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Biomedical subjects

S F Taylor

Publications and source records attributed to S F Taylor.

At least 19 recordsLinked to original sources

Measurement of the flux of ultrahigh energy cosmic rays from monocular observations by the High Resolution Fly's Eye experiment.

We have measured the cosmic ray spectrum above 10(17.2) eV using the two air-fluorescence detectors of the High Resolution Fly's Eye observatory operating in monocular mode. We describe the detector, phototube, and atmospheric calibrations, as well as the analysis techniques for the two detectors. We fit the spectrum to a model consisting of galactic and extragalactic sources.

Journal Article↗

Saturated state of the nonlinear small-scale dynamo.

We consider the problem of incompressible, forced, nonhelical, homogeneous, and isotropic MHD turbulence with no mean magnetic field and large magnetic Prandtl number. This type of MHD turbulence is the end state of the turbulent dynamo, which generates folded fields with small-scale direction reversals. We propose a model in which saturation is achieved as a result of the velocity statistics becoming anisotropic with respect to the local direction of the magnetic folds. The model combines the effects of weakened stretching and quasi-two-dimensional mixing and produces magnetic-energy spectra in remarkable agreement with numerical results at least in the case of a one-scale flow. We conjecture that the statistics seen in numerical simulations could be explained as a superposition of these folded fields and Alfvén-like waves that propagate along the folds.

Journal Article↗

Vesicular monoamine transporter concentrations in bipolar disorder type I, schizophrenia, and healthy subjects.

BACKGROUND: Previous analyses of vesicular monoamine transporter (VMAT2) binding in euthymic bipolar disorder type I (BDI) patients have shown increases of this presynaptic marker in the thalamus and ventral midbrain. To assess the diagnostic specificity of those findings, we compared VMAT2 concentrations between euthymic BDI patients, patients diagnosed with schizophrenia (SCH), and age-matched healthy volunteers. METHODS: Binding sites for VMAT2 were quantified with (+)-alpha-[11C]DTBZ (dihydrotetrabenazine) and positron emission tomography. Fifteen euthymic BDI and 12 SCH patients and 15 group-matched healthy controls were studied. [11C]DTBZ tracer transport and binding potentials were examined in the thalamus and ventral midbrain with factorial analyses of variance and post hoc Tukey's honestly significantly different tests. RESULTS: Analysis of variance detected diagnosis effects in binding potentials in both brain regions. Binding of VMAT2 in the thalamus was higher in BDI patients than in control subjects and SCH patients. Conversely, ventral brainstem binding was nearly identical between BDI and SCH patients and were higher than in the control group. CONCLUSIONS: The patterns of regional VMAT2 expression, and by extension, the concentration of monoaminergic synaptic terminals, differ between BDI, SCH, and a control group. These findings may relate to both similarities and differences in the presentation or clinical course of these syndromes and require further examination.

Adult↗

Context processing in older adults: evidence for a theory relating cognitive control to neurobiology in healthy aging.

A theory of cognitive aging is presented in which healthy older adults are hypothesized to suffer from disturbances in the processing of context that impair cognitive control function across multiple domains, including attention, inhibition, and working memory. These cognitive disturbances are postulated to be directly related to age-related decline in the function of the dopamine (DA) system in the prefrontal cortex (PFC). A connectionist computational model is described that implements specific mechanisms for the role of DA and PFC in context processing. The behavioral predictions of the model were tested in a large sample of older (N = 81) and young (N = 175) adults performing variants of a simple cognitive control task that placed differential demands on context processing. Older adults exhibited both performance decrements and, counterintuitively, performance improvements that are in close agreement with model predictions.

Adult↗

Disease and nonbattle injury related to peacekeeping operations in South America: summary patient care statistics for CABANAS 2000.

Peacekeeping operations and training for peacekeeping missions currently require far more time and personnel from our armed forces than previously. Although literature exists describing mortality, disease and nonbattle injury (DNBI), and medical support for peacekeeping operations in Europe, Africa, the Caribbean, and the Far East, none was found concerning operations and training for peacekeeping in South America. The present retrospective study presents an analysis of DNBI for forces participating in CABANAS 2000, an eight-nation peacekeeping training exercise held in Argentina. The mean DNBI rate for the 6-week period was 4.1 cases/100 personnel/week. Frequently cited causes for service member presentations for medical treatment were respiratory disease (43%), orthopedic disorders and injuries (25.9%), other miscellaneous medical conditions (8.5%), dermatologic complaints (6.9%), and diarrhea and intestinal complaints (6.5%). These findings indicate that peacekeeping operations and training in South America are relatively safe.

Female↗

Genetic heterogeneity in familial juvenile polyposis.

Juvenile polyposis syndrome (JPS) is an autosomal dominant syndrome characterized by multiple gastrointestinal hamartomatous polyps in the absence of the extraintestinal features that are classic for other hamartomatous polyposis syndromes, such as Bannayan-Riley-Ruvalcaba syndrome (BRRS) and Cowden disease (CD). About 50% of BRRS and >80% of CD demonstrate germ-line mutations in the tumor suppressor and dual phosphatase, PTEN. Germ-line mutation of PTEN as a cause for JPS in a child is controversial because extraintestinal manifestations that would exclude JPS could appear after adolescence, altering the clinical diagnosis. Here, we investigated a family in which the 55-year-old father, who lacks thyroid or skin findings characteristic of CD, demonstrated a germ-line mutation in PTEN that was passed to identical twin daughters, who both manifested JPS. The mutation was a deletion of five bases beginning seven bases from the start of exon 4 of PTEN, which caused aberrant transcripts by reverse transcription-PCR that were absent from a normal individual. Thus, mutations in PTEN are associated with JPS in addition to CD and some BRRS families, although the incidence of PTEN germ-line mutations in JPS might be more rare than that reported for SMAD4, a gene found to be mutated in approximately one-half of the JPS families investigated.

Adenomatous Polyposis Coli↗

Phasic and enduring negative symptoms in schizophrenia: biological markers and relationship to outcome.

Negative symptoms have been associated with poor response to neuroleptics, enlarged ventricles, cognitive impairment, and poor outcome in schizophrenia. These associations appear, however, to be dependent on the phase of study, suggesting that acute-phase (phasic) negative symptoms may be pathophysiologically distinct from enduring negative symptoms that persist through the residual phase. To compare correlates of enduring and phasic negative symptoms, we studied 60 drug-free schizophrenic patients (DSM-III-R and SADS/RDC) at baseline, 4 weeks after neuroleptic treatment, and assessed the 1 year outcome. We rated positive and negative symptoms at baseline and 4 weeks after treatment. At baseline, premorbid function, neuropsychological function, ventricle-brain ratio (VBR) and symptom response to an anticholinergic agent were assessed, and a two-night sleep EEG and 1mg dexamethasone suppression test (DST) were conducted. Phasic negative symptoms were defined as the change in negative symptoms (baseline to 4 weeks) and enduring negative symptoms as severity of negative symptoms at 4 weeks. Patients had varying proportions of phasic and enduring symptoms; the two did not define distinct subgroups. Phasic negative symptoms were significantly correlated with global treatment response, positive symptom treatment response, response to anticholinergic agent, baseline post-dexamethasone cortisol, and shortened REM latency. Enduring negative symptoms were significantly correlated with residual positive symptoms and global psychopathology, VBR, poor performance on neuropsychological testing, decreased slow-wave sleep, poor premorbid function, and poor 1 year outcome. These data suggest that phasic negative symptoms and enduring negative symptoms may be caused by different pathophysiological mechanisms.

Adult↗

The effect of graded aversive stimuli on limbic and visual activation.

Activation studies have shown that in response to evocative visual stimuli, brain activity increases in the visual cortex and limbic areas. However, non-affective characteristics of these images, such as color composition and visual complexity, confound the interpretation of these results. To address this issue, we had subjects rate over 100 images on aversive intensity (facial mutilation, dead bodies) and semantic complexity (number of objects subjects could name). From these images, we assembled digitized image sets of non-aversive, mild and strong intensity, balanced on semantic complexity and content (human faces and figures), and adjusted for color composition. A fourth condition consisted of a fixation cross on a blank screen. Thirteen subjects underwent eight positron emission tomography scans using the [(15)O] water methodology. Measurement of skin conductance was recorded simultaneously. All picture conditions, relative to the blank screen, activated the amygdalae and bilateral orbitofrontal cortex, while we found activation trends associated with increasing aversive content in the sub-lenticular region. Skin conductance increased during all picture conditions. Relative to the non-aversive pictures, aversive image content caused modulation of occipital and occipital-temporal cortex. These results demonstrated activation of the amygdala to salient, arousing stimuli, and not just aversive stimuli. In addition, they suggest that pictorial complexity, as indexed by our semantic measure, does not account for the modulation of visual cortex by aversive, emotional stimuli.

Adult↗

Limbic activation and psychophysiologic responses to aversive visual stimuli. Interaction with cognitive task.

We mapped regional brain activity and peripheral psychophysiologic responses, occurring in response to evocative emotional stimuli, and examined whether task instructions could modulate limbic activation. Ten subjects viewed pictures with neutral or aversive emotional content during simultaneous measurement of peripheral psychophysiology and brain activity with [15O]water positron emission tomography (PET). Cognitive task was manipulated by having the subjects rate the pictures or perform a recognition memory task. Aversive pictures, relative to neutral pictures, increased cerebral activity in bilateral amygdala, thalamic/hypothalamic area, midbrain, and left lateral prefrontal cortex, along with greater skin conductance responses (SCR). Voxel-by-voxel correlation coefficients between regional brain activity and SCR showed significant positive correlation peaks in the thalamus and right amygdala. Limbic activation was significantly greater during the rating condition compared to the recognition condition, suggesting that when task demands modify emotional responses, this modulation can occur at the level of limbic activity.

Adult↗

In vivo measurement of the vesicular monoamine transporter in schizophrenia.

Given evidence for excessive striatal dopamine activity in schizophrenia, we sought to test the hypothesis that dopaminergic innervation in the striatum is abnormally elevated, and a secondary hypothesis that age-related loss is accelerated. Twelve schizophrenic subjects on stable doses of medications, along with 12 age and sex-matched healthy control subjects, underwent positron emission tomography (PET) studies with [11C]dihydrotetrabenazine (DTBZ), which binds to the vesicular monoamine transporter, type 2 (VMAT2). DTBZ binding reflects principally dopaminergic projections in the striatum and appears in animal models, over treatment periods as long as two weeks, not to be regulated by antipsychotic drugs. Using an equilibrium analysis, we obtained measurements of the binding potential (BP) of [11C]DTBZ, as well as a transport (K(1)) measure, corresponding to regional cerebral blood flow. BP in the striatum showed no difference between the patient and control groups, and no differential effect of age. We did not find evidence supporting the hypothesis that excessive dopamine activity in schizophrenia could be explained by increased density of striatal dopamine terminals.

Adolescent↗

Schistosoma mansoni gene GP22 encodes the tegumental antigen sm25: (1) antibodies to a predicted B-cell epitope of Sm25 cross-react with other candidate vaccine worm antigens; (2) characterization of a recombinant product containing tandem-repeats of this peptide as a vaccine.

Monospecific antibodies against two putative epitopes of schistosome protein encoded by gene GP22 (182 codons, no introns) were used to probe worm extracts fractionated by lentil-lectin affinity chromatography or by electrophoresis. Anti-peptide-alpha (codons 70-84) exclusively identifies the N-glycanase-sensitive, 25 kDa tegumental glycoprotein Sm25 in the lectin-bound fraction of detergent-solubilized adult worm extract S3. In contrast, antipeptide-delta (codons 151-162) does not react with Sm25 but cross-reacts with other schistosome proteins, including candidate vaccine antigens paramyosin (Sm97) and glutathione-S-transferases (Sm26, Sm28, Sj26). Recombinant protein r4 x 47, constructed to express multiple copies of codon sequence 117-163 (containing delta), reacts with anti-delta and is uniquely recognized by protective Fischer twice-infected (F-2x) rat antiserum. Immunization with r4 x 47 induces antibodies with cross reactivities similar to anti-delta, but which also recognize Sm25. Despite these cross-reactivities with protective antigens, rodents vaccinated with r4 x 47 were not protected against cercarial infection. On the basis of these data, two hypotheses are proposed: (1) antigenic epitopes other than delta are present within the r4 x 47 sequence which induce antibodies reactive with Sm25 and/or (2) peptide-delta assumes alternative antigenic conformations, dependent upon the context of neighbouring sequences, some of which mimic epitopes of proteins encoded by other schistosome genes. These mimotopes are not targets of protective antibodies.

Amino Acid Sequence↗

Trauma patient outcome in an army Deployable Medical Systems environment compared with a medical center.

William Beaumont Army Medical Center is the second busiest trauma center in the Army. Recent facility renovations there necessitated the use of a temporary field hospital to serve as the Emergency Department, which included the initial evaluation and resuscitation of trauma patients by the trauma team. Although designed for the battlefield, the use of field medical equipment during renovation of military medical facilities is not a new concept. The MUST (Medical Unit Self-contained Transportable) and DEPMEDS (Deployable Medical Systems) have been used successfully during fixed-facility renovations. Previously described functions included inpatient services, outpatient care, and operating room facilities. However, no published information directly compares the use of these temporary structures with standard fixed facilities in the initial management of trauma patients. Trauma patients often present with complex concerns, are highly resource intensive, and their survival is dependent on efficient, timely care. We compared several aspects of patient outcome in the DEPMEDS versus the medical center.

Adolescent↗

Brain activation in PTSD in response to trauma-related stimuli.

BACKGROUND: Repetitive recall of traumatic memories and chronic intermittent hyperarousal are characteristic of posttraumatic stress disorder (PTSD). Hyperarousal and memory dysfunction implicates "limbic" brain regions, including the amygdaloid complex, hippocampal formation, and limbic cortex, such as the orbitofrontal and anterior cingulate areas. To investigate the neurobiologic role of these brain regions in PTSD, we measured regional cerebral blood flow in PTSD with single photon emission computerized tomography (SPECT) during a symptom provocation paradigm. METHODS: Fourteen Vietnam veterans with PTSD, 11 combat control subjects, and 14 normal control subjects were studied with [99mTc]HMPAO in two sessions 48 hours apart: one session after exposure to white noise and the other following exposure to combat sounds. Skin conductance, heart rate, and subjective experience were recorded at the time of the studies. RESULTS: Activation for all three groups occurred in the anterior cingulate/middle prefrontal gyrus. Activation in the region of the left amygdala/nucleus accumbens was found in PTSD patients only. Deactivation was found in all three groups in the left retrosplenial region. CONCLUSIONS: These findings implicate regions of the "limbic" brain, which may mediate the response to aversive stimuli in healthy individuals and in patients suffering from PTSD.

Arousal↗

Global cerebral blood flow increase reveals focal hypoperfusion in schizophrenia.

Recent functional neuroimaging strategies have evaluated cerebral blood flow (CBF) to determine specific sites of action of pharmacologic agents. Since many pharmacologic agents change global CBF, we investigated the effects of global CBF changes on regional perfusion with acetazolamide, which increases global CBF via non-neuronal mechanisms. We used the [15O]PET technique to measure CBF before and after we infused 8 schizophrenic patients and 10 healthy control subjects with acetazolamide. The rostral anterior cingulate cortex demonstrated a greater perfusion increase in the schizophrenic subjects after acetazolamide infusion, relative to other areas of the brain. During the baseline condition, this area showed relative hypoperfusion in our sample of schizophrenic subjects, consistent with previous functional neuroimaging studies. The results demonstrate the need for caution in interpreting CBF changes after pharmacologic challenge, because global CBF changes can confound the assessment of regionally-specific pharmacologic action.

Acetazolamide↗

The effect of emotional content on visual recognition memory: a PET activation study.

The emotional content of stimuli can enhance memory for those stimuli. This process may occur via an interaction with systems responsible for perception and memory or via the addition of distinct brain regions specialized for emotion which augment mnemonic processing. We performed an 15O PET study to identify neuroanatomical systems which encode visual stimuli with strong negative emotional valence compared to stimuli with neutral valence. Subjects also performed a recognition memory task for these same images, mixed with distracters of similar emotional valence. The experimental design permitted us to independently test effects of emotional content and recognition memory on regional activity. We found activity in the left amygdaloid complex associated with the encoding of emotional stimuli, although this activation appeared early in the scanning session and was not detectable during recognition memory. Visual recognition memory recruited the right middle frontal gyrus and the superior anterior cingulate cortex for both negative and neutral stimuli. An interaction occurred between emotional content and recognition in the lingual gyrus, where greater activation occurred during recognition of negative images compared to recognition of neutral images. Instead of distinct neuroanatomical systems for emotion augmenting memory, we found that emotionally salient stimuli appeared to enhance processing of early sensory input during visual recognition.

Adult↗

Interleukin 12 administration enhances Th1 activity but delays recovery from influenza A virus infection in mice.

Interleukin 12 (IL-12) directs the differentiation of undifferentiated T helper (Th0) cells to T helper type 1 (Th1) cells and induces a cell-mediated immune response. To evaluate the effect of IL-12 on the course of influenza A virus infection, BALB/c mice were administered a daily intraperitoneal dose of 1000 ng of IL-12 or saline on days -1 to +4 for a total of six treatments. The treatment generally enhanced Th1-mediated responses. IFNgamma lung concentrations were 1193 +/- 275 pg/100 microl in controls and 3693 +/- 745 pg/100 microl in IL-12-treated mice at day 5. IFNgamma levels were undetectable at day 13 in controls and 1335 +/- 220 pg/100 microl in IL-12-treated mice. Cytokine production was also assessed at the single-cell level for mediastinal lymph nodes. IL-12 treatment increased the number of IL-2- and IFNgamma-producing cells and decreased the number of IL-4- and IL-10-producing cells. IL-12 treatment decreased the anti-influenza antibody response, especially anti-influenza IgG1 antibody resulting in an increased IgG2a/IgG1 ratio. Primary pulmonary CTL activity on day 5 was low for both groups (10% specific lysis). Secondary CTL activity at day 11 was higher for control mice than for IL-12-treated mice on day 11 (44 versus 34%), but not on day 13. Despite this overall enhancement of Th1-mediated immune functions, the IL-12 treatment increased severity of the disease. Following infection, control and IL-12-treated mice decreased their body weight to approximately 75% of their initial weight. After day 5, the control mice started to recover, while IL-12-treated mice did not begin recovering until day 9. Pulmonary viral titers were 1.6 +/- 0.3 TCID50 in controls at day 5 compared to 2.4 +/- 0.3 for IL-12-treated mice (P < 0.01). In addition, control mice had significantly less severe inflammation and damage on histologic examination. Serum TNFalpha concentrations, undetectable in control mice, were elevated by IL-12 treatment up to 80 pg/ml at day 5 and decreased to zero at day 13. It is concluded that IL-12 administration to influenza-infected mice induces a switch from a Th2- to a Th1-mediated response, but inhibits recovery probably through induction of TNFalpha.

Animals↗