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Biomedical subjects

C Wood

Publications and source records attributed to C Wood.

At least 55 records · Page 3Linked to original sources
PubMed2000

Expression of a constitutively active form of phosphatidylinositol 3-kinase inhibits the induction of nitric oxide synthase in human astrocytes.

The present study underlines the importance of phosphatidylinositol 3-kinase (PI 3-kinase) in attenuating the induction of nitric oxide synthase (iNOS) in human astrocytes. Proinflammatory cytokines induced the production of nitric oxide (NO) and the expression of iNOS in human U373MG astrocytoma cells and primary astrocytes. Expression of a catalytically active p110 subunit (p110*) of PI 3-kinase but not that of a kinase-deficient mutant of p110 (p110-kd) induced an increase in PI 3-kinase activity and inhibited cytokine-induced production of NO and expression of iNOS. However, expression of p110* had no effect on the activation of NF-kB, suggesting that p110* inhibits the expression of iNOS without inhibiting the activation of NF-kB.

Animals↗
PubMed2000

KSHV-encoded CC chemokine vMIP-III is a CCR4 agonist, stimulates angiogenesis, and selectively chemoattracts TH2 cells.

Kaposi's sarcoma-associated herpesvirus (KSHV) encodes 3 genes that are homologous to cellular chemokines. vMIP-III, the product of open reading frame K4.1, is the most distantly related to human chemokines and has yet to be characterized. We have examined the interaction of vMIP-III with chemokine receptors, its expression in KS lesions, and its in ovo angiogenic properties. We show expression of vMIP-III in KS lesions and demonstrate the stimulation of angiogenesis by this chemokine, like vMIP-I and vMIP-II, in the chick chorioallantoic membrane assay. vMIP-III does not block human immunodeficiency virus entry through the coreceptors CCR3, CCR5, or CXCR4. However, vMIP-III is an agonist for the cellular chemokine receptor CCR4. CCR4 is expressed by TH2-type T cells. Consistent with this, vMIP-III preferentially chemoattracts this cell type. Because of these biologic properties and because it is expressed in KS lesions, vMIP-III may play an important role in the pathobiology of KS. (Blood. 2000;95:1151-1157)

Allantois↗
PubMed2000

Pea chloroplast carnitine acetyltransferase.

The purpose of this study was to resolve the controversy as to whether or not chloroplasts possess the enzyme carnitine acetyltransferase (CAT) and whether the activity of this enzyme is sufficient to support previously reported rates of fatty acid synthesis from acetylcarnitine. CAT catalyses the freely reversible reaction: carnitine + short-chain acylCoA <--> short-chain acylcarnitine + CoASH. CAT activity was detected in thc chloroplasts of Pisum sativum L. With membrane-impermeable acetyl CoA as a substrate. activity was only detected in ruptured chloroplasts and not with intact chloroplasts, indicating that the enzyme was located on the stromal side of the envelope. In crude preparations, CAT could only be detected using a sensitive radioenzymatic assay due to competing reactions from other enzymes using acetyl CoA and large amounts of ultraviolet-absorbing materials. After partial purification of the enzyme, CAT was detected in both the forward and reverse directions using spectrophotometric assays. Rates of 100 nmol of product formed per minute per milligram of protein were obtained, which is sufficient to support reported fatty acid synthesis rates from acetylcarnitine. Chloroplastic CAT showed optimal activity at pH 8.5 and had a high substrate specificity, handling C2-C4 acyl CoAs only. We believe that CAT has been satisfactorily demonstrated in pea chloroplasts.

Acetyl Coenzyme A↗
PubMed2000

[Patient-controlled analgesia for prolonged pain in the child. An open-label feasibility study of a standardized method].

BACKGROUND: Patient-controlled analgesia (PCA) has been shown to be superior to a continuous morphine infusion for the treatment of ongoing pain in children over five years of age. Nevertheless, prescription parameters such as the bolus dosage and the possible association of a continuous background infusion have not yet been standardized. PATIENTS AND METHODS: Thirty-three children, aged four to 17, hospitalized in a pediatric hematology ward, benefited from PCA with a standardized prescription: a bolus dosage of at least 25 mg/kg, without a background infusion. Morphine consumption, side effects and efficacy on pain relief were followed. RESULTS: Median of mean morphine consumption was 0.32 mg.kg-1.d-1. Median of maximal consumption was 0.58 mg.kg-1.d-1. Mean duration was nine days. No important side effects were noted, except in two patients. They presented prolonged constipation and a poor quality of nocturnal sleep, but they also had a major depressive syndrome persisting after resolution of pain. Efficacy was comparable to a continuous intravenous infusion, and nocturnal sleep was of good quality for 31 children. CONCLUSION: This standardized technique of PCA can be used extensively in children over five years of age. It can be used as a reference for further studies.

Adolescent↗
PubMed2000

Education and training of healthcare staff: the barriers to its success.

On-going developments in Britain's healthcare services are placing great demands on its workforce. If high quality care is to be maintained, education and training is needed to provide staff with the necessary knowledge and skills to adapt to their changing roles. A recent research project looking at the education and training needs of non-specialist staff caring for people with cancer identified a number of barriers that prevent education and training from meeting its full potential. These barriers include time, accessibility, financial issues, staff motivation and marketing and advertising and are discussed in this paper together with some possible solutions to overcome them. It is concluded that the planning and development of education and training must address these barriers if it is to be successful in increasing the knowledge and skills of staff, and thereby improve the quality of patient care.

Attitude of Health Personnel↗
PubMed2000

A general overview of the cancer education needs of non-specialist staff.

The aim of this study was to identify the cancer education needs of non-specialist staff. A qualitative design was used involving focus groups, individual and paired interviews, focusing on specialist staff, non-specialist staff and patients. Six key areas were identified where staff indicated a need for education and training. These included: (1) an overview of cancer, what it is and how it effects patients; (2) treatments and side-effects; (3) communication skills; (4) physical and practical issues; (5) care organisation, referral routes and staff roles; and (6) death and dying issues. Similarities in the views of specialists and non-specialist staff of all disciplines indicated a workforce who would benefit from support and training in cancer issues. This is important if we are to provide safe and optimal care to patients with cancer at all stages of the disease trajectory.

Attitude of Health Personnel↗
PubMed2000

Expression of a dominant-negative mutant of p21(ras) inhibits induction of nitric oxide synthase and activation of nuclear factor-kappaB in primary astrocytes.

The present study underlines the importance of p21(ras) in regulating the inducible nitric oxide synthase (iNOS) in primary astrocytes. Bacterial lipopolysaccharides induced the GTP loading of p21(ras), and the expression of a dominant-negative mutant of p21(ras) (Deltap21(ras)) inhibited lipopolysaccharide-induced GTP loading in rat primary astrocytes. To delineate the role of p21(ras) in the induction of iNOS, we examined the effect of Deltap21(ras) on the expression of iNOS and the production of nitric oxide. It is interesting that expression of Deltap21(ras) markedly inhibited the production of nitric oxide and the expression of iNOS in lipopolysaccharide- and proinflammatory cytokine (tumor necrosis factor-alpha, interleukin-1beta; interferon-gamma)-stimulated rat and human primary astrocytes. Inhibition of iNOS promoter-derived chloramphenicol acetyltransferase activity by Deltap21(ras) suggests that p21(ras) is involved in the transcription of iNOS. As activation of nuclear factor-kappaB (NF-kappaB) is necessary for the transcription of iNOS, we examined the effect of Deltap21(ras) on the activation of NF-kappaB. Expression of Deltap21(ras) inhibited the DNA binding as well as the transcriptional activity of NF-kappaB in activated astrocytes, suggesting that Deltap21(ras) inhibits the expression of iNOS by inhibiting the activation of NF-kappaB. These studies also suggest that inhibitors of p21(ras) may be used as therapeutics in nitric oxide- and cytokine-mediated neuroinflammatory diseases.

Animals↗
PubMed2000

Cloning of the bovine immunodeficiency virus gag gene and development of a recombinant-protein-based enzyme-linked immunosorbent assay.

An enzyme-linked immunosorbent assay (ELISA) was established for the rapid detection of specific bovine immunodeficiency virus (BIV) antibodies in cattle, using recombinant Gag protein as an antigen. The gag coding region from BIV was cloned into an expression vector, pQE32, which expressed high levels of recombinant protein from Escherichia coli. The ELISA was standardized by a checkerboard titration against known BIV-positive and -negative sera from cattle and a monoclonal antibody to the Gag protein. A total of 139 cattle serum samples, from the diagnostic laboratory at Kansas State University, Manhattan, and from the Dairy Station, Louisiana State University, Baton Rouge, were compared by ELISA and immunoblot assays for the detection of BIV-specific antibodies. Of 26 cattle sera samples which tested positive using the immunoblot assay, 23 were positive by ELISA, thus establishing a strong correlation between the two tests. The sensitivity and specificity of ELISA relative to immunoblotting were 0.88 and 0.93, respectively. ELISA proved to be as specific as immunoblotting but was much less time-consuming and easier to perform.

Animals↗
PubMed2000

Characterization of transcripts expressed from human herpesvirus 6A strain GS immediate-early region B U16-U17 open reading frames.

Several gene fragments of human herpesvirus 6 (HHV-6) have been shown to activate the human immunodeficiency virus (HIV) type 1 long terminal repeat (LTR). An open reading frame (ORF) designated B701 (Y. Geng, B. Chandran, S. F. Josephs, and C. Wood, J. Virol. 66:1564-1570, 1992), found within a 22-kb HHV-6A strain GS [HHV-6A(GS)] genomic fragment and a 3.8-kb SalI subfragment, was shown to activate the HIV LTR. B701, also known as HHV-6 U16, is located in the immediate-early B (IE-B) region of the genome. The sequence of the 3.8-kb genomic fragment of HHV-6A(GS) is nearly identical to the published sequence of HHV-6A strain U1102, with minor differences. The HHV-6A(GS) B701 ORF (U16) was used to screen an HHV-6A(GS) cDNA library, and two different but overlapping cDNAs were identified. These cDNAs represent differently spliced transcripts ending at different polyadenylation signals. The ORFs included in the cDNAs are positionally homologous to the human cytomegalovirus (HCMV) UL36 ORF. The ORF in one cDNA was generated by splicing together in frame ORFs U17 and U16, and the second cDNA included ORFs U16 and U15. A third differentially spliced cDNA (U16+), was identified by 5' rapid amplification of cDNA ends. The predicted protein was identical to the U16 portion of the U17/U16 spliced gene product but did not include the U17 portion. 5'-extension analyses of the mRNAs demonstrated that at least two potential transcription initiation sites were used to express the transcripts encoding U17 and U16 gene products. Single-stranded U16 and U17 gene-specific RNA probes hybridized with at least five RNA species from infected cells and demonstrated that the expression of these transcripts was differentially regulated. The U17/U16 spliced gene products were expressed at IE times after infection, but a multiply spliced gene product encoded by U16 was expressed as a late gene. The U17/U16 and the U16+ gene products transactivated the HIV LTR. Thus, while there are similarities to the HCMV UL36-UL38 gene family, some of the IE-B U17/U16 transcripts are unique to HHV-6.

Base Sequence↗
PubMed2000

Jembrana disease virus Tat can regulate human immunodeficiency virus (HIV) long terminal repeat-directed gene expression and can substitute for HIV Tat in viral replication.

Jembrana disease virus (JDV) is a bovine lentivirus genetically similar to bovine immunodeficiency virus; it causes an acute and sometimes fatal disease in infected animals. This virus carries a very potent Tat that can strongly activate not only its own long terminal repeat (LTR) but also the human immunodeficiency virus (HIV) LTR. In contrast, HIV Tat cannot reciprocally activate the JDV LTR (H. Chen, G. E. Wilcox, G. Kertayadnya, and C. Wood, J. Virol. 73:658-666, 1999). This indicates that in transactivation JDV Tat may utilize a mechanism similar to but not the same as that of the HIV Tat. To further study the similarity of JDV and HIV tat in transactivation, we first tested the responses of a series of HIV LTR mutants to the JDV Tat. Cross-transactivation of HIV LTR by JDV Tat was impaired by mutations that disrupted the HIV type 1 transactivation response element (TAR) RNA stem-loop structure. Our results demonstrated that JDV Tat, like HIV Tat, transactivated the HIV LTR at least partially in a TAR-dependent manner. However, the sequence in the loop region of TAR was not as critical for the function of JDV Tat as it was for HIV Tat. The competitive inhibition of Tat-induced transactivation by the truncated JDV or HIV Tat, which consisted only of the activation domain, suggested that similar cellular factors were involved in both JDV and HIV Tat-induced transactivation. Based on the one-round transfection assay with HIV tat mutant proviruses, the cotransfected JDV tat plasmid can functionally complement the HIV tat defect. To further characterize the effect of JDV Tat on HIV, a stable chimeric HIV carrying the JDV tat gene was generated. This chimeric HIV replicated in a T-cell line, C8166, and in peripheral blood mononuclear cells, which suggested that JDV Tat can functionally substitute for HIV Tat. Further characterization of this chimeric virus will help to elucidate how JDV Tat functions and to explain the differences between HIV and JDV Tat transactivation.

Animals↗
PubMed2000

Does vestibular habituation still have a place in the treatment of benign paroxysmal positional vertigo?

Particle repositioning procedures such as the Epley manoeuvre have become popular in the management of benign paroxysmal positional vertigo (BPPV) at the expense of more traditional therapies such as vestibular habituation. We prospectively analysed the response of consecutive patients presenting with BPPV to treatment with vestibular habituation exercises using a symptom score sheet before and after treatment. This same patient group was then followed up, on average three years, eight months after discharge, to determine their long-term response to treatment. The results of the study demonstrated an excellent short-term response rate to treatment but a high level of recurrence after discharge. Most patients who experienced further symptoms following discharge were however self-reliant and were able to return to their habituation exercises without the need for further medical input. The aim in the management of these patients must be to provide long-term self reliance as well as short-term cure and it may be that this has not yet been well demonstrated with the Epley manoeuvre. It must also be remembered that particle repositioning manoeuvres cannot be used in all patients for example those who suffer with cervical or thoracic spine pathology and that some will fail to respond at all. We believe that vestibular habituation retains a useful role in the treatment of BPPV.

Adult↗
PubMed2000

Comparisons of HIV-1 viral sequences in brain, choroid plexus and spleen: potential role of choroid plexus in the pathogenesis of HIV encephalitis.

Possible mechanisms of HIV transmission to the brain include direct viral infection of cerebral endothelium and hematogeneous dissemination of viral-infected lymphocytes and monocytes. Cerebrospinal fluid dissemination from a primary infection of choroid plexus (CPx) is an alternative mechanism supported by recent studies in our laboratory. We showed that HIV-infected asymptomatic patients as well as AIDS patients have HIV infection of the CPx; the cell types so infected included stromal monocytes and dendritic cells. To further explore the potential role of CPx in the pathogenesis of HIV encephalitis, we analyzed HIV sequences from brain, CPx, and spleen of four AIDS patients by extracting DNA from paraffin sections and amplifying the V3 region of the HIV env gene by PCR. Several different clones from each tissue were characterized. We found that viruses from the brain and spleen grouped into two distinct clusters, while viruses of the CPx contained viral strains that were a mixture of those found in the brain or spleen. Net charge analysis of the V3 tip region showed that the brain viral sequences had fewer positive charges than blood viral sequences. Our results support the hypothesis that CPx may be one of the sites where HIV-1 gains access to the brain from the blood and therefore contains viruses that are of both genotypes.

AIDS Dementia Complex↗
PubMed2000

Contribution of mitochondria and peroxisomes to palmitate oxidation in pea tissues.

Total, mitochondrial and peroxisomal palmitate oxidation capacities were compared in pea, from the dry seed to 14 days after imbibition. Total beta-oxidation varied over the measured time period and showed four peaks of activity at day 2, days 5-6, day 10 and days 12-13. The contribution of peroxisomal and mitochondrial beta-oxidation to this overall beta-oxidation varied. Over the first 48 h of seed germination, peroxisomal beta-oxidation accounted for 80-100% of the total observed beta-oxidation. The larger peaks of beta-oxidation at days 5-6, day 10 and days 12-13 were due primarily to mitochondrial beta-oxidation activity, which accounted for 70-90% of the observed total beta-oxidation at these times. The peaks of activity are related to observed stages in seedling development.

Carbon Dioxide↗