Neocortical long-term potentiation and long-term depression: site of expression investigated by infrared-guided laser stimulation.
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The synaptic site of expression of long-term potentiation (LTP) and long-term depression (LTD) is still a matter of debate. To address the question of presynaptic versus postsynaptic expression of neocortical LTP and LTD in a direct approach, we measured the glutamate sensitivity of apical dendrites of layer 5 pyramidal neurons during LTP and LTD. We used infrared-guided laser stimulation to release glutamate from its "caged" form with high spatial and temporal resolution. Responses to photolytically released glutamate and synaptically evoked EPSPs were recorded with patch-clamp pipettes from the neuronal somata. LTP and LTD could be induced by electrical stimulation at the same synapses in succession. The NMDA receptor-dependent LTD was accompanied by a decrease in the dendritic glutamate sensitivity, suggesting a postsynaptic expression of neocortical LTD. In contrast, LTP was never accompanied by a change in the dendritic glutamate sensitivity. A possible explanation for this finding is a presynaptic expression of neocortical LTP. Another set of experiments corroborated these results: Photolytic application of glutamate with a frequency of 5 Hz caused a long-lasting Ca2+ and NMDA receptor-dependent decrease in the dendritic glutamate sensitivity. In contrast, LTP of dendritic glutamate sensitivity was never induced by photostimulation, despite several experimental modifications to prevent washout of the induction mechanism and to induce a stronger postsynaptic Ca2+ influx. In conclusion, our findings provide strong evidence for a postsynaptic expression of neocortical LTD and favor a primarily presynaptic locus of neocortical LTP. (+info)
Characterization of human atherosclerosis by optical coherence tomography.
(50/891)
BACKGROUND: High-resolution visualization of atherosclerotic plaque morphology may be essential for identifying coronary plaques that cause acute coronary events. Optical coherence tomography (OCT) is an intravascular imaging modality capable of providing cross-sectional images of tissue with a resolution of 10 micro m. To date, OCT imaging has not been investigated in sufficient detail to assess its accuracy for characterizing atherosclerotic plaques. The aim of this study was to establish objective OCT image criteria for atherosclerotic plaque characterization in vitro. METHODS AND RESULTS: OCT images of 357 (diseased) atherosclerotic arterial segments obtained at autopsy were correlated with histology. OCT image criteria for 3 types of plaque were formulated by analysis of a subset (n=50) of arterial segments. OCT images of fibrous plaques were characterized by homogeneous, signal-rich regions; fibrocalcific plaques by well-delineated, signal-poor regions with sharp borders; and lipid-rich plaques by signal-poor regions with diffuse borders. Independent validation of these criteria by 2 OCT readers for the remaining segments (n=307) demonstrated a sensitivity and specificity ranging from 71% to 79% and 97% to 98% for fibrous plaques, 95% to 96% and 97% for fibrocalcific plaques, and 90% to 94% and 90% to 92% for lipid-rich plaques, respectively (overall agreement, kappa=0.83 to 0.84). The interobserver and intraobserver reliabilities of OCT assessment were high (kappa values of 0.88 and 0.91, respectively). CONCLUSIONS: Objective OCT criteria are highly sensitive and specific for characterizing different types of atherosclerotic plaques. These results represent an important step in validating this new intravascular imaging modality and will provide a basis for the interpretation of intracoronary OCT images obtained from patients. (+info)
Indocyanine green as a prospective sensitizer for photodynamic therapy of melanomas.
(51/891)
Spectroscopic, photochemical and biological properties of indocyanine green (ICG) are presented. Light over 800 nm is effectively absorbed by ICG. This property as well as photochemical behaviour of ICG make it a very suitable dye for photodynamic treatment of melanoma cells. Cytotoxicity of ICG itself and the effect of photodynamic therapy (PDT) were evaluated by following the growth of human (SKMEL 188) and mouse (S91) melanoma cells. The surviving fraction of the cells irradiated (lambda(ex) = 830 nm) vs non-irradiated, treated with the same dose of ICG, is significantly decreased (5- to 10-fold). These results show that ICG is a very promising dye for photodynamic therapy of melanomas. (+info)
Juvenile-onset localized scleroderma activity detection by infrared thermography.
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OBJECTIVE: The aim of this study was to define the clinical utility of infrared thermography in disease activity detection in localized scleroderma (LS). METHODS: We retrospectively reviewed 130 thermal images of 40 children with LS and calculated the sensitivity and specificity of thermography, comparing clinical descriptions of the lesions and contemporary thermographs. The reproducibility of thermography was calculated by using the weighted kappa coefficient to determine the level of agreement between two clinicians who reviewed the thermographs independently. RESULTS: The sensitivity of thermography was 92% and specificity was 68%. Full concordance between the two clinicians was observed in 91% of lesions, with a kappa score of 0.82, implying very high reproducibility of this technique. CONCLUSION: Our results demonstrate that thermography is a promising diagnostic tool when associated with clinical examination in discriminating disease activity, as long as it is applied to lesions without severe atrophy of the skin and subcutaneous fat. Further evaluation is needed to determine whether thermography can predict the future progression of lesions. (+info)
Phase I trial of an infrared pulsed laser device in patients with advanced neoplasias.
(53/891)
PURPOSE: The objective of this study was to evaluate the toxicity/radiant exposure/time relationship of an infrared pulsed laser device (IPLD) treatment in patients with advanced neoplasias. Karnofsky performance status (KPS), Spitzer quality of life index (QLI), and potential antitumor activity, if any, were also assessed. EXPERIMENTAL DESIGN: Seventeen patients (n = 17) received a daily IPLD radiant exposure of 4.5 x 10(5) J/m(2) (904 nm pulsed at 3 MHz) under a one-dose schedule and procedure design. Toxicity was evaluated under the parameters of the WHO; indirect toxic ocular effects were also monitored. KPS and QLI measurements were conducted before treatment and at six 3-months intervals. Scores for the seventh interval are the last available (range, 19-39 months). For statistical purposes, patients were classified into group 1, those alive at the end of the study, and group 2, those who had died. RESULTS: Dose-limiting toxicity was not observed. Five patients (n = 5) reported occasional headaches (grade 2), and four (n = 4) referred local pain (grade 2). In group 1 (n = 7), statistically significant increases in KPS and QLI were observed in all of the follow-up intervals compared with pretreatment values. One patient had a complete response, 1 a partial response, 4 stable diseases > or =12 months, and 1 progressive disease. In group 2 (n = 10), statistically significant increases in QLI were observed during the first two intervals. Eight patients had stable disease > or =6 months and 2 had uninterrupted progressive diseases. CONCLUSIONS: The IPLD treatment studied is safe for clinical use and may have potential effects on KPS, QLI, and antitumor activity in patients with advanced neoplasias. (+info)
Use of infrared thermography for monitoring stomatal closure in the field: application to grapevine.
(54/891)
This paper reviews and discusses strategies for the use of thermal imaging for studies of stomatal conductance in the field and compares techniques for image collection and analysis. Measurements were taken under a range of environmental conditions and on sunlit and shaded canopies to illustrate the variability of temperatures and derived stress indices. A simple procedure is presented for correcting for calibration drift within the images from the low-cost thermal imager used (SnapShot 225, Infrared Solutions, Inc.). The use of wet and dry reference surfaces as thresholds to eliminate the inclusion of non-leaf material in the analysis of canopy temperature is discussed. An index that is proportional to stomatal conductance was compared with stomatal measurements with a porometer. The advantages and disadvantages of a possible new approach to the use of thermal imagery for the detection of stomatal closure in grapevine canopies, based on an analysis of the temperature of shaded leaves, rather than sunlit leaves, are discussed. Evidence is presented that the temperature of reference surfaces exposed within the canopy can be affected by the canopy water status. (+info)
A targeted inhibition of DNA-dependent protein kinase sensitizes breast cancer cells following ionizing radiation.
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A major mechanism by which cancer cells become resistant to ionizing radiation (IR) and chemotherapy drugs is by enhanced DNA repair of the lesions; therefore, through inhibition of DNA repair pathways that tumor cells rely on to escape chemotherapy, we expect to increase the killing of cancer cells and reduce drug resistance. DNA-dependent protein kinase (DNA-PK) is a nuclear serine/threonine protein kinase essential for DNA repair as well as sensing and transmitting a damage signal to downstream targets leading to cell cycle arrest. We used a peptide cotherapy strategy to see whether a targeted inhibition of DNA-PK activity sensitizes breast cancer cells in response to IR or chemotherapy drug. A synthesized peptide representing the C terminus of Ku80 (HNI-38) selectively targeted and disrupted interaction between Ku complex and the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs) as well as the DNA binding activity of Ku that led to the inhibition of DNA-PK activity and reduction in double-stranded DNA break (dsb) repair activity. Furthermore, a peptide-based inhibitor with target sequence effectively inhibited the growth of breast cancer cells only in the presence of DNA damage, suggesting that the target peptide sensitizes cancer cells through blocking dsb DNA repair activity. Together, this study not only validates the involvement of the C terminus of Ku80 in Ku's DNA termini binding and interaction with DNA-PKcs, but also a supports physiological role for DNA-PK in IR or chemotherapy drug resistance of cancer cells. (+info)
Radiation dose-dependent maintenance of G(2) arrest requires retinoblastoma protein.
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In response to ionizing radiation (IR), cell cycle checkpoints are activated to provide time for DNA repair. Several different checkpoint mechanisms have been elucidated. However, mechanisms that regulate the duration of cell cycle arrest are not understood. Previous studies have shown that the retinoblastoma tumor suppressor protein (RB) is required for radiation-induced G1 arrest. Working with primary fibroblasts derived from Rb+/+ and Rb-/- mouse embryos, we show that RB also regulates the duration of G2 arrest. The initial G2 checkpoint response is enhanced in Rb-/- cells due to a defect in G1 arrest. However, the permanent arrest in G2 induced by higher doses of IR does not occur in Rb-/- cells. Rb-/- cells either resumed proliferation or underwent apoptosis at IR doses that caused the majority of Rb+/+ cells to arrest permanently in G2. The prolongation of G2 arrest in Rb+/+ cells correlated with a gradual accumulation of hypophosphorylated RB. Thus, regulation of the RB function may be an important aspect in the maintenance of cell cycle checkpoints in DNA damage response. (+info)