Biomedical subjects
Publications and source records attributed to N Martin.
Triazoline[4,5][60]fullerenes are strong electron acceptors that form with tetrathiafulvalene (TTF), a novel type of donor-acceptor dyad exhibiting efficient improved electron-transfer dynamics. In particular, a rapid photoinduced intramolecular electron transfer, forming a charge-separated state, is followed by a slow charge recombination to generate the fullerene triplet excited state in moderate quantum yields.
New substituted 2-amino-3-cyano-4H-pyrans have been studied by electron ionization (EI), chemical ionization (CI) and electrospray ionization (ESI) mass spectrometry. The retro-Diels-Alder reaction (RDA) is the main fragmentation pattern observed in the EI spectra forming an unsaturated ketone as the diene fragment. In contrast, a different RDA reaction takes place yielding an unsaturated amide as diene fragment together with the unsaturated ketone in the CI spectra. The MS/MS spectra obtained using an ESI source reveal that the favoured fragmentation by collision induced dissociation (CID) is the elimination of the substituent at the C4 position with formation of a stable pyrilium cation.
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OBJECTIVES: To quantify the width of the cement interface between ceramic inlays generated by the CEREC-2 CAD-CAM system and the tooth, and to determine the effect of cement viscosity on the interface width. METHODS: Standardised MOD cavities were cut in 15 human premolar teeth using a custom paralleling device. A ceramic inlay was made with a CEREC-2 CAD-CAM machine for each tooth. The inlays were cemented using one of three resin-based composite systems of varying viscosity; a hybrid microfilled posterior composite, a compomer restorative and a dual-cure luting composite. The teeth were subsequently sectioned and measurements were taken at 21 key points with the aid of an image-analysis light microscopy system. RESULTS: Statistical significance tests were applied to examine for difference in interface dimensions at specific points within each of the cement-groups and amongst groups. The interface space at the occlusal walls has a distinct wedge shape, being narrower at the external interface (50 microns, SD 15) than internally (211 microns, SD 38). There is no statistically significant difference in the interface dimensions of the gingival floor between the boxes that lie above and below the CEJ. There is no statistically significant difference in the width of the interface at any given point between the three cement groups. SIGNIFICANCE: There is a significant improvement in the fit of CEREC-2 restorations when compared with the original CEREC system. Cements of varying viscosity (within the measured range) may be used for cementation of these inlays, without adversely affecting the width of the interface. Caution must be exercised with light-activated composite cements to ensure adequate transmission of light through the ceramic and the underlying composite cement.
W. Ruml and A. Caramazza's (2000) analysis of the model of normal and aphasic lexical access proposed by G. S. Dell, M. F. Schwartz, N. Martin, E. M. Saffran, and D. A. Gagnon (1997) is completely at odds with current practice concerning the use of models in psychology. An evaluation of Dell et al.'s original claims using Ruml and Caramazza's model parameters sustains these claims in all respects.
PURPOSE: Hyperhomocysteinaemia has been linked to macrovascular disease. Our aim was to investigate whether there is a relationship between fasting plasma total homocysteine levels and retinal vascular disease. METHODS: We measured the homocysteine levels in 70 patients with arterial or venous retinal vessel occlusion and compared them with the levels in 85 controls without evidence of ischaemic heart disease. Homocysteine levels were determined by high-performance liquid chromatography with electrochemical detection and compared after logarithmic transformation. RESULTS: Homocysteine levels were found by univariate analysis (unpaired two-tailed t-test) to be significantly higher in the group with retinal artery occlusion than the group with retinal vein occlusion (p = 0.045) and in both groups compared with controls (18.4 and 13.8 vs 9.5 mumol/l; p = 0.0002 and < 0.0001, respectively). The controls, however, were significantly younger than the subjects (51.5 +/- 15.4 vs 66.2 +/- 11.9 years; p < 0.0001), but analysis of the results by age revealed significant differences between the groups and controls for the seventh decade (vein occlusions, p = 0.05) and for the eighth decade (artery occlusions, p = 0.037). Subgroup analysis of the retinal vessel occlusion group revealed significant differences in mean blood pressure between those with branch retinal vein occlusions (175/100 mmHg) and both those with central retinal vein occlusions (155/88 mmHg) and those with retinal artery occlusions (157/86 mmHg). Both vein occlusion subgroups also differed significantly with regard to homocysteine levels, branch < central (12.2 +/- 1.3 vs 15.0 +/- 1.6 mumol/l, p = 0.03). Multiple linear regression analysis revealed significant relationships between homocysteine levels and the presence of retinal vessel occlusion (p = 0.0002), serum creatinine (p = 0.001) and age (p = 0.003), but not gender. CONCLUSIONS: We conclude that homocysteine may be a risk factor for retinal vascular disease and could be simply and cheaply treated with folate and vitamins B6 and B12.
From 8,419 worldwide clinical isolates of Streptococcus pneumoniae obtained during 1997-1998, 69 isolates with reduced susceptibility or resistance to fluoroquinolones (FQs) were molecularly characterized. For the isolates in this prevalence study, only parC (Ser-79-->Tyr) and gyrA (Ser-81-->Phe or Tyr) mutations, especially in combination, were found to contribute significantly to resistance. These mutations influenced the FQ MICs to varying degrees, although the rank order of activity remains independent of mutation type, with ciprofloxacin the least active, followed by levofloxacin, gatifloxacin/grepafloxacin/moxifloxacin/sparfloxaci n/trovafloxacin, and clinafloxacin/sitafloxacin. Efflux likely plays a crucial role in reduced susceptibility for new hydrophilic FQs.
The aim of the present investigation was to see whether the kinematic synergy responsible for equilibrium control during upper trunk movement was preserved in absence of gravity constraints. In this context, forward trunk movements were studied during both straight-and-level flights (earth-normal gravity condition: normogravity) and periods of weightlessness in parabolic flights (microgravity). Five standing adult subjects had their feet attached to a platform, their eyes were open, and their hands were clasped behind their back. They were instructed to bend the trunk (the head and the trunk together) forward by approximately 35 degrees with respect to the vertical in the sagittal plane as fast as possible in response to a tone, and then to hold the final position for 3 s. The initial and final anteroposterior center of mass (CM) positions (i.e., 200 ms before the onset of the movement and 400 ms after the offset of the movement, respectively), the time course of the anteroposterior CM shift during the movement, and the electromyographic (EMG) pattern of the main muscles involved in the movement were studied under both normo- and microgravity. The kinematic synergy was quantified by performing a principal components analysis on the hip, knee, and ankle angle changes occurring during the movement. The results indicate that 1) the anteroposterior position of the CM remains minimized during performance of forward trunk movement in microgravity, in spite of the absence of equilibrium constraints; 2) the strong joint coupling between hip, knee, and ankle, which characterizes the kinematic synergy in normogravity and which is responsible for the minimization of the CM shift during movement, is preserved in microgravity. It represents an invariant parameter controlled by the CNS. 3) The EMG pattern underlying the kinematic synergy is deeply reorganized. This is in contrast with the invariance of the kinematic synergy. It is concluded that during short-term microgravity episodes, the kinematic synergy that minimizes the anteroposterior CM shift is surprisingly preserved due to fast adaptation of the muscle forces to the new constraint.
OBJECT: The goal of this study was to evaluate the utility of volume-rendered helical computerized tomography (CT) angiography in patients with intracranial aneurysms. The authors compared the abilities of CT angiography, digital subtraction (DS) angiography, and three-dimensional time-of-flight magnetic resonance (MR) angiography to characterize aneurysms. METHODS: Helical CT angiography was performed in 45 patients with suspected intracranial aneurysms by using volume-rendered multiplanar reformatted (MPR) images. Digital subtraction angiography was performed using biplane angiography. These studies and those performed using MR angiography were interpreted in a blinded manner. Two neurosurgeons and two interventional neuroradiologists independently graded the utility of CT angiography with respect to aneurysm characterization. Fifty-five aneurysms were detected. Of these, 48 were evaluated for treatment. Computerized tomography angiography was judged to be superior to both DS and MR angiography in the evaluation of the arterial branching pattern at the aneurysm neck (compared with DS angiography, p = 0.001, and with MR angiography, p = 0.007), aneurysm neck geometry (compared with DS angiography, p = 0.001, and with MR angiography, p = 0.001), arterial branch incorporation (compared with DS angiography, p = 0.021, and with MR angiography, p = 0.001), mural thrombus (compared with DS angiography, p < 0.001), and mural calcification (compared with DS angiography, p < 0.001, and with MR angiography, p < 0.001). For surgical cases, CT angiography had a significant impact on treatment path (p = 0.001), operative approach (p = 0.001), and preoperative clip selection (p < 0.001). For endovascular cases, CT angiography had an impact on treatment path (p < 0.02), DS angiography study time (p = 0.01), contrast agent usage (p = 0.01), and coil selection (p = 0.02). Computerized tomography angiography provided unique information about 39 (81%) of 48 aneurysms, especially when compared with DS angiography (p = 0.003). The sensitivity and specificity of CT angiography compared with DS angiography was 1. The sensitivity and specificity of CT and DS angiography studies compared with operative findings were 0.98 and 1, respectively. CONCLUSIONS: Computerized tomography angiography is equal to DS angiography in the detection and superior to DS angiography and MR angiography in the characterization of brain aneurysms. Information contained in volume-rendered CT angiography images had a significant impact on case management.
Several theoretical studies have suggested that large samples of randomly ascertained siblings can be efficiently used to ascertain phenotypically extreme individuals and increase power to detect genetic linkage. Phenotypes that can be reliably measured by questionnaire are of obvious utility for such selection strategies, as large numbers of individuals can be contacted without laborious individual interview. As the first step in developing a large randomly-ascertained family cohort in southwest England, a sample of 88,000 individuals, including more than 34,000 sibling pairs in 20,000 sibships, was administered the Eysenck Personality Questionnaire (EPQ) by commercial mailing. The sample age ranges were 20-67 years and comprised 59% males and 41% females. Descriptive properties of the EPQ scales are similar to those reported from other large family cohorts. Test-retest correlations on 1681 probands in the sample are substantial for the N-scale (r = 0.93), but somewhat more modest for the other scales (range r = 0.70-0.88). Phenotypic and sibling correlations correspond quite closely to those of twin studies.
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The aim of the present experiment was to study the central organization of equilibrium control during arm raising in the frontal plane. Nine adult subjects (five seniors and four young adults) were asked to raise their right arm to a horizontal position in the frontal plane in two support conditions (bipedal vs. unipedal) and two load conditions (unloaded vs. a 3.5-kg load added on the moving hand). No instructions were given concerning the movement speed. The movements were performed at about half the maximum speed achievable under reaction time conditions. The final lateral center of mass (CM) position 1 s after the movement offset, and the time course of the CM shift during the movement were studied in the four experimental conditions, using a CM compensation index. The electromyographic (EMG) pattern of the main muscles involved in the movement performance and in the postural control were studied in three out of nine subjects during movements performed at two velocities (at the preferred speed and as fast as possible). The results indicate that (1) the CM shift remains minimized in the frontal plane during the time course of the arm movement and during the final stabilization of the arm regardless of the stance and load conditions; (2) the time course of the CM compensation index remains stable during the first 400 ms after the movement onset, decreasing late in the movement and increasing again at the end of the stabilization stage. A modelisation suggests that the time course is the result of the interaction of two controls: a first one, putative feedforward, starting early and decreasing with time and a second one, putative feedback, starting late in the movement and increasing with time; (3) both early and late index values are influenced by the support and load conditions, the highest index values being observed during unipedal stance and load conditions; (4) activation of quadratus lomborum (QL) contralateral to the raising arm is time locked with the deltoidus activation of the raising arm in both fast and slow movements: this contralateral QL activation corresponds to an anticipatory postural adjustment (APA) aimed at minimizing the CM shift.
In 1979, a BALB/cJ mouse was identified with an exceptionally long body. This phenotype was found to be caused by a recessive mutation, designated longjohn (lgj), that mapped to the proximal region of chromosome 15. Several years later, a mouse with a similarly elongated body was identified in an outbred stock after chemical mutagenesis with ethylnitrosourea. This phenotype also was caused by a recessive mutation, designated strigosus (stri). The two mutations were found to be allelic. A third allele was identified in a DBA/2J mouse and was designated longjohn-2J (lgj(2J)). Analysis of skeletal preparations of stri/stri mice indicated that the endochondral ossification process was slightly delayed, resulting in an extended proliferation zone. A recent study reported that mice overexpressing brain natriuretic peptide, one of the members of the natriuretic peptide family, exhibit a skeletal-overgrowth syndrome with endochondral ossification defects. The Npr3 gene coding for type C receptor for natriuretic peptides (NPR-C), which is mainly involved in the clearance of the natriuretic peptides, mapped in the vicinity of our mouse mutations and thus was a candidate gene. The present study reports that all three mutations involve the Npr3 gene and provides evidence in vivo that there is a natriuretic-related bone pathway, underscoring the importance of natriuretic peptide clearance by natriuretic peptide type C receptor.
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BACKGROUND: Mutations in the CDKN2A gene confer susceptibility to cutaneous malignant melanoma (CMM); however, the population incidence of such mutations is unknown. Polymorphisms in CDKN2A have also been described, but it is not known whether they influence melanoma risk. We investigated the association of CDKN2A mutations and polymorphisms with melanoma risk in a population-based sample of families ascertained through probands with melanoma. METHODS: The 482 Queensland, Australia, families in our sample were characterized previously as having high, intermediate, or low family risk of CMM. Unrelated individuals (n = 200 families/individuals) drawn from the Australian Twin Registry served as control subjects. For individuals in the high-risk group, the entire CDKN2A gene coding region was screened for mutations by use of the polymerase chain reaction, agarose gel electrophoresis, allele-specific oligonucleotide (ASO) hybridization, and single-strand conformation polymorphism analysis. The intermediate- and low-risk families and control subjects were analyzed by ASO hybridization for a total of six recurring mutations as well as for polymorphisms at nucleotides (Nts) 442, 500, and 540. RESULTS: CDKN2A mutations were found only in the high-risk families (nine [10.3%] of 87). The prevalence of the Nt500G (guanosine) polymorphism increased linearly with increasing familial risk (two-sided P = .02) and was highest in the nine (primarily Celtic) families with CDKN2A mutations. After adjustment for ethnic origin, the relationship between risk group and the frequency of the Nt500G allele was weakened (P = .25); however, there was no relationship between ethnic origin and Nt500-polymorphism frequency among the control subjects. CONCLUSIONS: CDKN2A mutations are rare in this population (approximately 0.2% of all melanoma cases in Queensland) and appear to be associated with melanoma in only the most affected families. The Nt500G allele appears to be associated with familial risk, but this association probably reflects Celtic ancestry.
The electron impact mass spectra of new 5-acetyl-4-aryl-6-methyl-2(1H)pyridones have been studied. A dominant peak in all the spectra is due to cleavage of the CO-NH bond of the amido group with charge retention on the carbonyl group. This fragmentation is followed by a hydrogen rearrangement to the nitrogen atom forming ketene intermediates; this pathway leads to a highly stabilized ion which constitutes the base peak in the spectra in most of the compounds studied. Copyright 1999 John Wiley & Sons, Ltd.
To investigate the nature of somatic von Hippel-Lindau (VHL) mutations, we analyzed 173 primary sporadic human renal cell carcinomas for mutations of the VHL tumor suppressor gene, using polymerase chain reaction (PCR) and single-strand conformational polymorphism analysis (SSCP) of DNA. We detected abnormal SSCP pattern in 73 samples. After sequencing, we identified microdeletions in 58% of cases, microinsertions in 17%, nonsense mutations in 8%, and missense mutations in 17%. Among these mutations, 50% correspond to new mutations. VHL mutations were found only in the nonpapillary renal cell carcinoma (RCC) subtype, as previously reported. To compare somatic and germline mutations, we used the VHL database, which includes 507 mutations. The study of mutational events revealed a significant difference between somatic and germline mutations with mutations leading to truncated proteins observed in 78% of somatic mutations vs only 37% in germline mutations (P < 0.001). We postulated that a specific pattern of VHL mutations is associated with sporadic RCC. This pattern corresponds to mutations leading mainly to truncated proteins with few specific missense mutations. We then analyzed the occurrence of RCC in VHL families, based on the nature of mutations. We observed RCC in at least one member of the VHL families in 77% of cases with mutations leading to truncated proteins versus 55% in cases with missense mutations (P < 0.05). Thus, mutations resulting in truncated proteins may lead to a higher risk of RCC in VHL patients.