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Biomedical subjects

T Peters

Publications and source records attributed to T Peters.

At least 109 records · Page 6Linked to original sources
PubMed1996

Conformational analysis of blood group A trisaccharide in solution and in the binding site of Dolichos biflorus lectin using transient and transferred nuclear Overhauser enhancement (NOE) and rotating-frame NOE experiments.

The present study is concerned with the elucidation of the conformation of the blood group A trisaccharide (alpha-D-GalNAc(1-3)[alpha-L-Fuc(1-->2)] beta-D-Gal-O-R) in the combining site of Dolichos biflorus seed lectin by use of 400-MHz and 600-MHz NMR spectroscopy. D. biflorus lectin displays a unique specificity for GalNAc residues. It occurs in solution as a tetrameric assembly having a molecular mass of 110 kDa, with two carbohydrate-binding sites per molecule. First, NOE build-up curves were obtained for the free blood group A trisaccharide from one-dimensional transient NOE experiments. Simulated NOE build-up curves were constructed from an ensemble of low-energy conformers derived from previous investigations. The comparison of theoretical and experimental data indicates that an equilibrium between two families of low-energy conformers most likely reflects the solution behavior of the trisaccharide in solution. Two-dimensional transferred NOE and rotating-frame enhancements (ROE) were subsequently measured for the trisaccharide complexed with the D. biflorus seed lectin. In addition to the NOEs observed for the free trisaccharide, the transferred NOESY spectrum showed several new NOEs that were identified as spin diffusion using a rotating-frame NOESY (ROESY) experiment. Experimental interglycosidic transferred nuclear Overhauser effect (TRNOE) build-up curves were compared to theoretical curves calculated for both low-energy conformers located in the D. biflorus lectin-binding site. Calculations of theoretical TRNOE were performed using a combination of the full relaxation matrix and the protein-ligand exchange matrix. Comparison between experimental and simulated TRNOE volumes leads to the conclusion that one conformation of blood group A trisaccharide is selected upon binding by D. biflorus lectin.

ABO Blood-Group System↗
PubMed1996

Nonatherosclerotic causes of coronary artery narrowing--Part I.

Approximately 5% of patients with acute myocardial infarction do not have atherosclerotic coronary artery disease but have other causes for their luminal narrowing. The first part of this three-part review of nonatherosclerotic causes of coronary narrowing focuses on congenital coronary artery anomalies, coronary fistula, and high take-off position of coronary ostia.

Arterio-Arterial Fistula↗
PubMed1996

Nonatherosclerotic causes of coronary artery narrowing--Part III.

Approximately 5% of patients with acute myocardial infarction do not have atherosclerotic coronary artery disease but have other causes for their luminal narrowing. The third part of this three-part review of nonatherosclerotic causes of coronary narrowing focuses on coronary vasculitis, infectious diseases, Kawasaki's disease, metabolic disorders, metastatic disease, and substance abuse (cocaine).

Coronary Disease↗
PubMed1996

Coronary artery and saphenous vein graft remodeling: a review of histologic findings after various interventional procedures--Part I.

Catheter balloon angioplasty is a well accepted form of nonsurgical treatment of acutely and chronically obstructed coronary artery vessels. It is also the centerpiece for various new intervention techniques. Their morphologic effects on the site of obstruction has been termed "remodeling." Part I of this six-part series focuses on mechanisms of remodeling after various interventional techniques, particularly balloon angioplasty.

Angioplasty, Balloon, Coronary↗
PubMed1996

Coronary artery and saphenous vein graft remodeling: a review of histologic findings after various interventional procedures--Part II.

Catheter balloon angioplasty is a well accepted form of nonsurgical treatment of acutely and chronically obstructed coronary artery vessels. It is also the centerpiece for various new intervention techniques. Their morphologic effects on the site of obstruction has been termed "remodeling." Part II of this six-part series focuses on morphologic causes of acute closure after remodeling and discusses findings late after successful balloon angioplasty remodeling.

Adult↗
PubMed1996

Coronary artery and saphenous vein graft remodeling: A review of histologic findings after various interventional procedures--Part III.

Catheter balloon angioplasty is a well accepted form of nonsurgical treatment of acutely and chronically obstructed coronary artery vessels. It is also the centerpiece for various new intervention techniques. Their morphologic effects on the site of obstruction has been termed "remodeling." Part III of this six-part series focuses on intimal proliferation and chronic recoil in patients undergoing previous remodeling techniques by balloon angioplasty.

Adult↗
PubMed1996

Coronary artery and saphenous vein graft remodeling: a review of histologic findings after various interventional procedures--Part IV.

Catheter balloon angioplasty is a well accepted form of nonsurgical treatment of acutely and chronically obstructed coronary artery vessels. It is also the centerpiece for various new intervention techniques. Their morphologic effects on the site of obstruction has been termed "remodeling." Part IV of this six-part series focuses on morphologic correlates of coronary angiographic patterns of remodeling after balloon angioplasty and discusses effects of angioplasty on adjacent, nondilated vessels.

Adult↗
PubMed1996

Aconitine inhibits epileptiform activity in rat hippocampal slices.

The effect of aconitine, an alkaloid neurotoxin known to bind at site 2 of the sodium channel, was investigated on epileptiform activity in hippocampal slices by use of extracellular recordings in CA1 pyramidal cell layer. Epileptiform activity was induced by bicuculline, picrotoxin, penicillin, pentylenetetrazol or by omission of magnesium from the bathing medium, respectively. In every case aconitine (0.1 and 1 microM) blocked the multiple population spikes representing the epileptiform activity. The onset of inhibition was shorter by use of an increased concentration of the epileptogenic drug. Epileptiform activity evoked by pentylenetetrazol and low magnesium was first increased by aconitine followed by a rapid inhibition, while the bicuculline-, picrotoxin-, and penicillin-induced epileptiform discharges were immediately abolished.

Aconitine↗
PubMed1996

Subjective symptoms and quality of life in healthy subjects during a phase I study.

OBJECTIVE: Participants in a phase I study were interviewed in order to establish the incidence and variability of subjective symptoms and changes in quality of life during phase I trials. METHODS: The healthy subjects were randomized to receive a single dose of either 0.5 mg digoxin or an equivalent amount of each of four digitaloid mixtures every 14 days. The trial involved five 24-h monitoring periods. The duration of the study was 57 days. Wellbeing, subjective symptoms and quality of life were measured before, during and after the trial using the Freiburg Symptoms List (FSL), Wellbeing Scales (WBS), and Life Satisfaction Questionnaire (LSQ). RESULTS: Eight healthy subjects (25 years) were enrolled in the study. Their subjective symptoms were below the reference values for healthy subjects for each test but above the theoretical minimum and maximum values for total wellbeing, indicating that healthy subjects-not just patients-display subjective symptoms and impairment of wellbeing to a greater or lesser extent prior to a clinical trial. In terms of the total study population, comparison of the questionnaire scores before, during and after the study disclosed no significant changes in wellbeing or quality of life. However, some participants displayed marked intraindividual fluctuation. CONCLUSIONS: A careful exploration of the baseline symptoms is necessary even in healthy subjects to avoid observation bias. The symptom course differs greatly from individual to individual; therefore in a phase I study only group scores of wellbeing should be used to assess the possible effects of trial-related factors. A setting like the one used in our study does not impair the quality of life of healthy subjects and as such can be regarded as a fairly neutral means of measuring wellbeing.

Adolescent↗
PubMed1996

Electrophysiological effects of aconitine in rat hippocampal slices.

The electrophysiological effects of aconitine were investigated in the rat hippocampal slice and compared with those of veratridine. Both alkaloids are known to bind at site 2 of sodium channels and to block its inactivation. Extracellular recordings revealed that aconitine and veratridine exert inhibitory effects on neuronal excitability. Aconitine slowly and reversibly decreased the population spike recorded in the CA1 pyramidal cell layer. The reduction of the spike amplitude was similar whether orthodromically or antidromically activated. The aconitine-induced inhibition did not differ from that of veratridine. However, following washout of aconitine, the amplitude of the antidromic spike was increased compared to the control amplitude. The veratridine-induced inhibition was only partially reversible. This inhibition was also observed during suppression of synaptic transmission by a low Ca2+/high Mg2+-medium, indicating an inhibition of axonal conductance. The results show that in the absence of synaptic transmission the antidromic (alvear) spike is more sensitive to the inhibitory action of aconitine than the presynaptic fiber spike elicited by stimulation of the Schaffer collaterals. Furthermore, it is shown that aconitine acts in an activity-dependent manner, in that the latency of onset of the inhibition is prolonged when the stimulation frequency is decreased. Field excitatory postsynaptic potentials were also suppressed by aconitine, whereas excitatory postsynaptic currents recorded by the patch clamp technique were not influenced by aconitine when cells were held at -60 mV.

Aconitine↗
PubMed1996

(+/-)-kavain inhibits the veratridine- and KCl-induced increase in intracellular Ca2+ and glutamate-release of rat cerebrocortical synaptosomes.

The action of (+/-)-kavain on the veratridine, monensin and KCl-depolarization evoked increase in free cytosolic Ca2+ concentration ([Ca2+]i), and its influence on the release of endogenous glutamate from rat cerebrocortical synaptosomes were investigated. [Ca2+]i was fluorimetrically determined employing FURA as the Ca2+ sensitive fluorophore, and glutamate was detected by a continuous enzyme-linked fluorimetric assay. The incubation of synaptosomes in the presence of (+/-)-kavain up to a concentration of 500 mumol/l affected neither basal [Ca2+]i nor spontaneous release of glutamate, but dose-dependently reduced both veratridine-elevated [Ca2+]i (IC50 = 63.2 mumol/l) and glutamate-release (IC500 = 116.4 mumol/l). The inhibition of these parameters, attained with 500 mumol/l(+/-)-kavain, could be overcome by inducing an artificial Na+ influx, using monensin as a Na+ ionophore, An application of (+/-)-kavain after veratridine caused a decrease in veratridine-elevated [Ca2+]i, which was similar to the action of tetrodotoxin (TTX) with regard to time course, half-life of [Ca2+]i decline and the final steady state level of [Ca2+]i. Concomitantly, veratridine-induced glutamate-release was blocked. The results indicate that specific inhibition of voltage-dependent Na+ channels is a primary target of (+/-)-kavain, thus preventing a [Na+]i provoked increase in [Ca2+]i and glutamate-release. However, pathways related to the elevation of [Ca2+]i by [Na+]i itself, and the processes involved in normalization of elevated [Ca2+]i and glutamate-release downstream to enhanced [Ca2+]i, seems to be unaffected by (+/-)-kavain. Using KCl-depolarized synaptosomes, 400 mumol/l (+/-)-kavain reduced, in analogy to Aga-GI toxin, KCl-evoked [Ca2+]i and diminished the part of glutamate-exocytosis which is related to external Ca2+ to about 75% of control. At a concentration of 150 mumol/l, which is above the IC50 value necessary to block voltage-dependent Na+ channels, (+/-)-kavain affected neither basal nor the KCl-induced increase in [Ca2+]i. These results might suggest that (+/-)-kavain at concentrations sufficient to block Na+ channels completely. moderately inhibits the non-inactivating Ca2+ channels located on mammalian presynaptic nerve endings.

Animals↗
PubMed1996

The protective action of tetrodotoxin and (+/-)-kavain on anaerobic glycolysis, ATP content and intracellular Na+ and Ca2+ of anoxic brain vesicles.

Because recent reports point to Na+ channel blockers as protective agents directed against anoxia-induced neuronal damage including protection of anaerobic glycolysis, the influences of tetrodotoxin (TTX) and (+/-)-kavain on anoxic rat brain vesicles were investigated with respect to lactate synthesis, vesicular ATP content and cytosolic free Na+ and Ca2+ ([Na+]i, [Ca2+]i), both of the latter determined fluorometrically employing SBFI and FURA-2, respectively. After anoxia, basal lactate production was increased from 2.9 to 9.8 nmol lactate/min/mg protein. Although lactate synthesis seemed to be stable for at least 45 min of anoxia, as deduced from the linearity of lactate production, the ATP content declined continuously with a half life (tau 1/2) of 14.5 min, indicating that anaerobic glycolysis was insufficient to cover the energy demand of anoxic vesicles. Correspondingly, [Na+]i and [Ca2+]i increased persistently after anoxia by 22.1 mmol/l Na+ and 274.9 nmol/l Ca2+, determined 6.3 min after onset. An additional stimulation of vesicles with veratridine accelerated the drop of ATP (tau 1/2 = 5.1 min) and provoked a massive Na+ overload, which levelled off to 119 mmol/l Na+ within a few minutes. Concomitantly, [Ca2+]i increased linearly with a rate of 355 nmol Ca2+/l/min. Despite the massive perturbation of ion homeostasis, lactate production was unaffected during the first 8 min of veratridine stimulation. However, complete inhibition of lactate synthesis took place 30 min after veratridine was added. The Na+ channel blockers TTX and (+/-)-kavain, if applied before anoxia, preserved vesicular ATP content, diminished anoxia-induced increases in [Na+]i and [Ca2+]i and prevented both the veratridine-induced increases of [Na+]i and [Ca2+]i and the inhibition of lactate production. The data indicate a considerable Na+ influx via voltage-dependent Na+ channels during anoxia, which speeds up the decline in ATP and provokes an increase in [Ca2+]i. A massive Na+ and Ca2+ overload induced by veratridine failed to influence lactate synthesis directly, but initiated its inhibition.

Adenosine Triphosphate↗
PubMed1996

Structure and dynamics of oligosaccharides: NMR and modeling studies.

Recent advances in the conformational analysis of oligosaccharides have focused on protein-bound oligosaccharides, glycopeptides, and glycoproteins, as well as on the conformational dynamics about glycosidic linkages. Significant progress has been made possible by dramatic improvements in NMR techniques and advances in computational chemistry and technology. Transferred nuclear Overhauser effects have been used to infer the conformations of carbohydrate ligands bound to protein receptors such as antibodies, lectins and enzymes. The increased use of combined NMR spectroscopic and computational protocols has resulted in insights into the dynamics of glycan chains.

Animals↗
PubMed1996

A comparison of methods for measuring patient satisfaction with consultations in primary care.

BACKGROUND: Attention needs to be paid to comparing and standardizing methods for measuring patient satisfaction with consultations in primary care. OBJECTIVES: To compare the Medical Interview Satisfaction Scale (MISS) and the Consultation Satisfaction Questionnaire (CSQ) in terms of acceptability, distribution of responses, reliability and gather evidence of validity. In addition, to compare the scores of patients completing the questionnaires immediately after the consultation in the general practitioners' surgeries with those completing the questionnaires later at home. METHODS: The two questionnaires were bound as a single instrument with order determined at random. This was given to patients immediately after their consultations in eight practices in South Glamorgan. RESULTS: One hundred and ninety-eight of 316 (63%) patients completed and returned questionnaires. The distributions of patient satisfaction scores for the two questionnaires were very similar. For the MISS: mean 76.6% (SD 11.4); for the CSQ mean 7.2% (SD 12.6). Correlations between sub-scales ranged from 0.58-0.84 for the MISS and from 0.40-0.79 for the CSQ. The correlation between the overall scales was 0.82. Levels of reliability for the scales and sub-scales were fair to good ranging from 0.78-0.96 for the MISS and from 0.73-0.94 for the CSQ. CONCLUSIONS: The study does not identify one scale as being superior in psychometric terms, however by demonstrating consistency of responses it provides support for the scales as measures of patient satisfaction for use in primary care. The level of inter-correlation suggests that the sub-scales may not be clearly independent of each other and suggests that total scores may be preferred. Lower levels of satisfaction are expressed if patients complete questionnaires at home rather than in general practitioners' surgeries.

Adolescent↗
PubMed1996

Frequency-dependent inhibition of neuronal activity by lappaconitine in normal and epileptic hippocampal slices.

1. Extracellular recording of the stimulus-evoked population spike in the CA1 region of rat hippocampal slices in vitro was performed in order to investigate whether lappaconitine affects neuronal excitability. Lappaconitine is a diterpene alkaloid of plants of the Aconitum genus and has analgesic properties. 2. The results reveal an inhibitory action of lappaconitine (10 microM) manifested in a slow attenuation of the orthodromic and antidromic population spike. 3. The lappaconitine-induced inhibitory action was activity-dependent, that is, it was potentiated when frequency of electrical stimulation was increased. In contrast, washout of the neurotoxin was accelerated when stimulation frequency was decreased. 4. The activity-dependent action of lappaconitine raised the question of whether the drug is effective in suppressing the aberrant neuronal activity that occurs during an epileptic seizure. The results obtained from experiments on epileptic hippocampal slices demonstrated a selective reduction of the later spikes in the bursts with less effect on normal neuronal activity. 5. These data support the conclusion that lappaconitine, in addition to its antinociceptive effect, also has antiepileptic potency due to its highly activity-dependent mode of action.

Aconitine↗