Search PubMed⌕ Search

Biomedical subjects

A Lehmann

Publications and source records attributed to A Lehmann.

At least 55 records · Page 3Linked to original sources

Simultaneous myocardial revascularization and aortic valve replacement: stentless versus stented bioprostheses.

Implantation of stentless aortic valve prostheses is more time-consuming than implantation of conventional stented bioprostheses. Simultaneous myocardial revascularization can result in a considerably prolonged operation time. We reviewed our patients with regard to surgical aspects in the specific patient cohorts. From April 1996 to April 1999, 303 patients were operated for aortic valve disease with or without concomitant coronary artery revascularization. Mean age was 75 years, ranging between 36 and 90 years. Using the Medtronic Freestyle valve, the following techniques of implantation were used: subcoronary technique, 163 patients, 61.5%; root inclusion technique, 7 patients, 3.5%; total root replacement, 30 patients, 15%. Total hospital mortality rate was 5.6%, reflecting age and concomitant disease of these patients. For isolated aortic valve replacement, the mortality rate was 4.7% and 6.7% for combined procedures. Coronary artery patients who are not suitable for stentless valve implantation owing to extensive aortic root calcification have a higher perioperative mortality rate. Compared with the isolated valve replacement and despite more extensive surgery and prolonged operative time, simultaneous myocardial revascularization in patients with stentless prostheses implantation can be performed without an increased risk.

Adult↗

Subcellular distribution of proteasomes implicates a major location of protein degradation in the nuclear envelope-ER network in yeast.

26S proteasomes are the key enzyme complexes responsible for selective turnover of short-lived and misfolded proteins. Based on the assumption that they are dispersed over the nucleoplasm and cytoplasm in all eukaryotic cells, we wanted to determine the subcellular distribution of 26S proteasomes in living yeast cells. For this purpose, we generated yeast strains that express functional green fluorescent protein (GFP) fusions of proteasomal subunits. An alpha subunit of the proteolytically active 20S core complex of the 26S proteasome, Pre6/YOL038w, as well as an ATPase-type subunit of the regulatory 19S cap complex, Cim5/YOL145w, were tagged with GFP. Both chimeras were shown to be incorporated completely into active 26S proteasomes. Microscopic analysis revealed that GFP-labelled 20S as well as 19S subunits are accumulated mainly in the nuclear envelope (NE)-endoplasmic reticulum (ER) network in yeast. These findings were supported by the co-localization and co-enrichment of 26S proteasomes with NE-ER marker proteins. A major location of proteasomal peptide cleavage activity was visualized in the NE-ER network, indicating that proteasomal degradation takes place mainly in this subcellular compartment in yeast.

Adenosine Triphosphatases↗

Sample handling for proteome analysis.

The main factor limiting the sensitivity range for the identification of proteins isolated by two-dimensional (2-D) electrophoresis is sample handling: protein detection limits on the gel, losses during extraction and digestion, as well as interference of gel contaminants and detergents with the mass spectrometry (MS) detection increasing background noise. At the one hundred picomole level, losses are fairly negligible but when the amounts drop below 1 picomole (and subfemtomole peptide detection limits have been reported recently by MS), the losses become a critical point. In order to extend proteome analysis to include very low copy number proteins, methods must be developed to minimize losses and handling steps, maximize digestion and extraction yields, as well as to lower chemical noise. We present several methods that we have developed in our laboratory to: (i) increase the amount of material available in a sodium dodecyl sulfate (SDS)-free form which does not require staining, (ii) increase protein extraction and digestion yields and lower the contamination by autoproteolytic products, and (iii) allow direct modification of the peptide mixture to generate sequence tags.

Bacterial Proteins↗

Eye movements evoked by proprioceptive stimulation along the body axis in humans.

Proprioceptive input arising from torsional body movements elicits small reflexive eye movements. The functional relevance of these eye movements is still unknown so far. We evaluated their slow components as a function of stimulus frequency and velocity. The horizontal eye movements of seven adult subjects were recorded using an infrared device, while horizontal rotations were applied at three segmental levels of the body [i.e., between head and shoulders (neck stimulus), shoulders and pelvis (trunk stimulus), and pelvis and feet (leg stimulus)]. The following results were obtained: (1) Sinusoidal leg stimulation evoked an eye response with the slow component in the direction of the movement of the feet, while the response to trunk and neck stimulation was oriented in the opposite direction (i.e., in that of the head). (2) In contrast, the gain behavior of all three responses was similar, with very low gain at mid- to high frequencies (tested up to 0.4 Hz) but increasing gain at low frequencies (down to 0.0125 Hz). We show that this gain behavior is mainly due to a gain nonlinearity for low angular velocities. (3) The responses were compatible with linear summation when an interaction series was tested in which the leg stimulus was combined with a vestibular stimulus. (4) There was good correspondence of the median gain curves when eye responses were compared with psychophysical responses (perceived body rotation in space; additionally recorded in the interaction series). However, correlation of gain values on a single-trial basis was poor. (5) During transient neck stimulation (smoothed position ramp), the neck response noticeably consisted of two components -- an initial head-directed eye shift (phasic component) followed by a shift in the opposite direction (compensatory tonic component). Both leg and neck responses can be described by one simple, dynamic model. In the model the proprioceptive input is fed into the gaze network via two pathways which differ in their dynamics and directional sign. The model simulates either leg or neck responses by selecting an appropriate weight for the gain of one of the pathways (phasic component). The interaction results can also be simulated when a vestibular path is added. This model has similarities to one we recently proposed for human self-motion perception and postural control. A major difference, though, is that the proprioceptive input to the gaze-stabilizing network is weak (restricted to low velocities), unlike that used for perception and postural control. We hold that the former undergoes involution during ontogenesis, as subjects depend on the functionally more appropriate vestibulo-ocular reflex. Yet, the weak proprioceptive eye responses that remain may have some functional relevance. Their tonic component tends to stabilize the eyes by slowly shifting them toward the primary head position relative to the body support. This applies solely to the earth-horizontal plane in which the vestibular signal has no static sensitivity.

Adult↗

Enhancement of XPG mRNA expression by human interferon-beta in Cockayne syndrome cells.

Using PCR-differential display, we have searched for genes expressed specially in human interferon (HuIFn)-beta-treated Cockayne syndrome (CS) fibroblast cells. Eighteen expressed genes induced by HuIFN-beta were identified, the sequences of seven of which were highly homologous to previously cloned sequences. The cDNAs of six of these seven clones were similar to expression tagged sequences from unknown genes in databases and the remaining one was identical to the cDNA of the xeroderma pigmentosum XPG gene. These results, together with our previous finding of increased resistance to ultraviolet (UV) cell-killing of CS cells pretreated with HuIFN-beta prior to UV irradiation suggest that XPG might be one of the genes possibly involved in the HuIFN-beta-induced UV-resistance.

Cells, Cultured↗

RETRACTED: Pain management in cardiac surgery patients: comparison between standard therapy and patient-controlled analgesia regimen.

OBJECTIVE: To compare standard nurse-based pain therapy with a patient-controlled analgesia (PCA) regimen. DESIGN: Prospective, randomized study. SETTING: Single-institutional, clinical investigation in an urban, university-affiliated hospital. PARTICIPANTS: Sixty patients undergoing elective first-time cardiac surgery were included. INTERVENTIONS: In 30 patients, a standard analgesic regimen was used, and in 30 patients, a PCA regimen was used. The perioperative and postoperative management was similar for all patients. MEASUREMENTS AND MAIN RESULTS: Degree of sedation, satisfaction, and pain (by visual analog scale [VAS]) was assessed within the first 3 postoperative days. Vital capacity (VC) and forced expiratory volume in 1 second (FEV1) were measured using a portable spirometry system. Cortisol and troponin T (TnT) plasma levels were also measured. The expectation of pain was similar in both groups, and the postoperative pain score was significantly lower in the PCA than in the standard group throughout the study period. Significantly more piritramid was used in the PCA (total, 75.6 +/- 33.4 mg) than in the standard group (total, 20.1 +/- 31.9 mg). VC and FEV1 were significantly lower in the standard group compared with the PCA patients. Cortisol and TnT plasma levels were similar in both groups. Frequency of side effects were similar for both groups. CONCLUSION: Because of the beneficial effects with regard to degree of pain and satisfaction, pain management using PCA systems can be recommended for cardiac surgery patients. It appears to be superior to standard nurse-based pain therapy.

Analgesia, Patient-Controlled↗

[Asthenopic symptoms in cervical vertebrae syndrome].

The vertebral cervical syndrome is a clinical entity defined as a dysfunction of the cranio-cervical junction of traumatic or non traumatic cause. The authors report on asthenopic disorders occurring in such a syndrome. The fusion amplitude and the accommodation power were reduced in all patients and were a cause of delayed job recurrence. The treatment of fusion was long, painful and, in some cases, not successful. A depressive status associated with a prolonged job interruption were bad prognosis factors. A differential diagnosis has to be made with the so-called insurance neurotic reaction.

Accommodation, Ocular↗

MK-801 neurotoxicity in the guinea pig cerebral cortex: susceptibility and regional differences compared with the rat.

N-methyl-D-aspartate (NMDA) receptor antagonists induce transient vacuole formation in neurons of the retrosplenial cortex and, after higher doses, necrosis in the same region. To our knowledge, all studies demonstrating these effects have been carried out in rats or mice. The present study investigated whether vacuolization occurs in the guinea pig, rats being used as controls. Female Dunkin-Hartley guinea pigs (age 15-18 weeks) were given a single subcutaneous injection of saline or the non-competitive NMDA antagonist dizocilpine maleate [(+)-MK-801; 1, 4, or 12 mg/kg]. Female Sprague-Dawley rats (age 16 weeks) received saline or MK-801 (1 mg/kg). Whatever the dose of MK-801, guinea pigs showed only occasional vacuolated neurons in the retrosplenial cortex. However, affected neurons (mainly large pyramidal cells of layer V) were found in the frontoparietal neocortex. The reaction was limited after 1 mg/kg, and seemed to reach a maximum at 4 mg/kg. Rats injected with 1 mg/kg MK-801 showed an intense vacuole reaction in neurons from layers III-IV of the retrosplenial cortex, but no affected neurons were noted in neocortical areas. We conclude that there are significant species differences in susceptibility to, and location of, vacuolization induced by NMDA receptor antagonists.

Animals↗

Genetic detection: the need for psychosocial support in modern cancer prevention.

During recent years the gap between the rapid implementation of new technologies in cancer prevention and the slow development of a complementary psychological framework to conceptualize the transmission of genetic informations to patients has been deplored. Such a framework should include all psychological aspects surrounding the genetic consultation, reaching from the information and education of the general public to the impact of prophylactic surgery. While some of the psychological consequences of modern cancer prevention can not be fully foreseen and have first to be documented and analysed, others can easily be anticipated. The authors will try to outline a psychological framework that could help in facing potential negative effects of these beneficial preventive possibilities.

Adaptation, Psychological↗

Bicarbonate-sensitive cysteine induced elevation of extracellular aspartate and glutamate in rat hippocampus in vitro.

The effect of different concentrations of cysteine (0.125, 0.25, 0.5 and 1 mM) on the net efflux of endogenous amino acids was studied by the incubation of rat hippocampal slices. Addition of cysteine (1 mM) in bicarbonate containing low K+ medium (5 min) selectively increased the basal net efflux of glutamate and aspartate by 370% and 396%, respectively. High K+ media (50 mM) containing cysteine (1 mM) evoked the net efflux of glutamate and aspartate by 1454% and 1019%, respectively. The corresponding effects in control slices without cysteine were 669% and 404%, respectively. No changes were observed on the concentrations of GABA, glutamine and taurine. The cysteine oxidation products, cysteine sulfinate (0.5 microM) and cystine (0.25 mM) were without effects. The effect of cysteine (0.5 mM) was dramatically reduced in media with no added bicarbonate/CO2. Thus, cysteine in a bicarbonate-sensitive manner selectively increases the extracellular concentration of excitotoxic amino acids in adult rat brain in vitro, possibly by interfering with the carrier-mediated glutamate uptake/release.

Animals↗

Responses of the rat lower oesophageal sphincter (LOS) to vagal efferent activation.

Nitric oxide (NO) is a major candidate in vagal-induced LOS relaxation. Vagal adrenergic fibres also innervate the gastrointestinal tract including the LOS. This study investigates the role of these two and other mechanisms in LOS responses to vagal activation in the rat, and provides functional and anatomical evidence for a smooth muscle LOS in this species. LOS, gastric and oesophageal pressures were measured in urethane anaesthetized rats during vagal stimulation. The LOS pressure (LOSP) response to Vagal stimulation (5 mA, 10 Hz, 0.5 msec pulses, 5 sec) comprised three consecutive stages: (1) brief reduction of LOSP, (2) transient increase of LOSP and (3) prolonged reduction of LOSP. The influences of additive treatment with several antagonist drugs on the LOS response to vagal stimulation were investigated. L-NAME (100 mg kg-1) reduced stage 1 and increased stage 2. Subsequent treatment with either phentolamine (1 mg kg-1) or prazosin (200 micrograms kg-1) abolished stage 1. After phentolamine, atropine treatment (400 micrograms kg-1) abolished stage 2. Stage 3 was evident throughout experiments. In five additional studies, treatment with hexamethonium (30 mg kg-1) abolished stages 2 and 3 leaving stage 1, which was later abolished by phentolamine or atropine. In the LOS response to vagal stimulation, the following major mechanisms are therefore evident: nicotinic transmission in both excitation and inhibition, alpha-adrenergic and NO-mediated inhibition, muscarinic excitation, and non-adrenergic, non-NO inhibition (not characterized further). Characteristics of these different neurotransmitter influences may be important in LOS relaxation associated with swallowing and gastro-oesophageal reflux.

Animals↗

Development of brain damage after neonatal hypoxia-ischemia: excitatory amino acids and cysteine.

The aim of this study was to investigate the possible role of excitatory amino acids (EAAs) and cysteine in the development of brain damage after hypoxia-ischemia (HI) in neonates. In a rat model of neonatal HI, changes in extracellular (ec) amino acids in cerebral cortex were measured with microdialysis and correlated with the extent of brain damage at the site of probe placement. Extracellular concentrations of glutamate, aspartate and cysteine increased during HI and remained elevated during reperfusion. During HI the pattern of EAA changes was the same in the infarcted, undamaged and border zone regions. During reperfusion, however, the ec concentrations of glutamate, aspartate and cysteine were higher in infarcted and border zone areas compared to undamaged tissue. HI also produced a slight increase of tissue concentration of cysteine and decrease of tissue concentration of glutamate in parietal cortex of the HI hemisphere. The effect of cysteine on brain damage induced by HI and glutamate was also investigated. A subtoxic dose of cysteine potentiated glutamate toxicity in the arcuate nucleus and enhanced brain infarction after HI in neonatal rats. The results show that in neonatal HI the extracellular levels of EAAs during HI are not directly related to brain injury but the EAA levels during reflow predict the extent of infarction. Cysteine increases HI-induced brain injury and potentiates glutamate toxicity in neonatal rats. Speculatively, elevated level of cysteine during reperfusion may participate in the excitotoxic cascade leading to brain injury.

Animals↗

Effects of N-methyl-D-aspartate receptor antagonists on cisplatin-induced emesis in the ferret.

Glutamate may be a key transmitter in the emetic reflex arc. The present investigation focussed on the involvement of the NMDA subtype of glutamate receptors in cisplatin-induced emesis. Ferrets were injected with cisplatin (10 mg/kg i.v.) and either of the non-competitive NMDA receptor antagonists dextromethorphan or memantine, or the competitive receptor antagonist CGS 19755. In order to determine whether there is a synergism between NMDA blockers and 5-HT3 receptor antagonists, a submaximal dose of granisetron (0.05 mg/kg) was given alone or in combination with either dextromethorphan or memantine. The latency for the onset of emesis as well as the total number of vomits and retches over 3 hr were determined. In controls, the latency for emesis was 73 +/- 6 min and the total number of vomits and retches 143 +/- 17. The corresponding figures for animals treated with dextromethorphan, 10 and 20 mg/kg, were 89 +/- 19 min (p > 0.05) and 50 +/- 17 (p = 0.008), and 113 +/- 18 min (p > 0.05) and 22 +/- 9 (p = 0.004), respectively. At 10 mg/kg, dextromethorphan failed to enhance the antiemetic effect of granisetron which by itself provided 90% inhibition. While memantine (2.5 or 5.0 mg/kg) did not have an effect per se, it tended to reduce the antiemetic effect of granisetron. CGS 19755 (10 mg/kg) provided a partial protection against cisplatin-induced emesis (latency: 111 +/- 23, number of vomits and retches 30 +/- 11). None of the NMDA receptor antagonists was free of behavioural effects (e.g. some sedation) at antiemetic doses. It is concluded that NMDA receptor antagonists may afford protection against cisplatin-induced emesis but the specificity of this effect is uncertain since it may relate to general CNS depression.

Animals↗

Neuronal and glial handling of glutamate and glutamine during hypoosmotic stress: a biochemical and quantitative immunocytochemical analysis using the rat cerebellum as a model.

Biochemical and immunocytochemical analyses were performed to resolve how glutamate and glutamine are handled in rat cerebellar cortex in acute hypoosmotic stress. Rats were subjected to a 15-20% reduction in plasma osmolality by intraperitoneal injection of distilled water and then perfusion fixed after 4 or 8 h survival. Some rats in the latter group had their plasma isoosmolality restored by injections of hypertonic saline 4 h prior to perfusion. Water loading caused a pronounced increase in the tissue level of glutamine and an equimolar decrease in the level of glutamate after 4 h survival. The increase in glutamine was transient, as judged by analyses at 8 h survival. Light microscopic immunocytochemistry revealed a pronounced enhancement of the glutamine immunolabelling of glial cells (Golgi epithelial cells and astrocytes), including their perivascular end feet, and quantitative immunogold analyses at the electron microscopic level showed that this enhancement reflected a 50% increase in the intracellular concentration of fixed glutamine. Since water loading was associated with glial swelling this change corresponded to a several-fold increase in the glial content of glutamine. There was a modest reduction in the overall staining intensity for glutamate. The biochemical and immunocytochemical changes were reversed upon restoration of plasma osmolality by hypertonic saline. These findings suggest that hypoosmotic stress causes an increased conversion of glutamate to glutamine in glial cells and that the latter amino acid is subsequently lost from the tissue. The flux of glutamate carbon skeletons through the glutamine synthetase pathway in glia, prior to an efflux to the systemic circulation, may explain how glutamate, and excitatory transmitter and potential toxin, can be used as an organic osmolyte in brain tissue.

Animals↗