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Biomedical subjects

B Twomey

Publications and source records attributed to B Twomey.

13 recordsLinked to original sources
PubMed1992

Transcription of the genes encoding the small heat shock protein ubiquitin is unchanged in patients with systemic lupus erythematosus.

The heat shock proteins hsp90 and hsp70 have been shown to be over-expressed in peripheral blood mononuclear cells from SLE patients. We show, however, that transcription of the three genes encoding the small hsp ubiquitin is not enhanced in these patients. The over expression of hsp90 and hsp70 in SLE is likely therefore to reflect cellular events resulting in the specific induction of these hsps rather than a generalized induction of all hsp synthesis due to the stress of the disease or the presence of fever.

Gene Expression↗
PubMed1990

The effect of new potent selective inhibitors of protein kinase C on the neutrophil respiratory burst.

New potent inhibitors of protein kinase C were found to inhibit protein kinase C isolated from rat brain and human neutrophils, with a large degree of selectivity over cAMP-dependent kinase and Ca2+/calmodulin-dependent kinase. These novel compounds were potent inhibitors of the fluoride, diC8- and formyl-methionyl-leucyl-phenylalanine-mediated respiratory bursts in intact neutrophils. The opsonized zymosan-stimulated burst was only marginally affected by the compounds. These results differ from those obtained in studies with H7 and CI, (which are less potent and less specific protein kinase C inhibitors) and are consistent with the hypothesis that protein kinase C has a role in the transduction mechanism for the neutrophil oxidative burst stimulated with fluoride, formyl-methionyl-leucyl-phenylalanine and diC8.

Alkaloids↗
PubMed1990

The effect of putative protein kinase C inhibitors, K252a and staurosporine, on the human neutrophil respiratory burst activated by both receptor stimulation and post-receptor mechanisms.

1. Two compounds, reported to be potent inhibitors of protein kinase C (PKC), K252a and staurosporine, have been examined in order to gain further information as to the possible role played by PKC in the signal transduction sequence of the neutrophil respiratory burst as determined by superoxide (O2-) production. 2. A number of stimuli were used in the study, some acting at receptors i.e. fMet-Leu-Phe (fMLP), opsonized zymosan and heat-aggregated IgG (HAGG), one acting on a G-protein, fluoride, and two direct PKC activators, dioctanoylglycerol (diC8) and phorbol myristate acetate (PMA). 3. K252a and staurosporine inhibited the respiratory burst with all the stimuli but the order of agonist sensitivity was very different with the two inhibitors. 4. For K252a-induced inhibition of O2- release, the order of potency was fluoride greater than fMLP, HAGG greater than opsonized zymosan greater than PMA, DiC8. For staurosporine-induced inhibition of O2- release, the order of potency changed to fluoride greater than DiC8, PMA greater than HAGG, fMLP greater than opsonized zymosan. The significance of this unexpected difference in relative rank order of potency is discussed with reference to the reported mechanism of action of the two inhibitors and the events involved in the oxidative burst. 5. Staurosporine at low concentrations increased the fMLP-stimulated O2- response by 100%, the maximum effect occurring at 35 nM. 6. To the extent that the compounds used are specific inhibitors of PKC, these findings support a role for the enzyme PKC in stimulus-activation coupling in O2- generation with all the stimuli used in this study.

Alkaloids↗
PubMed1988

The effect of inhibition of both diacylglycerol metabolism and phospholipase A2 activity on superoxide generation by human neutrophils.

A 'cocktail' consisting of an inhibitor of diacylglycerol kinase (R59022, 10 microM), an inhibitor of diacylglycerol lipase (RHC80267, 10 microM), and an inhibitor of phospholipase A2 (either 100 microM indomethacin, or 100 microM sodium meclofenamate) markedly enhanced superoxide production by human neutrophils stimulated with post-receptor stimuli, fluoride and gamma-hexachlorocyclohexane. On the other hand, the response to the C3b/Fc receptor stimulus, opsonized zymosan, was marginally decreased whilst that to the Fc receptor stimulus, aggregated IgG, was virtually unaffected. Since the inhibitors used are deemed to inhibit the main routes of arachidonate production, these results call into question the role of arachidonate in the transduction of O2- generation by post-receptor stimuli, but support a role for arachidonate in receptor-mediated transduction.

Cyclohexanones↗
PubMed1986

Extrarenal arterial connections of the normal renal artery.

An angiographic study in cadavers has demonstrated connections between the renal artery and remote vessels including the intercostal, testicular, and inferior mesenteric arteries in subjects with no known history of renal disease. Such communications are a potential route by which embolic material introduced into the renal artery may inadvertently reach other organs.

Aged↗
PubMed1986

Diabetic orthostatic hypotension: the role of total exchangeable sodium and nephropathy.

The purpose of this report was to examine the influence of nephropathy and sodium balance on the orthostatic blood pressure and renin (PRA) responses of diabetic patients with orthostatic hypotension (OH). Four groups of similar age were studied: non-diabetic controls (n = 7), diabetics free of OH and other diabetic complications (n = 7), diabetics with OH but no nephropathy (n = 6), and diabetics with OH and nephropathy (24-hr urine protein greater than 400 mg, n = 6). In the diabetics with OH, mean systolic BP fell 49 and 47 mmHg on standing in the groups without and with nephropathy respectively. NaE (expressed as % predicted by leanness index) differed significantly between the groups and was 100 +/- 2 in the controls, 109 +/- 3 in the diabetics free of complications, 102 +/- 2 in the diabetics with OH free of nephropathy, and 121 +/- 6 in diabetics with OH and nephropathy (p less than 0.05 compared to diabetics with OH and no nephropathy). Both supine (r = 0.68, p less than 0.02) and upright (r = 0.78, p less than 0.005) mean arterial pressure correlated with NaE in diabetics with OH but not in the other groups. Upright PRA was greatest in diabetics with OH but no nephropathy and lowest in diabetics with OH and nephropathy. These findings suggest that the presence of nephropathy markedly influences sodium balance in diabetics with OH and has a substantial influence on orthostatic BP and PRA responses.

Adult↗
PubMed1985

Reducing errors in the accident department: a simple method using radiographers.

The assessments by radiographers of 1628 consecutive patients referred for radiography in the casualty department were analysed. The radiographers missed abnormalities in the radiographs in 68 of the cases. Casualty officers missed abnormalities in 63 cases, but only 35 patients were common to both groups. Twenty eight of the radiographs interpreted wrongly by casualty officers were interpreted correctly by radiographers; 16 of these 28 were thought by the accident and emergency consultant to be clinically important. It is suggested that a system whereby radiographers signal abnormalities should be standard practice.

Diagnostic Errors↗
PubMed1984

Should cholecystography or ultrasound be the primary investigation for gallbladder disease?

The conclusions drawn from a prospective survey of 500 patients examined by cholecystography (OCG) and ultrasound (UCG) are presented. First, both procedures were found to be highly accurate in detecting calculi, with false-negative rates of 1%. Secondly, if OCG is abandoned in favour of UCG, most acalculous adenomyomatosis (and many polyps) will not be diagnosed. If acalculous as well as calculous disease is regarded as clinically important, fluoroscopic OCG is the examination of choice. However, if a clinician wishes solely to find or exclude stones the investigations are equally accurate. Thirdly, since some calculi and some acalculous disease will be missed by either technique, serious consideration should be given to the further investigation of all gallbladders considered normal by either examination. A protocol is described which, though unorthodox, enables a decision on the status of the gallbladder to be made on a single visit to the radiology department.

Administration, Oral↗
PubMed1984

The fatty meal and acalculous gall-bladder disease.

The practice of routinely obtaining after fatty meal films during oral cholecystography has been questioned. A retrospective analysis of 45 cases of adenomyomatosis or polyps revealed that, in 28% of patients with adenomyomatosis, the gall-bladder appeared entirely normal before fat. It is concluded that, for the detection of acalculous gall-bladder disease, the fatty meal should be a routine part of oral cholecystography.

Cholecystography↗
PubMed1983

Poor metabolic control, hypertension and microangiopathy independently increase the transcapillary escape rate of albumin in diabetes.

Available evidence indicates that poor metabolic control and raised blood pressure each accelerate the development of diabetic microangiopathy. Microangiopathy is associated with excess albumin deposition in capillary basement membranes and it has been suggested that increased extravasation of plasma constituents may lead to basement membrane thickening. We measured the transcapillary escape rate of albumin, an indicator of the rate of extravasation of intravascular albumin from the circulation per unit time, following intravenous injection of 125I-human serum albumin. We examined the independent effects on the transcapillary escape rate of albumin of non-ketotic poor metabolic control, hypertension and microangiopathy. We studied non-diabetic control subjects and diabetic patients, initially when in non-ketotic poor metabolic control and again when control had been improved. We also studied normotensive well-controlled diabetic patients without microangiopathy, normotensive well-controlled diabetic patients with microangiopathy, hypertensive well-controlled diabetic patients without microangiopathy and hypertensive well-controlled diabetic patients with microangiopathy. The transcapillary escape rate of albumin was similar in non-diabetic control subjects (5.5 +/- 0.7%/h) and in both Type 1 (5.3 +/- 1.2%/h) and Type 2 (5.1 +/- 0.6%/h) normotensive diabetic patients without long-term complications. During poor metabolic control the transcapillary escape rate of albumin was significantly higher than in non-diabetic subjects (8.8 +/- 0.8%/h and 5.5 +/- 0.7%/h respectively, p less than 0.01). With improved control values fell significantly to 6.3 +/- 0.9%/h (p less than 0.02), not significantly different from control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMedDate not supplied

Exchangeable sodium and renin in hypertensive diabetic patients with and without nephropathy.

The objective of this study was to examine total exchangeable sodium, plasma-blood volume, and the status of the renin-angiotensin system in hypertensive diabetic patients with established nephropathy. We also evaluated hypertensive patients with diabetes who were free of clinically apparent nephropathy or other diabetic complications. Total exchangeable sodium (by 24Na dilution) was expressed as percentage predicted. Subjects were studied as inpatients receiving unrestricted sodium intake and in stable metabolic control. Total exchangeable sodium was 100 +/- 2% in controls (n = 42), higher (p less than 0.01) at 108 +/- 2% in normotensive patients with diabetes (n = 30), and higher still (p less than 0.005) in hypertensive patients with diabetic nephropathy (n = 16) 118 +/- 4% (p less than 0.05 vs normotensive diabetics). The value correlated with blood pressure only in diabetics with nephropathy (r = 0.61, p less than 0.01). Plasma renin activity, and blood and plasma volumes were similar in nephropathic diabetics and controls. Hypertensive patients with maturity-onset (type II) diabetes free of nephropathy (n = 18) were compared with nondiabetic controls (n = 16) and normotensive patients with type II diabetes (n = 18) of similar age. Total exchangeable sodium in the controls was 100 +/- 3%, higher (p less than 0.01) in normotensive diabetics at 109 +/- 2%, but not significantly elevated in hypertensive diabetics at 106 +/- 2%. Again, blood and plasma volumes did not differ among the groups. Plasma renin activity was suppressed (p less than 0.01) to a comparable degree in both normotensive and hypertensive patients with type II diabetes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗