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Biomedical subjects

S Wilson

Publications and source records attributed to S Wilson.

At least 19 recordsLinked to original sources
PubMed1999

Comparison of physical chemical properties of llama VHH antibody fragments and mouse monoclonal antibodies.

Antigen specific llama VHH antibody fragments were compared to antigen specific mouse monoclonal antibodies with respect to specificity, affinity and stability. The llama VHH antibody fragments and the mouse monoclonal antibodies investigated were shown to be highly specific for the protein antigen hCG or the hapten antigen RR-6. The affinity of the interaction between monovalent llama VHH antibody fragments and their antigen is close to the nanomolar range, similar to the bivalent mouse monoclonal antibodies studied. Llama VHH antibody fragments are similar to mouse monoclonal antibodies with respect to antigen binding in the presence of ammonium thiocyanate and ethanol. The results show that relative to antigen specific mouse monoclonal antibodies, antigen specific llama VHH fragments are extremely temperature stable. Two out of six llama VHHs are able to bind antigen specifically at temperatures as high as 90 degrees C, whereas four out of four mouse monoclonal antibodies are not functional at this temperature. Together with the finding that llama VHH fragments can be produced at high yield in Saccharomyces cerevisiae, these findings indicate that in the near future antigen specific llama VHH fragments can be used in for antibodies unexpected products and processes.

Animals↗
PubMed1999

Comforting strategies used during nasogastric tube insertion.

Nasogastric tube insertion is a procedure that commonly involves discomfort, yet requires the cooperation of the conscious patient. This study employed qualitative ethology to investigate how comforting strategies were used during the insertion of nasogastric tubes in trauma care. Practitioners used eight direct and indirect comforting strategies in uniquely patterned styles (technical, affective and blended). In addition, a form of 'team comforting' was implemented as multiple trauma team members made a concerted effort to complete the procedure. Further study is needed to explicate how the nurse's style affects the behavioural state displayed by the patient.

Emergency Nursing↗
PubMed1999

Phase I study of combination therapy with intravenous cidofovir and oral ganciclovir for cytomegalovirus retinitis in patients with AIDS.

Ganciclovir and cidofovir, two antiviral agents used in the treatment of cytomegalovirus (CMV) retinitis, have a synergistic effect inhibiting CMV replication in vitro. In a phase I study, seven patients with AIDS-related CMV retinitis were treated with cidofovir (5 mg/kg intravenously every 2 weeks) combined with ganciclovir (1 g orally three times a day). During a median of 5.5 months (range, 1-12 months) of combined therapy, only one patient had retinitis progression, and only two of 28 blood cultures (specimens of which were obtained on a monthly basis) yielded CMV. Dose-limiting adverse ocular effects (anterior uveitis [two patients] and hypotony [two patients]) occurred in three of seven patients. The results suggest that combination therapy with intravenous cidofovir and oral ganciclovir (a regimen that does not require indwelling central venous catheter access) might enhance clinical efficacy. Less frequent administration of cidofovir in combination with oral ganciclovir should be prospectively studied to determine if the incidence of treatment-associated toxicity might be reduced.

AIDS-Related Opportunistic Infections↗
PubMed1999

The effects of regular inhaled formoterol, budesonide, and placebo on mucosal inflammation and clinical indices in mild asthma.

The present study was designed to observe the effects of 8 wk of treatment with formoterol (Foradil) 24 microgram, budesonide 400 microgram, and matched placebo inhaled twice a day on inflammatory indices in the bronchial mucosa of 64 patients with mild atopic asthma. Biopsies were obtained at the start and 1 wk before stopping a 9-wk period of treatment, and inflammatory cell numbers were assessed in the submucosa and epithelium by immunohistochemistry. Regular formoterol significantly reduced the number of submucosal mast cells, with a similar trend for eosinophils but not activated T cells. A subgroup analysis conducted in biopsies with >= 10 eosinophils per mm2 revealed a significant reduction in eosinophil numbers when compared with both pretreatment baseline (p < 0.01) and changes after placebo (p < 0.01). Parallel, but less pronounced, effects were observed on mast cell but not on CD25(+) T cell numbers. There was no effect of any of the three treatments on BAL levels of mast cell or eosinophil mediators. We conclude that regular treatment with inhaled formoterol reduces rather than increases inflammatory cells in the mucosa of asthmatic patients. It is possible that these cellular effects of formoterol may contribute to the therapeutic efficacy of this drug when used regularly in the treatment

Administration, Inhalation↗
PubMed1999

Lymphocyte and eosinophil influx into alveolar tissue in nocturnal asthma.

We have shown in nocturnal asthma that alveolar tissue eosinophils are increased at night as compared with the proximal airway, and that they correlate with the overnight decrement in lung function. As the CD4+ cell is thought to be the principal orchestrating cell in eosinophil recruitment, we evaluated its presence in the proximal and distal airways in nocturnal asthma. Eleven patients with nocturnal asthma (NA) and 10 patients with non-nocturnal asthma (NNA) underwent two bronchoscopies with proximal airway endobronchial and distal alveolar tissue transbronchial biopsy in a random order at 4:00 P.M. and at 4:00 A.M. separated by 1 wk. Immunohistochemical staining and morphometric analysis were used to determine the number of CD3+, CD4+, and CD8+ cells and EG2+ eosinophils per mm2 in the epithelium, lamina propria, and alveolar tissue. At 4:00 A.M., the NA group had a significantly greater number of CD4+ cells in the alveolar tissue than the NNA group (9.8 cells/ mm2 [5.6-30.8, interquartile (IQ)] versus 1.5 cells/mm2 [0-6. 3, IQ], p = 0.04). Within the NA group, there were significantly greater numbers of CD3+, CD4+, CD8+, and EG2+ cells in the proximal airway lamina propria than in the distal airway at both 4:00 P.M. and 4:00 A.M. There were no differences within the epithelium between the groups at either time point. Only alveolar tissue, not airway tissue, CD4+ cells correlated inversely with the percentage predicted FEV1 at 4:00 A.M. (r = -0.68, p = 0.0018) and positively with the number of alveolar tissue EG2+ cells (r = 0.66, p = 0.01). These findings suggest that the CD4+ lymphocyte is increased in the alveolar tissue at night in nocturnal asthma as compared with non-nocturnal asthma.

Adult↗
PubMed1999

Wellness intervention with pregnant soldiers.

The purpose of this study was to measure the effects that wellness program intervention for pregnant soldiers, exercise and/or education, had on methods of delivery, pregnancy outcomes, rates of complications, Army Physical Fitness Test scores, and labor and delivery costs. The study consisted of a retrospective review and analysis of 823 active duty Army obstetric and newborn records, 181 Army Physical Fitness Test records, and 411 initial and 148 postpartum subjective questionnaires. Data were collected from records of soldiers who delivered at Madigan Army Medical Center (Tacoma, Washington) between January 1992 and December 1994. Group I (N = 211) included soldiers who received wellness intervention, group II (N = 147) included those who did not receive wellness intervention. Limited data from the records of soldiers who delivered before a wellness program was offered on post constituted group III, a historical control group (N = 413). Group IV included data from a high-risk population (N = 52) collected during the wellness program. Data were also divided into additional subgroups to ascertain if one aspect of the wellness program (i.e., exercise versus education) influenced any or all of the dependent variables. A soldier's data were excluded if a pregnancy was terminated before 20 weeks of gestation or if it was a multiple gestation. Demographic data and variables were compared using multivariate methods of analysis to evaluate the effect of the independent variable, wellness intervention. Results indicated that infants of the wellness group participants had proportionately increased gestational age and birth weight, with reduced incidence of the complications fetal bradycardia, hyperbilirubinemia, preeclampsia, and premature labor. Likewise, African-American female soldiers in this study, assessed in other studies as a high-risk group, had a lower incidence of premature delivery and low birth weight when they participated in wellness intervention. Of clinical interest, it appeared as though wellness intervention shortened labor duration and reduced the number of neonatal intensive care unit admissions and the number of neonatal intensive care unit days, which resulted in reduced health care costs.

Adult↗
PubMed1998

Schizosaccharomyces pombe rad32 protein: a phosphoprotein with an essential phosphoesterase motif required for repair of DNA double strand breaks.

The Schizosaccharomyces pombe Rad32 protein is required for repair of DNA double strand breaks, minichromosome stability and meiotic recombination. We show here that the Rad32 protein is phosphorylated in a cell cycle-dependent manner and during meiosis. The phosphorylation is not dependent on the checkpoint protein Rad3. Analysis of a partially purified protein preparation indicates that Rad32 is likely to act in a complex. Characterisation of the rad32-1 mutation and site-directed mutagenesis indicate that three aspartate residues in the conserved phosphoesterase motifs are important for both mitotic and meiotic functions, namely response to UV and ionising radiation and spore viability.

Adenosine Triphosphatases↗
PubMed1998

Characterisation of the neuropeptide Y receptor that mediates feeding in the rat: a role for the Y5 receptor?

Food intake was measured in freely fed rats following intracerebroventricular administration of neuropeptide Y (NPY) and several of its analogues and antagonists to investigate the hypothesis that the NPY Y5 receptor mediates feeding. Rat NPY (rNPY), rNPY(2-36) and rNPY(3-36) produced similar feeding responses over the dose range 0.7-7.0 nmol. Rat peptide YY (rPYY) was more potent and at least as efficacious as rNPY. [Leu31 Pro34]-rNPY (agonist potency: Y1 > Y5 > Y4 = y6) and human pancreatic polypeptide (hPP) produced flatter dose-response curves, suggesting partial agonism at the receptor(s). rNPY(13-36) (agonist potency: Y2 > Y5) had little activity and rPP was inactive. [D-Trp32]-NPY was a weak orexigenic agent given alone and, consistent with partial agonism, it markedly antagonised the response to porcine NPY (pNPY). Similarly, the receptor antagonist (Y1 > Y4) 1229U91 stimulated feeding slightly, and markedly inhibited rNPY-induced feeding. In contrast to a previous report, BIBP 3226 (70 nmol), another Y1 receptor antagonist, failed to inhibit the response to rNPY. Our data in vivo are inconsistent with findings that hPP, [Leu31 Pro34]-rNPY and [D-Trp32]-rNPY are full agonists at the rat cloned Y5 receptor. Thus, whilst the Y5 receptor may be involved, its participation as the sole receptor mediating the orexigenic action of NPY in the rat remains unproven.

Animals↗
PubMed1998

Phosphorylation of rat insulin-like growth factor binding protein-1 does not affect its biological properties.

Insulin-like growth factors (IGFs) I and II stimulate growth and expression of specific genes through binding to cell membrane receptors. IGF binding proteins also bind IGF-I with higher affinity than the receptor. They are found in the circulation and tissues and can modulate IGF actions. Human IGFBP-1 is phosphorylated on serine residues, which increases its affinity for IGF-I. An acidic, presumably phosphorylated, form of human IGFBP-1 inhibits IGF-I-stimulated DNA synthesis in cultured cells, while a less acidic, unphosphorylated form potentiates this function. Phosphorylation of human IGFBP-3, however, does not affect its affinity for IGF-I. Previously we found that multiple forms of rat IGFBP-1 are obtained by anion-exchange chromatography, raising the possibility that it also is phosphorylated, which led us to examine its properties. Phosphopeptide analysis of 32P-labeled, immunoprecipitated rat IGFBP-1 synthesized by H-4-II-EC3 rat hepatoma cells indicated that it is phosphorylated on two sites that were deduced to be ser107 and ser132 in the central nonconserved domain. Dephosphorylation of purified phosphorylated rat IGFBP-1 did not affect its affinity for IGF-I or its specific binding activity, and the dephosphorylated form inhibited DNA synthesis in 3T3 cells. Incubation of cells labeled with radioactive proline in the presence of monensin and brefeldin A, which inhibit secretion at different sites, led to intracellular accumulation of the least phosphorylated form of rat IGFBP-1, but prevented further phosphorylation. The results suggested that phosphorylation occurs at two sites in cells, the cis-Golgi and the trans-Golgi network. In summary, these studies have shown that rat IGFBP-1 is phosphorylated on two sites by reactions that occur in different secretory organelles and that similar to human IGFBP-3, but unlike human IGFBP-1, phosphorylation does not affect its affinity for IGF-I.

3T3 Cells↗
PubMed1998

An enhancer region within the copia untranslated leader contains binding sites for Drosophila regulatory proteins.

The untranslated leader region (ULR) of the Drosophila LTR retrotransposon copia is known to be critical to the element's expression in a variety of species. Two copia ULR size variants are prevalent in natural populations. The more transcriptionally active full length variants contain within their ULRs two tandemly repeated copies of a 28-bp region of dyad symmetry with a sequence similarity to the core sequence of the SV40 enhancer. The region of dyad symmetry contains two inverted repeats of a 8-bp motif (TTGTGAAA) that occurs at three additional locations within the ULR. The less active ULR gap variants differ from full length variants in that they contain only one copy of the 28-bp sequence. We show that the full length copia ULR in either orientation but not the gap ULR can significantly enhance expression of a minimal hsp 70 promoter. We demonstrate by EMSA that the full length ULR, the gap ULR and the 28-bp sequence are each capable of binding the Drosophila CCAAT/enhancer binding protein (DmC/EBP) and another previously uncharacterized factor, copia binding factor-1 (CBF-1). Another Drosophila protein previously implicated in fat body specific expression of the alcohol dehydrogenase gene (Adh), the Box-B-binding factor-2 (BBF-2), is also shown to bind to the copia ULR.

Animals↗
PubMed1998

Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior.

The hypothalamus plays a central role in the integrated control of feeding and energy homeostasis. We have identified two novel neuropeptides, both derived from the same precursor by proteolytic processing, that bind and activate two closely related (previously) orphan G protein-coupled receptors. These peptides, termed orexin-A and -B, have no significant structural similarities to known families of regulatory peptides. prepro-orexin mRNA and immunoreactive orexin-A are localized in neurons within and around the lateral and posterior hypothalamus in the adult rat brain. When administered centrally to rats, these peptides stimulate food consumption. prepro-orexin mRNA level is up-regulated upon fasting, suggesting a physiological role for the peptides as mediators in the central feedback mechanism that regulates feeding behavior.

Animals↗
PubMed1998

Tolerance to ischaemia and ischaemic preconditioning in neonatal rat heart.

Although there is much information on ischaemic preconditioning in the adult myocardium, this phenomenon has not yet been investigated in neonatal hearts. To examine the early development of cardiac tolerance to ischaemia and the possible protective effects of preconditioning, rat hearts isolated on days 1, 4 and 7 of postnatal life were perfused (Langendorff) with Krebs-Henseleit solution at constant pressure, temperature (37 degrees C) and rate (200 beats/min). Developed force (DF) of contraction was measured by an isometric force transducer, and analysed using an on-line computer. Hearts were exposed to 40 or 60 min of global ischaemia followed by 30 min of reperfusion. Preconditioning was induced by three 3-min periods of global ischaemia, each separated by 5-min periods of reperfusion. Developmental changes in expression of protein kinase C (PKC) isoforms, and their activation following preconditioning, were estimated using Western blot analysis. Recovery of contractile function during reperfusion decreased from day 1 (48 +/- 2%) to day 4 (42 +/- 1%) and day 7 (33 +/- 2%). Preconditioning failed to improve ischaemic tolerance on day 1 (46 +/- 2%) and on day 4 (43 +/- 3%), but pronounced effect was observed on day 7 (40 +/- 2%). Prolonging the period of sustained ischaemia from 40 to 60 min on day 1 did not lead to a better recovery of contractile function in preconditioned hearts. PKC isoforms alpha, delta, epsilon and zeta were expressed in the ventricular myocardium during the first week of life, but there was no evidence of translocation following preconditioning on day 7. It may be assumed that the decreasing tolerance of the heart to ischaemia during early postnatal life is counteracted by the development of an endogenous protection.

Animals↗