PubMed Health⌕ Search

Biomedical subjects

B Lawson

Publications and source records attributed to B Lawson.

At least 19 recordsLinked to original sources
PubMed2006

Administration of fludarabine-loaded autologous red blood cells in simian immunodeficiency virus-infected sooty mangabeys depletes pSTAT-1-expressing macrophages and delays the rebound of viremia after suspension of antiretroviral therapy.

A major limitation of highly active antiretroviral therapy is that it fails to eradicate human immunodeficiency virus (HIV) infection due to its limited effects on viral reservoirs carrying replication-competent HIV, including monocytes/macrophages (M/M). Therefore, therapeutic approaches aimed at targeting HIV-infected M/M may prove useful in the clinical management of HIV-infected patients. In previous studies, we have shown that administration of fludarabine-loaded red blood cells (RBC) in vitro selectively induces cell death in HIV-infected M/M via a pSTAT1-dependent pathway. To determine the in vivo efficacy of this novel therapeutic strategy, we treated six naturally simian immunodeficiency virus (SIV)-infected sooty mangabeys (SMs) with either 9-[2-(R)-(phosphonomethoxy)propyl]adenine (PMPA) only, fludarabine-loaded RBC only, or PMPA in association with fludarabine-loaded RBC. The rationale of this treatment was to target infected M/M with fludarabine-loaded RBC at a time when PMPA is suppressing viral replication taking place in activated CD4+ T cells. In vivo administration of fludarabine-loaded RBC was well tolerated and did not induce any discernible side effect. Importantly, addition of fludarabine-loaded RBC to PMPA delayed the rebound of viral replication after suspension of therapy, thus suggesting a reduction in the size of SIV reservoirs. While administrations of fludarabine-loaded RBC did not induce any change in the CD4+ or CD8+ T-cell compartments, we observed, in chronically SIV-infected SMs, a selective depletion of M/M expressing pSTAT1. This study suggests that therapeutic strategies based on the administration of fludarabine-loaded RBC may be further explored as interventions aimed at reducing the size of the M/M reservoirs during chronic HIV infection.

Adenine↗
PubMed2005

Exposure of garden birds to aflatoxins in Britain.

Aflatoxins are potent biological toxins that have been shown to exert a range of acute and chronic pathological effects. Multiple mortality events of waterfowl caused by acute aflatoxicosis have been documented in the USA. However, international concern has recently been expressed regarding the potential effects of chronic exposure of wildlife species to low levels of dietary aflatoxin. This study documents for the first time the presence of hepatic aflatoxin residues in British wild birds: two passerine species, the house sparrow (Passer domesticus) and greenfinch (Carduelis chloris). Further research is required to investigate the source of the dietary aflatoxins and their pathological significance, if any, for wild birds in Britain.

Aflatoxins↗
PubMed2003

Childhood medulloblastoma in northwest England 1954 to 1997: incidence and survival.

The incidence, survival patterns, and presenting symptoms of children with medulloblastoma were studied. Data were ascertained from the Manchester Tumour Registry which is population-based and has collected data on all childhood malignancies in northwest England since 1954. Incidence rates standardized to the European standard population were calculated and Poisson regression models were used to examine temporal changes in the incidence rates during the period 1954 to 1997. Kaplan-Meier survival curves were derived and used to study changes in survival patterns. World-standardized incidence rates were 5.5 per million child years in males and 3.4 per million child years in females. Incidence rates increased from the 1950s to the 1980s but have declined recently. The 5-year survival rate has improved from 29 to 58% with similar rates for males and females. The 1-year survival rate has also improved, but females had worse survival at this point (58%) than males (75%). The type of symptom or sign at presentation is strongly affected by age, with 10 of the 22 recorded symptoms or signs showing significant age differences. The older the child is, the more likely is the presentation to show pressure features of headache, vomiting, and ophthalmic signs. Younger children present with non-specific features such as lethargy, behavioural disturbance, or increasing head size. Ataxia is seen in about 75% of children across the age range.

Adolescent↗
PubMed2001

[Central pontine myelinolysis and hyponatremia. Clinical case].

There is a controversy whether central pontine myelinolysis can complicate either hyponatremia or its rapid correction. We report a 69 years old woman with a history of one month of vertigo, nausea, vomiting and diarrhea. She was admitted dehydrated ad stuporous, and initial laboratory values showed a serum sodium of 96 mEq/L. She was treated with dextrose 5% and 3% NaCl. Serum sodium raised to 120 mEq/L at the next day and the level of consciousness improved. At the 4th day of admission, the patient was again stuporous and with spastic quadriplegia. A magnetic resonance imaging showed a central and symmetrical pontine lesion on T1 and T2 weighed images. Thereafter, the patient experienced a progressive improvement of her neurological condition and was discharged three months later, moving her lower limbs. Nine month later she was able to walk.

Aged↗
PubMed2000

Hospital design. Room for improvement.

Psychiatric and orthopaedic patients treated in new or upgraded units rated their experience and treatment significantly higher than those on old wards. Length of stay on the new psychiatric unit was lower than in the old unit. Orthopaedic patients treated on a refurbished ward required fewer analgesics than those on the older ward. Patients treated in single rooms were more satisfied with their care than those treated in multiple-bed wards.

Health Facility Environment↗
PubMed1999

[Behavior disorder of the REM sleep in 2 documented cases with polysomnography].

We report a 69 years old male with a parkinsonian syndrome and a 50 years old female without neurological problems who showed violent behavior during REM sleep. Polysomnography showed that both bad tonic or phasic muscular activity during REM sleep and a REM sleep behavior disorder was diagnosed. Clonazepam was used in both, with good clinical response. This condition is frequently unrecognized and confused with nightmares, nocturnal delirium or other parasomnias.

Aged↗
PubMed1998

Geldanamycin, an hsp90/GRP94-binding drug, induces increased transcription of endoplasmic reticulum (ER) chaperones via the ER stress pathway.

Geldanamycin, a benzoquinone ansamycin, binds specifically to hsp90 and GRP94 in vitro and in vivo. Treatment of cells with geldanamycin alters the molecular chaperone function of hsp90, and as a result, blocks certain cytosolic proteins from reaching their mature form, inhibits their activity, and/or affects their stability. In contrast, little is known about either the effects of geldanamycin on GRP94, the endoplasmic reticulum (ER) homologue of hsp90, or the role of GRP94 in protein folding. In this study, we demonstrate in a variety of cell lines that geldanamycin is a potent inducer of the cellular response to stress in the ER, resulting in the transcriptional up-regulation of ER chaperones and expression of the gadd153/CHOP transcription factor. Their induction occurs through the unfolded protein response pathway originating in the ER and is not due to effects of the drug on hsp90. Geldanamycin increases the association of nascent proteins with BiP, which indicates that their folding and/or assembly has been altered. These data suggest that GRP94 may play an essential role in the maturation of a number of secretory pathway proteins.

3T3 Cells↗
PubMed1998

Aftereffects and sense of presence in virtual environments: formulation of a research and development agenda.

This report represents a committee summary of the current state of knowledge regarding aftereffects and sense of presence in virtual environments (VEs). The work presented in this article, and the proposed research agenda, are the result of a special session that was set up in the framework of the Seventh International Conference on Human Computer Interaction. Recommendations were made by the committee regarding research needs in aftereffects and sense of presence, and, where possible, priorities were suggested. The research needs were structured in terms of the short, medium, and long term and, if followed, should lead toward the effective use of VE technology. The 2 most critical research issues identified were (a) standardization and use of measurement approaches for aftereffects and (b) identification and prioritization of sensorimotor discordances that drive aftereffects. Identification of aftereffects countermeasures (i.e., techniques to assist users in readily transitioning between the real and virtual worlds), reduction of system response latencies, and improvements in tracking technology were also thought to be of critical importance.

Adaptation, Physiological↗
PubMed1996

Signals from the stressed endoplasmic reticulum induce C/EBP-homologous protein (CHOP/GADD153).

The gene encoding C/EBP-homologous protein (CHOP), also known as growth arrest and DNA-damage-inducible gene 153 (GADD153), is activated by agents that adversely affect the function of the endoplasmic reticulum (ER). Because of the pleiotropic effects of such agents on other cellular processes, the role of ER stress in inducing CHOP gene expression has remained unclear. We find that cells with conditional (temperature-sensitive) defects in protein glycosylation (CHO K12 and BHK tsBN7) induce CHOP when cultured at the nonpermissive temperature. In addition, cells that are defective in initiating the ER stress response, because of overexpression of an exogenous ER chaperone, BiP/GRP78, exhibit attenuated inducibility of CHOP. Surprisingly, attenuated induction of CHOP was also noted in BiP-overexpressing cells treated with methyl methanesulfonate, an agent thought to activate CHOP by causing DNA damage. The roles of DNA damage and growth arrest in the induction of CHOP were therefore reexamined. Induction of growth arrest by culture to confluence or treatment with the enzymatic inhibitor N-(phosphonacetyl)-L-aspartate did not induce CHOP. Furthermore, both a DNA-damage-causing nucleoside analog (5-hydroxymethyl-2'-deoxyuridine) and UV light alone did not induce CHOP. These results suggest that CHOP is more responsive to ER stress than to growth arrest or DNA damage and indicate a potential role for CHOP in linking stress in the ER to alterations in gene expression.

3T3 Cells↗
PubMed1995

The antidiuretic effect of pneumadin requires a functional arginine vasopressin system.

Pneumadin is an antidiuretic decapeptide, recently isolated from rat and human lung. Bolus intravenous injection of 5 nmol of pneumadin into water-loaded rats caused a rapid and significant antidiuresis and a reduction in Na+ and Cl- excretion. Pneumadin administration did not alter mean arterial pressure, right atrial pressure, heart rate or haematocrit. Bolus intravenous injection of 20 nmol of pneumadin into non-water-loaded rats caused a significant increase in arginine vasopressin (AVP) within 10 min. Pneumadin administration also increased circulating atrial natriuretic peptide (ANP) but did not alter aldosterone or plasma renin activity levels. Injection of pneumadin into water-loaded Brattleboro rats, which genetically lack circulating AVP, did not change urine flow, confirming that the pneumadin induced antidiuresis is AVP dependent. Radioactive pneumadin was cleared from the circulation with a t1/2 beta of 480.3 s. Radioactive pneumadin, isolated from plasma, eluted at an altered position on reverse phase HPLC, which indicated that the peptide was modified in vivo. This modification was also observed when synthetic pneumadin was incubated in rat plasma in vitro. Purification and sequencing of the modified synthetic peptide indicated that the modification is not a proteolytic cleavage. These results indicate that pneumadin injected into the rat caused an antidiuresis by altering circulating AVP levels.

Aldosterone↗
PubMed1995

In vivo expression of mammalian BiP ATPase mutants causes disruption of the endoplasmic reticulum.

BiP possesses ATP binding/hydrolysis activities that are thought to be essential for its ability to chaperone protein folding and assembly in the endoplasmic reticulum (ER). We have produced a series of point mutations in a hamster BiP clone that inhibit ATPase activity and have generated a species-specific anti-BiP antibody to monitor the effects of mutant hamster BiP expression in COS monkey cells. The enzymatic inactivation of BiP did not interfere with its ability to bind to Ig heavy chains in vivo but did inhibit ATP-mediated release of heavy chains in vitro. Immunofluorescence staining and electron microscopy revealed vesiculation of the ER membranes in COS cells expressing BiP ATPase mutants. ER disruption was not observed when a "44K" fragment of BiP that did not include the protein binding domain was similarly mutated but was observed when the protein binding region of BiP was expressed without an ATP binding domain. This suggests that BiP binding to target proteins as an inactive chaperone is responsible for the ER disruption. This is the first report on the in vivo expression of mammalian BiP mutants and is demonstration that in vitro-identified ATPase mutants behave as dominant negative mutants when expressed in vivo.

Adenosine Triphosphatases↗
PubMed1987

Brain oxidative phosphorylation following alteration in head position in preterm and term neonates.

An alteration in head position, which effects cerebral blood flow, may increase the risk for intraventricular hemorrhage in the critically ill infant. The purpose of this study was to evaluate in vivo cerebral oxidative metabolism as an index of tissue oxygen delivery reflecting brain blood flow, in healthy preterm and term infants following a change in head position. Cerebral phosphoenergetics using 31 phosphorus nuclear magnetic resonance spectroscopy were measured in 10 preterm and eight term infants following three different head positions: neutral, prone, and supine. All infants were clinically stable at the time of study. The phosphocreatine to inorganic phosphate ratio, an indicator of bioenergetic reserve, was determined. The mean +/- SD for phosphocreatine to inorganic phosphate ratio in the neutral position in preterm and term infants was 1.08 +/- 0.15 and 1.12 +/- 0.21, respectively, and did not change significantly following head turning. These data suggest that any alteration in cerebral blood flow as a result of a change in head position in the healthy neonate may be compensated by physiological and biochemical regulations so that no changes in brain oxidative phosphorylation are measurable.

Brain↗