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Biomedical subjects

M Aebi

Publications and source records attributed to M Aebi.

At least 19 recordsLinked to original sources
PubMed2002

A European spine registry.

New joint replacement registries are being widely implemented across national and international organizations. The need for a continuous long-term post-market surveillance of implants has been recognized, and has become increasingly important to ensure the quality of prosthetic components. Registry data with large case numbers represent an acceptable alternative to controlled randomized clinical trials, which are often difficult to conduct in orthopedic surgery. The variety of implants and procedures in spinal surgery not only induces the same need for long-term monitoring of post-surgical product performance as in the joint replacement subspecialties, but also renders essential the establishment of a comprehensive spine registry for all major pathologies and interventions. In cooperation with the M.E. Müller Institute for Evaluative Research in Orthopedic Surgery (MEM-CED) at the University of Berne, Switzerland, the Spine Society of Europe (SSE) has launched Spine Tango: the first modular and multilevel European online registry for spinal surgery. Within Spine Tango, the major challenge in registry design and structure is the definition of and agreement upon a core set of questions as a common European dataset. Additional questions for national or individual interest can also be dynamically added to the core dataset. An automated implant tracking system has also been setup, which allows highly precise product documentation without additional work for clinical staff members.

Europe↗
PubMed2001

The CWH8 gene encodes a dolichyl pyrophosphate phosphatase with a luminally oriented active site in the endoplasmic reticulum of Saccharomyces cerevisiae.

Mutations in the CWH8 gene, which encodes an ER transmembrane protein with a phosphate binding pocket in Saccharomyces cerevisiae, result in a deficiency in dolichyl pyrophosphate (Dol-P-P)-linked oligosaccharide intermediate synthesis and protein N-glycosylation (van Berkel, M. A., Rieger, M., te Heesen, S., Ram, A. F., van den Ende, H., Aebi, M., and Klis, F. M. (1999) Glycobiology 9, 243-253). Genetic, enzymological, and topological approaches were taken to investigate the potential role of Cwh8p in Dol-P-P/Dol-P metabolism. Overexpression of Cwh8p in the yeast double mutant strain, lacking LPP1/DPP1, resulted in an impressive increase in Dol-P-P phosphatase activity, a relatively small increase in Dol-P phosphatase activity, but no change in phosphatidate (PA) phosphatase activity in microsomal fractions. The Dol-P-P phosphatase encoded by CWH8 is optimally active in the presence of 0.5% octyl glucoside and relatively unstable in Triton X-100, distinguishing this activity from the lipid phosphatases encoded by LPP1 and DPP1. Stoichiometric amounts of P(i) and Dol-P are formed during the enzymatic reaction indicating that Cwh8p cleaves the anhydride linkage in Dol-P-P. Membrane fractions from Sf-9 cells expressing Cwh8p contained a 30-fold higher level of Dol-P-P phosphatase activity, a slight increase in Dol-P phosphatase activity, but no increase in PA phosphatase relative to controls. This is the first report of a lipid phosphatase that hydrolyzes Dol-P-P/Dol-P but not PA. In accord with this enzymatic function, Dol-P-P accumulated in cells lacking the Dol-P-P phosphatase. Topological studies using different approaches indicate that Cwh8p is a transmembrane protein with a luminally oriented active site. The specificity, subcellular location, and topological orientation of this novel enzyme are consistent with a role in the re-utilization of the glycosyl carrier lipid for additional rounds of lipid intermediate biosynthesis after its release during protein N-glycosylation reactions.

Animals↗
PubMed2001

Elevated synthetic activity in the convex side of scoliotic intervertebral discs and endplates compared with normal tissues.

STUDY DESIGN: We measured concentrations of specific molecules reflecting matrix synthesis and degradation in normal and scoliotic intervertebral discs and endplates. OBJECTIVES: The aim of this work was to quantitate markers of matrix turnover in normal versus adolescent idiopathic scoliotic intervertebral discs and cartilaginous endplates. SUMMARY OF BACKGROUND DATA: Changes in the intervertebral disc and endplate composition have been implicated as possible etiologic factors in the pathogenesis of adolescent idiopathic scoliosis. To better understand this process, it is important to compare the turnover of matrix components in scoliotic and normal intervertebral disc and endplate tissues. This comparison may help to improve our understanding of the role that disc and endplate tissues may play in the induction and/or progression of idiopathic scoliosis. METHODS: Fifteen scoliotic and 17 normal intervertebral discs and endplates were analyzed for their water, collagen, proteoglycan, and protein content. In addition, newly synthesized aggrecan and collagen Types I and II were measured. Percent total denatured collagen was also determined. RESULTS: The total collagen content was significantly lower in the scoliotic anulus and endplate regions, whereas glycosaminoglycan (GAG) content was significantly lower in the scoliotic endplates and nucleus regions. Conversely, total protein content was significantly higher in scoliotic endplates and elevated in scoliotic nucleus regions. Water content was significantly lower in the scoliotic anulus and endplate regions. When comparing the concave and convex regions of scoliotic endplates, there was no significant difference in concentration of any matrix component. The major difference in the synthetic marker levels relates to the synthesis of Type II collagen, which was higher in the nucleus, anulus, and endplate regions of scoliotic discs than in the corresponding regions of normal tissues. By contrast, the percent total denatured collagen was significantly elevated in the nucleus of normal tissues compared with the scoliotic ones. CONCLUSIONS: The higher collagen Type II synthetic levels and increased total protein content with no matrix turnover suggest that scoliotic changes are due to an altered and ineffective synthetic response to a pathologic mechanical environment.

Adolescent↗
PubMed2001

Intracellular functions of N-linked glycans.

N-linked oligosaccharides arise when blocks of 14 sugars are added cotranslationally to newly synthesized polypeptides in the endoplasmic reticulum (ER). These glycans are then subjected to extensive modification as the glycoproteins mature and move through the ER via the Golgi complex to their final destinations inside and outside the cell. In the ER and in the early secretory pathway, where the repertoire of oligosaccharide structures is still rather small, the glycans play a pivotal role in protein folding, oligomerization, quality control, sorting, and transport. They are used as universal "tags" that allow specific lectins and modifying enzymes to establish order among the diversity of maturing glycoproteins. In the Golgi complex, the glycans acquire more complex structures and a new set of functions. The division of synthesis and processing between the ER and the Golgi complex represents an evolutionary adaptation that allows efficient exploitation of the potential of oligosaccharides.

Animals↗
PubMed2001

Congenital disorders of glycosylation: genetic model systems lead the way.

N-linked glycosylation is the most frequent modification of secretory proteins in eukaryotic cells. The highly conserved glycosylation process is initiated in the endoplasmic reticulum (ER), where the Glc(3)Man(9)GlcNAc(2) oligosaccharide is assembled on the lipid carrier dolichylpyrophosphate and then transferred to selected asparagine residues of polypeptide chains. In recent years, several inherited human diseases, congenital disorders of glycosylation (CDG), have been associated with deficiencies in this pathway. The ER-associated glycosylation pathway has been studied in the budding yeast Saccharomyces cerevisiae, and this model system has been invaluable in elucidating the molecular basis of novel types of CDG.

Animals↗
PubMed2001

In vitro spore formation and completion of the asexual life cycle of Neozygites parvispora, an obligate biotrophic pathogen of thrips.

Capilliconidia, the asexual secondary spores of Neozygites parvispora (Zygomycetes, Entomophthorales) were produced in vitro either by entrapment of vegetative cells (hyphal bodies) in alginate pellets or after plating them onto water agar. Cultivation of the fungus for 3 days in a medium lacking hemolymph increased spore production 30 to 40-fold, and about 10% of the cells produced capilliconidia. The in vitro produced capilliconidia were infectious to Thrips tabaci and the fungus was reisolated from infected insects, thus completing its asexual life cycle under laboratory conditions. A decrease in capilliconidia production and a modification of the number of nuclei per spore were observed for isolates cultivated in vitro for more than 2 months, but subsequent host passages restored and increased sporulation efficiency without influencing the number of nuclei. Fungal cultures were stored at - 80 degrees C for up to 7 months, and the capability to sporulate and infect T. tabaci was preserved. A bioassay procedure for infecting T. tabaci with N. parvispora is described, the first mycosed insects dying usually after 8 d of incubation.

Alginates↗
PubMed2001

Htm1p, a mannosidase-like protein, is involved in glycoprotein degradation in yeast.

Misfolded proteins are recognized in the endoplasmic reticulum (ER), transported back to the cytoplasm and degraded by the proteasome. Processing intermediates of N-linked oligosaccharides on incompletely folded glycoproteins have an important role in their folding/refolding, and also in their targeting to proteolytic degradation. In Saccharomyces cerevisiae, we have identified a gene coding for a non-essential protein that is homologous to mannosidase I (HTM1) and that is required for degradation of glycoproteins. Deletion of the HTM1 gene does not affect oligosaccharide trimming. However, deletion of HTM1 does reduce the rate of degradation of the mutant glycoproteins such as carboxypeptidase Y, ABC-transporter Pdr5-26p and oligosaccharyltransferase subunit Stt3-7p, but not of mutant Sec61-2p, a non-glycoprotein. Our results indicate that although Htm1p is not involved in processing of N-linked oligosaccharides, it is required for their proteolytic degradation. We propose that this mannosidase homolog is a lectin that recognizes Man8GlcNAc2 oligosaccharides that serve as signals in the degradation pathway.

ATP-Binding Cassette Transporters↗
PubMed2001

An alternative cis-isoprenyltransferase activity in yeast that produces polyisoprenols with chain lengths similar to mammalian dolichols.

Dolichyl monophosphate (Dol-P) is a polyisoprenoid glycosyl carrier lipid essential for the assembly of a variety of glycoconjugates in the endoplasmic reticulum of eukaryotic cells. In yeast, dolichols with chain lengths of 14--17 isoprene units are predominant, whereas in mammalian cells they contain 19--22 isoprene units. In this biosynthetic pathway, t,t-farnesyl pyrophosphate is elongated to the appropriate long chain polyprenyl pyrophosphate by the sequential addition of cis-isoprene units donated by isopentenyl pyrophosphate with t,t,c-geranylgeranyl pyrophosphate being the initial intermediate formed. The condensation steps are catalyzed by cis-isoprenyltransferase (cis-IPTase). Genes encoding cis-IPTase activity have been identified in Micrococcus luteus, Escherichia coli, Arabidopsis thaliana, and Saccharomyces cerevisiae (RER2). Yeast cells deleted for the RER2 locus display a severe growth defect, but are still viable, possibly due to the activity of an homologous locus, SRT1. The dolichol and Dol-P content of exponentially growing revertants of RER2 deleted cells (Delta rer2) and of cells overexpressing SRT1 have been determined by HPLC analysis. Dolichols and Dol-Ps with 19--22 isoprene units, unusually long for yeast, were found, and shown to be utilized for the biosynthesis of lipid intermediates involved in protein N-glycosylation. In addition, cis-IPTase activity in microsomes from Delta rer2 cells overexpressing SRT1 was 7- to 17-fold higher than in microsomes from Delta rer2 cells. These results establish that yeast contains at least two cis-IPTases, and indicate that the chain length of dolichols is determined primarily by the enzyme catalyzing the chain elongation stage of the biosynthetic process.

Alkyl and Aryl Transferases↗
PubMed2001

Isolation and in vitro cultivation of the aphid pathogenic fungus Entomophthora planchoniana.

Entomophthora planchoniana is an important fungal pathogen of aphids. Although Entomophthora chromaphidis has been considered a synonym for E. planchoniana, the two species are now separated, and E. planchoniana is reported not to grow in vitro. In this paper, we describe for the first time the isolation and cultivation of this species. Entomophthora planchoniana was isolated from a population of Ovatus crataegarius (Homoptera, Aphididae), which was infected by E. planchoniana only. The isolates did not sporulate, but the sequence of the small subunit rDNA and the restriction fragment length polymorphism patterns of the first part of the large subunit rDNA and the ITS II region confirm that the isolates were E. planchoniana. The isolated fungus grew in a medium consisting of Grace's insect cell culture medium supplemented with lactalbumin hydrolysate, yeastolate, and 10% fetal bovine serum or in GLEN medium with 10% fetal bovine serum. Vegetative cells of E. planchoniana were long and club-shaped and did not stain with Calcofluor, thus suggesting that they were protoplasts.

Animals↗
PubMed2001

MPDU1 mutations underlie a novel human congenital disorder of glycosylation, designated type If.

Deficiencies in the pathway of N-glycan biosynthesis lead to severe multisystem diseases, known as congenital disorders of glycosylation (CDG). The clinical appearance of CDG is variable, and different types can be distinguished according to the gene that is altered. In this report, we describe the molecular basis of a novel type of the disease in three unrelated patients diagnosed with CDG-I. Serum transferrin was hypoglycosylated and patients' fibroblasts accumulated incomplete lipid-linked oligosaccharide precursors for N-linked protein glycosylation. Transfer of incomplete oligosaccharides to protein was detected. Sequence analysis of the Lec35/MPDU1 gene, known to be involved in the use of dolichylphosphomannose and dolichylphosphoglucose, revealed mutations in all three patients. Retroviral-based expression of the normal Lec35 cDNA in primary fibroblasts of patients restored normal lipid-linked oligosaccharide biosynthesis. We concluded that mutations in the Lec35/MPDU1 gene cause CDG. This novel type was termed CDG-If.

Amino Acid Sequence↗
PubMed2000

Effect of implant design and endplate preparation on the compressive strength of interbody fusion constructs.

STUDY DESIGN: A human cadaveric study on the compressive strength of different lumbar interbody fusion implants and endplate preparation techniques was performed. OBJECTIVES: To assess the axial compressive strength of an implant with peripheral endplate contact as opposed to full surface contact, and to assess whether removal of the central bony endplate affects the axial compressive strength. SUMMARY OF BACKGROUND DATA: The compressive strength of interbody fusion constructs has been compared between implants and bone grafts. Neither implant design nor endplate preparation has been shown to affect strength. Removal of the central bony endplate for bone grafts was noted to improve graft incorporation but also to facilitate subsidence. METHODS: A total of 44 vertebrae were tested in four experimental groups by combining two interbody implants (full-surface vs peripheral surface support) with two endplate preparation techniques (intact bony endplate vs removal of the central bony endplate). Specimens were tested to ultimate compressive failure using a 50 N/second ramped load. Yield strength and ultimate compressive strength were compared between groups using two-factor analysis of covariance. A P value less than 0.05 was considered significant. Stepwise linear regressions assessed the predictive power of age, bone mineral content, and the implant's normalized endplate coverage on yield strength and ultimate compressive strength. RESULTS: Neither implant design nor endplate preparation technique affected yield strength or ultimate compressive strength. Age, bone mineral content, and the normalized endplate coverage were strong predictors of yield strength (P < 0. 0001; r2 = 0.459) and ultimate compressive strength (P < 0.0001; r2 = 0.510). CONCLUSIONS: An implant with only peripheral support resting on the apophyseal ring offers axial mechanical strength similar to that of an implant with full support. Neither supplementary struts nor a solid implant face has any additional mechanical advantage, but reduces graft-host contact area. Removal of the central bony endplate is recommended because it does not affect the compressive strength and promotes graft incorporation.

Adolescent↗
PubMed2000

Minimally invasive bone harvesting tools.

The most readily available source for autologous bone graft used in spinal fusion (the gold standard) is the iliac crest. However, the open surgical approach for harvesting corticocancellous iliac bone is associated with a marked increase in morbidity. This study suggests two alternatives to the traditional open harvesting procedure. For anterior interbody fusion procedures using a cage, the autologous bone is harvested regionally from a neighboring vertebral body. Alternatively, using minimally invasive techniques, a custom bone graft harvester with a flexible tube and cutting tip allows harvesting of autologous bone from a single entry point at the iliac crest. The effect on the mechanical strength of a lumbar vertebra of removing a cylindrical regional bone graft was studied in a cadaveric model. The bone defect was filled using three different filler materials: a porous tri-calcium phosphate plug, a porous tantalum plug, and a self-setting calcium phosphate cement. After plug removal, the vertebral body's strength in flexion/compression loading was reduced significantly, but could be restored to at least intact values with any of the three filler materials. The minimally invasive bone graft harvester was tested in three cadaveric pelves. With the cutting tip being guided within the cortical boundaries of the pelvis, cancellous bone volumes of 10-20 cc could be harvested from each iliac bone. Regional bone graft harvest in anterior spine surgery is suggested to be anatomically safe and biomechanically acceptable. Any of the three filler materials can restore the vertebral body's mechanical strength, but the filler's long-term resorption/remodeling or osteointegration behavior is unknown. The minimally invasive bone graft harvester is a novel tool, which performed satisfactorily under laboratory conditions, but clinical results are still missing.

Bone Transplantation↗
PubMed2000

Synframe: a preliminary report.

Both endoscopic lumbar spinal surgery and the non-standardized and unstable retractor systems for the lumbar spine presently on the market have disadvantages and limitations in relation to the minimally invasive surgical concept, which have been gradually recognized in the last few years. In an attempt to resolve some of these issues, we have developed a highly versatile retractor system, which allows access to and surgery at the lumbar, thoracic and even cervical spine. This retractor system - Synframe - is based on a ring concept allowing 360 degrees access to a surgical opening in anterior as well as posterior surgery. The ring is concentrically laid over the surgical opening for the approach and is used as a carrier for retractor arms, which are instrumented with either different sizes or types of blades and/or different sizes of Hohmann hooks. In posterior surgery, nerve root retractors can also be installed. This ring also functions as a carrier for fiberoptic illumination devices and different sizes of endoscopes, used to transmit the surgical procedure out of the depth of the surgical exposure for both teaching purposes and for the surgical team when it has no longer direct visual access to the procedure. The ring is stable, being fixed onto the operating table, allowing precise minimally open approaches and surgical procedures under direct vision with optimal illumination. This ring system also opens perspectives for an integrated minimally open surgical concept, where the ring may be used as a reference platform in computer-navigated surgery.

Equipment Design↗
PubMed2000

Hybrid computer-guided and minimally open surgery: anterior lumbar interbody fusion and translaminar screw fixation.

Less invasiveness is the way forward for spinal surgery. Minimal disruption of tissue, preservation of muscle function, and restoration of normal spinal alignment are still the goals of most surgical procedures. An anterior lumbar fusion technique using a less invasive procedure with the addition of translaminar screws is described. The autograft is harvested from the vertebral body, thus avoiding the morbidity associated with an iliac crest bone graft. The operative steps for the procedure are described.

Bone Screws↗
PubMed2000

Cages: designs and concepts.

Many new interbody fusion cages have been recently developed, but clinical studies analyzing fusion outcome are still scarce. Radiological methods to assess fusion are not standardized and are often unreliable. Cages have been stated to provide good segmental distraction, provide axial load support and reduce segmental mobility, but there have been reports of failed fusions because of implant failure. This paper presents a critical opinion on current cage designs, stressing their clinical and biomechanical implications. Threaded cage designs compromise endplate integrity, and when placed in pairs have inherent limitations for distraction. Non-threaded cage designs usually preserve endplate integrity, but geometry may be inadequate to provide a good surface match to the endplate. The concept of an open frame type cage is believed to have biological advantages, because large graft volumes inside the cage can be in direct contact with host bone. Cadaveric tests suggest that open frame constructs have compressive strength similar to that of full surface contact cages. Restoration of segmental height, sagittal balance and increased neuroforaminal clearance are all functions of disc space distraction. The effect of cage instrumentation on axial load distribution, however, is not well understood. Biomechanical experiments strongly suggest supplementing cage instrumentation with posterior fixation, to achieve a marked increase in initial segmental stability. In the absence of gross segmental instability, micromotion at the host graft interface may still exist. As a result, fusion will never occur, instead a pseudoarthrosis will develop. For monitoring fusion, the use of non-metallic cages has distinct advantages, because no metal artifacts will disturb radiological assessment.

Equipment Design↗