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Biomedical subjects

S Murphy

Publications and source records attributed to S Murphy.

At least 343 records · Page 19Linked to original sources
PubMed1990

Familial adult medullary cystic disease with spastic quadriparesis: a new disease association.

We present two cases of familial adult medullary cystic disease with spastic quadriparesis, an association not previously described. Previous extrarenal associations of the nephronophthisis-medullary cystic disease complex were reported exclusively in childhood cases. Both patients have undergone successful cadaveric renal transplantation, with no evidence of their renal disease recurring. Further work is needed to elucidate the complex genetics of nephronophthisis.

Abnormalities, Multiple↗
PubMed1989

Purified octamer binding transcription factors stimulate RNA polymerase III--mediated transcription of the 7SK RNA gene.

We have analyzed the upstream promoter of the human 7SK RNA gene to determine which protein factors are involved in the transcription of this gene by RNA polymerase III. Using a reconstituted in vitro system, we show directly that octamer binding transcription factors (OTFs) are required for efficient transcription and that they interact with a series of nonconsensus OTF binding sites between positions -70 and -240. The same purified factors that stimulate RNA polymerase II-dependent transcription of the histone H2b gene (OTF-1) and an immunoglobulin light chain gene (OTF-2) also stimulate 7SK transcription by RNA polymerase III. Moreover, OTF-dependent stimulation requires a sequence between positions -48 and -65 that is homologous to the proximal sequence element of the class II snRNA genes. Our findings indicate that some transcription factors are utilized in the transcription of both class II and class III genes.

Base Sequence↗
PubMed1989

Tackling a bus with a toothbrush.

'Been there...done that...now what?' Is this what can be said of all dentists following Vocational Training? In fact, it is the title of a booklet given to all Ventures following an expedition with Operation Raleigh.

Dentistry↗
PubMed1989

Arachidonic acid evokes inositol phospholipid hydrolysis in astrocytes.

Astrocyte cultures prelabelled with [3H]inositol were exposed to arachidonic acid (AA) in the presence and absence of various agonists. AA alone evoked a dose-dependent increase in the accumulation of inositol phosphates (IP), an effect not secondary to eicosanoid synthesis and release but which was abolished by EGTA. Separation of the IP revealed that AA stimulated increases in inositol tris-, bis- and monophosphates. IP formation evoked by carbachol or norepinephrine was additive with AA, whereas IP formation by platelet activating factor (PAF) or ATP was non-additive with AA. These results suggest that AA released upon stimulation of astrocytes or other cells in the CNS could initiate and/or amplify intercellular signalling.

Animals↗
PubMed1989

The effect of prednisolone in Refsum's disease.

A 16 year old schoolgirl with an established peripheral neuropath (motor conduction velocity in peroneal nerve of 5 metres/sec., absent sural nerve potential and CSF protein of 160 mg%) presented with a progressive worsening to the point of physical incapacitation over the course of 23 days. Serum phytanic acid was 33 mg/100 ml. Following the exhibition of prednisolone she was discharged walking well after 5 days. After 3 weeks the steroid medication was stopped and a phytanic acid free diet instituted. Despite continued abnormal electrophysiological findings, (e.g. motor conduction velocity in peroneal nerve 3 metres/sec., and in ulnar nerve 8 metres/sec), she remains well three years later. It is probable that the steroid medication had a pronounced beneficial effect, though the mechanism of action remains unexplained.

Adolescent↗
PubMed1989

Albuterol treatment for children with asthma: a comparison of inhaled powder and aerosol.

A dose-ranging study and a 12-week treatment study were conducted in children with asthma, aged 4 to 12 years, to assess the efficacy and safety of albuterol inhaled as either an aerosol or as dry powder. Both studies were double-blind and placebo-controlled with randomized assignment to treatment. The dose-ranging study in 30 patients indicated that similar single doses of albuterol aerosol and powder had comparable effects with the intermediate doses (i.e., 180 micrograms of aerosol and 200 micrograms of powder) providing effective bronchodilation with minimal adverse effects. In the subsequent 12-week, parallel-group study, 204 children received albuterol as either aerosol, 180 micrograms, or powder, 200 micrograms four times a day. Both formulations were equally effective with no untoward cardiovascular effects and only one incident of mild tremor. Among those children who expressed a preference for one of the delivery systems, significantly more children preferred the powder (44% versus 26%, p less than 0.01). Albuterol taken four times a day as either aerosol or dry powder is both effective and well tolerated in children with asthma.

Administration, Inhalation↗
PubMed1989

Common mechanisms of promoter recognition by RNA polymerases II and III.

Recent results indicate that RNA polymerase III can use upstream promoters that are structurally and functionally very similar to those recognized by RNA polymerase II. The demonstration that RNA polymerases II and III can use the same transcription factors emphasizes the fundamental similarities between these distinct activities. It is also clear now that transcription factors can be functionally interchanged between distantly related species, indicating that the basic structures involved in promoter recognition are highly conserved throughout evolution.

Base Sequence↗
PubMed1989

ATP-evoked Ca2+ mobilisation and prostanoid release from astrocytes: P2-purinergic receptors linked to phosphoinositide hydrolysis.

Astrocyte cultures prelabelled with either [3H]inositol or 45Ca2+ were exposed to ATP and its hydrolysis products. ATP and ADP, but not AMP and adenosine, produced increases in the accumulation of intracellular 3H-labelled inositol phosphates (IP), efflux of 45Ca2+, and release of thromboxane A2 (TXA2). Whereas ATP-stimulated 3H-IP accumulation was unaffected, its ability to promote TXA2 release was markedly reduced by mepacrine, an inhibitor of phospholipase A2 (PLA2). ATP-evoked 3H-IP production was also spared following treatment with the cyclooxygenase inhibitor, indomethacin. We conclude that ATP-induced phosphoinositide (PPI) breakdown and 45 Ca2+ mobilisation occurred in parallel with, if not preceded, the release of TXA2. Following depletion of intracellular Ca2+ with a brief preexposure to ATP in the absence of extracellular Ca2+, the release of TXA2 in response to a subsequent ATP challenge was greatly reduced when compared with control. These results suggest that mobilisation of cytosolic Ca2+ may be the stimulus for PLA2 activation and, thus, TXA2 release. Stimulation of alpha 1-adrenoceptors also caused PPI breakdown and 45 Ca2+ efflux but not TXA2 release. The effects of ATP and noradrenaline (NA) on 3H-IP accumulation were additive, but their combined ability to increase 45Ca2+ efflux was not. Interestingly, in the presence of NA, ATP-stimulated TXA2 release was reduced. Our data provide evidence that functional P2-purinergic receptors are present on astrocytes and that ATP is the first physiologically relevant stimulus found to initiate prostanoid release from these cells.

Adenine Nucleotides↗
PubMed1989

Should we stop using theophylline for the treatment of the hospitalized patient with status asthmaticus?

Recent reviews and editorials have indicated that theophylline may not be effective for the therapy of acute severe asthma. This judgment is primarily based on data comparing the efficacy of theophylline to inhaled beta 2-agonists in the emergency room treatment of asthma. The authors believe that it is inappropriate to extrapolate data from short-term studies in the emergency room setting to the hospitalized patients with status asthmaticus. Studies of hospitalized patients in which the patients were monitored for at least 24 hours all demonstrate a positive therapeutic effect for theophylline. The possible reasons for the discrepancies between hospitalized patients and emergency room patients are discussed. Theophylline is still recommended for the management of the hospitalized patient with status asthmaticus.

Asthma↗
PubMed1989

Coronary artery bypass grafting for postinfarction angina pectoris.

The variables that predict increased operative risk and postoperative morbidity among patients who undergo coronary artery bypass grafting (CABG) early after myocardial infarction for persistent or recurrent ischemia are incompletely defined. In a recent 3-year interval (1985-1987), 240 patients underwent CABG within 30 days of a documented myocardial infarction. Thirty-day mortality was 3.3% (eight patients). Twenty variables were examined by univariate and multivariate analysis for their effects on early mortality. Left main coronary artery disease (p = 0.0003), female sex (p = 0.0059), and preoperative left ventricular dysfunction (increased left ventricular wall motion score) (p = 0.0135) were significant independent predictors of increased 30-day mortality. Postoperative inotropic support for low cardiac output was required for 55.6% of patients operated upon within 24 hours of infarction as compared with 11.6% of patients operated upon between 1 and 30 days (p less than 0.01). Significantly more patients undergoing emergent CABG required postoperative intra-aortic balloon pumping and inotropic support than those patients who underwent urgent or elective operation (23.8% vs. 4.6% and 52.4% vs. 10%, respectively) (p less than 0.01). Other studies confirm that preoperative left ventricular dysfunction, presence of cardiogenic shock, or intra-aortic balloon pumping are important predictors of operative risk. Other variables that may be important include advanced age, female sex, left main coronary artery disease, and anterior transmural infarction. The timing and urgency of operation have not been shown to be significant and independent determinants of increased operative risk.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

The Nottingham study of neurotic disorder: comparison of drug and psychological treatments.

210 psychiatric outpatients with generalised anxiety disorder (71), or panic disorder (74), or dysthymic disorder (65) diagnosed by an interview schedule for DSM-III were allocated by constrained randomisation to one of five treatments: diazepam (28), dothiepin (28), placebo (28), cognitive and behaviour therapy (84), and a self-help treatment programme (42). All treatments were given for 6 weeks and then withdrawn by 10 weeks. Ratings of psychopathology were made by psychiatric assessors blind to both treatment and diagnosis before treatment and at 2, 4, 6, and 10 weeks after randomisation. 18 patients had insufficient data for analysis because of early drop-out. There were no important differences in treatment response between the diagnostic groups, but diazepam was less effective than dothiepin, cognitive and behaviour therapy, or self-help, these three treatments being of similar efficacy. Significantly more patients in the placebo group took additional psychotropic drugs in the 10 week period, and those allocated to dothiepin and cognitive and behaviour therapy took the least.

Adult↗
PubMed1988

A role for protein kinase C in astrocyte glycogen metabolism.

Astrocytes accumulated 2-[3H]deoxyglucose (2-DG) from the incubation medium and incorporated a proportion of it into glycogen. When cells were exposed to the phorbol ester, phorbol 12-myristate 13-acetate (PMA), or the diacylglycerol analogue, dioctanoylglycerol, there was a 30% reduction in the amount of 3H recovered in the glycogen pool. This effect was abolished in cells which had been depleted of protein kinase C (PKC) by prior exposure to PMA. Activation of adenylate cyclase with forskolin caused an increase (40%) in glycogen labelling indicating enhanced glycogen turnover. However, this effect was potentiated when astrocytes were incubated with forskolin and PMA in combination. We suggest that there is an interaction between PKC and adenylate cyclase in the regulation of astrocyte glycogen metabolism.

Animals↗