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Biomedical subjects

G Davis

Publications and source records attributed to G Davis.

At least 91 records · Page 5Linked to original sources
PubMed1997

Phosphorylation-dependent monoclonal Tau antibodies do not reliably report phosphorylation by extracellular signal-regulated kinase 2 at specific sites.

Analysis of phosphorylation of tau, the microtubule-associated proteins hyperphosphorylated in Alzheimer's disease, is often performed using phosphorylation-sensitive monoclonal antibodies thought to report the presence or absence of one or two specific phosphorylations (cognate sites). Using several such antibodies we found a much more complicated relationship between phosphorylation at specific sites, as monitored by two-dimensional phosphopeptide mapping, and antibody recognition of these sites. Multiple phosphorylation of tau in several stages by the brain extracellular signal-regulated kinase 2 isoform PK40 suggested that phosphorylation at cognate sites is sometimes necessary (but not sufficient) to induce a change of antibody reactivity and in some cases is not even necessary in the background of multiple phosphorylation at other sites. No single phosphorylation site was found to be responsible for any level of gel mobility shift associated with phosphorylation. Tau acquired its maximal gel mobility retardation and final immunochemical profile at substoichiometric phosphorylation of most sites. This suggests that many alternate phosphorylation patterns can produce the same conformational and immunochemical presentation on sodium dodecyl sulfate-gel electrophoresis. Although PK40(erk2) prefers some phosphorylation sites, most notably Ser235, followed by Ser199 or Ser202 and Thr205, the phosphorylation of multiple Ser/Thr-Pro sites is not highly sequential. Ser396 is one of the least preferred sites and seems to require prior phosphorylation at Ser404.

Antibodies, Monoclonal↗
PubMed1997

Preattentive filling-in of visual surfaces in parietal extinction.

Unilateral brain damage frequently produces "extinction," in which patients can detect brief single visual stimuli on either side but are unaware of a contralesional stimulus if presented concurrently with an ipsilesional stimulus. Explanations for extinction have invoked deficits in initial processes that operate before the focusing of visual attention or in later attentive stages of vision. Preattentive vision was preserved in a parietally damaged patient, whose extinction was less severe when bilateral stimuli formed a common surface, even if this required visual filling-in to yield illusory Kanizsa figures or completion of partially occluded figures. These results show that parietal extinction arises only after substantial processing has generated visual surfaces, supporting recent claims that visual attention is surface-based.

Aged↗
PubMed1997

Coronary artery stenting postcardiac transplant: a report of two cases.

Coronary atherosclerosis remains a significant cause of morbidity and mortality following cardiac transplantation. Coronary artery bypass grafting, percutaneous transluminal coronary angioplasty, and directional coronary atherectomy have all been presented as attempted treatment options in this population with generally suboptimal results. Endovascular stenting is a new transcatheter treatment modality with unique potential advantages as compared to other transcatheter revascularization techniques. This report presents the use of endovascular stenting and 6-mo follow-up in two orthotopic cardiac transplant recipients with proximal stenotic posttransplant graft atherosclerosis.

Aged↗
PubMed1997

Transesophageal echocardiographic detection of complications after Cabrol's procedure.

Cabrol's procedure represents an improvement on earlier surgical techniques used in the management of a patient with aortic insufficiency associated with an aneurysm of the ascending aorta. We report a patient in whom the diagnosis of complications after a Cabrol procedure was facilitated by transesophageal echocardiography. The role of transesophageal echocardiography in the follow-up of these patients is discussed.

Abscess↗
PubMed1997

Combined radiotherapy and medical immunosuppression in the management of thyroid eye disease.

Although systemic steroids or orbital radiotherapy are effective in limiting the inflammatory response in thyroid eye disease (TED), there are reports of over 70% of treated patients requiring subsequent rehabilitative surgery: either orbital decompression or strabismus correction. This study investigated whether combined immunosuppression with primary orbital radiotherapy together with azathioprine and low-dose prednisolone, applied early in the active disease state, was more effective in treating TED. Forty consecutive patients with active TED were recruited. Orbital MRI (STIR sequence) was used to assess disease activity. Median duration of symptoms was 1.0 year. Subjects were treated with bilateral orbital radiotherapy (20 Gy in 10 fractions) and oral prednisolone and azathioprine. Pre- and post-treatment activity was measured clinically, including uniocular field of fixation, Mourits score and total eye score, until TED became inactive off all treatment. Before treatment, 15 subjects had signs of dysthyroid optic neuropathy, 35 had significant motility restriction and 38 had marked soft tissue signs. On average TED became inactive after 1.2 years (SD 0.7) of immunosuppression, and treatment was well tolerated. One patient required subsequent cosmetic orbital decompression, 6 had successful strabismus surgery and 13 required minor cosmetic lid surgery. Compared with previously reported treatment regimes we think that combined orbital radiotherapy and medical immunosuppression is far more effective than either treatment alone in the management of active TED, and led to fewer side effects of high-dose steroids. In particular there was more than a four-fold reduction in the requirement for orbital decompression and strabismus surgery.

Adult↗
PubMed1997

A functional role for illusory colour spreading in the control of focused visual attention.

In cases of modal completion, illusory colour spreading fills in the surface of a subjectively completed shape. In amodal completion, shapes are likewise completed, but now behind a partial occluder, so that filling in of illusory colour to the completed region no longer arises. We consider the possible functional effects that illusory colour spreading may exert on later stages of vision, and argue that comparisons of modal with amodal completion may be particularly revealing in this regard. It is hypothesised that cueing the inducers of a modally completed object should attract attention to the entire object, including the completed region, owing to the colour spreading there. By contrast, changes to the inducers of a comparable amodally completed object should only attract attention to the inducing regions themselves. This prediction is supported by findings in two experiments with stereoscopic displays, with control conditions ruling out nonattentional accounts, or explanations in terms of stereo disparity alone rather than the presence versus absence of illusory colour. We argue that illusory colours get filled in at quite early stages during modal completion, precisely so that later stages of vision, such as focused attention, can then be driven by the completed regions in the same way as for uniform regions that are physically present in the image.

Color Perception↗
PubMed1997

Genetic association between sensitivity to warfarin and expression of CYP2C9*3.

Cytochrome P4502C9 (CYP2C9) is largely responsible for terminating the anticoagulant effect of racemic warfarin via hydroxylation of the pharmacologically more potent S-enantiomer to inactive metabolites. Mutations in the CYP2C9 gene result in the expression of three allelic variants, CYP2C9*1, CYP2C9*2 and CYP2C9*3. Both CYP2C9*2 and CYP2C9*3 exhibit altered catalytic properties in vitro relative to the wild-type enzyme. In the present study, a patient was genotyped who had proven unusually sensitive to warfarin therapy and could tolerate no more than 0.5 mg of the racemic drug/day. PCR-amplification of exons 3 and 7 of the CYP2C9 gene, followed by restriction digest or sequence analysis, showed that this individual was homozygous for CYP2C9*3. In addition, patient plasma warfarin enantiomer ratios and urinary 7-hydroxywarfarin enantiomer ratios were determined by chiral-phase high performance liquid chromotography in order to investigate whether either parameter might be of diagnostic value in place of a genotypic test. Control patients receiving 4-8 mg warfarin/day exhibited plasma S:R ratios of 0.50 +/- 0.25:1, whereas the patient on very low-dose warfarin exhibited an S:R ratio of 3.9:1. In contrast, the urinary 7-hydroxywarfarin S:R ratio of 4:1 showed the same stereoselectivity as that reported for control patients. Therefore, expression of CYP2C9*3 is associated with diminished clearance of S-warfarin and a dangerously exacerbated therapeutic response to normal doses of the racemic drug. Analysis of the plasma S:R warfarin ratio may serve as a useful alternative test to genotyping for this genetic defect.

Anticoagulants↗
PubMed1996

Renal nerve responses to somatic nerve activation in stroke-prone spontaneously hypertensive rats.

In chloralose/urethane anaesthetised stroke-prone spontaneously hypertensive rats, blood pressure and integrated renal nerve activity were higher whereas heart rate was lower than in Wistar rats by 37, 146 and 11%, respectively (all P < 0.001). The renal nerve signal was subjected to fast Fourier transformation to generate power spectra. In the hypertensive rats, total spectral power was 400% (P < 0.01) and power at the heart rate frequency was 50% (P < 0.01) greater while phase and time differences were shorter (both P < 0.001) than in Wistar rats. Brachial nerve stimulation increased total power in Wistar and hypertensive rats (P < 0.05), but importantly, power at the heart rate frequency was decreased by 80% in Wistar whereas there was a 20% (P < 0.05) increase in hypertensive rats, while phase and time differences were raised only in hypertensive rats (P < 0.05). Bilateral cervical vagotomy of the hypertensive rats had minimal actions on most variables but phase and time differences were doubled compared to intact hypertensive animals, but brachial nerve stimulation decreased power at the heart rate frequency (P < 0.05) which was a very different response from intact rats. Resting blood pressure, heart rate, total power and power at the heart rate frequency in the carotid sinus denervated animals were lower than in intact hypertensive rats, between 17 and 71%, respectively, but increased during brachial nerve stimulation. These experiments demonstrated that whereas somatic sensory input can modulate the pattern of sympathetic nerve activity to the kidney under normal conditions, this does not occur in the hypertensive rat. This appears to be related to afferent information carried by the vagus which suppresses the normal response; the carotid sinus baroreceptors are devoted to organising the nerve activity in relation to the blood pressure pulse wave.

Animals↗
PubMed1996

Identification of a new antifungal target site through a dual biochemical and molecular-genetics approach.

The target site of the antifungal compound LY214352 [8-chloro-4-(2-chloro-4-fluorophenoxy) quinoline] has been identified through a dual biochemical and molecular-genetics approach. In the molecular-genetics approach, a cosmid library was prepared from an Aspergillus nidulans mutant that was resistant to LY214352 because of a dominant mutation in a single gene. A single cosmid (6A6-6) that could transform an LY214352-sensitive strain of A. nidulans to LY214352-resistance was isolated from the library by sib-selection. Restriction fragments from cosmid 6A6-6 containing the functional resistance gene were identified by transformation, and sequenced. The LY214352-resistance gene coded for a protein of 520 amino acids that had a 34% identity and a 57% similarity in a 333 amino-acid overlap to E. coli dihydroorotate dehydrogenase (DHO-DH). The results of a series of biochemical mechanism-of-action studies initiated simultaneously with molecular-genetic experiments also suggested that DHO-DH was the target of LY214352. Assays measuring the inhibition of DHO-DH activity by LY214352 in a wild-type strain (I50=40 ng/ml) and a highly resistant mutant (I50>100 microgram/ml) conclusively demonstrated that DHO-DH is the target site of LY214352 in A. nidulans. Several mutations in the DHO-DH (pyrE) gene that resulted in resistance to LY214352 were identified.

Antifungal Agents↗
PubMed1996

Balloon mitral valve dilatation as an aid to weaning from ventilatory support in patients with intractable pulmonary oedema caused by severe mitral stenosis.

Intractable pulmonary oedema in patients undergoing mechanical ventilation must be investigated as older patients with severe mitral stenosis can be rescued by balloon dilatation of the mitral valve, thus enabling elective cardiac surgery at reduced risk. We describe two such cases and discuss the role of transoesophageal echocardiography in the intensive care unit in the diagnosis and management of these patients.

Catheterization↗
PubMed1996

Nonvalvular myocardial involvement in metastatic carcinoid disease.

A patient with the unusual post mortem finding of myocardial metastatic carcinoid tumour without classical valvular or endocardial carcinoid disease is described. This rare occurrence may represent an aggressive type of carcinoid tumour, with metastatic disease occurring before the development of classical fibrous valvular and endocardial pathology.

Aged↗
PubMed1995

Renal sympathetic nerve responses to somato-sensory nerve stimulation in normotensive rats.

Blood pressure, heart rate and renal sympathetic nerve activity were recorded in groups of chloralose/urethane-anaesthetised intact, vagotomised and carotid sinus denervated Wistar rats before and during bilateral somatic afferent nerve stimulation from 0.1 to 3.2 Hz. Renal sympathetic nerve activity was subjected to power spectral and cross correlation analysis. Haemodynamic and integrated renal nerve responses to graded brachial nerve stimulation were not altered by either bilateral vagotomy or carotid sinus denervation and total power of the spectra, from 0-10 Hz, was similar in each group. The percentage power peak at heart rate in intact rats decreased with increasing stimulus frequency, from a control value of 19.2 +/- 1.9% to a minimum of 2.8 +/- 0.7% at 1.6 Hz, while coherence and phase were not altered. Conversely, the peak at the stimulus frequency rose with increasing stimulus frequency reaching 35.3 +/- 2.0% at 3.2 Hz. In the vagotomised group, power at heart rate was significantly lower at each stimulus frequency compared to intact rats although coherence was similar and the phase difference was larger. The peak power at stimulus frequency, coherence and phase difference were similar to those obtained in the intact rats. In the carotid sinus denervated rats, the percentage power at heart rate, coherence and phase difference were significantly smaller than in intact rats. The peak at the stimulus frequency and the phase difference were similar to those obtained in the intact rats whereas coherence was lower. These findings demonstrate that the pattern of renal nerve activity can be changed from one modulated by the baroreceptor to one driven by somatic afferent nerve activity. The vagus appears to play a minor role in the overall pattern of renal nerve activity with the primary controller being the carotid sinus baroreceptors. The data also show that the renal nerve response to somatic afferent nerve stimulation is independent of the afferent nerve input arising from either the atrial or the carotid sinuses.

Adrenergic Fibers↗
PubMed1995

Failure of high-dose oral acyclovir to suppress CMV viruria or induce ganciclovir-resistant CMV in HIV antibody positive patients.

Ninety-three symptomatic HIV antibody positive patients were randomized to receive zidovudine (ZDV) 600 mg/day and acyclovir (ACV) 4,800 mg orally per day versus ZDV 600 mg/day plus placebo. Urine was obtained at 3-month intervals and cultured for cytomegalovirus (CMV) in diploid fibroblast cells. The percent of urine specimens positive for CMV was 7.1% in the ZDV group and 5.8% in the ZDV plus ACV group (p = 0.55); 27% of patients had at least one urine culture positive for CMV while taking ZDV, versus 20% of patients taking the combination of ZDV plus ACV (p = 0.52). We conclude that ACV at a dosage of 4,800 mg/day does not suppress CMV excretion in urine of symptomatic HIV antibody positive patients taking concurrent ZDV. Use of ACV did not appear to induce resistance of CMV to ganciclovir since the ID50 of isolates from the two treatment groups did not differ.

Acyclovir↗