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Biomedical subjects

B Eaton

Publications and source records attributed to B Eaton.

At least 19 recordsLinked to original sources

Analysis of speech-related variance in rapid event-related fMRI using a time-aware acquisition system.

Speech production introduces signal changes in fMRI data that can mimic or mask the task-induced BOLD response. Rapid event-related designs with variable ISIs address these concerns by minimizing the correlation of task and speech-related signal changes without sacrificing efficiency; however, the increase in residual variance due to speech still decreases statistical power and must be explicitly addressed primarily through post-processing techniques. We investigated the timing, magnitude, and location of speech-related variance in an overt picture naming fMRI study with a rapid event-related design, using a data acquisition system that time-stamped image acquisitions, speech, and a pneumatic belt signal on the same clock. Using a spectral subtraction algorithm to remove scanner gradient noise from recorded speech, we related the timing of speech, stimulus presentation, chest wall movement, and image acquisition. We explored the relationship of an extended speech event time course and respiration on signal variance by performing a series of voxelwise regression analyses. Our results demonstrate that these effects are spatially heterogeneous, but their anatomic locations converge across subjects. Affected locations included basal areas (orbitofrontal, mesial temporal, brainstem), areas adjacent to CSF spaces, and lateral frontal areas. If left unmodeled, speech-related variance can result in regional detection bias that affects some areas critically implicated in language function. The results establish the feasibility of detecting and mitigating speech-related variance in rapid event-related fMRI experiments with single word utterances. They further demonstrate the utility of precise timing information about speech and respiration for this purpose.

Adult↗

Prion-removal capacity of chromatographic and ethanol precipitation steps used in the production of albumin and immunoglobulins.

BACKGROUND AND OBJECTIVES: Although there is no epidemiological evidence to suggest that classical Creutzfeldt-Jakob disease (CJD) is transmitted through blood or blood products, the variant form (vCJD) has been implicated in transmission via packed red blood cells. The potential threat of the infectious agent contaminating plasma pools has led to manufacturing processes being examined for capacity to remove prions. The objective of these studies was to examine the prion-removal potential of the chromatographic purification and ethanol precipitation steps used to fractionate immunoglobulins and albumin from human plasma. MATERIALS AND METHODS: Western blot assay was used to examine the partitioning of proteinase K-resistant scrapie prion protein (PrPsc) over DEAE Sepharose, CM Sepharose and Macro-Prep High Q chromatographic columns, utilizing microsomal scrapie 263K spiked into each scaled down feedstream and assayed after each chromatographic step. In further studies, bioassay in C57 black mice was used and spikes of 10 000 g clarified brain homogenate of scrapie ME7 were added to feedstreams before sequences of scaled down chromatographic or Cohn fractionation process steps. RESULTS: The microsomal spiking study with Western blot detection demonstrated substantial partitioning of PrPsc away from the target proteins in all ion exchange chromatographic steps examined. The log10 reduction factors (LRF) across DEAE Sepharose and CM Sepharose columns for albumin were > or = 4.0 and > or = 3.0 respectively. The reductions across DEAE Sepharose and Macro-Prep High Q for intravenous immunoglobulin were 3.3 and > or = 4.1 respectively. Bioassay demonstrated LRFs of >or = 5.6 across the combination of DEAE Sepharose and CM Sepharose columns in the albumin process and > or = 5.4 across the combination of DEAE Sepharose and Macro-Prep High Q columns in the intravenous immunoglobulin process. Bioassay studies also demonstrated a LRF of > or = 5.6 for immunoglobulin produced by Cohn fractionation. CONCLUSIONS: Using rodent-adapted scrapie as a model, the studies indicated that ion exchange chromatography, as well as Cohn immunoglobulin fractionation have the potential to effectively reduce the load of TSE agents should they be present in plasma pools.

Animals↗

The cleavage activation and sites of glycosylation in the fusion protein of Hendra virus.

Hendra virus (HeV) is an unclassified member of the Paramyxoviridae family that causes systemic infections in humans, horses, cats, guinea pigs and flying foxes. The fusion protein (F(0)) of members of the Paramyxoviridae family that cause systemic infections in vivo contains a basic amino acid-rich region at which the protein is activated by cleavage into two subunits (F(1) and F(2)). HeV F(0) lacks such a domain. We have determined the cleavage site in HeV F(0) by sequencing the amino terminus of the F(1) subunit and in view of the potential effect of glycosylation on the cleavage process have ascertained the sites at which F(0) is glycosylated. The results indicate that unlike other members of the family that replicate in cultured cells and cause systemic infections in vivo, cleavage of HeV F(0) occurs at a single lysine (reside 109) in the sequence Asp-Val-Lys- downward arrow-Leu. Although HeV genotypically resembles members of the Respirovirus and Rubulavirus genera in having potential N-linked glycosylation sites in both the F(1) and F(2) subunits, we show that phenotypically HeV may more closely resemble members of the Morbillivirus genus that contain N-linked glycans only in the F(2) subunit.

Amino Acid Sequence↗

Nipah virus: a recently emergent deadly paramyxovirus.

A paramyxovirus virus termed Nipah virus has been identified as the etiologic agent of an outbreak of severe encephalitis in people with close contact exposure to pigs in Malaysia and Singapore. The outbreak was first noted in late September 1998 and by mid-June 1999, more than 265 encephalitis cases, including 105 deaths, had been reported in Malaysia, and 11 cases of encephalitis or respiratory illness with one death had been reported in Singapore. Electron microscopic, serologic, and genetic studies indicate that this virus belongs to the family Paramyxoviridae and is most closely related to the recently discovered Hendra virus. We suggest that these two viruses are representative of a new genus within the family Paramyxoviridae. Like Hendra virus, Nipah virus is unusual among the paramyxoviruses in its ability to infect and cause potentially fatal disease in a number of host species, including humans.

Animals↗

Distal scaphoid resection arthroplasty for the treatment of degenerative arthritis secondary to scaphoid nonunion.

Nineteen patients with chronic scaphoid nonunion and associated degenerative arthritis between the distal fragment and the radial styloid were treated by resection of the distal fragment. All patients had a dorsal intercalated segment instability wrist collapse pattern with an average radiolunate angle of -32 degrees and a 10% reduction in the carpal height, both of which changed minimally during the follow-up period. The duration of the nonunion averaged 12 years and the follow-up period averaged 49 months. Range of motion improved 85% and grip improved 134%. Thirteen of the patients experienced complete pain relief. One patient required additional surgery and elected wrist arthrodesis. Resection of the distal fragment is not recommended for patients with capitolunate arthritis. Two of the 4 patients with capitolunate arthritis had persistent symptoms; 3 had progressive degenerative changes.

Adult↗

Describing traumatic responses and distress of community residents directly and indirectly exposed to an aircraft crash.

This study described the traumatic responses and the extent of psychological distress among residents who had been exposed directly or indirectly to an aircraft crash in Coventry, U.K. The direct exposure group consisted of 62 residents who were on the housing estate at the time of the accident and 20 who were not. They were interviewed on their subjective responses to the crash and then asked to fill in two distress measures: the Impact of Event Scale (IES) and the General Health Questionnaire (GHQ). The results showed a contrast between the responses of the two groups at the time of the crash. They also showed that the direct exposure group had a significantly higher score in the IES item of avoidance, the IES total, the GHQ items of somatization, social dysfunction, and the total score than the indirect exposure group had. Associations were then made between subjective responses and distress measures. Stepwise multiple regression analyses showed that for the direct exposure residents, the IES total was predicted by "whether they received professional help" and "whether they were worried about their safety after the crash." The GHQ total of the direct exposure residents was predicted by "anger about what had happened to them." For the indirect exposure residents, the IES total was predicted by "their present feelings when they heard planes flying over." There were no predictions found between responses and the GHQ total.

Accidents, Aviation↗

The fatigue of cancer.

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Attitude of Health Personnel↗

Prenatal alcohol exposure and communication, behavior, and nonverbal intelligence of 3 school-age children.

Associations of prenatal alcohol exposure in speech, language, behavioral, and intellectual development were investigated in three school-aged children diagnosed with Fetal Alcohol Syndrome, accompanied by Attention Deficit Hyperactivity Disorder. Each child showed similar patterns of moderate-to-severe dysfunctional behavior; however, their scores on speech, language and nonverbal intellectual measures were highly variable.

Attention Deficit Disorder with Hyperactivity↗

Distinct molecular events during secretory granule biogenesis revealed by sensitivities to brefeldin A.

The biogenesis of peptide hormone secretory granules involves a series of sorting, modification, and trafficking steps that initiate in the trans-Golgi and trans-Golgi network (TGN). To investigate their temporal order and interrelationships, we have developed a pulse-chase protocol that follows the synthesis and packaging of a sulfated hormone, pro-opiomelanocortin (POMC). In AtT-20 cells, sulfate is incorporated into POMC predominantly on N-linked endoglycosidase H-resistant oligosaccharides. Subcellular fractionation and pharmacological studies confirm that this sulfation occurs at the trans-Golgi/TGN. Subsequent to sulfation, POMC undergoes a number of molecular events before final storage in dense-core granules. The first step involves the transfer of POMC from the sulfation compartment to a processing compartment (immature secretory granules, ISGs): Inhibiting export of pulse-labeled POMC by brefeldin A (BFA) or a 20 degrees C block prevents its proteolytic conversion to mature adrenocorticotropic hormone. Proteolytic cleavage products were found in vesicular fractions corresponding to ISGs, suggesting that the processing machinery is not appreciably activated until POMC exits the sulfation compartment. A large portion of the labeled hormone is secreted from ISGs as incompletely processed intermediates. This unregulated secretory process occurs only during a limited time window: Granules that have matured for 2 to 3 h exhibit very little unregulated release, as evidenced by the efficient storage of the 15-kDa N-terminal fragment that is generated by a relatively late cleavage event within the maturing granule. The second step of granule biogenesis thus involves two maturation events: proteolytic activation of POMC in ISGs and a transition of the organelle from a state of high unregulated release to one that favors intracellular storage. By using BFA, we show that the two processes occurring in ISGs may be uncoupled: although the unregulated secretion from ISGs is impaired by BFA, proteolytic processing of POMC within this organelle proceeds unaffected. The finding that BFA impairs constitutive secretion from both the TGN and ISGs also suggests that these secretory processes may be related in mechanism. Finally, our data indicate that the unusually high levels of unregulated secretion often associated with endocrine tumors may result, at least in part, from inefficient storage of secretory products at the level of ISGs.

Animals↗

Decision and attribution bias in neurorehabilitation.

OBJECTIVE: Examine neurorehabilitation therapists' clinical predictions and attributions for outcomes. DESIGN: Single sample, repeated measures. PARTICIPANTS: A sample of 51 neurorehabilitation therapists selected from representative disciplines including occupational therapy, physical therapy, speech therapy, and recreation therapy. MAIN OUTCOME MEASURES: Self-report questionnaire on factors related to positive and negative outcomes in neurorehabilitation. Rank order listing of factors influencing outcome in neurorehabilitation. RESULTS: Without cuing, therapists did not identify injury severity as factor in outcome (p < .0001). Therapists also made internal attributions for positive outcomes and external attributions for negative outcomes (p < .0001). CONCLUSIONS: Neurorehabilitation therapists tend to ignore injury severity as factor in outcome unless encouraged to do so. Therapists accept personal responsibility for positive outcomes, but not for negative outcomes. Neurorehabilitation teams may benefit from education on factors affecting prognosis and attribution bias found in clinical practice.

Adult↗

Mortality among laboratory workers employed at the U.S. Department of Agriculture.

We evaluated the mortality of 835 white male and 36 female laboratory workers employed by the U.S. Department of Agriculture who died between January 1, 1970, and December 31, 1979. For males, the mortality odds ratio for all cancers was 1.0 (95% confidence interval = 0.8-1.2). Colon cancer, lymphosarcoma and reticulosarcoma, nonmalignant diseases of the blood and blood-forming organs, and suicide showed elevated mortality odds ratios. Only colon cancer showed an association with duration of employment as a laboratory worker. In an accompanying case-control study, the risk of colon cancer rose to 3.2 among those who had 20 or more years of employment as a laboratory worker. Among females, breast cancer was elevated (mortality odds ratio = 5.3; 95% confidence interval = 2.8-10.1).

Female↗

Mortality among agricultural extension agents.

The mortality experience of agricultural extension agents in the Cooperative Extension Service (CES) of the U.S. Department of Agriculture who died during the period January 1, 1970-December 31, 1979 (n = 1,495 white males) was evaluated in proportionate-mortality and case-control studies. The proportionate-mortality analysis was used to identify cancers that might be elevated in this occupational group compared with the U.S. white male population. All cancers with a significantly elevated proportionate-mortality ratio were more thoroughly evaluated in the case-control study, where there is presumably less of a selection bias in the comparison. In the case-control study, leukemia demonstrated a statistically significant linear trend with duration of employment as an extension agent. Smaller, but nonsignificant, trends were seen for non-Hodgkin's lymphoma, multiple myeloma, and brain cancer. The odds ratio for Hodgkin's disease and cancers of the colon, prostate, and kidney did not vary with the number of years on the job. These patterns resemble cancer risks seen among farmers, suggesting that agricultural factors may also play a role in the origin of these tumors among extension agents.

Adult↗

Biochemical characterization of fracture callus proteoglycans.

The changes in proteoglycan molecules during the initial stages of fracture healing in rats were characterized. Following extraction of callus proteoglycan components with dissociative solvents, the components were purified in a cesium chloride density gradient. The recovered proteoglycans were characterized with respect to their molecular size distribution using gel filtration chromatography and a centrifugal transport methodology. During this early healing period, a decrease was observed in the relative proportion of the aggregate and in the hydrodynamic size and sedimentation coefficients of these molecules. While some molecular degradation could have occurred during the early stages of fracture healing, the dominant change of the proteoglycan molecules seemed to be disaggregation. No significant difference was observed in the proportion of aggregates reformed when exogenous hyaluronate and link glycoproteins were allowed to interact with the two corresponding monomer preparations. The molecular changes of the proteoglycan molecules seem to parallel those occurring during endochondral calcification of rat epiphyseal cartilage.

Animals↗