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Biomedical subjects

B Fowler

Publications and source records attributed to B Fowler.

At least 91 records · Page 5Linked to original sources
PubMed1995

Hyperhomocysteinemia in premature arterial disease: examination of cystathionine beta-synthase alleles at the molecular level.

Hyperhomocysteinemia occurs in approximately 30% of the patients with premature occlusive arterial disease (POAD). Some of these exhibit significantly reduced fibroblast cystathionine beta-synthase (CBS) activities, suggesting that they may be heterozygous for CBS deficiency. To test this possibility, we studied cDNA derived from four well characterized patients with POAD, exhibiting hyperhomocysteinemia and reduced CBS activities, from four normal controls, and from four obligatory heterozygotes for CBS deficiency. Lysates of individual colonies of E.coli, containing full-length PCR-amplification products in the expression vector, pKK388.1, were tested for CBS activity. cDNA from at least seven of the eight possible independent POAD alleles encoded catalytically active, stable CBS which exhibited normal response to both PLP and AdoMet. The sequences of all 3'-untranslated regions of all seven isolated POAD alleles were identical to the normal, 'wild-type' CBS sequences. The results of the expression studies were confirmed for one POAD patient by determining the full-length cDNA sequences for both alleles; these were entirely normal over the complete length of the cDNA. In contrast, the screening method correctly distinguished mutant from normal alleles in all four obligatory heterozygotes studied. We conclude that CBS mRNAs from POAD individuals are free from inactivating mutations, including all 33 previously identified in heterozygous carriers and homocystinuric patients.

Alleles↗
PubMed1995

Cardiomyopathy in respiratory chain disorders.

Disorders of mitochondrial oxidative phosphorylation may disturb cardiac energy metabolism and cause cardiomyopathy. Twenty one cases from the literature and one further patient with cardiomyopathy due to biochemically defined respiratory chain defects were reviewed for clinical course, morphology, and pathophysiological mechanisms of the cardiomyopathy. All cases showed concentric hypertrophy of the myocardium without an outflow tract obstruction. In most patients the cardiomyopathy was diagnosed early in infancy and showed rapid deterioration with death before the age of 2 years. Hypertrophy of the myocardium appears to result from swelling of the cardiomyocytes caused by accumulation of mitochondria and by morphologically abnormal megamitochondria.

Cardiomyopathy, Hypertrophic↗
PubMed1995

The Perception of Teasing Scale (POTS): a revision and extension of the Physical Appearance Related Teasing Scale (PARTS).

This article describes the development and validation of a revised measure for the assessment of history of being teased about physical appearance. Study 1 involved the preliminary psychometric evaluation of the questionnaire on a sample of 227 college women, Two factors emerged: Weight-Related Teasing (WT) and Teasing About Abilities/Competencies (Competency Teasing; CT). The integrity of the factor structure of these two scales was established in Study 2 with a sample of 87 college women. Internal consistency ratios in this sample were also found to be acceptable. In Study 3, 92 college women were administered measures of body image, eating disturbance, and self-esteem to test for convergence with the Perception of Teasing Scale. Subjects also rated teasing items for frequency and effect (e.g., how upset they were by the teasing). Two-week test-retest reliabilities for these measures were acceptable. Weight-Related Teasing correlated to a greater degree with other measures than Competency Teasing. Regression analyses revealed the importance of a frequency versus effect dimension. Findings are discussed in light of recent research on developmental factors in body image and eating disturbance.

Journal Article↗
PubMed1995

A comparison of visual and auditory reaction time and P300 latency thresholds to acute hypoxia.

To investigate the influence of stimulus modality on the slowing produced by hypoxia, thresholds were estimated using reaction time (RT) and the event-related brain potential P300. Six trained subjects responded to oddball light flashes or tone pips while breathing low-oxygen mixtures that were manipulated to produce arterial blood oxygen saturations (SaO2) ranging from 77-86%. Both RT and P300 were slowed in a dose-dependent manner. The threshold for slowing was independent of stimulus modality for both measures, and estimated to be in the range 81-82% SaO2. P300 amplitude dissociated from the response time measures by exhibiting an inverted-U dose-response function. We draw three conclusions from these results: a) the failure to observe a higher visual threshold for the response time measures is inconsistent with the traditional belief that audition is relatively insensitive to hypoxia; b) the equal sensitivity of P300 latency and RT to hypoxia implicates stimulus evaluation processes in slowing; and c) P300 amplitude may reflect the activity of physiological compensatory mechanisms to hypoxia.

Adult↗
PubMed1995

Dissociation of the behavioral and subjective components of nitrogen narcosis and diver adaptation.

We investigated adaptation to nitrogen narcosis by compressing 11 highly experienced divers in a hyperbaric chamber to the equivalent of 54.6 meters of seawater once a day for 5 consecutive days. The behavioral component of narcosis was assessed with a serial choice-reaction time (RT) task, and the subjective component with a global magnitude estimate. Supplementary magnitude estimates were obtained with adjectives describing work effectiveness and body sensations. The results showed that there was no adaptation on the RT task, although learning was evident. In contrast, the global estimate dissociated from RT and showed clear adaptation by Day 3. The work effectiveness adjectives followed RT and did not show adaptation. Some body sensation adjectives showed clear adaptation, but others did not. These results lead to the conclusion that the anecdotal reports of adaptation by divers can probably be attributed to the subjective rather than the behavioral component of narcosis. Dissociation of these components suggests mediation by different brain mechanisms, and it is speculated that the gamma-aminobutyric acidA/benzodiazepine receptor complex, which has been implicated in both the anesthetic and anxiolytic properties of agents such as nitrous oxide, may be involved.

Adaptation, Physiological↗
PubMed1994

Discriminating the effects of triazolam on stimulus and response processing by means of reaction time and P300 latency.

The benzodiazepines slow information processing and the sites of this slowing were mapped using the Additive Factors Method in combination with the P300 component of the event-related brain potential. It was assumed that P300 largely reflects the time to evaluate a stimulus while reaction time (RT) reflects this time plus the time to select and execute a response. Twelve subjects were administered 0.25 mg triazolam in a repeated measures single-blind design. A visual 80-20% oddball task was used in which stimulus intensity and signal quality were manipulated with accuracy of responding held constant at a high level. RT and EEG data were collected simultaneously and the P300 elicited by the low probability stimuli was measured on a single trial basis. Triazolam slowed RT (172 ms, P < 0.0003) more than P300 (88 ms, P < 0.0007), but both measures exhibited a drug x stimulus intensity interaction. RT also exhibited a drug x signal quality interaction but P300 did not. These results suggest that triazolam has selective effects on perceptual processing by slowing an early pre-processing stage but not a later feature extraction stage. In addition, the drug appears to slow some aspect of response processing. This evidence is taken as support for a multiple process rather than a general sedation view of benzodiazepine effects on stages of processing.

Adult↗
PubMed1994

Coagulation factors and markers of activation of coagulation in homocystinuria (HOCY): a study in two siblings.

Homocystinuria due to cystathionine-beta-synthase deficiency (CBS-def-HOCY) initially often present with thromboembolic events. In most cases in which coagulation factors have been analysed, a deficiency of AT-IIIc and factor VIIc has been reported, the cause of which has not been elucidated. Activation of coagulation with consumption of coagulation factors has been postulated as the mechanism. This paper reports a longitudinal study of two patients: patient 1 with thromboembolic disease and his asymptomatic sister, patient 2. Before start of therapy in patient 1, a reduction of FVIIc, other coagulation factors, and AT-IIIc was found. Markers of activation of coagulation (F1 + 2, TAT, FM, D-dimers) were elevated only in patient 1, and only at the time of thrombotic complications. In patient 2 reduced levels of FVIIc and other coagulation proteins, and a low borderline AT-IIIc level was found. Thus, in the two patients, sustained activation of coagulation can be reasonably excluded to be the cause of low levels of coagulation proteins. Vitamin therapy with 15 mg folate and 600 mg pyridoxine per day led to almost complete normalization of amino acids in urine and plasma. Thrombosis has not recurred to date. FVIIc and the other coagulation proteins and AT-IIIc increased in parallel with the biochemical remission. Direct inhibition of the activity of AT-III and coagulation factor VIII and other factors by homocysteine was attempted in vitro but could not be shown at HC concentrations known to occur in the plasma of HOCY patients. Therefore, in these patients, deficient synthesis of coagulation factors and AT-III due to a disturbance of amino acid metabolism is still the most probable explanation for the observed low levels.

Adult↗
PubMed1994

P300 as a measure of workload during a simulated aircraft landing task.

The P300 component of the event-related brain potential was assessed as a measure of mental workload using 12 subjects who flew simulated visual flight rules final approaches and landings under workloads varied by manipulating turbulence and hypoxia. P300 was elicited with auditory and visual "oddball" subsidiary tasks requiring the detection of infrequent tones or flashes of an artificial horizon. The results showed that root mean square error flying performance was systematically degraded by both workload manipulations. P300 amplitude exhibited a complex pattern that was not strongly related to performance. By contrast P300 latency covaried closely with performance, increasing as a function of workload in both modalities. These results suggest that P300 latency indexes the slowing of perceptual/cognitive processing caused by workload and that this measure is sensitive to an important aspect of flying.

Adult↗
PubMed1994

Acute hypoxia fails to influence two aspects of short-term memory: implications for the source of cognitive deficits.

There has been considerable interest in the possibility that short-term memory (STM) plays a role in the cognitive deficits produced by hypoxia. Claims have been made that two aspects of STM are impaired, the storage of information and the speed of retrieval of information, but a close examination of the evidence reveals that the whole issue remains an open question. Each aspect was investigated in a separate experiment using well trained subjects who breathed low oxygen mixtures adjusted to control arterial oxyhemoglobin saturation between 64%-66%. Exp. 1 assessed storage capacity with the dichotic listening paradigm. Hypoxia degraded the accuracy of recall, but this was probably an impairment of auditory perception and there was no evidence that storage was impaired. Exp. 2 assessed retrieval speed with Sternberg's memory scanning paradigm. As expected, hypoxia increased reaction time, but this could be accounted for by the slowing of an early stage of perceptual processing. No evidence was found to indicate that stages involving either retrieval from STM or binary decision were slowed. We conclude that STM storage and retrieval are not directly affected by hypoxia, and propose that either direct or indirect slowing of the central executive of working memory may account for the cognitive deficits produced by this stressor.

Acute Disease↗
PubMed1993

Congenital absence of insulin cells in a neonate with diabetes mellitus and mutase-deficient methylmalonic acidaemia.

We report on a female neonate with diabetes mellitus and methylmalonic acidaemia, who died at age 16 days. Using immunocytochemistry, electron microscopy and in situ hybridisation, we were unable to demonstrate any insulin cells in the pancreatic islets. Methylmalonic acidaemia was caused by a methylmalonyl coenzyme A mutase apoenzyme defect. The metabolic crisis of the methylmalonic acidaemia aggravated the diabetes and may explain the failure of insulin therapy. Our results suggest that the infant suffered from a congenital absence of beta cells associated with a genetically transmitted mutase apoenzyme defect.

Autopsy↗
PubMed1993

Inhibition of human and murine cytosolic epoxide hydrolase by group-selective reagents.

1. Human and murine cytosolic epoxide hydrolase were inhibited by thiol-, imidazole- and carboxyl-selective reagents. They were not inhibited by amino-, guanido- or activated serine-selective reagents. 2. Murine, but not human, cytosolic epoxide hydrolase was inhibited by N-bromosuccinimide, a tryptophan selective reagent. 3. Based on sequence data from peptides isolated from CNBr digests, human and murine CEH share areas of sequence homology. Of the five unique human CEH CNBr peptides sequenced, three shared common sequences with one of the unique murine CEH CNBr peptides. The human and murine CEH peptides with common sequences had between 64 and 78% sequence identity. 4. A cysteine important for the activity of murine CEH appears not to be in the active site as judged by N-phenylmaleimide inhibition in the presence and absence of either (2S,3S)-2,3-epoxy-3-(4-nitrophenyl)glycidol, a competitive inhibitor, or trans-stilbene oxide, a substrate.

Amino Acid Sequence↗
PubMed1993

The slowing of visual processing by hypoxia.

An additive factors method (AFM) experiment was undertaken to determine whether the preprocessing and identification stages of information processing are implicated in the slowing of reaction time (RT) by hypoxia. The subjects (n = 14) responded at two levels of light intensity to pairs of lines that differed in length while breathing a low oxygen mixture that produced arterial oxyhaemoglobin saturations ranging between 64%-66%. The results showed a relatively large interaction between light intensity and hypoxia that was interpreted as evidence for slowing of the preprocessing stage. Differences in line length were plotted in terms of Crossman's confusion function and relatively small interactions with both hypoxia and light intensity were found, reflecting increases in slope. The light intensity x confusion level interaction was interpreted as evidence that AFM assumptions may not have been met completely in this experiment. This leads to the possibility that hypoxia slowed the identification stage indirectly rather than directly, although the latter hypothesis cannot be ruled out entirely at present. It is argued that visual slowing probably plays an important role in the disruption of perceptual-motor tasks by hypoxia.

Humans↗
PubMed1993

Dissociation of the effects of alcohol and amphetamine on inert gas narcosis using reaction time and P300 latency.

Alcohol exacerbates and amphetamine ameliorates the slowing of reaction time (RT) produced by inert gas narcosis. The event-related brain potential P300 was used to determine whether these drug effects involve stimulus- or response-related processes, since P300 largely reflects the time to evaluate a stimulus while RT reflects this time plus the time to select and execute a response. Subjects breathed nitrous oxide (N2O) alone and in combination with ethyl alcohol or dextroamphetamine while responding to visually presented names that differed in probability (the oddball paradigm). N2O slowed P300, but this measure was comparatively insensitive to the exacerbation and amelioration that were indexed by RT. Relative to N2O alone, an RT-P300 difference was found for amphetamine + N2O but not for alcohol + N2O. We conclude that exacerbation involves both stimulus- and response-related processes but amelioration involves only the latter. This pattern of results can be explained by a model in which the drugs modulate slowing via the two energetical dimensions of arousal and activation, which influence stimulus- and response-related processes, respectively.

Action Potentials↗
PubMed1993

Relationship between the event-related brain potential P300 and inert gas narcosis.

It is known that inert gas narcosis slows both reaction time (RT) and the event-related brain potential P300 in a correlated and dose-dependent manner. On the assumption that P300 reflects the time to evaluate a stimulus and RT reflects this time plus the time to select and execute a response, these results have been taken to indicate that the locus of the slowing produced by narcosis is early and influences stimulus evaluation processes. If this is the case, RT and P300 should be slowed identically when cognitive workload is manipulated. To test this prediction, subjects breathed 35% nitrous oxide and responded to differences in the intensity of either visual (Exp. 1, n = 8) or auditory (Exp. 2, n = 10) two-choice oddball stimuli with accuracy controlled at a high level. In both experiments narcosis slowed RT and P300 additively by increasing the intercept rather than the slope of the workload function, but these two measures diverged in one important respect; RT was slowed more than P300, as indicated by an RT-P300 difference analysis. It is concluded that, contrary to previous assumptions, narcosis produces two sources of slowing; one stimulus-related and indexed by P300 and the other response-related and indexed by the RT-P300 difference. Possible mechanisms underlying these sources are discussed.

Adult↗