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Biomedical subjects

R Shaw

Publications and source records attributed to R Shaw.

At least 73 records · Page 4Linked to original sources
PubMed1997

Effect of lamotrigine on carbamazepine epoxide/carbamazepine serum concentration ratios in adult patients with epilepsy.

Although lamotrigine (LTG) appears to have a low propensity to cause pharmacokinetic interactions with other medications, it has been suggested that LTG may interfere with the elimination of carbamazepine 10,11-epoxide (CBZE), the active metabolite of carbamazepine (CBZ). Evidence for this pharmacokinetic interaction is inconclusive and conflicting, however. We evaluated CBZ apparent oral clearance and the steady-state CBZE/CBZ serum concentration ratios in nine patients (30.8 +/- 7.7 years) with epilepsy prior to and following the initiation of adjunctive treatment with LTG. Overall, CBZ oral clearance was unchanged following the introduction of LTG (5.58 +/- 1.60 vs. 5.81 +/- 1.74 1/h, P = 0.630). Likewise, CBZE to CBZ serum concentration ratios were not significantly different (0.241 +/- 0.082 vs. 0.232 +/- 0.082, P = 0.782). These observations suggest that the addition of LTG did not result in a significant pharmacokinetic interaction involving either CBZ or CBZE.

Administration, Oral↗
PubMed1997

Real-time multichannel computerized electrogastrograph.

The purpose of this study was to develop a real-time multichannel computerized electrogastrograph (EGG) to measure and analyze electrical signals from the human abdominal surface. A soft-contact matrix composed of 25 cutaneous electrodes is embedded evenly in a latex mat. The mat can be firmly attached to the abdominal surface by drawing a vacuum between the matrix and the stomach. Twenty-five high-amplification filter/amplifiers provide a high signal-to-noise ratio and flat amplitude response for a signal between 0.02 and 0.12 Hz (1.2-7.2 cpm). The computer program provides waveform and frequency analysis for any chosen channel and mapping analyses for all 25 channels. A two-dimensional propagation exploration program was also developed. Using four different mapping analysis program subroutines, the optimal points for analyzing the EGG signals can be reliably found and variability of these locations can be observed easily. Results show differences in the EGG mappings of normal and abnormal subjects.

Adult↗
PubMed1997

Simultaneous detection and strain differentiation of Mycobacterium tuberculosis for diagnosis and epidemiology.

Widespread use of DNA restriction fragment length polymorphism (RFLP) to differentiate strains of Mycobacterium tuberculosis to monitor the transmission of tuberculosis has been hampered by the need to culture this slow-growing organism and by the level of technical sophistication needed for RFLP typing. We have developed a simple method which allows simultaneous detection and typing of M. tuberculosis in clinical specimens and reduces the time between suspicion of the disease and typing from 1 or several months to 1 or 3 days. The method is based on polymorphism of the chromosomal DR locus, which contains a variable number of short direct repeats interspersed with nonrepetitive spacers. The method is referred to as spacer oligotyping or "spoligotyping" because it is based on strain-dependent hybridization patterns of in vitro-amplified DNA with multiple spacer oligonucleotides. Most of the clinical isolates tested showed unique hybridization patterns, whereas outbreak strains shared the same spoligotype. The types obtained from direct examination of clinical samples were identical to those obtained by using DNA from cultured M. tuberculosis. This novel preliminary study shows that the novel method may be a useful tool for rapid disclosure of linked outbreak cases in a community, in hospitals, or in other institutions and for monitoring of transmission of multidrug-resistant M. tuberculosis. Unexpectedly, spoligotyping was found to differentiate M. bovis from M. tuberculosis, a distinction which is often difficult to make by traditional methods.

Bacterial Typing Techniques↗
PubMed1996

The pleckstrin homology domain of human beta I sigma II spectrin is targeted to the plasma membrane in vivo.

We have examined the in vivo targeting potential of the Pleckstrin Homology (PH) domain from human beta I sigma II spectrin using a novel Aequoria victoria green fluorescent protein (GFP) fusion vector constructed from a human codon optimized cDNA. This vector efficiently expresses both GFP and the GFP spectrin fusion protein in COS7 and other cell lines. GFP expressed alone shows only diffuse cytoplasmic staining which is not associated with the plasma membrane. In contrast the GFP-beta I sigma II spectrin PH domain fusion protein localizes under the plasma membrane of transfected COS7 cells in vivo. Fixation of cells transfected with GFP alone in -20 degrees C methanol results in the removal of all specific fluorescence. In contrast cells transfected with the GFP-beta I sigma II spectrin construct and fixed -20 degrees C methanol continue to show strong membrane fluorescence, consistent with a role for the spectrin PH domain in membrane localization in vivo.

Amino Acid Sequence↗
PubMed1996

Antioxidant-sensitive regulation of inflammatory-response genes in Kaposi's sarcoma cells.

Kaposi's sarcoma (KS) is a multifocal vascular lesion characterized by abnormal proliferation of endothelial-like KS cells linked to a pronounced leukocyte infiltration. KS lesions contain novel herpes-like DNA sequences, KSHV, hypothesized to originate from the viral pathogen for KS. Using cultured KS cells that retain the KSHV sequences, diverse signals, including tumor necrosis factor alpha, interleukin (IL) 1 beta, polyinosinic acid/polycytidylic acid and lipopolysaccharide, induced the expression of the cytokine IL-6 and cellular adhesion molecules involved in leukocyte recruitment, including vascular adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1). The thiol-antioxidant pyrrolidine dithiocarbamate (PDTC) selectively inhibited > 90% of the activation of nuclear factor kappa B-like DNA binding activity in KS cells. PDTC also reduced by > 85% induced levels of VCAM-1 and IL-6 at the mRNA, protein, and functional levels in KS cells. In contrast, PDTC did not inhibit the induced expression of either ICAM-1 or E-selectin. These studies show that PDTC differentially modulates the expression of inflammatory response genes in KS cells that contain KSHV, suggesting that reduction-oxidation-sensitive events are involved in the regulation of these genes. These studies also suggest that thiol-antioxidants such as PDTC may play a potentially therapeutic role in the treatment of KS by preventing induction of specific inflammatory response genes that may be involved in the pathogenesis of KS.

Animals↗
PubMed1996

Safety and security of information systems.

This paper discusses some of the similarities and differences between the attributes of safety and security. It places these attributes within the broader topic of dependability and tries to identify what aspects of safety and security are unique and which aspects may be viewed within the attributes of reliability and availability. The paper then suggests that, rather than analyse systems from the single perspective of safety or security, they should be analysed from the broader perspective of dependability.

Computer Security↗
PubMed1995

Activation of the double-stranded-RNA-activated protein kinase and induction of vascular cell adhesion molecule-1 by poly (I).poly (C) in endothelial cells.

Double-stranded RNA (dsRNA) induces the vascular cell adhesion molecule VCAM-1 to high levels of expression in human umbilical vein endothelial (HUVE) cells. Although VCAM-1 is also induced by the cytokine interleukin 1 beta (IL-1 beta), activation of the dsRNA-activated protein kinase (PKR) occurs only in response to incubation with dsRNA but not with IL-1 beta. Incubation of HUVE cells with the synthetic dsRNA, poly (I).poly (C), activates PKR with increased autophosphorylation, increased phosphorylation of the translation factor eIF2 alpha, and increased activation of the transcription factor NF-kappa B. Promoter analysis in HUVE cells using a VCAM-1 promoter linked to CAT reporter gene demonstrates that poly (I).poly (C) responsiveness resides in the minimal VCAM-1 promoter that contains two NF-kappa B sites, and deletion of the NF-kappa B sites eliminates basal and poly (I).poly (C)-induced CAT activity, supporting the importance of NF-kappa B in the poly (I).poly (C)-mediated induction of VCAM-1. In vitro studies using purified reagents demonstrate that PKR is capable of phosphorylating I kappa B alpha (the inhibitory subunit of NF-kappa B) in a dsRNA-dependent manner. This suggests that phosphorylation of I kappa B alpha by PKR could be an initial step in the activation of NF-kappa B by dsRNA. NF-kappa B is also activated by IL-1 beta in HUVE cells, but this activation occurs without increased PKR autophosphorylation or eIF2 alpha phosphorylation. Poly (I).poly (C) induces VCAM-1 mRNA levels that are dramatically higher and sustained longer than levels induced by IL-1 beta. Although phosphorylation of eIF2 alpha interferes with protein translation, sufficient VCAM-1 mRNA translation occurs in response to poly (I).poly (C) to yield VCAM-1 protein levels that are similar to levels that are induced by IL-1 beta. This suggests that the higher, sustained VCAM-1 mRNA levels that occur in response to incubation with poly (I).poly (C) compensate for the partial translational block resulting from increased eIF2 alpha phosphorylation. These studies indicate that transcriptional and translational regulatory events that occur in response to activation of PKR by dsRNA are important in the regulation of VCAM-1 gene expression in HUVE cells.

Cell Adhesion↗
PubMed1995

Binding of pleckstrin homology domains to WD40/beta-transducin repeat containing segments of the protein product of the Lis-1 gene.

In previous experiments we demonstrated an interaction between certain pleckstrin homology (PH) domains and regions containing the so-called WD40 (or beta-transducin) repeats of the beta subunit of trimeric G-proteins (G beta), a finding we here extend to the PH domains of the src-related tyrosine kinase TecIIa and the GTPase dynamin. To examine the possibility that WD40 repeats in molecules other than G beta might also bind PH domains we examined PAFAH-45, the protein product of the Lis-1 gene, which contains 7 WD40 repeats. We found that 1) Purified PAFAH-45 binds PH domain constructs in vitro. 2) Protein constructs expressing all 7 WD40 repeats of PAFAH-45 but lacking the N-terminal non WD40 region also bind PH domains of beta-adrenergic receptor kinase, beta-spectrin, TecIIa and dynamin but with a differing hierarchy of affinities than that seen with G beta. 3). PAFAH-45 WD40 repeats will reduce the binding of PH domains to brain G beta and brain G beta gamma will reduce the binding of PH domains to PAFAH-45. These data support the hypothesis that PH domain/WD40 interactions are involved in a wide variety of important protein/protein interactions.

Animals↗
PubMed1995

Myelin gene expression in glia treated with oligodendroglial trophic factor.

Oligodendroglia synthesize myelin in the CNS. In vitro, oligodendroglia may be identified by the binding of monoclonal antibodies against galactocerebroside, a myelin-specific galactolipid. Oligodendroglial trophic factor is a protein mitogen for cells of the oligodendroglial lineage. When oligodendroglia in cerebral white matter cultures are treated with oligodendroglial trophic factor, galactocerebroside-positive cells undergo mitosis but fail to express the myelin structural proteins, myelin basic protein and proteolipid protein. Oligodendroglia treated with oligodendroglial trophic factor, however, do express 2',3'-cyclic nucleotide 3'-phosphodiesterase and myelin-associated glycoprotein in a manner similar to oligodendroglia treated with platelet-derived growth factor. Oligodendroglial trophic factor, therefore, generates a population of somewhat 'immature' oligodendroglia, which are galactocerebroside, myelin-associated glycoprotein and 2', 3'-cyclic nucleotide 3' phosphodiesterase positive but myelin basic protein and proteolipid protein negative.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗
PubMed1995

Measuring the prevalence of bronchial hyper-responsiveness in children.

BACKGROUND: The aim of this study was to assess the effectiveness of an asthma prevalence video questionnaire (involving the audiovisual presentation of clinical asthma), a standard written questionnaire (based on the IUATLD Bronchial Symptoms Questionnaire) and a new written questionnaire (designed for an international study of asthma and allergies in childhood [ISAAC]) in predicting bronchial hyper-responsiveness (BHR) (PD20 < or = 7.8 mumol methacholine). METHODS: The IUATLD and video questionnaires were administered to 193 schoolchildren (13-16 years). The ISAAC questionnaire was administered to 87 of these children. All children subsequently underwent bronchial challenge to methacholine. RESULTS: The sensitivity and specificity for predicting BHR were similar for individual questions from the IUATLD and video questionnaires. The video questions with the highest Youden's index related to moderate wheezing at rest (0.46), severe wheezing at rest (0.38), and nocturnal wheezing (0.37). The ISAAC questionnaire was similar in effectiveness to the IUATLD questionnaire in predicting BHR. CONCLUSIONS: The video questionnaire is a valid method of assessing the prevalence of BHR, and may be particularly useful when comparing populations with differing languages and cultures. Some video questions appeared more effective than others in relation to predicting BHR. A new written questionnaire (ISAAC) designed for a large international asthma prevalence study in children also is an effective method for measuring the prevalence of BHR.

Adolescent↗
PubMed1994

Risk factors for asthma symptoms in Kawerau children.

AIMS: To study risk factors for asthma prevalence in Kawerau children aged 8-13 years. METHODS: Questionnaires on asthma symptoms and risk factors were completed in 1992 by parents of 708 Kawerau schoolchildren aged 8-13 years, a response rate of 82.0%; for a subgroup of children, stored serum samples from a 1984 survey were also analysed. RESULTS: The overall prevalence of current wheeze (21.3%) was similar to that observed in other New Zealand surveys. The prevalence of current wheeze was elevated in males (odds ratio (OR) = 1.7, 95% CI 1.2-2.5), in those who had been passively exposed to cigarette smoke from the primary caregiver (OR = 1.4, 95% CI 1.0-2.1), in those who had had pets in the home at age 0-5 years (OR = 1.9, 95% CI 1.2-2.9) and in those with one or more birth parents with asthma (OR = 2.1, 95% CI 1.4-3.1); current wheeze was less common in those with older children living in the same household (for 2 or more older children in the same household, OR = 0.5, 95% CI 0.2-1.0). In a small nested case-control study it was found that current wheeze was more common in those with high levels of IgE (OR = 6.4, 95% CI 1.3-36.4) or low levels of selenium (OR = 3.1, 95% CI 0.9-11.8) in stored serum collected 8 years previously. There was no difference in the proportions with current wheeze, or with diagnosed asthma between Maori and European children, but Maori children were more likely to have current frequent nocturnal wheeze (OR = 2.2, 95% CI 1.0-5.1), current severe wheeze (OR = 1.8, 95% CI 0.8-3.7) or to have been admitted to hospital with asthma (OR = 2.4, 95% CI 1.2-4.8). Passive exposure to tobacco smoke was more common among Maori children, but this only partially accounted for the greater asthma severity in Maori children, and the lower prescribing of prophylactic medications in this group may also have contributed. CONCLUSIONS: Multiple factors were associated with asthma symptoms in children in this age-group, including a family history of asthma, male gender, environmental tobacco smoke, environmental allergen exposure, atopy, and low selenium status. Further studies are required to assess the relative contributions of these factors to the prevalence of asthma in New Zealand.

Adolescent↗
PubMed1994

Binding of PH domains of beta-adrenergic receptor kinase and beta-spectrin to WD40/beta-transducin repeat containing regions of the beta-subunit of trimeric G-proteins.

Pleckstrin homology (PH) domains are found in numerous proteins important in signal transduction and cytoskeletal function. Several PH domains are now known to contain a binding site for the beta gamma subunits of trimeric G-proteins (G beta gamma), a finding which naturally raises the question of where on the G beta gamma complex these PH domains bind. Here we demonstrate binding of the PH domains of beta-adrenergic receptor kinase and beta-spectrin to the G beta subunit and not the G gamma subunit in a nitrocellulose gel replica assay. Furthermore, the C-terminal tryptic fragment of G beta containing only 5 WD40/beta-transducin (WD40) repeats also binds these two PH domains. Finally, constructs containing only WD40 repeats of G beta were shown to bind to beta-ARK and beta-spectrin PH domains in solution. These findings suggest that WD40 repeats of G beta are ligands for PH domains and have interesting implications for other proteins containing WD40 sequences.

Amino Acid Sequence↗
PubMed1994

Cloning sequencing and expression of the gene encoding the VP2 protein of the human group B rotavirus, ADRV.

Adult diarrheal rotavirus, ADRV, is a noncultivable human group B rotavirus. A complete cDNA copy of ADRV gene segment 2 has been cloned and sequenced. Gene segment 2 contains 2844 bases and encodes one long open reading frame beginning at base 14 and terminating at base 2812. Gene 2 encodes a protein containing 933 amino acids with a calculated molecular weight of 105.6 kDa and a pl of 5.5. The gene 2 polypeptide contains significant homology with the VP2 protein which comprises the core of group A rotavirus strains. The gene 2 protein has been expressed in a rabbit reticulocyte lysate in vitro and is identical in molecular mass with a protein previously demonstrated to be present on iodinated EDTA-treated virions and from in vitro translations of total ADRV mRNA. A recombinant baculovirus containing gene segment 2 has been constructed and used to express the encoded VP2 equivalent protein. The expressed VP2 protein is immunoprecipitable by hyperimmune anti-ADRV serum, porcine group B infection serum, and human convalescent serum but not by hyperimmune serum to group A rotavirus. Our results suggest that ADRV gene segment 2 encodes the VP2 protein equivalent to group A rotavirus strains present in the core of the group B virion.

Amino Acid Sequence↗
PubMed1994

Safety-critical software and current standards initiatives.

This paper sets out to examine the role of standards in the development of safety-critical software. It starts with a brief discussion on the nature and role of standards and then moves on to identify some of the standards making bodies. Safety-critical software is next discussed and the problems of software safety are contrasted with those of traditional electromechanical devices. There then follows a review of some of the current initiatives to produce standards addressing the development of safety-critical systems containing software. Two standards are then examined in detail to provide an insight into what requirements are placed on the developers of safety-critical software. Lastly, mention is made of some weaknesses that are inherent in today's standards, and some of the efforts that are being made to address these problems are discussed.

Accidents, Occupational↗