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Biomedical subjects

M Aebi

Publications and source records attributed to M Aebi.

14 recordsLinked to original sources

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

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

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

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

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

[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

[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

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

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

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

[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

Intracranial giant cell arteritis.

A case of giant cell arteritis of intracranial vessels diagnosed by autopsy is described. Giant cell arteritis of the proximal basal brain arteries was exceptionally marked in a man of 60 years. The clinical course, laboratory findings and the pathological alterations of the brain and intracranial blood vessels are described. The case is discussed on the basis of the literature on giant cell arteritis with cerebral symptoms as well as on granulomatous giant cells arteritis of the brain. A separation of these two entities does not seem justified.

Autopsy

Oligodendroglioma with a twenty-two year history. Clinicopathological case report.

Clinico-pathologic report of a patient with an oligodendroglioma who ran a 22-year course characterized by focal epileptic seizures of the Jaksonian type. The EEG remained normal for many years. Since the tumor had not been influenced by therapeutic measures, the histologic picture permitted considering some basic problems of origin, growth, and differentiation of oligodendrogliomas.

Adult

[The internal fixator in nontraumatic indications in spinal surgery].

This series includes 59 consecutive patients, 51 of whom had a minimum follow up of 2 years. The diagnosis was mechanical instability in 39, deformity in 11, and infection or tumor in 9 patients. The overall clinical results of the total group were good or fair in 88% of the patients. Pseudarthrosis occurred twice. We had on postoperative infection, one persistent and two reversible neurological complications. We found 13 broken screws and one rod breakage which had no clinical relevance. None of these asymptomatic complications required revision. The internal fixator has a great potential of correction in scoliotic and kyphotic deformities of the spine. It has not been shown to have the same potential in spondylolisthesis. A combined anterior and posterior stabilisation is needed in severe spondylolisthesis. We have found the internal fixator to provide satisfactory stability to allow fusion and good clinical results with a low rate of relevant complications.

Adolescent