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Biomedical subjects

J A Murphy

Publications and source records attributed to J A Murphy.

At least 37 records · Page 2Linked to original sources
PubMed1995

Reactions of oxyl radicals with DNA.

The importance of radical-induced damage to DNA is apparent from the ever-increasing number of publications in this area. This review focuses on the damage caused to DNA by reactive oxygen-centred radicals, however formed. These may be hydroxyl radicals, which arise either from the radiolysis of water by ionizing radiation (gamma-rays or X-rays), or from a purely chemical source. Alternatively, metal-bound oxyl radicals (M-O.) are also active intermediates in DNA-cleaving reactions and may be formed from synthetic compounds or from natural products such as bleomycin (BLM). Chemical mechanisms leading to the observed degradation products are covered in detail. The biological effects of some of the DNA base lesions formed are touched upon, concentrating on the molecular mechanisms behind the initial events that lead to mutagenesis.

Animals↗
PubMed1993

Chiral chromatography and multivariate quantitative structure-property relationships of benzimidazole sulphoxides.

Various benzimidazole sulphoxides were chirally resolved employing an amylase-based chiral stationary phase. The structure-property relationships of these compounds were investigated using calculated physicochemical properties, molecular modelling and multivariate statistical techniques. A data set of 254 molecular descriptors was used to represent the series of compounds. Analysis of the data set using principal components analysis and non-linear mapping suggested that the separation factor of each enantiomeric pair was associated with nine molecular properties and, in particular, molar refractivity of the Z substituent and the partial charge of atom 6. The separation factor of a sulphoxide not used in the analysis was well predicted thus suggesting that these models may be used to generalize.

Anti-Ulcer Agents↗
PubMed1993

The protein kinase C, calcium-independent and calcium-dependent kinase activities of glial cells in primary culture and subculture.

The activity of calcium-independent, calcium-dependent and calcium + phospholipid-dependent (protein kinase C) kinases in cytosol fractions from rat brain glial cells in primary culture and from subcultured astrocytes and in oligodendrocyte-type 2 astrocyte lineage glia has been measured with histone Type IIIS as substrate. Accurate measurement of protein kinase C activity was achieved only after chromatography of glial cytosols on DE-52 anion exchange columns to remove an endogenous inhibitor, identified tentatively as a phosphatase possibly of the protein phosphatase 2A class. The specific activity of protein kinase C in glial cell cytosol increased from 7.5 +/- 0.8 to 37.9 +/- 0.9 nmol32P incorporated/mg protein/10 min with increasing culture age. Protein kinase C activity in glial cytosol was significantly higher when primary cultures were grown in a defined medium lacking serum. Astrocyte-conditioned medium and phorbol esters caused a rapid translocation of glial cell protein kinase C activity from cytosol to membrane compartments. Myelin basic protein and protamine have been compared with histone as substrates for measurement of calcium-independent, calcium-dependent and calcium + phospholipid-dependent kinase activities in glial cytosol.

Animals↗
PubMed1990

Amiodarone: a postmarketing evaluation of monitoring for drug-induced toxicity.

Amiodarone, an antiarrhythmic drug with predominantly class III effects, has demonstrated serious adverse drug reactions and interactions. The Departments of Pharmacy and Cardiology retrospectively evaluated the monitoring parameters at this institution. Criteria based on current literature were developed. Twenty-six patients were administered amiodarone, qualifying for entry into the audit. Of these patients, seven were excluded because their medical records were unavailable or incomplete. The 19 eligible patients were hospitalized during initiation of therapy and followed in the Outpatient Cardiology Clinic. The collected data extracted from the medical charts were compared with the following elements of the criteria selected: baseline evaluation prior to the start of therapy; monitoring for signs of pulmonary, hepatic, thyroid, cardiac, ophthalmologic, neurologic, and dermatologic toxicity; and evaluation of potential drug interactions with digoxin and warfarin-type anticoagulants. The percentage of criteria elements appropriately monitored on each patient ranged from 82 to 100 percent, with an average of 91 percent. The most frequently overlooked parameters were warning the patient of a possible photosensitivity reaction, decreasing the digoxin dose if the patient was concurrently taking amiodarone, and performing a slit-lamp examination every six months. Frequent examination of the patient's total organ system and laboratory tests, in addition to patient education, are essential to safe monitoring of amiodarone therapy.

Amiodarone↗
PubMed1988

Stimulation of protein phosphorylation in mixed glial cell primary cultures and subcultures by the phorbol ester 12-O-tetradecanoylphorbol-13-acetate.

Glial cell primary cultures consisting of protoplasmic and fibrous astrocytes, oligodendrocytes and progenitor glial cells incubated in medium containing 0.5% foetal calf serum and treated with 25 nM 12-o-tetradecanoylphorbol-13-acetate (TPA) for periods between 15 and 60 min showed a stimulation of protein phosphorylation which was most prominent in a polypeptide with a molecular weight of about 80,000 Da. Glial subcultures consisting mainly of Type 2 astrocytes, oligodendrocytes and progenitor glia showed a similar TPA stimulation of 80,000 Da protein phosphorylation detectable within 1 min of phorbol ester addition. TPA treatment of primary glial cultures led to an enhancement of phospholipid turnover but exposure of primary glial cultures to concentrations of TPA up to 250 nM caused no morphological change in protoplasmic astrocytes. 4-Phorbol (4-PH) or dimethylsulfoxide (DMSO) was without effect on protein phosphorylation or lipid turnover in glial cultures.

Animals↗
PubMed1988

Protein kinase C activity in soluble fractions from glial cells in primary culture and subcultures.

Protein kinase C (calcium + phospholipid-dependent kinase) activity has been measured in soluble 100,000 g fractions from mixed glial cells in primary culture; in 12 day cultures the specific activity (mean +/- S.D.) was 184 +/- 10 pmol 32P incorporated/10 min/mg protein. In glial cell subcultures lacking protoplasmic astrocytes protein kinase C specific activity was lower. An inhibitor of protein kinase C in 100,000 g supernatants was removed by chromatography through DE-52 anion exchange resin increasing the specific activity of the calcium + phospholipid-dependent kinase about 20 times. Protein kinase C was also associated with membrane fractions from glial cells; the membrane-associated enzyme had a higher specific activity than in the cytoplasm.

Animals↗
PubMed1986

Assessment of long-term glycemia in type I diabetes using multiple blood glucose values stored in a memory-containing reflectometer.

The relationship between repetitive hemoglobin A1 values and daily blood glucose tests performed by 20 insulin-dependent diabetic outpatients was assessed over a six-week period using a modified reflectance meter capable of storing blood glucose determinations automatically. An average of four and a half determinations per subject per day was recorded with a range of average blood glucose values between 82 +/- 2 mg/dl and 316 +/- 5 mg/dl (mean +/- SE). The relationship between average blood glucose and hemoglobin A1 values was significant when hemoglobin A1 values at the end of the six-week period were correlated with the mean blood glucose level over that period (r = 0.55, p less than 0.02), but improved when a more remote hemoglobin A1 value obtained at 10 weeks was used (r = 0.64, p less than 0.005). Hemoglobin A1 values covering two-week intervals were extremely poor in reflecting average glycemia. The average fasting blood glucose level in these subjects was highly correlated with the overall daily blood glucose values (r = 0.89, p less than 0.0001), although the coefficients of variation of these parameters averaged 43 +/- 3 percent and 47 +/- 2 percent, respectively, and were greater than that of the hemoglobin A1 values over six weeks (10 +/- 2 percent). It is concluded that labile blood glucose control in patients with insulin-dependent diabetes is accurately reflected by the average fasting blood glucose level, although multiple determinations must be employed. Satisfactory assessment may be made by use of hemoglobin A1 value provided that the hemoglobin A1 determination follows a sufficiently long period of time, presumably related to the turnover of glycosylated hemoglobin.

Blood Glucose↗
PubMed1984

DOPA decarboxylase activity in the nervous system and the ctenidium of the freshwater clam, Musculium (Sphaerium) transversum.

Dopa decarboxylase was measured in ganglia, connectives, branchial nerve and ctenidium of the clam, Musculium transversum. DOPA decarboxylase inhibitors (STH, HMD, and alpha-methyl-DOPA) reduced the enzymatic activity in all extracts. Ligation and extirpation of the visceral ganglion and branchial nerve significantly decreased the enzymatic activity in the ctenidium. Scanning electron microscopic observations showed numerous degenerative changes in nerve cells with progressive destruction of axons within the branchial nerve. In conclusion, it appears that lateral ctenidial cilia are dependent upon the decarboxylase activity of the visceral ganglion and branchial nerve.

Animals↗
PubMed1980

Cellular morphology in haploid amphibian embryos.

External surfaces of haploid and diploid embryos of Bombina orientalis were examined with the scanning electron microscope to determine the possible contribution of cellular morphology to the amphibian haploid syndrome. Cellular anomalies were prevalent in all surface areas of haploid embryos. The epithelium appeared uneven due to the displacement of ciliated cells and the rounded surfaces of the non-ciliated cells. The ratio of ciliated to non-ciliated cells was altered in comparison to diploid embryos. Cells of the gill filaments and adhesive organs were abnormal in morphology, and the adhesive organs themselves were fused into a single large rudiment in haploid embryos. Uniformity of cell size was markedly reduced in head regions of haploid embryos with severe microcephaly. Haploid and diploid embryos elaborated mucoid matrices over the surface cells when removed from the fertilization envelope. It is apparent that aberrant cellular morphologies are widespread in haploid embryos, and it is likely that these defects are major contributors to the gross morphological anomalies of the haploid syndrome.

Animals↗
PubMed1979

Embryo surface morphology during post-gastrula development of the frog, Bombina orientalis, as revealed by scanning electron microscopy.

To further study the morphology of the developing amphibian embryo, and to provide a basis for the characterization of abnormal embryogenesis, surface features of the Bombina orientalis embryo during post-gastrula development were examined with the scanning electron microscope. Ciliated cells similar to those reported for Rama pipiens and Ambystoma mexicanum were observed in the epidermis. Epidermal secretory cells displaying large numbers of exocytotis apertures become prominent at the early tail bud stage and are prevalent through hatching. The surface features of the adhesive organs and gill filaments are also described. Removal of the embryo from the fertilization envelope resulted in the accumulation of a prominent mucoid matrix over the surface cells. These findings should be considered when experiments are designed which involve the effects of applied molecules on amphibian embryo epidermal cells.

Animals↗