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Biomedical subjects

B Riedel

Publications and source records attributed to B Riedel.

At least 19 recordsLinked to original sources

Auditory sequence learning: differential sensitivity to task relevant and task irrelevant sequences.

Using a serial reaction time task, this study examines whether learning of auditory sequences is possible without a corresponding motor response, i.e., by listening alone. The dual sequence paradigm used by Mayr (in Journal of the Experimental Psychology: Learning memory and cognition 22:350-354, 1996, Experiment 1) was adapted to the auditory domain. Four different actors spoke the same four colour words. These were presented such that speaker identity followed one sequence, and the word spoken followed a different sequence. Subjects were asked to respond (with a key press) to one of these dimensions (identity or word), and ignore the other. Results showed learning for either type of stimulus, but only when it was responded to. No learning of either type of auditory sequence by listening alone was found. The results add evidence to visual implicit learning studies that have failed to find learning of event sequences when spatial or response selection was not an important factor in processing. The findings are discussed in the context of implicit learning as a general and fundamental cognitive process.

Awareness↗

Integrated approach to off-pump coronary artery bypass surgery.

BACKGROUND: The Off-Pump Coronary Artery Bypass (OPCAB) technique is becoming more popular in many cardiac units throughout the world. This relatively new technique has prompted surgeons and anaesthetists to review and modify the routine approach to Coronary Artery Bypass Surgery (CABG). In this study we reviewed and analysed the outcome of an integrated anaesthetic and surgical peri-operative approach that allowed routine use of OPCAB and avoided the use of cardiopulmonary bypass (CPB). METHODS: We reviewed and analysed the data on the first consecutive 285 patients who were operated on using the OPCAB technique. These represent our initial experience with applying the OPCAB technique non-selectively for all patients over a period of 16 months. RESULTS: All patients had at least 2-vessel disease. 807 grafts were performed (mean 2.8 per patient) of which 647 (80%) were arterial (mean 2.3 per patient). 179 (63%) patients underwent total arterial revascularization. Eight patients required cardiopulmonary bypass; all other operations were completed off-pump. Complications--mortality 3 (1%); renal failure 24 (8%); stroke 3 (1%) and atrial fibrillation 60 (21%). CONCLUSION: This retrospective analysis shows that provided a combined and integrated anaesthetic and surgical approach is used, beating heart technique for CABG can be safely offered to all patients with a good outcome.

Blood Pressure↗

Sequence learning by action and observation: evidence for separate mechanisms.

In the Serial Reaction Time (SRT) task, participants respond to a set of stimuli the order of which is apparently random, but which consists of repeating sub-sequences. Participants can become sensitive to this regularity, as measured by an indirect test of reaction time, but can remain apparently unaware of the sequence, as measured by direct tests of prediction or recognition. Some researchers have claimed that this learning may take place by observation alone. We suggest that observational learning may be due to explicit acquired knowledge of the sequence, and is not mediated by the same processes which give rise to learning by action. In Expt 1, we show that it is very difficult to acquire explicit sequence knowledge under dual task conditions, even when participants are told that a regular sequence exists. In Expt 2, we use the same conditions to compare actors, who respond to the sequence during learning, and observers, who merely watch the stimuli. Furthermore, we manipulate the salience of the sequence, in order to encourage learning. There is no evidence of observational learning in these conditions, despite the usual effects of learning being demonstrated by actors. In Expt 3, we show that observational learning does occur, but only when observers have no secondary task and even then only reliably for a sequence which has been made salient by chunking subcomponents. We conclude that sequence learning by observation is mediated by explicit processes, and is eliminated under conditions which support learning by action, but make it difficult to acquire explicit knowledge.

Awareness↗

Thyroid hormone regulates slow skeletal troponin I gene inactivation in cardiac troponin I null mouse hearts.

Two main troponin I genes, cardiac (cTnI) and slow skeletal (ssTnI), are expressed in the mammalian heart under the control of a developmentally regulated program. ssTnI is expressed first in embryonic and fetal heart, and is then downregulated by an unknown mechanism after birth. Unlike other contractile protein genes, ssTnI is not re-expressed during hypertrophy or end-stage heart failure in rats and humans. In the present study, we also show that ssTnI re-expression does not occur in hypertrophic mouse heart. To investigate ssTnI downregulation further, cTnI knockout mice were used to examine a possible role for thyroid hormone. Northern blot analysis of euthyroid animals showed a time-dependent loss of ssTnI mRNA that was similar for wild-type, heterozygous and homozygous cTnI mutant mice. In cTnI null mice made hyperthyroid by l -thyroxine, the duration of ssTnI expression assessed by both mRNA and protein content was abbreviated compared with the euthyroid group. Hyperthyroid cTnI null mice also died significantly earlier than euthyroids (postnatal day 14 v day 18). In cTnI null mice made hypothyroid by addition of phenylthiouracil to the drinking water, ssTnI expression was prolonged and mice survived until day 20 or 21. Overall, the results indicate that inactivation of the ssTnI gene occurs even in the absence of cTnI mRNA and protein indicating that these are not critical signals for ssTnI down regulation in the heart. In contrast, thyroid hormone influences the time course of ssTnI expression and the life span of cTnI null mice probably through a transcriptional regulation of ssTnI in the heart.

Animals↗

Co-ordinate variations in methylmalonyl-CoA mutase and methionine synthase, and the cobalamin cofactors in human glioma cells during nitrous oxide exposure and the subsequent recovery phase.

We investigated the co-ordinate variations of the two cobalamin (Cbl)-dependent enzymes, methionine synthase (MS) and methylmalonyl-CoA mutase (MCM), and measured the levels of their respective cofactors, methylcobalamin (CH3Cbl) and adenosylcobalamin (AdoCbl) in cultured human glioma cells during nitrous oxide exposure and during a subsequent recovery period of culture in a nitrous oxide-free atmosphere (air). In agreement with published data, MS as the primary target of nitrous oxide was inactivated rapidly (initial rate of 0.06 h(-1)), followed by reduction of CH3Cbl (to <20%). Both enzyme activity and cofactor levels recovered rapidly when the cells were subsequently cultured in air, but the recovery was completely blocked by the protein-synthesis inhibitor, cycloheximide. During MS inactivation, there was a reduction of cellular AdoCbl and holo-MCM activity (measured in the absence of exogenous AdoCbl) to about 50% of pre-treatment levels. When the cells were transferred to air, both AdoCbl and holo-MCM activity recovered, albeit more slowly than the MS system. Notably, the regain of the holo-MCM and AdoCbl was enhanced rather than inhibited by cycloheximide. These findings confirm irreversible damage of MS by nitrous oxide; hence, synthesis of the enzyme is required to restore its activity. In contrast, restoration of holo-MCM activity is only dependent on repletion of the AdoCbl cofactor. We also observed a synchronous fluctuation in AdoCbl and the much larger hydroxycobalamin pool during the inactivation and recovery phase, suggesting that the loss and repletion of AdoCbl reflect changes in intracellular Cbl homoeostasis. Our data demonstrate that the nitrous oxide-induced changes in MS and CH3Cbl are associated with reversible changes in both MCM holoactivity and the AdoCbl level, suggesting co-ordinate distribution of Cbl cofactors during depletion and repletion.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗

Mobilization of the left and right fibrous trigones for relief of severe left ventricular outflow obstruction.

BACKGROUND: There is still no agreement about the optimal method of surgical relief of fixed subaortic stenosis, particularly the severe forms. OBJECTIVES: The purpose of this study was to describe a new technique for the relief of subaortic stenosis based on analysis of the functional anatomy of the left ventricular outflow tract and pathophysiologic features of subaortic stenosis. METHODS AND PATIENTS: We propose that one of the basic abnormalities in subaortic stenosis is interference with the hinge mechanism provided by the 2 fibrous trigones with progressive deposition of fibrous tissue in these angles. The technique described in this paper consists of excision of all components of the fibrous "ring," with mobilization of the left and right fibrous trigones. This results in the restoration of the normal dynamic behavior of the left ventricular outflow tract with maximal widening of the outflow tract as the result of backward displacement of the subaortic curtain and anterior leaflet of the mitral valve. This technique has been used in 57 consecutive patients who ranged in age between 5 months and 56 years (mean, 15.5 +/- 10.6 years). Gradients across the left ventricular outflow tract were between 45 and 200 mm Hg (mean, 86.7 mm Hg). Additional lesions were present in 10 patients, and 7 patients had had 8 previous operations on the left ventricular outflow tract. At operation, in addition to resection of subaortic stenosis, 3 patients had aortic valvotomy, 2 patients had homograft replacement of the aortic valve, 7 patients had patch closure of a ventricular septal defect, and 1 patient had open mitral valvotomy. RESULTS: There were 2 early deaths and 1 late sudden death during the follow-up period that ranged from 1 month to 25 years (mean, 15. 2 years). One patient experienced the development of endocarditis on the aortic valve 7 years after operation, which was successfully treated by homograft replacement. Postoperative gradients across the left ventricular outflow tract varied from no gradient to 30 mm Hg (mean, 8 mm Hg). There were no instances of recurrence of a gradient across the left ventricular outflow tract. CONCLUSION: It is concluded that mobilization of the left and right fibrous trigones results in durable relief of subaortic stenosis.

Adolescent↗

The pathophysiology and management of perioperative pulmonary hypertension with specific emphasis on the period following cardiac surgery.

Pulmonary hypertension, right ventricular dysfunction, and RV failure are common occurrences following CPB. The endothelium is now recognized as an important organ and is central to the pathophysiology and management of this condition. Current progress has arisen from the development of newer methods and the refinement of older methods attempting to protect the endothelium. Modern methods attempting to preserve endothelial function (thereby preventing pulmonary vasoconstriction and RV dysfunction) include new pharmacological inhibitors of the inflammatory response to CPB, improved myocardial protection using substrate enhanced cardioplegia, improved cardioplegia delivery techniques combined with monitoring by myocardial contrast TEE, and new minimally invasive surgical techniques not requiring extracorporeal support. Progress in therapeutic methods attempting to reverse pulmonary hypertension, RV dysfunction, and support of the failing right ventricle include the application of nitric oxide, prostacyclin, other pulmonary selective vasodilators, and improved ventricular assist devices that provide support to the right ventricle until recovery of the myocardium occurs or serve as a bridge to transplantation.

Cardiopulmonary Bypass↗

Disruption of a regulatory system involving cobalamin distribution and function in a methionine-dependent human glioma cell line.

Cobalamin metabolism and function were investigated at the levels from transcobalamin II (TCII) receptor to the cobalamin-dependent enzymes, methionine synthase and methylmalonyl-CoA mutase, in a methionine-dependent (P60) and a methionine-independent (P60H) glioma cell line. Using P60H as reference, the P60 cells cultured in a methionine medium had slightly lower TCII receptor activity and normal total cobalamin content, a moderately reduced microsomal and mitochondrial cobalamin(III) reductase activity but only trace amounts of the methylcobalamin and adenosylcobalamin cofactors. When transferred to a homocysteine medium without methionine, P60H cells showed a slightly enhanced TCII receptor activity, but the other cobalamin-related functions were essentially unchanged. In contrast, the methionine-dependent P60 cells responded to homocysteine medium with a nearly 6-fold enhancement of TCII receptor expression and a doubling of both the hydroxycobalamin content and the microsomal reductase activity. The mitochondrial reductase and the cobalamin-related processes further down the pathway did not change markedly. In both cell lines, TCII receptor activity was further increased when growth in homocysteine medium was combined with N2O exposure. These data suggest that low methionine and/or high homocysteine exert a positive feedback control on TCII receptor activity. The concurrent increase in hydroxycobalamin content and in microsomal reductase activity are either subjected to similar regulation or secondary to increased cobalamin transport. This regulatory network is most prominent in the methionine-dependent P60 cells harboring a disruption of the network in the proximity of cobalamin(III) reductase.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗

A comparison of the efficacy of stimulus control for medicated and nonmedicated insomniacs.

A sample of 21 medicated and 20 nonmedicated insomniacs participated in a sleep medication withdrawal program that provided education about sleep medication and a gradual medication withdrawal schedule. Ten medicated participants received stimulus control treatment and the withdrawal program, and 11 medicated participants served as a control group that received only the withdrawal program. Half of the nonmedicated participants received stimulus control, and the remaining nonmedicated participants served as a wait-list control condition. Medicated participants significantly reduced sleep medication use without significant deterioration on sleep, anxiety, or depression measures from baseline to 8-week follow-up. Stimulus control participants, unlike control group participants, showed significant improvement at follow-up for total sleep time, sleep efficiency, and sleep quality. Stimulus control participants also reported less daytime sleepiness than control participants after treatment. Nonmedicated participants exhibited a more positive response to stimulus control than medicated participants.

Adult↗

The Escherichia coli pgpB gene encodes for a diacylglycerol pyrophosphate phosphatase activity.

We provided genetic and biochemical evidence that supported the conclusion that the product of pgpB gene of Escherichia coli exhibited diacylglycerol pyrophosphate (DGPP) phosphatase activity. DGPP phosphatase activity was absent in pgpB mutant cells and was expressed at high levels in cells carrying the wild-type pgpB gene on a runaway replication plasmid. The pgpB mutant has been primarily characterized by a defect in phosphatidate (PA) phosphatase activity and also exhibits defects in lyso-PA phosphatase and phosphatidylglycerophosphate phosphatase activities. The defective PA phosphatase in the pgpB mutant was shown to be a Mg2+-independent PA phosphatase activity of the DGPP phosphatase enzyme. We characterized DGPP phosphatase activity in membranes from cells overproducing the pgpB gene product. DGPP phosphatase catalyzed the dephosphorylation of the beta phosphate of DGPP to form PA followed by the dephosphorylation of PA to form diacylglycerol. The specificity constant (Vmax/Km) for DGPP was 9.3-fold greater than that for PA. The pH optimum for the DGPP phosphatase reaction was 6. 5. Activity was independent of a divalent cation requirement, was potently inhibited by Mn2+ ions, and was insensitive to inhibition by N-ethylmaleimide. Pure DGPP phosphatase from Saccharomyces cerevisiae was shown to be similar to the E. coli DGPP phosphatase in its ability to utilize lyso-PA and phosphatidylglycerophosphate as substrates in vitro.

Cell Membrane↗

Purification and characterization of diacylglycerol pyrophosphate phosphatase from Saccharomyces cerevisiae.

Diacylglycerol pyrophosphate (DGPP) phosphatase is a novel membrane-associated enzyme that catalyzes the dephosphorylation of the beta phosphate of DGPP to yield phosphatidate and Pi. DGPP phosphatase was purified 33,333-fold from Saccharomyces cerevisiae by a procedure that included Triton X-100 solubilization of microsomal membranes followed by chromatography with DE53, Affi-Gel Blue, hydroxylapatite, and Mono Q. The procedure resulted in the isolation of an apparent homogeneous protein with a subunit molecular mass of 34 kDa. DGPP phosphatase activity was associated with the 34-kDa protein. DGPP phosphatase had a broad pH optimum between 6.0 and 8.5 and was dependent on Triton X-100 for maximum activity. The enzyme was inhibited by divalent cations, NaF, and pyrophosphate and was relatively insensitive to thioreactive agents. The turnover number (molecular activity) for the enzyme was 5.8 x 10(3) min-1 at pH 6.5 and 30 degrees C. DGPP phosphatase exhibited typical saturation kinetics with respect to DGPP (Km = 0.55 mol %). The Km value for DGPP was 3-fold greater than its cellular concentration (0.18 mol %). DGPP phosphatase also catalyzed the dephosphorylation of phosphatidate, but this dephosphorylation was subsequent to the dephosphorylation of the beta phosphate of DGPP. The dependence of activity on phosphatidate (Km = 2.2 mol %) was cooperative (Hill number = 2.0). DGPP was the preferred substrate for the enzyme with a specificity constant (Vmax/Km) 10-fold greater than that for phosphatidate. In addition, DGPP potently inhibited (Ki = 0.35 mol %) the dephosphorylation of phosphatidate by a competitive mechanism whereas phosphatidate did not inhibit the dephosphorylation of DGPP. DGPP was neither a substrate nor an inhibitor of pure phosphatidate phosphatase from S. cerevisiae. DGPP was synthesized from phosphatidate via the phosphatidate kinase reaction.

Cations, Divalent↗

Fibroblast growth factor-2-like immunoreactivity in auditory brainstem nuclei of the developing and adult rat: correlation with onset and loss of hearing.

Fibroblast growth factor-2 (FGF-2; basic FGF) is widely distributed in the developing and adult brain and has numerous effects on cultured and lesioned neural cells. The physiological role of FGF-2 in the unlesioned nervous system, however, is still not understood. We have studied the distribution of FGF-2 in the developing, adult, and functionally impaired central auditory system of the rat using specific antibodies and peroxidase-antiperoxidase immunocytochemistry. FGF-2-like immunoreactivity (FGF-2-IR) occurred in neuronal cell bodies and/or nerve fibers but was very rarely observed in glial cells. Several auditory brainstem nuclei, including the superior paraolivary nucleus, the medial superior olive, the lateral and ventral trapezoid nuclei, and the central nucleus, as well as the external cortex of the inferior colliculus, were entirely devoid of FGF-2-IR. In the dorsal cochlear nucleus, the lateral superior olive, and the nuclei of the lateral lemniscus, FGF-2-IR was not detectable in nerve cell bodies prior to adult age. Neurons in the medial geniculate body exhibited FGF-2-IR only transiently, from postnatal day (P) 5 until P16. Neurons in the medial nucleus of the trapezoid body were immunoreactive from P8 onwards. FGF-2-IR in anteroventral and posteroventral cochlear neurons disappeared at P14, i.e., at the onset of hearing, but immunoreactivity returned after P21. A transient expression of FGF-2 around the time when hearing function commences was observed in the dorsal cortex of the inferior colliculus.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗