An unusual atrial mass.
Giant coronary artery aneurysm is a rare manifestation of coronary artery disease. This patient presented at echocardiography and was successfully managed by surgical resection.
Cardiac Catheterization↗
Biomedical subjects
R A Jones
Publications and source records attributed to R A Jones.
Interleukin-1 promotes expression and phosphorylation of neurofilament and tau proteins in vivo.
Slow-release, IL-1-impregnated pellets implanted in rat cerebral cortex to simulate chronic overexpression of IL-1 significantly increased relative tissue levels of tau mRNA and of tau immunoreactivity in neuronal cell bodies and in swollen dystrophic neurites that also overexpressed phosphorylated and nonphosphorylated neurofilament epitopes. In addition, rats with IL-1-impregnated pellets, but not control rats or those with sham pellets, showed focal immunoreactivity for hyperphosphorylated tau epitopes present in paired helical filaments. Our results are consistent with an important driving role for IL-1 in the pathogenesis of Alzheimer-type neuronal and neuritic changes.
Animals↗
Determining 'threshold' levels for seed-borne virus infection in seed stocks.
There have been many advances in testing procedures to detect seed-borne virus infection in seed samples. However, scant attention has been given to the implications of improved test results in terms of the economic losses resulting from sowing seed stocks with different amounts of infection. For agricultural and horticultural industries to use the results of tests on representative samples, defined 'threshold' values for percentage seed infection are required that identify acceptable levels of risk of economic losses resulting from sowing the virus-infected seed stocks. Such information is provided by field experiments in which infected seed is sown and the consequences are followed in terms of virus spread, yield losses and infection of newly produced seed. These field experiments need to continue over several years at diverse sites so that they represent a wide range of infection scenarios. Extensive surveys to determine seed-borne virus occurrence in different regions are also required to define areas of greater or lesser risk of economic losses. In this paper, an example is described of how field experiments and surveys were used to define 'threshold' values of seed-borne Cucumber mosaic virus infection in an annual crop (lupin: Lupinus angustifolius) and two such examples are given for pasture species: Cucumber mosaic virus in subterranean clover (Trifolium subterraneum), and Alfalfa mosaic virus in annual burr medic (Medicago polymorpha). The aim of this paper is to encourage others to address the urgent need for similar 'threshold' information with other economically important combinations of seed-borne viruses and host plant.
Australia↗
Overexpression of the neuritotrophic cytokine S100beta precedes the appearance of neuritic beta-amyloid plaques in APPV717F mice.
Homozygous APPV717F transgenic mice overexpress a human beta-amyloid precursor protein (betaAPP) minigene encoding a familial Alzheimer's disease mutation. These mice develop Alzheimer-type neuritic beta-amyloid plaques surrounded by astrocytes. S100beta is an astrocyte-derived cytokine that promotes neurite growth and promotes excessive expression of betaAPP. S100beta overexpression in Alzheimer's disease correlates with the proliferation of betaAPP-immunoreactive neurites in beta-amyloid plaques. We found age-related increases in tissue levels of both betaAPP and S100beta mRNA in transgenic mice. Neuronal betaAPP overexpression was found in cell somas in young mice, whereas older mice showed betaAPP overexpression in dystrophic neurites in plaques. These age-related changes were accompanied by progressive increases in S100beta expression, as determined by S100beta load (percent immunoreactive area). These increases were evident as early as 1 and 2 months of age, months before the appearance of beta-amyloid deposits in these mice. Such precocious astrocyte activation and S100beta overexpression are similar to our earlier findings in Down's syndrome. Accelerated age-related overexpression of S100beta may interact with age-associated overexpression of mutant betaAPP in transgenic mice to promote development of Alzheimer-like neuropathological changes.
Aging↗
On the empirical proof of archetypes: commentary on Maloney (JAP 44, January 1999, 101-16).
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Consciousness↗
Tissue transglutaminase is an important player at the surface of human endothelial cells: evidence for its externalization and its colocalization with the beta(1) integrin.
We recently reported [J. Cell Sci. 110, 2461-2472 (1997)] that reduced expression of tissue transglutaminase (tTgase, type II) in human endothelial cell line ECV304 led to impaired cell spreading and adhesion; however, there is no immunocytochemical evidence for its presence and specific location at the surface of these cells. In this report we have stably transfected the same cell line with the cDNA for human tTgase which has been tagged at the C-terminus of the encoded protein with a 12-amino-acid peptide from protein kinase C epsilon. Using antibodies directed against this epitope tag peptide we show for the first time using immunogold electron microscopy and fluorescent immunocytochemistry the presence of cell surface-related tTgase. In cells undergoing attachment and cell spreading the enzyme appears to be concentrated at cell adhesion points which are rich in beta(1) integrin, suggesting that these areas may be the initial focal points for enzyme externalization. In more spread and confluent cells the enzyme appears more diffusely distributed along the basal membrane, with increased concentrations found at areas of cell-cell and cell-substratum contact. These findings strengthen the argument for the enzyme's role in cell-matrix interactions.
Base Sequence↗
Interlocked mismatch-aligned arrowhead DNA motifs.
BACKGROUND: Triplet repeat sequences are of considerable biological importance as the expansion of such tandem arrays can lead to the onset of a range of human diseases. Such sequences can self-pair via mismatch alignments to form higher order structures that have the potential to cause replication blocks, followed by strand slippage and sequence expansion. The all-purine d(GGA)n triplet repeat sequence is of particular interest because purines can align via G.G, A.A and G.A mismatch formation. RESULTS: We have solved the structure of the uniformly 13C,15N-labeled d(G1-G2-A3-G4-G5-A6-T7) sequence in 10 mM Na+ solution. This sequence adopts a novel twofold-symmetric duplex fold where interlocked V-shaped arrowhead motifs are aligned solely via interstrand G1.G4, G2.G5 and A3.A6 mismatch formation. The tip of the arrowhead motif is centered about the p-A3-p step, and symmetry-related local parallel-stranded duplex domains are formed by the G1-G2-A3 and G4-G5-A6 segments of partner strands. CONCLUSIONS: The purine-rich (GGA)n triplet repeat sequence is dispersed throughout the eukaryotic genome. Several features of the arrowhead duplex motif for the (GGA)2 triplet repeat provide a unique scaffold for molecular recognition. These include the large localized bend in the sugar-phosphate backbones, the segmental parallel-stranded alignment of strands and the exposure of the Watson-Crick edges of several mismatched bases.
Base Pair Mismatch↗
Liver poly(ADP-ribose)polymerase is resistant to cleavage by caspases.
In hepatocytes the DNA repair enzyme poly(ADP-ribose)polymerase (PARP) is not proteolytically cleaved during apoptosis. The reason for this was investigated using a cell-free system that consisted of isolated nuclei from hepatocytes or thymocytes and cytosolic extracts from hepatocytes or thymocytes undergoing apoptosis. It was found that liver PARP is resistant to proteolytic cleavage by the caspases present in the cytosolic extracts. Furthermore, liver PARP was not cleaved by recombinant human caspase-3. It is concluded that PARP proteolysis cannot be used as a marker for hepatocyte apoptosis.
Animals↗
Origin of the signal undershoot in BOLD studies of the visual cortex.
The nature of the signal undershoot observed in the inter-stimulation intervals in fMRI studies using a block paradigm consisting of alternating periods of visual stimulation and rest was investigated using the following single shot EPI sequences: gradient echo (GRE), spin echo (SE), spin echo with additional flow dephasing gradients and inversion recovery (IR) prepared SE. Both the GRE and SE sequences showed a significant signal undershoot during the inter-stimulation intervals. DeltaR(2)*/DeltaR(2) ratios of 3.7 +/- 0.9 and 3.1 +/- 0.7 were measured in the stimulation and inter-stimulation periods, respectively, with the latter being lower than that which would be consistent with a pure extra-vascular effect arising from an elevated venous blood volume and a normal deoxyhaemoglobin content post-stimulation. The addition of dephasing gradients to the SE sequence in order to attenuate the signal from spins flowing within larger vessels produced a four-fold reduction in the number of activated pixels but had little effect on the time intensity profile. Our interpretation of these results is that both extra- and intra-vascular BOLD effects are present in the inter-stimulation intervals and the lack of any effect of the dephasing gradient on the time-intensity profile indicates that the intra-vascular component probably occurs mainly in smaller vessels, such as venules, which are affected relatively little by the relatively weak dephasing gradient (b = 29 s/mm(2)) used in this study. For the IR-SE sequence the DeltaR(2) measured during the inter-stimulation intervals was similar to that seen with the SE BOLD sequence and thus was consistent with a residual BOLD effect, implying that perfusion changes in the capillary vessels did not contribute significantly to the signal undershoot.
Adult↗
Use of the mean transit time of an intravascular contrast agent as an exchange-insensitive index of myocardial perfusion.
A simple two-compartment model was used to study the effects of water exchange on the signal produced by an inversion recovery prepared rapid gradient-echo sequence during the first passage of a low dose of an intravascular contrast agent. Water exchange at intermediate rates of exchange (1-10 Hz) between the vascular and extravascular spaces caused the form of the signal changes during the first pass to be dependent on both the fractional sizes of the vascular and extravascular compartments and on the exchange rate. Unless the effects of exchange are minimized by using a very short inversion time, parameters such as the peak height and area under the curve will be affected by regional and/or pathological variations in the exchange rate and the size of the vascular fraction. The mean transit time (MTT) is, however, less affected by water exchange. Experimental first-pass data produced by intravascular low-dose injections of iron oxide particles were studied in five pigs at 0.5 T. The MTT as derived from the first-pass curves, without deconvolution with the arterial input function, was well correlated with the myocardial blood flow (MBF) as measured using radioactive microspheres (r = 0.70, n = 52, P < 0.01). Other first-pass parameters such as the peak height or area under the curve exhibited either a poorer, or no, correlation with the MBF. The data suggest that the MTT of the first pass of an intravascular contrast agent may be a robust, quantitative method for assessing myocardial blood flow in patients.
Animals↗
Magnitudes and orientations of the 15N chemical shift tensor of [1-15N]-2'-deoxyguanosine determined on a polycrystalline sample by two-dimensional solid-state NMR spectroscopy.
The magnitudes and orientations of the 15N chemical shift tensor of [1-15N]-2'-deoxyguanosine were determined from a polycrystalline sample using the two-dimensional PISEMA experiment. The magnitudes of the principal values of the 15N chemical shift tensor of the N1 nitrogen of [1-15N]-2'-deoxyguanosine were found to be sigma11 = 54 ppm, sigma22 = 148 ppm, and sigma33 = 201 ppm with respect to (15NH4)2SO4 in aqueous solution. Comparisons of experimental and simulated two-dimensional powder pattern spectra show that sigma33N is approximately collinear with the N-H bond. The tensor orientation of sigma33N for N1 of [1-15N]-2'-deoxyguanosine is similar to the values obtained for the side chain residues of 15Nepsilon1-tryptophan and 15Npi-histidine even though the magnitudes differ significantly.
Ammonium Sulfate↗
Comparative wear under four different tribological conditions of acetylene enhanced cross-linked ultra high molecular weight polyethylene.
In this study, the wear of ultra high molecular weight polyethylene (UHMWPE) (Grade RCH 1000) crosslinked by gamma irradiation in acetylene was compared to virgin (non-irradiated) UHMWPE using four different wear configurations: (i) unidirectional motion with a smooth counterface, (ii) multidirectional motion with a smooth counterface, (iii) unidirectional motion with a rough counterface and (iv) multidirectional motion with a rough counterface.
Journal Article↗
Amylase and 16S rRNA genes from a hyperthermophilic archaebacterium.
A hyperthermophilic and amylolytic prokaryote, designated Rt3, was isolated from a thermal spring near Rotorua, New Zealand. The 16S rRNA gene of Rt3 was cloned and sequenced with the aim of determining its phylogenetic affiliations. The phylogenetic analysis of this sequence, which included a selection of archaebacterial and eubacterial 16S rRNA sequences, indicates that Rt3 most likely belongs to the archaebacterial order Thermococcales. An amylase gene (amyA) from Rt3, encoding a highly thermostable amylase activity, was cloned and its DNA sequence determined. Transcriptional signals typical of archaebacteria were evident in this sequence. The sequence is homologous to a broad range of enzymes from the AMY superfamily and contains a typical N-terminal signal peptide. Phylogenetic analysis and comparison of structural features with other AMY superfamily enzymes reveals that, firstly, the closest homologues of the Rt3 amylase are members of the Bacillus and Plant alpha-amylase groups; and secondly, that the Rt3 amylase is closely related to only one other currently known archaebacterial enzyme, i.e. an (AMY superfamily) alpha-amylase from Natronococcus.
Amino Acid Sequence↗
Increased interleukin-1beta converting enzyme expression and activity in Alzheimer disease.
Increased expression of interleukin-1 in Alzheimer disease (AD) has been implicated as a driving force in neurodegenerative cascades that underlie the formation of neuritic plaques and neurofibrillary tangles, the spread of these neuropathological lesions across cerebral cortical regions, and the accompanying neuronal cell injury and loss. The beta isoform of interleukin-1 is generated from an inactive, 33-kDa precursor through the action of a specific interleukin-1beta converting enzyme (ICE), also known as caspase-1. We used mesial temporal tissue (hippocampus and parahippocampal cortex) obtained postmortem from Alzheimer and control patients for determinations of endogenous tissue ICE activity and for Western immunoblot analysis of tissue ICE concentrations. ICE activity in Alzheimer tissue was elevated 50-100% (p < 0.002, or better, at incubation times of 30 min to 10 h), and ICE protein level was elevated 180% (p = 0.01). Parahippocampal cortex of Alzheimer patients showed increased numbers of neurons with in situ evidence of DNA damage. Increased DNA degradation was also evident upon electrophoresis of isolated DNA. Overexpression and increased activity of ICE may contribute to neurodegeneration in AD through generation of biologically active interleukin-1, with consequent activation of interleukin-1-driven neurodegenerative cascades.
Alzheimer Disease↗
Multidisciplinary collaboration: a method for measurement.
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Cooperative Behavior↗
Recurrent pericardial effusion: the value of polymerase chain reaction in the diagnosis of tuberculosis.
A 23 year old army man presented with progressive dyspnoea and was found to have a massive pericardial effusion. Despite extensive investigations the cause remained elusive, until samples were sent for polymerase chain reaction (PCR). This case was unusual for several reasons and is a reminder of the atypical way in which tuberculosis infection can present and how a high index of suspicion should be maintained. It shows the importance of molecular biological advances in providing simple and rapid methods for arriving at the correct diagnosis, by way of nucleic acid probes and polymerase chain reaction.
Adult↗
Spontaneous and nitrosourea-induced primary tumors of the central nervous system in Fischer 344 rats chronically exposed to 836 MHz modulated microwaves.
We have tested an 836.55 MHz field with North American Digital Cellular (NADC) modulation in a 2-year animal bioassay that included fetal exposure. In offspring of pregnant Fischer 344 rats, we tested both spontaneous tumorigenicity and the incidence of induced central nervous system (CNS) tumors after a single dose of the carcinogen ethylnitrosourea (ENU) in utero, followed by intermittent digital-phone field exposure for 24 months. Far-field exposures began on gestational day 19 and continued until weaning at age 21 days. Near-field exposures began at 35 days and continued for the next 22 months, 4 consecutive days weekly, 2 h/day. SAR levels simulated localized peak brain exposures of a cell phone user. Of the 236 original rats, 182 (77%) survived to the termination of the whole experiment and were sacrificed at age 709-712 days. The 54 rats (23%) that died during the study ("preterm rats") formed a separate group for some statistical analyses. There was no evidence of tumorigenic effects in the CNS from exposure to the TDMA field. However, some evidence of tumor-inhibiting effects of TDMA exposure was apparent. Overall, the TDMA field-exposed animals exhibited trends toward a reduced incidence of spontaneous CNS tumors (P < 0. 16, two-tailed) and ENU-induced CNS tumors (P < 0.16, two-tailed). In preterm rats, where primary neural tumors were determined to be the cause of death, fields decreased the incidence of ENU-induced tumors (P < 0.03, two-tailed). We discuss a possible approach to evaluating with greater certainty the possible inhibitory effects of TDMA-field exposure on tumorigenesis in the CNS.
Animals↗
Solution structure of a Na cation stabilized DNA quadruplex containing G.G.G.G and G.C.G.C tetrads formed by G-G-G-C repeats observed in adeno-associated viral DNA.
We have applied NMR and molecular dynamics computations including intensity based refinement to define the structure of the d(G-G-G-C-T4-G-G-G-C) dodecanucleotide in 100 mM NaCl solution. The G-G-G-C sequence is of interest since it has been found as tandem repeats in the DNA sequence of human chromosome 19. The same G-G-G-C sequence is also seen as islands in adeno-associated virus, a human parvovirus, which is unique amongst eukaryotic DNA viruses in its ability to integrate site-specifically into a defined region of human chromosome 19. The d(G-G-G-C-T4-G-G-G-C) sequence forms a quadruplex in Na cation containing solution through head-to-tail dimerization of two symmetry-related stem-hairpin loops with adjacent strands antiparallel to each other around the quadruplex. The connecting T4 loops are of the lateral type, resulting in a quadruplex structure containing two internal G.G.G.G tetrads flanked by G.C.G.C tetrads. The G(anti).G(syn).G(anti).G(syn) tetrads are formed through dimerization associated hydrogen bonding alignments of a pair of Hoogsteen G(anti).G(syn) mismatch pairs, while the G(anti).C(anti).G(anti).C(anti) tetrads are formed through dimerization associated bifurcated hydrogen bonding alignments involving the major groove edges of a pair of Watson-Crick G.C base-pairs. The quadruplex contains two distinct narrow and two symmetric wide grooves with extensive stacking between adjacent tetrad planes. The structure of the quadruplex contains internal cavities that can potentially accommodate Na cations positioned between adjacent tetrad planes. Three such Na cations have been modeled into the structure of the d(G-G-G-C-T4-G-G-G-C) quadruplex. Finally, we speculate on the potential role of quadruplex formation involving G.G.G.G and G.C.G.C tetrads during the integration of the adeno-associated parvovirus into its target on human chromosome 19, both of which involve stretches of G-G-G-C sequence elements.
Chromosomes, Human, Pair 19↗