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Biomedical subjects

M J O'Donnell

Publications and source records attributed to M J O'Donnell.

At least 19 recordsLinked to original sources
PubMed1995

Synthesis and properties of a Hoechst-like minor-groove binding agent tethered to an oligodeoxynucleotide.

A small Hoechst-like DNA groove-binding fluorophore carrying a terminal bromoacetimido linker has been synthesized. Individual diastereomeric oligodeoxynucleotide dodecamers containing a thiol-based linker attached to an internucleotide phosphoramidate within a sequence of dA-dT residues were each covalently labeled with the new fluorophore. One isomer of the DNA-fluorophore conjugate (Isomer B) hybridizes to the complementary single-stranded target DNA and the presence of the tethered fluorophore results in both increased duplex stability and an enhanced fluorescent signal, presumably due to the fluorophore binding in the dA-dT rich minor groove. Duplex stability is increased by 2-3 degrees C and the fluorescence quantum yield for the fluorophore increases four-fold. In contrast, the other diastereomer (Isomer A) exhibits reduced helix stability (approximately 2 degrees C) and only slight changes in fluorescence intensity upon hybridization.

Base Sequence↗
PubMed1995

Fluid reabsorption and ion transport by the lower Malpighian tubules of adult female Drosophila.

The properties of the Malpighian tubules of Drosophila melanogaster change along their length. The upstream main segments secrete K(+)-rich fluid at a high rate. From this, the lower tubules reabsorb significant amounts of water and K+. Under stimulation, K+ reabsorption is accelerated. In addition, the lower tubules acidify the fluid passed to them by the main segments and secrete Ca2+ into it, adding to that transported there by the upstream epithelium. In contrast to the lumen-positive transepithelial potential difference (TEP) of the main segments, the TEP in the lower tubules is much lower and becomes lumen-negative close to their downstream junction with the common ureter. We suggest that the role of the lower tubule is to reduce the flow of K(+)-rich fluid that passes to the hindgut; this allows the hindgut to process the flow of excretory fluid more thoroughly.

Absorption↗
PubMed1991

The effect of predilatation on coronary angioplasty-induced vessel wall injury.

Fifty-four patients presenting with stenotic lesions in a major coronary artery visually estimated by diagnostic angiography to be greater than 90% but less than 100% were randomized to one of two angioplasty regimens, predilatation (group 1) or no predilatation (group 2). In group 1, the artery was initially dilated with a 2 mm balloon followed by a balloon that was considered by the operator to be the definitive size to fully dilate the target vessel. In group 2, the artery was dilated with a balloon deemed the definitive size to complete the angioplasty procedure. There were no statistical differences between groups with respect to age, sex, history of unstable angina, or prior acute myocardial infarction. There were also no significant differences in the angiographic characteristics of the coronary lesions including artery location, lesion length, concentric or eccentric morphology, tubular versus discrete stenosis, calcium in lesions, or lesions on a bend. Following angioplasty, luminal filling defects were present in 5% of the predilated group and in 9% of the nonpredilated group (p = NS). The incidence of luminal border haziness at the dilatation site did not differ between groups, seven (35%) in group 1 versus eight (24%) in group 2. Angiographic evidence of a linear dissection at the angioplasty site was also similar between groups, one (5%) in group 1 versus five (15%) in group 2. Occlusive complications were witnessed in 10% of the predilated group and 12% of the nonpredilated group (p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Angioplasty, Balloon, Coronary↗
PubMed1991

Transferrinuria in type 2 diabetes: the effect of glycaemic control.

Urinary excretion rates of transferrin, albumin, N-acetyl-beta-D-glucosaminidase (NAG) and alpha-1-microglobulin (A1M) were measured in type 2 (non-insulin-dependent) diabetic patients at diagnosis and after 6 and 12 weeks treatment. Initially 21 (53%) patients had elevated transferrin excretion rates. The proportion of patients with raised transferrin excretion rates fell to 30% at 6 weeks and 20% at 12 weeks with treatment of diabetes. At diagnosis 11 (28%) patients had elevated albumin excretion rates and 10 of these had elevated transferrin excretion rates. After 6 weeks treatment only six (15%) had elevated albumin excretion rates and by 12 weeks this number had fallen to four (10%). NAG and A1M levels also fell with treatment of diabetes. There were correlations between the transferrin excretion rate and albumin excretion rate (r = 0.86, P less than 0.0001), transferrin excretion rate and NAG (r = 0.46, P less than 0.0001), and transferrin excretion rate and A1M (r = 0.55, P less than 0.0001) at each visit. There were weaker correlations between the albumin excretion rate and A1M and NAG at each visit. The correlations between the transferrin excretion rate and markers of tubular function (NAG and A1M) suggest that tubular dysfunction may play a part in renal loss of transferrin in diabetes mellitus. There were no differences in transferrin excretion rates between patients with and without evidence of complications.

Adult↗
PubMed1991

Increased urinary transferrin excretion in exercising normoalbuminuric insulin-dependent diabetic patients.

The median rate of urinary transferrin excretion is greatly increased by exercise in subjects with uncomplicated type 1 (insulin-dependent) diabetes. This increase is proportionally far greater than that seen in urinary albumin excretion rate after the same exercise. Non-diabetic control subjects showed no rise in urinary transferrin excretion rate following exercise. N-acetyl-beta-D-glucosaminidase excretion rate was higher in diabetic than control groups but did not rise with exercise. Our results suggest that patients with apparently uncomplicated diabetes have abnormal renal function. In this group an elevated urinary transferrin excretion rate appears to be a more sensitive indicator of altered renal function than is elevated albumin excretion rate. The mechanism underlying exercise-induced urinary loss of transferrin remains to be elucidated.

Acetylglucosaminidase↗
PubMed1991

Abnormal blood pressure response to exercise in normoalbuminuric insulin dependent diabetic patients.

Eight male normoproteinuric Type I (insulin dependent) diabetic patients and eight age- and sex-matched non-diabetic control subjects were studied for their response to exercise. Systolic blood pressure showed an exaggerated response to exercise in the diabetic group (median 123, range 98-151 mmHg, pre-exercise vs. 187, 163-217 mmHg, immediately post exercise P less than 0.01) compared to the control group (median 112 (100-145) pre-exercise, 153 (138-178) post exercise). Resting noradrenaline levels were lower in the diabetic (D) compared with the control (C) group (D: 1.66, 0.55-3.92 nmol/l vs. C: 2.96, 2.04-4.49 nmol/l, P less than 0.02). Levels rose during exercise by 79% (25-307%) and 43% (4-90%) respectively (NS). Resting urinary sodium was raised in the diabetic group and fell during exercise (P less than 0.05) (D: 146, 74-244 mumol/min, C: 108.5 (83.4-151.0) pre-exercise vs. D: 73, 48-264 mumol/min, C: 81.7 (23.0-92.0) post exercise). Resting atrial natriuretic peptide levels were lower in the diabetic group (D: 10.1, 4.3-16.9 pmol/l vs. C: 16.0, 9.5-22.9 pmol/l, P less than 0.02) and levels rose significantly in both groups during exercise (D: 25.9, 5.2-38.9 pmol/l vs. C: 28.6, 17.3-47.2 pmol/l, P less than 0.05). We conclude that exercise provokes an exaggerated rise in systolic blood pressure and decrease in urinary sodium excretion in normoalbuminuric diabetic patients. These findings may reflect increased sensitivity to the renin-angiotensin-aldosterone system. Reduced atrial natriuretic peptide levels may stimulate sodium retention and increased blood pressure in early diabetes.(ABSTRACT TRUNCATED AT 250 WORDS)

Albuminuria↗
PubMed1991

The non-drug treatment of hypertension in the diabetic patient.

A wide range of non-pharmacological manoeuvres have been tried for the control of BP but the majority of studies have not examined diabetic patients. Alteration of individual dietary components is difficult to achieve and results difficult to interpret. A high fibre, low fat, moderate salt restricted diet is as efficacious as drug therapy in some hypertensive diabetic patients. Similar diets have been recommended for all diabetic patients by the British Diabetic Association and the European Association for the Study of Diabetes. This diet has the added advantage of improving glycaemic control and plasma lipid profiles. The benefits of behavioral modifications are variable, with some being better than placebo. Although there is no evidence for a hypertensive effect of smoking, it should be strongly discouraged in diabetic patients because of the added cardiovascular risk it places upon them. Studies of dietary control of BP indicate that a response should be observed after three months of treatment. If blood pressure remains elevated after this time the patient should be treated with pharmacological agents. Hyperinsulinaemia may be important in the pathogenesis of Type II diabetes, coronary artery disease and essential hypertension. Dietary manoeuvres which reduce plasma insulin levels may prove to be of benefit in all of these conditions, but as yet data are not available to support this hypothesis.

Alcohol Drinking↗
PubMed1989

Activity of the unstimulated renin-angiotensin-aldosterone system in type 1 diabetic patients with and without proteinuria.

There have been conflicting reports of the activity of the renin-angiotensin-aldosterone system in diabetes. We studied the activity of the unstimulated renin-angiotensin-aldosterone system in 73 consecutive Type 1 diabetic patients with varying degrees of albuminuria. Patients with elevated albumin excretion rates had elevated median plasma renin activity (macroalbuminuric 2.2, range 0.5-8.2, p less than 0.05; microalbuminuric 2.3, 0.7-7.1, p less than 0.001; vs normoalbuminuric 1.0, 0.2-4.5 nmol l-1 h-1) and higher systolic blood pressure (macroalbuminuric 141 +/- 27 vs normoalbuminuric 116 +/- 13 mmHg, mean +/- SD, p less than 0.01) compared with those with normal albumin excretion rates. Aldosterone secretion and function were normal in all patients studied.

Adult↗
PubMed1989

The setting of coronary angioplasty in multivessel disease: current status and future directions.

In summary, the use of coronary angioplasty in the setting of multivessel coronary disease has become more common in recent years. Reports indicate that, in carefully selected patients, a high initial success rate and low incidence of complications can be achieved. We have presented a schema for the triage of multivessel disease patients. Examples of each subgroup have been presented to illustrate the basis for this categorization. Our experience using this schema at the San Francisco Heart Institute has been valuable in understanding the initial and long-term results of coronary angioplasty in these patients. It is important that this paradigm (or a similar classification schema) be adopted to assist clinicians in making judgments about alternative approaches in patients with multivessel disease and to provide a common organization for the dissemination of research findings and collaboration among members of the medical community.

Angioplasty, Balloon, Coronary↗
PubMed1988

Effect of gliclazide on thromboxane B2, parameters of haemostasis, fluorescent IgG and lipid peroxides in non-insulin dependent diabetes mellitus.

Abnormalities of platelet aggregation, and increased levels of lipid peroxides and denatured proteins have been implicated in the pathogenesis of diabetic microangiopathy. Seventeen non-insulin dependent diabetics (mean age 65.7) on established sulphonylurea therapy were converted to an equivalent dose of gliclazide. They were studied at baseline and intervals to 36 weeks. Thromboxane B2 (TXB2) and beta thromboglobulin (beta TG) were measured by radioimmunoassay. Lipid peroxides were measured as total diene conjugates (DC) by scanning UV spectrophotometry and thiobarbituric acid reactivity (TBA) by absorbance at 532 nm. Oxidation products of proteins were represented by fluorescence/UV ratio of immunoglobulin G (*IgG) separated from serum by HPLC. Glycaemic control remained stable throughout the study. TXB2 fell from 734 +/- 233 ng/l at 0 weeks to 488 +/- 155 at 36 weeks, p less than 0.001 and beta TG from 120 +/- 70 ng/ml to 48 +/- 18 at 24 weeks, p less than 0.005. Lipid peroxides fell between 0 and 36 weeks; DC from 0.71 +/- 0.28 to 0.32 +/- 0.09, p less than 0.001 and TBA from 29.6 +/- 22.4 to 4.0 +/- 2.2, p less than 0.001. Fluorescent IgG ratio fell from 1.44 +/- 0.36 to 0.32 +/- 0.07, p less than 0.001. This data provides evidence for a specific action of gliclazide on thromboxane synthesis and platelet aggregation. This is independent of glycaemic control and may in part be mediated by the observed fall in lipid peroxides.

Aged↗
PubMed1985

Membrane-bound lactate dehydrogenases and mandelate dehydrogenases of Acinetobacter calcoaceticus. Purification and properties.

Procedures were developed for the optimal solubilization of D-lactate dehydrogenase, D-mandelate dehydrogenase, L-lactate dehydrogenase and L-mandelate dehydrogenase from wall + membrane fractions of Acinetobacter calcoaceticus. D-Lactate dehydrogenase and D-mandelate dehydrogenase were co-eluted on gel filtration, as were L-lactate dehydrogenase and L-mandelate dehydrogenase. All four enzymes could be separated by ion-exchange chromatography. D-Lactate dehydrogenase and D-mandelate dehydrogenase were purified by cholate extraction, (NH4)2SO4 fractionation, gel filtration, ion-exchange chromatography and chromatofocusing. The properties of D-lactate dehydrogenase and D-mandelate dehydrogenase were similar in several respects: they had relative molecular masses of 62 800 and 59 700 respectively, pI values of 5.8 and 5.5, considerable sensitivity to p-chloromercuribenzoate, little or no inhibition by chelating agents, and similar responses to pH. Both enzymes appeared to contain non-covalently bound FAD as cofactor.

Acinetobacter↗