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Biomedical subjects

T Peters

Publications and source records attributed to T Peters.

At least 91 records · Page 5Linked to original sources

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

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 VI of this six-part series focuses on atherectomy and restenosis tissue obtained by atherectomy procedures.

Angioplasty, Balloon↗

Calcium-dependent, sustained enhancement of excitability during washout of aconitine in rat hippocampal slices.

Extracellular recording of the stimulus-evoked population spike was performed in the CA1 area of rat hippocampal slices in order to investigate delayed effects of the plant alkaloids aconitine and veratridine. Veratridine (1 microM and 10 microM) suppressed the orthodromic and antidromic population spike. After washout of the drug, only a partial recovery was obtained. Aconitine (1 microM) exerted the same inhibitory action as veratridine. However, after washout, the spike amplitude was enhanced compared with the control. This enhancement of the spike amplitude was dependent on the concentration of aconitine and was maintained during the observation period of at least 2 h. Lowering the Ca2+ concentration of the bathing medium from 2.5 mM to 1.25 mM during application of aconitine attenuated recovery and prevented the enhancement observed during washout of the drug. Application of aconitine in the presence of CdCl2 as well as in the presence of inhibitors of protein kinase C and Ca2+/calmodulin-dependent protein kinase II prevented the increase in spike amplitude during washout with standard artificial cerebrospinal fluid. In contrast, the N-methyl-D-aspartate (NMDA) receptor antagonists D-AP5 and MK-801 as well as the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione were ineffective in abolishing the aconitine-induced enhancement. These data support the conclusion that different modes of action are involved in the effects of aconitine but not veratridine. It is concluded that the aconitine-induced increase in neuronal activity is mediated by intracellular Ca2+-dependent mechanisms leading to an activation of Ca2+-dependent protein kinases. This effect is independent of Ca2+ entrance through NMDA and non-NMDA receptors.

2-Amino-5-phosphonovalerate↗

Quasispecies analysis in hepatitis C virus infection by fluorescent single strand conformation polymorphism.

Hepatitis C virus (HCV) results frequently in chronic hepatitis and its sequelae liver cirrhosis and hepatocellular carcinoma. Interferon-alpha is at present the most effective treatment, resulting in a sustained response in about 20-25% of patients. HCV genotype, titer and quasispecies determine the success of treatment. In this study, fluorescent single strand conformation polymorphism (f-SSCP) was evaluated for the analysis of HCV quasispecies. Two sera from a chronically HCV-infected patient, obtained 6 years apart, were examined. The hypervariable region I (HVRI) of the HCV genome was amplified by reverse transcription and PCR. The PCR products were cloned and sequenced or fluorescein-labeled and subjected to f-SSCP. Both methods demonstrated a single HCV species in the early serum and multiple quasispecies in the late serum. Single clones of the heterogeneous virus population were used to optimize conditions for f-SSCP. The most important factors were the gel temperature and virus titer. At the optimal running temperature one base exchange in 218 bases was detectable. Repeat extractions and amplifications gave identical results. Dilution of the serum containing multiple quasispecies resulted in a 'loss' of species. Provided the running temperature is optimal and virus titer is sufficient, f-SSCP is shown to be fast and reliable for HCV quasispecies analysis.

Amino Acid Sequence↗

Kava extract ingredients, (+)-methysticin and (+/-)-kavain inhibit voltage-operated Na(+)-channels in rat CA1 hippocampal neurons.

The action of synthetic kava pyrones, (+)-methysticin and (+/-)-kavain, on voltage-operated Na(+)-channels was studied in whole-cell patch-clamped CA1 hippocampal neurons. In doses of 1-400 microM, both compounds exerted a rapid and reversible inhibition of the peak amplitude of Na(+)-currents. Shifting holding membrane potential (Vhold) to more positive values enhanced their blocking effect. The drugs studied did not demonstrate use-dependent properties at 10 Hz stimulation but shifted H infinity curve toward more negative potentials, accelerated time-course of inactivation and slowed down the recovery from inactivation. Voltage-dependence of Na(+)-channel inhibition can be explained by interaction of (+)-methysticin and (+/-)-kavain with resting closed and inactivated states of Na(+)-channel.

Animals↗

Attitude of emergency department patients toward HIV-infected health care workers.

A telephone survey of a random sample of adult emergency department (ED) patients was conducted at a university health science center. The purpose of the study was to determine the opinion of ED patients concerning the risk of human immunodeficiency virus (HIV) transmission and their willingness to be treated by HIV-infected physicians and nurses. Surveys from 107 ED patients were compiled and available for analysis. Ninety percent of the respondents were tolerant of an HIV-infected physician or nurse (HIV + HCW)performing noninvasive procedures. Fifty percent were tolerant of an HIV + HCW performing invasive procedures. Twenty-six percent of the patients said they would leave the department rather than be treated by an HIV + HCW. Patients older than 50 years were less tolerant (P = .004) and more likely to leave the ED (P = .001).

Adolescent↗

Conformational analysis of biantennary glycans and molecular modeling of their complexes with lentil lectin.

Some mannose-binding legume lectins show higher affinity for fucosylated glycans than for glycans without fucose. These lectins possess a secondary binding site. Owing to the possibility of additional fucose binding, oligosaccharides adopt different conformations depending on whether they contain fucose or not. To study these conformational differences, complexes of fucosylated and unfucosylated glycans with Lens culinaris lectin have been modeled. Starting points were X-ray structures of lentil lectin and complexes of the homologous Lathyrus ochrus lectin. The SYBYL molecular modeling package with the TRIPOS force field was used. Two different models were built, displaying in both a network of hydrogen bonds between the saccharide and the binding site. Furthermore, to compare the free and bound ligand, conformational analysis in the free state has been performed. A complete analysis of all possible disaccharide fragments has been performed using the MM3 force field. A CICADA analysis employing the same force field was carried out to study the complete oligosaccharide. Low-energy conformers found by CICADA were clustered in conformational families and analyzed in terms of flexibility and rotational barriers. All values of glycosidic torsion angles are in the range as calculated by MM3 for the disaccharides.

Binding Sites↗

Application of homonuclear 3D NMR experiments and 1D analogs to study the conformation of sialyl Lewis(x) bound to E-selectin.

The conformation of the sialyl Lewis(x) tetrasaccharide bound to E-selectin was previously determined from transfer NOE (trNOE) experiments in conjunction with a distance-geometry analysis. However, the orientation of the tetrasaccharide ligand in the binding site of E-selectin is still unknown. It can be predicted that the accurate quantitative analysis of all trNOEs, including those originating from spin diffusion, is one key to analyze the orientation of sialyl Lewis(x) in the binding pocket of E-selectin. Therefore, we applied homonuclear 3D NMR experiments and 1D analogs to obtain trNOEs that could not unambiguously be assigned from previous 2D trNOESY spectra, due to severe resonance-signal overlap. A 3D TOCSY-trNOESY experiment, a 1D TOCSY-trNOESY experiment, and a 1D trNOESY-TOCSY experiment of the sialyl Lewis(x)/E-selectin complex furnished new interglycosidic trNOEs and provided additional information for the interpretation of trNOEs that have been described before. A 2D trROESY spectrum of the sialyl Lewis(x)/E-selectin complex allowed one to identify the amount of spin-diffusion contributions to trNOEs. Finally, an unambiguous assignment of all trNOEs, and an analysis of spin-diffusion pathways, was obtained, creating a basis for a quantitative analysis of trNOEs in the sialyl Lewis(x)/E-selectin complex.

Carbohydrate Sequence↗

Antithrombotic action of the kava pyrone (+)-kavain prepared from Piper methysticum on human platelets.

(+)-Kavain, a 4-methoxy-alpha-pyrone prepared from Piper methysticum Forst. (Piperaceae), was investigated regarding its assumed antithrombotic action on human platelets which was deduced from its ability to suppress arachidonic acid (AA)-induced aggregation, exocytosis of ATP, and inhibition of cyclooxygenase (COX) and thromboxane synthase (TXS) activity, the latter two effects being estimated from the generation of prostaglandin E2 (PGE2) and thromboxane A2 (TXA2), respectively. Exogenously applied AA (100 mumol/l) provoked a 90% aggregation of platelets, the release of 14 pmol ATP, and the formation of either 220 pg TXA2 or 43 pg PGE2, each parameter being related to 10(6) platelets. An application of (+)-kavain 5 min before AA, dose-dependently diminished aggregation, ATP-release, and the synthesis of TXA2 and PGE2 with IC50 values of 78, 115, 71, and 86 mumol/l, respectively. The similarity of the IC50 values suggest an inhibition of COX by (+)-kavain as primary target, thus suppressing the generation of TXA2 which induces aggregation of platelets and exocytosis of ATP by its binding on TXA2-receptors.

Arachidonic Acids↗

Bicuculline-induced epileptiform activity in rat hippocampal slices: suppression by Aconitum alkaloids.

Alkaloids of Aconitum spec. (Ranunculaceae) are employed in traditional Chinese folk medicine as analgesics. The present study was designed in order to investigate the effects of the structurally related alkaloids aconitine, lappaconitine, and 6-benzoylheteratisine on experimentally induced epileptiform activity. Experiments were performed as extracellular recordings of stimulus evoked population spikes in rat hippocampal slices. Epileptiform activity was induced by bicuculline. All three alkaloids exerted an inhibitory action on excitability of hippocampal pyramidal cells in a frequency-dependent manner. The onset of inhibition was accelerated by increasing the frequency of electrical stimulation. Aconitine (1 microM) evoked a complete suppression of both normal and epileptiform activity, whereas lappaconitine (10 microM) and 6-benzoylheteratisine (10 microM) selectively diminished the epileptiform afterdischarges and the duration of the bursts, but spared the normal activity. The present findings suggest that the structurally related Aconitum alkaloids aconitine, lappaconitine, and 6-benzoylheteratisine possess an anticonvulsive potential. The predominant effect of these alkaloids is to suppress the spread of seizure activity, and they may therefore tend to distort epileptic events. However, despite their similar structure, they exert qualitatively and quantitatively different inhibitory effects.

Aconitine↗

Relaxation of evoked contractile activity of isolated guinea-pig ileum by (+/-)-kavain.

Kava pyrones are the pharmacologically active compounds of Piper methysticum Forst. In the present study, the effect of the synthetic kava pyrone (+/-)-kavain was investigated on evoked contractile activity of isolated guinea-pig ileum. (+/-)-Kavain (1 microM-1 mM) dose-dependently reduced contractions of ileum evoked by carbachol (10 microM), by BAY K 8644 (0.3 microM), or by substance P (0.05 microM). (+/-)-Kavain also inhibited the contractile responses induced by raising the extracellular K+ concentration from 4 to 20 mM and by blocking the K+ channel by barium chloride (1 mM) or 4-aminopyridine (0.3 mM). After pre-incubation with 1 microM nifedipine, carbachol (1 microM) evoked 18.2 +/- 14.3% of contraction at control (i.e. prior pre-incubation with nifedipine). This remaining response was completely abolished by high concentrations of (+/-)-kavain (400 microM). After treatment of the longitudinal ileum strips with pertussis toxin (PTX), carbachol (1 microM) evoked 27.0 +/- 6.2% of the control response in untreated ileum. These contractions were also blocked by (+/-)-kavain (400 microM). However, (+/-)-kavain had no effect on the caffeine-induced (20 mM) contractions of ileum strips, which were permeabilized with digitonin or beta-escin. Moreover, it failed to affect Ca(2+)-evoked contractions of skinned muscles. These results suggest that the kava pyrone (+/-)-kavain may act in a non-specific musculotropic way on the smooth muscle membrane.

Animals↗

Lactose-intolerance may induce severe chronic eczema.

The primary acquired lactase deficiency of the adult is known to cause various disturbances in the gastrointestinal tract while extraintestinal symptoms are unusual. Here we report on a histologically proven chronic eczema requiring corticosteroid treatment for several months. It was obviously induced by a concomitant lactose intolerance since the introduction of a lactose-free diet led to a complete disappearance of the eczema and allowed the discontinuation of the corticosteroid treatment. As far as we know, this is the first case report of an eczema caused by a lactose intolerance.

Adrenal Cortex Hormones↗

Did the introduction of general practice fundholding change patterns of emergency admission to hospital?

OBJECTIVES: To test the hypothesis that the introduction of general practice fundholding was associated with a change in the proportion of emergency admissions to hospital. METHODS: Before and after natural experiment with control group. The experimental group was first-wave fundholding general practices in the South Western Regional Health Authority, the control group was all practices that remained non-fundholding as of April 1993. Data were collected on episodes of care in hospitals in the South Western region involving cholecystectomy, hernia repair, intervertebral disc operation and prostatectomy. The additional impact of fundholding status on any underlying changes in proportions of emergency admissions was examined using multiple logistic regression. RESULTS: There was no evidence of an interaction between fundholding status and before/after time period. Odds ratios and confidence intervals for the interaction of general practice fundholding status and time were: prostatectomy 1.02 (0.77 to 1.34); hernia repair 0.94 (0.7 to 1.24); intervertebral disk operations 1.67 (0.8 to 3.47); prostatectomy 0.94 (0.69 to 1.27). CONCLUSIONS: The results provide no evidence that, in the first 2 years of the scheme, fundholding had an impact on the proportion of emergency admissions to hospital.

Budgets↗

Rates of rewarming, heart and respiratory rates and their significance for oxygen transport during arousal from torpor in the smallest mammal, the Etruscan shrew Suncus etruscus.

We investigated the process of rewarming from torpor with respect to respiratory and circulatory oxygen transport properties in the smallest mammal, the Etruscan shrew Suncus etruscus. In seven adult Etruscan shrews with a mean body mass of 2.4g, torpor was induced by deprivation of food and a cold environment. During arousal from torpor at an ambient temperature of 22 degrees C, the shrews actively rewarmed from the lowest mean (+/- S.D.) body temperature (Tb) of 12.1 +/- 1.2 degrees C to 20 degrees C at a rate of 0.43 +/- 0.14 degree C min-1, from 20 to 24 degrees C at a rate of 0.8 degree C min-1, and from 24 to 36 degrees C at a rate of 1.1 +/- 0.1 degrees C min-1. The mean rate from 12 degrees C to normothermia amounted to 0.83 degree C min-1, which is among the highest values recorded in mammals. During rewarming, the heart rate increased exponentially (Q10 = 2.2) from 100 to 800-1200 min-1, whereas the respiratory rate increased linearly from 50 to 600-800 min-1. These rates are higher than the heart and respiratory rates reported for other small mammals at the same Tb. The fraction of brown adipose tissue (BAT) was 9.2 +/- 1.6% of body mass, which is higher than in any other mammal. Up to a body temperature of approximately 17 degrees C, the heat for rewarming was mainly produced in the BAT; above this value, considerable activity of the skeletal muscles enhanced thermogenesis. Estimation of the mixed venous oxygen partial pressure showed that, at the tissue level, the rewarming process corresponds to heavy work conditions. The ventilatory system is adapted such that during rewarming, in addition to the appropriate oxygen transport capacity, there is also a capacity for hyperventilation.

Animals↗

[Hepatitis B virus mutants--clinical significance].

Hepatitis B virus (HBV) mutants have recently been identified in patients with acute or fulminant as well as chronic infections. Naturally occurring mutations have been identified in all viral genes and regulatory elements, most notably in the genes coding for the structural envelope and nucleocapsid proteins. Mutations in the gene coding for the hepatitis B surface antigen (HBsAg) may result in infection or viral persistence despite the presence of antibodies against HBsAg (anti-HBs) ("vaccine escape" or "immune escape"). Mutations in the gene encoding the pre-core/ core protein (pre-core stop codon mutant) result in a loss of hepatitis B e antigen (HBeAg) and seroconversion to antibodies to HBeAg (anti-HBe) with persistence of HBV replication (HBeAg minus mutant). Mutations in the core gene may lead among others to an "immune escape" due to a T cell receptor antagonism. Mutations in the gene coding for the polymerase/reverse transcriptase can be associated with viral persistence or resistance to nucleoside analogues. Thus, HBV mutations may affect the natural course of infection, viral clearance and response to antiviral therapy. Apart from the precore/core stop codon mutations, the exact contribution of specific mutations to diagnosis and therapy of HBV infection as well as patient management in clinical practice remain to be established.

Antibody Formation↗

Anticonvulsive action of (+/-)-kavain estimated from its properties on stimulated synaptosomes and Na+ channel receptor sites.

Kava pyrones are constituents of the intoxicating pepper (Piper methysticum Forst), which has been shown to be anticonvulsive. The question of how the excitability of neurons is affected was investigated by determining the interaction of (+/-)-kavain with epitopes (site 1, site 2) of voltage-dependent Na+ channels and the action of (+/-)-kavain on 4-aminopyridine-stimulated synaptosomes as model of repetitive firing neurons. [3H]Saxitoxin and [3H]batrachotoxin were used for radioligand-binding assays performed with synaptosomal membranes. Gultamate released from 4-aminopyridine-stimulated cerebrocortical synaptosomes and the cytosolic concentrations of Na+ and Ca2+ ([Na+]i, [Ca+]i) were detected fluorometrically by using an enzyme-linked assay, sodium-binding benzofuranisophthalate (SBFI) and Fura-2, respectively. (+/-)-Kavain failed to compete with [3H]saxitoxin up to 400 mumol/l but dose-dependently suppressed binding of [3H]batrachotoxin with an IC50 value of 88 mumol/l (Ki = 72 mumol/l) although displacement of [3H]batrachotoxin was restricted to 33% of control at 400 mumol/l (+/-)-kavain. In stimulated synaptosomes, 5 mmol/l 4-aminopyridine provoked an increase in [Na+]i and [Ca2+]i by 9 mmol/l Na+ and 235 nmol/l Ca2+. Comparable to the reduction in [3H]batrachotoxin binding, 400 mumol/l (+/-)-kavain suppressed the increase in [Na+]i and [Ca2+]i to 38 and 29% of control, respectively. Consistent with the increase in [Na+]i and [Ca2+]i, 5 mmol/l 4-aminopyridine provoked glutamate release (rate: 38 pmol/s*mg protein) which was dose-dependently diminished to 60% of control by 400 mumol/l (+/-)-kavain. KCl depolarization (40 mmol/l) provoked an increase in [Ca2+]i and glutamate release almost identical to the responses elicited by 4-aminopyridine but 400 mumol/l (+/-)-kavain suppressed only the rate of glutamate release by 9% of control. The data suggest an interaction of (+/-)-kavain with voltage-dependent Na+ and Ca2+ channels, thereby suppressing the 4-aminopyridine-induced increase in [Na+]i, [Ca2+]i and the release of endogenous glutamate.

4-Aminopyridine↗

Inhibition of neuronal activity in rat hippocampal slices by Aconitum alkaloids.

The structurally related Aconitum alkaloids aconitine, lappaconitine, and 6-benzoylheteratisine inhibited the orthodromic and antidromic population spike in hippocampal CA1 area in a frequency-dependent manner. Aconitine (1 microM) completely suppressed epileptiform activity induced by omission of Mg2+ as well as normal neuronal activity, whereas lappaconitine (10 microM) and 6-benzoylheteratisine (10 microM) diminished epileptiform activity by sparing normal neuronal activity.

Aconitine↗