Biomedical subjects
C Joachim
Publications and source records attributed to C Joachim.
The CT-based radial width of the temporal horn: pathological validation in AD without cerebrovascular disease.
BACKGROUND: Medial temporal lobe atrophy is one of the most accurate markers of Alzheimer's disease (AD). Given the wide availability of the CT in the routine diagnostic assessment of patients with cognitive disturbances, a CT-based marker of AD might be clinically useful. OBJECTIVE: To test the accuracy of a simple CT-based measure, the radial width of the temporal horn (rWTH). METHOD: The rWTH was taken in a group of 20 pathologically confirmed AD patients and 23 non demented persons enrolled in the Oxford Project to Investigate Memory and Aging (OPTIMA project). RESULTS: The rWTH was significantly larger in AD patients than controls. Using a cutoff value between 3.9 at 50 and 8.1 at 90 years, the rWTH was able to correctly classify 16/20 and 19/23 subjects with a sensitivity and a specificity of 80% and 83%. The overall accuracy was 81%. CONCLUSION: The CT measurement of the rWTH is a simple and reasonably sensitive marker of regional brain atrophy in AD.
Science and politics: a fatal mix?
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Direct determination of the energy required to operate a single molecule switch.
Using a noncontact atomic-force and scanning-tunneling microscope in ultrahigh vacuum, we have measured the switching energy of a single molecule switch based on the rotation of a di-butyl-phenyl leg in a Cu-tetra-3,5 di-tertiary-butyl-phenyl porphyrin. The mechanics and intramolecular conformation of the switched leg is controlled by the tip apex of the noncontact atomic-force microscope. The comparison between experimental and calculated force curves shows that the rotation of the leg requires an energy less than 100 x 10(-21) J, which is 4 orders of magnitude lower than state-of-the-art transistors.
Organic molecules acting as templates on metal surfaces.
The electronic connection of single molecules to nanoelectrodes on a surface is a basic, unsolved problem in the emerging field of molecular nanoelectronics. By means of variable temperature scanning tunneling microscopy, we show that an organic molecule (C90H98), known as the Lander, can cause the rearrangement of atoms on a Cu(110) surface. These molecules act as templates accommodating metal atoms at the step edges of the copper substrate, forming metallic nanostructures (0.75 nanometers wide and 1.85 nanometers long) that are adapted to the dimensions of the molecule.
Recording intramolecular mechanics during the manipulation of a large molecule.
The technique of single atom manipulation by means of the scanning tunneling microscope (STM) applies to the controlled displacement of large molecules. By a combined experimental and theoretical work, we show that in a constant height mode of manipulation the STM current intensity carries detailed information on the internal mechanics of the molecule when guided by the STM tip. Controlling and time following the intramolecular behavior of a large molecule on a surface is the first step towards the design of molecular tunnel-wired nanorobots.
Conformational changes of single molecules induced by scanning tunneling microscopy manipulation: a route to molecular switching.
A detailed experimental and theoretical investigation of the processes involved in the manipulation of individual specially designed porphyrin-based molecules by scanning tunneling microscopy at low temperature is presented. On a stepped Cu(211) surface, the interaction between tip and molecule was used to locally modify in a reversible way the internal configuration of a single molecule, thus drastically changing the tunneling current passing through it. Model calculations confirm that this manipulation realizes the principle of a conformational molecular switch.
Anosmia in dementia is associated with Lewy bodies rather than Alzheimer's pathology.
OBJECTIVES: To assess olfactory function of patients with dementia. Odour detection ability is impaired in clinical Parkinson's disease. Evidence of impaired detection in patients with clinically diagnosed Alzheimer's disease is inconsistent. No studies of olfaction have been neuropathologically validated. METHODS: The olfactory function of 92 patients with dementia and 94 controls was assessed using a simple bedside test as part of the Oxford Project To Investigate Memory and Ageing (OPTIMA). Neuropathological assessment was made of cortical Lewy bodies and substantia nigra (SN) cell counts and of Alzheimer's disease in all 92 patients, 22 of whom had SN Lewy bodies and 43 of whom had only Alzheimer's disease. RESULTS: Patients with Lewy bodies were more likely to be anosmic than those with Alzheimer's disease or controls. Patients with Alzheimer's disease were not more likely to be anosmic than controls. Nor was anosmia associated with degree of neurofibrillary tangles, as assessed by Braak stage. Among subjects with Lewy bodies, overall cortical Lewy body scores and Lewy body density in the cingulate were higher in those who were anosmic. Consensus clinical criteria for dementia with Lewy bodies had a sensitivity of 64% and specificity of 89%. In the absence of definite Alzheimer's disease, the criteria had sensitivity of 100%. In patients with definite Alzheimer's disease, anosmia was slightly more sensitive (55%) than the consensus criteria (33%). However, the addition of anosmia to the consensus criteria did not improve their overall performance. CONCLUSION: Dementia with Lewy bodies is associated with impaired odour detection. Misdiagnosis may have accounted for some previous reports of impaired odour detection in Alzheimer's disease. Simple but more sensitive tests of anosmia are required if they are to be clinically useful in identifying patients with dementia with Lewy bodies.
Electronics using hybrid-molecular and mono-molecular devices.
The semiconductor industry has seen a remarkable miniaturization trend, driven by many scientific and technological innovations. But if this trend is to continue, and provide ever faster and cheaper computers, the size of microelectronic circuit components will soon need to reach the scale of atoms or molecules--a goal that will require conceptually new device structures. The idea that a few molecules, or even a single molecule, could be embedded between electrodes and perform the basic functions of digital electronics--rectification, amplification and storage--was first put forward in the mid-1970s. The concept is now realized for individual components, but the economic fabrication of complete circuits at the molecular level remains challenging because of the difficulty of connecting molecules to one another. A possible solution to this problem is 'mono-molecular' electronics, in which a single molecule will integrate the elementary functions and interconnections required for computation.
Dementia with Lewy bodies: a pure case.
A pure case of autopsy-confirmed dementia with Lewy bodies (DLB) is described. The patient presented with distinctive verbal fluency deficits in the context of mild language impairment, intact recognition memory, and impaired paragraph recall. Neuroimaging (CT and SPECT) showed progressive medial temporal lobe atrophy. Neuropathology revealed Lewy bodies, degeneration in the substantia nigra, nucleus basalis of Meynert (Nakano & Hirano, 1984), and locus ceruleus, but no pathology characteristic of Alzheimer's disease. It is in this sense that the case is "pure" DLB. Early neuropsychological diagnosis of DLB is essential (Salmon et al., 1996) given the potentially fatal hazard of neuroleptics (McKeith et al., 1992) and the difficulties associated with clinical neurological diagnoses (Litvan et al., 1998).
Leukoaraiosis at presentation and disease progression during follow-up in histologically confirmed cases of dementia.
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Apolipoprotein E epsilon2 may be a risk factor for sporadic frontotemporal dementia.
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Nanoscale science of single molecules using local probes
Experiments on individual molecules using scanning probe microscopies have demonstrated an exciting diversity of physical, chemical, mechanical, and electronic phenomena. They have permitted deeper insight into the quantum electronics of molecular systems and have provided unique information on their conformational and mechanical properties. Concomitant developments in experimentation and theory have allowed a diverse range of molecules to be studied, varying in complexity from simple diatomics to biomolecular systems. At the level of an individual molecule, the interplays of mechanical and electronical behavior and chemical properties manifest themselves in an unusually clear manner. In revealing the crucial role of thermal, stochastic, and quantum-tunneling processes, they suggest that dynamics is inescapable and may play a decisive role in the evolution of nanotechnology.
Resonant optical tunnel effect through dielectric structures of subwavelength cross sections.
We show that optical tunnel effects through elongated structures of subwavelength cross sections can be enhanced by the appropriate structuration of the local dielectric function. Even under total internal reflection, transfer channels can be excited to perform spatially confined photonic transfer between transparent media linked by such subwavelength structures. The optical properties of such systems are analyzed using field susceptibilities, also known as electromagnetic Green's dyadics, which determine both the local density of photon states and the optical transmittance of the system. Green's dyadics obtained by solving numerically a set of dyadic Dyson equations are applied to study the optical properties of subwavelength structures connecting two semi-infinite materials.
Rotation of a single molecule within a supramolecular bearing
Experimental visualization and verification of a single-molecule rotor operating within a supramolecular bearing is reported. Using a scanning tunneling microscope, single molecules were observed to exist in one of two spatially defined states laterally separated by 0.26 nanometers. One was identified as a rotating state and the other as an immobilized state. Calculations of the energy barrier for rotation of these two states show that it is below the thermal energy at room temperature for the rotating state and above it for the immobilized state.
Comparison of pathological diagnostic criteria for Alzheimer disease.
Because the clinical picture of Alzheimer disease (AD) is often difficult to discriminate from other dementing illnesses, the diagnosis of AD requires neuropathological confirmation. However, for the pathological diagnosis of AD, there are no unanimously accepted criteria. The three currently used sets of pathological criteria (Khachaturian: Khachaturian, Arch Neurol 1985;42:1097-105; Tiemy: Tierney et al., Can J Neurol Sci 1986; 13:424-6; CERAD: Mirra et al., Neurology 1991;41:479-86) for the disease differ from each other considerably. We applied these criteria to the first 43 consecutive subjects (37 demented) with no neuropathology other than AD-type pathology from autopsies after longitudinal prospective clinical study in the Oxford Project to Investigate Memory and Ageing (OPTIMA). The results show that the CERAD category of definite AD corresponds closely with the cases that fulfill Tierney A3 inclusion criteria for AD. The combined CERAD categories of possible, probable, and definite AD correspond closely to cases fulfilling Khachaturian criteria forAD. The influence of a clinical diagnosis of dementia when Khachaturian and CERAD criteria were applied was considerable because between 9.3% and 90.7% of patients would have been categorized differently depending on whether clinical dementia was present or absent.
The effects of additional pathology on the cognitive deficit in Alzheimer disease.
The diagnosis of Alzheimer disease (AD) according to current criteria is a combined clinical and pathological exercise. The clinical discrimination of AD from other types of dementia may be complicated when the patient suffers from more than one disease. In particular the concomitant presence of other neurological conditions may significantly influence the severity of cognitive deficit. In this study we analyze the extent of the influence of vascular and other neurodegenerative pathology on the cognitive deficit in a consecutive series of 88 prospectively assessed elderly subjects. We find that, for any given level of cognitive deficit, the densities of either all plaques or neuritic plaques alone in the neocortex are significantly lower in cases of AD mixed with other CNS pathology than in cases of AD with no other CNS pathology. In AD combined with cerebrovascular disease, the total plaque density makes a significant contribution to cognitive deficit, while neurofibrillary tangle (NFT) densities do not. In contrast, in pure AD tangle density is the major determinant of cognitive deficit. Our findings draw attention to the influence of coexisting brain pathologies on the clinical manifestation of dementia in subjects with AD. These findings indicate that pathological diagnostic criteria for AD should take into account such additional pathology in demented subjects. They also improve understanding of the circumstances in which the amyloid component of AD can play a decisive role in precipitating clinical dementia.
Apolipoprotein-E genotyping in diagnosis of Alzheimer's disease.
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