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Biomedical subjects

S Hanson

Publications and source records attributed to S Hanson.

At least 19 recordsLinked to original sources

Murine serine proteases MASP-1 and MASP-3, components of the lectin pathway activation complex of complement, are encoded by a single structural gene.

Activation of the lectin pathway of complement is initiated by the binding to microbial carbohydrate structures of a multimolecular fluid-phase complex composed of a carbohydrate recognition subcomponent that associates with three specific serine proteases and an enzymatically inert protein of 19 kDa. The first carbohydrate recognition subcomponent of the lectin pathway identified was mannan-binding lectin (MBL), hence the serine proteases were named MBL-associated serine proteases (MASPs) and numbered according to the sequence of their discovery. Here we describe the primary structures of the two distinct serine proteases MASP-1 and MASP-3 in the rat (and of MASP-3 in the mouse), show their association with plasma MBL complexes, and demonstrate that in rat and mouse, as in man, MASP-1 and MASP-3 are encoded by a single structural gene. For both species, we present the genomic region and regulatory elements responsible for the processing of either MASP-1 or MASP-3 mRNA by alternative splicing/alternative polyadenylation. Furthermore, we demonstrate the evolutionary conservation of MASP-3 mRNA in cDNA transcripts from guinea pig, rabbit, pufferfish, and cow.

Alternative Splicing↗

Predictors of good outcome after intravenous tPA for acute ischemic stroke.

BACKGROUND: Thrombolytic therapy for acute ischemic stroke with IV alteplase is increasingly well established in North America but not elsewhere. Baseline factors that altered the response to alteplase were not identified by the National Institute of Neurological Disorders and Stroke tPA Stroke Study Group. METHODS: The authors gathered information from centers in the United States, Canada, and Germany on 1,205 patients with acute ischemic stroke treated with IV alteplase. The purpose was to identify independent factors that were predictive of good outcome using multivariable logistic regression modelling. The modified Rankin Scale score was dichotomized into good outcome (mRS 0 to 1) and poor outcome (mRS >1) as the primary outcome measure. RESULTS: In relative order of decreasing magnitude, milder baseline stroke severity, no history of diabetes mellitus, normal CT scan, normal pretreatment blood glucose level, and normal pretreatment blood pressure were independent predictors of good outcome among patients treated with IV alteplase for acute ischemic stroke. Confounding was observed among history of diabetes mellitus, CT scan appearance, baseline serum glucose level, and blood pressure, suggesting important relationships among these variables. CONCLUSIONS: Several factors were independently predictive of good outcome among patients with acute ischemic stroke treated with alteplase. These results require further confirmation before clinical implementation.

Acute Disease↗

Observer experience and Cup:Disc ratio assessment.

BACKGROUND: The validity of the Cup:Disc (C:D) ratio as a clinical measure depends on the level of agreement among observers. In this study, we investigated the effect of observer experience on interobserver and intraobserver agreement in C:D ratio estimation. METHODS: Nine 3rd-year (Yr3) and nine 4th-year (Yr4) optometry students and nine optometrists (Opt), determined C:D ratios from 26 optic disc photographs viewed monoscopically and stereoscopically. Observer agreement was investigated using weighted kappa (Kw) analysis. RESULTS: Interobserver agreement was higher (p < 0.01) among optometrists than among 4th-year students and higher (p < 0.01) among 4th-year than among 3rd-year students (mean Kw: Opt = 0.61; Yr4 = 0.51; Yr3 = 0.39). Stereoscopic estimates of C:D ratios were higher (p < 0.0001) than monoscopic estimates, and interobserver agreement was higher (p < 0.001) when evaluating the vertical rather than the horizontal C:D ratio. Intraobserver agreement (mean Kw: Opt = 0.67; Yr4 = 0.66; Yr3 = 0.62) did not vary significantly (p = 0.78) with experience. CONCLUSIONS: The extent to which an observer reproducibly assesses the C:D ratio from optic disc photographs (intraobserver agreement) does not increase with experience. However, the agreement between different observers in assessing the C:D ratio (interobserver agreement) increases with experience.

Clinical Competence↗

Synthesis of novel 5-substituted 3-amino-3,4-dihydro-2H-1-benzopyran derivatives and their interactions with the 5-HT1A receptor.

A series of new enantiomerically pure 3-amino-3,4-dihydro-2H-1-benzopyrans (3-aminochromans) has been synthesized from (R)- and (S)-5-methoxy-3-amino-3,4-dihydro-2H-1-benzopyran. The absolute configuration of the respective (R)- and (S)-enantiomers was deduced from X-ray crystallography of (R)-3-(N-isopropylamino)-5-methoxy-3,4-dihydro-2H-1-benzopyran, (R)-9a. Various 5-substituents were introduced via palladium-catalyzed carbonylation of N-substituted 3-amino-5-trifluoromethanesulfonyloxy-3,4-dihydro-2H-1-benzopyran. The effect of N- and 5-substitution on affinity for the 5-HT1A receptor was evaluated in competition experiments using rat hippocampal membranes and [3H]8-OH-DPAT as radioligand. Selected compounds were also tested for their affinity to the D1 (rat striatum), D2 (rat striatum), D2A (human cloned), and 5-HT2A (rat cortex) receptors. The intrinsic activity of the compounds was evaluated by measuring their effect on VIP-stimulated cAMP production in GH4ZD10 cells stably transfected with the 5-HT1A receptor. High-affinity compounds with high selectivity for the 5-HT1A receptor were found among structures substituted with carboxylate esters, amides, and ketones in the 5-position. Primary and secondary amines bound with lower affinity than tertiary amines. Larger substituents were well-tolerated by the receptor, but the smaller N-ethyl-N-isopropyl bound with lower affinity. Generally, the (R)-enantiomers displayed higher affinity for the 5-HT1A receptor than the corresponding (S)-enantiomers. In the present series of compounds, both full and partial agonists were found.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

A comparison of manual kinetic and automated static perimetry in obtaining ptosis fields.

OBJECTIVE: To compare examination time and visual field loss for ptosis fields obtained with manual kinetic (Goldmann) perimetry and automated static (Humphrey) perimetry. METHODS: Both eyes of 12 patients with bilateral aponeurogenic ptosis were prospectively examined using Goldmann and Humphrey (ptosis protocol) perimetry with the eyelids ptotic and taped into a normal position. RESULTS: Bilateral examination time for Goldmann fields was 10 +/- 2 minutes and for Humphrey fields was 50 +/- 10 minutes (P<.001, n = 12). Superior fields at the 12:00 meridian were 46 degrees +/- 6 degrees taped, and 28 degrees +/- 12 degrees untaped for Goldmann perimetry (P<.001), and 38 degrees +/- 8 degrees taped, and 24 degrees +/- 12 degrees untaped for Humphrey perimetry P<.001). Goldmann field loss was 18 degrees +/- 9 degrees (taped minus untaped). Humphrey field loss was 14 degrees +/- 13 degrees (P<.04, n = 24). Mean Goldmann radial fields were 56 degrees +/- 6 degrees taped and 39 degrees +/- 13 degrees untaped (P<.001). Goldmann superior hemifield areas were 5,167 +/- 964 degrees2 taped and 2,830 +/- 1,466 degrees2 untaped (P<.001). Humphrey mean vertical superior hemifield was 37 degrees +/- 9 degrees taped and 21 degrees +/- 11 degrees untaped (P<.001). Mean sensitivity of Humphrey fields was 15 +/- 3 dB taped and 9 +/- 5 dB untaped (P<.001). Mean vertical center of gravity was 23 degrees +/- 3 degrees taped and 16 degrees +/- 5 degrees untaped (P <.001). CONCLUSION: Goldmann manual kinetic and Humphrey automated static visual field testing are both effective in documenting ptosis associated visual field loss. Humphrey automated ptosis fields, as performed in this study, require longer examination times than Goldmann manual fields and may be a less sensitive indicator of field loss.

Adult↗

The introduction of the frontline management initiative in South Western Sydney Area Health Service.

This article provides an overview of the development and implementation of a management development strategy for the South Western Sydney Area Health Service (SWSAHS). The program, the Frontline Management Initiative (FMI), was introduced as a developmental tool which enabled managers to identify those competencies that they already possess and those which they need to develop. The FMI will be progressively implemented throughout the five sector health services of SWSAHS comprising approximately 1500 managers. This article outlines the introduction and experience of FMI in one sector health service, the development and assessment of a manager's portfolio, the pathway developed from FMI to university based health management courses, the lessons learnt and the future directions for management development.

Administrative Personnel↗

Abusive behavior is barrier to high-reliability health care systems, culture of patient safety.

Addressing abusive behavior in the medical workplace presents an important opportunity to deliver on the national commitment to improve patient safety. Fundamentally, the issue of patient safety and the issue of abusive behavior in the workplace are both about harm. Undiagnosed and untreated, abusive behavior is a barrier to creating high reliability service delivery systems that ensure patient safety. Health care managers and clinicians need to improve their awareness, knowledge, and understanding of the issue of workplace abuse. The available research suggests there is a high prevalence of workplace abuse in medicine. Both administrators at the blunt end and clinicians at the sharp end should consider learning new approaches to defining and treating the problem of workplace abuse. Eliminating abusive behavior has positive implications for preventing and controlling medical injury and improving organizational performance.

Agonistic Behavior↗

Economic effects of community versus hospital-based faculty pneumonia care.

To compare the length of stay and charges for patients with pneumonia admitted in 1995 to the teaching and nonteaching services of a Northeastern teaching hospital, we reviewed the charts of 237 patients. Patients cared for by hospital-based generalists working with housestaff (teaching service) were discharged more quickly and with lower or equivalent charges than patients cared for by community-based attending physicians working either with housestaff (private teaching service) or alone (nonteaching service). Academic teaching services staffed by general medicine faculty may provide efficient inpatient pneumonia care.

Adult↗

Molecular and cellular characterization of baboon C-Raf as a target for antiproliferative effects of antisense oligonucleotides.

C-Raf is a an essential member of the growth factor-ras pathway and a target for intervention strategies aimed at blocking cell proliferative responses. Excessive smooth muscle proliferation is considered one cause of the arterial closure in restenosis. Because of the similarity to the human cardiovascular system, a useful current animal model of the disease is a baboon model. As a foundation for animal studies employing antisense oligonucleotides, efforts were made to characterize the molecular and cellular biology of the baboon system. The nucleotide sequence of baboon c-raf cDNA was determined. Antisense phosphorothioate oligonucleotides specific to the 3'-UTR of c-raf mRNA from human and baboon were compared using primary baboon smooth muscle cells in culture. A particular human antisense oligonucleotide, referred to as ISIS 5132, was different by only 2 of 20 bases from the baboon sequence. The corresponding baboon antisense oligonucleotide ISIS 12959, however, was markedly more effective to inhibit c-raf mRNA, protein production, and DNA synthesis, and the results attest to the species specificity of the approach. After antisense treatment, c-raf mRNA levels dropped rapidly, whereas protein levels decreased with a half-life of roughly 24-48 hours, consistent with the antiproliferative effects. The data are discussed with regard to the profile of protein-protein interactions made by C-Raf and with the view that the baboon system closely parallels the human one at the signal transduction level. As this work progressed, a baboon cDNA homolog of a human c-raf-2 pseudogene was isolated, sequenced, and shown to be transcribed into mRNA.

Animals↗

Case management and patient reactions: a study of STD care in a province in Zambia.

Sexually transmitted disease (STD) case management was evaluated through observation and interviews at 2 urban and 4 rural health centres and 2 district hospital STD clinics in one urban and 2 rural districts in Central Province, Zambia. The analysis was limited to 59 patients (42 men and 17 women) who paid first visits for their disease and were managed by a clinical officer. The evaluation suffered from the lack of a standard for case management. Results showed that the patients engaged in risky sexual behaviour without being aware of the risks. At the health institutions, few patients were informed about condoms, the risk of HIV, and abstinence from sex during treatment and few were asked to notify their partners. Clinical officers with special STD training performed better than others but sill informed only one-fifth of the patients. Few clinical officers managed patients according to the syndromic approach recommended by the STD control programme.

Adolescent↗

Seasonal abundance and distribution of mosquitoes at a rural waste tire site in Illinois.

The species composition, abundance, and distribution of mosquito larvae in tires were determined on 3 dates at a relatively large rural tire dump (about 300,000 tires) in southeastern IL (Jasper County). Several observations at this site differed from those in previous reports about mosquitoes in tireyards, including 1) a relatively high percentage of tires positive for Aedes triseriatus larvae in an open-field area, 2) a greater abundance of Culex pipiens than Cx. restuans in late-season collections, 3) a seasonal change in the distribution of Aedes atropalpus larvae in tires from open field and edge of woods areas, and 4) the presence of Ae. albopictus as a major late-season species. Ae. albopictus adults were captured in sod-baited gravid traps along the edge of a wooded riparian area 200 m from the tire pile.

Aedes↗

Outbreak of Escherichia coli O157 phage type 2 infection associated with eating precooked meats.

Fourteen cases of Escherichia coli O157 infection were reported to the consultant in communicable disease control in Sunderland Health Authority in August 1995. E. coli O157 phage type 2, Vero cytotoxin 2 was isolated from the faeces of ten cases. Nine of the isolates were indistinguishable by Vero cytotoxin subtyping and analysis of chromosomal DNA. Two cases with haemolytic uraemic syndrome were confirmed serologically and two cases remained unconfirmed. A case control study showed infection with E. coli O157 to be associated with having eaten precooked meats from a single shop. Environmental investigations at the shop showed that cooked meats were stored close to raw beef, raw meats were left on preparation surfaces, and the same staff served both raw and cooked meats. This outbreak draws attention to standards of food preparation and handling in outbreaks of E. coli O157, the issue of cross contamination, and the need to improve local surveillance of haemolytic uraemic syndrome.

Adolescent↗

Effect of varying atrial sensitivity, AV interval, and detection algorithm on automatic mode switching.

UNLABELLED: Automatic mode switching (AMS) is absolutely dependent on atrial tachyarrhythmia detection. The effects of programming several features that could influence tachyarrhythmia detection were assessed in 18 patients (six women; mean age 64 years) with pacemakers having AMS capability. The atrial electrogram amplitude in sinus rhythm at implant (SR-EGM), last measured atrial sensing threshold prior to tachycardia (A-SENS), and atrial sensing threshold for effective AMS during atrial tachyarrhythmia (AMS-SENS) were obtained. Additionally, ten patients had AV intervals increased from 60 to 200 ms, while seven patients had detection algorithms made more stringent from 5 beats at 150 beats/min to 11 beats at 200 beats/min to assess their effects on AMS efficacy. RESULTS: Sensitivities:Mean SR-EGM = 3.55 mV; mean A-SENS = 2.06 mV; and mean AMS-SENS = 1.46 mV. Fourteen patients developed atrial fibrillation and four atrial flutter. Thirteen of 14 patients who developed atrial fibrillation sensed adequately at > or = 1.0 mV in normal sinus rhythm (NSR), but only six patients had effective AMS at these settings in atrial fibrillation. Three of four patients who developed atrial flutter had effective AMS at > or = 2.0 mV. AV Interval:AMS was effective in eight of ten patients at AV intervals up to 200 ms. One patient lost AMS at an AV interval of 120 ms. Algorithm: In two of seven patients, AMS was not effective if the detection algorithm was more stringent than five beats at 150 beats/min. CONCLUSIONS: (1) In atrial fibrillation, effective AMS requires more sensitive atrial settings than in NSR; (2) AV intervals as short as 120 ms can interfere with AMS function; and (3) More stringent detection algorithms may be inappropriate for effective AMS function.

Algorithms↗

Cloning and structure-function analysis of the Leishmania donovani kinetoplastid membrane protein-11.

This report describes the complete translated gene sequence, predicted secondary structure and lipid bilayer association of a novel kinetoplastid membrane protein (KMP-11) from Leishmania donovani promastigotes. KMP-11 was previously referred to as the lipophosphoglycan-associated protein (LPGAP). The isolation, species distribution and chemical characterization, including a partial protein sequence analysis and post-translational modifications, of this major membrane component have been described [Jardim, Funk, Caprioli and Olafson (1995) Biochem. J. 305, 307-313]. C.d. measurements of KMP-11 indicated a very high helical content estimated to be approximately 86% in trifluoroethanol. This was in agreement with computer-based secondary-structure analyses which predicted KMP-11 to be almost exclusively alpha-helical, with the protein adopting a helix-loop-helix motif. Arrangement of the residues located in the putative helical regions on an Edmundson helical wheel showed that this molecule could have a strongly amphipathic conformation and provided an explanation for how such a highly charged protein might be inserted into the plasma membrane. Evidence in support of KMP-11 association with lipid bilayers was provided by showing that KMP-11 could mediate carboxyfluorescein release from liposomes. These findings suggested that KMP-11 may function in part to increase bilayer pressure, stabilizing molecules such as lipophosphoglycan within the parasite pellicular membrane.

Amino Acid Sequence↗

Monoclonal antibodies against Haemophilus ducreyi lipooligosaccharide and their diagnostic usefulness.

Monoclonal antibodies against the lipooligosaccharide of Haemophilus ducreyi were produced. Two of them, MAHD6 and MAHD7, were found to be relatively, although not absolutely, specific and reacted with nearly all strains of Haemophilus ducreyi tested: 59 of 60 and 60 of 60, respectively. The diagnostic usefulness of MAHD7 was assessed. Clinical specimens collected in Zambia from patients with genital ulcers were tested using indirect immunofluorescence (IF), enzyme immunoassay (EIA), the polymerase chain reaction (PCR) and bacterial culture. Compared with culture, IF had a sensitivity of 100%; compared with PCR, sensitivity was 89%. The corresponding figures for the EIA were 83% and 74%, respectively. The sensitivity of culture compared with PCR was 63%. The results suggest that IF on genital smears using MAHD7 might be an excellent tool for the diagnosis of chancroid in high-prevalence populations. However, further evaluation of the specificity of this test is needed.

Adolescent↗