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1.
L A Geddes 《IEEE engineering in medicine and biology magazine》2002,21(3):102-103
Poiseuille, known for his law of fluid flow, which is the analog of Ohm's law, introduced the units (mmHg) by which we measure blood pressure by using the mercury manometer, which he described in his medical school thesis in 1828. For 50 years, mean blood pressure was all that could be measured because of the long response time of the mercury manometer. It is true that the height of the mercury column displayed pulsatile oscillations, but their amplitude was much less than that of pulse pressure. It is interesting to note that the slowly responding mercury manometer was made to display first systolic then diastolic pressure by means of an ingenious device that contained two oppositely directed check valves. It took from 1828 to 1903 for high-fidelity graphic recordings of blood pressure to appear in which systolic and diastolic pressures were believable. However, systolic and diastolic pressures were measurable since 1878 when Golz and Gaule created their ingenious valved device that permitted use of the slowly responding mercury manometer to display these pressures accurately 相似文献
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L A Geddes 《IEEE engineering in medicine and biology magazine》2006,25(6):92-93
This paper discusses the experiments conducted by physicist and physician Arsenne d'Arsonval on the effect of sinusoidal ac on the body, well before the era of electronics. d'Arsonval's first experiments were on the effect of ac on muscle contraction using frog muscle. He contrived a most ingenious device, which displayed the voltage curve and the force of muscle contraction on a smoked-drum kymograph. By using this instrument, along with various alternators such as the Gramme machine, d'Arsonval was able to show that the muscular contraction force decreased with increasing frequency of the electric current. d'Arsonval then turned his attention to the effect of high-frequency ac on the human body. To this end, he created a spark-gap generator of the type described by Hertz in 1888. d'Arsonval demonstrated two important facts: 1) muscle contraction force decreased with increasing frequency of the current and 2) substantial current could be passed through the body and it produced a sensation of warmth. This he proved with conductive and capacitive coupling. By his experiments, d'Arsonval laid the foundation for two new medical techniques: 1) electrosurgery and 2) diathermy. Today both fields are well established in medicine 相似文献
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L A Geddes 《IEEE engineering in medicine and biology magazine》2002,21(6):152-153
There are several psychiatric illnesses that are difficult to treat with drugs. Among these are schizophrenia, manic depression, and profound depression; many of these may involve a tendency to suicide. In 1938 U. Cerletti conducted convulsive experiments on pigs using power-line current applied to electrodes at various sites. The effect of current duration was also investigated. As yet it is not known which areas in the brain are the optimum targets for the therapeutic use of cranially applied current to treat psychiatric illnesses, although the frontal lobes appear to be the best targets. 相似文献
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Chen Guang Yu Vimala Bondada Hina Iqbal Kate L. Moore John C. Gensel Subbarao Bondada James W. Geddes 《International journal of molecular sciences》2022,23(1)
Microglia/astrocyte and B cell neuroimmune responses are major contributors to the neurological deficits after traumatic spinal cord injury (SCI). Bruton tyrosine kinase (BTK) activation mechanistically links these neuroimmune mechanisms. Our objective is to use Ibrutinib, an FDA-approved BTK inhibitor, to inhibit the neuroimmune cascade thereby improving locomotor recovery after SCI. Rat models of contusive SCI, Western blot, immunofluorescence staining imaging, flow cytometry analysis, histological staining, and behavioral assessment were used to evaluate BTK activity, neuroimmune cascades, and functional outcomes. Both BTK expression and phosphorylation were increased at the lesion site at 2, 7, 14, and 28 days after SCI. Ibrutinib treatment (6 mg/kg/day, IP, starting 3 h post-injury for 7 or 14 days) reduced BTK activation and total BTK levels, attenuated the injury-induced elevations in Iba1, GFAP, CD138, and IgG at 7 or 14 days post-injury without reduction in CD45RA B cells, improved locomotor function (BBB scores), and resulted in a significant reduction in lesion volume and significant improvement in tissue-sparing 11 weeks post-injury. These results indicate that Ibrutinib exhibits neuroprotective effects by blocking excessive neuroimmune responses through BTK-mediated microglia/astroglial activation and B cell/antibody response in rat models of SCI. These data identify BTK as a potential therapeutic target for SCI. 相似文献
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TL Tekirian TC Saido WR Markesbery MJ Russell DR Wekstein E Patel JW Geddes 《Canadian Metallurgical Quarterly》1998,57(1):76-94
The goals of this study were twofold: to determine whether species differences in Abeta N-terminal heterogeneity explain the absence of neuritic plaques in the aged dog and aged bear in contrast to the human; and to compare Abeta N-terminal isoforms in parenchymal vs cerebrovascular Abeta (CVA) deposits in each of the species, and in individuals with Alzheimer disease (AD) vs nondemented individuals. N-terminal heterogeneity can affect the aggregation, toxicity, and stability of Abeta. The human, polar bear, and dog brain share an identical Abeta amino acid sequence. Tissues were immunostained using affinity-purified polyclonal antibodies specific for the L-aspartate residue of Abeta at position one (AbetaN1[D]), D-aspartate at N1 (AbetaN1[rD]), and pyroglutamate at N3 (AbetaN3[pE]) and p3, a peptide beginning with leucine at N17 (AbetaN17[L]). The results demonstrate that each Abeta N-terminal isoform can be present in diffuse plaques and CVA deposits in AD brain, nondemented human, and the examined aged animal models. Though each Abeta N-terminal isoform was present in diffuse plaques, the average amyloid burden of each isoform was highest in AD vs polar bear and dog (beagle) brain. Moreover, the ratio of AbetaN3(pE) (an isoform that is resistant to degradation by most aminopeptidases) vs AbetaN17(L)-x (the potentially nonamyloidogenic p3 fragment) was greatest in the human brain when compared with aged dog or polar bear. Neuritic plaques in AD brain typically immunostained with antibodies against AbetaN1(D) and AbetaN3(pE), but not AbetaN17(L) or AbetaN1(rD). Neuritic deposits in nondemented individuals with atherosclerotic and vascular hypertensive changes could be identified with AbetaN1(D), AbetaN3(pE), and AbetaN1(rD). The presence of AbetaN1(rD) in neuritic plaques in nondemented individuals with atherosclerosis or hypertension, but not in AD, suggests a different evolution of the plaques in the two conditions. AbetaN1(rD) was usually absent in human CVA, except in AD cases with atherosclerotic and vascular hypertensive changes. Together, the results demonstrate that diffuse plaques, neuritic plaques, and CVA deposits are each associated with distinct profiles of Abeta N-terminal isoforms. 相似文献
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Q Guo W Fu J Xie H Luo SF Sells JW Geddes V Bondada VM Rangnekar MP Mattson 《Canadian Metallurgical Quarterly》1998,4(8):957-962
Prostate apoptosis response-4 (Par-4) is a protein containing both a leucine zipper and a death domain that was isolated by differential screening for genes upregulated in prostate cancer cells undergoing apoptosis. Par-4 is expressed in the nervous system, where its function is unknown. In Alzheimer disease (AD), neurons may die by apoptosis, and amyloid beta-protein (A beta) may play a role in this. We report here that Par-4 expression is increased in vulnerable neurons in AD brain and is induced in cultured neurons undergoing apoptosis. Blockade of Par-4 expression or function prevented neuronal apoptosis induced by Ab and trophic factor withdrawal. Par-4 expression was enhanced, and mitochondrial dysfunction and apoptosis exacerbated, in cells expressing presenilin-1 mutations associated with early-onset inherited AD. 相似文献