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Biomedical subjects

B Fowler

Publications and source records attributed to B Fowler.

At least 109 records · Page 6Linked to original sources
PubMed1990

P300 latency indexes nitrogen narcosis.

This experiment investigated the effects of nitrogen narcosis on reaction time (RT) and P300 latency and amplitude. Ten subjects breathed either air or a non-narcotic 20% oxygen-80% helium (heliox) mixture in a hyperbaric chamber at 6.5, 8.3 and 10 atmospheres absolute (ATA). The subjects responded under controlled accuracy conditions to visually presented male or female names in an oddball paradigm. Single-trial analysis revealed a strong relationship between RT and P300 latency, both of which were slowed in a dose-related manner by hyperbaric air but not by heliox. A clear-cut dose-response relationship could not be established for P300 amplitude. These results indicate that P300 latency indexes nitrogen narcosis and are interpreted as support for the slowed processing model of inert gas narcosis.

Adult↗
PubMed1989

Complete sequence of the human tissue factor gene, a highly regulated cellular receptor that initiates the coagulation protease cascade.

Tissue factor (TF) is the high-affinity receptor for plasma factors VII and VIIa. TF plays a role in normal hemostasis by initiating the cell-surface assembly and propagation of the coagulation protease cascade. Outside the vasculature, TF expression is highly dependent upon cell type. TF can also be induced by inflammatory mediators to appear on monocytes and vascular endothelial cells as a component of cellular immune responses. As an initial step toward elucidating the regulatory regions involved in control of TF gene expression, we have established the organization of the 12.4 kbp human TF gene and its complete DNA sequence. There are six exons separated by five introns. Within intron 5, we have mapped the single nucleotide difference which leads to the previously described MspI polymorphism; the same intron also contains an apparently polymorphic PstI site. The TF gene also contains three full-length Alu repeats and one partial Alu repeat. A single major transcription start site was identified 26 bp downstream from a TATA consensus promoter element. The putative promoter and first exon are located within a 1.2 kbp region of very high G + C content which fits the criteria of an HTF island. A cluster of predicted binding sites for a number of known transcription factors was found to coincide with this putative promoter region. These factors included AP-1 and AP-2 which can mediate the effects of phorbol esters, agonists known to induce TF expression in monocytes and vascular endothelial cells.

Amino Acid Sequence↗
PubMed1989

Chorionic villus sampling: diagnostic uses and limitations of enzyme assays.

Control ranges for enzymes in uncultured chorionic villi were established, based on: (1) 21 of 22 enzymes (mainly lysosomal) in villi had similar properties to the enzyme in cultured fibroblasts; (2) isoenzyme patterns in villi were similar to those in fibroblasts for five lysosomal enzymes but different for aryl sulphatases; (3) control ranges were determined for 12 enzymes in abortion villi and for 21 enzymes in biopsy villi, values tending to be higher in the latter for those enzymes studied in both types of sample; (4) storage of samples under various conditions revealed no major changes in activity of seven lysosomal enzymes. A number of potential pitfalls in the use of chorionic villus samples for diagnosis of metabolic disorders by enzyme assay are described: (1) the presence of aryl sulphatase C in chorionic villi, an isoenzyme which may interfere in assays of aryl sulphatase A; (2) the presence of maternal enzyme in chorionic villus material illustrated by the detection of the A isoenzyme of B-hexosaminidase in chorionic villus from a pregnancy affected with Sandhoff's disease; (3) the finding of falsely normal levels of alpha-iduronidase in chorionic villus samples from a pregnancy affected with Hurler's disease, probably due to contamination with maternal tissue which has relatively high levels of this enzyme compared with fetal chorionic material: (4) the inadequacy of indirect assays of incorporation of radiolabel into macromolecules using chorionic villi, for example [14C]propionate incorporation for prenatal diagnosis of methylmalonic aciduria. Provided that such pitfalls are recognized and great care is taken in selection of villus samples and interpretation of results, chorionic villus sampling allows reliable prenatal diagnosis of a large number of disorders using enzyme assays.

Chorionic Villi Sampling↗
PubMed1989

The effects of hyperbaric air in combination with ethyl alcohol and dextroamphetamine on serial choice-reaction time.

The effects of ethyl alcohol (1.5 ml/kg body weight) and dextroamphetamine (15 mg) on nitrogen narcosis were investigated in two experiments using a 2-, 3- and 4-choice serial reaction time (RT) task with accuracy held constant. Narcosis was induced with air at 6.4 atmospheres absolute (ATA) and a heliox mixture was used as a control. Heliox at 6.4 ATA did not affect RT. Alcohol alone and air at 6.4 ATA increased the intercept of the Hick-Hyman function whereas amphetamine alone decreased it. The increased intercept with air at 6.4 ATA was exacerbated additively by alcohol and ameliorated antagonistically by amphetamine. The slope of the Hick-Hyman function was unaffected. Frequency distributions were shifted as a whole and their shapes were unaltered. It is concluded that these data are consistent with the slowed processing model which proposes that the effects of narcosis on performance are due to a decrease in arousal in conjunction with secondary changes in task strategy.

Adult↗
PubMed1989

Narcosis has additive rather than interactive effects on discrimination reaction time.

A central feature of the impairment in performance produced by inert gas narcosis, which poses a threat to divers breathing compressed air, is a slowing of reaction time (RT). To investigate the locus of this slowing, the effects of 35% nitrous oxide on Crossman's confusion function were determined using line-length and weight discrimination tasks, with accuracy held constant. For both tasks narcosis slowed RT by increasing the intercept rather than the slope of Crossman's function. These results are interpreted in terms of additive factors method logic as being consistent with the predictions of the slowed processing model that has been proposed to account for the effects of narcosis on human performance.

Confusion↗
PubMed1989

Nitrogen narcosis and ethyl alcohol increase the gain of the vestibular ocular reflex.

The effects of air, helium-oxygen (6.4 ATA), and ethyl alcohol (40% by volume at a dose of 1.5 ml/kg body weight) were examined on the gain, number of beats, and phase lag of the vestibular ocular reflex (VOR) by means of electronystagmography (n = 7). It was found that hyperbaric air and alcohol, both alone and in combination, produced approximately the same increase in the velocity of the slow phase component of the nystagmus, thereby elevating the gain of the system to unity. Hyperbaric helium-oxygen did not influence the gain. These findings suggest that nitrogen nacrosis differentially impairs the system controlling the VOR. It is proposed that this impairment may help to explain the disorientation sometimes associated with nitrogen narcosis.

Adult↗
PubMed1988

First trimester prenatal diagnosis of Sandhoff's disease.

Chorionic villus sampling was performed on two patients with a previous family history of Sandhoff's disease. Total beta-hexosaminidase (Hex) activity in case 1 was within the normal range (case 1: 6365 mumol/h/g protein; control range: 3227-24 495 mumol/h/g protein). The beta-hexosaminidase isoenzyme pattern was found to be normal. These results were confirmed on cultured amniotic fluid cells. In case 2, the total Hex activity was 672 mumol/h/g protein, i.e., 7 per cent of the control mean (10,085 mumol/h/g protein), and chromatography demonstrated that more than 50 per cent of this activity was due to the abnormal isoenzyme beta-hexosaminidase S (Hex S). The fetus was predicted to be affected by Sandhoff's disease and this was confirmed on fetal tissues after termination of pregnancy. This study demonstrates that a fetus affected by Sandhoff's disease can be reliably diagnosed during the first trimester of pregnancy.

Adult↗
PubMed1988

First trimester diagnosis of methylmalonic aciduria.

We have studied methylmalonyl CoA mutase activity in control chorionic villi to establish the potential use of assays performed directly on this tissue for prenatal diagnosis of methylmalonic aciduria. We report the detection of a fetus affected with the apo-mutase deficient form of this condition at 9 weeks' gestation. Methylmalonyl CoA mutase was markedly deficient in chorionic villi, approximately 2.5 per cent of the mean control value. However, incorporation of label from [14C]-propionate into protein was 10 and 40 per cent of the mean control value, respectively, in two portions of the same biopsy, highlighting potential problems in the use of this indirect assay. Normal results were obtained in chorionic villus samples from four other pregnancies 'at risk' for methylmalonic aciduria which were subsequently shown to be unaffected with this condition. The diagnosis in the affected pregnancy was confirmed by demonstration of a marked deficiency of methylmalonyl CoA mutase activity in villi obtained at termination and in cultured fetal fibroblasts. Reduced incorporation of [14C]-propionate label into protein was also found in these tissues.

Amino Acid Metabolism, Inborn Errors↗
PubMed1988

The effects of nitrous oxide on P300 and reaction time.

This experiment investigated the effects of 3 concentrations (15%, 25% and 35%) of nitrous oxide (N2O) on reaction time (RT) and P300 latency and amplitude. Ten subjects responded to visually presented male or female names in an oddball paradigm with accuracy controlled at a high level. The results were analysed on a single-trial basis. Nitrous oxide increased both RT and P300 latency in a dose-related manner and these variables showed a strong between-dose correlation (r = 0.67). Nitrous oxide also decreased P300 amplitude but only up to the 25% dose. The between-dose correlation for P300 amplitude and RT was negligible (r = -0.14). These results suggest that P300 latency is an index of N2O narcosis and are interpreted as indicating that narcosis involves the slowing of stimulus evaluation processes.

Adult↗
PubMed1988

Correlates of amylase and lipase levels in chronic dialysis patients.

Serum lipase and amylase isoenzymes were measured in 44 chronic hemodialysis patients, 16 CAPD patients and 22 normal volunteers. The enzyme levels of the two patient groups were similar and were significantly higher than those of the volunteer group. The ratio of pancreatic to salivary amylase was similar in all three groups. Anuric patients in both dialysis groups had higher enzyme levels than those with residual urine output. Linear regression analysis was done to attempt to identify factors which were good predictors of enzyme levels. Although no such factors were found in the hemodialysis group, in the CAPD group there were significant correlations between the degree of azotemia and the magnitude of enzyme elevations. Further studies are needed to determine the relative importance of oversecretion and underexcretion in the genesis of the amylase and lipase elevations found in dialysis patients.

Amylases↗
PubMed1988

Effect of arteriovenous shunting on plasma vasopressin levels in the anesthetized dog.

Studies were performed in dogs anesthetized with chloralose to establish the plasma arginine vasopressin (AVP) response to 30-minute periods of femoral arteriovenous (AV) shunting at levels of either 10%, 30%, or 50% of control cardiac output. Significant increases in cardiac output, heart rate, and total body peripheral resistance (shunt resistance excluded), suggesting decreased sinoaortic baroreceptor activity, occurred at shunt fractions greater than 10%. There were no significant changes in plasma concentrations of AVP at any level of AV shunting. In separate studies, significant elevations in plasma AVP levels were observed in vagotomized dogs during AV shunting of 50% of control cardiac output. These results indicate that AV shunting less than or equal to 50% of cardiac output does not acutely alter plasma AVP levels in the intact dog and that cardiopulmonary receptors with vagal afferents suppress AVP release that might otherwise occur in this canine model of AV shunting.

Anesthesia↗
PubMed1987

Increased excretion of propan-1,3-diol and 3-hydroxypropionic acid apparently caused by abnormal bacterial metabolism in the gut.

Three patients who died in infancy showed an unusual urinary organic acid pattern with excessive excretion of 3-hydroxypropionic acid but none of the other metabolites normally associated with propionyl-CoA carboxylase deficiency. Propan-1,3-diol was present in the urine in all three cases. In the two patients examined propionyl-CoA carboxylase activity was not deficient in cultured skin fibroblasts. A fourth patient, also severely ill, showed similar urinary abnormalities. Feeding a medium-chain triglyceride-rich diet to this patient increased the ratio of 3-hydroxypropionic acid to propan-1,3-diol and resulted also in the appearance of malonic acid in the urine. These abnormal metabolites disappeared on the administration of neomycin and presumably were produced by gut bacteria.

Aging↗
PubMed1987

Aryl sulphatase isoenzymes of chorionic villi: implications for prenatal diagnosis.

Prenatal diagnosis of metachromatic leucodystrophy (MLD) is based on demonstrating a deficiency of aryl sulphatase A (ASA) in the fetus. To evaluate the place of chorionic villus sampling for prenatal diagnosis of this condition, the properties of ASA were compared in chorionic villi and cultured skin fibroblasts. Considerable differences with respect to pH optimum, Km values and linearity with incubation time were found. These differences can be explained by the presence of aryl sulphatase C (ASC), a major component in chorionic villi and placenta. This isoenzyme was shown to have activity towards p-nitrocatechol sulphate (NCS) thereby interfering in the colorimetric assay most often used to detect MLD (Baum et al., 1959)

Cerebroside-Sulfatase↗
PubMed1987

Krabbe's disease: first trimester diagnosis confirmed on cultured amniotic fluid cells and fetal tissues.

Chorionic villi obtained during the first trimester from a pregnancy at risk for Krabbe's disease were shown to have reduced cerebroside-beta-galactosidase (E.C.3.2.1.46) activity using the artificial substrate trinitrophenylaminolauryl galactocerebroside (TNPAL-galactocerebroside). Assay of this enzyme in cultured amniotic fluid cells following amniocentesis, performed at the patient's request confirmed the diagnosis. Termination of pregnancy was performed and subsequent enzyme studies of the fetal tissues were consistent with the diagnosis of Krabbe's disease, thus confirming that chorionic villi can be used for first trimester diagnosis of this condition.

Amniocentesis↗