Biomedical subjects
Publications and source records attributed to P M Bradley.
Microbial reductive dechlorination of [1,2-14C]trichloroethene to [14C]cis-dichloroethene and [14C]vinyl chloride was observed at 4 degrees C in anoxic microcosms prepared with cold temperature-adapted aquifer and river sediments from Alaska. Microbial anaerobic oxidation of [1,2-14C]cis-dichloroethene and [1,2-14C]vinyl chloride to 14CO2 also was observed under these conditions.
Post-synaptic GABA(B) responses (slow, late hyperpolarisations which can be eliminated by perfusion with phaclofen) can be recorded in vitro from many, but not all, neurones in the intermediate medial hyperstriatum ventrale (IMHV). The IMHV is an area of the chick forebrain which is remarkable for its plasticity, and for its essential role in two specific types of early learning-imprinting, and a form of one-trial passive-avoidance learning. Post-synaptic GABA(B) responses are strongly statistically associated with other properties (such as high membrane resistance) which are, themselves, dependent on a bird's past history. There is also evidence that their incidence changes with prior training in vivo and with age. GABA(B) hyperpolarisations are always offset to a varying extent by excitatory NMDA components. These two components follow a very similar time-course, so that the duration and (to a lesser extent), the magnitude of a response is controlled by the balance between the two systems. The evidence suggests that this balance fluctuates, and that its fluctuations determine the extent to which any neurone can function as a coincidence detector.
In developing Wistar albino rats, ventral horn muscle afferent boutons are lost following corticospinal innervation. Motor cortex lesions rescue a proportion of these boutons and perturb activity dependent expression of cJun and parvalbumin (PV) in the spinal cord. Therefore, we tested whether activity-dependent competition between corticospinal and proprioreceptive afferents determines the balance of these inputs to motor output pathways by delivering the inhibitory GABA agonist muscimol unilaterally to the forelimb motor cortex using slow release polymer implants from postnatal day 7 (P7) coincident with corticospinal synaptogenesis. Controls received saline. Inhibition of immature cortical neurons by muscimol was confirmed with separate in vitro electrophysiological recordings. After P28, spinal cord sections were immunostained for PV, cJun and muscle afferents transganglionically labelled with cholera toxin-B (CTB). Unilateral inhibition reduced contralaterally the number of PV positive spinal cord neurons and muscle afferent boutons in the dorsolateral ventral horn, compared to controls, and significantly altered the distribution of motoneuronal cJun expression. Separately, descending tracts were retrogradely traced with CTB from the cervical hemicord contralateral to implants. Forelimb sensorimotor cortex sections were immunostained for either CTB or PV. In muscimol treated animals, significantly fewer neurons expressed PV in the inhibited hemicortex, but as many CTB labelled corticospinal neurons were present as in controls, along with an equally large corticospinal projection from contralateral to the implant, significantly greater than in controls. Unexpectedly, unilateral inhibition of the motor cortical input did not lead to an expanded muscle afferent input. Instead, this was reduced coincident with development of a bilateral corticospinal innervation.
Microbial degradation of methyl tert-butyl ether (MTBE) was observed in surface water-sediment microcosms under anaerobic conditions. The efficiency and products of anaerobic MTBE biodegradation were dependent on the predominant terminal electron-accepting conditions. In the presence of substantial methanogenic activity, MTBE biodegradation was nominal and involved reduction of MTBE to the toxic product, tert-butyl alcohol (TBA). In the absence of significant methanogenic activity, accumulation of [14C]TBA generally decreased, and mineralization of [U-14C]MTBE to 14CO2 generally increased as the oxidative potential of the predominant terminal electron acceptor increased in the order of SO4, Fe(III), Mn(IV) < NO3 < O2. Microbial mineralization of MTBE to CO2 under Mn(IV)-or SO4-reducing conditions has not been reported previously. The results of this study indicate that microorganisms inhabiting the sediments of streams and lakes can degrade MTBE effectively under a range of anaerobic terminal electron-accepting conditions. Thus, anaerobic bed sediment microbial processes may provide a significant environmental sink for MTBE in surface water systems throughout the United States.
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The intermediate, medial hyperstriatum ventrale (IMHV) is an area of the forebrain of the domestic chick which exhibits great plasticity. Moreover, there is a strong link between plasticity in the IMHV and specific changes in behaviour. The IMHV in vitro is still plastic, and many of its physiological properties are age-dependent, peaking in slices taken from 3- or 4-day-old birds. This 'window' coincides with an important transitional period in a chick's normal behavioural development. It has also been claimed that reversal training is at its most effective in 3- and 4-day-old birds - a proposition which was confirmed by the experiments reported here. A combination of in vivo training followed by in vitro electrophysiology also revealed that the function of low-threshold N-methyl-D-aspartate receptors (one of the age-related variables) is negatively related to the effectiveness of reversal training, when age is held constant.
Microbial communities indigenous to a shallow groundwater system near Beaufort, SC, degraded milligram per liter concentrations of methyl tert-butyl ether (MTBE) under natural and artificial oxic conditions. Significant MTBE biodegradation was observed where anoxic, MTBE-contaminated groundwater discharged to a concrete-lined ditch. In the anoxic groundwater adjacent to the ditch, concentrations of MTBE were > 1 mg/L. Where groundwater discharge occurs, dissolved oxygen (DO) concentrations beneath the ditch exceeded 1.0 mg/Lto a depth of 1.5 m, and MTBE concentrations decreased to <1 microg/L prior to discharge. MTBE mass flux calculations indicate that 96% of MTBE mass loss occurs in the relatively small oxic zone prior to discharge. Samples of a natural microbial biofilm present in the oxic zone beneath the ditch completely degraded [U-14C]MTBE to [14C]CO2 in laboratory liquid culture studies, with no accumulation of intermediate compounds. Upgradient of the ditch in the anoxic, MTBE- and BTEX-contaminated aquifer, addition of a soluble oxygen release compound resulted in oxic conditions and rapid MTBE biodegradation by indigenous microorganisms. In an observation well located closest to the oxygen addition area, DO concentrations increased from 0.4 to 12 mg/L in <60 days and MTBE concentrations decreased from 20 to 3 mg/L. In the same time period at a downgradient observation well, DO increased from <0.2 to 2 mg/L and MTBE concentrations decreased from 30 to <5 mg/L. These results indicate that microorganisms indigenous to the groundwater system at this site can degrade milligram per liter concentrations of MTBE under natural and artificial oxic conditions.
The photophysical properties of Rh(2)(O(2)CCH(3))(4)(L)(2) (L = CH(3)OH, THF = tetrahydrofuran, PPh(3) = triphenylphosphine, py = pyridine) were explored upon excitation with visible light. Time-resolved absorption shows that all the complexes possess a long-lived transient (3.5-5.0 micros) assigned as an electronic excited state of the molecules, and they exhibit an optical transition at approximately 760 nm whose position is independent of axial ligand. No emission from the Rh(2)(O(2)CCH(3))(4)(L)(2) (L = CH(3)OH, THF, PPh(3), py) systems was detected, but energy transfer from Rh(2)(O(2)CCH(3))(4)(PPh(3))(2) to the (3)pipi excited state of perylene is observed. Electron transfer from Rh(2)(O(2)CCH(3))(4)(PPh(3))(2) to 4,4'-dimethyl viologen (MV(2+)) and chloro-p-benzoquinone (Cl-BQ) takes place with quenching rate constants (k(q)) of 8.0 x 10(6) and 1.2 x 10(6) M(-1) s(-1) in methanol, respectively. A k(q) value of 2 x 10(8) M(-1) s(-1) was measured for the quenching of the excited state of Rh(2)(O(2)CCH(3))(4)(PPh(3))(2) by O(2) in methanol. The observations are consistent with the production of an excited state with excited-state energy, E(00), between 1.34 and 1.77 eV.
Microorganisms indigenous to stream and lake bed sediments, collected from 11 sites throughout the United States, demonstrated significant mineralization of the fuel oxygenate, methyl-tert-butyl ether (MTBE). Mineralization of [U-14C]MTBE to 14CO2 ranged from 15 to 66% over 50 days and did not differ significantly between sediments collected from MTBE contaminated sites and from sites with no history of MTBE exposure. This result suggests that even the microbial communities indigenous to newly contaminated surface water systems will exhibit some innate ability to attenuate MTBE under aerobic conditions. The magnitude of MTBE mineralization was related to the sediment grain size distribution. A pronounced, inverse correlation (p < 0.001; r2 = 0.73) was observed between the final recovery of 14CO2 and the percentage content of silt and clay sized grains (grain diameter < 0.125 mm). The results of this study indicate that the microorganisms that inhabit the bed sediments of streams and lakes can degrade MTBE efficiently and that this capability is widespread in the environment. Thus aerobic bed sediment microbial processes may provide a significant environmental sink for MTBE in surface water systems throughout the United States and may contribute to the reported transience of MTBE in some surface waters.
Mineralization of [U-(14)C]methyl t-butyl ether (MTBE) to (14)CO(2) without accumulation of t-butyl alcohol (TBA) was observed in surface-water sediment microcosms under denitrifying conditions. Methanogenic activity and limited transformation of MTBE to TBA were observed in the absence of denitrification. Results indicate that bed sediment microorganisms can effectively degrade MTBE to nontoxic products under denitrifying conditions.
Extracellular recording techniques were used to study the effects of the nitric oxide releasing agents diethylamine-NO (DEA-NO) and S-nitroso-N-acetyl-penicillamine (SNAP) on synaptic transmission in the intermediate and medial part of the hyperstriatum ventrale (IMHV), a part of the domestic chick forebrain that is essential for some forms of early learning. The field response evoked by local electrical stimulation was recorded in the IMHV in an in vitro slice preparation. DEA-NO (100-200 mgr) significantly depressed the field response in a concentration dependent and reversible manner. However, the depression produced by perfusion with 400 mgr DEA-NO, was not reversed following washout of the drug. With 400 mgr DEA-NO, NO reaches a maximum concentration of 10 mgr at 2 min of perfusion, and then declines slowly. SNAP (400 mgr) produced an effect similar to 400 mgr DEA-NO. Neither the immediate nor the longer-term depressive effect of NO is mediated by activation of guanylyl cyclase because in the presence of both low and high doses of ODQ, a potent and selective inhibitor of NO-stimulated guanylyl cyclase, NO produced the same depression of the field response. There is evidence however that the IMHV possesses c-GMP responsive elements since direct perfusion of 8-Br-cGMP (1 mM) produced a long-term but not an immediate depression. The long-term depression produced by 400 mgr DEA-NO was eliminated in the presence of either a selective adenosine A(1) receptor antagonist or an ADP-ribosyltransferase inhibitor. It was also possible to prevent the long-term effect in the presence of tetraethyl ammonium a K(+)-channel blocker. These results suggest that the NO may be acting presynaptically in a synergistic fashion with the adenosine A(1) receptor to depress transmitter release.
SETTING: Public hospital, Victoria, Australia. OBJECTIVE: To evaluate the effect of multidrug treatment and isoniazid (INH) chemoprophylaxis on the tuberculin interferon-y assay (QIFN) in 19 patients with culture-confirmed Mycobacterium tuberculosis and 119 health care workers (HCWs) with tuberculin skin tests (TST) > or =15 mm. DESIGN: Patients with M. tuberculosis were treated with standard medication and tested with QIFN at diagnosis and at regular intervals over a 12-month period. All HCWs, 59 (50%) of whom were prescribed INH chemoprophylaxis, were tested with QIFN at baseline, 2, 4, 6 and 12 months. RESULTS: QIFN results in patients with tuberculosis were consistent and reproducible. At the initial time point QIFN assays were positive for M. tuberculosis in 67%, and once positive, the QIFN assay remained so over the 12-month period. In the HCWS, initial QIFN assays were positive in 73 (61%). During the 12-month study, 91 HCWs had a QIFN assay on at least two occasions. The overall reproducibility between tests was fair (kappa statistic = 0.45), and was little affected by administration of INH. CONCLUSION: These data suggest that although the QIFN assay is generally positive in patients with proven tuberculosis, it does not provide clinically useful information during the first 12 months of treatment with multidrug chemotherapy or INH chemoprophylaxis.
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Production of 14CO2 from [1,2-14C] dichloroethene (DCE) or [1,2-14C] vinyl chloride (VC) was quantified in aquifer and stream-bed sediment microcosms to evaluate the potential for microbial mineralization as a pathway for DCE and VC biodegradation under aerobic, Fe(III)-reducing, SO4-reducing, and methanogenic conditions. Mineralization of [1,2-14C] DCE and [1,2-14C] VC to 14CO2 decreased under increasingly reducing conditions, but significant mineralization was observed for both sediments even under anaerobic conditions. VC mineralization decreased in the order of aerobic > Fe(III)-reducing > SO4-reducing > methanogenic conditions. For both sediments, VC mineralization was greater than DCE mineralization under all electron-accepting conditions examined. For both sediments, DCE mineralization was at least two times greater under aerobic conditions than under anaerobic conditions. Although significant microbial mineralization of DCE was observed under anaerobic conditions, recovery of 14CO2 did not differ substantially between anaerobic treatments.
Anaerobic oxidation of [1,2-C]dichloroethene to CO(2) under Mn(IV)-reducing conditions was demonstrated. The results indicate that oxidative degradation of partially chlorinated solvents like dichloroethene can be significant even under anoxic conditions and demonstrate the potential importance of Mn(IV) reduction for remediation of chlorinated groundwater contaminants.
Anaerobic oxidation of [1,2-14C]vinyl chloride and [1, 2-14C]dichloroethene to 14CO2 under humic acid-reducing conditions was demonstrated. The results indicate that waterborne contaminants can be oxidized by using humic acid compounds as electron acceptors and suggest that natural aquatic systems have a much larger capacity for contaminant oxidation than previously thought.
A comparative study of 164 serum samples was carried out to determine the specificity and sensitivity of the indirect antiglobulin test (IAGT) in three different formulations: physiologic saline, low-ionic solution (RAM), and RAM supplemented with polyethylene glycol (PEG). Serum samples containing mostly weak antibodies (anti-D, -C, -E, -c, -Jka, -Fya, -K, -S, -Lea, -Lua, -M, -Cob, -P1, -I, and -Kna) were used in a 10-minute IAGT in which PEG-IAGTs were compared with saline- IAGTs and RAM-IAGTs. With the exception of anti-P1, anti-I, and an anti-Lea, PEG-IAGTs detected all the antibodies tested compared with 72.3% and 77.4% for saline-IAGTs and RAM-IAGTs, respectively. The end-point titers of at least 82% of antibodies detected by PEG-IAGTs were 1-3 dilutions higher than those by saline- and RAM-IAGTs. When specificity of PEG-IAGTs was tested using 268 randomly selected, fresh (< 1 day old) blood samples, PEG-IAGT detected 11 out of 268 samples as positive compared with 7 out of 268 by both saline-IAGTs and RAM-IAGTs. The four antibodies that were not detected were identified as anti-D, anti-E, anti-Bga, and an autoantibody known previously to be only reactive with papain-pretreated red cells. No nonspecific reactions were detected by PEG-IAGTs and no hemolysis was evident in any of the IAGTs. PEG-IAGTs were more sensitive than saline- and RAM-IAGTs. PEG-IAGTs detected all weak, clinically significant antibodies as well as four antibodies that were otherwise undetected by saline-IAGT or RAM-IAGT. The overall sensitivity of the PEGIAGT was 96.3% compared with 84.1% and 73.2% for the RAM- and saline-IAGT, respectively.