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Biomedical subjects

N Martin

Publications and source records attributed to N Martin.

At least 37 records · Page 2Linked to original sources
PubMed2002

Cardiovascular risk assessment in patients with retinal vein occlusion.

AIM: Patients with retinal vein occlusions (RVO) are at increased risk of cardiovascular disease (CVD). The risk of future CVD was determined using the Framingham algorithm and this risk estimate was used to guide decisions about preventative treatment for CVD in RVO patients. METHODS: 107 unselected RVO patients were studied. After excluding 18 patients because of age, missing data, or pre-existing cardiovascular disease, the calculated coronary heart disease risks (cCHDR) and calculated cardiovascular disease risks (cCVDR) were calculated on the 89 remaining and compared with both the standardised risk and the published incidence of CHD in England by t test or chi(2) test. RESULTS: The mean 10 year cCVDR was significantly higher than the Framingham standardised risk for all RVOs (20.6% (1.2%) v 15.7% (1.1%), p = 0.009) and female RVOs (17.8% (1.2%) v 12.7% (1.0%), p = 0.022) in particular. The 10 year cCHDR, compared to the actual incidence of CHD in England between the ages of 30 and 74 years, was > 15% in twice as many males than expected (62% v 28%, p <0.0001). This rose to almost six times when cCHDRs greater than 30% were compared (17% v 3%, p = 0.002). There was a fourfold increase in the proportion of female RVO patients with a cCHDR above 15% (40% v 9%, p <0.0001) and at a cCHDR of 30% and above (10% v 0%, p = 0.004). There were also significant differences in the cCHDR between central and branch RVO (both sexes). The branch form of RVO (BRVO) having higher cCHDRs because of systolic hypertension (164.1 (21.6) mm Hg v 149.5 (23.5) mm Hg, p = 0.003) and age (61.7 (8.3) years v 56.7 (10.6) years, p = 0.017). CONCLUSIONS: RVO is the presenting complaint in a group of patients at increased risk of CVD and is in agreement with the long term follow up data demonstrating an increased mortality from CVD in patients with RVO. The Framingham algorithm can accurately determine the cCHDR (or cCVDR) to assist the clinician in deciding who to treat in accordance with the Joint British Societies' guidelines, with particular regard to hypertension, lipid lowering, and the use of aspirin therapy.

Aged↗
PubMed2001

Anion directed assembly of a dinuclear double helicate.

The synthesis and structural characterisation of the diamino-bis-pyridine ligand L2 and its diammonium-bispyridinium salt [(H4L2Cl)2].6Cl.H2O 1, are reported; X-ray diffraction studies reveal that chloride coordination causes the latter to adopt a double-helicate structure in the solid-state.

Journal Article↗
PubMed2001

Synthesis, crystal structure determination, and biological properties of the DNA-dependent protein kinase (DNA-PK) inhibitor 3-cyano-6-hydrazonomethyl-5-(4-pyridyl)pyrid-[1H]-2-one (OK-1035).

The first reported synthesis of the DNA-PK inhibitor 3-cyano-6-hydrazonomethyl-5-(4-pyridyl)pyrid-[1H]-2-one (OK-1035) is described. The structure of OK-1035 was validated by X-ray crystallography. An IC(50) value of 100 microM was determined for inhibition of DNA-PK, and this is approximately 12-fold higher than that reported previously.

Chromones↗
PubMed2001

VIDA: a virus database system for the organization of animal virus genome open reading frames.

VIDA is a new virus database that organizes open reading frames (ORFs) from partial and complete genomic sequences from animal viruses. Currently VIDA includes all sequences from GenBank for Herpesviridae, Coronaviridae and Arteriviridae. The ORFs are organized into homologous protein families, which are identified on the basis of sequence similarity relationships. Conserved sequence regions of potential functional importance are identified and can be retrieved as sequence alignments. We use a controlled taxonomical and functional classification for all the proteins and protein families in the database. When available, protein structures that are related to the families have also been included. The database is available for online search and sequence information retrieval at http://www.biochem.ucl.ac.uk/bsm/virus_database/ VIDA.html.

Animals↗
PubMed2001

A rapid classification protocol for the CATH Domain Database to support structural genomics.

In order to support the structural genomic initiatives, both by rapidly classifying newly determined structures and by suggesting suitable targets for structure determination, we have recently developed several new protocols for classifying structures in the CATH domain database (http://www.biochem.ucl.ac.uk/bsm/cath). These aim to increase the speed of classification of new structures using fast algorithms for structure comparison (GRATH) and to improve the sensitivity in recognising distant structural relatives by incorporating sequence information from relatives in the genomes (DomainFinder). In order to ensure the integrity of the database given the expected increase in data, the CATH Protein Family Database (CATH-PFDB), which currently includes 25,320 structural domains and a further 160,000 sequence relatives has now been installed in a relational ORACLE database. This was essential for developing more rigorous validation procedures and for allowing efficient querying of the database, particularly for genome analysis. The associated Dictionary of Homologous Superfamilies [Bray,J.E., Todd,A.E., Pearl,F.M.G., Thornton,J.M. and Orengo,C.A. (2000) Protein Eng., 13, 153-165], which provides multiple structural alignments and functional information to assist in assigning new relatives, has also been expanded recently and now includes information for 903 homologous superfamilies. In order to improve coverage of known structures, preliminary classification levels are now provided for new structures at interim stages in the classification protocol. Since a large proportion of new structures can be rapidly classified using profile-based sequence analysis [e.g. PSI-BLAST: Altschul,S.F., Madden,T.L., Schaffer,A.A., Zhang,J., Zhang,Z., Miller,W. and Lipman,D.J. (1997) Nucleic Acids Res., 25, 3389-3402], this provides preliminary classification for easily recognisable homologues, which in the latest release of CATH (version 1.7) represented nearly three-quarters of the non-identical structures.

Computational Biology↗
PubMed2001

An overview of the retro-Diels-Alder reaction in semiunsaturated heterocyclic rings: mass spectra of new substituted 1,4,5,6,7,8-hexahydroquinolines and their oxo-analogues 5,6,7,8-tetrahydro-4H-chromenes.

Electron impact ionization (EI), chemical ionization (CI), electrospray ionization (ESI) and tandem mass spectrometry (MS/MS) were used to investigate a number of relatively large and structurally related new heterocycles such as substituted 1,4,5,6,7,8-hexahydroquinolines and their oxa-analogues 5,6,7,8-tetrahydro-4H-chromenes. In the EI spectra the hexahydroquinolines undergo the loss of the substituent attached at the C4 position, while the 4H-chromenes undergo a retro-Diels-Alder reaction (RDA) after elimination of the C4 substituent. Under chemical ionization conditions the RDA reaction is observed only for the 4H-chromenes. The ESI-MS/MS spectra reveal results similar to the EI and CI spectra, since the 4H-chromenes undergo RDA reactions while the hexahydroquinolines form a very stable even-electron pyridium ion derived from the loss of the C4 substituent.

Journal Article↗
PubMed2001

Genetic and physical delineation of the region overlapping the progressive motor neuropathy (pmn) locus on mouse chromosome 13.

The mouse autosomal recessive mutation progressive motor neuropathy (pmn) results in early onset motor neuron disease with rapidly progressing hindlimb paralysis, severe muscular wasting, and death at 4--6 weeks of age. pmn is thus considered a good animal model for motor neuron diseases and the characterization of the causative gene should help in understanding the biological causes of human spinal muscular atrophies. Here we report the generation of a physical map based on a high-resolution and high-density genetic map encompassing the pmn locus on mouse chromosome 13. We have positioned the pmn locus and a cluster of markers cosegregating with it within a genetic interval of 0.30 cM, delineated by two clusters of markers. We have constructed an approximately 850-kb contig of BACs spanning the pmn critical region. This BAC contig contains the breakpoint of synteny between mouse chromosome 13 and human 1q and 7p regions and lays the foundation for identifying at the molecular level such a breakpoint region. The physical and genetic maps provided a support for the identification of five transcription units positioned in the nonrecombinant interval, and constitute invaluable tools for the identification of other candidate genes for the pmn mutation.

Alleles↗
PubMed2001

Fluvastatin therapy improves microcirculation in patients with hyperlipidaemia.

The purpose of this study was to investigate the effect of fluvastatin on the microcirculation of patients with hyperlipidaemia (low-density lipoprotein cholesterol > 160 mg/dL, triglycerides < 350 mg/dl) inadequately controlled by diet. After a dietary run-in of 4 weeks, patients were randomised in a double-blind study to receive fluvastatin 40 mg twice daily (n = 24) or placebo (n = 24) for 12 weeks. The effect on microcirculation was assessed using capillary microscopy and laser Doppler fluxmetry at the nailfold at baseline and at 6 and 12 weeks after initiation of therapy. Capillaroscopy showed that fluvastatin improved microcirculation, i.e. time to peak flow during postocclusive reactive hyperaemia dropped from 19.7 +/- 7.2 s at baseline to 12.3 +/- 9.5 s at week 6 (P < 0.01) and 10.6 +/- 6.5 s at week 12 (P < 0.0001). These results were confirmed using laser Doppler fluxmetry to study microcirculation in thermoregulatory capillaries at the same site. A significant decrease in total and LDL-cholesterol was achieved during fluvastatin therapy. In conclusion, fluvastatin therapy improves microcirculation in nutritive as well as thermoregulatory capillaries in hypercholesterolaemic patients within 6 weeks.

Anticholesteremic Agents↗
PubMed2001

Public perceptions of environmental quality: a survey study of beach use and perceptions in Los Angeles County.

Despite documented successes in the battle to clean up the coastal waters of Southern California, Los Angeles County residents continue to view the ocean more as a place of pollution than a vibrant and healthy place for bathing and swimming. This study shows that residents of Los Angeles County tend to hold perceptions of marine water quality that are at odds with data on bacteriological measures of water quality collected by local sanitation districts (and reported by not-for-profit Heal the Bay). Summary results of a survey of 400 randomly chosen households in Los Angeles County are given. Respondents were asked about their beach use and perceptions of environmental quality: both coastal water quality and air quality. The results suggest that perceptions of coastal water quality may be influenced less by "current coastal education campaigns" and more by the media and other factors.

Adult↗
PubMed2001

Expansion behaviour of compomer restoratives.

This study measured the dimensional changes due to hygroscopic expansion that occur in five commercially available compomer restorative materials using a computer-controlled laser micrometer. The materials tested were; [C] = Compoglass-F (Vivadent); [D] = Dyract AP (Dentsply DeTrey); [E] = Elan (Kerr); [F] = F2000 (3M); [H] = Hytac (Espe). Twelve discs of each test material were prepared, 10 mm diameter x 1 mm thickness. All specimens were kept dry for 48 h during polymerisation. Two control specimens of each group were kept in a desiccating chamber; five specimens in deionized water at 37 degrees C and five specimens in artificial saliva (Salivace, Penn) at 37 degrees C. The diameter of each disc was measured automatically across 200 points by rotation through the laser beam. These measurements, together with weight measurements, were carried out at intervals over a 2 month period. At 2 months, the mean % changes in volume after water immersion were: [C] = 2.45% (SD = 0.10); [D] = 1.50% (SD = 0.12); [E] = 1.53% (SD = 0.09); [F] = 1.69% (SD = 0.12); [H] = 1.44% (SD = 0.18). Specimens immersed in artificial saliva showed expansion rates identical to those immersed in water with the exception of material [H] at 1.73% (SD = 0.02) (p = 0.01). All specimens immersed in saliva showed a greater weight gain than those in water. The time taken to reach 90% of the final expansion varied from 7 days [F] to 50 days [H].

Compomers↗
PubMed2001

The effect of surface coating on the bond strength of machinable ceramics.

This study examined the nature of the surface presented by a machinable feldspathic porcelain and by a machinable glass-ceramic for bonding to conventional composite luting agents and measured the bond strengths which may be achieved with various surface treatments. There was no significant difference between the bond strengths achieved to etched porcelain, Silicoated porcelain or etched glass-ceramic. Silicoated glass-ceramic specimens showed a significantly higher adhesive assembly strength (p = 0.02). Examination of the fractured specimens showed that in all cases the failure involved part cohesive failure of the ceramic surface and part failure at the cement-ceramic interface.

Acid Etching, Dental↗
PubMed2001

H-7 and fetal calf serum (FCS) act synergistically to increase apoptosis in the KB line of human oral carcinoma cells.

There is a high incidence of oral squamous cell carcinoma (SCC) worldwide. The survival rate is among the lowest of the major cancers and has not improved significantly over the past two decades. The KB line of human oral carcinoma cells is a useful experimental system for studies of the biology of oral SCC. In a previous study, we reported inhibition of KB cell proliferation and stimulation of desmosome formation in confluent cultures treated with 20 microM H-7 (1-(5-isoquinolinylsulfonyl)-2-methylpiperazine). In the present study, the effects of this protein kinase C (PKC) inhibitor on the survival of KB cells were investigated. Apoptotic cells were detected using a combination of Hoechst 33258 nuclear stain, TUNEL technique and ultrastructural analysis. Our results indicated that H-7 significantly increased apoptosis in KB cells in a dose-dependent manner. Maximal stimulation occurred at 100 microM, the highest dose of H-7 tested. Apoptotic cells exhibited nuclear fragmentation, chromatin condensation and apoptotic bodies. Interestingly, H-7 and fetal calf serum (FCS) acted synergistically to increase apoptosis in KB cells, suggesting that there is a serum activated subpopulation of H-7 target cells in the cultures. The underlying mechanism of activation remains to be elucidated. Our study suggests that the PKC inhibitor H-7 is a potentially useful cytostatic agent for oral carcinoma cells.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed2001

Feminist bioethics and psychiatry.

Feminist bioethics is a relatively new field, the major works in which only started to appear in the late 1980s. At first feminist bioethicists focused mainly on issues of particular concern to women such as reproduction. Recently, papers have begun to appear that show that a feminist analysis can be brought to bear on any subject traditional bioethics discusses. So far, however, feminist bioethics has not been brought to bear on psychiatry. There have been feminist critiques of psychiatry and feminist discussions of certain diagnostic categories that disproportionately affect women, but these are concerned with women's issues within psychiatry and how psychiatry has been used to oppress women. Certainly these are important, but what has been missing is a discussion of psychiatry in the sense that feminist bioethics suggests a general critique of psychiatry and the rethinking of the practice of psychiatry, regardless of whether the specific instances involved are women's issues. In this paper I look at what such a feminist bioethical intervention into psychiatry would look like.

Bioethics↗
PubMed2001

Association of GSTT1 non-null and NAT1 slow/rapid genotypes with von Hippel-Lindau tumour suppressor gene transversions in sporadic renal cell carcinoma.

The von Hippel-Lindau (VHL) tumour suppressor gene is commonly mutated in renal cell carcinoma of clear cell type (CCRCC). We investigated the possible relationship between VHL mutations in sporadic CCRCC and polymorphism of genes encoding enzymes involved in carcinogen metabolism: two cytochrome P450 monooxygenases (CYP1A1 and CYP2D6), one NAD[P]H:quinone oxidoreductase (NQO1), three glutathione S-transferases (GSTM1, GSTT1 and GSTP1) and two arylamine N-acetyltransferases (NAT1 and NAT2). We analysed DNA from tumour and nontumoural kidney tissue from 195 CCRCC patients. Single VHL mutations were identified in 88 patients and double mutations were present in two patients. Nine of 18 transversions were GC to TA, four were AT to TA, four were GC to CG and one was AT to CG. Ten of 19 transitions were GC to AT and nine were AT to GC. We also identified 53 frameshifts and two GC to AT at CpG. An excess of transversions was observed in a subset of patients with active GSTT1 [GSTT1 (+) genotype] and probably defective NAT1 (NAT1 S/R variant genotype). All 18 transversions were in GSTT1 (+) patients, whereas only 76% of transitions (P = 0.05) and 81% of the other mutations (P = 0.06) occurred in this genotype. We found that 28% of the transversions were in the NAT1 S/R genotype versus 12% of the transitions (P = 0.40) and 4% of the other mutations (P = 0.01). This suggests that pharmacogenetic polymorphisms may be associated with the type of acquired VHL mutation, which may modulate CCRCC development.

Acetyltransferases↗
PubMed2001

Immunohistological study of entheses in spondyloarthropathies: comparison in rheumatoid arthritis and osteoarthritis.

OBJECTIVE: To determine which inflammatory cell types are present in entheses from patients with spondyloarthropathy (SpA) compared with patients with rheumatoid arthritis (RA) or osteoarthritis (OA). METHODS: Enthesis specimens were obtained during orthopaedic procedures in eight patients with SpA, four with RA, and three with OA. After decalcification, the lymphocyte subsets (CD3, CD4, CD8, CD20) in the bone marrow component of each enthesis were measured by an immunohistochemical technique. RESULTS: Oedema and an inflammatory infiltrate were present in all the SpA specimens, being clearly predominant in the bone marrow component of the entheses. The density of all cell types in the bone marrow was significantly higher in the SpA group than in the two other groups. The cell type CD3+ showed the greatest difference between the SpA and RA groups, being increased fivefold in the SpA group. Within the SpA group, CD3+ cells were considerably more numerous than CD20+ cells-a difference from the RA group-and the predominant T cells were CD8+. CONCLUSION: Persistent oedema with an inflammatory infiltrate composed predominantly of CD8+ cells was noted in the entheses of patients with SpA, being predominant in the bone marrow. These results suggest that CD8+ cells may have a key role in local inflammation in SpAs.

Adult↗
PubMed2001

Interaction of rapid nongenomic cardiovascular aldosterone effects with the adrenergic system.

Interactions between the renin-angiotensin-aldosterone system and the adrenergic system are complex and have mainly been attributed to angiotensin II, with knowledge about aldosterone action much less advanced. Only recently has evidence been forthcoming that aldosterone blunts the baroreceptor reflex and lowers heart rate variability in humans. Both effects point to an adrenergic-like action of aldosterone. It has been proposed that this blunting of baroreceptor sensitivity is mediated nongenomically and that nongenomic aldosterone action itself is modulated by the adrenergic system. The aim of the present study was to prove the hypothesis of an interaction between the autonomic nervous system and rapid, nongenomic aldosterone effects. We conducted a randomized, double blind, 8-fold cross-over trial on 18 healthy male volunteers. After pretreatment with the beta-blocking agent esmolol, the beta-agonist dobutamine, the alpha(1)-agonist phenylephrine, or placebo, placebo (0.9% NaCl) or aldosterone (0.5 mg) was injected. After aldosterone injection the peak plasma levels were supraphysiological, reaching nanomolar concentrations. Primary target variables were differences in changes in mean arterial blood pressure, systemic vascular resistance, and cardiac output depending on the pretreatment. Cardiovascular parameters were measured by impedance cardiography during the maintained infusion of the adrenergic modulators for 45 min. Comparing pretreatments, diverse acute, and thus nongenomic, effects of aldosterone on mean arterial blood pressure were observed. After esmolol pretreatment, aldosterone caused an increase in mean arterial blood pressure by 4.1%, whereas after dobutamine pretreatment mean arterial blood pressure decreased by 1.6%, and the difference was statistically significant (P < 0.01). These effects were significant (P < 0.005) for the first 12 min, underlining their nongenomic nature. Our data support the hypothesis that aldosterone, via nongenomic mechanisms, has diverse effects on the cardiovascular system that depend on the preexisting adrenergic state. Furthermore, aldosterone blunts the blood pressure-lowering effect of the beta-blocking agent esmolol by a nongenomic mechanism.

Adrenergic alpha-Agonists↗