Search PubMed⌕ Search

Biomedical subjects

J Watson

Publications and source records attributed to J Watson.

At least 109 records · Page 6Linked to original sources
PubMed1998

Functional effects of the muscarinic receptor agonist, xanomeline, at 5-HT1 and 5-HT2 receptors.

Xanomeline [3(3-hexyloxy-1,2,5-thiadiazol-4-yl)-1,2,5,6-tetrahydro-1-me thylpyridine] has been reported to act as a functionally selective muscarinic partial agonist with potential use in the treatment of Alzheimer's disease. This study examined the functional activity of xanomeline at 5-HT1 and 5-HT2 receptors in native tissue and/or human cloned receptors. Xanomeline had affinity for muscarinic receptors in rat cortical membranes where the ratio of the displacement affinity of [3H]-Quinuclidinyl benzilate vs that of [3H]-Oxotremorine-M was 16, indicative of partial agonist activity. Radioligand binding studies on human cloned receptors confirmed that xanomeline had substantial affinity for M1, M2, M3, M4, M5 receptors and also for 5-HT1 and 5-HT2 receptor subtypes. Carbachol and xanomeline stimulated basal [35S]-GTPgammaS binding in rat cortical membranes with micromolar affinity. The response to carbachol was attenuated by himbacine and pirenzepine with pA2 of 8.2, 6.9 respectively consistent with the response being mediated, predominantly, via M2 and M4 receptors. Xanomeline-induced stimulation of [35S]-GTPgammaS binding was inhibited by himbacine with an apparent pKb of 6.3, was not attenuated by pirenzepine up to 3 microM and was inhibited by the selective 5-HT1A antagonist WAY100635 with an apparent pKb of 9.4. These data suggest the agonist effect of xanomeline in this tissue is, in part, via 5-HT1A receptors. Similar studies on human cloned receptors confirmed that xanomeline is an agonist at human cloned 5-HT1A and 5-HT1B receptors. In studies using the fluorescent cytoplasmic Ca2+ indicator FLUO-3AM, xanomeline induced an increase in cytoplasmic Ca2+ concentration in SH-SY5Y cells expressing recombinant human 5-HT2C receptors. Atropine antagonized this response, consistent with mediation via endogenously-expressed muscarinic receptors. In the presence of atropine, xanomeline antagonized 5-HT-induced cytoplasmic changes in Ca2+ concentration in cells expressing h5-HT2A, h5-HT2B and h5-HT2c receptors with potencies similar to its affinity at these receptors. These studies indicate that xanomeline is a potent agonist at 5-HT1A and 5-HT1B receptors and an antagonist at 5-HT2 receptor subtypes.

Animals↗
PubMed1998

Older women, medication use and nursing care.

The purpose of this study is to listen to and interpret the experiences of independent older women in the community regarding their medication use. Their experiences were examined regarding medication information, sources of information, types of medication used, relationships with health care professionals and social support systems. The techniques used for data collection included guided qualitative semistructured interviews based on the principle of empowerment and notions of ideal and nonhierarchical communication. The emergent themes show that for these older women general practitioners were important in their medication experiences. Whilst trusted as carers in the acute care setting, registered nurses did not play a role in the medication experiences of these older women. Registered nurses are perceived as 'traditional carers' associated with medical and acute care settings. Although medication issues emerged that ideally required attention, the older women in this study generally perceived themselves to be capable of actively managing their health and medication use.

Aged↗
PubMed1998

Silencer and enhancer regions in the human CD95 (Fas/APO-1) gene with sequence similarity to the granulocyte-macrophage colony-stimulating factor promoter: binding of single strand-specific silencer factors and AP-1 and NF-AT-like enhancer factors.

The CD95 (Fas/APO-1) apoptosis receptor is expressed in a variety of tissues and transiently upregulated in lymphocytes during activation-induced cell death. A silencer (S1; -1035 to -1008) and an adjacent enhancer (E1; -1007 to -964) region have been mapped in the CD95 gene. The S1 region shows similarity to binding sites for the transcriptional repressor NF-GMb, which prefers binding to single-stranded DNA. The E1 contains an everted repeat of two CATTA/T elements spaced by 2 bp (ER2). Such motifs are directly repeated in the CLE0 region of the human granulocyte-macrophage colony-stimulating factor (huGM-CSF) promoter. A motif (TGATGTCA) which matches a CREB site and is similar to an AP-1 site is embedded within ER2. Sequence-specific binding of nuclear factors to single-stranded S1 probes involved, to some extent, a central heptamer motif (ATCCAAA) also present in E1. Competition binding studies suggested that AP-1 or AP-1 components, as well as factors related, but not identical, to NF-AT bound to E1 probes. S1-binding-proteins/complexes of 47, 77, and 100 kDa were detected by Southwestern analysis and ultraviolet crosslinking. Complexes of 70 and 80 kDa were formed with a double-stranded E1 probe in UV-crosslinking, whereas Southwestern analysis with this probe revealed single binding species of 59 and 113 kDa. ER2 autonomously enhanced transcription from the heterologous HSV tk promoter in a cell type-specific manner only in the absence of the S1 region. This analysis has identified a small region in the CD95 gene containing adjacent opposing regulatory elements which are likely to be involved in the cell type- and activation state-specific gene expression under physiologic conditions.

Animals↗
PubMed1998

The self-reported well-being of employees facing organizational change: effects of an intervention.

The objective of this study was to investigate the self-reported well-being of employees facing organizational change, and the effect of an intervention. It was a controlled intervention study. Subjects were allocated to study and control groups, and brief individual counselling was offered to the subjects in the study groups. Questionnaire measures were administered before and after counselling (a 3-month interval), and non-counselled subjects also completed questionnaires at the same times. The setting was 15 estate offices in an urban local authority Housing Department. Subjects comprised the total workforce of the Housing Management division: 193 employees, male and female, aged 22-62 years, facing compulsory competitive tendering between 1994-97. Main outcome measures were baseline and comparative measures of psychological morbidity, including the General Health Questionnaire (GHQ) and the Occupational Stress Indicator (OSI). Questionnaire response rates were 72% and 47% on first and second occasions respectively. The uptake of counselling was 37%. In comparison with (1) the UK norms for the OSI and (2) the norms for a similar occupational group, this group of workers were under more work-related pressure and their self-reported health was markedly poorer. They were not however at a disadvantage in terms of coping strategies. Those accepting the offer of counselling were subject to greater levels of work stress, had poorer self-reported health and markedly lower levels of job satisfaction than those who did not. Questionnaire scores were not significantly different before and after counselling, giving no evidence of treatment effects on symptomatology. However, almost all subjects rated counselling as having been extremely helpful. This study suggests that adverse effects on staff facing organizational change may be ameliorated by improved management practice.

Adult↗
PubMed1998

Personal experience with ultrasound-assisted lipoplasty: a pilot study comparing ultrasound-assisted lipoplasty with traditional lipoplasty.

Body contouring with traditional suction-assisted lipoplasty is currently the most commonly performed aesthetic surgical procedure. In competent hands, traditional lipoplasty has a low complication rate, a short recovery period, and a high patient satisfaction rate. Body contouring with ultrasound-assisted lipoplasty has recently gained considerable attention, and its proponents have claimed many benefits over the traditional method. This pilot study consists of one surgeon's clinical experience with ultrasound-assisted lipoplasty in 100 cases. In 63 of these patients, ipsilateral traditional lipoplasty and contralateral ultrasound-assisted lipoplasty were done on one or more body areas. These patients were blinded in the study. Complication rates, lipocrits from the aspirate, postoperative ecchymosis, postoperative swelling, patient satisfaction, and surgeon satisfaction were then compared for each patient studied. Ten randomly selected patients were also evaluated by an independent panel of reviewers who compared ecchymosis and swelling in ultrasound-assisted versus traditional lipoplasty-treated areas. Their observations in this subset of 10 patients were subjected to statistical analysis. This initial pilot study failed to prove most of the benefits attributed to ultrasound-assisted lipoplasty by other surgeons. However, the method is an evolving technology, and the authors remain optimistic about the role of ultrasound in body sculpting surgery.

Aged↗
PubMed1998

Streptomyces griseus protease B: secretion correlates with the length of the propeptide.

Streptomyces griseus protease B, a member of the chymotrypsin superfamily, is encoded by a gene that express a pre-pro-mature protein. During secretion the precursor protein is processed into a mature, fully folded protease. In this study, we constructed a family of genes which encode deletions at the amino-terminal end of the propeptide. The secretion of active protease B was seen to decrease in an exponential manner according to the length of the deletion. The results underscore the intimate relationship between folding and secretion in bacterial protease expression. They further suggest that the propeptide segment of the zymogen stabilizes the folding of the mature through many small binding interactions over the entire surface of the peptide rather than through a few specific contacts.

Binding Sites↗
PubMed1998

ELAV protein HuA (HuR) can redistribute between nucleus and cytoplasm and is upregulated during serum stimulation and T cell activation.

ELAV proteins are implicated in regulating the stability and translation of cytokine and growth regulatory mRNAs such as GM-CSF, IL-2, c-myc, c-fos and GLUT1 by binding to their AU-rich 3'UTRs. The tissue-specific ELAV protein HuB (aka. Hel-N1) is predominantly cytoplasmic and has been shown to stabilize GLUT1 and c-myc mRNAs and to increase their translation following ectopic expression in 3T3-L1 cells. We report that the most widely expressed mouse ELAV protein, mHuA, is predominately nuclear in cultured NIH-3T3 cells, but is localized in the cytoplasm during early G1 of the cell cycle. Therefore, much like the primarily cytoplasmic HuB, HuA becomes temporally localized in the cytoplasm where it can potentially regulate the stability or translation of bound mRNAs. Moreover, we report that stimulation of mouse spleen cells using either mitogenic or sub-mitogenic levels of anti-CD3/CD28 resulted in a dramatic increase in the level of HuA. Upregulation of HuA corresponds to previously documented increases in cytokine expression which are due to increased mRNA stability following T cell activation. Consistent with these findings, HuA was down regulated in quiescent cells and upregulated in 3T3 cells following serum stimulation. The increase of murine HuA during the cell cycle closely resembles that of cyclin B1 which peaks in G2/M. Together with our earlier studies, these data indicate that mammalian ELAV proteins function during cell growth and differentiation due in part to their effects on posttranscriptional stability and translation of multiple growth regulatory mRNAs. This supports the hypothesis that ELAV proteins can function as transacting factors which affect a default pathway of mRNA degradation involved in the expression of growth regulatory proteins.

3T3 Cells↗
PubMed1998

Perceptual strategies in phonological disorder: assessment, remediation and evaluation.

Evidence is presented that immature perceptual strategies are a contributory factor to developmental phonological disorder. The findings endorse the current re-focusing of attention on the role of perception in disordered speech and language acquisition and also highlight the need for more precise assessment and remediation techniques. Technical developments working towards providing these are reviewed and implications for future clinical practice discussed.

Auditory Perceptual Disorders↗
PubMed1998

Positive biochemical effects of a bioartificial liver support system (BALSS) in a porcine fulminant hepatic failure (FHF) model.

This study describes biochemical changes in the plasma and blood of pigs with devascularised livers treated in a bioartificial liver support system (BALSS). Porcine hepatic cells were incubated with collagen-coated dextran microspheres (CDM) for 3 hours and the medium tested to determine cellular metabolic activity. Incubation continued for a further 18 hours during which the hepatic cells attach to the CDM. The CDM-attached cells were inoculated into a hollow fibre bioreactor which was part of an extracorporeal support system. Hepatic cell content of the bioreactor was 6 x 10(9) cells. The system was tested in a controlled trial in pigs prepared in a surgical model of fulminant hepatic failure (FHF). When plasma from FHF pigs was circulated through the device containing hepatic cells, there was significantly less increase in the accumulation of ammonia and most amino acids, together with a decrease in plasma lactate and of one amino acid, compared to control experiments when hepatic cells were excluded. We conclude that primary porcine hepatocytes can contribute beneficial metabolic function in a BALSS.

Adenosine Triphosphate↗
PubMed1998

Compartment syndrome: new insights.

Long recognized as a potential problem in trauma patients or victims of acute extremity ischemia, compartment syndrome is seen in other patient populations as well. In such patients, the absence of timely diagnosis and effective treatment inevitably results in loss of extremity neuromuscular function. New insights into the pathophysiology of compartment syndrome provide opportunities for earlier and more accurate recognition as well as the possibility that the morbid consequences of the syndrome might be mitigated or in certain settings even prevented.

Compartment Syndromes↗
PubMed1997

Ro31-8220 inhibits protein kinase C to block the phorbol ester-stimulated release of choline- and ethanolamine-metabolites from C6 glioma cells: p70 S6 kinase and MAPKAP kinase-1beta do not function downstream of PKC in activating PLD.

The use of bisindolylmaleimide derivatives of staurosporine as selective inhibitors of protein kinase C (PKC) is in doubt following the report by Alessi [FEBS Lett. 402 (1997) 121-123] that Ro31-8220 and GF109203X are potent in vitro inhibitors of p70 S6 kinase and mitogen-activated protein kinase-activated protein kinase-1beta, as well as of PKC. Here we show that the phorbol ester-stimulated release of choline- and ethanolamine-metabolites from C6 glioma cells due to phospholipid hydrolysis by phospholipase D (PLD) is not inhibited by rapamycin or PD98059, specific inhibitors respectively of p70 S6 kinase and MAPKK (MEK) and thus of MAPKAP kinase-1beta but is still completely blocked by Ro31-8220. We conclude therefore that p70S6k and MAPKAP kinase-1beta as well as MAPK are not involved in signalling pathways downstream of PKC that regulate phorbol ester-stimulated phospholipid turnover and that the inhibitory action of Ro31-8220 occurs by blocking PKC which regulates at least one pathway to PLD activation. The PI-3 kinase inhibitor, wortmannin, inhibits the phorbol ester-stimulated release of ethanolamine- but not choline-metabolites from C6 cells suggesting that different PLD isoforms regulate the turnover of PtdEth and PtdCho in C6 cells. Both PLD isoforms are activated via PKC but the PtdEth-PLD is also regulated via a wortmannin-sensitive pathway.

Androstadienes↗