity to the developing hindlimb bud.

Animals↗
PubMed1999

Comparison of pregnancy-specific interventions to a traditional treatment program for cocaine-addicted pregnant women.

Alcohol and drug use in pregnancy is a significant concern. There is a paucity of treatment programs for substance-abusing pregnant women, especially if indigent. Furthermore, treatment retention is compromised when the drug of choice is crack-cocaine. This paper reports the results of a study comparing treatment retention of cocaine-abusing indigent pregnant women before and after incorporating pregnancy-specific interventions. Audits were performed on 603 charts of women enrolled between 1988 and 1994 in either a traditional treatment program (n = 114) or in the Pregnancy Substance Abuse Program (PSAP) (n = 489). Differences in treatment retention were found between the two treatment groups. Drop-out rates from the inpatient component of treatment were significantly lower in the PSAP group than in the control group (11.3% vs. 38.6%, p < .001). There was a higher rate of completion of outpatient treatment in the PSAP compared to the control group (34.4% vs. 13.5%, p < .005). These results were achieved with a 2-day decreased inpatient stay. Treatment retention improved when specialized interventions were provided, at minimal additional cost. These results have implications for other publicly funded treatment programs.

Aftercare↗
PubMed1999

The small heat shock-related protein-20 is an actin-associated protein.

PURPOSE: The activation of cyclic nucleotide-dependent signaling pathways in vascular smooth muscle is important for the prevention of vein graft spasm and neointimal hyperplasia. Cyclic nucleotide-dependent relaxation is associated with an increase in the phosphorylation of a small heat shock-related protein (HSP20). In this investigation, we examined the mechanisms by which HSP20 may modulate relaxation. METHODS: The relaxation responses of the bovine carotid artery smooth muscles were determined in a muscle bath. HSP20 phosphorylation was quantitated with isoelectric-focusing immunoblots. The association with actin was determined with coimmunoprecipitation and cosedimentation. Molecular sieving columns were used to examine the macromolecular associations of HSP20. RESULTS: The activation of cyclic nucleotide signaling pathways leads to the complete relaxation of carotid smooth muscle. This relaxation response is associated with an increase in the phosphorylation of HSP20. Actin coimmunoprecipitated with HSP20, and the association of actin with recombinant HSP20 in vitro was phosphorylation-state dependent. Finally, HSP20 exists in large (>100 kDa) aggregates, which dissociate with the activation of cyclic nucleotide signaling pathways. CONCLUSION: These data support a role of HSP20 phosphorylation in mediating smooth muscle relaxation, possibly via a direct interaction of large aggregates of HSP20 with the contractile elements.

Actins↗
PubMed1999

Expression of GATA-2 in the developing avian rhombencephalon.

Here we describe the expression pattern of GATA-2 in the developing chick hindbrain. We found that during the early period of neurogenesis this gene specifically labels a particular neuronal subtype, the contralateral vestibular-acoustic neurons of rhombomere 4, and that expression of this gene in these cells is transient. We also found that GATA-2 labels a broader territory of the ventral neural tube at later stages. As well as this hindbrain expression, we also describe expression of GATA-2 in the otic vesicle, oculomotor nucleus, third nerve and metanephros.

Animals↗
PubMed1999

Maternal and child constitutional factors and the frequency of melanocytic naevi in children.

This study examined the association between numbers of benign melanocytic naevi in 7-year-old children in Oxfordshire born in 1988-9 with their mother's arm naevus count, and maternal and child pigmentation factors. We believe this is the first time that the relationship between child and maternal naevus counts has been reported. A high naevus count in the child was associated with male sex (P = 0.009), freckling (P = 0.001) and propensity of the child to burn in the sun (P = 0.05). A low naevus count was observed in red-haired children (P = 0.02). The strongest association of child's naevus count was with a high maternal arm naevus count, independent of the child's pigmentation factors (trend P < 0.0001). Maternal pigmentation factors were not associated with child's naevus count independent of the child's own pigmentation factors. Maternal arm naevus counts may be a better predictor of child naevus count than the child's own pigmentation factors and children. There has not been examination, however, of the relationship between naevus counts in children and those in their parents. We therefore conducted a study of the occurrence of naevi in children aged 7-8 years in Oxfordshire, examining, in addition to sex and pigmentation factors in the child, the relationship of maternal pigmentation factors and maternal naevus counts with naevi in their offspring.

Age Factors↗
PubMed1999

Pharmacological characterization of mucin secretion from CHO-K1-hNK(1)R cells.

Numerous respiratory diseases increase mucin secretion from human airways. Several investigators hypothesize that mucin secretion from airway epithelium is NK(1)-receptor mediated. We have developed a mucin secretion assay using CHO-K1 cells transfected with the human NK(1)receptor (CHO-K1-hNK(1)R) that respond to NK(1)-specific agonists. Cells were labeled with [(3)H]-glucosamine and stimulated with agonists including Ac-[Arg(6), Sar(9), Met(O(2))(11)] Substance P(6-11) (ASMSP; NK(1)-specific), [beta-Ala(8)]-Neurokinin A(4-10) (BANK; NK(2)-specific), or human neutrophil elastase (HNE). Basal mucin secretion from CHO-K1-hNK(1)R and non-transfected cells was similar. Stimulation of CHO-K1-hNK(1)R, but not CHO-K1, with ASMSP or BANK concentration-dependently increased mucin secretion (pD(2)value[Emax] = 8.9(1)+/-0.1(3)[175%] and 7.56+/-0.05[100%], respectively). SR140333 (NK(1)antagonist), but not SR48968 (NK(2)antagonist), decreased ASMSP- and BANK-induced mucin release from CHO-K1-hNK(1)R. In these cells, endothelin-1, angiotensin II, serotonin, phenylephrine, senktide, and methacholine showed negligible effects on mucin secretion. A similar lack of effect of these agonists was observed in non-transfected CHO-K1 cells. HNE increased mucin release four to five fold in both cell types. These studies demonstrate that stimulation of CHO- K1-hNK(1)R with ASMSP and BANK causes robust and NK(1)-selective mucin release.

Angiotensin II↗
PubMed1999

Reduction of transition metals by human (THP-1) monocytes is enhanced by activators of protein kinase C.

Macrophages oxidize low density lipoprotein (LDL) by enzymatic and non-enzymatic mechanisms; however, it is evident that macrophage reduction of transition metals can accelerate LDL oxidation in vitro, and possibly in vivo. Distinct cellular pathways contribute to this process, including trans-plasma membrane electron transport (TPMET), and production of free thiols or superoxide. Here, we explore the role of protein kinase C (PKC) in regulating transition metal reduction by each of these redox-active pathways, in human (THP-1) monocytes. We demonstrate that PKC agonists and/or inhibitors modulate reduction of transition metals by monocytes: both thiol-independent (direct) and thiol-dependent (indirect) pathways for transition metal reduction are enhanced by PKC activation, suggesting a potential strategy for therapeutic intervention.

Cell Line↗
PubMed1999

Chemical differences between long and short amosite asbestos: differences in oxidation state and coordination sites of iron, detected by infrared spectroscopy.

OBJECTIVES: Short fibres of amosite asbestos (SFA), obtained by ball milling of long fibres (LFA), have been shown to be less pathogenic than long fibres. Accumulating evidence suggests an important role for differences in surface chemistry between fibres. Iron has been implicated in the pathogenesis of asbestos fibres. In this study infrared (IR) spectroscopy was used to compare LFA and SFA in terms of the coordination and oxidation state of iron at the three cation sites (M1, M3, M1). METHODS: Infrared was used to examine LFA ad SFA, when dry and when hydrated in the presence and absence of the chelators desferroxamine and ferrozine. With appropriate software the proportions of iron and its oxidation states in the overlapping peaks were resolved and assigned, and the three coordination sites were identified. Data were obtained from 10 samples of both lengths of fibre for each of the four treatments. Iron release was also monitored. RESULTS: Iron was significantly more oxidised in LFA than SFA. Further oxidation of the dry fibres with water, ferrozine, or desferroxamine tended to abolish these differences. There were also significant differences between the proportions of iron held in the different coordination sites of the fibres. For LFA, a higher proportion of its iron was held in the cation sites coordinating less with iron and more with Mg. Interestingly, the sites coordinating single irons were significantly more oxidised than multiple sites. The single iron sites were more oxidised in LFA than SFA and were more readily oxidised by the treatments. CONCLUSIONS: Important chemical differences between LFA and SFA were found. There seemed to be some mobility of iron near the surface. Based on these data it is speculated that the 1 iron surface site may be important in pathogenesis.

Asbestos, Amosite↗
PubMed1999

Evidence for collapsin-1 functioning in the control of neural crest migration in both trunk and hindbrain regions.

Collapsin-1 belongs to the Semaphorin family of molecules, several members of which have been implicated in the co-ordination of axon growth and guidance. Collapsin-1 can function as a selective chemorepellent for sensory neurons, however, its early expression within the somites and the cranial neural tube (Shepherd, I., Luo, Y. , Raper, J. A. and Chang, S. (1996) Dev. Biol. 173, 185-199) suggest that it might contribute to the control of additional developmental processes in the chick. We now report a detailed study on the expression of collapsin-1 as well as on the distribution of collapsin-1-binding sites in regions where neural crest cell migration occurs. collapsin-1 expression is detected in regions bordering neural crest migration pathways in both the trunk and hindbrain regions and a receptor for collapsin-1, neuropilin-1, is expressed by migrating crest cells derived from both regions. When added to crest cells in vitro, a collapsin-1-Fc chimeric protein induces morphological changes similar to those seen in neuronal growth cones. In order to test the function of collapsin-1 on the migration of neural crest cells, an in vitro assay was used in which collapsin-1-Fc was immobilised in alternating stripes consisting of collapsin-Fc/fibronectin versus fibronectin alone. Explanted neural crest cells derived from both trunk and hindbrain regions avoided the collapsin-Fc-containing substratum. These results suggest that collapsin-1 signalling can contribute to the patterning of neural crest cell migration in the developing chick.

Animals↗