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Biomedical subjects

S Carlson

Publications and source records attributed to S Carlson.

At least 55 records · Page 3Linked to original sources

Selective interference reveals dissociation between auditory memory for location and pitch.

Effects of interfering task-irrelevant tones varying in location or pitch on auditory location and pitch n-back tasks were investigated to study whether there is segregation of spatial and non-spatial information processing in the auditory working memory. The subjects performed spatial and non-spatial auditory 1- and 2-back tasks with and without location or pitch interference. In the 1-back tasks, location but not pitch interference significantly impaired location task performance whereas pitch but not location interference disrupted pitch task performance. In the 2-back tasks, neither the location nor the pitch task performance was differentially disrupted by the distractors, suggesting that there is memory load-dependent segregation in the handling of location and pitch information in the neuronal networks engaged in auditory working memory.

Acoustic Stimulation↗

Selective interference reveals dissociation between memory for location and colour.

The aim was to study whether there is indication of a dissociation in processing of visuospatial and colour information in working memory in humans. Experimental subjects performed visuospatial and colour n-back tasks with and without visuospatial and colour distractive stimuli presented in the middle of the delay period to specifically affect mnemonic processing of task-related information. In the high memory-load condition, the visuospatial, but not the colour, task was selectively disrupted by visuospatial but not colour distractors. When subvocal rehearsal of the memoranda in the colour task was prevented by articulatory suppression; colour task performance was also selectively disrupted by distractors qualitatively similar to the memoranda. The results support the suggestion that visual working memory for location is processed separate from that for colour.

Adult↗

The BALB/c mouse as an animal model for progressive sensorineural hearing loss.

To develop the BALB/c mouse strain as an animal model for the study of progressive sensorineural hearing loss, mice ranging in age from young adult through middle age were studied. Auditory brainstem response thresholds, histopathology [cytocochleograms for hair cells, the packing density of spiral ganglion cells (SGCs), the number of neurons and overall size of the anterior ventral cochlear nucleus (AVCN)], and behavioral paradigms (prepulse inhibition, fear-potentiated startle) were compared with previous data from C57BL/6J (C57) and DBA/2J (DBA) mouse strains. Progressive high frequency hearing loss in BALB/c mice was generally more rapid than C57 and slower than DBA (e.g. mean thresholds for 16 kHz: 10-month-old BALB/c mice = 71 dB SPL; 55-day-old DBA mice = 79 dB SPL; 12-month-old C57 mice = 50 dB SPL). Like the other strains, BALB/c exhibited a progressive loss of hair cells and SGCs that was most severe in the cochlear base and least severe in the middle turns; however, BALB/c mice had relatively more SGC loss in the apex. Unlike C57 and DBA, no loss of neurons was observed in the AVCN following cochlear pathology (although AVCN volume was reduced). Like the other strains, successful fear conditioning was obtained with a 12 kHz conditioned stimulus. Prepulse inhibition showed that middle and low frequency tones (4-12 kHz) became more salient as high frequency hearing declined. Similar results had been previously obtained with C57 and DBA mice and were interpreted as reflecting hearing-loss-induced plasticity in the central auditory system.

Acoustic Stimulation↗

Distribution of cortical activation during visuospatial n-back tasks as revealed by functional magnetic resonance imaging.

Human neuroimaging studies conducted during visuospatial working memory tasks have inconsistently detected activation in the prefrontal cortical areas depending presumably on the type of memory and control tasks employed. We used functional magnetic resonance imaging to study brain activation related to the performance of a visuospatial n-back task with different memory loads (0-back, 1-back and 2-back tasks). Comparison of the 2-back versus 0-back tasks revealed consistent, bilateral activation in the medial frontal gyrus (MFG), superior frontal sulcus and adjacent cortical tissue (SFS/SFG) in all subjects and in six out of seven subjects in the intraparietal sulcus (IPS). Activation was also detected in the inferior frontal gyrus, medially in the superior frontal gyrus, precentral gyrus, superior and inferior parietal lobuli, occipital visual association areas, anterior and posterior cingulate areas and in the insula. Comparison between the 1-back versus 0-back tasks revealed activation only in a few brain areas. Activation in the MFG, SFS/SFG and IPS appeared dependent on memory load. The results suggest that the performance of a visuospatial working memory task engages a network of distributed brain areas and that areas in the dorsal visual pathway are engaged in mnemonic processing of visuospatial information.

Adolescent↗

Caudal pontine reticular formation of C57BL/6J mice: responses to startle stimuli, inhibition by tones, and plasticity.

C57BL/6J (C57) mice were used to examine relationships between the behavioral acoustic startle response (ASR) and the responses of neurons in the caudal pontine reticular formation (PnC) in three contexts: 1) responses evoked by basic startle stimuli; 2) the prepulse inhibition (PPI) paradigm; and 3) the effects of high-frequency hearing loss and concomitant neural plasticity that occurs in middle-aged C57 mice. 1) Responses (evoked action potentials) of PnC neurons closely paralleled the ASR with respect to latency, threshold, and responses to rapidly presented stimuli. 2) "Neural PPI" (inhibition of responses evoked by a startle stimulus when preceded by a tone prepulse) was observed in all PnC neurons studied. 3) In PnC neurons of 6-mo-old mice with high-frequency (>20 kHz) hearing loss, neural PPI was enhanced with 12- and 4-kHz prepulses, as it is behaviorally. These are frequencies that have become "overrepresented" in the central auditory system of 6-mo-old C57 mice. Thus neural plasticity in the auditory system, induced by high-frequency hearing loss, is correlated with increased salience of the inhibiting tones in both behavioral and neural PPI paradigms.

Acoustic Stimulation↗

Effects of music and white noise on working memory performance in monkeys.

It has been suggested that Mozart's music may have beneficial effects on the performance of cognitive tasks in humans. In the present study the effects of Mozart's piano music, white noise, simple rhythm and silence were studied on the performance of a delayed response (DR) task in monkeys. The acoustic treatments were given for 15 min, either before or during DR testing. The acoustic treatments did not affect DR performance when given before testing. However, Mozart's piano music played during DR testing caused a significant deterioration in the performance of the monkeys, whereas white noise improved it. It is suggested that Mozart's music serves as distractive stimulation during DR performance thus affecting working-memory-related neuronal processing and performance. White background noise, on the other hand, may improve DR performance by protecting against environmental distraction during testing.

Acoustic Stimulation↗

Visuospatial mnemonic load modulates event-related slow potentials.

Electroencephalographic slow wave potentials were recorded during the performance of visuospatial working memory tasks. The aim was to study the effects of varying mnemonic loads on slow potentials, and to dissociate the contribution of mnemonic and motor components. Subjects were tested with three spatial delayed matching-to-sample tasks in which the mnemonic load varied while the preparatory motor demands remained constant. The delay-related slow potential was more negative during the tasks in which the subjects had to memorize the locations of six or four stimuli than when only one location had to be memorized. Significant differences between the slow potentials in the tasks with different mnemonic loads were recorded at frontal and temporal recording sites. Since the preparatory motor requirements were similar in all tasks, the modulation of slow potentials reflects working memory processing rather than motor preparatory activity.

Adolescent↗

The effects of alpha-2 agonist, medetomidine and its antagonist, atipamezole on reaction and movement times in a visual choice reaction time task in monkeys.

Alpha-2 adrenoceptor agonists have been shown to improve the working memory task performance of aged monkeys. Suggestions offered to explain this finding include improved short-term memory processing, slight sedation, and decreased distractiveness. Although sedation is evident at high doses, it may also contribute to the working memory task performance at low doses. The aim of the present work was to find out whether the positive effects of an alpha-2 agonist, medetomidine, on working memory performance could be explained by its sedative effects. This was accomplished by measuring the reaction and movement times of monkeys performing a visual choice reaction time task under the influence of medetomidine or its antagonist atipamezole. In the task a trial began with the monkey holding a central pad. After a short period one of two lateral light emitting diodes was turned on for 300 ms and the monkeys were trained to release the central bar and touch either of the bars, situated below the diodes, depending on the location of the stimulus. The reaction and movement times were significantly longer than on saline control only at the highest dose of medetomidine (10.0 micrograms/kg). At the lowest dose of atipamezole (0.01 mg/kg), the reaction times were significantly shorter than on saline control. The results of this study demonstrate that low doses of medetomidine, which have earlier been shown to improve working memory performance, do not induce sedation as measured by reaction and movement times.

Adrenergic alpha-Agonists↗

Unrecognized pregnancy in the overdosed or poisoned patient.

A 22-year-old woman was found in bed unresponsive and hypotensive after an apparent overdose. Subsequent workup in the emergency department identified a ruptured ectopic pregnancy and extensive hemoperitoneum. A significant delay occurred when emergency physicians excluded the possibility of pregnancy because of the patient's normal menstrual history. A qualitative serum or urine pregnancy test is recommended in all women of child-bearing age who present with poisoning or drug overdose.

Adult↗

The ClpP protein, a subunit of the Clp protease, modulates ail gene expression in Yersinia enterocolitica.

Yersinia enterocolitica is a gastrointestinal pathogen of humans and animals. Ail is a 17kDa cell-surface protein that confers on Y. enterocolitica resistance to serum killing and the ability to attach to and invade cells in vitro. The ail gene of Y. enterocolitica is regulated by temperature and growth phase. In stationary phase, ail transcript is only detected when bacteria are grown at the host temperature of 37 degrees C. Our laboratory previously described a group of mini-Tn10 mutants, which expressed ail in stationary phase at 28 degrees C. In one of these mutants, DP5102::mini-Tn10 3-2, the mini-Tn 10 inserted into a gene encoding a protein with 90.3% identity to the ClpP protease subunit from Escherichia coli. Expression of ail in stationary phase at 28 degrees C was also derepressed in a directed Y. enterocolitica clpP mutant. Analysis of ail transcripts in the wild-type and clpP mutant strains indicated that there is a single start site of transcription of ail and that the effect of the clpP mutation was on the initiation of transcription at this site. Similar to E. coli, a clpX homologue was identified downstream of clpP. The Y. enterocolitica clpP gene complemented the clpP mutant phenotype, repressing the expression of both ail transcript levels and cell surface-expressed Ail protein. Thus, ClpP has a role in the modulation of ail transcription in Y. enterocolitica.

ATPases Associated with Diverse Cellular Activitie↗

Randomized, double-blind study of intravenous human albumin in hypoalbuminemic patients receiving total parenteral nutrition.

OBJECTIVE: To determine whether replacement of human albumin will improve a patient's prognosis. DESIGN: A randomized, double-blind, controlled study in which 25 g of human albumin vs. placebo was administered intravenously daily. SETTING: A university-affiliated hospital. PATIENTS: Thirty-six patients with hypoalbuminemia (serum albumin of <2.5 g/dL), receiving total parenteral nutrition. None of the patients had known cancer, cirrhosis, or nephrotic syndrome. INTERVENTIONS: Each patient received at least 6 days of therapy (6 to 24 days of albumin; 7 to 32 days of placebo). Four subjects were excluded from the study since they received therapy for <6 days. One patient was excluded from the study after nephrotic syndrome was identified. Albumin metabolic rates for those patients receiving albumin were estimated using the formula: Metabolism of albumin = 25 g/day + (albumin 1 - albumin 2)(Vd)/days, where albumin 1 and 2 are the serum albumin concentrations (g/L) at the beginning and end of the serum sampling intervals, respectively; Vd is the volume of distribution (L); and days relates to the number of days of the sampling interval. MEASUREMENTS AND MAIN RESULTS: Sixteen patients received albumin; 15 patients received placebo. One patient receiving placebo and two patients receiving albumin died within 30 days. One patient who received placebo and three patients who received albumin developed sepsis or bacteremia; four patients who received placebo and seven patients who received albumin developed pneumonia during the study (NS). The serum albumin increased in all patients receiving intravenous albumin, but one patient received intravenous albumin for only 6 days. The mean serum albumin concentration increased by 1.42 g/dL in the albumin patients, and increased by 0.29 in the placebo patients (p < .0001 by unpaired t-test). Mean initial albumin metabolism was 17.4 g/day (0.3 g/kg/day). At the end of therapy, albumin metabolism was 20.5 g/day (0.36 g/kg/day) (paired t-test, p = .4, NS). CONCLUSIONS: a) The administration of intravenous albumin to hypoalbuminemic patients receiving total parenteral nutrition does not improve morbidity or mortality. b) Albumin metabolic rates, initially related to the catabolic state, are high; later, these rates are high related to filling of the albumin space and gluconeogenesis. c) On the basis of the high albumin catabolic rates at the end of the infusion, doses of albumin of <25 g/day might be sufficient to replace albumin stores.

Double-Blind Method↗

Dissociation of mnemonic coding and other functional neuronal processing in the monkey prefrontal cortex.

Single-neuron activity was recorded in the prefrontal cortex of three monkeys during the performance of a spatial delayed alternation (DA) task and during the presentation of a variety of visual, auditory, and somatosensory stimuli. The aim was to study the relationship between mnemonic neuronal processing and other functional neuronal responsiveness at the single-neuron level in the prefrontal cortex. Recordings were performed in both experimental situations from 152 neurons. The majority of the neurons (92%) was recorded in the prefrontal cortex. Nine of the neurons were recorded in the dorsal bank of the anterior cingulate sulcus and two in the premotor cortex. Of the total number of neurons recorded in the prefrontal area, 32% fired in relation to the DA task performance and 39% were responsive to sensory stimulation or to the movements of the monkey outside of the memory task context. Altogether 42% of the recorded neurons were neither activated by the various stimuli nor by the DA task performance. Three types of task-related neuronal activity were recorded: delay related, delay and movement related, and movement related. The majority of the task-related neurons (n = 33, 73%) fired in relation to the delay period. Of the delay-related neurons, 26 (79%) were spatially selective. The number of spatially selective delay-related neurons of the whole population of recorded neurons was 18%. Twelve task-related neurons (27%) fired in relation to the response period of the DA task. Five of these neurons changed their firing rate during the delay period and were classified as delay/movement-related neurons. Contrary to the delay-related neurons, less than half (42%) of the response-related neurons were spatially selective. The majority (70%) of the delay-related neurons could not be activated by any of the sensory stimuli used and did not fire in relation to the movements of the monkey. The remaining portion of the delay-related neurons was activated by stationary and moving visual stimuli or by visual fixation of an object. In contrast to the delay-related neurons, the majority (66%) of the task-related neurons firing in relation to the movement period were also responsive to sensory stimulation outside of the task context. The majority of these neurons responded to visual stimulation, visual fixation of an object, or tracking eye movements. One neuron gave a somatomotor and another a polysensory response. The majority (n = 37, 67%) of all neurons responding to stimulation outside of the task context did not fire in relation to the DA task performance. The majority of their responses was elicited by visual stimuli or was related to visual fixation of an object or to eye movements. Only six neurons fired in relation to auditory, somatosensory, or somatomotor stimulation. This study provides further evidence about the significance of the dorsolateral prefrontal cortex in spatial working memory processing. Although a considerable number of all DA task-related neurons responded to visual, somatosensory, and auditory stimulation or to the movements of the monkey, most delay-related neurons engaged in the spatial DA task did not respond to extrinsic sensory stimulation. These results indicate that most prefrontal neurons firing selectively during the delay phase of the DA task are highly specialized and process only task-related information.

Animals↗

The delicate balance of law and ethics: a model for health administration educators.

The purpose of this paper is to provide a model for educators involved in teaching interrelated ethical, moral and legal dilemmas confronting health care delivery. For purposes of discussion, the AIDS epidemic is used as an example. Similarly complex issues, such as invitro fertilization, transplantation policy, etc. could also be analyzed using this model. A review of federal law, including a number of relevant cases, and their relationship of fundamental ethics issues is provided.

Acquired Immunodeficiency Syndrome↗

Fear-potentiated startle in two strains of inbred mice.

The fear-potentiated startle paradigm has been used with great success to examine conditioned fear in both rats and humans. The purpose of this study was to examine fear-potentiated startle in inbred mice. One-month-old C57BL/6J (C57) and DBA/2J (DBA) mice were given tone + foot shock training trials. The amplitude of the acoustic startle reflex was measured in the presence and absence of the tone both before and after training. Both strains showed fear-potentiated startle after training as evidenced by larger startle amplitudes in the presence of the tone than in its absence. However, the magnitude of fear-potentiated startle was greater in DBA mice than in C57 mice. These results not only demonstrate fear-potentiated startle in mice for the first time but also suggest that fear-potentiated startle can be influenced by characteristics of the mouse strain.

Acoustic Stimulation↗

The behavioral salience of tones as indicated by prepulse inhibition of the startle response: relationship to hearing loss and central neural plasticity in C57BL/6J mice.

Adult C57BL/6J mice exhibit high-frequency, sensorineural hearing loss accompanied by physiological changes in the upper auditory brainstem and cortex, referred to as hearing-loss induced (HLI) plasticity: as high-frequency sensitivity declines, many neurons come to respond better to still-audible, middle-frequency tones (especially 12-16 kHz). We used prepulse inhibition (PPI) to assess the relationship between the behavioral salience of tones and HLI plasticity. The ability of a tone 'prepulse' (S1), presented 100 ms before a startle-eliciting tone (S2), to 'inhibit' startle responses was measured in normal-hearing 1-month-olds and 5-month-olds with high-frequency hearing loss. Tone bursts of 4, 8, 12, 16, and 24 kHz were used as S1s and S2s in all possible combinations. PPI was significantly improved (more inhibition) in 5-month-olds with 12 or 16 kHz S1s. This effect was not influenced by S2 frequency or the size of the startle evoked by S2-only stimuli (smaller for high-frequency S2s in older mice). The increased salience of 12-16 kHz S1s in 5-month-old C57 mice parallels changes in the central representation of tone frequency and implies a behavioral effect of HLI plasticity.

Acoustic Stimulation↗

Carboxy-terminal vesicular stomatitis virus G protein-tagged intestinal Na+-dependent glucose cotransporter (SGLT1): maintenance of surface expression and global transport function with selective perturbation of transport kinetics and polarized expression.

The Na+-dependent glucose transporter (SGLT1) mediates absorption of luminal glucose by the intestine. However, available intestinal cell lines that recapitulate a monolayer phenotype only express SGLT1 at low levels. Thus, to facilitate studies of the biology of SGLT1 function in epithelial monolayers, we engineered an epitope-tagged construct containing the YTDIEMNRLGK sequence (from the vesicular stomatitis virus G protein). The tag was placed at the carboxyl terminus since this is the least conserved portion of SGLT1. Transiently transfected COS-1 cells demonstrated surface expression of the immunoreactive protein and enhanced Na+-dependent glucose uptake that was phloridzin-sensitive (a specific competitive inhibitor of SGLT1). However, subsequent detailed analyses of epitope-tagged SGLT1 using stably transfected clones derived from the Caco-2 human intestinal epithelial cell line revealed substantial effects of the epitope on critical functions of SGLT1. When compared with native SGLT1 transfectants, the apparent Km for sugar transport was increased 23-fold (313 microM to 7.37 mM for native versus epitope-tagged SGLT1). In contrast, the apparent KNa for epitope-tagged SGLT1 was similar to that for native SGLT1. Permeabilization studies indicated that the C-terminal epitope tag was intracellular and thus could not directly disrupt extracellular ligand-binding sites. Immunolocalization and functional assays designed to detect polarized surface expression indicated that epitope tagging resulted in loss of apical targeting and enrichment of basolateral expression. Functional isolation of the small apical pool of epitope-tagged SGLT1 (by selective inhibition of basolateral epitope-tagged SGLT1) revealed that, despite the documented kinetic alterations in sugar transport, epitope-tagged SGLT1 could promote absorptive Na+ currents. These data show that 1) the C terminus of SGLT1 is intracellular; 2) disruption of protein structure by addition of a C-terminal tag leads to selective modifications of SGLT1 function; 3) the kinetics of sugar transport can be altered independently of influences on the Na+-binding site of SGLT1; and 4) the weak basolateral targeting sequence present within the epitope tag is dominant over endogenous SGLT1 apical targeting information and can direct polytopic membrane protein localization. The data also caution that subtle effects of foreign sequences must be considered when epitope tagging polytopic membrane proteins.

Amino Acid Sequence↗

Maximizing the referral of older women for screening mammography.

The primary care physician is in a crucial position to facilitate mammography referral of women older than 50 years. Physician underestimation of the importance of the physician role or overestimation of patient resistance can result in lost opportunities for referral. Research is summarized on the impact of physician encouragement on use of mammography and on sources of reluctance to get mammography as reported by patients. Common patients' concerns are discussed. Mammography referral can usually be accomplished successfully by raising the issue and briefly addressing patients' concerns in regard to breast cancer and screening mammography.

Breast Neoplasms↗