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D Robertson

Publications and source records attributed to D Robertson.

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

Experimental investigation of alternative pre-stress components for a 3-1 connectivity multilayer piezoelectric-polymer composite ultrasonic transducer.

The most popular configuration for piezoelectric-polymer composites has pillars of piezoelectric ceramic supported by a polymer matrix and material with this structure is now widely available commercially. However, it has significant disadvantages for use in multilayer devices for non-mass-loaded operation below approximately 50 kHz. An alternative configuration is therefore reported here, in which interconnected fingers of piezoelectric ceramic surround polymer plates. This can be termed 3-1 connectivity, since the piezoceramic is fully connected in three dimensions and the polymer in only one. The configuration has been found to have significant manufacturing advantages which feed through to enhanced performance compared with practical 1-3 connectivity multilayer devices. For many potential applications, high-power operation is required, and it is unclear if the multilayer structure has sufficient internal strength to maintain its integrity at high strains. Therefore, an investigation has been carried out into alternative pre-stressing component designs. These comprise back and front stainless steel plates of different shapes, connected by a number of stainless steel rods. In this paper, the fundamental performance of a multilayer device is illustrated with electrical impedance and surface displacement measurements in air, without pre-stressing. Then measurements are reported from three different clamping configurations. It is shown that good results can be achieved at spot frequencies with a suitable clamp, but that unsuitable clamps prevent even this, and broadband performance is unlikely to be achieved easily.

Journal Article↗
PubMed2002

Expression of caveolin-1 in human brain microvessels.

Caveolae are microinvaginations of the cell plasma membrane involved in cell transport and metabolism as well as in signal transduction; these functions depend on the presence of integral proteins named caveolins in the caveolar frame. In the brain, various caveolin subtypes have been detected in vivo by immunocytochemistry: caveolin-1 and -2 were found in rat brain microvessels, caveolin-3 was revealed in astrocytes. The aim of this study was to identify the site(s) of cellular expression of caveolin-1 in the microvessels of the human cerebral cortex by immunofluorescence confocal microscopy and immunogold electron microscopy. Since in the barrier-provided brain microvessels tight relations occur between the endothelium-pericyte layer and the surrounding vascular astrocytes, double immunostaining with caveolin-1 and the astroglia marker, glial fibrillary acidic protein, was also carried out. Immunocytochemistry by confocal microscopy revealed that caveolin-1 is expressed by endothelial cells and pericytes in all the cortex microvessels; caveolin-1 is also expressed by cells located in the neuropil around the microvessels and identified as astrocytes. Study of the cortex microvessels carried out by immunoelectron microscopy confirmed that in the vascular wall caveolin-1 is expressed by endothelial cells, pericytes, and vascular astrocytes, and revealed the association of caveolin-1 with the cell caveolar compartment. The demonstration of caveolin-1 in the cells of the brain microvessels suggests that caveolin-1 may be involved in blood-brain barrier functioning, and also supports co-ordinated activities between these cells.

Blood-Brain Barrier↗
PubMed2002

Inputs from the cochlea and the inferior colliculus converge on olivocochlear neurones.

Medial olivocochlear (MOC) neurones, located in the superior olivary complex, can suppress cochlear gain by their action on the cochlear outer hair cells. Inputs from the contralateral cochlea and the inferior colliculus (IC) have been separately shown to increase activity of MOC neurones. In this study we have investigated in guinea-pigs under barbiturate anaesthesia the interactions between these two inputs by combining electrical stimulation of the IC with acoustic stimulation of the contralateral cochlea. Electrical stimulation of the IC resulted in a significant suppression of the amplitude of the compound action potential (CAP) of the auditory nerve to test tones. This suppression was equivalent to an average decrease in sound intensity of 5.7 dB and 3.7 dB for contralateral and ipsilateral stimulation, respectively. Acoustic stimulation of the contralateral cochlea with broadband noise produced no detectable change in the amplitude of the CAP in the test cochlea in all but one animal. However, simultaneous electrical stimulation of the IC and acoustic stimulation of the contralateral cochlea resulted in a reduction in CAP amplitude that was markedly larger than that produced by IC stimulation alone. The suppression with the addition of contralateral noise was equivalent to a mean reduction in sound intensity of 8.7 dB with contralateral and 5.7 dB with ipsilateral IC stimulation. We hypothesise that excitatory input from the contralateral cochlea converges with excitatory input from the IC on the MOC neurones and in this way augments the activity of these neurones, resulting in a larger peripheral effect.

Acoustic Stimulation↗
PubMed2002

Dual action of olivocochlear collaterals in the guinea pig cochlear nucleus.

Axons of olivocochlear neurones in the superior olivary complex terminate on hair cells of the cochlea, reducing the sensitivity to sound. These axons also have collateral branches to neurones in the cochlear nucleus, the first processing centre in the brainstem. Anatomical data show that these collaterals terminate mainly in the granule cell area but their precise neuronal targets and the effects they might have are unknown. We have studied the effects of these collaterals in guinea pigs, by electrically stimulating the olivocochlear axons at the floor of the IVth ventricle while recording single neurone responses in the cochlear nucleus. We eliminated the peripheral effects of olivocochlear stimulation either by destruction of the target receptor cells using chronic administration of kanamycin, or by acute perfusion of the cochlea with strychnine, a specific blocker of the postsynaptic receptors. Electrical stimulation of the olivocochlear axons in normal animals caused a variety of effects on cochlear nucleus neurones. In some neurones, there was suppression of spontaneous firing and a reduction in sensitivity to sound, while in others there was an excitatory effect of olivocochlear axon stimulation. When the peripheral olivocochlear action was eliminated, we still found both inhibition and excitation in the cochlear nucleus. These results show that the effects of olivocochlear stimulation on cochlear nucleus responses are not a simple passive reflection of peripheral changes but are a result of complex interactions between peripheral suppression of afferent input and collateral-mediated excitation and possibly also inhibition.

Action Potentials↗
PubMed2002

The mitochondrial common deletion in Parkinson's disease and related movement disorders.

The mitochondrial 4977-bp common deletion has been reported in some studies to occur exclusively or with increased frequency in the midbrain of patients with Parkinson's disease (PD). Other studies could not confirm these results; rather, it was suggested that the mitochondrial common deletion is associated with aging in the midbrain and not PD. One possible explanation for these conflicting results is the difficulty in quantifying mitochondrial DNA deletions or mutations in the whole midbrain or substantia nigra (SN) while only a subset of midbrain neurons degenerate in PD. In addition, none of the studies has addressed the cell types with the common deletion within the midbrain. In this study we used in situ hybridization to detect the common deletion in sections of midbrain from patients with PD, multiple system atrophy-parkinsonian type (MSA-P), progressive supranuclear palsy (PSP), dementia with Lewy bodies (DLB), age-matched controls, and individuals of different ages. The results demonstrated that the mitochondrial common deletion accumulated primarily in neurons but not glia in both the SN and other midbrain regions. There was no significant difference in the number or distribution of neurons with the common deletion or the average of the mean densities (AMD) of staining with the common deletion in nigral neurons among patients with PD, MSA-P, PSP, DLB, or age-matched controls. In addition, there was no difference in the number or distribution of neurons with the common deletion in nigral neurons between any age group, although there was a tendency for the common deletion to increase in the non-nigral neurons in older patients. These data indicate that accumulation of the 4977-bp common deletion in mitochondrial DNA in midbrain occurred primarily in neurons, and by this cytological approach, it was not associated with nigral neurodegeneration in the common movement disorders or aging.

Adolescent↗
PubMed2001

Sequential modulation of cardiac autonomic control induced by cardiopulmonary and arterial baroreflex mechanisms.

BACKGROUND: Nonhypotensive lower body negative pressure (LBNP) induces a reflex increase in forearm vascular resistance and muscle sympathetic neural discharge without affecting mean heart rate. We tested the hypothesis that a reflex change of the autonomic modulation of heartbeat might arise during low intensity LBNP without changes of mean heart rate. METHODS AND RESULTS: Ten healthy volunteers underwent plasma catecholamine evaluation and a continuous recording of ECG, finger blood pressure, respiratory activity, and central venous pressure (CVP) during increasing levels of LBNP up to -40 mm Hg. Spectrum and cross-spectrum analyses assessed the changes in the spontaneous variability of R-R interval, respiration, systolic arterial pressure (SAP), and CVP and in the gain (alpha(LF)) of arterial baroreflex control of heart rate. Baroreceptor sensitivity was also evaluated by the SAP/R-R spontaneous sequences technique. LBNP began decreasing significantly: CVP at -10, R-R interval at -20, SAP at -40, and the indexes alpha(LF) and baroreceptor sensitivity at -30 and -20 mm Hg, compared with baseline conditions. Plasma norepinephrine increased significantly at -20 mm Hg. The normalized low-frequency component of R-R variability (LF(R-R)) progressively increased and was significantly higher than in the control condition at -15 mm Hg. CONCLUSIONS: Nonhypotensive LBNP elicits a reflex increase of cardiac sympathetic modulation, as evaluated by LF(R-R), which precedes the changes in the hemodynamics and in the indexes of arterial baroreflex control.

Adult↗
PubMed2001

Linking molecular and bedside research: designing a clinical research infrastructure.

For 40 years the General Clinical Research Centers (GCRCs) have provided the infrastructure in Academic Medical Centers (AMCs) in the United States, which enabled and facilitated the extraordinary achievements of twentieth century patient-oriented research. The GCRC program in the United States represents a central theme linking molecular and clinical research directed at elucidating mechanisms of human disease. The GCRC can provide the necessary infrastructure and critical intellectual mass to reach a deeper understanding of human biology and to bring better health to persons in both developed and developing countries. A well-organized GCRC program should encompass educational as well as scientific components. It must be developed with an appropriate quality control infrastructure to provide physician-scientists a broad base of training in ethical principles in conduct of research and in scientific design and modern technology. The Human Genome Project has brought unprecedented opportunities to clinical investigators, but taking full advantage of them will require a rebirth of the GCRC as a program capitalizing on local strengths and differences, a more multicentric program, and a program reaching outside the GCRC walls, beyond institutional walls, and into the community. The GCRCs can appropriately be the clinical arm of the human genome project, harnessing the genetic revolution for human health. The GCRC model can provide a conceptual base on which new international patient-oriented research infrastructures can develop.

Academic Medical Centers↗
PubMed2001

Orthostatic intolerance in Behcet's disease.

Neurological manifestations are known to occur in patients with Behcet's Disease (BD) and significantly affect the clinical course of the disease. Nevertheless, the prevalence, pattern and severity of autonomic impairment in such patients have yet to be defined. In this paper, we presented a BD patient with orthostatic tachycardia. Non-invasive standardized autonomic function tests revealed no evidence of autonomic impairment, but profound orthostatic tachycardia accompanied by abnormal catecholamine increase was observed upon standing. The diagnosis of Orthostatic Intolerance (OI) was made and initial symptomatic therapy was started. The contribution of an immunological damage to components of neural pathways in the pathogenesis of the autonomic involvement can be assumed.

Adult↗
PubMed2001

Inhibition of signal transduction by the Hsp90 inhibitor 17-allylamino-17-demethoxygeldanamycin results in cytostasis and apoptosis.

17-Allylamino-17-demethoxygeldanamycin (17AAG) is a first-in-class heat shock protein 90 (Hsp90) molecular chaperone inhibitor to enter clinical trials. The downstream molecular and cellular consequences of Hsp90 inhibition are not well defined. 17AAG has shown activity against human colon cancer in cell culture and xenograft models. In this study, we demonstrated that in addition to depleting c-Raf-1 and inhibiting ERK-1/2 phosphorylation in human colon adenocarcinoma cells, 17AAG also depleted N-ras, Ki-ras, and c-Akt and inhibited phosphorylation of c-AKT: A consequence of these events was the induction of cell line-dependent cytostasis and apoptosis, although the latter did not result from dephosphorylation of proapoptotic BAD: One cell line, KM12, did not exhibit apoptosis and in contrast to the other cell lines overexpressed Bag-1, but did not express BAX: Taken together with other determinants of 17AAG sensitivity, these results should contribute to a more complete understanding of the molecular pharmacology of 17AAG, which in turn should aid the future rational clinical development and use of the drug in colon and other tumor types.

Adenocarcinoma↗
PubMed2001

Electronic publishing of science: better late than never.

The time required for medical publication in the print literature has changed little in 200 years, whereas scientific discovery now proceeds at a dizzying pace. There is a growing disjunction between the efficiency of science and the inefficiency of scientific reporting. Electronic publication as proposed for PubMedCentral is a logical solution to this problem.

Humans↗
PubMed2001

N-terminal intramolecularly conserved histidines of three domains in Gonyaulax luciferase are responsible for loss of activity in the alkaline region.

Gonyaulax luciferase is a single-chain ( approximately 137 kDa) polypeptide comprising 111 N-terminal amino acids followed by three contiguous homologous domains (377 amino acids each). Each domain has luciferase activity, accounting for the earlier observation that proteolytic fragments ( approximately 35 kDa) of luciferase are active. The activity of the full-length native enzyme is maximal at pH 6.3, dropping to near zero at pH 8; the activity of fragments also peaks at pH 6.3 but remains high at 8. While the activity loss at higher pH might be thought to be associated with the conformation of the full-length protein, we show here that this is a property of individual domains. The three intramolecularly homologous domains, separately cloned and expressed in Escherichia coli as fusion proteins, exhibit pH-activity curves similar to that of the full-length enzyme. For each domain the removal of approximately 50 N-terminal amino acids resulted in an increase in the ratio of luciferase activity at pH 8 relative to that at pH 6.3, such that their pH-activity profiles mimicked that of the proteolytic fragments reported earlier. Replacement of N-terminal histidines by alanine by site-directed mutagenesis identified four that are involved in the loss of activity at high pH. This system illustrates an unusual, possibly unique mechanism for pH regulation of enzyme activity, which has been postulated to be responsible for the control of the characteristic flashes of bioluminescence.

Amino Acid Sequence↗
PubMed2001

Proteomic analysis reveals a novel set of cell wall proteins in a transformed tobacco cell culture that synthesises secondary walls as determined by biochemical and morphological parameters.

A cell suspension culture of a tobacco (Nicotiana tabacum L. cv. Petit Havana) cell line derived from a cultivar transformed with the Tcyt gene from Agrobacterium, which leads to high endogenous levels of cytokinin, has been established. This cell line shows increased cell aggregation, elongated cells and a 5-fold increase in wall thickness. If allowed to carry on growing it can form a single mass without shedding cells into the medium. When analysed at an earlier growth stage, these cultures were found to produce improved levels of vascular nodule formation than in other systems that employ exogenous cytokinin. This differentiation was optimised with respect to sucrose and auxin signals in order to induce maximum production of cells with thickened walls and a morphology characteristic of fibre cells and tracheids, in addition to cells that remain meristematic. In order to establish the validity of this system for studying secondary wall formation, the walls and associated biosynthetic changes were analysed in these cells by chemical analysis of the walls, changes in activities of enzymes of xylan and monolignol synthesis, and expression of mRNAs coding for enzymes of lignin biosynthesis. The wall composition of the transformed cells was compared with that determined for primary walls from a typical untransformed tobacco cell line. Recovery of wall material was 50% greater in the transformed culture. In this material a major difference was found in the pectin fraction where there was a distinct difference in size distribution together with a lower level of methylation for the transformed line, which may be related to increased adhesiveness. There were increased amounts of xylan, although the ratio of xyloglucan to xylan content was not substantially different due to the mixture of cell types. There was also an increase in cellulose and phenolic components. Increased activity of enzymes involved in the synthesis of xylan as a marker for the secondary wall occurred around the time of tracheid differentiation and coincided with a broad peak of cinnamyl alcohol dehydrogenase activity. The expression of mRNAs coding for enzymes of the general phenylpropanoid pathway, phenylalanine ammonia-lyase, cinnamate 4-hydroxylase, catechol O-methyl transferase was relatively constitutive in the cultures while transcripts of ferulate 5-hydroxylase, cinnamoyl CoA-reductase, cinnamyl alcohol dehydrogenase and lignin peroxidase were induced. The walls of the transformed cells also showed considerable differences in the subset of extractable proteins from that found in primary walls of tobacco when these were subjected to proteomic analysis. Many of these proteins appear to be novel and not present in primary walls. However an Mr-32,000 chitinase, an Mr-34,000 peroxidase, an Mr-65,000 polyphenoloxidase/laccase and possibly an Mr-68,000 xylanase could be identified as well as structural proteins.

Alcohol Oxidoreductases↗
PubMed2001

Chiari I malformation as a cause of orthostatic intolerance symptoms: a media myth?

There is much interest in a putative relationship between Chiari I malformation and symptoms of orthostatic intolerance. It has been reported at scientific meetings that a number of patients with chronic fatigue syndrome or fibromyalgia have Chiari I malformation, or hindbrain compression in the absence of Chiari, and that they experience improvement after decompression surgery. Many of these patients have symptoms of orthostatic intolerance. A connection between Chiari I malformation and these conditions has been discussed in newspaper articles and on national television programs. Patients have also had access to much information on this topic via the Internet. Unfortunately, the Chiari I malformation and orthostatic intolerance connection is almost entirely unsupported by peer-reviewed literature. The purpose of this article is to provide an objective review of the available information.

Arnold-Chiari Malformation↗
PubMed2001

Aqueous leaching properties and environmental implications of cadmium, lead and zinc trimercaptotriazine (TMT) compounds.

2,4,6-Trimercaptotriazine, trisodium salt nonahydrate (TMT-55) is a commercial product that is widely used to chemically precipitate cadmium, lead, zinc and other heavy metals from wastewaters and contaminated natural waters. When mixed with aqueous solutions of TMT-55, aqueous solutions of either reagent-grade zinc, cadmium, or lead salts precipitate crystalline "Zn-TMT", amorphous or crystalline "Cd-TMT" or amorphous "Pb-TMT" (M3[S3C3N3]2.nH2O, where M=Cd2+, Pb2+, and Zn2+ and n> or = 0) that may eventually crystallize if stored in air. Laboratory aqueous leaching studies over 78-106 days using pH 3 HCl, distilled water (pH 6) and pH 9-10 NaOH evaluated the stability of the Cd-, Pb-, and Zn-TMT precipitates. Under pH 3 conditions, the amorphous Cd- and Pb-TMT compounds converted to their crystalline forms and amorphous Cd-TMT also crystallized in distilled water. Otherwise, no decomposition products were detected in the leached solid residues. When compared with the aqueous solubilities of corresponding sulfides and most hydroxides, the TMT compounds were significantly more soluble in distilled water and pH 3 HCl.

Cadmium↗