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Biomedical subjects

M A Keane

Publications and source records attributed to M A Keane.

9 recordsLinked to original sources
PubMed2001

Reverse engineering of metabolic pathways from observed data using genetic programming.

Recent work has demonstrated that genetic programming is capable of automatically creating complex networks (such as analog electrical circuits and controllers) whose behavior is modeled by linear and non-linear continuous-time differential equations and whose behavior matches prespecified output values. The concentrations of substances participating in networks of chemical reactions are also modeled by non-linear continuous-time differential equations. This paper demonstrates that it is possible to automatically create (reverse engineer) a network of chemical reactions from observed time-domain data. Genetic programming starts with observed time-domain concentrations of input substances and automatically creates both the topology of the network of chemical reactions and the rates of each reaction within the network such that the concentration of the final product of the automatically created network matches the observed time-domain data. Specifically, genetic programming automatically created metabolic pathways involved in the phospholipid cycle and the synthesis and degradation of ketone bodies.

Biomedical Engineering↗
PubMed2000

Anhydride modified cantharidin analogues. Is ring opening important in the inhibition of protein phosphatase 2A?

A series of anhydride modified cantharidin analogues have been synthesised and screened for their ability to inhibit protein phosphatase 2A. Surprisingly only analogues capable of undergoing a facile ring opening of the anhydride moiety displayed any significant inhibition. Subsequent NMR experiments indicated that 7-oxobicyclo[2.2.1]heptane-2,3-dicarboxylic acid was the major (sole) species under assay conditions. The ability of these modified anhydro-cantharidin analogues to inhibit protein phosphatase 2A varies from 4 (16) to 100% (8) at 100 microM test concentration.

Anhydrides↗
PubMed1999

Detoxifying chlorine rich gas streams using solid supported nickel catalysts.

Catalytic hydrogen treatment is presented as a viable low energy means of treating/detoxifying concentrated chlorinated gas streams to generate recyclable raw materials. Nickel (1.5% w/w and 15.2%) loaded silica and nickel (2.2% w/w) exchanged Y zeolite catalysts have been used to hydrotreat a range of chlorophenols (CPs), dichlorophenols (DCPs), trichlorophenols (TCPs) and pentachlorophenol (PCP) over the temperature interval 473 K</=T</=573 K. In every instance the nickel catalysts were 100% selective in cleaving the chlorine component from the ring, leaving the aromatic nucleus and hydroxyl substituent intact. The effects of varying process time and temperature are considered in terms of phenol yield and the ultimate partitioning of chlorine in the parent organic and product inorganic hosts. Chlorine removal rates, hydrodechlorination selectivity and apparent activation energies are also provided. Prolonged exposure of the catalysts to the concentrated chlorine gas streams resulted in an irreversible loss of activity which is related to the total concentration of chlorine that had been hydroprocessed. Hydrodechlorination proceeds via irreversible stepwise and/or concerted routes as is illustrated for the treatment of 2,3,5-TCP. Increasing the nickel content was found to raise the overall detoxification efficiency while the use of a zeolite support introduced spatial constraints which had a strong bearing on process selectivity.

Catalysis↗
PubMed1995

A histological basis for the 'sonographic snowstorm' in opportunistic infection of the liver and spleen.

We report 3 cases of opportunistic infection of the liver and spleen due to Pneumocystis carinii, Candida albicans and Aspergillus with an unusual but similar sonographic appearance. In the patient with Pneumocystis we report for the first time this same appearance in the bowel and pleura. Histology showed either extensive fibrosis or focal fibrinous exudates as the underlying cause. Calcification, though present, was scanty and was not thought to be the likely explanation for the appearances.

Adult↗
PubMed1992

Institutional Review Board (IRB) review lacks impact on the readability of consent forms for research.

Consent forms in research are a source of current and retrospective information for the subject, a "prompt" for the person who is obtaining consent, and a documentation of the "informed" consent process and its adequacy. Occasionally, these forms may be administered by inexperienced trainees or ancillary personnel, and thus stand virtually alone. Therefore, the forms must be inherently comprehensible to the subjects. To test whether this is the case, 65 new applications were randomly selected from 13 consecutive IRB agendas, and their consent documents were computer-analyzed (Flesch/Fry scoring) after correction for expected confounding features, such as lists, tables, and polysyllabic proper names and jargon. Mean U.S. school grade for 70% comprehension (Fry score) was 15.03 +/- 0.19 (standard error of the mean), implying readability by 37.4 +/- 1% of the U.S. adult population. In contrast, a consecutive sampling of 21 Ann Landers columns yielded a mean Fry score of 7.67 +/- 0.5 (p < 0.01; readable by 75 +/- 3%). Fifteen Reader's Digest articles yielded a mean Fry score of 9.95 +/- 0.65 (p < 0.01; readable by 59.1 +/- 3%), and 15 "Talk of the Town" columns from The New Yorker averaged a grade level of 13.3 +/- 0.83; p < 0.01; readable by 42.7% +/- 4.8%). No document was improved by more than one grade level by the IRB review process, and most were unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

Comprehension↗
PubMed1986

Pharmacokinetics and effects on blood pressure of a single oral dose of milrinone in healthy subjects and in patients with renal impairment.

Milrinone, a new, nonglycosidic inotropic agent with peripheral vasodilating properties, was given as a single oral 5 mg dose to 7 healthy subjects, 7 patients with moderate renal impairment (CRI I, creatinine clearance 30-63 ml/min) and 7 patients with severe renal impairment had hypertension. The mean urinary recovery of milrinone was 82% in healthy subjects, the renal clearance was 288 ml/min and the plasma half-life (t1/2) was 0.94 h. In CRI the mean plasma t1/2 was prolonged (CRI I 1.78 h, CRI II 3.24 h). There was a significant linear relationship between creatinine clearance and the elimination rate constant, and between creatinine clearance and the renal clearance of milrinone. During the study day there was a tendency to a decrease in supine BP from 1 to 6-8 h after dosing, with the maximal decrease at 2-3 h (healthy subjects 118/71----107/56, CRI 159/95----136/79 mmHg). The same degree of change was seen in standing BP. A slight rise in standing HR was seen from 2-6 h after dosing. Changes in BP and HR are difficult to evaluate since the study was not placebo-controlled. The plasma elimination rate of milrinone was decreased in CRI and dose adjustment may be necessary. Placebo-controlled studies of milrinone in hypertensive patients would be required to validate its possible antihypertensive effect.

Adult↗