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Biomedical subjects

T M Griffin

Publications and source records attributed to T M Griffin.

11 recordsLinked to original sources
PubMed2000

Protection against endotoxemia by HSP70 in rodent cardiomyocytes.

Clinical and experimental studies have shown that myocardial dysfunction is an early event during endotoxemia or septic shock. Several reports have shown that rodents submitted to a mild heat shock become resistant to lipopolysaccharides (LPS) or sepsis. The most abundant of the heat shock proteins (HSP), the HSP70, has been postulated to be the principal mediator of the observed protection against endotoxemia. We have tested the hypothesis that a protective effect against endotoxemia is achievable by the increased presence of the HSP70 in rodent cardiomyocytes. We have found that a transgenic mouse line overexpressing the rat HSP70 gene in the heart exhibits an increased tolerance to LPS treatment (control estimated survival function [S(t)] = 0.538, transgenic S(t) = 0.787, P < 0.05). Interestingly, the increased presence of the HSP70 in the hearts of these mice results in a decrease in the activation of the inducible nitric oxide synthase (iNOS) after LPS treatment. We conclude that HSP70 protection against LPS is most probably mediated through the modulation of iNOS activation and the subsequent decreased synthesis of nitric oxide in cardiomyocytes.

Adenoviridae↗
PubMed1999

Walking in simulated reduced gravity: mechanical energy fluctuations and exchange.

Walking humans conserve mechanical and, presumably, metabolic energy with an inverted pendulum-like exchange of gravitational potential energy and horizontal kinetic energy. Walking in simulated reduced gravity involves a relatively high metabolic cost, suggesting that the inverted-pendulum mechanism is disrupted because of a mismatch of potential and kinetic energy. We tested this hypothesis by measuring the fluctuations and exchange of mechanical energy of the center of mass at different combinations of velocity and simulated reduced gravity. Subjects walked with smaller fluctuations in horizontal velocity in lower gravity, such that the ratio of horizontal kinetic to gravitational potential energy fluctuations remained constant over a fourfold change in gravity. The amount of exchange, or percent recovery, at 1.00 m/s was not significantly different at 1.00, 0.75, and 0.50 G (average 64.4%), although it decreased to 48% at 0.25 G. As a result, the amount of work performed on the center of mass does not explain the relatively high metabolic cost of walking in simulated reduced gravity.

Aged↗
PubMed1998

Calcium- and protein kinase C-dependent activation of the tyrosine kinase PYK2 by angiotensin II in vascular smooth muscle.

Angiotensin II (Ang II) induces vascular smooth muscle cell (VSMC) growth by activating Gq-protein-coupled AT1 receptors, which leads to elevation of cytosolic Ca2+ ([Ca2+]i) and activation of protein kinase C (PKC) and mitogen-activated protein kinases. To assess the link between these Ang II-induced signaling events, we examined the effect of Ang II on the proline-rich tyrosine kinase (PYK2), previously found to be activated by a variety of stimuli that increase [Ca2+]i or activate PKC. PYK2 distribution was demonstrated in rat aortic tissue and in cultured VSMC by immunohistochemistry, revealing a cytosolic distribution distinct from smooth muscle alpha-actin, focal adhesion kinase, or paxillin. The involvement of PYK2 in Ang II signaling was measured by immunoprecipitation and immune complex kinase assays. Treatment of quiescent VSMC with Ang II resulted in a concentration- and time-dependent increase in PYK2 tyrosine phosphorylation and kinase activity in PYK2 immunoprecipitates. PYK2 phosphorylation was inhibited by AT1 receptor blockade and was attenuated by downregulation of PKC or the chelation of [Ca2+]i. Treatment with either phorbol ester or Ca2+ ionophore also increased PYK2 phosphorylation, suggesting that PKC activation and/or increased [Ca2+]i are both necessary and sufficient to activate PYK2. Activation of PYK2 by Ang II was also associated with increased PYK2-src complex formation, suggesting that PYK2 activation represents a potential link between Ang II-stimulated [Ca2+]i and PKC activation with downstream signaling events such as mitogen-activated protein kinase activation involved in the regulation of VSMC growth.

Actins↗
PubMed1998

Force treadmill for measuring vertical and horizontal ground reaction forces.

We constructed a force treadmill to measure the vertical, horizontal and lateral components of the ground-reaction forces (Fz, Fy, Fx, respectively) and the ground-reaction force moments (Mz, My, Mx), respectively exerted by walking and running humans. The chassis of a custom-built, lightweight (90 kg), mechanically stiff treadmill was supported along its length by a large commercial force platform. The natural frequencies of vibration were >178 Hz for Fz and >87 Hz for Fy, i.e., well above the signal content of these ground-reaction forces. Mechanical tests and comparisons with data obtained from a force platform runway indicated that the force treadmill recorded Fz, Fy, Mx and My ground-reaction forces and moments accurately. Although the lowest natural frequency of vibration was 88 Hz for Fx, the signal-to-noise ratios for Fx and Mz were unacceptable. This device greatly decreases the time and laboratory space required for locomotion experiments and clinical evaluations. The modular design allows for independent use of both treadmill and force platform.

Biophysical Phenomena↗
PubMed1994

Prevalence of impaired cerebrovascular reserve in patients with symptomatic carotid artery disease.

Cerebrovascular reserve (CVR) was studied in 104 consecutive patients with symptomatic carotid territory disease and ipsilateral internal carotid artery stenosis. Overall, 30 of 104 patients (29 per cent) had impaired CVR. The frequency of CVR impairment increased with the severity of internal carotid artery stenosis: impairment was present in none of 11 patients with stenosis of less than 50 per cent, four of 24 with stenosis of 50-69 per cent, 14 of 41 with stenosis of 70-89 per cent and 12 of 28 with stenosis of 90-99 per cent. Patients presenting with a stroke were significantly more likely to have impaired CVR than those with transient ischaemic attacks and/or amaurosis fugax (odds ratio 3.7 (95 per cent confidence interval (c.i.) 1.5-9.0)), as were those with a residual neurological deficit (odds ratio 4.3 (95 per cent c.i. 1.6-11.5)) and evidence of infarction from computed tomography (odds ratio 3.8 (95 per cent c.i. 1.6-9.4)).

Adult↗
PubMed1994

Evidence for a reflex provoking contraction of the renal pelvis (with some comments on its clinical implications).

The effect of swallowing a small quantity of water or of solid food (biscuit) on the renogram curve was observed in 177 patients. Swallowing provoked contraction of the renal pelvis in 63% of the kidneys with a pelvicalyceal system which was neither obstructed nor dilated, with expulsion of a substantial fraction of the contents within 30 s. This did not occur in obstructed or denervated kidneys, nor in patients with a high transection of the spinal cord. Evidence is adduced that this contraction is mediated reflexly. This effect may be used diagnostically to distinguish physiological dilatation from obstruction. The implications when performing and interpreting renography are discussed.

Adolescent↗
PubMed1994

Developmental changes in narrative and non-narrative discourse in children with and without brain injury.

This study presents a set of narrative and non-narrative tasks and analytic procedures for examining the discourse development of children with perinatal brain injury and typically developing children. Three oral discourse genres were collected at ages 5, 6, and 7: script, picture description, and replica play narration. Genre performances were assessed for the presence of hypothesized genre features. Results suggest these tasks and procedures are able to characterize development in discourse abilities for both a normative group and for children with perinatal brain injury. The group of children with brain injury produced shorter discourse performance with more off-task talk. This group also showed difficulty in fully differentiating the various genre types and in creating integrated discourse performances. However, most of these children demonstrated considerable growth in control of genre features over this time period. The possible utility of these tasks and procedures for clinical assessment is discussed.

Brain Injuries↗
PubMed1993

Serial imaging of the carotid bifurcation and cerebrovascular reserve after carotid endarterectomy.

A radioisotopic method of quantifying mean cerebral transit time was used to assess the immediate effects of carotid endarterectomy on cerebrovascular reserve (CVR) in 69 patients. In addition, serial postoperative data were acquired on CVR, clinical status and non-invasive imaging of the internal carotid arteries in 56 patients over a period of 6-48 (median 24) months. Twenty-one patients (30 per cent) had preoperative evidence of impaired CVR in the symptomatic hemisphere. Within 4 days of surgery, however, reserve had returned to normal in 17 of the 21 patients. During follow-up, four of the 56 patients developed recurrent stenosis (> 50 per cent) or occlusion of the artery operated on but only two of these had impairment of CVR and none was symptomatic. Three patients suffered recurrent transient ischaemic attacks (TIAs) but none had recurrent internal carotid artery disease or impaired CVR. One patient suffered a TIA in the territory of the non-operated artery during follow-up in association with disease progression and CVR impairment. However, the TIA preceded recognition of either of these changes. Twelve other patients had (or developed) stenosis (> 50 per cent) in the non-operated artery during follow-up but none was symptomatic or developed impairment of CVR. Although assessment of CVR provided useful information on the frequency of haemodynamic compromise before carotid endarterectomy and on the natural history of disease progression, neither serial assessment of reserve nor non-invasive imaging of the carotid bifurcation influenced clinical practice during follow-up.

Blood Flow Velocity↗
PubMed1992

A method of computerised isotope dynamic proctography.

Patients with long-standing constipation were examined by radioisotope proctography. A radiolabelled synthetic potato mash was inserted intrarectally and the dynamic changes during simulated defaecation recorded using a gamma-camera. Computer images from the stored data illustrate changes in the anorectal angle and pelvic floor. The median (and 95% confidence intervals) of the anorectal angles were: at rest 105 degrees (101 degrees, 116 degrees), on voluntary contraction of the pelvic floor by 'squeezing' 91 degrees (81 degrees, 98 degrees), on straining 120 degrees (107 degrees, 137 degrees) and during evacuation 126 degrees (116 degrees, 153 degrees). The pelvic floor movements were: pelvic floor ascent on voluntary contraction 28 mm (9, 34 mm), pelvic floor descent on straining -8 mm (-14, -4 mm) and descent during evacuation -27 mm (-34, -11 mm). Useful additions to previous methods are measurement of the completeness of rectal evacuation 58% (42, 77%), the defaecation time 64 s (50, 138 s) and the defaecation rate 0.9%/s (0.4, 1.4%/s).

Anal Canal↗