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V Walsh

Publications and source records attributed to V Walsh.

At least 37 records · Page 2Linked to original sources
PubMed2000

Plasticity revealed by transcranial magnetic stimulation of early visual cortex.

We applied single-pulse transcranial magnetic stimulation (TMS) to the occipital pole of healthy subjects while they performed a forced-choice visual letter-identification task. We found three separate periods when TMS suppressed performance; the first period is best explained by TMS-induced blinking whereas the last two periods are best explained by TMS-induced disruption of letter-processing in the early visual cortex. Unexpectedly, we also found that TMS-induced suppression progressively disappeared during three weeks of repeated TMS experiments. However, it was only suppression during the last two periods that disappeared; suppression during the first period remained undiminished. When subjects were then presented with dimmer letters, suppression reappeared. The most likely explanation is a practice-induced increase in neuronal activity in the early visual cortex.

Adult↗
PubMed2000

Neuropsychology: the touchy, feely side of vision.

Some visual attributes, such as colour, are purely visual, but others, such as orientation and movement, can be perceived by touch or audition. A magnetic stimulation study has now shown that the perception of tactile orientation may be influenced by visual Information.

Animals↗
PubMed2000

Transcranial magnetic stimulation in cognitive neuroscience--virtual lesion, chronometry, and functional connectivity.

Fifteen years after its introduction by Anthony Barker, transcranial magnetic stimulation (TMS) appears to be 'coming of age' in cognitive neuroscience and promises to reshape the way we investigate brain-behavior relations. Among the many methods now available for imaging the activity of the human brain, magnetic stimulation is the only technique that allows us to interfere actively with brain function. As illustrated by several experiments over the past couple of years, this property of TMS allows us to investigate the relationship between focal cortical activity and behavior, to trace the timing at which activity in a particular cortical region contributes to a given task, and to map the functional connectivity between brain regions.

Behavior↗
PubMed2000

Transcranial magnetic stimulation and cognitive neuroscience.

Transcranial magnetic stimulation has been used to investigate almost all areas of cognitive neuroscience. This article discusses the most important (and least understood) considerations regarding the use of transcranial magnetic stimulation for cognitive neuroscience and outlines advances in the use of this technique for the replication and extension of findings from neuropsychology. We also take a more speculative look forward to the emerging development of strategies for combining transcranial magnetic stimulation with other brain imaging technologies and methods in the cognitive neurosciences.

Animals↗
PubMed2000

High FUS/TLS expression in acute myeloid leukaemia samples.

Retinoic acid has the ability to induce differentiation in some myeloid leukaemia cell lines and has been used to induce remission in acute promyelocytic leukaemia patients. We have analysed changes in gene expression, by differential display, in HL60 cells exposed to all-trans retinoic acid (ATRA) for only 1 h. Only about 0.4% of the genes examined by this technique showed changes in expression level, and all four of the gene fragments identified were downregulated during the short 1 h exposure. Two of the fragments were novel, a third was MYC and the fourth was the FUS proto-oncogene. Northern analysis showed that FUS was downregulated within 1 h only during induced neutrophil differentiation but not at all during induced monocyte differentiation. Unlike the sensitive cell lines, ATRA-resistant cell lines did not show a downregulation of FUS over a 24 h period of exposure to ATRA. Using a semiquantitative PCR analysis, no difference in FUS levels was observed between ATRA-sensitive and -resistant cell lines. A similar analysis was carried out on primary acute myeloid leukaemia (AML), peripheral stem cell harvests (PBSC) and cord blood samples. The PBSC and cord blood samples had FUS levels that were similar or generally less than the cell lines. However, much higher levels were seen in 63% of the AML samples examined. The data presented are consistent with previous reports for a role for FUS in the promotion and maintenance of cellular proliferation.

Acute Disease↗
PubMed2000

Visual field asymmetries in attention and learning.

It has been suggested that attentional resolution is greater in the lower than in the upper visual field. As there is no corresponding asymmetry between the areas in the primary visual cortex where the input from upper and lower visual fields is processed, an 'attentional filter' has been proposed to act in one or more higher visual cortical areas in order to constrict the availability of visual information to the level of awareness. To investigate this, a visual search array was presented to the entire visual field and reaction times from upper and lower visual fields compared. In a second experiment, subjects were trained in detecting targets in different visual fields. There was no significant difference between reaction times for targets presented in either upper or lower visual fields when the array was presented to the entire visual field. However, when the array was restricted to either the upper or lower visual fields, reaction times were significantly slower for detection in the upper visual field.

Adolescent↗
PubMed2000

An in vivo and in vitro comparison of the effects of b2-a2 and b3-a2 p210BCR-ABL splice variants on murine 32D cells.

The Philadelphia (Ph) chromosome, a characteristic cytogenetic marker of chronic myeloid leukaemia (CML), is caused by a reciprocal translocation juxtaposing the 3' region of the ABL gene onto the 5' region of the BCR gene. Due to conservation of the reading frame, but depending on the site of the breakpoint in the BCR gene, two alternatively spliced variants of the p210BCR-ABL mRNA (known as b2-a2 and b3-a2) are produced. To investigate whether there are any biological differences between these splice variants we have transfected the b3-a2 or b2-a2 cDNA into a murine myeloid cell line, 32D. We have also included the previously prepared 32Dp210 cell line (which expresses the b3-a2 transcript) in all of our comparisons. RT-PCR analysis indicated that transcription levels were comparable between the variants. Morphological examination of the cells expressing either of the BCR-ABL transcripts indicated that these cells were more mature with increased cytoplasm:nuclear ratios compared to the 32D parental and 32Dneo vector control cells. However, the 32Dp210 cells had a very different appearance from the other panel members and flow karyotyping indicated a clonal evolution and cytogenetic instability in these cells alone. At 10(6) and 10(7) cell doses all 32D cells expressing BCR-ABL caused ill health and tissue infiltration in SCID mice with such rapidity that statistical analysis was not informative. However, at the 10(5) and 10(4) dosage levels there were similar survival rates between mice injected with 32Db2-a2 or 32Db3-a2 while mice injected with 32Dp210 had a significantly shorter survival time. The study of this 32D cell line panel indicated that there were no overt differences in the biological properties conferred by the b3-a2 or b2-a2 transcripts to the 32D cells although these transcripts were able to confer in vitro and in vivo biological effects. This panel of BCR-ABL expressing 32D cells provides a useful model for CML disease progression studies.

Alternative Splicing↗
PubMed2000

Abnormalities of adherent layers grown from bone marrow of patients with myelodysplasia.

Myelodysplastic syndromes (MDS) are characterized by a clonal disorder of haemopoiesis with defective growth in vitro. The long-term culture system was used to examine aspects of stromal function in MDS patients. Primary long-term cultures of MDS bone marrow showed poor myelopoiesis with progenitors being detected for a median 3.5 weeks (n = 12) compared with 18 weeks in cultures of normal marrow (n = 10; P < 0.0001). The haemopoietic function of adherent layers was assessed in secondary co-cultures seeded with 5 x 10(6) cord blood mononuclear cells on irradiated normal (n = 27; aged 38-82 years) or MDS (n = 32; aged 41-86 years) adherent layers (> 60% confluent). The median myeloid progenitor number/cord blood co-culture was 135 in 5-week-old cultures with normal adherent layers and 22 in those with MDS layers (P < 0.0001). Myeloid colonies were detectable for a median 11 weeks with normal adherent layers and 6 weeks with MDS adherent layers (P < 0.0001); erythroid colonies were detectable for 7 weeks (normal) compared with 5 weeks (MDS) (P < 0.01). The differences in granulocyte-macrophage colony forming unit (CFU-GM) generation were not related to patient age. Cells from adherent layers of at least half of the primary normal (n = 48) and MDS (n = 26) long-term cultures expressed cytokines [interleukin (IL)-3, IL-1 beta, thrombopoietin (Tpo) and erythropoietin (Epo)] and receptors for retinoic acid (RAR alpha) [IL-2, IL-3, macrophage colony stimulating factor (M-CSF) (Fms) and Tpo (Mpl)]. Only IL-1 beta expression was reduced in week-5 MDS cultures compared with those from normal marrows (P < 0.05). There was also a highly significant decline in IL-1 beta expression in normal (but not MDS) adherent layers between week 5 and week 10. Thus, the adherent layers in cultures grown from MDS patients were haemopoietically defective and showed abnormal IL-1 beta expression.

Adult↗
PubMed1999

Inhibition of mitochondrial function in HL60 cells is associated with an increased apoptosis and expression of CD14.

The myelomonocytic cell line HL60 can be induced by a variety of chemical agents to differentiation to either neutrophils or monocytes. Examination of gene expression, by differential display, in cells induced to monocytes with 1alpha,25-dihydroxyvitamin D(3) or neutrophils with all-trans retinoic acid (ATRA) identified a number of clones with altered patterns of expression over the period of differentiation. One of these clones was the mitochondrial gene NADH dehydrogenase subunit 4 (ND4) which showed a differential pattern of expression between the neutrophil and monocyte lineages. The potential of mitochondrial inhibitors to induce differentiation was investigated by treating the HL60 cells with either the NADH dehydrogenase inhibitor, Rotenone, the complex III inhibitor, Antimycin A, or the highly specific mitochondrial ATP-synthase inhibitor, Oligomycin. Although functional assays of differentiation did not produce any positive results, all the inhibitors resulted in a dramatic increase in CD14 expression at day 1, with CD38 markers not observed until day 3. The increased expression of CD14 was accompanied by a decrease in viability and all CD14 positive cells were also positive for Annexin V, a marker of apoptosis. These results suggest that inhibition of the components of the mitochondrial pathways may lead to the marking of some cells, via CD14, for cell death, whilst allowing commitment to differentiation to occur in the surviving population.

ADP-ribosyl Cyclase↗
PubMed1999

Timing of activity in early visual cortex as revealed by transcranial magnetic stimulation.

To determine the timing of visual processing in the early visual cortex, we applied single pulse transcranial magnetic stimulation to the occipital pole of healthy subjects while they were engaged in a forced-choice visual letter-identification task. We found two separate periods of activity, the first ranging from 20 to 60 ms after the onset of the visual stimulus, and the second ranging from 100 to 140 ms after the onset of the visual stimulus. We suggest that these two periods reflect necessary activity in V1, before and after re-entry.

Adult↗
PubMed1999

Short-term memory for colour following posterior hemispheric lesions in man.

Short-term memory for colour was studied in five patients with circumscribed posterior hemispheric lesions. It was impaired independently of colour discrimination in one and more than colour discrimination in two patients. Two patients were normal in colour short-term memory, one with normal and one with deficient colour discrimination performance. Deficient performance in colour short-term memory was associated with bilateral lesions of the inferior occipitotemporal junction including the lateral part of the fusiform gyrus or with a unilateral lesion of the left parieto-occipital convexity. An additional colour constancy deficit was found in the former but not the latter condition. Thus, colour short-term memory can be affected independently of colour discrimination or colour constancy, and may depend on at least two distinct neural circuits.

Adult↗
PubMed1999

Cortical function: jump-starting the brain.

Magnetic stimulation as used in studies of the human brain may not merely disrupt cognitive functions, but also enhance them. The direction of the effect may depend on the frequency of stimulation as much as the area of the brain that is stimulated.

Animals↗
PubMed1999

The role of the parietal cortex in visual attention--hemispheric asymmetries and the effects of learning: a magnetic stimulation study.

Our previous studies of the role of the parietal cortex in visual learning and attention showed that the right parietal cortex is required for normal performance on conjunction visual search tasks but that its role depends on whether subjects are naive or trained on the task. Here we extend these findings in two Experiments. Experiment 1 shows that magnetic stimulation of the left parietal cortex also impairs performance (measured as reaction time) on conjunction visual search tasks, but only when the target is present in the right (contralateral) visual field. Stimulation of the same region on a feature detection task speeds up performance significantly when the target is in the left (ipsilateral) visual field. Experiment 2 explores further the role of the right parietal cortex in learning conjunction search tasks. Stimulation of the right parietal cortex in subjects who had already trained on some visual search tasks did not impair performance on a novel motion/form conjunction task even though the search was clearly serial. Stimulation of area V5, however, severely disrupted performance on the same task. These data indicate that the role of the parietal cortex may change much earlier in the course of training than initially thought.

Adult↗
PubMed1999

Cancer chemotherapy, biodiversity, public and private property: the case of the anti-cancer drug taxol.

The drug taxol has been hailed by many in the cancer community as a major breakthrough in the treatment of cancer. It has already been approved in use against ovarian and advanced breast cancer in many countries worldwide. Taxol has also promoted profound debates in the policy arena not, as one might expect, because of the characteristics or purposes of the drug itself, but because of other far-reaching effects. Taxol is a complex compound found in the bark of the Pacific yew tree, primarily in Oregon and Washington in the USA. The bark was first collected in 1962 and cytotoxicity demonstrated in 1964. Yet it was not until 1989 that the first results of clinical trials were reported. In the US taxol was then rushed through the Food and Drug Administration's regulatory procedures, approval being granted for use in refractory ovarian cancer in 1992. The controversies surrounding taxol surfaced in 1989 and grew substantially over the next few years. In this paper we examine two principal controversies concerning taxol, the first of which focused on apparent conflicts between the needs of environmental protection and those of cancer chemotherapy. Although the media portrayed this as a clash of interests between the environment and people with cancer, we argue that it was an attempt to increase lay participation in biomedical decision making and policy formulation. The second controversy was between health policy and the transfer of public scientific property to the corporate sector. The pharmaceutical company Bristol-Myers Squibb was given exclusive rights to provide taxol from Pacific yew trees under a Co-operative Research and Development Agreement signed in 1991. While this was seen to be in the US Government's (as well as the company's) interest, it provoked a public reaction questioning the terms and consequences of the transfer of publicly generated scientific knowledge to the private sector.

Antineoplastic Agents, Phytogenic↗
PubMed1999

A primer of magnetic stimulation as a tool for neuropsychology.

Transcranial magnetic stimulation (TMS) offers the neuropsychologist a 'virtual lesion' method of investigating the effects of cortical dysfunction. Classical neuropsychology relies on patients with irreversible, and often diffuse brain lesions and these factors place limitations on the inferences that can be drawn about normal brain function. Thus the neuropsychologist is constrained by the extent to which the damaged brain undergoes reorganisation and by the inability to address questions regarding the timing of cognitive functions. TMS can disrupt cognitive functions for a few tens of milliseconds (although some effects of TMS can be seen for longer), with spatial resolution in the order of a centimetre and therefore allows one to study the role of brain areas without the masking effects of cortical reorganisation. The spatial and temporal resolutions are not unique to TMS but because TMS can be used as a temporary interference technique, it has a functional resolution with which one can address questions beyond the range of other neuroimaging and patient studies. Here we outline how TMS produces transitory 'lesion' effects, examine how the effects of stimulation spread in depth and breadth across the cortex and discuss the principles of the use of TMS in neuropsychology. Finally, we also itemise some issues of safety.

Cerebral Cortex↗