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Biomedical subjects

G Davis

Publications and source records attributed to G Davis.

At least 37 records · Page 2Linked to original sources
PubMed1998

Ambulatory urodynamics of female soldiers.

The purpose of this study was to assess the accuracy of ambulatory urodynamic monitoring compared with conventional urodynamic studies for the detection of exercise-induced urinary incontinence in the female soldier. Fifty active duty female soldiers with exercise-induced urinary incontinence and 10 asymptomatic control soldiers underwent conventional multichannel cystometry and then ambulatory monitoring during work or exercise. Ambulatory monitoring detected a greater number of abnormalities than conventional multichannel urodynamic studies in exercise-induced urinary incontinence. This greater sensitivity is valuable in formulating more effective treatment. Behavioral interventions were effective in treating exercise-induced urinary incontinence in this population. Test results normalized after behavioral intervention. It is neither cost-effective nor efficacious to require sophisticated urodynamic testing before instituting behavioral interventions.

Adult↗
PubMed1997

Identification and cloning of human placental bikunin, a novel serine protease inhibitor containing two Kunitz domains.

Interrogation of the public expressed sequence tag (EST) data base with the sequence of preproaprotinin identified ESTs encoding two potential new members of the Kunitz family of serine protease inhibitors. Through reiterative interrogation, an EST contig was obtained, the consensus sequence from which encoded both of the novel Kunitz domains in a single open reading frame. This consensus sequence was used to direct the isolation of a full-length cDNA clone from a placental library. The resulting cDNA sequence predicted a 252-residue protein containing a putative NH2-terminal signal peptide followed sequentially by each of the two Kunitz domains within a 170-residue ectodomain, a putative transmembrane domain, and a 31-residue hydrophilic COOH terminus. The gene for this putative novel protein was mapped by use of a radiation hybrid panel to chromosome 19q13, and Northern analysis showed that the corresponding mRNA was expressed at high levels in human placenta and pancreas and at lower levels in brain, lung, and kidney. An endogenous soluble form of this protein, which was designated as placental bikunin, was highly purified from human placenta by sequential kallikrein-Sepharose affinity, gel filtration, and C18 reverse-phase chromatography. The natural protein exhibited the same NH2 terminus as predicted from the cloned cDNA and inhibited trypsin, plasma kallikrein, and plasmin with IC50 values in the nanomolar range.

Amino Acid Sequence↗
PubMed1997

Frequent genital herpes simplex virus 2 shedding in immunocompetent women. Effect of acyclovir treatment.

Reactivation of herpes simplex virus type 2 (HSV-2) occurs intermittently as perceived clinically and by viral culture. We performed a series of studies to evaluate the frequency and pattern of HSV-2 reactivation using both viral isolation and HSV PCR assay. Daily samples of genital secretions were obtained from 27 HSV-2 seropositive women; a subset of subjects obtained samples while receiving oral acyclovir 400 mg PO twice a day. HSV DNA was detected in genital swab specimens on 28% of 1,410 d compared with 8.1% of days by viral isolation. 11 of 20 women had HSV DNA detected on > 20% of days, 4 on > 50%, and 2 on > 75% of days; in contrast, none of the women shed on > 21% of days by viral isolation. The daily administration of oral acyclovir promptly reduced the frequency of HSV DNA detection by a median of 80%. Within 3-4 d of discontinuing daily acyclovir, HSV DNA again appeared in the genital area. HSV-2 shedding in the genital mucosa occurs much more frequently than previously appreciated. This frequent reactivation likely plays a role in the epidemic spread of genital herpes worldwide.

Acyclovir↗
PubMed1997

B7.2 expressed by T cells does not induce CD28-mediated costimulatory activity but retains CTLA4 binding: implications for induction of antitumor immunity to T cell tumors.

The B7 family of costimulatory molecules provides the second signal necessary for activation of T cells. In the absence of the second signal, responding T cells become anergic. Although predominantly expressed on professional APCs, recent evidence shows that the B7 molecules are also expressed on T cells. To study the functions of B7 molecules on T cells, we transfected murine B7.1 (CD80) and B7.2 (CD86) cDNAs into the EL4 T cell thymoma cell line and examined the transfectants for their ability to costimulate T cell proliferation in vitro and to induce antitumor immunity in vivo. Here we show that although EL4-B7.1 cells costimulate T cells and induce tumor regression, EL4-B7.2 transfectants failed to costimulate T cell proliferation or induce tumor regression. To understand the cellular basis for this difference, we examined the binding of EL4-B7.1 and EL4-B7.2 to CTLA4 and CD28. Whereas EL4-B7.1 cells bound both CTLA4-Ig and CD28-Ig, EL4-B7.2 transfectants preferentially bound CTLA4-Ig, but not CD28-Ig. Similar binding data were obtained with freshly isolated murine T cells, which have been shown to constitutively express B7.2. Our data suggest, therefore, that B7.2 expressed on T cells may not costimulate but instead inhibit the T cell response by preferential binding to CTLA4.

Abatacept↗
PubMed1997

Reduced cytochrome oxidase and memory dysfunction after chronic brain ischemia in aged rats.

The effects of chronic cerebrovascular ischemia on memory function and cytochrome oxidase (CO) activity were investigated. Cerebrovascular insufficiency was induced by permanent bilateral carotid artery ligation (2-VO) in 19 month old rats. Sham surgery in no-vessel occlusion (no-VO) rats were used for controls. Memory function was tested 1 week prior to surgery and then weekly for 21 days using the Morris water maze. Regional brain activity of CO was measured 4 weeks after surgery by quantitative histochemistry. Histologic examination of brain slices was used to evaluate any neuropathology present. Results showed that 2-VO rats were significantly impaired in the water maze task at each testing period with respect to no-VO controls. In addition, CO activity in 2-VO rats was markedly reduced only in the dorsal CA1 region of the hippocampus and in the posterior parietal cortex. These brain regions are involved in visuo-spatial memory mechanisms. Analysis of other brain regions in 2-VO rats did not reveal further CO activity changes. There were no damaged or loss of neurons in 2-VO or no-VO groups in any region examined, including CA1 and posterior parietal cortex. The CA1 region however, is known to undergo neuronal loss 25 weeks after chronic 2-VO suggesting that this vascular insult can induce a slowly-evolving cascade consisting of neuronal damage, atrophy and death. The present findings indicate that reduced CO activity in CA1 and posterior parietal regions can predict neural damage and atrophy prior to structural perikaryal pathology following chronic brain ischemia. In addition, the data shows that neuronal energy metabolic deficiency may initiate visuo-spatial memory impairment in this aging rat model.

Aging↗
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↗