Biomedical subjects
Publications and source records attributed to I Munro.
We demonstrate an optically sectioned fluorescence lifetime imaging microscope with a wide-field detector, using a convenient, continuously tunable (435-1150 nm) ultrafast source for fluorescence imaging applications that is derived from a visible supercontinuum generated in a microstructured fiber.
Fluorescence imaging of green fluorescent protein (GFP) may be used to locate proteins in live cells and fluorescence lifetime imaging (FLIM) may be employed to probe the local microenvironment of proteins. Here we apply FLIM to GFP-tagged proteins at the cell surface and at an inhibitory natural killer (NK) cell immunological synapse (IS). We present a novel quantitative analysis of fluorescence lifetime images that we believe is useful to determine whether apparent FLIM heterogeneity is statistically significant. We observe that, although the variation of observed fluorescence lifetime of GFP-tagged proteins at the cell surface is close to the expected statistical range, the lifetime of GFP-tagged proteins in cells is shorter than recombinant GFP in solution. Furthermore the lifetime of GFP-tagged major histocompatibility complex class I protein is shortened at the inhibitory NK cell IS compared with the unconjugated membrane. Following our previous work demonstrating the ability of FLIM to report the local refractive index of GFP in solution, we speculate that these lifetime variations may indicate local refractive index changes. This application of our method for detecting small but significant differences in fluorescence lifetimes shows how FLIM could be broadly useful in imaging discrete membrane environments for a given protein.
We report the development of a high-speed wide-field fluorescence-lifetime imaging (FLIM) system that provides fluorescence-lifetime images at rates of as many as 29 frames/s. A FLIM multiwell plate reader and a potentially portable FLIM endoscopic system operating at 355-nm excitation have been demonstrated.
We report a case of malignant intraventricular meningioma with CSF drop metastases and an implantation metastatic subgaleal nodule in a 53-year-old woman. Malignant intraventricular meningiomas are rare with only seven cases being reported in the literature. These tumours can be very aggressive and one should consider immediate postoperative radiotherapy.
The local environment of the Pb atom in Pb(x)Sn(1-x)S solid solution was studied by EXAFS technique. The shortest Pb-S bond length in orthorhombic samples was found to be by approximately 0.2 A shorter than in cubic PbS. This indicates that the 6s2 lone pair of Pb is stereochemically active in the SnS host. Strong correlations found in the distribution of metal atoms in the second shell show that the orthorhombic samples can be considered as solid solutions with unexpectedly strong short-range order. One can expect that the short-range order in PbSnS2 may result in formation of superstructures with space groups C(7)2v or C(2)2v.
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Sixty-seven surgeons, members of the International Craniofacial Surgery Society, responded to a questionnaire focused on assessing the incidence and risk of cranial plate and screw translocation intracranially in infants undergoing cranial surgery. Despite screws, plates, and wires being evident intracranially in individual cases, no apparent increase in seizure frequency or susceptibility to head trauma was noted in this preliminary study.
This report represents the findings of an Expert Panel on the safety of Sanguinaria extract used in Viadent oral rinse and toothpaste products and represents an independent review of the Sanguinaria extract toxicologic data base. It is based on reviews and discussions of the data base by all members of the Expert Panel on Sanguinaria extract. The Panel concluded that the data base on Sanguinaria extract is substantial and indicates that Sanguinaria extract is safe in its present use in Viadent products based on a large margin of safety between levels of human exposure and levels found to produce minimum effect or to be without adverse effect in animals. The panel further concluded that published literature suggesting an association between human exposure to Sanguinaria extract and potential reproductive, cardiovascular, or ocular toxicity, or carcinogenicity is largely anecdotal, unfounded, and not corroborated by or consistent with the substantial data base that was subjected to peer review.
This study is a prospective report of the cases of 135 patients who were slated for coronary artery bypass grafting and selected according to designated criteria. Patients received, in addition to an interview, a comprehensive cognitive, neuropsychologic, and personality assessment 2 weeks before operation and 3, 12, and 24 months after operation. Of the available sample, 82.3% completed the full study. There was no evidence of intellectual or neuropsychologic impairment after operation. Most patients returned to preoperative status 3 months after bypass grafting. Further improvement may continue 12 and 24 months after operation. The personality tests revealed that anticipation of the operation resulted in signs of emotional arousal and distress, which dissipated after a successful surgical outcome. Similarly, return to work and quality of life was enhanced. The current study represents the first systematic, longer-term follow-up of the psychologic and social consequences of coronary artery bypass grafting operations. The findings of this study are discussed within a model of social reconstitution after the successful resolution of a life-threatening medical condition.
Site-directed mutagenesis has been used to generate two mutant Bacillus stearothermophilus lactate dehydrogenases: in one, Trp-150 has been replaced with a tyrosine residue and, in the other, both Trp-150 and -80 are replaced with tyrosines. Both enzymes are fully catalytically active and their affinities for substrates and coenzymes, and thermal stabilities are very similar to those of the native enzyme. Time-resolved fluorescence measurements using a synchrotron source have shown that all three tryptophans in the native enzyme fluoresce. By comparing the mutant and native enzymes it was possible, for the first time, to assign, unambiguously, lifetimes to the individual tryptophans: Trp-203 (7.4 ns), Trp-80 (2.35 ns) and Trp-150 (less than 0.3 ns). Trp-203 is responsible for 75-80% of the steady-state fluorescence emission, Trp-80 for 20%, and Trp-150 for less than 2%.
The present experiments demonstrated that the within session patterns of ethanol consumption of animals given unrestricted access to both food and water can be controlled by altering the schedule of access to ethanol. The first experiment demonstrated that the number of ethanol responses emitted per bout was inversely related to the number of one hour access periods presented per session. In a second experiment, ethanol access was limited to only the dark period of a 12 hour light-dark cycle. Total daily ethanol responding was similar to that of animals that had access to ethanol 23 hours a day. Further restrictions on ethanol availability by restricting access to the last 20 minutes of each hour of the dark period, resulted in an increase in the number of responses emitted per bout.
Sixteen male albino rats were divided into two groups of eight animals and maintained at either their free-feeding or at 80% of their free-feeding weight. For four animals, access to 8% ethanol was unrestricted, for the remaining four, access was restricted to eight 20-min access periods per day. Mean amounts of ethanol consumed per bout were greater during restricted access than during unrestricted access for food-deprived animals but not for free-feeding animals. Total daily ethanol consumption was greatest when animals were food deprived and access to ethanol unrestricted. Total fluid consumption and the within session distribution of water and ethanol responding were affected by feeding condition. For food-deprived animals, the amount of water consumed per session remained relatively constant. The increase in ethanol consumption over sessions resulted in an increase in total fluid consumption. For the free-feeding animals, increases in ethanol consumption resulted in decreases in water consumption so that total fluid consumption remained constant. In addition, food-deprived animals consumed all their daily water intake at the beginning of each session when food was present. Free-feeding animals consumed water throughout the session.
The pharmacokinetics of isoxicam, a new non-steroidal anti-inflammatory drug, were studied in 20 osteoarthritis patients with varying degrees of renal insufficiency. A wide variation in pharmacokinetic parameters was seen between individuals but there was no suggestion that renal function influenced pharmacokinetics. Steady state plasma isoxicam concentrations varied from 20 micrograms/ml to 130 micrograms/ml, while the plasma half-life varied from 23 hours to 58 hours. Despite a reduction in urinary prostaglandin E2 excretion, isoxicam administration did not alter renal function over a 4-week period.
Time-resolved measurements of the fluorescence anisotropy of an extrinsic dye-group attached to lactate dehydrogenase from B. stearothermophilus revealed that the rotational correlation time of the enzyme at low concentrations is 55 ns, while at high enzyme concentrations or in the presence of fructose 1,6-bisphosphate (Fru-1,6-P2) the correlation time increases to 95 ns. These correlation times are consistent with a change in Mr from 85 000 +/- 12 000 (dimer) to 150 000 +/- 22 000 (tetramer) and show that the tetrameric state can be induced either by raising the protein concentration or by the addition of the ligand. We have confirmed this change in molecular weight by gel-filtration experiments. In the ligand-induced tetramer, two Fru-1,6-P2 molecules are bound.
The present experiment demonstrated that patterns of ethanol consumption can be controlled by altering the schedule of ethanol availability. Thirty-two male albino rats, maintained at 80% of their ad libitum weight, were first exposed to 10 base-line sessions in which access to either 8 or 32% ethanol was unrestricted. Each subject was then exposed to one of four restricted access schedules for 30 sessions. During each 23-hr session, the ethanol access period was held constant at 20 min while the time between ethanol access periods was either 70, 160, 340 or 700 min. After restricted access, all subjects were returned to unrestricted access for 10 sessions. Water was continually available throughout the experiment. When ethanol access periods occurred every 70 or 160 min, animals at both concentrations consumed more ethanol (grams per kilogram) than during the initial period of unrestricted access. When the time between ethanol access periods was 340 or 700 min, animals consumed an equal amount or half as much, respectively, as during unrestricted access. Analysis of responding revealed that the mean amount of ethanol consumed per bout was greater during restricted than during unrestricted access. The longer the time between access periods the greater the amount consumed per bout. Upon return to unrestricted access, total daily consumption increased, but the amount consumed per bout decreased to base-line levels.
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