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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
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↗
PubMed2001

Genetics of cognition: outline of a collaborative twin study.

A multidisciplinary collaborative study examining cognition in a large sample of twins is outlined. A common experimental protocol and design is used in The Netherlands, Australia and Japan to measure cognitive ability using traditional IQ measures (i.e., psychometric IQ), processing speed (e.g., reaction time [RT] and inspection time [IT]), and working memory (e.g., spatial span, delayed response [DR] performance). The main aim is to investigate the genetic covariation among these cognitive phenotypes in order to use the correlated biological markers in future linkage and association analyses to detect quantitative-trait loci (QTLs). We outline the study and methodology, and report results from our preliminary analyses that examines the heritability of processing speed and working memory indices, and their phenotypic correlation with IQ. Heritability of Full Scale IQ was 87% in the Netherlands, 83% in Australia, and 71% in Japan. Heritability estimates for processing speed and working memory indices ranged from 33-64%. Associations of IQ with RT and IT (-0.28 to -0.36) replicated previous findings with those of higher cognitive ability showing faster speed of processing. Similarly, significant correlations were indicated between IQ and the spatial span working memory task (storage [0.31], executive processing [0.37]) and the DR working memory task (0.25), with those of higher cognitive ability showing better memory performance. These analyses establish the heritability of the processing speed and working memory measures to be used in our collaborative twin study of cognition, and support the findings that individual differences in processing speed and working memory may underlie individual differences in psychometric IQ.

Adolescent↗
PubMed2001

Peginterferon alfa-2a (40 kDa) monotherapy: a novel agent for chronic hepatitis C therapy.

Current therapy for hepatitis C remains far from optimal. The modification of IFN by the attachment of a polyethylene glycol (PEG) moiety has produced long-lasting IFNs. A 40 kDa branched peginterferon alfa-2a (40 kDa) (PEG-IFN alfa-2a) has unique pharmacokinetic and pharmacodynamic properties. PEG-IFN alfa-2a is absorbed in a sustained manner and its clearance is reduced substantially compared with IFN alfa-2a, resulting in sustained serum drug concentrations. These constant serum drug levels stay above the EC(50) values (effective concentration 50%) needed for antiviral, antiproliferative and immunomodulatory actions. Sustained virological responses were significantly greater in patients who received PEG-IFN alfa-2a versus IFN alfa-2a, with a similar side effect profile. Histological improvements were seen in patients who achieved sustained virological responses and were frequently observed among patients who did not achieve a virological response. The advantages of PEG-IFN alfa-2a were also seen in patients with cirrhosis or hepatitis C virus (HCV) genotype 1.

Animals↗
PubMed2001

Effect of task-relevant cues and state anxiety on motor performance.

12 experienced, female trampolinists participated in a field study designed to test the conscious processing hypothesis, which predicts that the combination of task-relevant knowledge and high state anxiety will impair motor performance. Results supported the hypothesis; however, an alternative attentional explanation of the data was also identified.

Adult↗
PubMed2001

Aroma compound production in cheese curd by coculturing with selected yeast and bacteria.

The microorganisms involved in cheese ripening produce various volatile compounds and induce typical flavors that contribute to cheese variety. To investigate aroma compound generation of cheese microflora, we used a dynamic headspace-gas chromatography-mass spectrometry analysis. To obtain good sensitivity and repeatability of quantification, dynamic headspace conditions and sample preparation were first optimized and led to an extraction set up in which samples were heated at 60 degrees C and diluted with water without pH adjustment. Then three different yeasts and three Geotrichum candidum commonly used in mold surface ripened cheeses were studied in pure culture in a cheese model medium. Thirty-nine cocultures of these three yeasts, the three G. candidum, and five bacteria were studied in the same medium to assess the interaction between microorganisms on aroma compound production. Twenty-four volatile compounds belonging to different chemical classes (alcohols, aldehydes, esters, sulfides, terpenes) were identified and quantified. Yeasts and especially Kluyveromyces lactis produced large amounts of alcohols, aldehydes, esters, and terpenes when cultured alone or in association. Geotrichum candidum and especially G. candidum strain G3 generated the largest amount of sulfides when cultured alone or in association. Finally, bacteria also produced aroma compounds but, except for Brevibacterium linens strain B5, which produced dimethyl trisulfide and ketones, no specific trend in the production of particular aroma compounds could be evidenced.

Bacteria↗
PubMed2001

Posterior restorations--a clinical view.

This paper examines the state-of-the-art in the direct restoration of posterior teeth. The existing paradigms for the management of caries are questioned and some existing methods of cavity preparation are reviewed. Dental restorations need to be durable but able to adapt to a changing environment brought about by wear of the adjacent tooth substance and by fatigue processes within the tooth itself. The wear of restorative materials needs to be matched to that of the tooth, otherwise differential loss of either the restorative material or the enamel may destabilize the occlusion. Esthetic instability due to natural darkening of the tooth with age, punctuated by clinical intervention with bleaching procedures, adds a further dimension to the concept of a permanent restoration. Clinical methods that minimize the disruptive effects of dental restorations upon the remaining tooth structure are a continuing challenge.

Bicuspid↗
PubMed2001

CEREC: science, research, and clinical application.

Computer-aided design/computer-aided manufacture (CAD/CAM), as embodied in the CEREC system, enables the fabrication of high-quality esthetic ceramic restorations chairside. Resin cements are used to complete the clinical process, providing a high-strength, stress-free adhesive assembly. The current generation of CEREC technology can be used to create restorations with a repeatable 50-micron adhesive interface width. Systematic analysis of the literature on clinical trials of CEREC restorations indicates a high level of clinical success. CEREC technology is compatible with contemporary, conservative cavity preparation design and limits pulpal trauma by completing complex restorations in a single visit. The occlusal form of CEREC restorations can be machined with full regard to the patient's occlusion, using functionally generated pathway recordings.

Ceramics↗
PubMed2000

Intramolecular electronic interactions in conjugated ferrocene-pi-extended-tetrathiafulvalene donor-pi-donor molecular hybrids

The synthesis of new hybrid ferrocene and pi-extended tetrathiafulvalene (TTF) donor(1)-pi-donor(2) molecular assemblies 16a-c has been carried out by a Wittig-Horner reaction of the respective phosphonate esters 15a-c with 2-(2-ferrocenylvinyl)-9, 10-anthraquinone (18) prepared by olefination of ferrocenecarboxaldehyde (14) and the anthraquinone phosphonium salt 17. Electrochemical studies show that the D(1)-pi-D(2) (D = donor) molecular assemblies 16a-c essentially retain the redox characteristics of both ferrocene and the pi-extended TTF components and the effects of solvent, temperature, scan rate, and working electrode are significant. Most importantly, pronounced intramolecular electronic interactions between the two donor moieties were observed by cyclic voltammetry and Osteryoung square wave voltammetry in both the ground and charged states. Semiempirical calculations support the electrochemical observations.

Journal Article↗
PubMed2000

A new photoactive and highly soluble C(60)-TTF-C(60) dimer: charge separation and recombination

The covalent linkage of two [60]fullerene cores to a tetrathiafulvalene (TTF) donor affords a soluble and photoactive C(60)-TTF-C(60) triad. Spectroscopic and photophysical characterization of the C(60)-TTF-C(60) triad are given. Although the cyclic voltammetry measurements reveal no notable interaction between the chromophores in the ground state, photophysical data show that in the excited state an intramolecular electron transfer, evolving from the TTF donor to the singlet state of C(60), prevails, yielding a long-lived charge separated radical pair.

Journal Article↗
PubMed2000

Synthesis and characterization of novel optically active polyarylene vinylenes with controlled effective conjugation length

New chiral and soluble binaphthyl derivatives (12 and 13) endowed with carboxaldehyde or cyanomethyl functional groups have been prepared as suitable building blocks for the synthesis by Knoevenagel condensation of a series of optically active block copolymers (1-7) with controlled effective conjugation length. A variety of functionalized co-monomers (14-19) have been prepared by different synthetic procedures to be used in further polymerization reactions with binaphthyl derivatives 12 and 13. Depending upon the nature of the co-monomers, it is possible to tune the wavelength of the new polymers, which is very close to that of the respective repeating units. Fluorescence measurements on polymers 1-3 reveal a strong blue-green emission with Stokes shifts of 74-107 nm. Theoretical calculations at the semiempirical AM-1 level have been carried out on model compounds, and the calculated torsion angles are in agreement with the electronic spectra data. Finally, the redox properties of the polymers prepared (1-7) were determined by cyclic voltammetry, and an amphoteric behavior with oxidation potentials ranging from 1.1 to 1.6 V and reduction potentials close to -1.5 V was found.

Journal Article↗
PubMed2000

New chiral binaphthyl building blocks: synthesis of the first optically active tetrathiafulvalene and 11,11,12,12-tetracyano-9, 10-anthraquinodimethane dimers

New enantiomerically pure binaphthyl derivatives bearing triphenylphosphine or phosphonate groups have been synthesized and used as building blocks to prepare the first optically active TTF and TCAQ dimers. Due to the restricted rotation of the two naphthalene rings, binaphthyl derivatives are ideal candidates to be used as nonplanar spacers between electroactive units in the search for materials with enhanced dimensionality. The electronic absorption spectra of dimers in which the electroactive unit is in conjugation with the naphthalene fragment reveal the presence of intramolecular photoinduced electron-transfer process from the TTF to the naphthalene unit in 5 and 6 and from the naphthalene moiety to the TCAQ unit in 7. Electrochemical studies on the new dimers show the redox potentials of TTF and TCAQ units as well as the oxidation wave for the naphthalene moiety and reveal no significant electronic interaction between the two electroactive units, which is in agreement with the results obtained from theoretical calculations at the PM-3 level which indicate that the angle between rings in the binaphthyl systems ranges from 75 to 80 degrees.

Journal Article↗
PubMed2000

[60]Fullerene adducts with improved electron acceptor properties [In Process Citation]

The synthesis of C(60)-based dyads in which the C(60) core is covalently attached to a strong electron acceptor moiety such as quinones, TCNQ or DCNQI derivatives, has been carried out by 1, 3-dipolar cycloaddition of "in situ" generated azomethyne ylides or nitrile oxides to C(60). As expected, the obtained pyrrolidino[3', 4':1,2][60]fullerenes exhibit reduction potentials of the C(60) framework which are cathodically shifted in comparison with the parent C(60). In contrast, isoxazolo[4',5':1,2][60]fullerenes show reduction waves for the fullerene core that are anodically shifted in comparison with the parent C(60), which indicates that they are remarkably stronger acceptors than C(60).The electron acceptor organic addend also undergoes an anodic shift due to the electronic interaction with the C(60) moiety. The molecular geometry of pyrrolidinofullerenes has been calculated at the semiempirical PM3 level and reveals a highly distorted geometry for the acceptor moiety in compound 13, and a most stable conformation in which both dicyanomethylene units are far away from the C(60) surface.

Journal Article↗