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Biomedical subjects

A Schweizer

Publications and source records attributed to A Schweizer.

At least 73 records · Page 4Linked to original sources
PubMed1994

Influence of duration of lateral decubitus on the spread of hyperbaric tetracaine during spinal anesthesia: a prospective time-response study.

Searching for a differential spinal block between dependent and nondependent sides, we evaluated a prospective randomized time-response study of the influence of the duration of lateral decubitus on the spread of hyperbaric local anesthetic solution during spinal anesthesia in 60 patients undergoing lower limb surgery. In a lateral position with the operated side dependent, all patients received 12 mg of lyophilized tetracaine with 0.2 mg epinephrine in 2.5 mL 10% dextrose and were randomized into four groups according to the duration of lateral decubitus after spinal injection: Group 0, patients immediately turned supine after spinal injection; Group 6, 6 min in lateral decubitus then supine; Group 12, 12 min in lateral decubitus then supine; Group 18, 18 min in lateral decubitus then supine. There was no difference in maximum sensory level between both sides in the same group nor between the four groups. In all four groups a comparable number of patients had a Grade 4 motor block on the dependent as well as on the nondependent side. A positive correlation found between duration of lateral decubitus and duration of sensory block on the dependent side suggested a preferential spread of hyperbaric local anesthetics. This differential spread was confirmed by the positive correlation between the duration of lateral decubitus and the difference in duration between dependent and nondependent sides of both sensory and motor blocks. However, because of the minimal differences between groups, we believe there is no reason to routinely maintain patients in the lateral position after performing spinal anesthesia.

Adult↗
PubMed1993

Characterization of a novel 63 kDa membrane protein. Implications for the organization of the ER-to-Golgi pathway.

Owing to the lack of appropriate markers the structural organization of the ER-to-Golgi pathway and the dynamics of its membrane elements have been elusive. To elucidate this organization we have taken a monoclonal antibody (mAb) approach. A mAb against a novel 63 kDa membrane protein (p63) was produced that identifies a large tubular network of smooth membranes in the cytoplasm of primate cells. The distribution of p63 overlaps with the ER-Golgi intermediate compartment, defined by a previously described 53 kDa marker protein (here termed ERGIC-53), as visualized by confocal laser scanning immunofluorescence microscopy and immunoelectron microscopy. The p63 compartment mediates protein transport from the ER to Golgi apparatus, as indicated by partial colocalization of p63 and vesicular stomatitis virus G protein in Vero cells cultured at 15 degrees C. Low temperatures and brefeldin A had little effect on the cellular distribution of p63, suggesting that this novel marker is a stably anchored resident protein of these pre-Golgi membranes. p63 and ERGIC-53 were enriched to a similar degree by the same subcellular fractionation procedure. These findings demonstrate an unanticipated complexity of the ER-Golgi interface and suggest that the ER-Golgi intermediate compartment defined by ERGIC-53 may be part of a greater network of smooth membranes.

Animals↗
PubMed1993

A reversibly palmitoylated resident protein (p63) of an ER-Golgi intermediate compartment is related to a circulatory shock resuscitation protein.

The recently identified 63 kDa membrane protein, p63, is a resident protein of a membrane network interposed in between rough ER and Golgi apparatus. To characterize p63 at the molecular level a 2.91 kb cDNA encoding p63 has been isolated from a human placenta lambda gt10 cDNA library. Sequence analysis of tryptic peptides prepared from isolated p63 confirmed the identify of the cloned gene. The translated amino acid sequence consists of 601 amino acids (65.8 kDa) with a single putative membrane-spanning region and a N-terminal cytoplasmic domain of 106 amino acids. The human p63 cDNA exhibits a high level of sequence identify to the pig hepatic cDNA 3AL (accession number M27092) whose expression is enhanced after resuscitation from circulatory shock. An additional remarkable feature of p63 is that it becomes reversibly palmitoylated when intracellular protein transport is blocked by the drug brefeldin A. Overexpression of p63 in COS cells led to the development of a striking tubular membrane network in the cytoplasm. This suggests that the protein may be determinant for the structure of the p63 compartment.

Amino Acid Sequence↗
PubMed1992

The endoplasmic reticulum-Golgi intermediate compartment.

The recent identification of an endoplasmic reticulum-Golgi intermediate compartment has added to the complexity of the structural and functional organization of the early secretory pathway. Protein sorting along the endoplasmic reticulum-Golgi pathway depends on different signals and mechanisms, some of which guarantee recycling from various levels of the Golgi apparatus to biosynthetically earlier compartments.

Animals↗
PubMed1991

Pharmacological properties of five diclofenac metabolites identified in human plasma.

Five metabolites of diclofenac sodium (Voltarol) have been identified in human plasma. All five metabolites were more than 50 times less potent than diclofenac in inhibiting PGE2 production in zymosan-stimulated mouse macrophages and LTC4 synthesis was not inhibited in these cells. Anti-inflammatory activity (adjuvant arthritis and carragheenan-induced paw oedema in rats) and analgesic activity (phenyl-p-benzoquinone writhing, mouse) of the metabolites were at least 10 times lower when compared to diclofenac. There was a good correlation between in vitro PGE2 inhibition and in vivo activities for diclofenac and its metabolites indicating that inhibition of prostaglandin synthesis is a major mechanism responsible for their pharmacological actions.

Animals↗
PubMed1991

The isolated ER-Golgi intermediate compartment exhibits properties that are different from ER and cis-Golgi.

A procedure has been established in Vero cells for the isolation of an intermediate compartment involved in protein transport from the ER to the Golgi apparatus. The two-step subcellular fractionation procedure consists of Percoll followed by Metrizamide gradient centrifugation. Using the previously characterized p53 as a marker protein, the average enrichment factor of the intermediate compartment was 41. The purified fraction displayed a unique polypeptide pattern. It was largely separated from the rough ER proteins ribophorin I, ribophorin II, BIP, and protein disulfide isomerase, as well as from the putative cis-Golgi marker N-acetylglucosamine-1-phosphodiester-alpha-N-acetylglucosaminidase, the second of the two enzymes generating the lysosomal targeting signal mannose-6-phosphate. The first enzyme, N-acetylglucosaminylphosphotransferase, for which previous biochemical evidence had suggested both a pre- and a cis-Golgi localization in other cell types, cofractionated with the cis-Golgi rather than the intermediate compartment in Vero cells. The results suggest that the intermediate compartment defined by p53 has unique properties and does not exhibit typical features of rough ER and cis-Golgi.

Animals↗
PubMed1991

Comparison of hypobaric, hyperbaric, and isobaric solutions of bupivacaine during continuous spinal anesthesia.

This study was designed to compare the anesthetic properties of hypobaric bupivacaine with those of isobaric and hyperbaric solutions when administered in the supine position in an elderly population undergoing hip surgery using continuous spinal anesthesia. Plain bupivacaine (0.5%) was mixed with equal volumes of 10% dextrose (hyperbaric), 0.9% NaCl (isobaric), or distilled water (hypobaric) to obtain 0.25% solutions. In a double-blind fashion, all patients received 3 mL (7.5 mg) of their particular solution injected through the spinal catheter in the horizontal supine position. The sensory level obtained in the hyperbaric group (median, T4; range, T3-L3) was significantly higher than in both the isobaric (median, T11; range, T6-L1) and hypobaric (median, L1; range, T4-L3) groups. A motor blockade of grade 2 or 3 was obtained in 14 of 15 and 12 of 15 patients in, respectively, the hyperbaric and isobaric groups, but only in 8 of 15 patients in the hypobaric group. After the initial injection of 3 mL (7.5 mg), a sensory level of T10 and a motor blockade of grade 2 or 3 was obtained in 14 of 15, 5 of 15, and 3 of 15 patients in the hyperbaric, isobaric, and hypobaric groups, respectively. All remaining patients received 1 or 2 additional milliliters (2.5-5 mg) and achieved these required anesthetic conditions, except for one patient in the hyperbaric group and eight patients in the hypobaric group in whom anesthesia was achieved with hyperbaric tetracaine. The decrease in mean arterial pressure was significantly more severe in the hyperbaric (30%) than in either the isobaric (18%) or hypobaric (14%) groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1990

Microtubule-dependent retrograde transport of proteins into the ER in the presence of brefeldin A suggests an ER recycling pathway.

Characteristics of brefeldin A (BFA)-induced redistribution of Golgi proteins into the endoplasmic reticulum (ER) and its relationship to an ER retrieval pathway were investigated. Retrograde movement of Golgi proteins into the ER occurred via long, tubulovesicular processes extending out of the Golgi along microtubules. Microtubule-disrupting agents (i.e., nocodazole), energy poisons, and reduced temperatures inhibited this pathway. In BFA-treated cells Golgi proteins appeared to cycle between the ER and an intermediate compartment marked by a 53 kd protein. Addition of nocodazole disrupted this dynamic cycle by preferentially inhibiting retrograde movement, causing Golgi proteins to accumulate in the intermediate compartment. In the absence of BFA, such an ER cycling pathway appeared to be followed normally by the 53 kd protein but not by Golgi proteins, as revealed by temperature shift experiments. We propose that BFA induces the interaction of the Golgi with an intermediate "recycling" compartment that utilizes a microtubule-dependent pathway into the ER.

Animals↗
PubMed1990

Quantitative radiographic diagnosis of osteo-arthritis of the knee-joint in the C57BL mouse.

Comparative histopathological and radiographic investigations in the C57BL mouse model of spontaneous osteo-arthritis of the knee-joint indicate that there is a relation between quantitative radiographic diagnosis and semiquantitative histopathological diagnosis. Statistical analysis based on a set of quantitative radiographic parameters of the mouse knee-joint shows that the greater part of the radiographic information reflecting the histopathological degree of the osteo-arthritis is contained in the projection areas of the lateral and medial meniscus: progression of the osteo-arthritic process is accompanied with enlargement of the menisci. On the basis of these observations, a radiography score for the osteo-arthritis has been constructed, which consists of a weighted sum of the - suitably transformed - projection areas of the lateral and medial meniscus. In addition to the size of the menisci, the width of the joint space is also a useful quantitative parameter of osteo-arthritis of the mouse knee-joint.

Animals↗
PubMed1990

Identification of an intermediate compartment involved in protein transport from endoplasmic reticulum to Golgi apparatus.

We have studied the role of a previously described tubulovesicular compartment near the cis-Golgi apparatus in endoplasmic reticulum (ER)-to-Golgi protein transport by light and immunoelectron microscopy in Vero cells. The compartment is defined by a 53-kDa transmembrane protein designated p53. When transport of the vesicular stomatitis virus strain ts045 G protein was arrested at 39.5 degrees C, the G protein accumulated in the ER but had access to the p53 compartment. At 15 degrees C, the G protein was exported from the ER into the p53 compartment which formed a compact structure composed of vesicular and tubular profiles in close proximity to the Golgi. Upon raising the temperature to 32 degrees C, the G protein migrated through the Golgi apparatus while the p53 compartment resumed its normal structure again. These results establish the p53 compartment as the 15 degrees C intermediate of the ER-to-Golgi protein transport pathway.

Animals↗
PubMed1989

Pseudomonas aeruginosa outer membrane lipoprotein I gene: molecular cloning, sequence, and expression in Escherichia coli.

Lipoprotein I (OprI) is one of the major proteins of the outer membrane of Pseudomonas aeruginosa. Like porin protein F (OprF), it is a vaccine candidate because it antigenically cross-reacts with all serotype strains of the International Antigenic Typing Scheme. Since lipoprotein I was expressed in Escherichia coli under the control of its own promoter, we were able to isolate the gene by screening a lambda EMBL3 phage library with a mouse monoclonal antibody directed against lipoprotein I. The monocistronic OprI mRNA encodes a precursor protein of 83 amino acid residues including a signal peptide of 19 residues. The mature protein has a molecular weight of 6,950, not including bound glycerol and lipid. Although the amino acid sequences of protein I of P. aeruginosa and Braun's lipoprotein of E. coli differ considerably (only 30.1% identical amino acid residues), peptidoglycan in E. coli, are identical. Using lipoprotein I expressed in E. coli, it can now be tested whether this protein alone, without P. aeruginosa lipopolysaccharide contaminations, has a protective effect against P. aeruginosa infections.

Amino Acid Sequence↗
PubMed1989

Anticoagulation by ancrod for carbon dioxide removal by extracorporeal membrane lung in the dog.

Ten dogs were subjected to defibrinogenation with an intravenous perfusion of ancrod (1 unit/kg) (Arvin, Knoll AG, Ludwigshafen, Federal Republic of Germany) over a 2 1/2 hour period. Six of them were subjected to extracorporeal elimination of carbon dioxide with a polypropylene membrane lung by means of veno-venous bypass. The remaining four dogs did not undergo extracorporeal circulation and served as control subjects. In both groups, ancrod administration itself resulted in a marked drop in alpha 2-antiplasmin (33% and 67%, respectively, of the baseline values) and in slight but significant decreases in factor II and plasminogen activities of 25% and 20%, respectively (p less than 0.05), in the group subjected to carbon dioxide removal. There were no significant changes in platelet number or factor V and antithrombin III activities. During the 6-hour bypass period, platelet count and antithrombin III and factor II and V levels decreased significantly. No bleeding was observed. Histologic examination of lung biopsy tissue showed no pathologic features. Analysis of the membrane of the artificial lungs revealed no fibrin deposits. In the control group, except for a drop in alpha 2-antiplasmin levels (54%), no significant changes in hemostatic parameters occurred during the corresponding 6 hours. We conclude that, despite the drop in coagulation factors and in alpha 2-antiplasmin activity during bypass, ancrod can be considered as a valuable alternative anticoagulant for extracorporeal carbon dioxide removal.

Ancrod↗
PubMed1989

The pharmacological profile of CGP 28238, a novel highly potent anti-inflammatory compound.

CGP 28238 (6-(2,4-difluorophenoxy)-5-methylsulfonylamino-1-indanone ) exhibits very potent anti-inflammatory activity in rat adjuvant arthritis (ED40 = 0.05 mg/kg, p.o.) and pronounced analgesic and antipyretic activity in acute models in mice and rats (ED50 2-5 mg/kg, p.o.), but has clear advantages over reference NSAIDs with respect to gastro-intestinal tolerability. Threshold doses for gastro-intestinal ulcerogenicity in rats after single and repeated (10x) doses were found to be 30 mg/kg, p.o., and prostaglandin (PGE2) production in rat gastric and ileal mucosa was only marginally inhibited (ED50 greater than 30 mg/kg, p.o.). On the other hand, PGE2 production in rat inflammatory exudate and thromboxane synthesis in rat blood were inhibited with ED50 values of less than or equal to 2 mg/kg, p.o. Although CGP28238 does not inhibit cyclooxygenase in bovine seminal vesicle microsomal preparations (IC50 greater than 10(-3) mol/l), potent inhibition of prostaglandin synthesis was shown in various in vitro systems using human and animal cells with IC50 values of less than 10(-6) mol/l. IL-1-stimulated bone resorption and PGE2 production in murine calvarial cultures were inhibited with IC50 values of 3 x 10(-7) and 2 x 10(-8) mol/l, respectively. 5-Lipoxygenase (murine macrophages), phospholipase A2 (human PMN) and phospholipase C (human platelets) were not inhibited. CGP 28238 may represent a novel highly potent anti-inflammatory compound with improved gastro-intestinal safety.

Analgesics↗
PubMed1988

Molecular consequences of truncations of the first exon for in vitro splicing of yeast actin pre-mRNA.

A defined minimum length of the first exon is required for the generation of spliced products from a synthetic yeast actin mRNA-precursor in vitro. If the first exon is 1, 2, 3 or 5 nucleotides long, only the first step of the splicing reaction can take place. A transcript starting with the first nucleotide of the intron does not get converted into any of the normally obtained splicing products or intermediates. On the other hand, spliceosome assembly does not depend on the presence of a first exon.

Actins↗