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Biomedical subjects

B Weaver

Publications and source records attributed to B Weaver.

At least 19 recordsLinked to original sources

Spinal muscular atrophy type 1: A noninvasive respiratory management approach.

STUDY OBJECTIVE: To determine whether spinal muscular atrophy (SMA) type 1 can be managed without tracheostomy and to compare extubation outcomes using a respiratory muscle aid protocol vs conventional management. DESIGN: A retrospective cohort study. METHODS: Eleven SMA type 1 children were studied during episodes of respiratory failure. Nine children required multiple intubations. Along with standard treatments, these children received manually and mechanically assisted coughing to reverse airway mucus-associated decreases in oxyhemoglobin saturation. Extubation was not attempted until, most importantly, there was no oxygen requirement to maintain oxyhemoglobin saturation greater than 94%. After extubation, all patients received nasal ventilation with positive end-expiratory pressure. Successful extubation was defined by no need to reintubate during the current hospitalization. RESULTS: Two children have survived for 37 and 66 months and have never been intubated despite requiring 24-h nasal ventilation since 5 and 7 months of age, respectively. One other child underwent tracheostomy for persistent left lung collapse and inadequate home care, another for need for frequent readmission and intubation, and one child was lost to follow-up 3 months after successful extubation. The other six children have been managed at home for 15 to 59 (mean 30.4) months using nocturnal nasal ventilation after an episode of respiratory failure. The nine children were successfully extubated by our protocol 23 of 28 times. The same children managed conventionally were successfully extubated 2 of 20 times when not using this protocol (p < 0.001 by the two-tailed Fisher's Exact t Test). CONCLUSION: Although intercurrent chest colds may necessitate periods of hospitalization and intubation, tracheostomy can be avoided throughout early childhood for some children with SMA type 1.

Child, Preschool

Scene-based and object-centered inhibition of return: evidence for dual orienting mechanisms.

We investigated whether inhibition of return (IOR) could be observed in location-based, scene-based, and object-centered frames of reference. IOR was found to move both with a separate cued object (scene-based) and with a location within a single rotating object (object-centered). Importantly, however, IOR was also associated with the environmental location cued when cuing was of a separate object (scene-based), whereas facilitation of the cued location was found when cuing was of a component within an object. These results suggest that location is of central importance to scene-based representations of separate objects, which appear to be encoded in viewer-centered coordinates, whereas environmental locus is of little relevance when attention orients within a single object. The results also provide further evidence for the coexistence of both excitation and inhibition associated with uninformative exogenous cues.

Adult

Cloning, expression, and characterization of chicken tissue inhibitor of metalloproteinase-2 (TIMP-2) in normal and transformed chicken embryo fibroblasts.

Rous sarcoma virus-transformed chicken embryo fibroblasts (RSVCEF), when compared to normal CEF, produce elevated levels of matrix metalloproteinase-2 (MMP-2) that exists in a form free of complexed tissue inhibitor of metalloproteinase-2 (TIMP-2). In order to ascertain whether the increased levels of TIMP-free MMP-2 in RSVCEF cultures are due to diminished expression of TIMP-2 or alterations in TIMP-2 that diminish its MMP-2 binding ability, it was necessary to clone, characterize, and express chicken TIMP-2 cDNA. The TIMP-2 cDNA was cloned from a chick embryo lambda gt11 library by RT-PCR using primers based on amino-acid sequences determined from isolated TIMP-2. The deduced amino acid sequence for chicken TIMP-2 is 81% identical to human TIMP-2; most of the sequence differences lie in the carboxyl terminal portion of chicken TIMP-2. Northern analysis of mRNA levels in CEF and RSVCEF demonstrates that TIMP-2 mRNA levels are increased in RSVCEF. However, TIMP-2 protein levels, relative to proMMP-2 levels, appear to decrease upon transformation and suggest additional control of TIMP-2 at the post-transcriptional level. Addition of recombinantly expressed TIMP-2 to RSVCEF cultures causes a disappearance of TIMP-free (TF) proMMP-2 with a corresponding increase in the TIMP-complexed (TC) proMMP-2 levels, demonstrating that TF proMMP-2 is capable of converting to TC pro-MMP-2 when free TIMP-2 is available. Surprisingly, RSVCEF cultures manifest a TIMP-2 population that is not complexed to MMP-2, despite the coexistence of TIMP-free proMMP-2. Gel-filtration analysis indicates that this uncomplexed TIMP-2 exhibits an apparent molecular weight of 50 kDa, indicating it is not free TIMP-2 and that it exists in transformed cultures in a noncovalent complex with an undefined molecule. Thus transformed cells can alter the TIMP-2/MMP-2 balance by transcriptional and post-translational modifications, yielding a population of inhibitor-free, proteolytically active MMP2.

Amino Acid Sequence

Cytomegalovirus activates interferon immediate-early response gene expression and an interferon regulatory factor 3-containing interferon-stimulated response element-binding complex.

Interferon establishes an antiviral state in numerous cell types through the induction of a set of immediate-early response genes. Activation of these genes is mediated by phosphorylation of latent transcription factors of the STAT family. We found that infection of primary foreskin fibroblasts with human cytomegalovirus (HCMV) causes selective transcriptional activation of the alpha/beta-interferon-responsive ISG54 gene. However, no activation or nuclear translocation of STAT proteins was detected. Activation of ISG54 occurs independent of protein synthesis but is prevented by protein tyrosine kinase inhibitors. Further analysis revealed that HCMV infection induced the DNA binding of a novel complex, tentatively called cytomegalovirus-induced interferon-stimulated response element binding factor (CIF). CIF is composed, at least in part, of the recently identified interferon regulatory factor 3 (IRF3), but it does not contain the STAT1 and STAT2 proteins that participate in the formation of interferon-stimulated gene factor 3. IRF3, which has previously been shown to possess no intrinsic transcriptional activation potential, interacts with the transcriptional coactivator CREB binding protein, but not with p300, to form CIF. Activating interferon-stimulated genes without the need for prior synthesis of interferons might provide the host cell with a potential shortcut in the activation of its antiviral defense.

2-Aminopurine

The effects of practice on object-based, location-based, and static-display inhibition of return.

We report two experiments that examine the effects of practice on object-based, location-based, and static-display inhibition of return (IOR). The results are clear: All three effects get smaller with practice. These findings are at odds with the results of Müller and von Mühlenen (1996), who failed to observe object-based IOR and detected no effect of practice on static-display IOR. However, their subjects were more practiced than ours prior to data collection. We suggest, therefore, that the reducing effect of practice on IOR have occurred in their unrecorded practice sessions. We also discuss a two-process model in which IOR is seen as the net effect of underlying inhibitory and excitatory processes. In such models (e.g., Solomon & Corbit, 1974), practice often results in a reduction of the net effect of the two processes.

Adolescent

Cloning and characterization of soluble and transmembrane isoforms of a novel component of the murine type I interferon receptor, IFNAR 2.

This report describes the cloning of cDNAs encoding transmembrane and soluble isoforms of a novel chain of the murine type I interferon (IFN) receptor and characterization of its capability to bind ligand and transduce signals. The transmembrane receptor (murine IFNAR 2c) has an extracellular domain of 215 amino acids and an intracellular domain of 250 amino acids, with 48% amino acid and 71% nucleotide identity with human IFNAR 2c. The cDNA for the soluble murine receptor (IFNAR 2a) encodes a 221-amino acid polypeptide identical to the first 210 amino acids of IFNAR 2c plus a novel 11 amino acids. Northern blot analyses show that murine IFNAR 2 is expressed as two transcripts of 4 kilobases encoding the transmembrane isoform and 1.5 kilobases encoding the more abundant soluble isoform. Studies using primary murine cells that lack IFNAR 1 show that IFNAR 2 is expressed, and cells bind type I IFN ligand, but do not transduce signals as detected by electrophoretic mobility shift assays of ISGF3 or GAF complexes binding to their cognate oligonucleotides. These cells show no effects on the ability of IFNgamma to activate these complexes. These studies demonstrate that the IFNAR 2 transmembrane (2c) and soluble (2a) isoforms are conserved between the human and mouse and that IFNAR 2c has intrinsic ligand binding activity, but no intrinsic signal transducing activity as measured in this study.

Amino Acid Sequence

Object-based facilitation and inhibition from visual orienting in the human split-brain.

Object-based attention was examined in 2 split-brain patients. A precued object could move within a visual field or cross the midline to the opposite field. Normal individuals show an inhibition in detecting signals in the cued object whether it moves within or between fields. Both patients showed this effect when the cued object moved within a visual field. When it crossed the midline into the opposite visual field, however, detection was faster in the cued box. These results reveal both facilitatory and inhibitory effects on attention that are object based and may last for several hundred milliseconds. However, the inhibition requires an intact corpus callosum for interhemispheric transfer, whereas the facilitation is transferred subcortically.

Adult

Prostatic acid phosphatase levels (enzymatic method) from completely sectioned, clinically benign, whole prostates.

Clinically benign, whole untrimmed prostates were obtained from 104 patients at autopsy, completely sectioned, and examined microscopically. The histological and gross findings of the prostate were correlated with premortem prostatic acid phosphatase levels (PAP, enzymatic method, ACA, Dupont Co.) to determine how often carcinoma of the prostate (CAP) affected PAP levels and to identify other findings within the prostate associated with elevated PAP levels. Sixty (58%) prostates did not have CAP, 34 (33%) had CAP smaller than 1 ml in volume, and 10 (10%) had CAP larger than 1 ml in volume. PAP levels were elevated (greater than 1 U/L) in 8 of 60 (13%) prostates without CAP, in 2 of the 34 (6%) prostates with CAP smaller than 1 ml, and in 1 of the 10 (10%) prostates with CAP larger than 1 ml. These differences were not statistically significant. Likewise, a statistically significant correlation between PAP levels and patient age, patient race, severe inflammation, of high grade prostatic intraepithelial neoplasia (PIN) was not found. However, there was a statistically significant correlation between PAP levels and prostate weight (p < 0.0001). This study suggest that PAP cannot distinguish between patients with clinically undetected CAP and patients without CAP. Furthermore, elevated PAP levels are often not due to metastatic CAP and additional evidence should be present, even in patients with known CAP, before an elevated PAP level is considered to be conclusive evidence of metastatic CAP.

Acid Phosphatase

Inhibition of return to successively cued spatial locations: commentary on Pratt and Abrams (1995).

J. Pratt and R.A. Abrams (1995) reported that the inhibition of return of attention is found only for the most recently attended of 2 cued locations. This study does not dispute their findings, but suggests that a more ecologically valid experiment would have more than 2 possible target locations. Twelve male students participated in an experiment in which the target may occur in 1 of 4 possible locations, after 3 of those locations have been cued exogenously in sequence. Inhibition of return was found for each of the cued locations. This result suggests that inhibition may be an important mechanism for aiding visual search in complex environments.

Adult

Characteristics of prostatic infarcts and their effect on serum prostate-specific antigen and prostatic acid phosphatase.

OBJECTIVES: To determine how prostatic infarcts affect serum prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) levels. METHODS: Two hundred eighteen clinically benign, whole prostates were obtained at autopsy, completely sectioned, and examined histologically. PSA and PAP levels were determined from premortem serum. RESULTS: Six of the 218 (2.8%) prostates had infarcts. The infarcts were usually multiple and usually located in the central and/or middle concentric zones of the middle third of the prostate without a preference for a particular lobe. Serum PSA by immunoradiometric assay were elevated in all 6 cases. Serum PAP by both enzymatic assay (ACA), and immunoradiometric assay were available for 5 cases and were elevated by both methods in 2 cases, approached elevated levels by both methods in 1 case, and were normal by both methods in 2 cases. The PSA and PAP levels appeared to be affected more by the age than by the size of the infarct. CONCLUSIONS: Prostatic infarcts elevate PSA levels more frequently than PAP levels, and prostatic infarcts may be responsible for some unexplained elevations of serum PSA and PAP levels.

Acid Phosphatase

Falls on a neurorehabilitation unit: reassessment of a prevention program.

We conducted a retrospective case-control study of falls over a four year period on a 30 bed neurorehabilitation unit at the Burke Rehabilitation Hospital to characterize the nature of falls and identify factors associated with falling. The most common diagnoses treated on the unit were traumatic spinal cord injury, brain injury, and multiple sclerosis; stroke patients are treated on another service. Falls represented 72 percent of all incident reports made to the Nursing Office during the study period. One hundred seventeen (117) falls occurred in 82 patients during a time when the unit census was 28,622 patient days, yielding a rate of 1,439 falls per 1,000 patient years. One hundred fourteen (114) patients admitted with no history of falling during the same period were selected randomly for comparison. Most falls were associated with no injury (n = 96) or minor injury (n = 18). The most significant injuries occurred in three cases with lacerations requiring sutures. Falls occurred with greatest frequency during the first and fourth quartiles of the hospital stay, during the evening and while bed transfers were being performed. No association between falling and patient age, sex, diagnosis, number of medications, use of sedating medications, presence of motor, visual or cognitive impairment or orthostatic hypotension was evident. An increased risk of falling was associated with physician orders for Posey restraints. The implication of these findings for falls prevention programs is discussed.

Accidental Falls

Object-based and environment-based inhibition of return of visual attention.

Efficient search for an object often requires that attention be prevented from returning to recently examined environmental loci. M. I. Posner and Y. A. Cohen (1984) proposed that inhibition of return (IOR) of visual attention is a search mechanism that prevents such attentional perservation. The internal representations upon which IOR functions were examined and the following conclusions were drawn: First, IOR mechanisms have access to both object- and environment-based representations. Second, environment-based inhibition can be associated with a featureless environmental location, whereas the object-based mechanism requires that attention be oriented to a visible object. These findings are discussed in terms of physiological pathways that may mediate location- and object-based effects.

Attention

The acquisition of lysophosphatidylcholine by African trypanosomes.

Bloodstream forms of the African trypanosome, Trypanosoma brucei, can acquire substantial amounts of exogenous lysophospholipid. Lysophosphatidylcholine uptake is through a pathway consisting of three enzymes, phospholipase A1, acyl-CoA ligase, and lysophosphatidylcholine:acyl-CoA acyltransferase. The pathway enables the organism to acquire fatty acids and phospholipid head groups such as choline. Radiolabeling and 13C NMR studies show that two molecules of lysophosphatidylcholine are used to generate one molecule of cellular phosphatidylcholine. The three enzymes are associated with the trypanosomal plasma membrane and are accessible to exogenous substrates. The first enzyme, phospholipase A1, generates free fatty acid from exogenous lysophospholipid, which the second enzyme, a ligase, uses to form acyl-CoA. The fatty acyl-CoA formed by this route is in a separate pool from that derived from exogenous free fatty acid and is used by the third enzyme, acyltransferase, to acylate a second molecule of exogenous lysophospholipid. Acyltransferase is accessible to exogenous and endogenous acyl-CoA. The high activity of this pathway in bloodstream forms, compared with procyclic culture form trypanosomes, suggests that it may play a role in the acquisition of fatty acids for synthesis of the membrane form of the variant surface glycoprotein. Extracellular myristoyllysophosphatidylcholine can be used by trypanosomes as a source of myristate in remodeling the lipid anchor of the variant surface glycoprotein.

Acyltransferases

Effect of zinc sulfate and acetylcysteine on experimental gastric ulcer: in vitro study.

A small ulcer produced in vitro by monopolar electrocoagulation on endoscopically obtained human antral biopsies and incubated in Trowel T-8 medium at 37 degrees C for 8 h has many histologic features of chronic gastric ulcer in man. Zinc sulfate and acetylcysteine in low concentrations had a significant healing effect in this ulcer model. Since the beneficial effect of zinc sulfate and acetylcysteine was counteracted by N-ethylmaleimide, a known blocker of sulfhydryl compounds, the beneficial effect of these two compounds probably was mediated through sulfhydryl compounds. Using special stain, N-(4-aminophenyl)maleimide, the sulfhydryl groups were localized in the epithelial cells of the surface layer and gastric glands.

Acetylcysteine

Inhibitory mechanisms of attention in identification and localization tasks: time course and disruption.

It has been proposed that 1 component of the mechanism of visual selective attention is active inhibition of distracting information. A series of studies examines the time course of inhibition and the possible interfering effects of other task demands. Results demonstrate that inhibition can last at least 7 s after selection processes and that it is unaffected by predictable, unrelated intervening events. However, intervening events that are less predictable, or are the same as the inhibited stimulus, disrupt inhibition. Such results motivate a reconsideration of the previous view of distractor inhibition as a transient, fragile phenomenon.

Adolescent

Object-centred inhibition of return of visual attention.

Our response to visual events can be delayed at positions we have recently examined attentively. Such inhibition could organize visual search through static scenes by suppressing those loci already searched, but this mechanism would fail in moving scenes as objects' locations then change during search. We cued attention to a moving object and found subsequent inhibition at the locus the object later occupied. This implies that previously examined objects are suppressed. Such object-centred inhibition would be highly adaptive, but would require a sophisticated neural implementation for a mechanism held to be sub-cortical.

Adult