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M Wilkinson

Publications and source records attributed to M Wilkinson.

At least 37 records · Page 2Linked to original sources

Path coalescence transition and its applications.

We analyze the motion of a system of particles subjected to a random force fluctuating in both space and time, and experiencing viscous damping. When the damping exceeds a certain threshold, the system undergoes a phase transition; the particle trajectories coalesce. We analyze this transition by mapping it to a Kramers problem which we solve exactly. In the limit of weak random force we characterize the dynamics by computing the rate at which caustics are crossed, and the statistics of the particle density in the coalescing phase. Last but not least we describe possible realizations of the effect, ranging from trajectories of raindrops on perspex surfaces to animal migration patterns.

Journal Article↗

Developmental regulation of leptin gene expression in rat brain and pituitary.

We have previously reported the expression of leptin mRNA and protein in adult rat brain and pituitary gland. We report here the presence of leptin and leptin receptor mRNA in neonatal female rat brain and pituitary using RT-PCR as well as leptin and leptin receptor immunoreactivity in neonatal rat brain. In addition, we describe age-related changes in leptin mRNA expression in female rat brain and pituitary from postnatal day 2 to 28, evaluated using semi-quantitative RT-PCR analysis. Age-related differences in leptin (ob) mRNA levels were tissue-dependent. The most striking developmental changes were noted in the pituitary and cerebral cortex. In the pituitary, ob mRNA levels were maximal during postnatal days 7-14 and fell sharply by postnatal day 22. In cortex, ob mRNA levels were low in neonatal pups (day 2-7) but increased significantly between postnatal days 14 and 28. Leptin mRNA was detectable at postnatal day 2 in hypothalamus and subcutaneous fat. No significant differences in the level of expression were observed between postnatal day 2 and 28. Serum leptin levels were highest at day 7-14 and decreased significantly by day 21-28, coincident with the fall in pituitary leptin expression. The high levels of leptin expression in the neonatal pituitary suggest that this gland may contribute to the circulating leptin levels during early postnatal development, when adipose deposits are minimal. These data indicate that regulation of leptin gene expression in the postnatal period is tissue-dependent, a finding, which suggests that local leptin expression may have important functional significance in the development of the brain-pituitary system.

Age Factors↗

Rheumatology: 14. Diagnosis and management of anterior knee pain.

A 32-year-old male runner visits his family physician in late spring complaining of pain in his knees over the past month. The pain is mostly anterior but is not well localized. It is aggravated by running, especially on hills, but subsides after the patient stops running. The patient has kept fit during the winter by swimming and occasional cross-country skiing. He has no history of obvious trauma or a noticeable injury.

Adult↗

Transcriptional regulation of the leptin gene promoter in rat GH3 pituitary and C6 glioma cells.

Leptin was originally believed to be an exclusively adipocyte-derived hormone regulating appetite and energy balance. It has recently become apparent that leptin is actively expressed in a number of other tissues including the CNS and pituitary, as well as brain- and pituitary-derived cell lines. However, the factors controlling leptin expression in cells of neuroectodermal origin are unknown. The mouse leptin gene 5'-flanking DNA contains multiple AP-1 and SRF-1 binding sites as well as a consensus CRE site at -491 to -482 bp. In addition, a number of potential PIT1 and Oct-1 binding sites may contribute to leptin gene transcription in pituitary and brain. We have used leptin promoter-luciferase reporter constructs to examine the regulation of the leptin promoter in 3T3-L1 preadipocytes, C6 glioma cells, and GH3 pituitary cells in response to serum and hormonal stimuli. Cells were transiently transfected with reporter constructs containing either the proximal 500 bp of the leptin promoter (-500-luc) or 6000 bp of the leptin gene 5' flanking region (-6000-luc). Functional analysis indicates that the leptin promoter is constitutively active in all 3 cell lines. Transcriptional activity was significantly higher with a -500 to +9 promoter than with a construct containing -6000 to +9 bp of 5' flanking DNA, indicating the presence of repressor elements which may contribute to the tissue-specific regulation of leptin expression. However, qualitatively similar results were observed with both constructs in response to serum and hormonal manipulation. Leptin promoter activity was significantly stimulated by serum in all cell lines, although to varying extents. In contrast, the response of the leptin promoter to insulin, IGF-1 and dibutyryl cAMP was cell-type specific and dependent on the presence or absence of FBS in the culture medium. Insulin, IGF-1 and dibutyryl cAMP each caused an approximately two-fold stimulation of leptin promoter activity in 3T3-L1 cells under serum-free conditions, but had no significant effect in the presence of 10% FBS. In contrast, dibutyryl cAMP markedly stimulated leptin promoter activity (5-8-fold) in C6 or GH3 cells in the presence or absence of FBS, whereas insulin or IGF-1 had minimal effects. These findings support our previous studies on the regulation of leptin steady state mRNA levels in C6 cells and demonstrate tissue-specific differences in the regulation of leptin gene transcription in adipose vs. neuroectodermal tissues.

3T3 Cells↗

Sleep deprivation-induced c-fos and junB expression in the rat brain: effects of duration and timing.

Expression of the immediate-early genes (IEGs) c-fos and junB in the rat brain was studied in response to sleep deprivation (SD) starting at four time points during the light phase of a 12:12 light:dark cycle. Animals were confined to slowly rotating wheels for 3 or 6 h in order to prevent sleep. The numbers of c-Fos- and JunB-immunoreactive cells were assessed in seven brain regions previously reported to respond to SD with increased c-fos expression (medial preoptic area (MPA), cortex, anterior and posterior paraventricular thalamic nuclei, amygdala, caudate-putamen, and laterodorsal tegmental nucleus). While c-Fos was induced by SD in all regions studied, there were differences in levels of induction depending on the duration of deprivation and on the timing of the deprivation period during the light phase. The most robust induction occurred in most regions in response to 3-h deprivation periods beginning 3 h into the light phase. A similarly timed peak of induction was observed in the MPA and cortex after 6 h of SD. In two regions, the posterior paraventricular thalamic nucleus and amygdala, 6 h of deprivation induced greater c-Fos immunoreactivity than did 3 h of deprivation, collapsed across all phases tested. Increased JunB immunoreactivity in response to either duration of deprivation was more limited and was significant only in the MPA, cortex, caudate-putamen and amygdala. c-Fos and JunB immunoreactivity in the paraventricular hypothalamic nucleus was low and similar in control and deprived animals. These results indicate that both duration of prior wakefulness and time of day influence the extent of IEG expression differentially in brain regions responsive to SD. The results also suggest that the posterior paraventricular thalamic nucleus and amygdala might be primarily responsive to length of wakefulness (sleep drive), while the MPA and anterior paraventricular thalamic nucleus might integrate input related to both homeostatic sleep drive and circadian clock influences on sleep regulation.

Animals↗

Effects of a 2- to 4-week course of repetitive transcranial magnetic stimulation (rTMS) on neuropsychologic functioning, electroencephalogram, and auditory threshold in depressed patients.

BACKGROUND: The safety of repetitive transcranial magnetic stimulation (rTMS) has only previously been formally studied in volunteers receiving a single session of stimulation or in a small number of depressed subjects receiving a 2-week treatment course. This study examined safety issues in depressed subjects receiving up to 4 weeks of rTMS. Efficacy results from this study have been previously reported. METHODS: Eighteen subjects with DSM-IV major depression participated in a 2-week, parallel, double-blind, sham-controlled study of rTMS treatment. Twelve subjects then went on to receive 4 weeks active rTMS in an open follow-up. We examined the effects of rTMS on neuropsychologic function (up to 4 weeks), auditory threshold (up to 6 weeks exposure to rTMS noise), and an electroencephalogram (after 2 weeks). Data were analyzed by repeated measures analysis. RESULTS: There were trends for improvement in neuropsychologic performance, probably due to practice effects. No mean changes in auditory threshold occurred, but two patients showed mild high-frequency hearing loss after several weeks of rTMS. Electroencephalograms in two patients, one of whom had sham stimulation, showed minor abnormality. CONCLUSIONS: No significant mean deficits were demonstrated in this cohort. Overall, rTMS for up to 4 weeks is safe, but individual results suggest caution and the need for further investigation of the safety of several weeks of rTMS.

Adult↗

Spectral correlations: understanding oscillatory contributions.

We give a different derivation of a relation obtained using a supersymmetric nonlinear sigma model by Andreev and Altshuler [Phys. Rev. Lett. 72, 902 (1995)], which connects smooth and oscillatory components of spectral correlation functions. We show that their result is not specific to the random matrix theory. Also, we show that despite an apparent contradiction, the results obtained using their formula are consistent with earlier perspectives on random matrix models.

Journal Article↗

Understanding of literal truth, ironic criticism, and deceptive praise following childhood head injury.

Children with closed head injury (CHI) have semantic-pragmatic language problems that include difficulty in understanding and producing both literal and nonliteral statements. For example, they are relatively insensitive to some of the social messages in nonstandard communication as well as to words that code distinctions among mental states. This suggests that they may have difficulty with comprehension tasks involving first- and second-order intentionality, such as those involved in understanding irony and deception. We studied how 6- to 15-year-old children, typically developing or with CHI, interpret scenarios involving literal truth, ironic criticism, and deceptive praise. Children with severe CHI had overall poorer mastery of the task. Even mild CHI impaired the ability to understand the intentionality underlying deceptive praise. CHI, especially biologically significant CHI, appears to place children at risk for failure to understand language as externalized thought.

Child↗

Systemic allergic contact dermatitis to 8-methoxypsoralen (8-MOP).

Photochemotherapy with psoralens and UVA (PUVA) is widely used in the treatment of psoriasis and many other skin conditions. Cutaneous adverse reactions to 8-methoxypsoralen (8-MOP) appear to be rare and may be difficult to distinguish from phototoxicity or UV-induced polymorphic light eruption. We describe a patient who had a systemic allergic contact dermatitis to 8-MOP develop during her second course of PUVA treatment for psoriasis.

Adult↗

Intraoperative quick parathyroid hormone versus same-day parathyroid hormone testing for minimally invasive parathyroidectomy: a cost-effectiveness study.

BACKGROUND: Intraoperative quick parathyroid hormone (QPTH) measurement is claimed to eliminate failures during minimally invasive parathyroidectomy. The cost-effectiveness of QPTH (ie, true cost of avoiding a failed operation) needs careful evaluation. METHODS: In 92 consecutive patients who underwent minimally invasive parathyroidectomy via a small lateral incision, QPTH was estimated preoperatively and at 5, 10, and 15 minutes postparathyroidectomy. QPTH results were subsequently compared with the procedure outcome. Cost-effectiveness analysis was performed for 3 subsequent theoretical management strategies: QPTH not performed, QPTH results available intraoperatively, and parathyroid hormone and serum calcium levels measured routinely with results made available the same day. RESULTS: With criteria for cure being a decrease in the QPTH measurement to less than 50% of preoperative levels and to within normal range, QPTH predictions were true positive in 78 patients; false-negative in 7; false-positive in 1; and true negative in 2. The true cost of using QPTH measurement to avoid a failed operation was 19,801.19 US dollars, with 7 patients undergoing unnecessary conversion. Routine same-day parathyroid hormone and calcium measurements significantly reduced this to 624.73 dollars. Sensitivity analysis with varying cost assumptions demonstrated cost-effectiveness analysis to be robust. CONCLUSIONS: The fact that 97% of patients will be cured regardless of QPTH testing combined with its false-negative rates significantly reduces the cost-effectiveness of the test when compared with same-day parathyroid hormone testing.

Adult↗

Intraoperative parathyroid hormone monitoring fails to detect double parathyroid adenomas: a 2-institution experience.

BACKGROUND: We hypothesized that intraoperative parathyroid hormone monitoring (IOPTH) reliably would detect double parathyroid adenomas. METHODS: This was a retrospective study of 20 patients undergoing conventional parathyroidectomy with resection of exactly 2 abnormal glands. Full exploration was performed regardless of IOPTH values, which were measured after anesthetic induction and 5 and 10 minutes following removal of the first abnormal parathyroid gland. Failure to fall below 50% of baseline value by 10 minutes following resection of the first gland indicated the presence of multiglandular disease. RESULTS: All patients were cured. All excised glands were hypercellular on histology. Mean IOPTH values in 9 of the 20 patients with true negative results (noncurative decrease, another gland present) were 66% +/- 7% at 5 minutes and 83% +/- 15% at 10 minutes. The IOPTH values in 11 of the 20 patients with false positive results (curative decrease, another gland present) were 28% +/- 4% at 5 minutes and 18% +/- 2% at 10 minutes. The false positive rate of IOPTH was 55%. CONCLUSIONS: We found that IOPTH failed to reliably detect the presence of double parathyroid adenomas. These data suggest that caution should be exercised when terminating limited parathyroid exploration based on a curative fall in IOPTH values.

Adenoma↗

His mother-tongue: from stuttering to separation, a case history.

This paper delineates the transference and countertransference experiences in the analysis of a patient whose presenting symptom and main concern was his stutter. I suggest that oral-sadistic rather than anal-sadistic hostile elements may be identified in this patient's particular stutter. I focus on its significance in terms of object relationship: my patient's struggle to 'get born', to emerge as a separate other. I argue that early symbiotic fusion needs in conflict with the need to separate produce his stutter. Speech and language are seen as the vehicle for separation and the stutter as a flight from separateness back to an illusion of fusion with mother.

Adult↗