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S F Taylor

Publications and source records attributed to S F Taylor.

At least 37 records · Page 2Linked to original sources
PubMed1998

Immunogenicity and efficacy of DNA vaccines encoding influenza A proteins in aged mice.

Influenza is a leading cause of morbidity and mortality in older persons. The current influenza vaccine is only modestly successful, in part because of an age-related decline in immunogenicity and also because it induces only type-specified immunity. To overcome this, we evaluated DNA vaccines encoding A/PR8/34 haemagglutinin (HA) and nucleoprotein (NP) in young and aged BALB/c mice. Control mice were given formalin-inactivated A/PR8/34, control DNA, or a non-lethal dose of PR8. Aged mice given HA DNA developed slightly lower anti-HA serum antibodies than young mice; however, both young and aged mice were protected from a homotypic PR8 challenge. Following vaccination with NP DNA, both young and aged mice developed anti-NP bulk cytotoxic T-lymphocyte (CTL) activity and pCTL frequency similar to control animals. When challenged with a low dose of A/HK/68 (H3N2) influenza virus, both young mice and aged mice showed significant protection as measured by inhibition of weight loss. When challenged with a relatively high dose of A/HR/68 (H3N2) influenza virus, however, the anti-NP vaccine only partially protected young mice and failed to protect aged mice. These data demonstrate that DNA-based vaccines are immunogenic in aged animals, but suggest that factors other than the age-related decline in CTL activity also contribute to the increased morbidity and mortality of influenza in the elderly.

Aging↗
PubMed1997

Influenza infection of beta 2-microglobulin-deficient (beta 2m-/-) mice reveals a loss of CD4+ T cell functions with aging.

Following influenza infection, aged mice have prolonged viral shedding that is presumably due to lower anti-influenza class I-restricted CD8+ CTL activity. To examine alternative viral clearance mechanisms in immunosenescense, we infected young (1.5-2.5 month) and aged (15-18 month) class I and CD8+-deficient beta 2m-/- mice with influenza A/Port Chalmers/1/73 (H3N2). We found that 40% of young beta 2m-/- mice were shedding virus from the lung on day 9 (mean titer of 0.3 log10 TCID[50]), with a maximal anti-influenza class II CTL activity of 68+/-2% on day 7. In contrast, 100% of aged beta 2m-/- mice were still shedding virus (mean titer of 3.0 log10 TCID[50]) from the lung on day 9 with a peak CTL activity of 15+/-6%. Aged beta 2m-/- mice also had significantly lower pulmonary IFN-gamma levels, serum anti-influenza neutralizing Ab, and anti-influenza mucosal IgA titers, as well as a less intense pulmonary inflammatory response on early days of infection. Th2-mediated cytokines were dysregulated. We conclude that there are multiple mechanisms responsible for the age-related delay in recovery from influenza. These include decreased anti-influenza class II-restricted CTL activity, pulmonary IFN-gamma levels, and serum neutralizing Ab. Taken together, these findings show a loss of CD4+ T cell functions with aging.

Aging↗
PubMed1997

Isolation of specific interference processing in the Stroop task: PET activation studies.

The Stroop task, in which subjects must name the color of letters that spell color words different than the color-to-be-named, provides an important experimental paradigm for the study of selective attention. Cerebral blood flow activation studies have not always demonstrated consistent activation patterns; inconsistent results may reflect nonspecific responses, such as arousal or anticipation, rather than cerebral networks specific to Stroop interference processing. In order to identify regions consistently implicated in Stroop interference processing, we undertook two experiments with a Stroop interference paradigm and contrasting lexical and nonlexical control conditions. In our first experiment, standard Stroop stimuli, e.g., the word "RED" displayed in a green font, were contrasted with color naming of the font of noncolor words and color naming of a false font. In our second experiment, we compared Stroop stimuli with colored symbols and a control condition designed to elicit nonspecific interference-taboo words displayed in color fonts. Only two brain regions showed a consistent CBF change in both experiments. Activation in the left inferior frontal gyrus reflected processing more specific to the Stroop task, while deactivation in the right superior temporal gyrus occurred for the Stroop and the taboo conditions, consistent with more nonspecific processing. Activation in the anterior cingulate cortex occurred in only one comparison in one experiment and may not reflect functions central to overcoming Stroop interference.

Adult↗
PubMed1997

Vitamin E supplementation decreases lung virus titers in mice infected with influenza.

Effects of vitamin E (E) supplementation on influenza infection were examined in young and old C57BL/6NIA mice fed 30 or 500 ppm of E for 6 weeks and subsequently infected with influenza A/Port Chalmers/1/73 (H3N2). Old mice fed 30 ppm of E had significantly higher lung virus titers on days 2 and 7 after infection than young mice fed 30 ppm of E. Titers on all 3 days were significantly lower in old mice fed 500 ppm of E than in those fed 30 ppm. Significant effects of E on lung virus titers in young mice were observed on only day 5, but E caused more reduction of virus titers in old than in young mice (25-fold vs. 15-fold). An age-associated decline in NK cell activity was restored by 500 ppm of E in old but not young mice. Pulmonary cytotoxic T lymphocyte activity on day 7 was not affected by age or E. These experiments demonstrate that high doses of E significantly enhance influenza viral clearance in aged mice but only modestly affect young mice.

Animals↗
PubMed1997

PET study of greater visual activation in schizophrenia.

OBJECTIVE: The authors tested the hypothesis that photic visual stimuli cause a greater blood flow activation response in subjects with schizophrenia than in normal subjects. METHOD: Eleven medicated patients with schizophrenia and 10 normal subjects were studied with [15O]H2O positron emission tomography to measure perfusion during photic stimulation at four different rates. RESULTS: The activation at three out of four rates of visual stimulation was greater for the patients with schizophrenia than it was for the normal subjects. CONCLUSIONS: Further investigation into the mechanisms of activation during sensory stimulation in schizophrenia is warranted.

Acetazolamide↗
PubMed1996

Retinotopy of the human retinal nerve fibre layer and optic nerve head.

The organisation of the primate nerve fibre layer and optic nerve head with respect to eccentricity or the positioning of central and peripheral axons remains controversial. Crystals of the carbocyanine dyes DiI (1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate), or DiA (4-[4-didecylaminostryryl]-N-methylpridiniumiodide) were used to trace retinal ganglion cell axons within the nerve fibre layer, optic nerve head, and optic nerve. The present study demonstrated that peripheral retinal axons were scattered throughout the vitreal-scleral depth of the nerve fibre layer. This scattered distribution was maintained as the fibres passed through the optic nerve head and into the optic nerve. Axons of the arcuate bundles showed a bias towards the scleral portions of the nerve fibre layer and a variable degree of fibre scatter across the nerve fibre layer which was not as evident in labelling from other retinal regions. There was a rough topographic representation within the optic nerve head according to retinal circumference such that both peripheral and central fibres were mixed within a wedge extending from the periphery to the centre of the nerve. Foveal fibres occupied a large proportion of the temporal aspect of the optic nerve head and nerve, whereas fibres from areas temporal to the fovea appeared to be displaced to more superior and inferior regions. Consistent with the scleral bias seen in the retina, arcuate fibres maintained a peripheral position as they passed through the optic nerve head and occupied a more peripheral position in the nerve. The present results suggest that any degree of order present within the optic nerve is not an active process; optic axons are not instructed to establish a retinotopic order within the initial portions of the visual pathway.

Adult↗
PubMed1996

Biological predictors of 1-year outcome in schizophrenia in males and females.

This paper describes a prospective study designed to ascertain the predictive value of biological factors associated with schizophrenia in males and females. In a sample of 59 medication-free schizophrenic inpatients (41 males; 18 females), we assessed the correlation of four factors--rapid eye movement (REM) sleep latency, delta (slow-wave) sleep, dexamethasone suppression test (DST) cortisol levels, and ventricle-brain ratio (VBR)--with several dimensions of outcome at 1-year post-discharge. In the total sample, shorter REM latency was associated with poor outcome on all dimensions measured: rehospitalization, employment, social activity, symptomatology, and global functioning. However, none of the other biological factors were associated with any measure of outcome. The predictive value of REM latency appeared to be gender-specific; in general, the relationships between reduced REM latency and poor outcome were consistently noted in females, but were not significant in males. These results suggest that a common, possibly gender-related, pathophysiological mechanism might underlie both abnormal REM latency and poor outcome. The findings underscore the importance of considering gender differences in studies of schizophrenia.

Electroencephalography↗
PubMed1996

Cerebral blood flow activation and functional lesions in schizophrenia.

This article reviews functional neuroimaging studies which measure task-specific changes in neuronal activity in schizophrenia, usually indexed by cerebral blood flow. Twenty-four published reports employing an activation strategy to study schizophrenia are reviewed. Eleven of these studies examined prefrontal function in schizophrenia, mostly with the Wisconsin Card Sort, and almost all have found some failure of the patients to demonstrate task-related increases in prefrontal blood flow. However, activation studies using simple sensory and motor tasks have also demonstrated abnormal activation, both as excessive and as deficient neuronal responses. A picture of a generally poor ability to organize brain activity emerges in schizophrenia. Dysfunction in a specific region, such as the prefrontal cortex, may indicate a primary functional lesion of the illness, or a salient feature of more widespread dysfunction of distributed and interactive brain networks. Progress in understanding will depend upon better knowledge of the functional neuroanatomy of the brain and the employment of neurobehavioral probes which can reliably assess a spectrum of brain networks which produce simple as well as complex function.

Arousal↗
PubMed1996

Biological predictors of suicidality in schizophrenia.

The objective of this study was to determine whether polysomnographic rapid eye movement (REM) sleep abnormalities and cortisol response to the dexamethasone suppression test (DST) differentiate between schizophrenic patients with and without a history of suicidal behaviour. We assessed a sample of 96 schizophrenic in-patients at the end of a 2-week medication-free period with the DST, polysomnography, and an extensive clinical assessment battery. Patients exhibiting suicidal behaviour were significantly more likely to have increased total REM time and increased total REM activity. We found no significant relationship between suicidal behaviour and DST non-suppression. This study confirms a previous finding suggesting an association between REM sleep abnormalities and suicidal behaviour in schizophrenia. It is postulated that this observed association may be related to serotonergic dysfunction in schizophrenia.

Adult↗
PubMed1996

Oral immunization with a replication-deficient recombinant vaccinia virus protects mice against influenza.

Mice immunized with two intragastrically administered doses of a replication-deficient recombinant vaccinia virus containing the hemagglutinin and nucleoprotein genes from H1N1 influenza virus developed serum anti-H1 immunoglobulin G (IgG) antibody that completely protected the lungs from challenge with H1N1. Almost all of the mice given two intragastric doses also developed mucosal anti-H1 IgA antibody, and those with high anti-H1 IgA titers had completely protected noses. Intramuscular injection of the vaccine protected the lungs but not the noses from challenge. We also found that the vaccine enhanced recovery from infection caused by a shifted (H3N2) influenza virus, probably through the induction of nucleoprotein-specific cytotoxic T-lymphocyte activity. A replication-deficient, orally administered, enteric-coated, vaccinia virus-vectored vaccine might safely protect humans against influenza.

Administration, Oral↗
PubMed1996

Hepatic oxidant injury and glutathione depletion during total parenteral nutrition in weanling rats.

Hepatobiliary dysfunction occurs commonly in infants on prolonged parenteral nutrition alimentation; however, the underlying mechanisms causing liver injury are poorly understood. We postulated that oxidant stress played a significant role in parenteral nutrition-induced liver abnormalities and tested this hypothesis in a rat model. Weanling male rats received 8 days of total parenteral nutrition (TPN) through a central venous catheter (TPN group), pair feeding of rat chow and placement of a central venous catheter (sham group), or ad libitum feedings of rat chow (control group). After 8 days of TPN, serum alanine aminotransferase and cholylglycine levels were elevated, hepatocellular steatosis was present, hepatic mitochondria had dilated intracristal spaces, and lipid peroxidation of mitochondria was increased compared with sham and control groups. Hepatic glutathione levels decreased to 16% of control values after 5 days of TPN; this was followed by mitochondrial lipid peroxidation and elevated serum cholylglycine levels after 8 days of TPN. Sham and control rats showed no evidence of mitochondrial lipid peroxidation or liver injury after 8 days. Removal of metabisulfate from TPN solutions and addition of cysteine HCl or choline had no major effect on these findings. Bacterial translocation was not increased in TPN rats. These data suggest that glutathione depletion and oxidant stress are important factors in the pathogenesis of TPN-induced liver abnormalities in the weanling rats.

Animals↗
PubMed1995

Requirement for a beta 2-microglobulin-associated Fc receptor for acquisition of maternal IgG by fetal and neonatal mice.

There is considerable evidence to suggest that an FcR similar in structure to class I MHC Ags, neonatal Fc receptor (FcRn), transports IgG across the intestinal epithelium of suckling mice. However, this has not previously been shown definitively, nor has it been shown whether FcRn is the only, or even the major, IgG transporter in the neonatal mouse gut. We report here that neonatal mice homozygous for a targeted disruption of the beta 2microglobulin (beta 2m) gene, which encodes one subunit of FcRn, had reduced FcRn alpha-chain at the lumenal plasma membrane of intestinal cells. These mice had strikingly lower serum IgG levels during the first month after birth than littermates that possessed functional FcRn. Furthermore, we found by fostering mice on mothers with a different IgG allotype that all of the IgG in sera of beta 2m-/- mice was endogenous, and that none was obtained from milk. We conclude that FcRn is the only transporter of IgG from mother to young in the mouse. The onset of IgG synthesis in mice that received no milk IgG lagged behind that in siblings with normal IgG transport, suggesting that maternal IgG stimulates Ab production in the neonate. We noted no difference between the IgG concentrations in the milk of beta 2m-/- and beta 2m+/- mice, indicating that FcRn is not involved in the secretion of IgG into milk.

Animals↗
PubMed1995

Beta 2-microglobulin-deficient mice demonstrate class II MHC restricted anti-viral CD4+ but not CD8+ CTL against influenza-sensitized autologous splenocytes.

Mice transgenic for beta 2-microglobulin gene deletion (beta 2M-/-) can clear respiratory pathogens but at a slower rate than control mice. How these mice eliminate virus is not known, but the process is believed to involve CD4+ T cells. Recent studies from other laboratories have suggested a role for CD8+ cytotoxic T lymphocytes (CTLs) in both recognition of beta 2M deficient cells by allogeneic mice and rejection of MHC-incompatible tumor cells by beta 2M-/- mice. After influenza inoculation, we found no evidence for anti-influenza CD8 CTL activity from the lungs or spleens of beta 2M-/- mice. Anti-influenza CD4+, class-II restricted CTL activity was demonstrated from both the lungs and spleens. We next used mitogen-stimulated splenocytes from beta 2M-/- mice for targets in an in vitro CTL assay. This method for determining MHC class II CTL activity showed that the lungs and spleens of influenza-infected beta 2M-/- mice contained precursors to CD4+, but not CD8+, effector CTLs. The data indicate that CD8+ CTLs have no role in anti-viral activity in beta 2M-/- mice. Development of anti-tumor CTLs and anti-viral CTLs may arise via different mechanisms.

Animals↗
PubMed1995

Pulmonary immune response of young and aged mice after influenza challenge.

After influenza challenge, aged mice have prolonged viral shedding that correlates with lower splenic cytotoxic T lymphocyte (CTL) activity. To evaluate the age-related pulmonary cell-mediated immune response to influenza, pulmonary lymphocytes were obtained from young and aged mice at various days after respiratory tract infection with nonlethal influenza A/PC/1/73 (H3N2) virus. In young mice, pulmonary CTL activity peaked at 48% +/- 2% on day 7 after infection. Pulmonary CTL activity peaked 1 day later in aged mice and at about half the activity (24% +/- 5%). The majority of the cells recovered from the lungs in both age groups were CD3+, CD8+ T cells. Histologic examination of the lungs revealed that aged mice had significantly less inflammation than young mice. Therefore, after influenza challenge there was a large influx of lymphocytes into the lungs of both young and aged mice, but the cells from young mice were more active on a per-cell basis. In a further experiment, challenge with a more virulent strain of influenza produced higher mortality in young mice than in aged mice. Thus the higher CTL activity of young animals leads to more rapid virai clearance, but this may be at a price to the host--that is, more immunopathologic damage.

Aging↗
PubMed1994

Changes in medial cortical blood flow with a stimulus-response compatibility task.

Previous work has suggested that human subjects engaged in tasks, like the Stroop task, that require response selection utilize the medial frontal cortex. We used positron emission tomography to measure blood flow changes in a stimulus-response compatibility task designed to maximize the demand on response selection processes. We report significant activation in the cingulate sulcus (Brodman's area 32) and a correlation of activity in this region with faster response time for an incongruent stimulus-response task.

Brain↗