Effect of optode separation on brain penetration in adults.
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Adult↗
Biomedical subjects
S M Bailey
Publications and source records attributed to S M Bailey.
On the origin of lateral asymmetry.
Lateral asymmetry refers to unequal fluorescent intensity between adjacent regions of sister chromatids. It has been observed in the centromeric regions of mitotic chromosomes of mouse or human origin when cells are grown in 5-bromo-2'-deoxyuridine (BrdU) for a single round of DNA synthesis. The chromosome-orientation fluorescence in situ hybridization (CO-FISH) technique was used with pseudodiploid mouse cells to show that the regions of asymmetrical brightness coincide with major satellite repetitive DNA, and that the more heavily BrdU-substituted chromatid is the one that fluoresces less brightly. These observations support a 20 year old hypothesis on the origin of lateral asymmetry. Other observations suggest that differential loss of DNA from the heavily substituted chromatid also contributes to lateral asymmetry.
Animals↗
The effect of track structure on cell inactivation and chromosome damage at a constant LET of 120 keV/micrometer.
The influence of track structure on chromosome damage and cell inactivation are being investigated. Plateau-phase normal human fibroblast cultures were irradiated with gamma rays, and He, Ne and Ar ions. Particle velocities were chosen so that all beams had an LET of 120 keV/micrometer. In this constant-LET experimental design, the radial distribution of excitations and ionizations about the particle track is the most significant variable. Using premature chromosome condensation, chromatin breaks were measured at two time points, promptly after irradiation and after a prolonged incubation to allow for repair. These measurements give an indication of both initial chromosomal damage and also residual damage that is either not repaired or is misrepaired. Survival was measured under the same conditions. Results indicate that the RBEs for both cell inactivation and, to a lesser extent, chromosome damage decrease as particle energy increases.
Alpha Particles↗
CO-FISH reveals inversions associated with isochromosome formation.
Despite the likely prevalence and documented biological impact of inverted DNA sequences in humans and other species, our ability to detect them on a routine basis is limited. The technique of chromosome orientation fluorescence in situ hybridization (CO-FISH) was used to detect obligate chromosome inversions associated with isochromosome formation in two human cell lines. Simultaneous hybridization of a strand-specific telomeric probe allowed us to deduce the absolute orientation of repetitive DNA sequences associated with the inverted region. These results show that, in principle, CO-FISH could be used to detect virtually any type of inversion, including those likely to escape detection by other methods. Prospective applications of the technique are discussed in relation to its principal limitation, the present availability of suitable single-stranded DNA probes.
Base Sequence↗
A new method for detecting pericentric inversions using COD-FISH.
A new approach for detecting chromosomal inversions, based on the recently developed technique of chromosome orientation and direction fluorescence in situ hybridization (COD-FISH), is presented. COD-FISH is a strand-specific modification of standard FISH technology which allows the hybridization of single-stranded probes to one, and only one, chromatid of a metaphase chromosome. It can be used to determine the absolute 5'-to-3' direction of DNA target sequences with respect to the short-to-long arm direction of a given chromosome. Since an inversion reverses the orientation of DNA sequences within the inverted region, an inversion becomes detectable as a "switch" in probe signal from one chromatid to the other, when compared to a reference probe outside of the inverted region. Pericentric inversions in chromosomes 1, 8, 10, and X, which had previously been identified by chromosome banding, were analyzed by the COD-FISH technique. The results presented here demonstrate that COD-FISH can be used for the detection of pericentric inversions and that, in some instances, it provides additional information not obtainable by more conventional methods of cytogenetic analysis. Practical limitations of the COD-FISH technique are also discussed.
Centromere↗
A new visual image rating scale for females: correlations with measures of relative fatness, weight dissatisfaction, and body-esteem.
A new Visual Image Rating Scale for females was developed from a computer-reconstructed photograph to produce figures with realistic three-dimensional contour and different types of fat and muscle distribution. Correlations between choice of figures selected by a group of college women on two occasions two weeks apart gave significant test-retest stability. To estimate the construct validity of the scale in assessing body satisfaction, at the time the scale was first administered 77 undergraduate women were asked to select the figure closest to their current physique and to complete the Body-esteem Scale. Figure selection was highly correlated with relative fatness as measured by Body Mass Index and with scores on the Weight Concern subscale of the Body-esteem Scale. The utility of the scale for women of color or for women of a wider range of age and socioeconomic status remains to be evaluated.
Adult↗
Alpha-particle-induced sister chromatid exchange in normal human lung fibroblasts: evidence for an extranuclear target.
We investigated the relationship between nuclear hits by alpha particles and the subsequent occurrence of sister chromatid exchanges (SCEs) in normal human diploid lung fibroblasts (HFL1). Cells were exposed to 238Pu alpha particles at doses ranging from 0.4-12.9 cGy and subsequently analyzed for SCEs. A significant increase in SCE frequency was observed even at the lowest dose examined. The extent of induction of SCEs in the HFL1 cells showed dose dependency in the very low dose range, i.e. 0.4-2.0 cGy. Thereafter, induction of SCEs was independent of dose. Based on measurements of the nuclear areas of the HFL1 cells in conjunction with target theory calculations, the lowest dose resulted in an approximately 8.6-fold increase in the percentage of cells showing excessive SCEs over the theoretically expected percentage of cells whose nuclei were calculated to be traversed by one or more alpha particles. The extent of the discrepancies between theoretically expected and experimentally observed frequencies of SCEs became progressively reduced with increasing radiation dose. We additionally determined that SCEs induced by the alpha particles have no significant dependency on the time of cell collection after exposure to a selected dose of alpha particles, thereby confirming that the differences between the theoretically predicted and observed SCE frequencies were not due to an artifact of the time of cell sampling for the SCE measurements. These results obtained with normal human cells are similar to those of other investigators who observed excessive SCEs in immortalized rodent cells beyond that which could be attributed exclusively to nuclear traversals by alpha particles. Such consistent findings point to the existence of an alternative, extranuclear target through which alpha particles cause DNA damage, as detected by SCE analysis. The existence of an extranuclear compartment as a target for alpha particles may have important implications for the susceptibility of lung cells to the DNA-damaging effects of alpha-particle exposure due to the inhalation of radon progeny.
Alpha Particles↗
Investigation of alternative prodrugs for use with E. coli nitroreductase in 'suicide gene' approaches to cancer therapy.
The most commonly employed 'suicide' gene/prodrug system used in cancer gene therapy is the herpes simplex virus thymidine kinase (HSVtk)/ganciclovir system. We have examined the efficacy of an alternative approach utilising the E. coli nitroreductase B enzyme with CB1954 and a variety of other prodrugs. V79 cells transfected with a nitroreductase expression vector were up to 770-fold more sensitive to CB1954 than control non-expressing cells. In general other prodrugs which were found by HPLC to act as substrates for purified E. coli nitroreductase also exhibited increased cytotoxicity against the nitroreductase-expressing cells, although this correlation was not absolute. In particular nitrofurazone (97-fold) and additional aromatic nitro-compounds (nine- to 50-fold) showed a large differential whereas the quinones and the antimetabolite, B-FU, were less effective (< three-fold). The results support the possibility of using nitroreductase and CB1954 for 'suicide gene' therapy and in addition suggest that alternative prodrugs, such as nitrofurazone, warrant further investigation in this novel approach.
Animals↗
Current and ideal physique choices in exercising and nonexercising college women from a pilot athletic image scale.
An Athletic Image Scale including female physiques with and without muscular definition is currently in the developmental phase. With shading, contouring, and three-dimensionality not offered previously on figure-rating scales, this instrument was designed to examine an apparent growing interest on the part of women in atheletic body-image ideals. The athletic level of each figure on the scale was based on responses of a group of college women. The 30-figure pilot scale was then tested by rating current and ideal body-shape preferences of two groups of first-year college women, 65 who exercised regularly and 45 who engaged in no regular exercise. Analysis showed no relationship between current and ideal physique choice and exercise status. Most exercising and nonexercising women chose a mesomorphic ideal physique with upper-body muscularity unlikely to occur without substantial amounts of physical activity. The associations among exercise status, figure choice, subscale scores on the Eating Disorder Inventory, and Self-esteem Scale scores were also examined. Women choosing moderately mesomorphic figures as their current shape had the lowest Body Dissatisfaction scale scores on the Eating Disorder Inventory irrespective of exercise status. Current- and ideal-shape preferences were not related to self-esteem scores. The pilot Athletic Image Scale offered several figures which seemed to be relevant to women although it must be noted that the scale purposely emphasized particular physiques. Even so, it is important to recognize that greater than sixty percent of the women preferred images with athletic physiques which are not offered on figurerating scales presently in use.
Adult↗
Relationship of body fat distribution with cardiovascular risk factors in healthy Chinese.
The relationships between six body girths (shoulder, midarm, waist, hip, thigh, and calf) and cardiovascular risk factors (systolic and diastolic blood pressures and glucose, triglyceride, lipoprotein cholesterol, and apolipoprotein levels) were examined in 407 healthy Chinese urban workers in Taipei, Taiwan who were between 40 to 59 years old. Canonical correlation analysis revealed significant associations of upper body adiposity (shoulder, midarm, and waist girths) with cardiovascular risk factors in all subgroups assessed: men, premenopausal women, and postmenopausal women. Waist girth and hip girth were consistent and important variables, and weighted in the opposite direction. Waist-hip ratio (WHR) was the best descriptor of centralized adiposity. Centralized fat distribution was positively associated with blood pressure and glucose, triglyceride, and apolipoprotein (apo) B levels, and negatively associated with high-density-lipoprotein (HDL) cholesterol and apo A-I levels in this population. Body fat distribution had an effect independent of body mass index and accounted for some of the differences in triglyceride, HDL cholesterol, apo A-I, and apo B concentrations among men, premenopausal women, and postmenopausal women. Our findings in a Chinese population are similar to data from other studies in Western populations, and are consistent with the hypothesis that centralized adiposity is related to cardiovascular risk factors independent of general obesity.
Adipose Tissue↗
Oxygen radical formation in well-washed rat liver microsomes: spin trapping studies.
The generation of hydroxyl radicals by rat liver microsomes was monitored by spin trapping with 5,5-dimethylpyrroline N-oxide (DMPO). The results confirm and extend previous data which demonstrated that hydroxyl radicals are produced by microsomes in the presence of NADPH and O2, and without the exogenous addition of iron. No EPR signals could be detected unless catalase activity which was associated with the microsomes could be substantially diminished. Addition of azide was the most effective means of eliminating catalase activity, but azide also reacted rapidly with hydroxyl radicals, forming azidyl radicals which were in turn trapped by DMPO. Extensive washing and preincubation of microsomes with 3-amino-1,2,4-triazole in the presence of H2O2 were evaluated as alternative methods of decreasing the catalase contamination of microsomes. Although neither method completely eliminated microsomal catalase activity, addition of azide was no longer necessary for hydroxyl radical detection with DMPO. When highly washed microsomal preparations were tested, weak signals of the superoxide radical adduct of DMPO could also be detected. These data indicate that the sensitivity of spin trapping in microsomal systems can be improved substantially when care is taken to eliminate cytosolic contaminants such as catalase.
Animals↗
Cyclopropamitosenes: novel bioreductive anticancer agents--mechanism of action and enzymic reduction.
The mechanism of action of cyclopropamitosenes, novel bioreductive anticancer agents, has been investigated using a unique combination of chemical and biochemical techniques. The compounds 4 function as reductively activated alkylating agents under chemical reducing conditions, and the biochemical experiments establish that the methoxy- and aziridinyl-derivatives 4a and 4b behave differently upon bioreduction.
Alkylating Agents↗
Brain swelling in first hour after coronary artery bypass surgery.
Six patients undergoing routine coronary artery bypass surgery were examined by magnetic resonance imaging of the brain before surgery, immediately afterwards, and 6-18 days later. Brain swelling was visible in all six patients on the immediate postoperative scan. In five patients who had later scans the swelling had subsided. No major neurological deficits were seen, and the patients were extubated successfully within 3 h of the operation. The mechanism of the cerebral swelling is uncertain, but it may provide insight into the cause of neurophysiological deficits seen after coronary artery surgery.
Aged↗
Effect of alcohol on gastric emptying in volunteers.
We have examined the effect of alcohol on the gastric emptying rate of a liquid meal in 10 volunteers. Each volunteer was allocated randomly to receive, on three occasions, no alcohol, 3 units or 6 units of alcohol. Gastric emptying was measured using applied potential tomography. The rate of gastric emptying as measured by the time to 50% emptying (T50) was delayed significantly (P < 0.01) after alcohol 6 units (median 45.0 min (range 19-90 min)) compared with control (23.0 min (13-36 min)) and there was little change after alcohol 3 units (25.5 min (10-65 min)) [corrected].
Adult↗
Near infrared spectroscopy in adults. Does the Invos 3100 really measure intracerebral oxygenation?
Does the Invos near infrared spectroscopy monitor detect intracranial oxygenation, or reflect oxygenation of extracerebral tissues? The change in Invos regional cerebral oxygenation was studied during a doubling of middle cerebral artery flow with hypercapnia. There was no significant change in regional cerebral oxygenation, which suggests that the Invos does not reflect intracerebral oxygenation, possibly because of its narrow optode separation. The use of near infrared spectroscopy in adults may require a more powerful machine.
Adult↗
Organizational and morphological features of cat sacrocaudal motoneurons.
We have investigated the organizational and morphological features of motoneurons from cat sacrocaudal spinal cord, the portion of the neuraxis that innervates the tail. This information is pertinent for development of a new model of spinal cord injury. An understanding of sacrocaudal circuitry is essential for physiological and behavioral assessment of the effects of sacrocaudal lesions. Observations from Nissl-stained sections corroborated Rexed's cytoarchitectural scheme. Putative motoneurons were located within two regions of the ventral horn: the ventromedial nucleus (lamina IX) and the nucleus commissuralis. To map motoneuron pools, cholera toxin-horseradish peroxidase conjugate was injected into each dorsal tail muscle. The dorsomedial muscle was innervated by ipsilateral nucleus commissuralis motoneurons. The dorsolateral and intertransversarius muscles were innervated by ipsilateral lamina IX and nucleus commissuralis motoneurons. Cell bodies of retrogradely labeled sacrocaudal motoneurons ranged from 22 to 82 microns in diameter; the unimodal distributions peaked between 45 and 50 microns. Dendritic trees of motoneurons, revealed by retrograde labeling or by intracellular injection with horseradish peroxidase, were extensive. Five to eight primary dendrites originated from the cell body. Dendritic branches extended throughout the ipsilateral ventral gray matter, with processes spreading into the surrounding white matter and the base of the dorsal horn. Dendrites from motoneurons with their soma in the lateral portion of lamina IX formed a longitudinal plexus at the gray/white border. Medial dendrites from motoneurons in the nucleus commissuralis formed bundles in the ventral gray commissure and spread throughout the contralateral ventral horn. It is speculated that contralateral dendrites subserve synchronized co-contraction of medial muscles from both sides of the tail.
Animals↗
Structure-activity relationships for DT-diaphorase reduction of hypoxic cell directed agents: indoloquinones and diaziridinyl benzoquinones.
The flavoenzyme DT-diaphorase has the potential either to bioactivate or to detoxify different bioreductive cytotoxins. Elucidation of structural features governing the ability to act as a substrate for DT-diaphorase should facilitate rational optimization or elimination of this reductive pathway for a particular class of bioreductive drug. We have examined structure-activity relationships governing both the cytotoxicity and the DT-diaphorase mediated reduction of two groups of bioreductive alkylating agents: (1) Indoloquinones related to EO9 [3-hydroxy-methyl-5-aziridinyl-1-methyl-2-(1H-indole-4,7-dione)prop-beta - en-alpha-ol]; and (2) derivatives of diaziridinyl benzoquinone or diaziquone [2,5-bis(carboethoxyamino)-3,6-diaziridinyl-1,4-benzoquinone]. The rat U.K. 256 Walker tumor cell line and the human HT29 colon carcinoma line were studied because of their high DT-diaphorase content. Enzyme activity was measured spectrophotometrically by dicoumarol inhibitable cytochrome c reduction in the presence of drug, and aerobic cytotoxicity was assessed by the MTT assay. EO9 acted as a good substrate for both enzyme preparations and was highly potent in each cell line, especially in Walker tumor cells (ID50 0.039 nM). AZQ was also reduced efficiently and gave an ID50 of 6 nM in the Walker tumor line. Slight modifications in structure resulted in large variations in both DT-diaphorase metabolism and toxicity for both types of agent. There was a clear tendency for the most efficiently reduced analogues to exhibit greater cytotoxic potency. Inclusion of an aziridine moiety in the structure appears to be desirable, but not essential, for both rapid reduction and cytotoxicity. There was no evidence of active site-directed enzyme inhibition.
Animals↗
Gastric emptying after minor gynaecological surgery. The effect of anaesthetic technique.
Gastric emptying was measured using the paracetamol absorption method in 30 patients immediately after a general anaesthetic for minor gynaecological surgery and in 10 female controls. Anaesthesia was induced with either propofol alone, propofol and alfentanil (4.5 micrograms.kg-1) or propofol and fentanyl (1.4 micrograms.kg-1) and maintained with intermittent propofol and 66% nitrous oxide in oxygen. Gastric emptying was delayed significantly in all patient groups when compared with volunteers. However, the delay in gastric emptying was similar in the three patient groups.
Acetaminophen↗