PubMed Health⌕ Search

Biomedical subjects

N Carter

Publications and source records attributed to N Carter.

At least 19 recordsLinked to original sources
PubMed2002

Multiphoton versus confocal high resolution z-sectioning of enhanced green fluorescent microtubules: increased multiphoton photobleaching within the focal plane can be compensated using a Pockels cell and dual widefield detectors.

Multiphoton excitation was originally projected to improve live cell fluorescence imaging by minimizing photobleaching effects outside the focal plane, yet reports suggest that photobleaching within the focal plane is actually worse than with one photon excitation. We confirm that when imaging enhanced green fluorescent protein, photobleaching is indeed more acute within the multiphoton excitation volume, so that whilst fluorescence increases as predicted with the square of the excitation power, photobleaching rates increase with a higher order relationship. Crucially however, multiphoton excitation also affords unique opportunities for substantial improvements to fluorescence detection. By using a Pockels cell to minimize exposure of the specimen together with multiple nondescanned detectors we show quantitatively that for any particular bleach rate multiphoton excitation produces significantly more signal than one photon excitation confocal microscopy in high resolution Z-axis sectioning of thin samples. Both modifications are readily implemented on a commercial multiphoton microscope system.

Bacteria↗
PubMed2001

Role of snoring and daytime sleepiness in occupational accidents.

To establish whether snoring and excessive daytime sleepiness (EDS), the main symptoms of obstructive sleep apnea syndrome, influence the risk of occupational accidents a population-based, prospective study was performed. In 1984, 2,874 men aged 30-64 answered questions on snoring and EDS. Ten years later 2,009 (73.8% of the survivors) responded to a follow-up questionnaire including work-related questions and potential confounders. Information on occupational accidents during 1985-1994 was obtained from national register data. A total of 345 occupational accidents were reported by 247 of the men (12.3%). Multivariate analysis revealed that men who reported both snoring and EDS at baseline were at an increased risk of occupational accidents during the following 10 yr, with an adjusted odds ratio of 2.2 (95% CI 1.3-3.8) after adjusting for age, body mass index, smoking, alcohol dependence, years at work, blue-collar job, shift work, and exposure to noise, organic solvents, exhaust fumes, and whole-body vibrations. However, no significant increased risk was found for snorers without EDS or nonsnorers with EDS. We conclude that sleepy, male snorers have an increased risk of occupational accidents. The results indicate that early identification and treatment of sleep-disordered breathing may reduce the number of injuries at work.

Accidents, Occupational↗
PubMed2001

Il-4 therapy prevents the development of proteinuria in active Heymann nephritis by inhibition of Tc1 cells.

The role of IL-4, a key Th2 cytokine, in promoting or inhibiting active Heymann nephritis (HN) was examined. HN is induced by immunization with Fx1A in CFA, and proteinuria in HN is associated with subepithelial IgG and C3 deposition and infiltration of CD8(+) T-cytotoxic 1 (Tc1) cells and macrophages into glomeruli, as well as induction of Abs to Crry. Treatment with rIL-4 from the time of Fx1A/CFA immunization stimulated an earlier IgG1 response to Fx1A, induced anti-Crry Abs, and up-regulated IL-4 mRNA in lymphoid tissue, but did not alter proteinuria. Treatment with MRCOx-81, an IL-4-blocking mAb, resulted in greater proteinuria, which suggests endogenous IL-4 regulated the autoimmune response. Delay of rIL-4 treatment until 4 wk post-Fx1A/CFA immunization and just before the onset of proteinuria prevented the development of proteinuria and reduced Tc1 cell infiltrate in glomeruli. Delayed treatment with IL-4 had no effect on titer or isotype of Abs to Fx1A or on Ig, C3, and C9 accumulation in glomeruli. Treatment with rIL-13, a cytokine that alters macrophage function such as rIL-4, but has no direct effect on T or B cell function, reduced glomerular macrophage infiltrate, but did not prevent proteinuria or CD8+ T cell infiltrate. Anti-Crry Abs were paradoxically only induced with rIL-4 therapy, not in HN controls with proteinuria. It was concluded that the rIL-4 effect was probably by inhibition of Tc1 cells, which normally mediate the glomerular injury that results in proteinuria.

Animals↗
PubMed2001

Vitamin D receptor gene polymorphisms are associated with breast cancer risk in a UK Caucasian population.

There is increasing evidence that vitamin D can protect against breast cancer. The actions of vitamin D are mediated via the vitamin D receptor (VDR). We have investigated whether polymorphisms in the VDR gene are associated with altered breast cancer risk in a UK Caucasian population. We recruited 241 women following a negative screening mammogram and 181 women with known breast cancer. The VDR polymorphism Bsm I, an intronic 3' gene variant, was significantly associated with increased breast cancer risk: odds ratio bb vs BB genotype = 2.32 (95% CI, 1.23-4.39). The Bsm I polymorphism was in linkage disequilibrium with a candidate translational control site, the variable length poly (A) sequence in the 3' untranslated region. Thus, the 'L' poly (A) variant was also associated with a similar breast cancer risk. A 5' VDR gene variant, Fok I, was not associated with breast cancer risk. Further investigations into the mechanisms of interactions of the VDR with other environmental and/or genetic influences to alter breast cancer risk may lead to a new understanding of the role of vitamin D in the control of cellular and developmental pathways.

Adult↗
PubMed2001

Initial sequencing and analysis of the human genome.

The human genome holds an extraordinary trove of information about human development, physiology, medicine and evolution. Here we report the results of an international collaboration to produce and make freely available a draft sequence of the human genome. We also present an initial analysis of the data, describing some of the insights that can be gleaned from the sequence.

Animals↗
PubMed2001

Prevalence of restless legs syndrome among men aged 18 to 64 years: an association with somatic disease and neuropsychiatric symptoms.

Standardized diagnostic criteria determined by the International Restless Legs Syndrome Study Group were used to investigate the current prevalence of restless legs syndrome (RLS). Possible associations between RLS and neuropsychiatric and somatic complaints were also investigated. A random sample of 4,000 men living in central Sweden were sent a questionnaire that included questions about sleep habits, symptoms of sleepiness, and somatic and neuropsychiatric complaints. Four symptom questions accepted as minimal diagnostic criteria for RLS were also included. Odds (OR) ratios and 95% confidence interval (CI) for different variables were calculated by means of multivariate logistic regression; 5.8% of the men suffered from RLS. The prevalence of RLS increased with age. Sleep-related complaints were more frequent among the RLS sufferers. Complaints of headache at awakening and daytime headache were reported three to five times more frequently among RLS sufferers and there was a tendency toward reported social isolation related to RLS. Subjects with RLS more frequently reported depressed mood (OR, 2.6; 95% CI, 1.8-3.8), and complained more often of reduced libido (OR, 2.2; 95% CI, 1.4-3.3). RLS sufferers more frequently reported hypertension (OR, 1.5; 95% CI, 0.9-2.4) and heart problems (OR, 2.5; 95% CI, 1.4-4.3). Results show that restless legs syndrome is common among men. It is hypothesized that RLS may be associated with several somatic and neuropsychiatric symptoms.

Adult↗
PubMed2001

Mycophenolate mofetil treatment accelerates recovery from experimental allergic encephalomyelitis.

Mycophenolate mofetil (MM) acts through its metabolite mycophenolic acid to inhibit inosine monophosphate dehydrogenase (IMPDH), an enzyme essential for purine synthesis in lymphocytes. Oral treatment with MM from the day of immunization for 2 weeks significantly delayed both the development of active experimental allergic encephalomyelitis (EAE) in Lewis rats and reduced the antibody response to myelin basic protein (MBP). MM did not deplete T and B cells, nor did it prevent induction of Th1 or Th2 cytokine in the regional nodes. Treatment of EAE with MM at the onset of clinical symptoms resulted in more rapid recovery from EAE than in control or cyclosporin A (CsA)-treated. MM-treated rats had less infiltration of T cells, B cells, macrophages and dendritic cells into brainstems than either the control or CsA-treated. MM-treated brainstems also had lower level of mRNA for Thl (IL-2, IL-12Rbeta2, IFN-gamma), Th2 (IL-4, IL-10) cytokines and TNF-alpha and TGF-beta compared to that in CsA and controls groups. This study shows MM was superior to CsA in the treatment of EAE and acted by reducing the inflammatory infiltrate, not by suppression of Ig response or by promotion of regulatory cells such as Th2 or Th3.

Animals↗
PubMed2001

Variation in melanin content and composition in type V and VI photoexposed and photoprotected human skin: the dominant role of DHI.

A combination of techniques, including high-performance liquid chromatography (HPLC), spectrophotometric measurements, and a novel method for quantifying melanosome morphology, were applied to the analysis of melanin content and composition in highly pigmented (Fitzpatrick type V and VI) human skin. We found that total epidermal melanin content is significantly elevated in photoexposed type V and VI skin (approximately 1.6 x), while analysis of individual melanin components suggests that pheomelanin content increases only slightly, whereas 5,6-dihydroxyindole-2-carboxylic acid (DHICA)-eumelanin and to a greater extent 5,6-dihydroxyindole (DHI)-eumelanin content are both markedly elevated. Analysis of the relative composition of epidermal melanin in these subjects revealed that DHI-eumelanin is the largest single component (approximately 60-70%), followed by DHICA-eumelanin (25-35%), with pheomelanin being a relatively minor component (2-8%). Moreover, there was a comparative enrichment of DHI-eumelanin at photoexposed sites, with a corresponding decline in the relative contributions from DHICA-eumelanin and pheomelanin. There was also a good correlation and close agreement between the concentration of spheroidal melanosomes determined by morphological image analysis and the concentration of pheomelanin determined by a combination of HPLC and spectrophotometric analysis (r = 0.89, P < 0.02). This study demonstrates the usefulness of melanosome morphology analysis as a sensitive new method for the quantification of melanin composition in human skin. The data also suggest that DHI-eumelanin formation is the dominant pathway for melanin synthesis in heavily pigmented (Fitzpatrick V and VI) skin types in vivo, and is the favoured pathway when melanin production is increased in chronically photoexposed skin.

Biopsy↗
PubMed2001

Reversal of experimental allergic encephalomyelitis with non-mitogenic, non-depleting anti-CD3 mAb therapy with a preferential effect on T(h)1 cells that is augmented by IL-4.

This study examined whether therapy with a non-mitogenic, non-activating anti-CD3 mAb (G4.18) alone, or in combination with the T(h)2 cytokines, could inhibit induction or facilitate recovery from experimental allergic encephalomyelitis (EAE) in Lewis rats. G4.18, but not rIL-4, rIL-5 or anti-IL-4 mAb, reduced the severity and accelerated recovery from active EAE. A combination of rIL-4 with G4.18 was more effective than G4.18 alone. The infiltrate of CD4(+) and CD8(+) T cells, B cells, dendritic cells, and macrophages in the brain stem was less with combined G4.18 and IL-4 than G4.18 therapy or no treatment. Residual cells had preferential sparing of T(r)1 cytokines IL-5 and transforming growth factor-beta with loss of T(h)1 markers IL-2, IFN-gamma and IL-12Rbeta2, and the T(h)2 cytokine IL-4 as well as macrophage cytokines IL-10 and tumor necrosis factor-alpha. Lymph nodes draining the site of immunization had less mRNA for T(h)1 cytokines, but T(h)2 and T(r)1 cytokine expression was spared. Treatment with G4.18, rIL-4 or rIL-5 from the time of immunization had no effect on the course of active EAE. MRC OX-81, a mAb that blocks IL-4, delayed onset by 2 days, but had no effect on severity of active EAE. G4.18 also inhibited the ability of activated T cells from rats with active EAE to transfer passive EAE. This study demonstrated that T cell-mediated inflammation was rapidly reversed by a non-activating anti-CD3 mAb that blocked effector T(h)1 cells, and spared cells expressing T(h)2 and T(r)1 cytokines.

Animals↗
PubMed2001

Are coroners' necropsies necessary? A prospective study examining whether a "view and grant" system of death certification could be introduced into England and Wales.

AIMS: To determine whether the cause of death could be accurately predicted without the need for a necropsy, and thus to consider whether a "view and grant" system of issuing a cause of death could be introduced into England and Wales. METHOD: A one year prospective necropsy study was performed incorporating 568 deaths. Before necropsy, in each case the cause of death was predicted from the available history without examination of the body, and this cause was then compared with the cause of death found at necropsy. RESULTS: The ability of the pathologist involved in the study to predict a cause of death before necropsy, either while in the mortuary or as a paper exercise, was shown to vary between 61% and 74% of cases. After the necropsy, the number of correct predicted causes of death ranged from 39% to 46%. Ischaemic heart disease was found to be the most common and most accurately predicted cause of death. Some natural diseases were frequently misdiagnosed, whereas certain types of unnatural disease were always identified correctly. CONCLUSIONS: This study highlights the advantages and disadvantages of a view and grant system. Although it identifies a potential use of such a system, in some cases such as natural cardiac disease, because of the potentially high diagnostic error rate, the continuation of the present system of postmortem examination as part of the coroner's enquiry is recommended.

Autopsy↗
PubMed2001

Restless Legs Syndrome among working-aged women.

A random sample of 200 women, aged 18-64 years, living in a county in mid-Sweden, was sent a questionnaire that included questions about sleep habits, symptoms of sleepiness and neuropsychiatric complaints. Standardized diagnostic criteria determined by the International Restless Legs Syndrome Study Group were used to investigate the prevalence of restless legs syndrome (RLS). Possible associations between RLS and neuropsychiatric complaints were also investigated. Odds ratios for different variables were calculated by means of multivariate logistic regression. 11.4% of the women suffered from RLS. Sleep-related complaints were more frequent among RLS sufferers than among nonsufferers. Complaints of daytime headache were reported 5 times more frequently among RLS sufferers, and there was a tendency towards social isolation related to RLS. Subjective problems in performing work due to sleepiness were ninefold among the women with RLS. These results indicate that RLS together with an association to neuropsychiatric symptoms is common among working-aged women.

Adolescent↗
PubMed2001

Carbonic anhydrase II associated with plasma membrane in a human pancreatic duct cell line (CAPAN-1).

The subcellular distribution of carbonic anhydrase II, either throughout the cytosol or in the cytoplasm close to the apical plasma membrane or vesicular compartments, suggests that this enzyme may have different roles in the regulation of pH in intra- or extracellular compartments. To throw more light on the role of pancreatic carbonic anhydrase II, we examined its expression and subcellular distribution in Capan-1 cells. Immunocytochemical analysis by light, confocal, and electron microscopy, as well as immunoblotting of cell homogenates or purified plasma membranes, was performed. A carbonic anhydrase II of 29 kD associated by weak bonds to the inner leaflet of apical plasma membranes of polarized cells was detected. This enzyme was co-localized with markers of Golgi compartments. Moreover, the defect of its targeting to apical plasma membranes in cells treated with brefeldin A was indicative of its transport by the Golgi apparatus. We show here that a carbonic anhydrase II is associated with the inner leaflet of apical plasma membranes and with the cytosolic side of the endomembranes of human cancerous pancreatic duct cells (Capan-1). These observations point to a role for this enzyme in the regulation of intra- and extracellular pH.

Carbonic Anhydrases↗
PubMed2001

The role of sodium channels in disease.

Native sodium channels exist as polypeptide multimers of an alpha-subunit (260 kDa) and subsidiary and smaller beta-subunits, which are divided into at least three subtypes--beta(1), beta(2) and beta(3). The alpha-subunits are structurally diverse, arising from multiple sodium channel genes and alternative splicing events. Recent progress has led to a good understanding of the molecular structure of sodium channels, how they work and the significance of their expression in particular cell types. This, coupled with experimental studies linking particular isoforms with particular disease states and the discovery of distinct human sodium channelopathies (specific mutations in specific isoforms that cause a variety of diseases, including paralysis, long QT syndrome and epilepsy), is beginning to reveal how particular sodium channel subtypes underlie specific pathologies. All this provides great potential for the development of new therapies. The first generation of sodium channel blockers has led to a broad-spectrum anticonvulsant that is now widely used (lamotrigine) and an impressive neuroprotective agent that is in clinical trials for stroke (sipatrigine). The development of the next generation of sodium channel blockers will be greatly facilitated by elaboration of the pharmacology of the various isoforms, which itself is dependent upon the existence of reliable, rapid and high-throughput assays for sodium channel activity.

Journal Article↗
PubMed2001

Androgen-linked control of carbonic anhydrase III expression occurs in rat perivenous hepatocytes; an immunocytochemical study.

Carbonic anhydrase (CA) isozymes CAII and CAIII were assayed by a radioimmunosorbent technique in liver cytosolic fractions and in isolated hepatocytes of adult male and female rats. Male livers contained 0.16 mg of CAII and 57 mg of CAIII per g cytosolic protein. Corresponding values for female livers were 0.34 mg CAII and 4 mg CAIII. Similar values and differences between CAII and III were found in isolated hepatocytes. Neonatal and adult castration of males reduced the CAIII levels to those of the females. Treatment with testosterone for three weeks restored the copulatory behaviour in the males castrated at adult age, but restored only partially the levels of CAIII. No significant effects of the endocrine manipulations were seen on CAII. Oophorectomy, with or without testosterone substitution, had no significant effect on CAII and CAIII levels in female rats. Immunohistochemistry and histochemistry showed that the regulation of CAIII is confined to perivenous hepatocytes. CAIII can therefore serve as a useful marker in the separation of these cells. CAIII appears to belong to the proteins and enzymes of the rat liver, known to be regulated via the hypothalamo-pituitary-liver axis. It may be used as a model of gene regulation in perivenous hepatocytes.

Androgens↗