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Biomedical subjects

B L Schwartz

Publications and source records attributed to B L Schwartz.

At least 19 recordsLinked to original sources
PubMed2000

The phenomenology of real and illusory tip-of-the-tongue states.

The tip-of-the-tongue state (TOT) is the phenomenological experience that a word is on the verge of being recalled. Most research has been directed at TOT etiology and at retrieval processes occurring during a TOT. In this study, TOT phenomenology was examined. In Experiment 1, strong TOTs were more likely than weak TOTs to be followed by correct recognition, and resolution (later recall) of TOTs was higher for strong than for weak TOTs, but only for commission errors. In Experiment 2, emotional TOTs were more likely to be resolved and recognized than nonemotional TOTs. In Experiment 3, imminence was defined as the feeling that retrieval is about to occur. Imminent TOTs were more likely to be followed by resolution and recognition than were nonimminent TOTs. Illusory TOTs (TOTs for unanswerable questions) tended to be weaker, less emotional, and less imminent than TOTs for answerable questions.

Adult↗
PubMed1999

Stress and a glycinergic intervention interact in the modulation of MK-801-elicited mouse popping behavior.

The ability of D-cycloserine, a partial glycine agonist, to modulate mouse popping behavior elicited by MK-801, a noncompetitive NMDA receptor antagonist, was studied in unstressed and stressed mice. In unstressed animals, D-cycloserine (5.6 and 10 mg/kg) attenuated the ability of MK-801 (1.0 mg/kg) to elicit this behavior. However, the ability of D-cycloserine to attenuate MK-801-elicited mouse-popping behavior was not evident in stressed mice, 24 h after they were forced to swim for up to 10 min in cold water. Thus, the therapeutic value of glycinergic interventions may be limited by environmental factors, such as stress.

Animals↗
PubMed1999

Visual scanning of facial expressions in schizophrenia.

The authors previously observed that schizophrenic patients generated fewer fixations of < or = 50.1 ms in response to faces than did a clinical control group. This study examined whether deficits in short-duration eye movements were related to patients' problems in gestalt perception of faces. Faces were presented in upright and inverted orientations to examine the effects of distorting facial gestalts on eye movements. Normal subjects generated more saccades of < or = 50.1 ms to upright than to inverted faces. Patients' saccades of < or = 50.1 ms did not differ between orientations. Patterns of fixations and of saccades > 50.1 ms did not differ between groups. The results may indicate deficits in these patients in search strategies that underlie perception of facial gestalts.

Adult↗
PubMed1998

Effect of visual cues, vital signs, and protocols on triage: a prospective randomized crossover trial.

STUDY OBJECTIVES: We sought to compare triage designations derived from in-person and telephone interviews and systematically examine the effect of visual cues, vital signs, and complaint-based protocols on the triage process. METHODS: We conducted a 2-phase, prospective, observational study employing a randomized, crossover design in a university teaching hospital emergency department. In both phases, every eligible patient underwent sequential in-person and telephone triage interviews conducted by certified ED triage nurses. After taking a history, each nurse chose 1 of 5 hypothetical triage designations and, after being told the patient's vital signs, again selected a designation. Phase 1 designations were based solely on nurses' clinical expertise. In phase 2, both nurses used complaint-based protocols. RESULTS: Agreement between telephone and in-person designations was poor (percent agreement, 43.1% to 48.8%; kappa,.19 to.26; taub,.34 to.45 for the 4 primary comparisons). Knowledge of vital signs and use of protocols did not improve agreement or increase identification of patients requiring admission to hospital. CONCLUSION: These data establish that telephone and in-person triage are not equivalent and suggest that visual cues may play an important role in the triage process. It is unclear whether telephone triage is an adequate method of assigning patients to an appropriate level of care.

Adolescent↗
PubMed1998

Visual scanning of faces correlates with schizophrenia symptomatology.

1. The purpose of this study was to examine whether quantitative measures of visual scanning of faces correlated with the severity of symptoms in patients with schizophrenia. 2. Preattentive visual fixations (fixations less than or equal to 50.1 ms in duration) were measured while 16 subjects with chronic schizophrenia and 38 comparison subjects scanned slides of human faces. 3. A significant inverse correlation was found between the number of preattentive fixations exhibited during 10 seconds of facial scanning and total Brief Psychiatric Rating Scale (BPRS) scores. 4. This study suggests that measures that probe preattentive processing during scanning of faces could represent a novel paradigm for studying the symptoms of schizophrenia.

Adult↗
PubMed1998

The mismeasure of memory: when retrieval fluency is misleading as a metamnemonic index.

The experiments address the degree to which retrieval fluency--the case with which information is accessed from long-term memory--guides and occasionally misleads metamnemonic judgments. In each of 3 experiments, participants' predictions of their own future recall performance were examined under conditions in which probability or speed of retrieval at one time or on one task is known to be negatively related to retrieval probability on a later task. Participants' predictions reflected retrieval fluency on the initial task in each case, which led to striking mismatches between their predicted and actual performance on the later tasks. The results suggest that retrieval fluency is a potent but not necessarily reliable source of information for metacognitive judgments. Aspects of the results suggest that a basis on which better and poorer rememberers differ is the degree to which certain memory dynamics are understood, such as the fleeting nature of recency effects and the consequences of an initial retrieval. The results have pedagogical as well as theoretical implications, particularly with respect to the education of subjective assessments of ongoing learning.

Female↗
PubMed1998

The relation of output order and commission errors in free recall and eyewitness accounts.

We explored the relation between output order and the likelihood of a commission error in free recall under both laboratory and eyewitness conditions. In Experiment 1, participants studied a list of 20 unrelated words and, after a five-minute distractor task, were asked to recall those words. Whereas the items that participants recalled were mostly correct, commission errors were more likely to occur at the end of a participant's output. In Experiment 2, participants viewed a police film depicting an armed robbery. Participants described the perpetrators, their truck, and the sequence of events during the robbery. When describing the perpetrators or the truck, commission errors were more likely to occur at the end of the output. However, when describing the sequence of events, commission errors were more likely to occur in the middle of the output. In Experiment 3, we replicated the finding that commission errors are likely to occur at the end of the output order when participants are describing people. We speculate on the potential application of this finding and its theoretical underpinnings.

Analysis of Variance↗
PubMed1998

Illusory tip-of-the-tongue states.

The tip-of-the-tongue state (TOT) is the phenomenological experience that a target word is on the verge of being recalled. An illusory TOT occurs when a person experiences a TOT, but the actual target is either unavailable, forgotten, or never learned. Illusory TOTs were induced by asking participants to answer questions that did not have correct answers. In Experiment 1, an episodic-memory paradigm, participants were shown fictional animals, some of which were accompanied by the animal's name (identified targets) and some of which were not (unidentified targets). Some participants experienced TOTs for unidentified targets. In Experiment 2, a semantic-memory paradigm, participants were asked general-information questions, some of which were questions with no correct answer. Every one of the 31 participants experienced at least one illusory TOT. The characteristics of illusory TOTs are discussed in light of inferential and direct-access views of TOTS.

Humans↗
PubMed1997

Methylene blue adjuvant therapy of schizophrenia.

There is growing interest in the role of the nitric oxide (NO) pathway in idiopathic psychotic disorders such as schizophrenia. In this preliminary study, we examined the therapeutic efficacy of methylene blue (MB), a "downstream" inhibitor of one of NO's actions, administered orally as an adjuvant to conventional neuroleptic medications. Specifically, MB blocks NO's activation of soluble guanylyl cyclase. MB has previously been reported to have therapeutic effects in the treatment of psychosis and mania. Preclinical data also suggest that MB might possess antipsychotic potential. Participants in the current study were eight patients with schizophrenia who had incomplete responses to conventional antipsychotics (as evidenced by a Brief Psychiatric Rating Scale [BPRS] total score of 35 or more). These patients completed a 4-week open-label study with a 1 week "off", 2 week "on", and one final week "off" design. Measures of treatment efficacy were the BPRS, Schedule for the Assessment of Negative Symptoms, and Clinical Global Improvement Scale administered weekly. Final scores for each outcome measure item were based on the consensus of at least two trained raters present during each rating interview. A statistically significant, albeit modest, decrease in the severity of psychopathology was observed while the subjects were taking MB, and psychopathology significantly worsened when MB was discontinued. The results suggest a need for further study with MB or perhaps other NO-dependent guanylyl cyclase-inhibiting medications.

Adult↗
PubMed1997

Effects of nifedipine, a calcium channel antagonist, on cognitive function in schizophrenic patients with tardive dyskinesia.

We examined whether nifedipine, a calcium channel antagonist, added to a stable regimen of neuroleptic medication would affect cognition in patients with chronic schizophrenia or schizoaffective disorder who had tardive dyskinesia. Fifteen patients with tardive dyskinesia were treated with nifedipine (60 mg daily) or matching placebo for 4 weeks and then were crossed over from nifedipine to placebo or from placebo to nifedipine for another 4 weeks. At the end of each 4-week phase of the study, the patients performed a rotary pursuit test of procedural learning and a dementia scale assessing general cognitive abilities. Nifedipine improved performance in the rotary pursuit test and conceptual abilities in the dementia scale compared with placebo, but only for patients who first were exposed to the tests during the placebo condition. These results provide preliminary evidence that calcium channel antagonists might enhance learning and memory in schizophrenic patients with tardive dyskinesia.

Aged↗
PubMed1997

Frontal cortical atrophy and negative symptoms in patients with chronic alcohol dependence.

It has been suggested that frontal lobe pathology is associated with negative symptoms in patients with chronic alcoholism. In his exploratory study, the authors examined 19 chronic alcoholic inpatients on an alcohol treatment unit and found a significant relationship between severity of frontal atrophy (as measured by CT) and negative symptoms (as measured by the Scale for the Assessment of Negative Symptoms).

Adolescent↗
PubMed1996

Screening derivatized peptide libraries for tight binding inhibitors to carbonic anhydrase II by electrospray ionization-mass spectrometry.

This paper describes the use of electrospray ionization-mass spectrometry (ESI-MS) to screen two libraries of soluble compounds to search for tight binding inhibitors for carbonic anhydrase II (EC 4.2.1.1). The two libraries, H2NO2SC6H4C(O)NH-AA1-AA2-C(O)NHCH2CH2CO2H where AA1 and AA2 are L-amino acids (library size: 289 compounds) or D-amino acids (256 compounds), were constructed by attaching tripeptides to the carboxyl group of 4-carboxybenzenesulfonamide. Screening of both libraries yielded, as the tightest binding inhibitor, compound 1 (AA1 = AA2 = L-Leu; binding constant Kb = 1.4 x 10(8) M-1). The ability of ESI-MS to estimate simultaneously the relative binding affinities of a protein to soluble ligands in a library, if general, should be useful in drug development.

Amino Acid Sequence↗
PubMed1996

Impaired motor skill learning in schizophrenia: implications for corticostriatal dysfunction.

We assessed skill learning in young and older schizophrenic patients using the rotary pursuit task. Schizophrenic patients displayed impaired learning on this task compared with normal control subjects, but older patients were not more impaired than young ones. The patients' rotary pursuit learning was not correlated to the severity of abnormal movements or to their treatment with medication, but it was associated to conceptual abilities assessed on the Dementia Rating Scale (Mattis 1988). An impairment in acquiring motor procedures in this task might reflect neuropsychological deficits associated with corticostriatal pathology.

Adult↗
PubMed1996

Electrospray mass spectrometric investigation of the chaperone SecB.

Electrospray ionization mass spectrometry was used to investigate the structure of the Escherichia coli chaperone protein SecB. It was determined that the N-terminal methionine of SecB has been removed and that more than half of all SecB monomers are additionally modified, most likely by acetylation of the N-terminus or a lysine. The use of gentle mass spectrometer interface conditions showed that the predominant, oligomeric form of SecB is a tetramer that is stable over a range of solution pH conditions and mass spectrometer interface heating (i.e., inlet capillary temperatures). At very high pH, SecB dimers are observed. SecB contains a region that is hypersensitive to cleavage by proteinase K and is thought to be involved in conformational changes that are crucial to the function of SecB. We identified the primary site of cleavage to be between Leu 141 and Gln 142. Fourteen amino acids are removed, but the truncated form remains a tetramer with stability similar to that of the intact form.

Bacterial Proteins↗
PubMed1996

d-Cycloserine enhances implicit memory in Alzheimer patients.

We tested the ability of d-cycloserine, a partial glycine agonist acting at the N-methyl-D-aspartate (NMDA) receptor complex, to improve implicit memory in Alzheimer patients in a parallel-group, placebo-controlled, double-blind study. One-hundred eight patients with probable Alzheimer's disease of mild to moderate severity received d-cycloserine (5, 15, or 50 mg) or placebo twice daily for 10 weeks. We then evaluated their ability to identify perceptually degraded words, some of which were repeated over multiple trials across 3 days. Implicit memory performance of words repeated across trials was significantly enhanced for the patients who received 15 mg d-cycloserine compared with those who received placebo. These findings support development of NMDA receptor-mediated glutamatergic interventions for the treatment of Alzheimer-related memory disorders.

Aged↗
PubMed1995

Bio-affinity characterization mass spectrometry.

A new approach, bio-affinity characterization mass spectrometry (BACMS), aimed at providing a more rapid, sensitive and potentially more flexible alternative to techniques presently employed for the characterization of noncovalent interactions in mixtures, such as would be encountered in combinatorial chemistry, in presented. BACMS avoids some of the difficulties and potential artifacts associated with affinity chromatography since the noncovalent associations occur in solution; thus, BACMS avoids the requirement of solid support media and the development of non-interfering linker species. This paper describes the conceptual basis for the methodology and its potential use in applications which include the screening of high affinity ligands in support of new drug development. BACMS exploits new Fourier-transform ion cyclotron resonance (FTICR) mass spectrometry technologies which, when coupled to electrospray ionization (ESI), allow the investigation of specific noncovalent complexes formed in solution. BACMS utilizes the well-known attributes of FTICR, such as the high resolution mass analysis and (MS)n (n > or = 2) capabilities; however, it is even more directly a result of recently developed techniques involving quadrupolar excitation, such as selected-ion accumulation. These tools are demonstrated and the results illustrate the extraordinary sensitivity achievable (solution concentration of 1 x 10-9 M without the use of separations prior to ESI). Thus, the new capabilities demonstrated here, in conjunction with ESI, will be useful for the investigation of very low relative concentration noncovalent association directly from solution, and promote a faster alternative for combinatorial mixture screening and analysis.

Animals↗
PubMed1995

Engineered chimeric streptavidin tetramers as novel tools for bioseparations and drug delivery.

We report the construction of chimeric streptavidin tetramers that are composed of subunits of both wild-type (WT) streptavidin and genetically-engineered streptavidin variants designed for enhanced bioseparation and drug delivery performance. Subunit mixing is accomplished by guanidine thiocyanateinduced denaturation of an equimolar mixture of WT streptavidin and the respective site-directed mutant, followed by renaturation and reassociation of mixed tetramers. In the first example, we demonstrate the mixing of WT subunits with an Asn49Cys (N49C) mutant. The WT/n49C tetramers can be used for site-specific and stoichiometric attachment of therapeutics/imaging agents or targeting proteins through the genetically-engineered thiol while retaining unhindered access to biotin-binding at the WT subunits. Second, we demonstrate that the His127Cys mutation (H127C) results in a streptavidin mutant that forms a disulfide-linked dimer under non-reducing conditions. Mixing of H127C and WT streptavidin subunits results in chimeric tetramers where both the stoichiometry (WT:H127C::1:1) and subunit architecture is controlled by the unique disulfide bridge engineered into H127C. In the third example, WT subunits were mixed with the subunits of a site-directed mutant, Trp120Ala (W120A), which displays a biotin dissociation constant that is enhanced by more than 10(4) compared to WT streptavidin. The W120 biotin-binding affinity is sufficiently high (Ka approximately equal to 10(7) M-1) to immobilize the mutant on a biotinagarose affinity chromatography column, but the engineered off-rate allows for facile elution with excess biotin at physiological pH, whereas WT streptavidin is irreversibly immobilized on the column. We demonstrate that the purified WT/W120A chimeric tetramers combine the advantages of both subunits, allowing for irreversible immobilization of biotinylated targets at the WT subunit, while retaining the reversible separation capabilities of the W120A subunits via biotin-agarose affinity chromatography.

Dimerization↗