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Biomedical subjects

J Michael Williams

Publications and source records attributed to J Michael Williams.

13 recordsLinked to original sources
PubMed2006

The attenuation of auditory neglect by implicit cues.

This study examined implicit semantic and rhyming cues on perception of auditory stimuli among nonaphasic participants who suffered a lesion of the right cerebral hemisphere and auditory neglect of sound perceived by the left ear. Because language represents an elaborate processing of auditory stimuli and the language centers were intact among these patients, it was hypothesized that interactive verbal stimuli presented in a dichotic manner would attenuate neglect. The selected participants were administered an experimental dichotic listening test composed of six types of word pairs: unrelated words, synonyms, antonyms, categorically related words, compound words, and rhyming words. Presentation of word pairs that were semantically related resulted in a dramatic reduction of auditory neglect. Dichotic presentations of rhyming words exacerbated auditory neglect. These findings suggest that the perception of auditory information is strongly affected by the specific content conveyed by the auditory system. Language centers will process a degraded stimulus that contains salient language content. A degraded auditory stimulus is neglected if it is devoid of content that activates the language centers or other cognitive systems. In general, these findings suggest that auditory neglect involves a complex interaction of intact and impaired cerebral processing centers with content that is selectively processed by these centers.

Acoustic Stimulation↗
PubMed2006

Brain mapping of deception and truth telling about an ecologically valid situation: functional MR imaging and polygraph investigation--initial experience.

PURPOSE: To examine the neural correlates during deception and truth telling by using a functional magnetic resonance (MR) imaging technique and an ecologically valid task and to compare the results with those of a standard polygraph examination. MATERIALS AND METHODS: All subjects gave written informed consent for this HIPAA-approved study, which was approved by the institutional review board of Drexel University. Eleven healthy subjects (five female and six male subjects; mean age, 28.9 years) were randomly assigned to the group of guilty subjects or the group of nonguilty subjects. Each group consisted of two separate functional MR imaging conditions: "lie-only condition" and "truth-only condition." The lie-only condition was used to compare brain activity during a known lie to control questions and a subjective lie to relevant questions. The truth-only condition was used to compare brain activity during a known truthful response to control questions and a subjective truthful response to relevant questions. Functional MR images were acquired with an echo-planar sequence, and statistical analysis was performed. Physiologic responses were measured with a standard four-channel polygraph instrument. RESULTS: During the deception process, specific areas of the frontal lobe (left medial and left inferior frontal lobes), temporal lobe (right hippocampus and right middle temporal gyrus), occipital lobe (left lingual gyrus), anterior cingulate, right fusiform gyrus, and right sublobar insula were significantly active. During the truth telling process, specific areas of the frontal (left subcallosal gyrus or lentiform nucleus) and temporal (left inferior temporal gyrus) lobes were significantly active. The polygraph examination revealed 92% accuracy in deceptive subjects and 70% accuracy in truthful subjects. CONCLUSION: Specific areas of the brain involved in deception or truth telling can be depicted with functional MR imaging.

Adult↗
PubMed2005

Integrated zone comparison polygraph technique accuracy with scoring algorithms.

The Integrated Zone Comparison Technique (IZCT) was utilized with computerized polygraph instrumentation as part of a blind study in the detection of deception. Three scoring algorithms: ASIT Poly Suite (Academy for Scientific Investigative Training's Horizontal Scoring and Algorithm for Chart Interpretation), PolyScore 5.5, and the Objective Scoring System (OSS) were assessed in the interpretation of the charts generated. Where "Inconclusives" were excluded, accuracy for the IZCT with all three algorithms was 100%. When "Inconclusives" were counted as errors, overall accuracy for the IZCT with ASIT Poly Suite was 90% and accuracy with PolyScore and the Objective Scoring System was 72%.

Algorithms↗
PubMed2005

Practical synthesis of the new carbapenem antibiotic ertapenem sodium.

[reaction: see text] A practical synthesis for the large-scale production of the new carbapenem antibiotic, [4R,5S,6S]-3-[[(3S,5S)-5-[[(3-Carboxyphenyl)amino]carbonyl]-3-pyrrolidinyl]thio]-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid monosodium salt (ertapenem sodium, 1), has been developed. The synthesis features the novel use of 1,1,3,3-tetramethylguanidine as base for the low-temperature reaction of a thiol, derived from trans-4-hydroxy-L-proline, with the carbapenem nucleus activated as the enol phosphate. Hydrogenolysis of a p-nitrobenzyl ester is effected using a palladium on carbon catalyst to give an overall yield for the two steps of 90%. The use of bicarbonate in the hydrogenolysis was key in providing protection of the pyrrolidine amine as the sodium carbamate improving both the performance of the reaction and the stability of the product. This discovery made processing at manufacturing scale possible. Experimental evidence for the formation of the sodium carbamate is provided. A remarkably expedient process for the simultaneous purification and concentration of the aqueous product stream relies on ion-pairing extraction for the removal of the water-soluble 1,1,3,3-tetramethylguanidine. Crystallization then affords 59-64% overall yield of the monosodium salt form of the product.

Anti-Bacterial Agents↗
PubMed2005

Asymmetric hydrogenation of N-sulfonylated-alpha-dehydroamino acids: toward the synthesis of an anthrax lethal factor inhibitor.

A novel and highly enantioselective Ru-catalyzed hydrogenation of N-sulfonylated-alpha-dehydroamino acids has been discovered and demonstrated in the synthesis of an anthrax lethal factor inhibitor (LFI). Herein, this methodology is used to prepare N-sulfonylated amino acids in up to 98% ee. This unprecedented hydrogenation uses a chiral Ru catalyst rather than Rh as typical for acylated dehydroamino acids and esters, and this work reports the first asymmetric hydrogenation of a tetrasubstituted dehydroamino acid derivative using a Ru catalyst. [reaction: see text]

Amino Acids↗
PubMed2004

Practical synthesis of a potent hepatitis C virus RNA replication inhibitor.

A practical, efficient synthesis of 1, a hepatitis C virus RNA replication inhibitor, is described. Starting with the inexpensive diacetone glucose, the 12-step synthesis features a novel stereoselective rearrangement to prepare the key crystalline furanose diol intermediate. This is followed by a highly selective glycosidation to couple the C-2 branched furanose epoxide with deazapurine.

Antiviral Agents↗
PubMed2004

Palladium-catalyzed cyanation of aryl bromides promoted by low-level organotin compounds.

A novel method for palladium-catalyzed cyanation of aryl bromides promoted by low-level tri-n-butyltin chloride or cyanide is described. The method features low catalyst loading and mild reaction conditions. KCN is used as the cyanide source. Only trace levels of the tri-n-butyltin compound are required to achieve high conversion and yield in the cyanation of aryl bromides, iodides, and triflates.

Journal Article↗
PubMed2004

Highly diastereoselective heterogeneously catalyzed hydrogenation of enamines for the synthesis of chiral beta-amino acid derivatives.

Pure (Z)-enamines readily prepared from beta-ketoesters and amides using (S)-phenylglycine amide were hydrogenated with very high diastereoselectivities (up to 200:1) using heterogeneous catalysis. Hydrogenolytic cleavage of the (S)-phenylglycine amide afforded the corresponding chiral beta-aminoesters and amides. The high geometrical purity of the (Z)-enamine and a simple activation procedure for the PtO2 catalyst are essential in achieving high selectivity.

Amides↗
PubMed2003

Diffusion tensor imaging of the hippocampal formation in temporal lobe epilepsy.

BACKGROUND AND PURPOSE: Diffusion tensor imaging (DTI) is a noninvasive technique that can be used to assess the integrity of cerebral tissue. The purpose of this study was to assess DTI measurements in the hippocampal formation (HF) and to investigate the role of DTI in lateralizing the seizure focus in temporal lobe epilepsy (TLE). METHODS: We evaluated 12 patients with unilateral TLE and 14 healthy subjects. We collected diffusion-weighted images along six different directions with a b value of 1000 s/mm(2), as well as an image acquired without diffusion weighting (b = 0 s/mm(2)). A 1.5-T imager was used to acquire 17 (3-mm) coronal sections covering the temporal lobes. We compared the mean diffusivity (trace D) and fractional anisotropy (FA) from symmetrical voxels by sampling the anterior HF bilaterally. We compared measurements with the EEG, high-resolution MR imaging, and clinical information. RESULTS: The patient group had significantly increased diffusivity and decreased FA in the HF ipsilateral to the seizure focus, as compared with values in the contralateral HF. When compared with healthy subjects, patients had significantly higher mean diffusivity in the ipsilateral HF; ipsilateral FA values were lower and did not reach statistical significance. Measurements in the contralateral HF did not show differences. Left-right and absolute diffusivity indices lateralized the abnormal HF in eight and five of 12 patients, respectively. CONCLUSION: Abnormal DTI measurements and the epileptogenic HF are associated in unilateral TLE. This finding may reflect hippocampal sclerosis and may aid in presurgical evaluation.

Adult↗
PubMed2002

Efficient one-pot synthesis of the 2-aminocarbonylpyrrolidin-4-ylthio-containing side chain of the new broad-spectrum carbapenem antibiotic ertapenem.

An efficient synthesis of the 2-aminocarbonylpyrrolidin-4-ylthio containing side chain of ertapenem (MK-0826) is described. Starting material N-(O,O-diisopropyl phosphoryl)-trans-4-hydroxy-L-proline is converted in a one-pot process to (2S)-cis-3-[[(4-mercapto-2-pyrrolidinyl)carbonyl]amino]benzoic acid monohydrochloride in 70-75% overall yield via a series of six reactions. The development of each of these reactions and the isolation of the product is discussed in detail.

Anti-Bacterial Agents↗
PubMed2002

Evidence for a dysfunctional prefrontal circuit in patients with an impulsive aggressive disorder.

Humans with lesions to the orbital/medial prefrontal cortex and interconnected areas display impulsive aggressive behavior. To examine further the relationship between impulsive aggression and orbital/medial prefrontal dysfunction, we measured the behavioral performance of psychiatric patients with a disorder characterized by impulsive aggression, Intermittent Explosive Disorder (IED). Presently, no evidence exists for a localized brain lesion in IED subjects. However, on the basis of the location of brain lesions that produce acquired impulsive aggression, we hypothesized that IED subjects would exhibit test performance similar to patients with lesions to the orbital/medial prefrontal cortex. Subjects with IED and controls were administered three tests sensitive to lesions of the orbital/medial prefrontal circuit: the Iowa Gambling Task, facial emotion recognition, and odor identification, and two control tests of working memory. On the gambling task, IED subjects continued to make disadvantageous decisions throughout the 100 trials, whereas controls learned to avoid disadvantageous decisions. On the facial recognition test, IED subjects were impaired at recognizing "anger," "disgust," and "surprise," and they were biased to label neutral faces with "disgust" and "fear." On odor identification, IED subjects were mildly anosmic and were impaired relative to controls. However, on the working memory control tests, both groups performed similarly. Across tests, the performance of IED subjects resembles the performance of patients with orbital/medial prefrontal lesions in previous studies. These results extend the link between dysfunction of the orbital/medial prefrontal circuit and impulsive aggressive behavior.

Adult↗
PubMed1986

Depression and hemispheric site of cerebral vascular accident.

In order to investigate the possible role of left and right hemisphere neural structures in the manifestation of depression, 50 left brain damaged and 50 right brain damaged stroke inpatients were administered the Zung Depression Scale (ZD S) during the course of the rehabilitation phase of their treatment. These subjects were randomly chosen from all stroke patients receiving rehabilitation services who could be administered the ZDS. Approximately 30% of these subjects, regardless of the site of lesion, were clinically depressed. The severity of depression was independent of demographic factors and time since injury. Right brain damaged patients reported significantly more sleep disturbance, psychomotor agitation and pervasive sense of sadness. These results were discussed in light of previous findings that damaged to the left hemisphere results in greater depression. A model of reactive depression that results from neurological disability was proposed to partially account for these findings.

Journal Article↗