PubMed Health⌕ Search

Biomedical subjects

David Berry

Publications and source records attributed to David Berry.

At least 19 recordsLinked to original sources
PubMed2006

Heparin localization and fine structure regulate Burkitt's lymphoma growth.

Burkitt's lymphoma (BL) is a B-cell malignancy associated with the Epstein-Barr virus (EBV). Mounting evidence has implicated heparan sulfate proteoglycans and heparan sulfate-like glycosaminoglycans (HSGAGs) in the initiation, severity, and progression of the malignancy. The importance of HSGAGs in regulating BL cell growth was therefore examined. Extracellular exogenous heparin inhibited cell growth >30%, while heparin internalized with poly(beta-amino ester)s promoted proliferation up to 58%. The growth-modulating effects of heparin and internalized heparin were dependent on cell surface HSGAGs, PI3K, and Erk/Mek. Treatment of cells with protamine sulfate or with heparinases potently inhibited proliferation, with the greatest effects induced by heparinase I. Cell surface HSGAGs therefore play an important role in regulating BL proliferation and may offer a potential target for therapeutic intervention.

Burkitt Lymphoma↗
PubMed2006

Microbial ecology of drinking water distribution systems.

The supply of clean drinking water is a major, and relatively recent, public health milestone. Control of microbial growth in drinking water distribution systems, often achieved through the addition of disinfectants, is essential to limiting waterborne illness, particularly in immunocompromised subpopulations. Recent inquiries into the microbial ecology of distribution systems have found that pathogen resistance to chlorination is affected by microbial community diversity and interspecies relationships. Research indicates that multispecies biofilms are generally more resistant to disinfection than single-species biofilms. Other recent findings are the increased survival of the bacterial pathogen Legionella pneumophila when present inside its protozoan host Hartmannella vermiformis and the depletion of chloramine disinfectant residuals by nitrifying bacteria, leading to increased overall microbial growth. Interactions such as these are unaccounted for in current disinfection models. An understanding of the microbial ecology of distribution systems is necessary to design innovative and effective control strategies that will ensure safe and high-quality drinking water.

Animals↗
PubMed2006

Axonal protection achieved in a model of multiple sclerosis using lamotrigine.

Axonal degeneration is a major cause of permanent disability in multiple sclerosis (MS). Recent observations from our and other laboratories suggest that sodium accumulation within compromised axons is a key, early step in the degenerative process, and hence that limiting axonal sodium influx may represent a mechanism for axonal protection in MS. Here we assess whether lamotrigine, a sodium channel-blocking agent, is effective in preventing axonal degeneration in an animal model of MS, namely chronic-relapsing experimental autoimmune encephalomyelitis (CR-EAE). When administered from 7 days post-inoculation, lamotrigine provided a small but significant reduction in the neurological deficit present at the termination of the experiments (averaged over three independent experiments; vehicle: 3.5+/-2.7; lamotrigine: 2.6+/-2.0, P<0.05) and preserved more functional axons in the spinal cord (measured as mean compound action potential area; vehicle: 31.7 microV.ms+/-23.0; lamotrigine: 42.9+/-27.4, P<0.05). Histological examination of the thoracic spinal cord (n=71) revealed that lamotrigine treatment also provided significant protection against axonal degeneration (percentage degeneration in dorsal column; vehicle: 33.5 %+/-38.5; lamotrigine: 10.4 %+/-12.5, P<0.01). The findings suggest that lamotrigine may provide a novel avenue for axonal protection in MS.

Action Potentials↗
PubMed2006

Interactions between antiepileptic and antipsychotic drugs.

Antiepileptic and antipsychotic drugs are often prescribed together. Interactions between the drugs may affect both efficacy and toxicity. This is a review of human clinical data on the interactions between the antiepileptic drugs carbamazepine, valproic acid (sodium valproate), vigabatrin, lamotrigine, gabapentin, topiramate, tiagabine, oxcarbazepine, levetiracetam, pregabalin, felbamate, zonisamide, phenobarbital and phenytoin with the antipsychotic drugs risperidone, olanzapine, quetiapine, clozapine, amisulpride, sulpiride, ziprasidone, aripiprazole, haloperidol and chlorpromazine; the limited information on interactions between antiepileptic drugs and zuclopenthixol, periciazine, fluphenazine, flupenthixol and pimozide is also presented. Many of the interactions depend on the induction or inhibition of the cytochrome P450 isoenzymes, but other important mechanisms involve the uridine diphosphate glucuronosyltransferase isoenzymes and protein binding. There is some evidence for the following effects. Carbamazepine decreases the plasma concentrations of both risperidone and its active metabolite. It also decreases concentrations of olanzapine, clozapine, ziprasidone, haloperidol, zuclopenthixol, flupenthixol and probably chlorpromazine and fluphenazine. Quetiapine increases the ratio of carbamazepine epoxide to carbamazepine and this may lead to toxicity. The data on valproic acid are conflicting; it may either increase or decrease clozapine concentrations, and it appears to decrease aripiprazole concentrations. Chlorpromazine possibly increases valproic acid concentrations. Lamotrigine possibly increases clozapine concentrations. Phenobarbital decreases clozapine, haloperidol and chlorpromazine concentrations. Phenytoin decreases quetiapine, clozapine, haloperidol and possibly chlorpromazine concentrations. There are major gaps in the data. In many cases there are no published clinical data on interactions that would be predicted on theoretical grounds.

Anticonvulsants↗
PubMed2006

Oxidative stress in humans following the Pringle manoeuvre.

BACKGROUND: Oxidative stress is induced in the liver by application of the Pringle manoeuvre. Malondialdehyde is a carbonyl compound formed during lipid peroxidation and prostaglandin biosynthesis, which combines with DNA to form a number of adducts. Among them is the DNA adduct; 3-(2-deoxybeta-dierythropentafuranosyl) pyr [1, 2-alpha]-purin-10 (3H) one or M1G. This study was undertaken to determine the suitability of M1G as a novel marker of ischemia-reperfusion injury in the liver and its correlation with both the length of Pringle clamp application and the overall length of the operation. METHODS: Normal and colorectal liver metastatic tissues were obtained in 12 patients before and after application of the Pringle manoeuvre. All samples were snap-frozen in liquid nitrogen at -80 degree centigrade. DNA was extracted and M1G quantification was performed by immunoslotblot analysis. RESULTS: M1G levels in normal liver tissue were 4.0+/-1.0 per 10(7) nucleotides before the Pringle manoeuvre and 7.4 +/-1.0 per 10(7) nucleotides after the Pringle manoeuvre (mean+/-standard deviation) (P<0.05 by ANOVA). M1G levels in malignant liver tissue were 2.5+/-1.4 per 10(7) nucleotides before the Pringle manoeuvre and 6.5+/-1.9 adducts per 10(7) nucleotides after the Pringle manoeuvre (P<0.05). Adduct levels in normal liver tissue showed a significant correlation with cumulative period of Pringle application. CONCLUSIONS: This is the first time that the tissue levels of M1G before and after application of the Pringle manoeuvre have been studied. The results show that the Pringle manoeuvre exerts significant oxidative stress in human hepatocytes, which is Pringle-time dependent. The results highlight the potential for oxidative DNA adducts levels as a tool for measuring the severity of ischemia-reperfusion injury.

Adult↗
PubMed2005

Adipocyte-derived collagen VI affects early mammary tumor progression in vivo, demonstrating a critical interaction in the tumor/stroma microenvironment.

The interactions of transformed cells with the surrounding stromal cells are of importance for tumor progression and metastasis. The relevance of adipocyte-derived factors to breast cancer cell survival and growth is well established. However, it remains unknown which specific adipocyte-derived factors are most critical in this process. Collagen VI is abundantly expressed in adipocytes. Collagen(-/-) mice in the background of the mouse mammary tumor virus/polyoma virus middle T oncogene (MMTV-PyMT) mammary cancer model demonstrate dramatically reduced rates of early hyperplasia and primary tumor growth. Collagen VI promotes its growth-stimulatory and pro-survival effects in part by signaling through the NG2/chondroitin sulfate proteoglycan receptor expressed on the surface of malignant ductal epithelial cells to sequentially activate Akt and beta-catenin and stabilize cyclin D1. Levels of the carboxyterminal domain of collagen VIalpha3, a proteolytic product of the full-length molecule, are dramatically upregulated in murine and human breast cancer lesions. The same fragment exerts potent growth-stimulatory effects on MCF-7 cells in vitro. Therefore, adipocytes play a vital role in defining the ECM environment for normal and tumor-derived ductal epithelial cells and contribute significantly to tumor growth at early stages through secretion and processing of collagen VI.

Adipocytes↗
PubMed2005

Characterization of chemisorbed hyaluronic acid directly immobilized on solid substrates.

Hyaluronic acid (HA) has a number of potential biomedical applications in drug delivery and tissue engineering. For these applications, a prerequisite is to understand the characteristic of HA films directly immobilized to solid substrates. Here, we demonstrate that high molecular weight HA can be directly immobilized onto hydrophilic substrates without any chemical manipulation, allowing for the formation of an ultrathin chemisorbed layer. Hyaluronic acid is stabilized on these surfaces through hydrogen bonding between the hydrophilic moieties in HA [such as carboxylic acid (-COOH) or hydroxyl (-OH) groups] with silanol (-SiOH), carboxylic acid or hydroxyl groups on the hydrophilic substrates. Despite the water solubility, the chemisorbed HA layer remained stable on glass or silicon oxide substrates for at least 7 days in phosphate-buffered saline. Furthermore, HA immobilized on silicon and other dioxide surfaces in much higher quantities than other polysaccharides including dextran sulfate, heparin, heparin sulfate, chondroitin sulfate, dermatan sulfate, and alginic acid. This behavior is related to the molecular entanglement and intrinsic stiffness of HA as a result of strong internal and external hydrogen bonding as well as high molecular weight. These results demonstrate that HA can be used to coat surfaces through direct immobilization.

Absorption↗
PubMed2005

Pharmacological and histological characterisation of nicotine-kindled seizures in mice.

The present study reports that it is possible to induce kindling by repeated injections of nicotine. The newly characterised nicotine-kindling model was compared with that of pentylenetetrazole (PTZ) kindling. Mice were kindled by repeated injection of PTZ (37 mg/kg), or nicotine (2.3 mg/kg), and the effect of the anti-epileptic drugs (AED) levetiracetam (LEV), tiagabine (TGB) and phenytoin (PHT) on seizures in kindled and naive mice were investigated. C-Fos immunoreactivity (Fos IR) was used to investigate differences in neuronal activity pattern between PTZ-, nicotine kindled and naive animals. PTZ kindled animals mainly showed increased Fos IR in limbic regions, whereas Fos IR in nicotine kindled animals was increased in the entorhinal cortex, medial habenula and the compact part of substantia nigra. Fully kindled PTZ-induced seizures were inhibited by LEV (ED50=13.6+/-7.8 mg/kg), TGB (ED50=0.3+/-0.04 mg/kg) but not PHT (ED50>40 mg/kg) whereas fully kindled nicotine-induced seizures were inhibited by LEV (ED50=1.4+/-0.4 mg/kg), TGB (ED50=0.3+/-0.06 mg/kg) and PHT (ED50=9.2+/-2.4 mg/kg). These differences in efficacy of AEDs were not due to changes in plasma levels in the various models. In conclusion, repeated administration of nicotine can induce a kindling-like phenomenon and the model showed significantly different Fos IR pattern and pharmacology to that of PTZ kindling.

Animals↗
PubMed2005

Beta-amino ester polymers facilitate in vivo DNA transfection and adjuvant plasmid DNA immunization.

Increased in vivo expression of intramuscularly delivered plasmid DNA will be essential for clinical success in gene therapy and plasmid DNA vaccination. We screened polymers from a library of beta-amino esters for their ability to augment transgene expression as measured by beta-galactosidase activity and cellular immune responses. Among the candidates identified in this screen, poly[(1,6-di(acryloxyethoxy)hexane)-co-(4-aminobutanol)] enhanced plasmid DNA transgene expression by sevenfold (P=0.0001) and its immunogenicity by 70% (P=0.03). We found that polymers with moderately hydrophobic backbones and terminal alcohol groups facilitated transfection most effectively in vivo. We also observed a log-linear correlation (R2=0.93) between peak cellular immune responses and transgene activity in all evaluated polymer-plasmid DNA formulations, clarifying the relationship between immunogenicity and the quantity of expressed antigen.

Animals↗
PubMed2005

Cognitive sequelae of intravenous amphetamine self-administration in rats: evidence for selective effects on attentional performance.

Characterizing the nature and severity of cognitive deficits associated with chronic stimulant abuse may provide new insights into the neural substrates of drug addiction because such deficits may contribute to the chronic relapsing nature of compulsive drug use. This investigation examines in rats the long-term cognitive consequences of intravenously self-administered amphetamine, specifically on performance of a 5-choice serial reaction time task (5-CSRTT), which assesses visuo-spatial attention and impulsivity. Rats experienced 5 days of intravenous (i.v.) amphetamine self-administration and were then withdrawn for a period of 9 days, during which time testing on the 5-CSRTT took place. This was repeated on five consecutive occasions for a period of 10 weeks. Controls experienced identical training on the 5-CSRTT but during the self-administration sessions received yoked i.v. infusions of normal saline. The results reveal a selective and reproducible pattern of deficits on the 5-CSRTT following repeated withdrawal from amphetamine self-administration, with deleterious effects on the speed and accuracy of responding as well as increased omission errors. Premature (impulsive) responding, perseveration, and food consumption latencies were not significantly affected. Deficits in attentional performance fully recovered 4-5 days after amphetamine cessation and there was no evidence of any long-term disturbances, even when the attentional load was increased. However, following a 2-month abstinence period, abnormalities in the subsequent effects of acute noncontingent amphetamine were found, with increased omissions, slower response times, and reduced impulsivity. Thus, contingent i.v. amphetamine administration has both short- and long-term consequences, which may be relevant to the complex disturbances that accompany drug addiction.

Amphetamine↗
PubMed2005

Analysis of pregabalin at therapeutic concentrations in human plasma/serum by reversed-phase HPLC.

A selective and sensitive HPLC method is described for assay of the new antiepileptic drug pregabalin in serum/plasma. Following acetone precipitation of the sample, the drug was derivatized with picryl sulfonic acid (PSA) before chromatography on a C8 column. No interference from coadministered antiepileptics has been observed. The assay is calibrated over the range 0.5 mg/L to 8 mg/L. In addition to qualitative and quantitative validation data for the assay, concentration measurements in predose samples from a group of patients with dose escalated to 600 mg/d pregabalin are presented. The drug concentrations measured were in the range 2.8-8.2 mg/L at steady state. The method is robust and will be suitable for monitoring pregabalin therapy.

Anticonvulsants↗
PubMed2005

Dimeric fibroblast growth factor-2 enhances functional recovery after focal cerebral ischemia.

PURPOSE: The purpose of this study was to examine the effects of dimerized basic fibroblast growth factor (dFGF), a novel engineered growth factor, in a model of functional recovery following focal cerebral infarction (stroke) in rats. METHODS: A focal stroke was made in mature male rats by occlusion of the middle cerebral artery (MCA). dFGF was administered by intracisternal injection at one and three days after stroke. Tests to evaluate sensorimotor recovery of the contralateral limbs were done during the next three weeks after stroke. RESULTS: dFGF significantly enhanced recovery of sensorimotor function in limb placing and body swing tests compared to vehicle treatment. There were no differences in body weight or infarct volume in dFGF- vs. vehicle-treated animals. CONCLUSIONS: dFGF represents a potential treatment to enhance functional recovery after stroke and offers several advantages over bFGF, including stability and independence from extracellular heparan sulfates.

Animals↗
PubMed2004

Quantitative assessment of FGF regulation by cell surface heparan sulfates.

Heparin/heparan sulfate-like glycosaminoglycans (HSGAGs) modulate the activity of the fibroblast growth factor (FGF) family of proteins. Through interactions with both FGFs and FGF receptors (FGFRs), HSGAGs mediate FGF-FGFR binding and oligomerization leading to FGFR phosphorylation and initiation of intracellular signaling cascades. We describe a methodology to examine the impact of heparan sulfate fine structure and source on FGF-mediated signaling. Mitogenic assays using BaF3 cells transfected with specific FGFR isoforms allow for the quantification of FGF1 and FGF2 induced responses independent of conflicting influences. As such, this system enables a systematic investigation into the role of cell surface HSGAGs on FGF signaling. We demonstrate this approach using cell surface-derived HSGAGs and find that distinct HSGAGs elicit differential FGF response patterns through FGFR1c and FGFR3c. We conclude that this assay system can be used to probe the ability of distinct HSGAG species to regulate the activity of specific FGF-FGFR pairs.

Animals↗
PubMed2004

Poly(beta-amino ester)s promote cellular uptake of heparin and cancer cell death.

Heparin/heparan sulfate-like glycosaminoglycans (HSGAGs) are involved in diverse cellular processes in the extracellular matrix (ECM). The biological effect of HSGAGs depends on disaccharide content and physiological location within the ECM. HSGAGs are also brought into cells during membrane transcytosis and growth factor signaling while protein bound. We sought to probe the impact of free HSGAGs within the cell by using heparin as a model HSGAG. A library of poly(beta-amino ester)s, which internalize DNA, was examined for the capacity of its members to internalize heparin. Fourteen polymers enabled heparin internalization. The most efficacious polymer reduced murine melanoma cell growth by 73%. No glycosaminoglycan was as efficacious as highly sulfated, full-length heparin. Internalized heparin likely interferes with transcription factor function and subsequently induces apoptotic cell death. Therefore, internalized heparin is a novel mechanism for inducing apoptosis of cancer cells.

Animals↗
PubMed2004

Haemorrhage from pancreatic pseudocysts presenting as upper gastrointestinal haemorrhage.

Haemorrhage is a rare but frequently fatal complication of pancreatic pseudocysts. The high mortality associated with pancreatic haemorrhage makes prompt and aggressive management essential. Occasionally, haemorrhage may present atypically, leading to delay in its diagnosis and management. This report details a case of pancreatic haemorrhage presenting as an upper gastrointestinal bleed and discusses the subsequent management. When managing patients with pancreatic pseudocysts who present with the stigmata of upper gastrointestinal bleeding, the possibility that the bleeding originates from the pancreas must always be borne in mind.

Acute Disease↗
PubMed2004

Patient information following emergency laparoscopy for right iliac fossa pain.

Laparoscopy is increasingly used as a diagnostic and therapeutic tool in the management of emergency surgical admissions. Laparoscopic scars give little clue to the operation performed. Hence, the future assessment of patients re-admitted with abdominal pain, often needs to rely on the patient's own account of the operation performed. This study attempted to evaluate the quality of communication between surgeons and patients regarding the results of their laparoscopy and how much information was retained by the patients on discharge. Seventy-seven patients were identified from computerised medical records. A detailed case note review was undertaken looking at operative findings, procedure performed, and documentation of surgeon-to-patient communication. A questionnaire was posted to patients asking their opinion regarding the quality of communication from surgeons. The questionnaire asked specific questions regarding the patient's understanding of the operation performed and its findings. Overall communication between surgeons and patients was good. However, a small proportion of patients were unsure of their diagnosis and what therapeutic procedure had been performed following laparoscopy. This included one patient (out of 28 who had undergone laparoscopic appendectomy) who was unsure if their appendix had been removed. Two from 12 patients diagnosed with pelvic pathology at laparoscopy who were unclear of their diagnosis and two patients with histologically normal appendices who thought their appendices had been inflamed at removal. Greater effort must be made to inform patients of their laparoscopic findings and any therapeutic procedure performed. We recommend the use of written information leaflets to be sent to the patient's home address to ensure that all patients are fully aware of their laparoscopic findings. For any future emergency admission, the patient's knowledge of any previous surgery and whether their appendix is in situ is of considerable diagnostic value to the assessing clinician. More effort must be made to enable patients to retain such necessary information.

Abdominal Pain↗
PubMed2004

Systematic reaction to electrolytic treatment of pig livers in vivo.

BACKGROUND: Only a minority of secondary liver tumours are amenable to segmental resection and as a result, considerable research has been focused on developing ablative methods to destroy liver metastases. Many of these methods are limited by the development of a systemic inflammatory response mediated by cytokines such as interleukin-8 (IL-8) and tumour necrosis factor alpha (TNF-alpha). The aim of the present study was to determine if a systemic reaction occurred following electrolytic treatment of pig livers in vivo, by measuring biochemical indices of liver function and cytokines such as IL-8 and TNF-alpha. METHODS: Seventeen white domestic pigs were subjected to varying electrolytic doses ranging from 100 C to 800 C. Blood samples were taken at hourly intervals before, during and after electrolysis. Blood parameters measured included markers of liver enzyme activity; albumin, alkaline phosphatase, gammaglutaryl transferase and aspartate transaminase. Cytokine response to electrolysis was measured using enzyme-linked immunosorbent assays for IL-8 and TNF-alpha. RESULTS: Aspartate transaminase levels showed a clear and progressive rise post-electrolysis peaking at 2 h post-procedure. IL-8 and TNF-alpha levels showed only very mild variation with no significant response to electrolysis. This lack of association was borne out regardless of the electrolytic dose administered. CONCLUSION: Electrolysis is not accompanied by a significant systemic inflammatory response, reducing the risk of systemic inflammatory response, acute respiratory distress syndrome and other immune response mediated end-organ damage. Follow-up studies are needed in human trials.

Animals↗