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Biomedical subjects

A Lehmann

Publications and source records attributed to A Lehmann.

At least 37 records · Page 2Linked to original sources
PubMed2000

Effects of repeated administration of baclofen on transient lower esophageal sphincter relaxation in the dog.

The metabotropic gamma-aminobutyric acid (GABA) receptor (GABA(B) receptor) agonist baclofen inhibits transient lower esophageal sphincter relaxation in dogs, ferrets, and humans. Since transient lower esophageal sphincter relaxations are the major cause of gastroesophageal reflux, GABA(B) receptor agonists may have a therapeutic value in the treatment of gastroesophageal reflux disease. However, repeated stimulation of the GABA(B) receptor may induce receptor desensitization which, depending on the magnitude, would limit the therapeutic effect. The aim of the present study was to follow the effects of baclofen on transient lower esophageal sphincter relaxation in the dog after repeated administration. The effect of 7 micromol/kg baclofen b.i.d. (given intragastrically) on transient lower esophageal sphincter relaxation and related parameters was determined in four dogs. Transient lower esophageal sphincter relaxations stimulated by infusion of liquid nutrient and insufflation of air were quantified after placebo and then after the 1st, 13th, and 27th dose. Baclofen reduced the number of transient lower esophageal sphincter relaxations without affecting their duration, and the latency to the first transient lower esophageal sphincter relaxation was prolonged. Basal sphincter pressure was unaffected by baclofen, and the number of reflux episodes and esophageal acid exposure decreased. There was a statistically insignificant numerical decrease (approximately 30%) in the effect of baclofen on transient lower esophageal sphincter relaxation after the seventh dose but this was not further accentuated after the 27th dose. The effect on latency was also reduced with repeated dosing, but again, the effects after the 1st, 13th, and 27th doses were not statistically significant. The attenuation of acid exposure and reflux episodes was unaltered after repeated dosing. Three of the dogs greatly reduced their food intake within the first 2-3 days but this side effect was resolved subsequently. It is concluded that repeated dosing of baclofen leads to mild tolerance development in terms of the effects on transient lower esophageal sphincter relaxation, but that the tolerance is much less pronounced than that previously reported in other animal models.

Animals↗
PubMed2000

A method for the chemical generation of N-terminal peptide sequence tags for rapid protein identification.

We describe a method for generating multiple small sequences from the N terminal of peptides in unseparated protein digests by stepwise thioacetylation and acid cleavage. The mass differences between a series of N-terminally degraded peptides give short sequences of defined length. Such short "sequence tags" together with the mass of the parent peptide can be used to identify the protein in a database. The sequence ladders are generated without the use of chain terminators or sample aliquoting and the degradation reagents are water soluble so that the chemistry can be carried out on peptides immobilized on C-18 reversed-phase supports without any peptide loss due to washing with organic solvents as occurs in Edman type sequencing. The entire procedure can be automated, and we describe a prototype device for the parallel analysis of multiple samples. We demonstrate the effectiveness of this chemical tagging method in a comparison with Edman sequencing, peptide mass fingerprinting, and MS/MS analysis of crude protein fractions obtained from an HPLC separation of the Escherichia coli ribosome complex which consists of 57 proteins. We show that chemical tagging is a viable first-pass high-throughput identification method to be used prior to an in depth MS/MS analysis.

Amino Acid Sequence↗
PubMed2000

Immunocytochemical distribution of the GABA(B) receptor splice variants GABA(B) R1a and R1b in the rat CNS and dorsal root ganglia.

The anatomical distribution of the GABA(B) receptor (GBR) splice variants GBR1a and 1b in the CNS has not previously been studied. In the present study, distribution of the splice variants was mapped using immunohistochemistry. Polyclonal antibodies against splice variant unique epitopes were raised in rabbits. Affinity purified antibodies were used according to routine immunohistochemical procedures in sections from the rat CNS or dorsal root ganglia (DRG). The staining intensity was high in the cerebral cortex but lower in basal ganglia and the hippocampus. In the cerebellum, there was a marked difference in the distribution of GBR1a- and 1b-like immunoreactivity (LI). GBR1a-LI was preferentially localised in the granule cell layer whilst GBR1b-LI was mostly found in Purkinje cells and in the molecular layer. Cell bodies of the deep cerebellar nuclei stained for the GBR1a antibody while terminals surrounding the cell bodies were strongly labelled with the GBR1b antibody. A similar pre- vs postsynaptic pattern was seen in several nuclei ventral or caudal to the cerebellum (e.g. the cochlear nucleus, the facial nucleus, the spinal cord) but not in regions rostral to the cerebellum. In the spinal cord, strong labelling for both antibodies was seen in the dorsal horn. The GBR1b but not the GBR1a antibody stained tanycytes in the epithelium of the 3rd ventricle and in the central canal at the brain stem level. DRG neurons were positive for both the GBR1a and 1b antibody, but the former stained the cells much more intensely. Satellite cells were labelled with the GBR1b antibody. The most important aspect of these findings is that in some nuclei, GBR1b may mediate inhibition of transmitter release while in the same regions, GBR1a may mediate postsynaptic inhibition. Further, the observations support previous findings that GBR1b is the predominant splice variant in Purkinje cells.

Animals↗
PubMed2000

Pneumoperitoneum secondary to endoscopic harvest of saphenous vein graft.

Endoscopic harvest of saphenous vein graft for coronary artery bypass grafting decreases leg wound complications compared with traditional longitudinal incision. A case of pneumoperitoneum secondary to endoscopic harvest of saphenous vein using insufflation of carbon dioxide is reported. Hypercarbia, increased peak airway pressure, but no significant changes of hemodynamics, or myocardial ischemia were noted. The management of this rare complication is described.

Angina Pectoris↗
PubMed2000

Diagnostic value of urinary alanine aminopeptidase and N-acetyl-beta-D-glucosaminidase in comparison to alpha 1-microglobulin as a marker in evaluating tubular dysfunction in glomerulonephritis patients.

To estimate the diagnostic value of tubular parameters, the urinary alanine aminopeptidase (AAP), N-acetyl-beta-D-glucosaminidase (NAG) and the alpha(1)-microglobulin (a1M) of 150 patients with histologically proven glomerulonephritis (GN) were determined. In addition, the reabsorption rate of the proximal tubule and the fractional excretion of sodium, the free water clearance and the renal function were assessed by inulin and p-aminohippurate (PAH) clearance. Compared to healthy controls, urinary AAP, NAG and a1M were found significantly elevated in GN patients. Morphological tubular changes were confirmed by significant differences in urinary laboratory parameters. In patients with tubular atrophy, the diagnostic sensitivity and specificity were calculated as follows: AAP (0.94/0.35), NAG (0.75/0.59) and a1M (0.73/0.52). In patients showing tubular protein droplets, the values were 0.90/0.17 for AAP, 0.78/0.76 for NAG and 0.84/0.74 for a1M and in patients with interstitial fibrosis, the values were AAP (0.95/0.35), NAG (0.75/0. 46) and a1M (68/0.38). Urinary AAP, NAG and a1M reflect histologically proven tubulus alteration in GN, although in most cases, the renal function is still intact. AAP indicates very early tubular impairment and, in some cases, AAP is elevated although NAG and a1M are still within normal ranges. We suggest that the enzyme activities are useful in the diagnostics of early stages of the disease.

Acetylglucosaminidase↗
PubMed2000

Control of transient lower esophageal sphincter relaxations and reflux by the GABA(B) agonist baclofen in normal subjects.

BACKGROUND & AIMS: Transient lower esophageal sphincter (LES) relaxations are the major mechanism of gastroesophageal reflux in normal subjects and in most patients with reflux disease. gamma-Aminobutyric acid (GABA) is an important inhibitory neurotransmitter within the central nervous system which is present in regions of the brainstem that are believed to mediate transient LES relaxations. The aim of this study was to investigate the effect of a GABA(B) agonist baclofen on postprandial gastroesophageal reflux and transient LES relaxations. METHODS: In 20 healthy volunteers, esophageal motility and pH were measured, with the subjects in the sitting position, for 3 hours after a 3000-kJ mixed nutrient meal. On separate days at least 1 week apart, 40 mg oral baclofen or placebo was given 90 minutes before the meal. RESULTS: Baclofen significantly reduced the rate of reflux episodes by more than 60% from 1.0 (0.3-2.7) to 0.3 (0-1.0) per hour (median [interquartile range]). Baclofen also reduced the rate of transient LES relaxations from 5.7 (4.9-7.8) to 2.2 (1.3-3.8) per hour and increased basal LES pressure from 8.7 +/- 1.4 to 10.8 +/- 0.8 mm Hg. CONCLUSIONS: In normal human subjects, the GABA(B) agonist baclofen significantly inhibits gastroesophageal reflux by inhibition of transient LES relaxations. These findings suggest that GABA(B) agonists may be useful as therapeutic agents for the management of reflux in patients with gastroesophageal reflux disease.

Adolescent↗
PubMed2000

Expression of CD44 during early development of the chick embryo.

CD44, the major cell-surface receptor for hyaluronate, is expressed on many cell types to mediate different functions including cell activation, homing and adhesion. The early pattern of CD44 expression was determined in the avian embryo by using a specific monoclonal antibody in whole-mount and tissue sections. CD44 was first expressed on cephalic neural fold cells and later on by subpopulations of pre-and migratory cranial neural crest cells. Trunk neural crest cells did not express CD44. At the 18-20 somite stage, CD44 expressing cells were also localized in the caudal region of the embryo, in the mesoderm of the remaining primitive streak and in the caudal ectoderm and above the secondary neural tube during the process of cavitation. In addition, some hemopoietic cells present in the blood stream were also CD44 positive.

Animals↗
PubMed2000

The spike of S phase cyclin Cig2 expression at the G1-S border in fission yeast requires both APC and SCF ubiquitin ligases.

We describe a novel set of oscillation mechanisms for the fission yeast S phase cyclin Cig2, which contains an authentic destruction box and is destroyed at anaphase via the APC/cyclosome (APC/C). Unlike the mitotic cyclin Cdc13, however, Cig2 mRNA and protein peak at the G1/S boundary and decline to low levels in G2 and M phases. We show here that SCF(Pop1, Pop2) plays a role in transcriptional periodicity, as pop mutations result in constitutive cig2(+) transcripts. The instability of Cig2 during G2 and M is independent of either the APC/C or Pop1/Pop2, but requires Skp1, a core component of SCF. These data indicate that the APC/C and SCF control Cig2 levels differentially at different stages of the cell cycle.

Anaphase↗
PubMed2000

Electroencephalogram bispectral index predicts hemodynamic and arousal reactions during induction of anesthesia in patients undergoing cardiac surgery.

OBJECTIVE: To evaluate hemodynamic and clinical responses to induction of anesthesia and intubation at 3 different values of the electroencephalogram bispectral index (BIS). DESIGN: Prospective randomized trial. SETTING: University-affiliated hospital. PARTICIPANTS: Forty-five patients undergoing elective coronary artery bypass graft surgery. INTERVENTIONS: Patients were assigned to 3 groups (n = 15 for each group). Anesthesia was induced with midazolam, sufentanil, and pancuronium. In each group, sufentanil was titrated to a BIS value of 60, 50, or 40 before intubation. Mean arterial blood pressure, heart rate, incidence of coughing, tearing, and need for fluid replacement or injections of norepinephrine were recorded before intubation as well as immediately and 1 and 2 minutes after intubation. MEASUREMENTS AND MAIN RESULTS: Thirteen patients intubated at a BIS value of 60 coughed and 14 experienced tearing after intubation, whereas no patient of the other groups showed signs of arousal. Mean arterial blood pressure remained stable in the BIS 60 and 50 groups, whereas in the BIS 40 group it decreased significantly to lower values before and after intubation. Patients in the BIS 40 group needed significantly more fluid replacement and injections of norepinephrine compared with the other groups. No significant changes in heart rate were detected. CONCLUSIONS: Electroencephalogram BIS predicts hemodynamic and arousal reaction resulting from induction of anesthesia and endotracheal intubation. BIS value should be kept at 50 before intubation to ensure safe hemodynamic conditions during induction of anesthesia in cardiac surgical patients.

Anesthesia, Inhalation↗
PubMed2000

Comparison of two different anesthesia regimens in patients undergoing aortocoronary bypass grafting surgery: sufentanil-midazolam versus remifentanil-propofol.

OBJECTIVE: To compare intraoperative hemodynamics and depth of anesthesia using sufentanil-midazolam (SM) versus remifentanil-propofol (RP) anesthesia. DESIGN: Prospective, randomized study. SETTING: Clinical investigation in an urban, university-affiliated hospital. PARTICIPANTS: Forty patients undergoing elective first-time coronary artery bypass graft surgery. INTERVENTIONS: Twenty patients were anesthetized using SM and 20 patients using RP. MEASUREMENTS AND MAIN RESULTS: Hemodynamic monitoring included a 5-lead electrocardiogram, a radial artery catheter, and a pulmonary artery catheter. Depth of anesthesia was assessed using bispectral index (BIS). Data were obtained after induction of anesthesia (T1), after sternotomy (T2), after pericardiotomy (T3), 5 minutes after cardiopulmonary bypass (CPB) (T4), after closure of thorax (T5), and at the end of surgery (T6). The 2 groups were comparable with regard to demographic and perioperative data. There were no significant differences of any hemodynamic parameter at any time between the 2 groups. In both groups, systemic vascular resistance increased at T2 and decreased at T4 from baseline value (p < 0.05). Cardiac index increased at T4 in both groups from baseline value (p < 0.05); 55% of the patients of both groups needed low-dose dobutamine after CPB. During CPB, 40% of the RP patients needed norepinephrine versus 35% of the SM patients. BIS was lower in the RP than in the SM group at T2 and T3 (p < 0.05). BIS values indicating intraoperative awareness were not noted. CONCLUSION: Both anesthesia regimens provided stable hemodynamics and adequate anesthesia in patients undergoing coronary artery bypass graft surgery.

Aged↗
PubMed2000

Chromosome evolution in the genus Poecilimon (Orthoptera, Tettigonioidea, Phaneropteridae).

Cytotaxonomic analysis of 20 species and subspecies of the genus Poecilimon using C-banding pattern, chiasma frequency, and morphometric characteristics of the chromosomes were described. Using a cladistic analysis the chromosome data provided a basis to produce a phylogenetic tree which was compared with a tree based on morphological characters and DNA sequence data. There are important differences in the grouping of data sets to species obtained on the basis of morphology/DNA analyses and that based on chromosomes. The explanation of the differences between C-banding patterns and taxonomic proximity is probably that the C-banding pattern changes quickly as the result of the high degree of variation of constitutive heterochromatin.

Animals↗
PubMed1999

Activation of the GABA(B) receptor inhibits transient lower esophageal sphincter relaxations in dogs.

BACKGROUND & AIMS: Transient lower esophageal sphincter relaxation (TLESR) appears to be the most frequent motor event responsible for gastroesophageal reflux. Because TLESRs are considered to be triggered by activation of gastric mechanoreceptors, and because the gamma-aminobutyric acid type B (GABA(B))-receptor agonist baclofen is known to inhibit transmitter release from mechanosensitive afferents, the effects of baclofen on TLESRs in the dog were assessed. METHODS: A total of 183 recordings of the pharyngeal, esophageal, lower esophageal sphincter, and gastric pressures as well as measurement of esophageal pH were performed in 15 awake dogs. Racemic baclofen, its enantiomers, and the GABA(B)-receptor antagonist CGP36742 were administered before stimulation of TLESRs by a liquid meal and air insufflation. The pharmacodynamics of baclofen were compared with its pharmacokinetics. RESULTS: Baclofen dose-dependently inhibited TLESRs, with a 50% effective dose (ED(50)) of 1.0 micromol/kg after intravenous administration. The maximal inhibition amounted to approximately 80%. Intragastric baclofen was almost equally effective (ED(50), 1.8 micromol/kg), compatible with the complete oral availability of the drug (100%). The inhibitory effect of baclofen resided in the pharmacologically active R enantiomer, and CGP36742 reduced some of the effects of baclofen. CONCLUSIONS: Baclofen is a potent and efficacious inhibitor of TLESRs and reflux in the dog. Activation of the GABA(B) receptor may be a new approach to the treatment of reflux disease.

Animals↗
PubMed1999

GFP-labelling of 26S proteasomes in living yeast: insight into proteasomal functions at the nuclear envelope/rough ER.

26S proteasomes are multisubunit protease complexes that play the central role in the ubiquitin-dependent protein degradation pathway. The proteolytically active core is formed by the 20S proteasome. Regulatory subunits, principally the 19S cap complex, confer the specificity towards ubiquitinated substrates and an ATP-dependence on proteolysis. Green fluorescence protein (GFP)-tagged versions of either an alpha-subunit of the 20S core or an ATPase subunit of the 19S cap complex were functionally incorporated into the protease complex, thus allowing to monitor the subcellular distribution of 26S proteasomes in living yeast. Our localization studies suggest that proteasomal proteolysis mainly occurs at the nuclear envelope (NE)/rough ER. Implications of proteasomal functions at the NE/rough ER are discussed in the context of published work on ER degradation and with regard to possible targeting mechanisms.

Adenosine Triphosphatases↗
PubMed1999

Influence of different intragastric stimuli on triggering of transient lower oesophageal sphincter relaxation in the dog.

Gastro-oesophageal reflux in the dog is mainly caused by transient lower oesophageal sphincter relaxation (TLOSR), the major stimulus for which is distension of the stomach. The possibility that liquid and/or acid sensors in the proximal stomach reduce the incidence and/or shorten the duration of TLOSR was addressed in the present study. Manometric recordings of the pharynx, oesophagus, lower oesophageal sphincter and stomach were made in awake dogs equipped with an oesophagostomy. TLOSRs were induced by insufflation of air or infusion of liquid nutrients with varying pH. Intragastric distension with air provoked TLOSRs with a significantly shorter duration than those seen after distension with liquid (4.3 +/- 0.5 vs 9.6 +/- 0.3 sec; P < 0.05). There were fewer TLOSRs at high intragastric pH (pH 5.0: 3.1 +/- 0.5/90 min) than at low pH (pH 1.5: 5.5 +/- 0.9/90 min, P < 0.05). Successfully propagated peristalsis following a TLOSR was more common after stimulation with liquid than with air. It can be concluded that there are H(+)-sensing mechanisms in the stomach which stimulate triggering of TLOSR. In addition, the reduced duration of TLOSR during air insufflation shows that the physical state of the distending stimulus can affect the patterning of TLOSR.

Animals↗
PubMed1999

Dynamic cardiomyoplasty in patients with end-stage heart failure: anaesthetic considerations.

Dynamic cardiomyoplasty is used increasingly for patients with chronic heart failure, with approximately 500 cases having been performed. The latissimus dorsi muscle is prepared maintaining its vascular supply and the muscle flap is wrapped around the heart and connected to a cardiomyostimulator. The muscle is later stimulated synchronously with ventricular systole to augment the heart. Our experience of 22 patients with chronic heart failure (NYHA III-IV) undergoing dynamic cardiomyoplasty is described from the anaesthetist's point of view. Two patients are reported as case reports. The challenge is to manage patients with severely impaired left ventricular function, who do not obtain immediate benefit from the operation. Our experience supports the importance of early use of inotropic agents.

Adult↗
PubMed1999

Inhibition of transient LES relaxations and reflux in ferrets by GABA receptor agonists.

Transient lower esophageal sphincter (LES) relaxation is the major mechanism of gastroesophageal reflux. This study uses an established ferret model to evaluate GABA(B) receptor agonists' ability to reduce triggering of transient LES relaxations. One hundred sixty manometric/pH studies were performed on 18 conscious ferrets. In untreated animals, intragastric infusion of 25 ml glucose (pH 3.5) led to 2.0 +/- 0.6 reflux episodes over the first 30 min. Twenty-nine of forty-seven reflux episodes occurred during transient LES relaxation, and 18 occurred after downward drifts (<1 mmHg/s) in basal LES pressure. The GABA(B) receptor agonists baclofen (7 micromol/kg ip), CGP-44532, and SKF-97541 (both ED(50) <0.3 micromol/kg) reduced reflux episodes and transient LES relaxations. The putative peripherally selective GABA(B) receptor agonist 3-aminopropylphosphinic acid (80-240 micromol/kg) was ineffective, as was the GABA(A) receptor agonist muscimol (5 micromol/kg). Baclofen's inhibition of transient LES relaxations and reflux was unaffected by low-affinity GABA(B) receptor antagonists CGP-35348 and CGP-36742 at 100 micromol/kg but was reversed by higher-affinity CGP-54626 and CGP-62349 (0.7 micromol/kg) or by CGP-36742 at 200 micromol/kg. Therefore, GABA(B) receptor inhibition of reflux shows complex pharmacology. Our and other data indicate the therapeutic potential for these drugs.

Animals↗
PubMed1999

The Concept of Docking/Protecting Groups in Biohydroxylation.

A general principle for biohydroxylation, in which time-consuming screening and enrichment techniques are avoided, is demonstrated by the introduction of a docking/protecting group into the substrate. This facilitates acceptance by the microorganism and allows the use of a narrow range of microorganisms, for example Beauveria bassiana ATTC 7159 (B. b.), for the hydroxylation of compounds with diverse structures. After the biohydroxylation, the docking/protecting group is removed (see scheme).

Journal Article↗