Biomedical subjects

M Aebi

Publications and source records attributed to M Aebi.

At least 127 records · Page 7Linked to original sources

PubMed1992

The yeast WBP1 is essential for oligosaccharyl transferase activity in vivo and in vitro.

Asparagine-linked N-glycosylation is a highly conserved and functionally important modification of proteins in eukaryotic cells. The central step in this process is a cotranslational transfer of lipid-linked core oligosaccharides to selected Asn-X-Ser/Thr-sequences of nascent polypeptide chains, catalysed by the enzyme N-oligosaccharyl transferase. In this report we show that the essential yeast protein WBP1 (te Heesen et al., 1991) is required for N-oligosaccharyl transferase in vivo and in vitro. Depletion of WBP1 correlates with a defect in transferring core oligosaccharides to carboxypeptidase Y and proteinase A in vivo. In addition, in vitro N-glycosylation of the acceptor peptide Tyr-Asn-Leu-Thr-Ser-Val using microsomal membranes from WBP1 depleted cells is reduced as compared with membranes from wild-type cells. We propose that WBP1 is an essential component of the oligosaccharyl transferase in yeast.

Alleles↗

PubMed1992

Genetic and physical mapping of the WBP1 locus close to CENV.

The WBP1 locus, encoding an essential component of the N-oligosaccharyl transferase, was mapped both genetically and physically. The gene is located on chromosome V between CENV and gcn4. The distance from CENV sequences is 2 kb.

Amino Acid Sequence↗

PubMed1992

Survivorship analysis of pedicular fixation systems in the treatment of degenerative disorders of the lumbar spine: a comparison of Cotrel-Dubousset instrumentation and the AO internal fixator.

We retrospectively analyzed the frequency and clinical consequences of pedicular fixation system failure in 50 patients who underwent Cotrel-Dubousset transpedicular instrumentation (CDI), and 46 patients who underwent AO internal fixator (IF) instrumentation for similar indications. After 2 years, 14 implants in the CDI group and 13 in the IF group had failed. The overall probability of implant survival was similar in both groups (CDI, 71.9% versus IF, 71.7%). However, more implant failures were associated with nonunion, loss of reduction, and nerve-root compromise in the IF group (four versus none) than in the CDI group. Implant failure usually occurred after solid fusion, and did not significantly affect the short-term clinical results. Therefore, implant failure does not a priori indicate failure of the operation.

Adolescent↗

PubMed1992

Pedicle fixation devices in the treatment of adult lumbar scoliosis.

Segmental pedicle screw instrumentation in adult lumbar scoliosis allows better curve correction and restoration of lumbar lordosis. In a retrospective study, to assess the value of this fixation, 9 patients treated with the AO Internal Fixator and 18 with Cotrel-Dubousset instrumentation were reviewed. Mean age at surgery was 60 years (range, 40-88), and curves were measured between 22 degrees and 82 degrees. At follow-up (mean of 56 months for the AO Internal Fixator and 42 months for Cotrel-Dubousset instrumentation), the average curve correction was better than 50% Overall satisfactory clinical results with pain relief and improved walking distance were noted in 86% of the patients. Using this technique no postoperative deaths or neurologic deficits occurred. Only a few complications and a 4% pseudarthrosis rate could be observed. Our study shows that the age of the patients with degenerative scoliosis is not a contraindication for major surgery. Meticulous posterior spine release before instrumentation is essential for curve correction and bone fusion. Lumbar lordosis is more easily restored with Cotrel-Dubousset instrumentation, which seems to correspond to the incidence of low back pain. Cases with evident neurologic deficits are best treated by additional nerve decompression.

Adult↗

PubMed1992

Interferon regulatory factor-1 (IRF-1) activates the synthetic IRF-1-responsive sequence (GAAAGT)4 in Saccharomyces cerevisiae.

In appropriate mammalian cells, interferon regulatory factor-1 (IRF-1) can activate the virus-responsive element of the IFN-beta promoter (VRE beta") or the synthetic oligonucleotide (GAAAGT)4. The latter contains two copies of the functional equivalent of PRDI, one of the regulatory domains of VRE beta". We prepared yeast strains containing an IRF-1 expression plasmid under the control of the galactose-inducible Gal1 promoter and a reporter plasmid with either (GAAAGT)4, VRE beta", or other test sequences placed upstream of a minimal promoter linked to the beta-galactosidase coding sequence. Upon induction of IRF-1 expression, the (GAAAGT)4-containing promoter was activated, but VRE beta" and all other sequences tested were inactive. Our results showed that IRF-1 belongs to a class of higher eukaryotic transcription factors that can interact with the yeast transcriptional machinery. Our findings also raised the question why the duplicate PRDI-like sequences in (GAAAGT)4 can be activated by IRF-1 synthesized in yeast, but not VRE beta", which also contains at least two PRDI-like sequences.

Base Sequence↗

PubMed1992

[Surgical treatment of spondylolisthesis with mild displacement by pedicular fixation and posterolateral fusion in adults].

Thirty-two consecutive adults with low-grade spondylolisthesis treated by stabilisation with the AO Internal Fixator and posterolateral fusion have been retrospectively reviewed with a mean follow-up time of 4 years (range, 24 to 71 months). There were 17 grade I and 15 grade II spondylolisthesis. Eight patients had degenerative and 24 patients had isthmic spondylolisthesis. An unisegmental fusion was performed in 4 cases, a bisegmental fusion in 25 cases and 3 patients had a multisegmental fusion. There was one deep infection and one nerve root compromise (3 per 100). Satisfactory results were achieved in 84 per 100 of the patients. There was non-union. This study suggests that transpedicular fixation and posterolateral fusion significantly enhances the rate of solid union to an extent which outweighs the risk of neurological complications due to the screw insertion. Fusion in situ in patients with low-grade spondylolisthesis is recommended as well as nerve root revision for all adults with concomitant radioculopathy. However, this review does not specifically support the use of the AO-internal fixator, but rather that of transpedicular fixation in general.

Adult↗

PubMed1992

[Technique of surgical correction of post-traumatic kyphosis].

The correction of posttraumatic kyphosis in the thoracolumbar region almost always requires a combined anterior and posterior approach because of the particular anatomic situation and the pathomorphologic changes. We suggest that the patient be placed in a right lateral decubitus position. This allows dual access to the spine by a posterior midline approach and a retroperitoneal thoracolumbar approach, so that simultaneous anterior and posterior manipulation, correction and stabilization of the spine are possible with no need to turn the patient intraoperatively. Thus, compared with two-or three-stage procedures, the duration of the operation and of stay in hospital can be reduced. This is a retrospective review of the first six patients (average age: 35 years) treated with this approach between 1987 and 1990. All patients suffered from incapacitating back pain that was unresponsive to nonoperative treatment. The surgical procedure was performed at an average of 29 months (range, 5 months to 7 years) after fracture. The average postoperative correction of kyphosis (18 degrees to 45 degrees) was 75%. In addition, two patients had posttraumatic scoliosis (10 degrees and 12 degrees), which was completely corrected. The only complication was partial fracture of a vertebral body in one case, which occurred during the reduction manoeuvre but had no consequences. Three of the patients had complete relief of pain. The remaining three reported persistent pain, although they had good objective clinical and radiological results. The failure to eliminate pain in these patients is thought to be a result of their long-standing (2-7 years) symptomatic posttraumatic deformities. Therefore, we feel that early correction of symptomatic kyphosis is mandatory.

Adult↗

PubMed1991

Analysis of yeast prp20 mutations and functional complementation by the human homologue RCC1, a protein involved in the control of chromosome condensation.

Mutations in the PRP20 gene of yeast show a pleiotropic phenotype, in which both mRNA metabolism and nuclear structure are affected. srm1 mutants, defective in the same gene, influence the signal transduction pathway for the pheromone response. The yeast PRP20/SRM1 protein is highly homologous to the RCC1 protein of man, hamster and frog. In mammalian cells, this protein is a negative regulator for initiation of chromosome condensation. We report the analysis of two, independently isolated, recessive temperature-sensitive prp20 mutants. They have identical G to A transitions, leading to the alteration of a highly conserved glycine residue to glutamic acid. By immunofluorescence microscopy the PRP20 protein was localized in the nucleus. Expression of the RCC1 protein can complement the temperature-sensitive phenotype of prp20 mutants, demonstrating the functional similarity of the yeast and mammalian proteins.

Alleles↗

PubMed1991

Treatment of spondylolysis and spondylolisthesis with Cotrel-Dubousset instrumentation: a preliminary report.

We treated 50 consecutive patients with Cotrel-Dubousset instrumentation (CDI) for symptomatic spondylolisthesis. Average follow-up was 25 months. Fusion in situ was performed in 32 of 44 patients with mild spondylolisthesis, while 12 patients had reduction in conjunction with neural decompression. Two of six patients with severe spondylolisthesis who were treated via a single posterior approach had loss of reduction and nonunion. In another patient a Grade III spondylolisthesis could not be reduced via a posterior approach. Seventy-six percent of the patients had a good clinical result. The rate of solid fusion was 96%. One nerve root compromise recovered completely. One superficial wound infection healed uneventfully. This study suggests that combined anterior and posterior fusion is required for permanent and sufficient correction of severe spondylolisthesis even with CDI. Low-grade spondylolisthesis should be reduced only in conjunction with neural decompression.

Adolescent↗

PubMed1991

Direct anterior fixation of dens fractures with a cannulated screw system.

Anterior screw fixation of dens fractures appears to be an optimal method of treatment for these injuries. Anatomic dens fracture reduction with stable internal screw fixation satisfies the established principles of the AO/ASIF. Iatrogenic trauma is minimized by the use of an anterior surgical approach, and no supplemental bone grafting is required. This procedure is quite prone to complications when performed improperly or in contraindicated situations. The use of meticulous surgical technique along with a newly designed cannulated screw system has evolved this procedure into an established form of treatment at our department. Since 1982, 23 patients were treated with direct screw fixation of dens fractures. The overall rate of fracture union was 92.3%, and fracture resolution averaged 5.5 months. The major complication rate of 17% (4/23) resulted from inappropriate use of this technique. The 11 most recent cases, all of which involved stabilization with cannulated screws, resulted in only a single complication (9%) and an average fracture healing time of 3.5 months. A recommended operative technique for anterior screw fixation of dens fractures will be presented along with a discussion of potential sources of difficulty or failures.

Bone Screws↗

PubMed1991

Treatment of cervical spine injuries with anterior plating. Indications, techniques, and results.

This study analyzed 86 patients who sustained a cervical spine injury and who had 93 anterior surgical interventions of the cervical spine. The average age of the patients was 39 years, the mean follow-up 40 months. Twenty-two patients had predominantly vertebral body fractures (burst or tear-drop fractures) and were treated by bisegmental anterior bone grafting and plating. Sixty-four patients had predominantly posterior lesions, either discoligamentous or osteoligamentous, and were treated by unisegmental bone grafting and plating. Forty-three patients were neurologically intact. There were no relevant complications except in one patient, who needed reoperation because of a secondary redislocation due to a technically insufficient osteosynthesis. The technique of anterior bone grafting and plating is shown to be straight-forward, atraumatic, and reliable for predominantly anterior lesions as well as for posterior injuries when performed properly. This clinical experiences does not support experimental data and earlier clinical work, which advocate posterior surgery over anterior surgery and assert that anterior surgery should not be done in predominantly posterior lesions.

Adult↗

PubMed1991

Application and results of the AO internal fixation system in nontraumatic indications.

The AO internal skeletal fixation system (ISFS) permits posterior spine fixation to be restricted to the vertebrae immediately adjacent to the lesion and allows manipulation of each instrumented vertebra in three planes. In a prospective study to assess the value of this fixation for adult spinal disorders, 68 patients were reviewed. The device was used in spondylolisthesis, postlaminectomy instability, post-traumatic kyphosis, degenerative scoliosis, spinal stenosis, tumors, and infections. A total of 322 transpedicular screws have been inserted without neurologic complication. Satisfactory results were achieved in 88% of the patients, and only four pseudarthroses (6%) occurred. The ISFS provides rigid stabilization to enhance bone graft consolidation and to allow rapid postoperative mobilization in a light external orthosis.

Bone Screws↗

PubMed1991

Atlanto-axial fusion with transarticular screw fixation.

We reviewed 161 patients, from four centres in Switzerland, who had undergone posterior fusion of the upper cervical spine with transarticular screw fixation of the atlanto-axial joints. They were followed up for a mean 24.6 months. The vertebral artery and the medulla escaped injury and only 5.9% of the complications were directly related to the screws. The rate of pseudarthrosis was 0.6%.

Adolescent↗

PubMed1991

An essential 45 kDa yeast transmembrane protein reacts with anti-nuclear pore antibodies: purification of the protein, immunolocalization and cloning of the gene.

A yeast membrane protein was isolated by its binding to tRNA Sepharose column. The 45 kDa protein shares characteristics with rat liver nuclear pore proteins in having reactivity with a monoclonal antibody (RL1) raised against rat liver nuclear pore proteins and by the binding of wheat germ agglutinin (WGA), indicating the presence of N-acetylglucosamine (GlcNAc) moieties. Immunofluorescence microscopy and cell fractionation experiments indicate that the protein is located in the nuclear envelope and the endoplasmic reticulum of the cell. The gene for the 45 kDa protein was cloned using degenerate oligonucleotides derived from the N-terminal protein sequence and confirmed by internal peptide sequences. The gene was named WBP1. The protein coding sequence of the WBP1 gene reveals an ER entry signal peptide and a C-terminal membrane spanning domain. Topological studies indicate that the C-terminus of the protein is located in the cytoplasm. The cytoplasmic tail of the protein contains the K-K-X-X signal known to be sufficient for retention of transmembrane proteins in higher eukaryotic cells. Gene disruption experiments show that the 45 kDa protein is essential for the vegetative life cycle of the yeast cell.

Amino Acid Sequence↗

PubMed1991

[Development in conservatively treated scoliosis in patients with myelomeningocele (patients of the years 1964-1977)].

The advances in urological and neurosurgical management in myelomeningocoele patients have led to an increased survival rate. The extremely complex spinal deformity presents a major treatment challenge. Clinical and radiological evolution of scoliosis treated conservatively for at least 10 years was studied. Eighty-nine myelomeningocoele patients born between 1964 and 1977 were reviewed. Thirty-one (35%) were noted to have scoliosis (10 congenital type, 21 developmental type). All congenital forms showed rapid progression despite brace treatment, often to curvatures in excess of 100 degrees. Among the developmental type, curves detected prior to 10 years (10 cases before 5 years, 6 cases between 6 and 10 years) were rapidly progressive beyond 70 degrees. Curves detected after 10 years (5 patients) never exceeded 30 degrees. Because of this natural history, conservative treatment should be limited to developmental forms less than 50 degrees. Spinal stabilization is indicated in all curvatures over 50 degrees without awaiting adulthood.

Adolescent↗

PubMed1991

[Ventral direct screw fixation in dens fractures].

Direct anterior screw fixation of odontoid fractures is indicated in type II and occasionally type III fractures according to the Anderson and d'Alonzo classification. This fracture treatment follows the generally accepted concepts of surgical treatment of limb fractures. It is direct osteosynthesis of a fracture by screw fixation with interfragmentary compression and differs fundamentally from all other treatment methods in spinal fractures, where the treatment is combined with fusion and definite immobilization of a motion segment. The iatrogenic trauma is minimal by using an anterior surgical approach and no supplemental bone grafting is required. The postoperative care is very simple, and the fusionless fracture fixation has a better functional outcome. With the introduction of cannulated screws, which can be inserted over K-wires, the surgical procedure has been further simplified and minimizes the peroperative risks. After initial complications in the first series of 17 patients, the most recent 15 cases were without complications. This stresses the fact that this surgical procedure should only be done by spine surgeons who are familiar with the upper cervical spine and osteosynthesis techniques.

Adolescent↗

PubMed1990

Purification and properties of yeast ATP (CTP):tRNA nucleotidyltransferase from wild type and overproducing cells.

ATP (CTP):tRNA nucleotidyltransferase (EC 2.7.7.25) has been purified from wild type cells of the yeast Saccharomyces cerevisiae, as well as from a strain that overproduces the activity. Purification from the wild type strain was accomplished with a multistep protocol including ammonium sulfate fractionation, anion exchange chromatography, gel filtration, and affinity chromatography. The purified enzyme is near homogeneity as evidenced by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and at 59,000 Da is smaller than reported previously. A similar molecular mass is obtained by gel filtration demonstrating that the enzyme is active as a monomer. The pH optimum for the enzyme is around 9.5. The apparent KM values for ATP and CTP were determined to be 5.6 x 10(-4) M and 1.8 x 10(-4) M, respectively. Purification of the enzyme from the overproducing cells was accomplished by a three step protocol with high yield. The nucleotidyltransferase activity from the overproducing cells had a KM for CTP indistinguishable from that of the wild type enzyme, and the mobility of the protein on sodium dodecyl sulfate gels was the same regardless of the source. Thus, the overproducing strain appears to be a good source for large amounts of yeast nucleotidyltransferase for further biochemical and structural studies.

Chromatography↗

PubMed1990

Isolation of a temperature-sensitive mutant with an altered tRNA nucleotidyltransferase and cloning of the gene encoding tRNA nucleotidyltransferase in the yeast Saccharomyces cerevisiae.

We have isolated a yeast mutant, ts352, that is temperature-sensitive for growth. The mutation has a general effect on mRNA metabolism and a specific effect on tRNA biosynthesis. Cells shifted to the nonpermissive temperature accumulate tRNAs that are shorter than mature tRNAs. The increased ability of these tRNAs to accept ATP demonstrates that growth of the ts352 mutant at the nonpermissive temperature results in accumulation of tRNA with defective 3' ends. The activity of ATP (CTP):tRNA-specific tRNA nucleotidyltransferase can readily be measured in extracts from wild type but not mutant cells. We have cloned and sequenced the wild type allele of the ts352 gene and find significant similarity between the yeast protein sequence predicted from the DNA sequence and the protein predicted from the sequence of the Escherichi coli tRNA nucleotidyltransferase gene. Expression of the yeast gene on a multicopy plasmid increases the activity of the tRNA nucleotidyltransferase in extracts. We conclude that the defect in the ts352 mutant is in the gene coding for yeast tRNA nucleotidyltransferase and that we have isolated the yeast gene that codes for this enzyme.

Amino Acid Sequence↗