Biomedical subjects

C Wood

Publications and source records attributed to C Wood.

At least 37 records · Page 2Linked to original sources

PubMed2001

Mitochondrial and peroxisomal beta-oxidation capacities of organs from a non-oilseed plant.

Until recently, beta-oxidation was believed to be exclusively located in the peroxisomes of all higher plants. Whilst this is true for germinating oilseeds undergoing gluconeogenesis, evidence demonstrating mitochondrial beta-oxidation in other plant systems has refuted this central dogma of plant lipid metabolism. This report describes a comparative study of the dual mitochondrial and peroxisomal beta-oxidation capacities of plant organs. Oxidation of [1-(14)C] palmitate was measured in the cotyledons, plumules and radicles of Pisum sativum L., which is a starchy seed, over a 14 day period from the commencement of imbibition. Respiratory chain inhibitors were used for differentiating between mitochondrial and peroxisomal beta-oxidation. Peroxisomal beta-oxidation gave a steady, baseline rate and, in the early stages of seedling development, accounted for 70-100% of the beta-oxidation observed. Mitochondrial beta-oxidation gave peaks of activity at days 7 and 10-11, accounting for up to 82% of the total beta-oxidation activity at these times. These peaks coincide with key stages of seedling development and were not observed when normal development was disrupted by growth in the dark. Peroxisomal beta-oxidation was unaffected by etiolation. Since mitochondrial beta-oxidation was overt only during times of intense biosynthetic activity it might be switched on or off during seedling development. In contrast, peroxisomes maintained a continuous, low beta-oxidation activity that could be essential in removing harmful free fatty acids, e.g. those produced by protein and lipid turnover.

Acyl-CoA Oxidase↗

PubMed2001

A prospective study of quality of life in ALS patients treated with noninvasive ventilation.

Noninvasive positive pressure ventilation prolongs survival in ALS but its effect on quality of life is unknown. The authors prospectively studied quality of life using the SF-36 questionnaire in a cohort of 16 ventilated patients with ALS. Noninvasive positive pressure ventilation improved scores in the "Vitality" domain by as much as 25%, for periods of up to 15 months, despite disease progression. Noninvasive positive pressure ventilation did not cause reduced quality of life, as any fall in scores in the ventilated group were comparable to those seen in a control group. In conclusion, noninvasive positive pressure ventilation enhances quality of life when used to treat sleep-disordered breathing in patients with ALS.

Aged↗

PubMed2001

Developmental regulation of transcription by a tissue-specific TAF homolog.

Alternate forms of the general transcription machinery have been described in several tissues or cell types. However, the role of tissue-specific TBP-associated factors (TAF(II)s) and other tissue-specific transcription components in regulating differential gene expression during development was not clear. Here we show that the cannonball gene of Drosophila encodes a cell type-specific homolog of a more ubiquitously expressed component of the general transcription factor TFIID. cannonball is required in vivo for high level transcription of a set of stage- and tissue-specific target genes during male gametogenesis. Regulation of transcription by cannonball is absolutely required for spermatogenesis, as null mutations block meiotic cell cycle progression and result in a complete failure of spermatid differentiation. Our results demonstrate that cell type-specific TAF(II)s play an important role in developmental regulation of gene expression.

Alleles↗

PubMed2001

A database of protein expression in lung cancer.

We have developed a comprehensive approach to identifying molecular changes in lung cancer that includes both genomic and proteomic analyses. The related effort has produced a large amount of data pertaining to gene expression at the RNA and protein levels. As a result, we have constructed a database that contains protein expression data on lung cancer as well as other relevant data including DNA microarray derived data. A large number of proteins that are expressed in different types of lung cancer have been identified and have been correlated with the expression measures for their corresponding genes at the RNA level. The database is intended to facilitate our effort at developing novel classification schemes for lung cancer and the identification of novel markers for early diagnosis.

Biomarkers, Tumor↗

PubMed2001

Identification of androgen-regulated genes in the prostate cancer cell line LNCaP by serial analysis of gene expression and proteomic analysis.

A common therapy for nonorgan-confined prostate cancer involves androgen deprivation. To develop a better understanding of the effect of androgen on prostatic cells, we have analyzed gene expression changes induced by dihydrotestosterone (DHT) in the androgen responsive prostate cancer line LNCaP, at both RNA and protein levels. Changes at the RNA level induced by DHT were determined by means of serial analysis of gene expression (SAGE), and protein profiling was done by means of quantitative two-dimensional polyacrylamide gel electrophoresis. Among 123,371 transcripts analyzed, a total of 28,844 distinct SAGE tags were identified representing 16,570 genes. Some 351 genes were significantly affected by DHT treatment at the RNA level (p < 0.05), of which 147 were induced and 204 repressed by androgen. In two independent experiments, the integrated intensity of 32 protein spots increased and 12 decreased at least two-fold in response to androgen, out of a total of 1031 protein spots analyzed. The change in intensity for most of the affected proteins identified could not be predicted based on the level of their corresponding RNA. Our study provides a global assessment of genes regulated by DHT and suggests a need for profiling at both RNA and protein levels for a comprehensive evaluation of patterns of gene expression.

Androgens↗

PubMed2001

Kaposi's sarcoma-associated herpesvirus/human herpesvirus-8 ORF50 gene product contains a potent C-terminal activation domain which activates gene expression via a specific target sequence.

The ART (Activator of Replication and Transcription) protein of Kaposi's sarcoma-associated herpesvirus (KSHV), or human herpesvirus-8 (HHV-8), is encoded by the ORF50 gene. It is expressed as an immediate-early gene and plays a crucial role in the transition between latency and productive infection. HHV-8 ART is a transcriptional transactivator which can up-regulate viral gene expression. Transient expression assays showed that ART strongly activated ORF57 and K8 promoter-directed gene expression in both CV-1 and BJAB cells. The ART target site was mapped to a 40-bp region compassing nt 81904 to 81943 on the ORF57 promoter. When linked upstream to a heterologous SV40 promoter, this region by itself was able to confer ART responsiveness. This 40-bp segment contains a 16-bp consensus sequence which is also found in the K8 promoter region located between nt 74769 to 74784. Deletion of the fragment including this 16-bp consensus abrogated the ART responsiveness of the K8 promoter. The role of this 16-bp consensus in ART transactivation was further supported by site-directed mutagenesis. Mutations of the conserved nucleotides within the 16-bp consensus in the ORF57 promoter dramatically impaired its responsiveness to ART. Fusion protein analysis with chimeric proteins containing the DNA binding domain of yeast transactivator Gal4 (residues 1 to 147) and different ART segments defined an acidic C-terminal region (amino acids [aa] 527 to 634) as a potent activator. Deletions of this activation domain in the ART protein resulted in a decrease or loss of its ability to activate ORF57 and K8 promoters containing the ART responsive element in transfected cells. How the ART activation domain activates ORF57 and K8 gene expression through the 16-bp consensus sequence remains to be determined.

Basic-Leucine Zipper Transcription Factors↗

PubMed2001

Characterization of Kaposi's sarcoma-associated herpesvirus/human herpesvirus-8 ORF57 promoter.

Kaposi's sarcoma-associated herpesvirus (KSHV) is a recently discovered human gamma herpesvirus (HHV-8) that plays an important role in Kaposi's sarcoma development. Here, we further characterize the regulation of the early HHV-8 gene, open reading frame 57 (ORF57). ORF57 is a spliced gene consisting of two exons with a 108-bp intron near the 5' end. The ORF57 mRNA can potentially be initiated at two different start sites, and its expression can be significantly stimulated by ORF50, an HHV-8 immediate early gene. The target site for ORF50 transactivation was mapped to a 40-bp fragment compassing nt 81904 to 81943 in the ORF57 promoter. Our study on the regulation of ORF57 expression by ORF50 provides the basis for further studies on the regulation of HHV-8 lytic gene expression.

Animals↗

PubMed2001

Sensitivity of the spiny dogfish (Squalus acanthias) to waterborne silver exposure.

The physiological effects of waterborne silver exposure (added as AgNO(3)) on spiny dogfish, Squalus acanthias, were evaluated at 30, 200 and 685 microg silver per l in 30 per thousand seawater. These concentrations cover the toxic range observed for freshwater teleosts, where silver is extremely toxic, to seawater teleosts which tolerate higher silver concentrations. However, these levels are considerably higher than those that occur in the normal environment. At 685 microg l(-1), dogfish died within 24 h. Causes of death were respiratory as well as osmoregulatory failure. Arterial P(a)O(2) rapidly declined below 20 Torr, and blood acidosis (both respiratory and metabolic) occurred. Urea excretion increased dramatically and plasma urea dropped from 340 to 225 mM. There were pronounced increases in plasma Na(+), Cl(-), and Mg(2+), indicative of ionoregulatory failure due to increased diffusive permeability as well as inhibited NaCl excretion. At 200 microg l(-1), fish died between 24 and 72 h of silver exposure. The same physiological events occurred with a small time delay. At 30 microg l(-1), effects were much less severe, although slight mortality (12.5%) still occurred. Respiratory alkalosis occurred, together with moderate elevations in plasma Na(+) and Cl(-) levels. Silver accumulated to the highest concentrations on gills, with only low levels in the intestine, in accord with the virtual absence of drinking. Na(+)/K(+)-ATP-ase activities of gill and rectal gland tissue were impaired at the highest silver concentration. Normal gill function was impaired due to swelling and fusion of lamellae, lamellar aneurism and lifting of the lamellar epithelium. Our results clearly indicate that this elasmobranch is much more sensitive (about 10-fold) to silver than marine teleosts, with silver's toxic action exerted on the gill rather than on the intestine, in contrast to the latter.

Animals↗

PubMed2001

Abnormal executive function in attention deficit hyperactivity disorder: the effect of stimulant medication and age on spatial working memory.

OBJECTIVE: This study sought to examine the factors associated with spatial working memory and the use of strategies to impairments in spatial working memory in children with attention deficit hyperactivity disorder (ADHD). The developmental trajectories for spatial working memory in medicated and medication naïve children with ADHD were investigated. In addition, the effect of psychostimulant medication on deficits in spatial working memory was examined. METHOD: A cross-sectional study compared performance between 21 psychostimulant medicated children with ADHD, 27 medication naïve children with ADHD and 26 matched control subjects on computerized tests of spatial memory and spatial working memory. RESULTS: Compared with the controls, performance in medication naïve children with ADHD was significantly worse on the spatial working memory task. There was no difference in performance between the medicated children with ADHD and the control subjects on this same task, despite the ongoing symptoms of ADHD in the former group. The pattern of normal and abnormal performance in the ADHD groups was age-independent. CONCLUSIONS: Deficits in executive functions related to spatial working memory do occur in children with ADHD, although the magnitude of these deficits is not related to the child's age or the level of ADHD symptoms. These deficits were not present in the current sample of children who were receiving psychostimulant medication.

Age Factors↗

PubMed2001

Embryo splitting: a role in infertility?

Embryo splitting may be used to increase the potential fertility of couples requiring IVF. Using cattle as a model, it is possible to increase pregnancy rates from 70% per transfer of good quality in-vivo-produced embryos, to 110% by transferring the two demi-embryos resulting from the bisection of one embryo. The 30-40% greater chance of conception would reduce costs for the government, health authorities and patients, and reduce stress, time and complications for women having IVF treatment. Embryo splitting may also provide donor embryos for infertile couples that cannot conceive naturally or with IVF. The shortage of children for adoption and donor embryos may be overcome by the production of demi-embryos.

Animals↗

PubMed2001

Plumage and mitochondrial DNA haplotype variation across a moving hybrid zone.

We analyze variation in phenotypes and mitochondrial DNA (mtDNA) haplotypes over the breeding ranges of hermit and Townsend's warblers and across two of their three hybrid zones. Within these two hybrid zones, we demonstrate that the placement, shape, and width of transitions in seven plumage characters are remarkably similar, suggesting that a balance between dispersal and sexual selection keeps these hybrid zones narrow. A consistent asymmetry in these character transition curves suggests that Townsend's warblers have a selective advantage over hermit warblers, which is presumably due to the aggressive superiority of Townsend's over hermit males (Pearson and Rohwer 2000). An association between plumage and mtDNA haplotypes shows that pure Townsend's warblers, but not pure hermit warblers, immigrate into these hybrid zones, further supporting the competitive superiority of Townsend's warblers over hermit warblers. The mitochondrial haplotype transitions across these hybrid zones are much wider than the phenotypic transitions and provide no indication that the mtDNA haplotypes representing these two warblers are selectively maintained. More importantly, the phenotypically pure populations of Townsend's warblers throughout a 2,000-km coastal strip north of the Washington hybrid zones contain a preponderance of hermit warbler mtDNA haplotypes. This result suggests massive movement of the hybrid zone between these warblers during the 5,000 years since their most recent interglacial contact. We develop a model to explain the phenotypic and genetic divergence between these warblers and the evolution of their dramatic differences in aggressiveness; we also show how differences in male aggression, in combination with biased pairing patterns, can explain the haplotype footprint recording the historical movement of this hybrid zone.

Aggression↗

PubMed2001

The current status of polycystic ovary syndrome.

The importance of polycystic ovary syndrome (PCOS) has recently received much publicity. Whereas previously it was thought simply to be a disorder which was characterised by irregular ovulation, there is now evidence to show that it is a systemic metabolic disease determined genetically and inherited. As well as treating the presenting problem which, for gynaecologists is usually one of irregular menstruation and anovulation, or sometimes signs of hyperandrogenism, we believe that women should also be screened for their lipid status and insulin resistance. Advice on behaviour modification such as increased exercise and dietary adjustment should be recommended in addition to the treatment for ovulation induction. In the future, the use of insulin sensitising agents may become important in the treatment of PCOS.

Cardiovascular Diseases↗

PubMed2001

Differentiation of two bovine lentiviruses by a monoclonal antibody on the basis of epitope specificity.

Bovine immunodeficiency virus (BIV) and Jembrana disease virus (JDV) are bovine lentiviruses that are closely related genetically. A recombinant fusion protein containing the capsid protein of BIV expressed in Escherichia coli was used to immunize mice and produce monoclonal antibodies. Six hybridomas specific for BIV capsid protein were identified, and one antibody, designated 10H1, was characterized further. Competitive binding assays were performed to analyze the topography of antigenic determinants by enzyme-linked immunosorbent assay and demonstrated the existence of at least three distinct antigenic determinants on capsid protein. The monoclonal antibody reacted specifically with both BIV capsid and the recombinant fusion protein in Western immunoblot analyses. However, it did not react with the recombinant capsid fusion protein of JDV, indicating that BIV contains at least one unique epitope in the capsid protein that is absent in JDV. Further mapping of the epitope by chemical cleavage analysis identified that the epitope is located at the 6.4-kDa N terminus of the 29-kDa capsid protein. This monoclonal antibody assay will be valuable for distinguishing the two closely related lentiviruses by Western blotting.

Animals↗

PubMed2001

Identification of a cellular protein that interacts and synergizes with the RTA (ORF50) protein of Kaposi's sarcoma-associated herpesvirus in transcriptional activation.

Lytic reactivation of Kaposi's sarcoma-associated herpesvirus (KSHV), or human herpesvirus 8, from latency requires transcriptional transactivation by the viral protein RTA encoded by the ORF50 gene. Very little is known about how RTA functions and the cellular factors that may be involved in its transactivation function. Using the yeast two-hybrid system, we have identified a human cellular protein that can interact with KSHV RTA. The cellular protein, referred to as the human hypothetical protein MGC2663 by GenBank, is encoded by human chromosome 19. This protein is 554 amino acids (aa) in size and displays sequence similarity with members of the Krueppel-associated box-zinc finger proteins (KRAB-ZFPs). MGC2663 expression could be detected in all primate cell lines tested, and its expression level was neither stimulated nor inhibited by RTA. MGC2663 specifically synergizes with RTA to activate viral transcription, and overexpression of MGC2663 in the presence of RTA further enhances RTA transactivation of several viral promoters that were identified as targets for RTA. Coimmunoprecipitation and pull-down assays further demonstrated that MGC2663 interacts with RTA both in vivo and in vitro, and the N-terminal 273 aa of KSHV RTA and the potential zinc finger domain of MGC2663 are required for their interaction. Our results indicate that this novel human cellular protein, MGC2663, named K-RBP (KSHV RTA binding protein) due to its RTA binding feature, specifically interacts with the KSHV RTA protein and functions as a cellular RTA cofactor to activate viral gene expression. Though its normal cellular function needs to be further studied, K-RBP may play a significant role in mediating RTA transactivation in vivo.

Binding Sites↗

PubMed2001

Tissue and wound healing effects of short duration postoperative oxygen therapy.

The purpose of this study was to determine the effects of 28% oxygen given in the first 36 hours after surgery on tissue oxygen, collagen deposition, and clinical healing outcomes. Twenty-four subjects having cervical spine surgical procedures participated in a randomized, repeated-measures pilot study of tissue and healing effects of postoperative supplemental oxygen. The treatment group (n = 13) received 28% oxygen for the first 36 postoperative hours, whereas the control group (n = 11) was maintained on room air. Subcutaneous tissue oxygen and temperature were measured at intervals up to 36 hours postsurgery. Wound healing was evaluated by hydroxyproline content in a subcutaneous polytetrafluoroethylene tube removed on the 7th postoperative day. Clinical outcomes were evaluated for the 30 days post-hospital discharge. Subjects in the treatment group had significantly higher tissue oxygen tension overall, and at postoperative hours 1, 2, 18, and 36, with mean values 10 to 20 mm Hg higher than control subjects. Significant differences were not found in hydroxyproline levels or clinical wound outcome measures. Low level, short duration, supplemental oxygen increased and sustained wound tissue oxygen and was well tolerated by subjects. Larger studies of populations at risk for wound complications are needed to investigate variables of dose and duration of oxygen therapy in relation to clinical and cellular wound healing outcomes.

Adult↗

PubMed2001

How many inpatients at an acute hospital have palliative care needs? Comparing the perspectives of medical and nursing staff.

The primary aim of this prospective face-to-face interview survey was to identify the proportion of inpatients at an acute hospital (Royal Hallamshire Hospital, Sheffield, UK) considered to have palliative care needs by medical and nursing staff directly responsible for their care. During the 1-week period of the survey (6-10 September 1999), 452 inpatients were present in the hospital. Nursing staff were interviewed for 99% of patients; medical staff for 81%. Staff interview data were supplemented by case note review. Overall, 23% of the total inpatient population were identified as having palliative care needs and/or being terminally ill by staff and 11% were considered suitable for referral to a specialist palliative care bed. However, there was a low level of concurrence between medical and nursing staff as to which individual patients had palliative care needs (although this increased with perceived increased proximity to death), including which would be suitable for referral to a specialist palliative care bed. A need for further palliative care education for medical and nursing staff working within acute hospital settings was identified to ensure that the best use is made of hospital-based specialist palliative care services.

Acute Disease↗

PubMed2001

Restoration of reproductive potential following expiration or removal of melengestrol acetate contraceptive implants in golden lion tamarins (Leontopithecus rosalia).

Although reversible contraception is important to successful management of small populations, there are concerns about the reversibility of melengestrol acetate (MGA), the most commonly used implant in captive animals. Female golden lion tamarins (Leontopithecus rosalia) placed in potential breeding situations after surgical MGA implant removal showed a 75% return to reproduction within 2 yr, unlike golden-headed tamarins (Leontopithecus chrysomelas), which have had a 29% return to reproduction following implant removal. This rate was indistinguishable from the breeding probability for newly formed pairs involving nonimplanted females. Litter size, stillbirth rate, and infant survival rate were not significantly different between nonimplanted and implant-removed female golden lion tamarins. However, females with implants left in (and assumed to have expired) showed higher stillbirth and infant mortality rates than did females with implants removed. For seven female golden lion tamarins for which reproductive histories before and after MGA implantation were available, litter size was unaffected by MGA implantation and subsequent removal. Infant survival rate for these females appeared to be lower after removal but was indistinguishable from rates in the nonimplanted females. Prior reproductive experience, length of time with an implant, and age of the females did not affect the probability of breeding for females after removal of the implants. Overall, breeding probability of nonimplanted females declined with age. Although the results of this study confirm the reversibility of MGA implants in golden lion tamarins, there appear to be some effects on viability of offspring, particularly offspring born to females with implants left in and presumed expired.

Age Factors↗

PubMed2001

Human herpesvirus 8 can be transmitted through blood in drug addicts.

Human Herpes virus type-8 (HHV-8) seroprevalence was studied in a population of HIV positive intravenous drug users (IVDUs) from Argentina. Analysis of this population also indirectly made it possible to study HHV-8 blood transmission, because these individuals frequently engage in needle sharing behavior and are capable of acquiring a broad array of blood borne pathogens, including Hepatitis B/C virus. The seroprevalence of HHV-8 in IVDUs was compared to a group of non-IVDUs and HIV negative individuals. Of the 223 individuals tested, 13.45% were HHV-8 positive, 16.99% in the IVDUs group, and 5.71% in the non-IVDUs. Among HIV positive IVDUs, 25/144 (17.36%) were also HHV-8 seropositive. The seropositivity rate of HHV-8 in HIV negative IVDUs was 11.1%. In contrast, HHV-8 seroprevalence in HIV negative heterosexual individuals without drug usage behavior was even lower (5.71%). The rate of HHV-8 infection in HIV positive IVDUs was three times as high compared to the non IVDU HIV negative individuals, suggesting that IVDU is a risk for HHV-8 infection. Furthermore, it was found that IVDUs showed a very high rate of Hepatitis B/C (52.77%), which also correlate with HHV-8 infection in this population (23.68%). All Hepatitis B/C positive individuals were also HIV positive. Our data confirm other studies showing that individuals who share needles are at risk for acquiring Hepatitis B/C and HIV infections. In addition, our results suggest that they are also at risk to acquiring HHV-8 infection by the same route.

Adult↗