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Biomedical subjects

S Wood

Publications and source records attributed to S Wood.

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

General-practice-based nurse specialists-taking a lead in improving the care of people with epilepsy.

Epilepsy is almost as common as diabetes and some 750 people with epilepsy die suddenly and prematurely each year. Unfortunately, the management of epilepsy has been much neglected and services often remain fragmented and difficult for patients to understand. We employed a nurse specialist in epilepsy to work with practice nurses in a group of general practices to promote better care, to make patients aware of sources of help and support, and to provide information about issues such as driving, employment and pregnancy. Over 70% of patients with epilepsy attended 'clinics' run by the specialist nurse and many previously unidentified problems were successfully resolved-including misdiagnosis, over-medication and lack of awareness of the side-effects of antiepileptic drugs. Nurse specialists in epilepsy, working with groups of general practices but in collaboration with hospital specialists and voluntary organizations, can take a lead role in facilitating joint working between all those involved in service provision, in training practice nurses and others in the special needs of people with epilepsy and in providing support in hospital clinics.

Adolescent↗
PubMed2000

The use of the neuropsychiatric inventory in nursing home residents. Characterization and measurement.

The authors assessed the validity of the nursing home version of the Neuropsychiatric Inventory-Nursing Home Version (NPI-NH), comparing the responses of certified nurses' aides (CNAs) and licensed vocational nurses (LVNs) with research observations. Correlations were significant but moderate for all of the domains of the NPI-NH (delusions, hallucinations, agitation/aggression, depression, apathy, disinhibition, euphoria, irritability/lability, and aberrant motor disturbances) except anxiety and appetite disturbance. The LVNs' ratings showed consistently higher correlations with the researchers' behavioral observations than did the CNAs', but were moderate and generally better for residents with high levels of neuropsychiatric symptoms, thus, caution should be used with any untrained rater in the nursing home setting. The NPI-NH used by non-research staff can be useful in identifying residents with significant neuropsychiatric disturbances, but may be limited as an instrument for tracking behavioral changes.

Adult↗
PubMed2000

Analysis of the N gene hypersensitive response induced by a fluorescently tagged tobacco mosaic virus.

The hypersensitive response (HR) triggered on Nicotiana edwardsonii by tobacco mosaic virus was studied using a modified viral genome that directed expression of the green fluorescent protein. Inoculated plants were initially incubated at 32 degrees C to inhibit the N gene-mediated HR. Transfer to 20 degrees C initiated the HR, and fluorescent infection foci were monitored for early HR-associated events. Membrane damage, which preceded visible cell collapse by more than 3 h, was accompanied by a transient restriction of the xylem within infection sites. Following cell collapse and the rapid desiccation of tissue undergoing the HR, isolated, infected cells were detected at the margin of necrotic lesions. These virus-infected cells were able to reinitiate infection on transfer to 32 degrees C, however, if maintained at 20 degrees C they eventually died. The results indicate that the tobacco mosaic virus-induced HR is a two-phase process with an early stage culminating in rapid cell collapse and tissue desiccation followed by a more extended period during which the remaining infected cells are eliminated.

Cell Death↗
PubMed1999

Analysis of oxidative DNA damage and HPRT mutations in humans after hyperbaric oxygen treatment.

DNA damage induced by reactive oxygen species (ROS) seems to play an important role in the induction of mutations and cancer. We have recently shown that hyperbaric oxygen (HBO) treatment of volunteers (i.e., exposure to 100% oxygen at a pressure of 2.5 ATA) induces DNA damage detected in leukocytes with the comet assay. Using formamidopyrimidine-DNA glycosylase (FPG protein) we provided indirect evidence for the induction of oxidative DNA base damage. We now comparatively evaluated FPG-sensitive sites with the comet assay and 7,8-dihydro-8-oxo-deoxyguanosine (8-OHdG) with HPLC analysis after a single HBO. As 8-OHguanine (8-OHgua) is one of the major DNA modifications induced by ROS and a pre-mutagenic lesion, we looked for HBO-induced mutations at the HPRT locus with the T cell cloning test. We also determined the genotypes for glutathione transferases (GST) and tested a possible influence of the GSTM1 and GSTT1 genotypes on the sensitivity of subjects against HBO-induced genotoxicity. Our results indicate that despite a clear induction of FPG-sensitive sites no increased levels of 8-OHdG and no induction of HPRT mutations was detected in lymphocytes after HBO. Furthermore, the DNA effects in the comet assay and the mutant frequencies in the HPRT test seem to be unrelated to the GST genotypes of the test subjects.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1999

Genomic organization, expression, and chromosome location of the human SNAIL gene (SNAI1) and a related processed pseudogene (SNAI1P).

Some of the zinc finger proteins of the snail family are essential in the formation of mesoderm during gastrulation and the development of neural crest and its derivatives. We have isolated the human SNAIL gene (HGMW-approved symbol SNAI1) and describe its genomic organization, having sequenced a region spanning more than 5882 bp. The human SNAIL gene contains three exons. The SNAIL transcript is 2. 0 kb and is found in placenta and adult heart, lung, brain, liver, and skeletal muscle. It codes for a protein of 264 amino acids and 29.1 kDa. This protein contains three classic zinc fingers and one atypical zinc finger. The human SNAIL protein is 87.5, 58.7, 50.9, 50.7, 55.4, and 31.5% identical to mouse Snail, chicken snail-like, zebrafish snail1, zebrafish snail2, Xenopus snail, and Drosophila snail proteins, respectively. The zinc finger region is 95.5% identical between human and mouse Snail. Because Drosophila snail and twist are important regulators during mesoderm development and because human TWIST mutations have been implicated in craniosynostosis, a cohort of 59 patients with craniosynostosis syndromes were screened for SNAIL mutations. None were found. By somatic cell and radiation hybrid mapping panels, SNAIL was localized to human chromosome 20q13.2, between markers D20S886 and D20S109. A SNAIL-related, putative processed pseudogene (HGMW-approved symbol SNAI1P) was also isolated and maps to human chromosome 2q33-q37.

Adult↗
PubMed1999

An in vitro study of the use of photodynamic therapy for the treatment of natural oral plaque biofilms formed in vivo.

Seven-day oral plaque biofilms have been formed on natural enamel surfaces in vivo using a previously reported in situ device. The devices are then incubated with a cationic Zn(II) phthalocyanine photosensitizer and irradiated with white light. Confocal scanning laser microscopy (CSLM) of the biofilms shows that the photosensitizer is taken up into the biomass of the biofilm and that significant cell death is caused by photodynamic therapy (PDT). In addition, the treated biofilms are much thinner than the control samples and demonstrate a different structure from the control samples, with little evidence of channels and a less dense biomass. Transmission electron microscopy (TEM) of the in vivo-formed plaque biofilms reveals considerable damage to bacteria in the biofilm, vacuolation of the cytoplasm and membrane damage being clearly visible after PDT. These results clearly demonstrate the potential value of PDT in the management of oral biofilms.

Biofilms↗
PubMed1999

Confirmation of linkage in X-linked infantile spasms (West syndrome) and refinement of the disease locus to Xp21.3-Xp22.1.

The syndrome of infantile spasms, hypsarrhythmia, and mental retardation (West syndrome) is a classical form of epilepsy, occurring in early infancy, which is etiologically heterogeneous. In rare families, West syndrome is an X-linked recessive condition, mapped to Xp11.4-Xpter (MIM 308350). We have identified a multi-generation family from Western Canada with this rare syndrome of infantile spasms, seen exclusively in male offspring from asymptomatic mothers, thereby confirming segregation as an X-linked recessive trait. Using highly polymorphic microsatellite CA-repeat probes evenly distributed over the entire X chromosome, linkage to markers DXS7110, DXS989, DXS1202, and DXS7106 was confirmed, with a maximum LOD score of 3.97 at a theta of 0.0. The identification of key recombinants refined the disease-containing interval between markers DXS1226 and the adrenal hypoplasia locus (AHC). This now maps the X-linked infantile spasms gene locus to chromosome Xp21.3-Xp22.1 and refines the interval containing the candidate gene to 7.0 cM. Furthermore, this interval overlaps several loci previously linked with either syndromic or non-syndromic X-linked mental retardation (XLMR), including one recognized locus implicated in neuroaxonal processing (radixin, RDXP2). Collectively, these studies lend strong support for the presence of one or more genes intrinsic to brain development and function, occurring within the critical interval defined between Xp21.3-Xp22.1.

Chromosome Mapping↗
PubMed1999

The hypothalamic-pituitary-adrenal axis response to endotoxin is attenuated during lactation.

Pregnancy and lactation are times of prolonged physiological changes affecting the neuroendocrine and immunological systems. One well-characterized change is the neuroendocrine hyporesponsiveness to acute stressful stimuli. We have now designed studies to see whether there is an alteration in the response of the hypothalamic-pituitary-adrenal (HPA) axis to an immunological inflammatory challenge and to ascertain whether lactating animals show altered neural and endocrine responses to inflammatory stimuli. Lactating (day 9-12 postpartum) or virgin control Sprague-Dawley female rats were injected with either 200 microg of endotoxin (lipopolysaccharide, LPS ) or sterile saline given i.p. Trunk blood or jugular blood was collected from the animals at 2 h or hourly over 6 h after injection. Both plasma adrenocorticotropic hormone (ACTH) and corticosterone concentrations were significantly higher in saline treated lactating animals compared with the virgin group. LPS significantly elevated circulating levels of plasma ACTH and corticosterone in both virgin and lactating animals compared with saline controls, however, hormone responses to LPS were significantly reduced in lactating animals relative to virgin controls. Corticosterone-binding globulin concentrations were lower in lactating animals compared to virgin animals and LPS decreased concentrations in virgin, but not lactating rats. Analysis of cfos mRNA in the paraventricular nucleus (PVN) of the hypothalamus revealed that 2 h following injection there was a increase in cfos expression only in the virgin animals treated with LPS, compared to all other treatment conditions. Corticotropin-releasing hormone (CRH) mRNA expression was overall greater in virgin animals, but was increased to similar extent in both virgin and lactating animals treated with LPS. Primary arginine vasopressin (AVP) mRNA transcripts were increased 2 h following LPS injection, but a greater increase in expression was seen in virgin animals. These data demonstrate that there is a lower level of free circulating glucocorticoid in response to inflammatory stimuli and suggests that communication between the immune and endocrine systems may be altered during lactation.

Adrenocorticotropic Hormone↗
PubMed1999

Modelling of the disulphide-swapped isomer of human insulin-like growth factor-1: implications for receptor binding.

Insulin-like growth factor-1 (IGF-1) is a serum protein which unexpectedly folds to yield two stable tertiary structures with different disulphide connectivities; native IGF-1 [18-61,6-48,47-52] and IGF-1 swap [18-61,6-47, 48-52]. Here we demonstrate in detail the biological properties of recombinant human native IGF-1 and IGF-1 swap secreted from Saccharomyces cerevisiae. IGF-1 swap had a approximately 30 fold loss in affinity for the IGF-1 receptor overexpressed on BHK cells compared with native IGF-1. The parallel increase in dose required to induce negative cooperativity together with the parallel loss in mitogenicity in NIH 3T3 cells implies that disruption of the IGF-1 receptor binding interaction rather than restriction of a post-binding conformational change is responsible for the reduction in biological activity of IGF-1 swap. Interestingly, the affinity of IGF-1 swap for the insulin receptor was approximately 200 fold lower than that of native IGF-1 indicating that the binding surface complementary to the insulin receptor (or the ability to attain it) is disturbed to a greater extent than that to the IGF-1 receptor. A 1.0 ns high-temperature molecular dynamics study of the local energy landscape of IGF-1 swap resulted in uncoiling of the first A-region alpha-helix and a rearrangement in the relative orientation of the A- and B-regions. The model of IGF-1 swap is structurally homologous to the NMR structure of insulin swap and CD spectra consistent with the model are presented. However, in the model of IGF-1 swap the C-region has filled the space where the first A-region alpha-helix has uncoiled and this may be hindering interaction of Val44 with the second insulin receptor binding pocket.

3T3 Cells↗
PubMed1999

The medical dictionary for regulatory activities (MedDRA).

The International Conference on Harmonisation has agreed upon the structure and content of the Medical Dictionary for Regulatory Activities (MedDRA) version 2.0 which should become available in the early part of 1999. This medical terminology is intended for use in the pre- and postmarketing phases of the medicines regulatory process, covering diagnoses, symptoms and signs, adverse drug reactions and therapeutic indications, the names and qualitative results of investigations, surgical and medical procedures, and medical/social history. It can be used for recording adverse events and medical history in clinical trials, in the analysis and tabulations of data from these trials and in the expedited submission of safety data to government regulatory authorities, as well as in constructing standard product information and documentation for applications for marketing authorisation. After licensing of a medicine, it may be used in pharmacovigilance and is expected to be the preferred terminology for international electronic regulatory communication. MedDRA is a hierarchical terminology with 5 levels and is multiaxial: terms may exist in more than 1 vertical axis, providing specificity of terms for data entry and flexibility in data retrieval. Terms in MedDRA were derived from several sources including the WHO's adverse reaction terminology (WHO-ART), Coding Symbols for a Thesaurus of Adverse Reaction Terms (COSTART), International Classification of Diseases (ICD) 9 and ICD9-CM. It will be maintained, further developed and distributed by a Maintenance Support Services Organisation (MSSO). It is anticipated that using MedDRA will improve the quality of data captured on databases, support effective analysis by providing clinically relevant groupings of terms and facilitate electronic communication of data, although as a new tool, users will need to invest time in gaining expertise in its use.

Adverse Drug Reaction Reporting Systems↗
PubMed1999

Effects of ethanol on leptin secretion and the leptin-induced luteinizing hormone (LH) release from late juvenile female rats.

BACKGROUND: Chronic ethanol (EtOH) exposure lowers serum insulin-like growth factor-1 (IGF-1) and luteinizing hormone (LH) levels and also delays female puberty, similar to the deficits in the reproductive system that occur during leptin deficiency. Leptin administration restores fertility and gonadotropin secretion in the ob/ob mouse and can induce recovery of reproductive function in food-restricted animals. This study assessed the effects of EtOH on serum leptin levels, and whether exogenous leptin administration could restore IGF-1 and LH levels in the EtOH-treated animals. METHODS: In the first study, 29-day-old female rats were divided into control and EtOH-treated groups, each of which received their respective diet regimen for 5 consecutive days. The EtOH-treated animals were subdivided and received an intraperitoneal injection of either leptin (100 microg/0.1 ml) or saline twice daily. Control animals also received intraperitoneal saline injections twice daily. On day 34, animals were killed, and serum leptin, LH, and IGF-1 were measured by RIA. In a second study we assessed the acute effects of a single 3 g/kg dose of EtOH on the ability of leptin to act centrally to induce LH release. For this, leptin (1 microg) was administered via a third ventricular (3V) cannula and blood sampling via jugular cannula. In a third experiment, animals were again subjected to a chronic feeding regimen. When 34 days old, they were killed and the anterior pituitaries removed and incubated in a static incubation system for 60 min to establish basal LH release, then for an additional 60 min in medium containing leptin (10(-7) M). RESULTS: Chronic EtOH exposure lowered serum leptin (p < 0.01), IGF-1 (p < 0.01), and LH (p < 0.05) levels. Leptin administration to EtOH-treated animals did not restore serum IGF-1 levels. This peptide did, however, effectively restore LH levels to normal, but did not advance the timing of puberty. Acute EtOH administration was found to block leptin-induced LH release following central administration of the peptide. Conversely, anterior pituitaries from control and 5-day EtOH-treated animals that were incubated in vitro released (p < 0.01) equal amounts of LH in response to leptin (10(-7) M). CONCLUSIONS: These data demonstrate that EtOH administration not only can suppress peripheral levels of leptin, but also blocks its central action to facilitate LH secretion. Although replacement of leptin can reverse the EtOH-induced suppression of LH by a direct action at the level of the pituitary, it cannot elevate serum IGF-1; a peripheral signal that acts centrally to stimulate LH releasing-hormone (LHRH)/LH release during the juvenile-peripubertal transition period, and thus accelerates the initiation of female puberty. These results demonstrate further the complex actions and interactions of multiple hormones involved in the pubertal process and the vulnerability of their actions to the toxic effects of EtOH.

Age Factors↗
PubMed1999

Someone to talk to? The role of loneliness as a factor in the frequency of GP consultations.

BACKGROUND: There are many reasons why people frequently consult their general practitioner (GP). Although loneliness is increasingly recognized as a problem affecting well-being for elderly people, it has rarely been addressed as a predictor of frequency of consultation. AIM: To examine whether loneliness is associated with rates of GP consultations (home and surgery visits). METHOD: Analysis of data collected in face-to-face interviews at the second wave of a longitudinal health survey of two adult age cohorts living in four socially contrasting urban localities in Glasgow City. There were a total of 691 subjects: 142 males and 176 females aged 40 years at interview; and 167 males and 206 females aged 60 years at interview. Frequency of reported GP consultations in the past 12 months at home or in the surgery was examined. RESULTS: After controlling for sociodemographic and socioeconomic variables and health, loneliness was significantly associated with frequency of consultation at the surgery but not with the frequency of home visits. CONCLUSION: Loneliness may still be underestimated as a factor related independently to frequency of consultations with a GP at the surgery.

Adult↗
PubMed1998

Human SLUG gene organization, expression, and chromosome map location on 8q.

SLUG is a member of the snail family of zinc finger proteins. It is involved in epithelial to mesenchyme cell transition during neurulation and plays a role in limb bud development. We have isolated and described the human SLUG gene by sequencing a region spanning 4034 bp. The human SLUG gene contains three exons. The SLUG transcript is 2.2 kb and is found in placenta and adult heart, pancreas, liver, kidney, and skeletal muscle, and it codes for a protein of 268 amino acids and 29.989 kDa. This protein contains five zinc finger regions. The human SLUG protein is 95, 93, and 88% homologous to mouse, chicken, and Xenopus slug, respectively, but shows only 47% homology to mouse Snail. The zinc finger region is 100% identical between human and mouse Slug. Slug maps to the long arm of chromosome 8, closely linked to D8S2090 between D8S519 and D8S1098.

Amino Acid Sequence↗
PubMed1998

Alcohol-mediated increases in acetaminophen hepatotoxicity: role of CYP2E and CYP3A.

This commentary focuses on the roles of CYP3A and CYP2E in alcohol-mediated increases in acetaminophen hepatotoxicity. CYP2E has been considered to be the main form of P450 responsible for such toxicity in animals and humans. However, CYP3A, which is also induced by alcohol, has been shown to have a greater affinity for acetaminophen than CYP2E. Previous experiments implicating CYP2E in alcohol-mediated increases in acetaminophen hepatotoxicity have used inhibitors of this form of P450 that are now proving to be non-specific. Triacetyloleandomycin (TAO) is a potent inhibitor of CYP3A that maintains specificity in vitro over a large concentration range. In rats treated with ethanol or the combination of ethanol and isopentanol, the major higher chain alcohol in alcoholic beverages, TAO protects animals from increases in acetaminophen hepatotoxicity, suggesting a major role of CYP3A. CYP2E may not have a major role due to the rapid loss of induced levels in the absence of continued exposure to ethanol. Knockout mice, which are being used to define the role of particular proteins in biological responses, have been developed for CYP2E1 and CYP1A2 but not CYP3A. Cyp2e1(-/-) and Cyp1a2(-/-) mice are more resistant to acetaminophen hepatotoxicity than wild-type strains, even though the amounts of the other forms of P450s are unaltered in the liver. These findings suggest that the relative amounts of P450s and not just kinetic characteristics determine their role in acetaminophen hepatotoxicity. The clinical implications of the findings that CYP3A can have a major role in acetaminophen-mediated hepatotoxicity are discussed.

Acetaminophen↗