PubMed Health⌕ Search

Biomedical subjects

G Price

Publications and source records attributed to G Price.

At least 19 recordsLinked to original sources
PubMed2006

A novel imaging technique as an adjunct to the in vivo diagnosis of nonmelanoma skin cancer.

BACKGROUND: Spectrophotometric intracutaneous analysis (SIAscopy) is a light-based imaging system capable of producing rapid images of melanin, blood and collagen of the skin. Although the SIAscope has been investigated for melanoma diagnosis, no formal study has been conducted to determine its use in the diagnosis of nonmelanoma skin cancer (NMSC). OBJECTIVES: A prospective study was conducted to investigate the potential for the SIAscope to diagnose NMSC. METHODS: In total, 302 consecutive patients were recruited into the study, 363 lesions being scanned. Logistic regression analysis was used to construct a predictive model for NMSC diagnosis and receiver-operator characteristic curves were used to assess overall accuracy of the model. RESULTS: A sensitivity of 98.0%, specificity of 95.7% and overall accuracy of 98.2% was found for NMSC diagnosis by the SIAscope model. CONCLUSIONS: Results suggest that the SIAscope may be a useful adjunct in the diagnosis of NMSC.

Adolescent↗
PubMed2006

Severe acidosis in patients taking metformin--rapid reversal and survival despite high APACHE score.

BACKGROUND: Metformin has been shown to reduce complications and mortality from Type 2 diabetes mellitus, and is increasingly used to treat this condition. This agent is, however, associated with a rare but serious risk of lactic acidosis. CASE REPORT: We present cases of 10 patients with Type 2 diabetes mellitus who developed acute renal failure and severe lactic acidosis. Despite the severity of their illness, all patients but one survived. CONCLUSIONS: The increasing prevalence of Type 2 diabetes and its treatment with metformin might result in more cases of lactic acidosis. However our case report demonstrates that early and aggressive treatment with haemofiltration can improve outcomes even in the presence of severe acidosis.

APACHE↗
PubMed2005

The corpus callosum in first episode schizophrenia: a diffusion tensor imaging study.

BACKGROUND: Neuropathological and imaging studies suggest that corpus callosum abnormalities (CC) are present in schizophrenia, but it remains to be determined whether these abnormalities are present at illness onset. Diffusion tensor imaging (DTI), which is more sensitive than conventional magnetic resonance imaging (MRI) in detecting subtle structural changes in the organisation and integrity of white matter tracts, is an ideal tool to investigate this question. OBJECTIVE: To determine whether CC abnormalities are present at illness onset in schizophrenia. METHODS: Twenty patients (14 men, six women) with first episode schizophrenia and 29 controls (11 men, 18 women) were studied. Both high resolution volumetric T1-weighted images and DTI were acquired. Regions of interest (ROI) were placed in the splenium and genu of the CC and fractional anisotropy (FA) and diffusivity (D) measured. RESULTS: No differences in FA or D were detected in these regions between patients and controls. In women, irrespective of group membership, FA was significantly lower and there was a trend for D to be higher than in men, indicating less barriers to diffusion in females. CONCLUSION: The negative findings of this study suggest that in the early stages of schizophrenia there is no disruption to the integrity of the CC and raise the possibility that the neuropathological abnormalities may appear later and be progressive, at least in some patients.

Adolescent↗
PubMed2004

Use of recombinant factor VIIa to treat life-threatening non-surgical bleeding in a post-partum patient.

Ongoing bleeding from patients who have an acquired coagulopathy post-surgery is a common problem. Strategies that are available to combat this problem revolve around the replacement of coagulation factors, platelets, and red blood cells as necessary. These strategies are not always successful and a more direct approach to activating the coagulation system can be more effective and in some instances life saving. We describe the use of recombinant factor VIIa in a patient with ongoing post partum bleeding.

Adult↗
PubMed2004

Difficult extubation: calming the sympathetic storm.

Tracheal extubation can evoke an equally strong haemodyamic stress response as tracheal intubation. We present a patient with myocardial infarction who repeatedly failed tracheal extubation. He developed acute pulmonary oedema following each attempt at tracheal extubation due to sympathetic overactivity. A change of approach with extubation under propofol sedation followed by continued sympatholysis with dexmedetomidine infusion allowed successful extubation.

Aged↗
PubMed2003

Metformin lactic acidosis, acute renal failure and rofecoxib.

A patient with acute renal failure associated with lactic acidosis as a result of concurrent treatment with metformin is described. Rofecoxib may have been a precipitating factor. The risk of renal failure with the use of traditional NSAIDs is well known. However, what is less well appreciated is the role that the COX 2 inhibitors may play in the development of renal failure which, when it occurs in a patient on metformin, can lead to a potentially disastrous outcome.

Acidosis, Lactic↗
PubMed2002

Can warfarin be continued during dental extraction? Results of a randomized controlled trial.

A randomized controlled trial was set up to investigate whether patients who were taking warfarin and had an International Normalised Ratio (INR) within the normal therapeutic range require cessation of their anticoagulation drugs before dental extractions. Of 109 patients who completed the trial, 52 were allocated to the control group (warfarin stopped 2 days before extraction) and 57 patients were allocated to the intervention group (warfarin continued). The incidence of bleeding complications in the intervention group was higher (15/57, 26%) than in the control group (7/52, 14%) but this difference was not significant. Two patients in the study required hospital review for bleeding and all other episodes of bleeding were controlled by patients at home. Continuing warfarin when the INR is < 4.1 may lead to an increase in minor post-extraction bleeding after dental extractions but we found no evidence of an increase in clinically important bleeding. As there are risks associated with stopping warfarin, the practice of routinely discontinuing it before dental extractions should be reconsidered.

Acetaminophen↗
PubMed2002

(E)-2(R)-[1(S)-(Hydroxycarbamoyl)-4-phenyl-3-butenyl]-2'-isobutyl-2'-(methanesulfonyl)-4-methylvalerohydrazide (Ro 32-7315), a selective and orally active inhibitor of tumor necrosis factor-alpha convertase.

Tumor necrosis factor-alpha (TNF-alpha), a cytokine secreted by inflammatory cells, has been implicated in several inflammatory disease states. (E)-2(R)-[1(S)-(Hydroxycarbamoyl)-4-phenyl-3-butenyl]-2'-isobutyl-2'-(methanesulfonyl)-4-methylvalerohydrazide (Ro 32-7315), is a potent, orally active inhibitor of the TNF-alpha convertase (TACE), an enzyme responsible for proteolytic cleavage of the membrane bound precursor, pro-TNF-alpha. Ro 32-7315 inhibited a recombinant form of TACE (IC(50) = 5.2 nM) with selectivity over related matrix metalloproteinases. In a cellular assay system, THP-1 cell line, and in human and rat whole blood, Ro 32-7315 significantly reduced lipopolysaccharide (LPS)-induced TNF-alpha release with IC(50) values of 350 +/- 14 nM (n = 5), 2.4 +/- 0.5 microM (n = 5), and 110 +/- 18 nM (n = 5), respectively. Oral administration of Ro 32-7315 to Wistar rats caused a dose-dependent inhibition of LPS-induced release of systemic TNF-alpha with an ED(50) of 25 mg/kg. Treatment (days 0-14) of Allen and Hamburys hooded rats with Ro 32-7315 (2.5, 5, 10, and 20 mg/kg, i.p., twice daily) significantly reduced adjuvant-induced secondary paw swelling (42, 71, 83, and 93%, respectively) as compared with the vehicle group. In the Ro 32-7315-treated group, the reduced paw swelling was associated with improved lesion score and joint mobility. Furthermore, in a placebo-controlled, single-dose study, Ro 32-7315 given orally (450 mg) significantly suppressed ex vivo, LPS-induced TNF-alpha release in the whole-blood samples taken from healthy male and female volunteers (mean inhibition of 42% over a 4-h duration, n = 6). These data collectively support the potential use of such a compound for the oral treatment of inflammatory disorders.

ADAM Proteins↗
PubMed2001

Activated JNK phosphorylates the c-terminal domain of MLK2 that is required for MLK2-induced apoptosis.

MAP kinase signaling pathways are important mediators of cellular responses to a wide variety of stimuli. Signals pass along these pathways via kinase cascades in which three protein kinases are sequentially phosphorylated and activated, initiating a range of cellular programs including cellular proliferation, immune and inflammatory responses, and apoptosis. One such cascade involves the mixed lineage kinase, MLK2, signaling through MAP kinase kinase 4 and/or MAP kinase kinase 7 to the SAPK/JNK, resulting in phosphorylation of transcription factors including the oncogene, c-jun. Recently we showed that MLK2 causes apoptosis in cultured neuronal cells and that this effect is dependent on activation of the JNK pathway (Liu, Y. F., Dorow, D. S., and Marshall, J. (2000) J. Biol. Chem. 275, 19035-19040). Furthermore, dominant-negative MLK2 blocked apoptosis induced by polyglutamine-expanded huntingtin protein, the product of the mutant Huntington's disease gene. Here we show that as well as activating the stress-signaling pathway, MLK2 is a target for phosphorylation by activated JNK. Phosphopeptide mapping of MLK2 proteins revealed that activated JNK2 phosphorylates multiple sites mainly within the noncatalytic C-terminal region of MLK2 including the C-terminal 100 amino acid peptide. In addition, MLK2 is phosphorylated in vivo within several of the same C-terminal peptides phosphorylated by JNK2 in vitro, and this phosphorylation is increased by cotransfection of JNK2 and treatment with the JNK activator, anisomycin. Cotransfection of dominant-negative JNK kinase inhibits phosphorylation of kinase-negative MLK2 by anisomycin-activated JNK. Furthermore, we show that the N-terminal region of MLK2 is sufficient to activate JNK but that removal of the C-terminal domain abrogates the apoptotic response. Taken together, these data indicate that the apoptotic activity of MLK2 is dependent on the C-terminal domain that is the main target for MLK2 phosphorylation by activated JNK.

Animals↗
PubMed2001

Demonstration of the genetic stability and temporal expression of select members of the lyme disease spirochete OspF protein family during infection in mice.

Infection with Lyme disease spirochetes can be chronic. This suggests that the spirochetes are capable of immune evasion. In a previous study we demonstrated that the ospE gene family, which is one of three gene families whose members are flanked at their 5' end by the highly conserved upstream homology box (UHB) element, undergoes mutation and rearrangement during infection. This results in the generation of antigenically distinct variants that may contribute to immune evasion. In this study we have assessed the genetic stability of the UHB-flanked ospF gene family during infection in mice. Using postinfection clonal populations of Borrelia burgdorferi B31MI, PCR amplicons were generated for three members of the ospF gene family after a 3-month infection time frame. The amplicons were analyzed by single-nucleotide polymorphism pattern analysis and DNA sequencing. Members of the ospF gene family were found to be stable during infection, as no mutations or rearrangements were detected. An analysis of the humoral immune response to these proteins during infection revealed that the immune response to each is specific and that there is a delayed humoral immune response to some OspF protein family members. These analyses suggest that there is a temporal component to the expression of these genes during infection. In addition to a possible contribution to immune evasion, members of the OspF protein family may play specific roles at different stages of infection.

Animals↗
PubMed2000

Major DNA replication initiation sites in the c-myc locus in human cells.

DNA replication initiation sites and initiation frequencies over 12. 5 kb of the human c-myc locus, including 4.6 kb of new 5' sequence, were determined based on short nascent DNA abundance measured by competitive polymerase chain reaction using 21 primer sets. In previous measurements, no comparative quantitation of nascent strand abundance was performed, and distinction of major from minor initiation sites was not feasible. Two major initiation sites were identified in this study. One predominant site has been located at approximately 0.5 kb upstream of exon 1 of the c-myc gene, and a second new major site is located in exon 2. The site in exon 2 has not been previously identified. In addition, there are other sites that may act as less frequently used initiation sites, some of which may correspond to sites in previous reports. Furthermore, a comparison of the abundance of DNA replication intermediates over this same region of the c-myc locus between HeLa and normal skin fibroblast (NSF) cells indicated that the relative distribution was very similar, but that nascent strand abundance in HeLa cells was approximately twice that in NSF relative to the abundance at the lamin B2 origin. This increased activity at initiation sites in the c-myc locus may mainly be influenced by regulators at higher levels in transformed cells like HeLa.

Cells, Cultured↗
PubMed2000

Reduction of anxiety during MR imaging: a controlled trial.

An anxiety reduction protocol was developed and evaluated for routine use with neurology and neuropsychiatry patients undergoing brain or spinal scans. Thirty five patients underwent standard procedures, with limited information given in advance. Twenty nine experimental patients received a booklet giving information about the scanning procedure and advice on cognitive strategies for anxiety reduction, a tape-recorded demonstration of scanner noise, a visit to the control room before entering the scanner, a device to signal for adjustment of music volume, precise timings of each scan, and a clock visible during scanning. Anxiety was measured before, during, and after scanning, using subjective ratings and a retrospective version of the Spielberger State Anxiety Scale. There was no difference in anxiety between groups immediately prior to the scan and immediately after entering the scanner. Patients in the experimental group were significantly less anxious during the scan than control patients, as measured by mean anxiety ratings made during the imaging procedure and by retrospective State Anxiety scores completed immediately after leaving the scanner. The results show that scan-related anxiety can be reduced by introducing these simple changes to MR imaging procedures, with minimal cost, no special training of staff, and no disruption of the running of the MR Unit.

Adult↗
PubMed2000

Rat protein kinase c zeta gene contains alternative promoters for generation of dual transcripts with 5'-end heterogeneity.

Protein kinase C (PKC) zeta is a phospholipid-dependent serine/threonine kinase that appears to perform important cell signaling functions. Two forms of PKC zeta RNA, with different 5' ends, have been reported. The major form (zeta) is expressed in most, if not all tissues, while the minor form (zeta'), which encodes the catalytic domain of the enzyme without most of its regulatory domain, is predominant in normal brain and certain rat prostate tumors. We report here the structure of the 5' end of the rat PKC zeta gene, demonstrating that both forms of RNA can be transcribed from the same gene through the use of alternative promoters and splicing. In luciferase reporter constructs, progressive deletions of the PKC zeta and zeta' 5' flanking sequences yielded activities that were higher in the cell lines expressing endogenous PKC zeta and zeta' RNAs, respectively. Also, multiple PCRs across different introns of the PKC zeta gene indicate that recent duplication of the gene or the existence of a closely related pseudogene in the rat genome are unlikely.

5' Untranslated Regions↗
PubMed2000

The peripheral benzodiazepine binding site in the brain in multiple sclerosis: quantitative in vivo imaging of microglia as a measure of disease activity.

This study identifies by microautoradiography activated microglia/macrophages as the main cell type expressing the peripheral benzodiazepine binding site (PBBS) at sites of active CNS pathology. Quantitative measurements of PBBS expression in vivo obtained by PET and [(11)C](R)-PK11195 are shown to correspond to animal experimental and human post-mortem data on the distribution pattern of activated microglia in inflammatory brain disease. Film autoradiography with [(3)H](R)-PK11195, a specific ligand for the PBBS, showed minimal binding in normal control CNS, whereas maximal binding to mononuclear cells was found in multiple sclerosis plaques. However, there was also significantly increased [(3)H](R)-PK11195 binding on activated microglia outside the histopathologically defined borders of multiple sclerosis plaques and in areas, such as the cerebral central grey matter, that are not normally reported as sites of pathology in multiple sclerosis. A similar pattern of [(3)H](R)-PK11195 binding in areas containing activated microglia was seen in the CNS of animals with experimental allergic encephalomyelitis (EAE). In areas without identifiable focal pathology, immunocytochemical staining combined with high-resolution emulsion autoradiography demonstrated that the cellular source of [(3)H](R)-PK11195 binding is activated microglia, which frequently retains a ramified morphology. Furthermore, in vitro radioligand binding studies confirmed that microglial activation leads to a rise in the number of PBBS and not a change in binding affinity. Quantitative [(11)C](R)-PK11195 PET in multiple sclerosis patients demonstrated increased PBBS expression in areas of focal pathology identified by T(1)- and T(2)-weighted MRI and, importantly, also in normal-appearing anatomical structures, including cerebral central grey matter. The additional binding frequently delineated neuronal projection areas, such as the lateral geniculate bodies in patients with a history of optic neuritis. In summary, [(11)C](R)-PK11195 PET provides a cellular marker of disease activity in vivo in the human brain.

Adult↗
PubMed1999

Identification of initiation sites for DNA replication in the human dnmt1 (DNA-methyltransferase) locus.

Vertebrates have developed multiple mechanisms to coordinate the replication of epigenetic and genetic information. Dnmt1 encodes the maintenance enzyme DNA-methyltransferase, which is responsible for propagating the DNA methylation pattern and the epigenetic information that it encodes during replication. Direct sequence analysis and bisulfite mapping of the 5' region of DNA-methyltransferase 1 (dnmt1) have indicated the presence of many sequence elements associated with previously characterized origins of DNA replication. This study tests the hypothesis that the dnmt1 region containing these elements is an origin of replication in human cells. First, we demonstrate that a vector containing this dnmt1 sequence is able to support autonomous replication when transfected into HeLa cells. Second, using a gel retardation assay, we show that it contains a site for binding of origin-rich sequences binding activity, a recently purified replication protein. Finally, using competitive polymerase chain reaction, we show that replication initiates in this region in vivo. Based on these lines of evidence, we propose that initiation sites for DNA replication are located between the first intron and exon 7 of the human dnmt1 locus.

Chromosome Mapping↗
PubMed1999

Separation-of-function mutations in Saccharomyces cerevisiae MSH2 that confer mismatch repair defects but do not affect nonhomologous-tail removal during recombination.

Yeast Msh2p forms complexes with Msh3p and Msh6p to repair DNA mispairs that arise during DNA replication. In addition to their role in mismatch repair (MMR), the MSH2 and MSH3 gene products are required to remove 3' nonhomologous DNA tails during genetic recombination. The mismatch repair genes MSH6, MLH1, and PMS1, whose products interact with Msh2p, are not required in this process. We have identified mutations in MSH2 that do not disrupt genetic recombination but confer a strong defect in mismatch repair. Twenty-four msh2 mutations that conferred a dominant negative phenotype for mismatch repair were isolated. A subset of these mutations mapped to residues in Msh2p that were analogous to mutations identified in human nonpolyposis colorectal cancer msh2 kindreds. Approximately half of the these MMR-defective mutations retained wild-type or nearly wild-type activity for the removal of nonhomologous DNA tails during genetic recombination. The identification of mutations in MSH2 that disrupt mismatch repair without affecting recombination provides a first step in dissecting the Msh-effector protein complexes that are thought to play different roles during DNA repair and genetic recombination.

Alleles↗