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Biomedical subjects

R Hicks

Publications and source records attributed to R Hicks.

At least 19 recordsLinked to original sources

Trial-to-trial variability of corticospinal volleys in human subjects.

The trial-to-trial variability of the different components of corticospinal volleys evoked by transcranial electrical stimulation of the motor cortex using a constant stimulus intensity was measured from epidural recordings during surgery to correct scoliosis. The recordings were made when there was no operative interference, and blood pressure, temperature, ventilation and anaesthetic regimen were stable. A simple D wave with a single negative peak of 10-30 microV amplitude was recorded in 4 patients. It varied little in amplitude (S.D.s < 8% for 100 consecutive single responses). In 4 patients the stimulus was adjusted to produce a complex D wave with 3 components, the earliest 2 of which arise from subcortical/brain-stem sites. The variability of amplitude of these components was high (S.D.s of 13-50%), but the variability of latency was low (S.D.s of 2-3%). Eighteen I waves were recorded in 6 of the subjects. Their variability from trial to trial was similar to that of the components of the complex D wave. It is argued that there would be greater trial-to-trial variability of the corticospinal volley in the awake state, particularly when the stimulus was magnetic rather than electrical. Explanations for changes in the compound muscle action potential produced by transcranial stimulation, electrical or magnetic, must take into account that a constant stimulus does not evoke an identical descending volley.

Adolescent

Transcranial electrical stimulation of the motor cortex in man: further evidence for the site of activation.

1. The motor cortex was stimulated electrically (vertex anode; cathode 6 cm lateral) in neurologically normal subjects undergoing surgery for scoliosis, and the evoked corticospinal volleys were recorded from the spinal cord using epidural electrodes. 2. Stimuli > 330 V produced a complex D-wave volley containing three separate peaks, with high-threshold components, 0.8 ms (D2) and 1.6 ms (D3), in advance of the lowest-threshold component (D1). As stimuli increased up to 1500 V, D3 replaced the later components completely, but there was no further latency 'jump'. 3. Brainstem stimulation using electrodes over each mastoid process produced a descending volley that had the same latencies as D3. At threshold, stimulation of the brainstem or spinal cord attenuated the D wave evoked by simultaneous cortical stimulation. 4. It is concluded that transcranial electrical stimulation of the motor cortex at high intensities can access corticospinal neurones at the pyramidal decussation, and that stimulation of the brainstem (and the spinal cord) preferentially accesses corticospinal axons. At threshold, motor cortex stimulation probably activates corticospinal neurones at or near the cerebral cortex.

Adolescent

v-mos-transformed cells fail to enter quiescence but growth arrest in G1 following serum withdrawal.

The product of the mos protooncogene normally functions in the induction of meiosis and regulation of cell-cycle progression in oocytes. Here we have investigated the cell-cycle progression of NIH3T3 cells transformed by the v-mos gene. Flow cytometric analysis showed that logarithmically growing v-mos-transformed cells do not differ from their nontransformed counterparts in the distribution of cells in the G1, S, and G2/M phases. Likewise, after serum withdrawal for 48 h, both normal and v-mos-transformed NIH3T3 cells have essentially ceased proliferation, as analyzed by flow cytometry, [3H]thymidine and BrdU incorporation into newly synthesized DNA, and mitotic indexes. However, while the normal NIH3T3 cells are arrested in a quiescent state, the v-mos-transformed cells are arrested in early to mid G1, prior to the point where cells require certain amino acids for proliferation (V point). In agreement with these different arrest points, the v-mos-transformed cells enter S phase following serum stimulation within about 8 h, without the additional 4- to 6-h lag period characteristically displayed by the parental NIH3T3 cells. In addition, we show a lack of expression of a growth arrest-specific gene product, gas1, in the serum-arrested v-mos-transformed cells. These data demonstrated that v-mos-transformed cells display growth characteristics that differ fundamentally from those of normal cells or cells transformed by overexpression of myc [1]. Our results suggest that the v-mos oncoprotein transforms cells, at least in part, by preventing exit from the cell cycle into quiescence.

3T3 Cells

Direct comparison of corticospinal volleys in human subjects to transcranial magnetic and electrical stimulation.

1. The effects of graded transcranial magnetic and anodal electrical stimulation of the human motor cortex were compared in human subjects undergoing orthopaedic operations on the spine, before and after withdrawal of volatile anaesthesia. Corticospinal volleys were recorded from the spinal cord in the low-cervical and low-thoracic regions (six subjects) or the mid-thoracic region (two subjects) using bipolar electrodes inserted into the epidural space. 2. Electrical stimuli were delivered using anode at the vertex and cathode 7 cm laterally. The corticospinal volley at threshold consisted of a single deflection with a mean latency to peak of 4.17 ms at the rostral recording site. With further increases in stimulus strength the latency of this D wave shortened in two steps, first by 0.89 ms (seven subjects) and then by a further 0.8 ms (two subjects), indicating that the site of activation of some corticospinal neurones had shifted to deep subcortical sites. 3. When volatile anaesthetics were given, a corticospinal volley could not be defined in three subjects with magnetic stimuli of 70, 80 and 100% maximal stimulator output with the coil at the vertex (Novametrix Magstim 200, round coil, external diameter 14 cm). In the remaining five subjects, the component of lowest threshold was a D wave recorded at the rostral site at 4.0 ms when stimulus intensity was, on average, 70%. With stimuli of 90-100% a total of five small I waves could be defined in the five subjects (i.e. on average one I wave per subject). 4. After cessation of volatile anaesthetics in seven subjects, the thresholds for D and I waves were lower and their amplitudes were greater. The D wave remained the component of lowest threshold in all subjects, appearing at the low-cervical level with magnetic stimuli of 50%. However, in three subjects I waves also appeared at D wave threshold, and the D wave was smaller than with electrical stimulation at I wave threshold. There was no consistent change in latency of the magnetic D wave as stimulus intensity was increased to 100%. 5. These findings suggest that the previously reported difference in latency of the EMG potentials produced in upper-limb muscles by anodal stimulation and magnetic stimulation of the human motor cortex is not because the corticospinal volley induced by magnetic stimulation lacks a D wave.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent

Potentiation of etoposide-induced cytotoxicity and DNA damage in CCRF-CEM cells by pretreatment with non-cytotoxic concentrations of arabinosyl cytosine.

Pretreatment of the human lymphoblastoid cell line CCRF-CEM with 0.02 microM arabinosyl cytosine (ara C) enhances both the cytotoxic and the DNA-damaging effects of etoposide. This concentration of ara C is itself non-cytotoxic and results in no detectable DNA damage as measured by alkaline elution. Ara C pretreatment results in the synchronisation of cells, a 24-h pretreatment resulting in the accumulation of cells in the early S phase. The sensitivity of cells to etoposide-induced cytotoxicity was increased 2.5 times and DNA damage was enhanced 1.66 times by this pretreatment. Maximal potentiation of etoposide-induced DNA damage (2.06-fold increase) was observed after 48 h continuous treatment with ara C, but no further enhancement of cytotoxicity occurred. Cell-cycle analysis demonstrated that 48 h ara C treatment resulted in the accumulation of cells in the late S/G2M phase. Cells returned to a normal cell-cycle distribution within 24 h of the removal of ara C, and the potentiation of etoposide activity was then reduced to a 1.3- to 1.4-fold level. DNA damage induced by etoposide following ara C pretreatment was qualitatively identical to that produced by etoposide alone, suggesting a mechanism involving topoisomerase II. To investigate this possibility, we measured topoisomerase II protein levels by immunoblotting. Measurement of topoisomerase II levels in whole-cell lysates of ara C-pretreated cells showed a 3- to 5-fold increase in topoisomerase levels relative to total protein content. This suggests that elevated enzyme levels may be responsible for the increased sensitivity of ara C-pretreated cells to etoposide.

Cell Cycle

Assessment of corticospinal and somatosensory conduction simultaneously during scoliosis surgery.

The function of descending motor pathways and that of ascending sensory pathways in the spinal cord were monitored at the same time in 120 patients undergoing surgery for scoliosis. Transcranial electrical stimulation of the motor cortex was performed simultaneously with stimulation of the tibial nerves in the popliteal fossae, and the descending and ascending volleys were recorded from the spinal cord at two levels using epidural electrodes. Stable recordings of both volleys have been obtained in all neurologically normal patients and in many with pre-existing neurological deficits. The experimental conditions which resulted in reliable recordings were explored in select patients and include: a vertex-anode/lateral cathode montage for transcranial stimulation, epidural recording of evoked corticospinal and somatosensory volleys at two spinal levels, a high-pass filter of 500 Hz, and stable anaesthesia. The epidural recording allows full muscle relaxation and the use of volatile anaesthetics; recording at two levels allows a deterioration in function to be identified quickly and distinguished from an artifactual change.

Anesthetics

Anodal and cathodal stimulation of the upper-limb area of the human motor cortex.

In 18 neurologically normal subjects the corticofugal volleys evoked by anodal and cathodal electrical stimulation of the motor cortex were recorded using epidural electrodes at the high-thoracic and low-thoracic regions of the spinal cord during surgery for scoliosis. At and just above threshold, anodal and cathodal stimulation of the upper-limb area and motor cortex produced a D wave that propagated to the low-thoracic region. The stimulus intensity required to produce D waves was significantly lower with anodal stimulation. I waves were recorded at higher stimulus intensities than the D wave but not more readily with cathodal stimulation. There was no significant difference in the extent to which stimulus intensity had to be increased above D-wave threshold to produce I waves with the two stimulus polarities, and the number of I waves was the same when the stimulus was increased by the same amount above D-wave threshold. After withdrawal of isoflurane, I waves could not be recorded when the stimulus intensity was below D-wave threshold with either stimulus polarity. Anodal stimulation over the upper-limb area remained more effective than cathodal stimulation in producing both D and I waves. These results indicate that, at threshold, regardless of anaesthesia, anodal and cathodal stimuli access upper-limb corticospinal neurons directly at a similar site, the anodal stimuli being more effective. In addition, the results suggest that some corticospinal neurons in the upper-limb area of motor cortex have projections to lumbar segments.

Adolescent

Corticospinal volleys evoked by electrical stimulation of human motor cortex after withdrawal of volatile anaesthetics.

1. In twenty-two neurologically normal patients undergoing surgery for scoliosis, corticospinal volleys to transcranial electrical stimulation of the motor cortex were recorded from the spinal cord using epidural electrodes. While anaesthesia was maintained by nitrous oxide and narcotics, volatile anaesthetics were withdrawn to determine whether such agents had a depressant effect on the evoked corticospinal volley. 2. Profound changes were documented in liminal D waves, there being an increase in amplitude averaging 392% following withdrawal of the volatile anaesthetic. There was a proportionately smaller increase (averaging 26%) in supraliminal D waves; these had a complex bifid or trifid shape indicating that some corticofugal axons were being activated deep to cortex. In general the effect on the D wave of withdrawing the anaesthetic agent was similar to that of increasing stimulus intensity. 3. Withdrawal of isoflurane dramatically increased the number of I waves and their mean amplitude. In the absence of isoflurane, I3 (mean latency 3.5 ms after the D wave) became the dominant I wave. The amplitude of I2 (mean latency 2.2 ms) became slightly smaller. The change in I waves could not be likened to an increase in stimulus intensity, because I waves invariably increase in, or remain of the same, amplitude as stimulus intensity is increased. 4. These findings indicate that changes in motor cortex excitability can result in major changes in the corticospinal volley produced by transcranial electrical stimulation, affecting both the D wave and I waves. They caution against identifying a cortical action solely on the basis of a change in the responses to magnetic stimulation of motor cortex but no such change to electrical stimulation.

Adolescent

Identification of murine thymocyte populations capable of extensive proliferation in serially passaged thymic organ cultures.

Using the approach of titrating precursor cells into mouse thymus organ cultures and serial passage, we have sought to compare the proliferative capacities of cells derived from adult and embryonic thymus and related haemopoietic tissues. We find that cells derived from the liver and thymus of day 14 embryos are capable of extensive proliferation in such cultures (surviving for at least 12 weeks) whereas cells derived from adult sources (blood and thymus) display a much more restricted lifespan and potential for division. Analysis of sequentially passaged thymic lobes shows that cells lacking CD4 and CD8 (CD4- and CD8-) and a subset of single CD8 positives are selectively expanded in these cultures. A preliminary study of the CD4-CD8- populations in these lobes suggest that these include cells expressing surface CD3 (in association with either TCR alpha beta or TCR gamma delta) and a subset of CD4-CD8-CD3-. These findings suggest that sequential passage of thymocytes in organ culture may be a useful alternative strategy for characterising cells with high proliferative potential, resident in the thymus and also for probing their lineage relationships.

Animals

Loss of the first permanent molar and caries experience of adjacent teeth.

The caries experience of the occlusal and distal surfaces of the second premolars and the occlusal and mesial surfaces of the second permanent molars was examined in four groups of subjects aged 19-20 years. Group 1 comprised subjects with first permanent molars present, Group 2 subjects with early loss of the first permanent molar (before the age of 11-12 years), Group 3 subjects with late loss of the first permanent molar (after 11-12 years but before 15-16 years) and Group 4 included a combination of Group 2 and Group 3. Loss of the first permanent molar was associated with increased caries or restorations in the occlusal surfaces of adjacent teeth, but reduced caries or restorations in the proximal surfaces of adjacent teeth. Early loss of the first molar was associated with significantly greater caries or restoration experience in proximal surfaces than late loss, but no difference was detected for occlusal surfaces.

Adolescent

The expression of MHC class II (Ia) antigens on mouse keratinocytes following epicutaneous application of contact sensitizers and irritants.

The expression of MHC class II (Ia) antigens on mouse keratinocytes was studied following both the induction and elicitation of contact sensitivity, and after primary irritant reactions. IA+ and IE+ keratinocytes were detected, using an indirect immunofluorescence assay on epidermal sheets, only after the induction and elicitation of contact sensitivity with the sensitizers oxazalone, picryl chloride and 2,4-dinitrochlorobenzene but not with formaldehyde. Ia+ keratinocytes were not detected after epicutaneous application of the non-sensitizing irritants croton oil, SDS and anthralin, or following attempted sensitization of nude mice, suggesting that the expression of Ia antigen on keratinocytes during contact sensitivity reactions is T-cell mediated. Because Ia antigen expression on keratinocytes could be detected only several days after induction or elicitation of contact sensitivity, and contact sensitization could also be demonstrated to occur independently of aberrant Ia expression, Ia+ keratinocytes cannot be involved in the initiation of these reactions. However, they might be important in exerting an immunomodulatory influence during the later stages of the responses to certain sensitizers.

Animals

Auto- and polyreactivity of IgM from CD5+ and CD5- cord blood B cells.

The presence of the CD5 (67 kDa) molecule on the surface of B cells has been considered a marker for cells producing auto- and polyreactive antibodies. Cord blood B lymphocytes (rich in CD5+ B cells) have been sorted into CD5 positive and negative populations by flow cytometry using monoclonal antibodies to CD20 and CD5. Clones of these populations were obtained by immortalization with Epstein-Barr virus. Clones derived from both CD5+ and CD5- B cells produced IgM which was auto- and polyreactive with a higher frequency of these specificities in the CD5+ population. These data indicate that expression of surface CD5 on cord blood B cells is not a definitive marker of an auto/polyreactive population.

Antibodies, Monoclonal

Contact sensitivity (allergic contact dermatitis) to bis(tri-n-butyltin) oxide in mice.

Contact sensitivity (allergic contact dermatitis) to bis(tri-n-butyltin) oxide (TBTO) was demonstrated in the mouse. TBTO (in an acetone:olive olive oil vehicle) or acetone:olive oil alone (as a control) were applied to the shaved flank under an occlusive patch and animals were challenged on the dorsum of the ear 6 days later. Ear swelling was then measured using an engineer's micrometer, 2, 24, 48 or 72 h thereafter. Significant differences in ear swelling between control and TBTO-sensitized animals were found 24 h after challenge: thereafter the elicitation reaction declined rapidly whilst irritant swelling in control animals increased. Maximal elicitation of TBTO sensitivity could only be elicited by concentrations of TBTO that caused irritation. In a separate experiment, a single application of TBTO to the ears of naive animals provoked increase in auricular lymph node weight, cell yield and proliferation of lymph node cells during overnight culture. These data support the conclusion that TBTO is a contact sensitizer and illustrate the potential usefulness of the quantitative methods of contact sensitivity assessment which have been developed in the mouse.

Animals

The impact of curriculum-based suicide prevention programs for teenagers: an 18-month follow-up.

In a long-term follow-up of a study designed to assess the impact of school-based suicide prevention curricula on high school students, a group of 174 students from two high schools who were exposed to a prevention program were compared with a group of 207 control students from two additional high schools who were not exposed to the curriculum. A questionnaire, designed to measure the effects of the prevention program on actual help-seeking behaviors and suicide morbidity during the follow-up period, was administered 18 months after delivery of the program. The study failed to find convincing evidence of any program effect.

Adolescent