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Biomedical subjects

S Wilson

Publications and source records attributed to S Wilson.

At least 397 records · Page 22Linked to original sources

Pharmacology of saccadic eye movements in man. 1. Effects of the benzodiazepine receptor ligands midazolam and flumazenil.

A paradigm for assessing benzodiazepine receptor sensitivity was developed using intravenous midazolam in normal volunteers. After administration of incremental doses of midazolam, alterations in saccadic eye movement parameters and psychological self ratings were assessed. Significant changes included dose-dependent slowing of peak velocity, peak acceleration, peak deceleration, reduced saccade acceleration/deceleration ratio and saccade accuracy, and increased sedation self-ratings. Changes in saccade variables and sedation ratings were significantly correlated, and also correlated with plasma midazolam concentrations. No significant changes were seen in saccade latency or anxiety self-ratings. Pharmacological specificity of these changes was demonstrated by their reversal with the benzodiazepine antagonist flumazenil. This challenge paradigm appears to be a sensitive means of assessing benzodiazepine receptor function in man.

Adult↗

Pharmacology of saccadic eye movements in man. 2. Effects of the alpha 2-adrenoceptor ligands idazoxan and clonidine.

The effects of alpha 2-adrenoceptor agonists and antagonists on saccadic eye movements were studied in normal volunteers using the agonist clonidine and the antagonist idazoxan. Changes in blood pressure, heart rate, and several psychological self-ratings were also recorded. Clonidine produced marked slowing of peak saccade velocity, acceleration and deceleration, with deceleration affected more than acceleration, but had no effect on saccade error or latency measurements. In contrast, most saccade parameters were not altered by idazoxan, although fatigue effects were eliminated. Blood pressure, heart rate, and self ratings of alertness were increased by idazoxan and reduced by clonidine, with opposite effects noted on sedation self-ratings. There were no correlations between the clonidine-induced changes in saccade parameters and changes in self-ratings. Although the slowing of some saccade parameters by clonidine may imply that alpha 2-adrenoceptors are involved in control of saccades, it may also be due to sedation. Although alpha 2-adrenoceptor antagonists may abolish fatigue effects, they cannot increase them over baseline values.

Adrenergic alpha-Antagonists↗

Effects of vitamin or mineral deficiency on the morphology of medullary bone in laying hens.

Adult laying hens were fed diets deficient in phosphorus, calcium, calcium and phosphorus, and vitamin D3 to determine their effects on bone histology and parathyroid gland size. The phosphorus deficient diet caused an insignificant decrease in parathyroid size while the other diets caused significant increases. A considerable amount of individual variation in medullary bone volume and osteoid seam width was observed in all groups but, despite this, the calcium, calcium and phosphorus and vitamin D3 deficient diets clearly resulted in increased osteoid. Birds receiving diets deficient in calcium and phosphorus, and in vitamin D3 for longer periods were observed to have partially or completely resorbed medullary bone. Osteodystrophia fibrosa was noted in vitamin D3 deficient birds which had no follicular activity.

Animals↗

Ocular hypotensive effects of medetomidine and its analogs.

The ocular hypotensive effects of medetomidine, a relatively selective alpha 2-agonist, and its analogs were tested in rabbits and cats and their inhibition of adenylate cyclase in the isolated bovine ciliary process was also studied. It was found that topical unilateral administration of medetomidine (0.5-2.0%) to the normotensive rabbits produced a dose-dependent bilateral decrease in IOP with peak reduction in IOP at 2 hr in the treated eye and 1 hr in the untreated eye. A dose-dependent mydriasis was also observed in the treated eye. The dose-response curves of medetomidine and its analogs showed that the ranked order of intrinsic activity at lowering IOP was medetomidine greater than or equal to MPV-1440 greater than detomidine greater than MPV-1441 and MPV-305 BII. At concentrations lower than those used in rabbits, topical application of medetomidine to the normotensive cats lowered IOP in both treated and untreated eyes. Medetomidine and detomidine caused a dose-dependent inhibition of isoproterenol-stimulated adenylate cyclase activity. Detomidine was found to be a partial agonist producing about 43% of maximum inhibition obtained by medetomidine. The IOP efficacy of these alpha 2-agonists paralleled their effects on adenylate cyclase activity. The results demonstrated that these imidazoline derivatives are effective ocular hypotensive agents which may be useful in understanding the contribution of alpha 2-receptors to the regulation of IOP.

Adenylyl Cyclase Inhibitors↗

Living with a wife undergoing chemotherapy.

This study explicates the experience of living with a woman undergoing chemotherapy from the perspective of her husband. Data include 48 unstructured, open-ended face-to-face or telephone interviews with 14 informants and the diary of one informant. A substantive theory depicts the process through which husbands experience their wives' chemotherapy treatment for cancer. A three-stage model was developed, consisting of identifying the threat, engaging in the fight and becoming a veteran. Buffering was identified as the basic social process that explained the behaviors of husbands throughout this experience. It is proposed that when the disease reoccurs and chemotherapy is recommended, the process begins again.

Adult↗

Cloning and DNA sequence of amiC, a new gene regulating expression of the Pseudomonas aeruginosa aliphatic amidase, and purification of the amiC product.

Using in vitro-constructed deletions and subcloned DNA fragments, we have identified a new gene, amiC, which regulates expression of the inducible Pseudomonas aeruginosa aliphatic amidase activity. The DNA sequence of the gene has been determined, and an open reading frame encoding a polypeptide of 385 amino acids (molecular mass, 42,834 Da) has been identified. A search of sequence libraries has failed to find homologies with other published sequences. The amiC translation termination codon (A)TGA overlaps the initiation codon for the downstream amiR transcription antitermination factor gene, implying that the amiCR operon is coordinately regulated. Disruption of the amiC open reading frame by insertion and deletion leads to constitutive amidase synthesis, suggesting that AmiC is a negative regulator. This is confirmed by the finding that a broad-host-range expression vector carrying amiC (pSW41) represses amidase expression in a series of previously characterized P. aeruginosa amidase-constitutive mutants. The AmiC polypeptide has been purified from PAC452(pSW41), and N-terminal amino acid sequencing has confirmed the gene identification.

Amidohydrolases↗

Comparison of commercially available group B streptococcal latex agglutination assays.

Detection of group B streptococcus (GBS) antigen in urine by latex particle agglutination (LPA) may facilitate the rapid diagnosis of GBS sepsis. We sought to compare three commercial LPA assays with specimens that were spiked with type-specific antigen, group-specific antigen, or type III organisms. There were sensitivity differences between the assays, but the Bactigen assay performed best, detecting as little as 1 ng of GBS group-specific antigen per ml in urine and as few as 10(5) CFU of GBS type III organisms per ml in urine, serum, and cerebrospinal fluid.

Adult↗

Airway inflammation and atopic asthma: a comparative bronchoscopic investigation.

Flexible fibre-optic bronchoscopy under local anaesthesia has been used to investigate the cellular airway events in atopic asthma. The findings have been compared to those from atopic individuals without asthma and non-atopic healthy controls, in an attempt to discern those changes relevant to clinical disease expression. Immunohistochemical and electron-microscopic analyses of airway biopsies identified that an atopic diathesis is associated with tissue eosinophil infiltration and mast cell degranulation. The eosinophilia was greatest in those atopic individuals with asthma. Flow-cytometric analysis of airway lavage revealed significantly enhanced T lymphocyte activation in clinical asthma. These findings are consistent with the hypothesis that T lymphocyte activation, through cytokine release, amplifies the tissue eosinophilia in asthma and that this combination is associated with clinical disease expression.

Asthma↗

Elevated activity of low molecular weight insulin-like growth factor-binding proteins in sera of vitamin C-deficient and fasted guinea pigs.

We have previously reported that scorbutic and fasted guinea pig sera contain an insulin-like growth factor-I (IGF-I)-reversible inhibitor of collagen, proteoglycan, and DNA synthesis in cultured cells. Here we report that IGF-binding protein (IGFBP) activity is increased in serum containing the inhibitor [125I]IGF-I or -II bound to these sera was eluted in the 30- to 50-kDa region of an S200 gel column. [125I]IGF-I affinity cross-linking analysis revealed that a 38-kDa cross-linked species increased markedly in fasted and scorbutic sera, with a lesser increase in a 34-kDa species, while scorbutic sera also yielded a 44-kDa species. Gel filtration of unlabeled sera showed a 10-fold increase in the activity of two proteins in the 30- to 50-kDa region from the experimental sera. Their activity correlated with their ability to inhibit binding of [125I]IGF-I to its cellular receptor, suggesting that they have the potential to inhibit IGF-I-dependent functions. Ligand blotting showed that 29 and 35-kDa IGFBPs were almost undetectable in normal serum, but were dramatically induced by scurvy and fasting, so that they accounted for close to 40% of the total circulating BPs. Total IGFBP-3 in the experimental sera was increased about 30%, while there was little effect of scurvy or fasting on the level of BP-3 activity isolated by acid extraction of the high mol wt region of the S200 column. An IGF-I analog with normal affinity for the 30- to 50-kDa BPs from fasted and scorbutic sera, but with reduced affinity for the cell receptor, was equivalent to IGF-I in reversing the inhibition of collagen synthesis by scorbutic guinea pig serum in human fibroblasts. Thus, reversal of inhibition appears to require initial saturation of IGFBPs. The overall results suggest that two circulating IGFBPs with unoccupied binding sites are induced in vitamin C-deficient or fasted guinea pigs and may be responsible for inhibition of IGF-I-dependent functions by sera from these animals.

Animals↗

Patient monitoring in the conscious sedation of children for dental care.

Monitoring physiologic parameters in young patients sedated for dental care using noninvasive electronic monitors is a relatively new phenomenon. Several reasons contribute to the increased use of electronic monitors during these sedations, including rapid advances in technology and concerns for patient safety. This is a review of the most recent studies reporting the use of electronic monitors when sedating pediatric patients for delivery of dental care. The function, advantages, and shortcomings of several electronic monitors in this setting are discussed.

Anesthesia, Dental↗

Outcome predictors in selection of balloon angioplasty or surgery for peripheral arterial occlusive disease. Veterans Administration Cooperative Study No. 199.

In a selected group of men, surgical bypass and percutaneous balloon angioplasty (PTA) are equally effective therapy for ileo-femoropopliteal occlusive disease, provided immediate PTA failures are disregarded. Can we predict those patients likely to experience immediate PTA failure? Do any preintervention factors exist that favor PTA or surgical bypass for the remaining patients? Logistic regression analysis determined variables predictive of failure for the 19 immediate PTA failures and for the 17 patients with PTA and the 24 patients with surgical bypass who failed after initial intervention but before the end of 2 years. Two hundred sixty-three patients were enrolled. The analysis evaluated patient characteristics (age, weight, smoking status, diabetic status, and sickness impact profile score) as well as lesion site, percent lesion stenosis, runoff status, hemodynamic parameters, and indications. Two independent predictors of immediate PTA failure were diastolic hypertension (p = 0.032) and percent stenosis of study site (p = 0.035). The probability equation defined by the logistic regression analysis delineates patients at high risk for immediate PTA failure. Interestingly, no factor uniquely predicted delayed PTA or surgical failure. These data suggest that selected patients with diastolic hypertension and a severely stenotic or occluded artery are poor candidates for PTA. Either PTA or surgical bypass is effective therapy for the remaining patients.

Angioplasty, Balloon↗

Molecular cloning and expression of a hexameric Drosophila heat shock factor subject to negative regulation.

We report the cloning of the transcriptional activator of heat shock genes, HSF, from Drosophila. The predicted sequence of Drosophila HSF protein is surprisingly divergent from that of yeast HSF, except in regions important for DNA binding and oligomerization. A segment of the DNA binding domain of HSF bears an intriguing similarity to the putative DNA recognition helix of bacterial sigma factors, while the oligomerization domain contains an unusual arrangement of conserved hydrophobic heptad repeats. Drosophila HSF produced in E. coli under nonshock conditions forms a hexamer that binds specifically to DNA with high affinity and activates transcription from a heat shock promoter in vitro. In contrast, when HSF is expressed in Xenopus oocytes, maximal DNA binding affinity is observed only after heat shock induction. These results suggest that Drosophila HSF has an intrinsic affinity for DNA, which is repressed under nonshock conditions in vivo.

Amino Acid Sequence↗

Antibody-mediated activation of Drosophila heat shock factor in vitro.

Eukaryotic cells respond to elevated temperatures by rapidly activating the expression of heat shock genes. Central to this activation is heat shock-inducible binding of the transcriptional activator, termed heat shock factor (HSF), to common regulatory elements, which are located upstream of all heat shock genes. The DNA binding activity of the inactive form of Drosophila HSF was induced in vitro by treatment with polyclonal antibodies to the purified, in vivo-activated factor. This finding, together with observations that high temperature and low pH activate HSF binding in vitro, suggests that the inactive form of HSF can directly recognize and transduce the heat shock signal without undergoing a covalent modification of protein structure.

Animals↗