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Biomedical subjects

D Pond

Publications and source records attributed to D Pond.

16 recordsLinked to original sources
PubMed1998

Electromagnetic field-induced stimulation of Bruton's tyrosine kinase.

Here we present evidence that exposure of DT40 lymphoma B-cells to low energy electromagnetic fields (EMF) results in activation of phospholipase C-gamma 2 (PLC-gamma2), leading to increased inositol phospholipid turnover. PLC-gamma2 activation in EMF-stimulated cells is mediated by stimulation of the Bruton's tyrosine kinase (BTK), a member of the Src-related TEC family of protein tyrosine kinases, which acts downstream of LYN kinase and upstream of PLC-gamma2. B-cells rendered BTK-deficient by targeted disruption of the btk gene did not show enhanced PLC-gamma2 activation in response to EMF exposure. Introduction of the wild-type (but not a kinase domain mutant) human btk gene into BTK-deficient B-cells restored their EMF responsiveness. Thus, BTK exerts a pivotal and mandatory function in initiation of EMF-induced signaling cascades in B-cells.

Agammaglobulinaemia Tyrosine Kinase↗
PubMed1998

Stimulation of Src family protein-tyrosine kinases as a proximal and mandatory step for SYK kinase-dependent phospholipase Cgamma2 activation in lymphoma B cells exposed to low energy electromagnetic fields.

Here, we present evidence that exposure of DT40 lymphoma B cells to low energy electromagnetic field (EMF) results in a tyrosine kinase-dependent activation of phospholipase Cgamma2 (PLC-gamma2) leading to increased inositol phospholipid turnover. B cells rendered PLC-gamma2-deficient by targeted disruption of the PLC-gamma2 gene as well as PLC-gamma2-deficient cells reconstituted with Src homology domain 2 (SH2) domain mutant PLC-gamma2 did not show any increase in inositol-1,4,5-trisphosphate levels after EMF exposure, providing direct evidence that PLC-gamma2 is responsible for EMF-induced stimulation of inositol phospholipid turnover, and its SH2 domains are essential for this function. B cells rendered SYK-deficient by targeted disruption of the syk gene did not show PLC-gamma2 activation in response to EMF exposure. The C-terminal SH2 domain of SYK kinase is essential for its ability to activate PLC-gamma2. SYK-deficient cells reconstituted with a C-terminal SH2 domain mutant syk gene failed to elicit increased inositol phospholipid turnover after EMF exposure, whereas SYK-deficient cells reconstituted with an N-terminal SH2 domain mutant syk gene showed a normal EMF response. LYN kinase is essential for the initiation of this biochemical signaling cascade. Lymphoma B cells rendered LYN-deficient through targeted disruption of the lyn gene did not elicit enhanced inositol phospholipid turnover after EMF exposure. Introduction of the wild-type (but not a kinase domain mutant) mouse fyn gene into LYN-deficient B cells restored their EMF responsiveness. B cells reconstituted with a SH2 domain mutant fyn gene showed a normal EMF response, whereas no increase in inositol phospholipid turnover in response to EMF was noticed in LYN-deficient cells reconstituted with a SH3 domain mutant fyn gene. Taken together, these results indicate that EMF-induced PLC-gamma2 activation is mediated by LYN-regulated stimulation of SYK, which acts downstream of LYN kinase and upstream of PLC-gamma2.

Animals↗
PubMed1996

News from the divisions: diabetes shared care.

It is not surprising that diabetes care has been a very active area for divisional projects and activities. Diabetes is prevalent in the community (up to one million Australians) and in general practice (1% of GP encounters). Optimal cost-effective diabetes management involves collaboration between general practice and public and private health services--one of the purposes for which divisions were created. Because diabetes is a multisystem chronic disease requiring multi-disciplinary interventions, it has also been a model for applying the health outcomes approach in general practice, especially in New South Wales.

Australia↗
PubMed1992

Sleep disordered breathing and cognitive function in a retirement village population.

Sleep disordered breathing (SDB) may be associated with cognitive dysfunction in non-demented elderly people. A random sample of 96 retirement village residents were given both neuropsychological assessment and overnight sleep monitoring with a portable microprocessor based system (Vitalog PMS-8). Respiratory disturbance index (RDI) was calculated as the number of apnoeas and hypopnoeas per hour of sleep. RDI was not associated with 'memory', 'verbal', and 'motor' factors identified from the analysis of cognitive tests, but was associated with the 'cerebral efficiency' factor (R2 = 0.21, p less than 0.0001). Seventy-three subjects had repeat neuropsychological tests, median time to follow-up being 17 months. Baseline RDI did not predict changes in scores on the two factors identified from the second analysis. We conclude that mild to moderate disturbance of breathing during sleep is not associated with cognitive dysfunction in non-demented subjects.

Activities of Daily Living↗
PubMed1992

Sleep-disordered breathing in elderly people and subjective sleep-wake disturbance.

Sleep-disordered breathing and subjective reports of sleep-wake disturbances are both common in elderly people but previous studies investigating the relationship between the two have produced uncertain results. We hypothesized that there is no relationship between sleep-disordered breathing and subjective reports of sleep-wake disturbance. Ninety-three random-sampled retirement-village residents, mean age 77.6 years, were monitored overnight with a portable microprocessor-based system. The respiratory disturbance index (RDI) was used as a measure of sleep-disordered breathing. Subjects were interviewed regarding sleep-wake patterns and snoring history and the Mini Mental State Examination, Geriatric Depression Scale and Nelson Adult Reading Test were administered. The sleep-wake responses were entered into a principal components analysis. Two components, reflecting night-time and daytime disturbance, accounted for 34% of the variance. Multiple regression analyses were performed using RDI as a continuous dependent variable, and three predictor variables, night-time, and daytime disturbance and history of snoring. Together, these variables accounted for only 2% of the variance. We conclude there is no relationship between mild and moderate sleep-disordered breathing and subjective sleep-wake disturbance in this population.

Aged↗
PubMed1991

Night-to-night variability of disturbed breathing during sleep in an elderly community sample.

Night-to-night variability of breathing and oxygenation during sleep was examined with portable monitoring equipment in 30 residents of a retirement village. Subjects had a variety of health problems as might be expected in the elderly, but all were living independently in self-contained units. None had clinical features to suggest obstructive sleep apnea. Two pairs of consecutive nights were studied, separated by 4-6 months. Satisfactory recordings on all four nights were obtained in 15 subjects, and in these subjects variability of measurements was examined across nights 1-4 using the kappa (K) statistic. There was low but significant agreement in estimated total sleep time (K = 0.23, p less than 0.01) and estimated wakefulness after sleep onset (K = 0.18, p less than 0.05) as assessed with a wrist actigraph. Good agreement was found among measures of disturbed breathing during sleep whether expressed in terms of numbers of events [respiratory disturbance index (RDI), K = 0.62, p less than 0.0001], their duration (event minutes, K = 0.53, p less than 0.0001), or associated disturbance of oxygenation (% cumulative time less than 90% SaO2, K = 0.50, p less than 0.001, n = 9). Twenty-eight subjects had at least two nights' satisfactory recordings. Although some of these individuals showed considerable variation in RDI, this had little overall effect on classification of them into normal (RDI less than or equal to 15) and abnormal groups. The accuracy of the first night's recording in predicting classification derived from recording on three or four nights was 83%.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1989

Interrater reliability of computer-assisted scoring of breathing during sleep.

Twenty-six records of sleep and breathing obtained with a portable monitoring system from elderly subjects were scored by three raters with computer assistance to examine interrater reliability of scoring. Raters were a medical student, a nurse practitioner, and a family physician, all of whom had at least one month's experience with the equipment. Agreement among raters was measured with the unweighted kappa statistic. Significant agreement was observed for all variables, although agreement was better for variables describing breathing (range of kappa 0.71-0.87) than for those describing sleep (range of kappa 0.34-0.57). Complete agreement among the three raters on diagnostic classification occurred in 17 cases. In the remaining 9 cases, 2 raters agreed, whereas the third differed by not more than one category for type of disturbance (e.g., normal versus hypopnea, hypopnea versus apnea) or severity (e.g., mild versus moderate). There was only one disagreement among raters for the 9 subjects with severe respiratory disturbance. We conclude that interrater reliability of identifying and characterizing breathing disturbance during sleep as recorded by portable monitoring is high among trained raters using computer assistance.

Aged↗
PubMed1987

Evaluation of a microprocessor-based portable home monitoring system to measure breathing during sleep.

Study of the epidemiology of disturbances of breathing during sleep was hampered until recently by the need to conduct studies in the laboratory, with attendant inconvenience and limited sample sizes. We assessed the accuracy of a microprocessor-based portable monitoring system (Vitalog PMS-8, Vitalog Corp., CA) to detect and classify episodes of disturbed breathing during sleep in 14 patients with sleep apnea by simultaneously recording oxygenation and thoracoabdominal motion on the portable system and a polygraph. Each patient slept in the laboratory for 1 night. In two subjects, the portable system failed to record thoracoabdominal signals. In the remaining subjects, the portable system detected 78% of 2,340 episodes of disturbed breathing, but the recorded information was not sufficient to allow confident classification into central or obstructive events. The positive predictive value of disturbed breathing detected by the portable system was 64%, Respiratory disturbance indices (RDI) computed from the polygraph and portable records were correlated (r = 0.70; p less than 0.01), and all patients with sleep apnea were correctly diagnosed by the portable system. The portable system overestimated arterial oxygen saturation (SaO2) recorded by an ear oximeter (Biox IIA, Ohmeda, CO) but the error was less than 10% of the true value at SaO2 greater than 60%. Seven normal subjects were studied while awake to examine the accuracy of volume measurements made by the portable system and the system's ability to detect paradoxical thoracoabdominal motion of various degrees. Absolute measurement of tidal volume was inaccurate, but detection rate of paradoxical thoracoabdominal motion was excellent (97%). We conclude that the portable system is sufficiently sensitive to allow detection of patients with breathing disorders during sleep, but further developments are necessary before the system can be relied on for accurate classification of apneas and hypoventilation.

Adult↗