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Biomedical subjects

M Aebi

Publications and source records attributed to M Aebi.

At least 55 records · Page 3Linked to original sources
PubMed2000

Posterolateral and anterior interbody spinal fusion models in the sheep.

Posterolateral and anterior interbody spinal arthrodesis is a frequent procedure, but high nonunion rates are reported and harvesting autologous bone graft from the iliac crest significantly increases morbidity. Bone graft substitutes are an alternative, but to date clinical results are not conclusive. Bone substitutes can be organic or inorganic, biologic or synthetic. They can have osteoconductive properties, inductive properties or both. Animal experiments are essential to investigating bone substitutes using biomechanical and histologic methods not available in clinical studies. Few authors reported on instrumented anterior fusion models, but none used the sheep model. In the current study posterolateral and anterior interbody fusion models in sheep are described. Both models used instrumented fusions, applying porous mineral scaffolds, alone or mixed with bone. The surgical techniques are described step-by-step and potential difficulties are highlighted. Preliminary results are reported for the posterolateral fusion model using coralline graft substitutes. The coral granules mixed with locally harvested bone had fusion outcomes similar to pure autologous bone. The graft substitute showed marked resorption between 12 and 20 weeks. All fusions had bone cortex and good trabecular connectivity. Histologic evaluation suggests after 20 weeks nearly the entire surface of the substitute is covered with new bone. Porous mineral bone substitutes mixed with locally harvested autologous bone are thought to be a valid alternative for posterolateral fusions.

Animals↗
PubMed2000

Deficiency of dolichol-phosphate-mannose synthase-1 causes congenital disorder of glycosylation type Ie.

Congenital disorders of glycosylation (CDG), formerly known as carbohydrate-deficient glycoprotein syndromes, lead to diseases with variable clinical pictures. We report the delineation of a novel type of CDG identified in 2 children presenting with severe developmental delay, seizures, and dysmorphic features. We detected hypoglycosylation on serum transferrin and cerebrospinal fluid beta-trace protein. Lipid-linked oligosaccharides in the endoplasmic reticulum of patient fibroblasts showed an accumulation of the dolichyl pyrophosphate Man(5)GlcNAc(2) structure, compatible with the reduced dolichol-phosphate-mannose synthase (DolP-Man synthase) activity detected in these patients. Accordingly, 2 mutant alleles of the DolP-Man synthase DPM1 gene, 1 with a 274C>G transversion, the other with a 628delC deletion, were detected in both siblings. Complementation analysis using DPM1-null murine Thy1-deficient cells confirmed the detrimental effect of both mutations on the enzymatic activity. Furthermore, mannose supplementation failed to improve the glycosylation status of DPM1-deficient fibroblast cells, thus precluding a possible therapeutic application of mannose in the patients. Because DPM1 deficiency, like other subtypes of CDG-I, impairs the assembly of N-glycans, this novel glycosylation defect was named CDG-Ie.

Amino Acid Sequence↗
PubMed1999

Molecular basis of carbohydrate-deficient glycoprotein syndromes type I with normal phosphomannomutase activity.

Carbohydrate deficient glycoprotein syndromes (CDGS) are inherited disorders in glycosylation. Isoelectric focusing of serum transferrin is used as a biochemical indicator of CDGS; however, this technique cannot diagnose the molecular defect. Even though phosphomannomutase (PMM) deficiency accounts for the great majority of known CDGS cases (CDGS type Ia), newly discovered cases have significantly different clinical presentations than the PMM-deficient patients. These differences arise from other defects affecting the biosynthesis of N-linked oligosaccharides in the endoplasmic reticulum and in the Golgi compartment. The most notable is the loss of phosphomannose isomerase (PMI) (CDGS type Ib). It causes severe hypoglycemia, protein-losing enteropathy, vomiting, diarrhea, and congenital hepatic fibrosis. In contrast to PMM-deficiency, there is no developmental delay nor neuropathy. Most symptoms in the PMI-deficient patients can be successfully treated with dietary mannose supplements. Another defect is the lack of glucosylation of the lipid-linked oligosaccharide precursor. The clinical features of this form of CDGS are milder, but similar to, PMM-deficient patients. Yeast genetic and biochemical techniques were critical in unraveling these disorders since many of the defective genes were known in yeast and corresponding mutants were available for complementation. Yeast strains carrying mutations in the homologous genes are likely to provide conclusive identification of the primary defects in novel CDGS types that affect the synthesis and transfer of precursor oligosaccharides.

Carbohydrate Sequence↗
PubMed1999

A mutation in the human ortholog of the Saccharomyces cerevisiae ALG6 gene causes carbohydrate-deficient glycoprotein syndrome type-Ic.

Carbohydrate-deficient glycoprotein syndrome (CDGS) represents a class of genetic diseases characterized by abnormal N-linked glycosylation. CDGS patients show a large number of glycoprotein abnormalities resulting in dysmorphy, encephalopathy, and other organ disorders. The majority of CDGSs described to date are related to an impaired biosynthesis of dolichyl pyrophosphate-linked Glc3Man9GlcNAc2 in the endoplasmic reticulum. Recently, we identified in four related patients a novel type of CDGS characterized by an accumulation of dolichyl pyrophosphate-linked Man9GlcNAc2. Elaborating on the analogy of this finding with the phenotype of alg5 and alg6 Saccharomyces cerevisiae strains, we have cloned and analyzed the human orthologs to the ALG5 dolichyl phosphate glucosyltransferase and ALG6 dolichyl pyrophosphate Man9GlcNAc2 alpha1,3-glucosyltransferase in four novel CDGS patients. Although ALG5 was not altered in the patients, a C-->T transition was detected in ALG6 cDNA of all four CDGS patients. The mutation cosegregated with the disease in a Mendelian recessive manner. Expression of the human ALG5 and ALG6 cDNA could partially complement the respective S. cerevisiae alg5 and alg6 deficiency. By contrast, the mutant ALG6 cDNA of CDGS patients failed to revert the hypoglycosylation observed in alg6 yeasts, thereby proving a functional relationship between the alanine to valine substitution introduced by the C-->T transition and the CDGS phenotype. The mutation in the ALG6 alpha1,3-glucosyltransferase gene defines an additional type of CDGS, which we propose to refer to as CDGS type-Ic.

Amino Acid Sequence↗
PubMed1999

The dolichol pathway of N-linked glycosylation.

The oligosaccharide substrate for the N-linked protein glycosylation is assembled at the membrane of the endoplasmic reticulum. Dolichyl pyrophosphate serves as a carrier in this biosynthetic pathway. In this review, we discuss the function of the lipid carrier dolichol in oligosaccharide assembly and give an overview of the biosynthesis of the different sugar donors required for the building of the oligosaccharide. Yeast genetic techniques have made it possible to identify many different loci encoding specific glycosyltransferases required for the precise and ordered assembly of the dolichyl pyrophosphate-linked oligosaccharide. Based on the knowledge obtained from studying this pathway in yeast, we compare it to the process of N-linked protein glycosylation in archaea. We suggest that N-linked glycosylation in eukaryotes and in archaea share a common evolutionary origin.

Amino Acid Sequence↗
PubMed1999

Immunohistochemical analysis of type-X-collagen expression in osteoarthritis of the hip joint.

Conflicting data have been reported on the spatial distribution of type X-collagen expression in osteoarthritis, and no concise data exist on a possible correlation between type X-collagen expression and clinical and radiological alterations. Well defined clinical and radiological data were compared with histopathological and immunohistochemical findings to investigate the expression of type-X collagen in osteoarthritis of the hip joint. Femoral heads were obtained in toto from 11 patients undergoing routine hip arthroplasty for femoral neck fractures (n = 3) or osteoarthritis (n = 8) and from 13 patients (age: 12 days to 69 years) without any evidence of hip-joint pathology. Whole coronal sections from the femoral head were decalcified for routine histology and immunohistochemical analysis with use of type-specific monoclonal antibodies to type-X collagen. Our results demonstrate that type-X collagen is consistently found in osteoarthritic cartilage and is absent from normal adult cartilage (including the region of calcified cartilage). Except for the occurrence of type-X collagen in the middle zone of articular cartilage in advanced stages of osteoarthritis, there is no specific change in the staining pattern or intensity for the collagen during osteoarthritis, particularly when the staining is related to clinical and radiological parameters. Hardly more than 20% of the extracellular matrix stained for type-X collagen; therefore, we suggest that, in most cases, this type of collagen may not play a direct biomechanical role in the weakening of osteoarthritic cartilage but rather may contribute indirectly to a disturbance of the disc biomechanics by altering matrix-molecule interaction. However, expression of type-X collagen may indicate a change in chondrocyte phenotype that consistently coincides with the formation of chondrocyte clusters, one of the first alterations in osteoarthritis visible on histologic examination.

Adolescent↗
PubMed1999

Unusual presentation of spinal cord compression related to misplaced pedicle screws in thoracic scoliosis.

Utilization of thoracic pedicle screws is controversial, especially in the treatment of scoliosis. We present a case of a 15-year-old girl seen 6 months after her initial surgery for scoliosis done elsewhere. She complained of persistent epigastric pain, tremor of the right foot at rest, and abnormal feelings in her legs. Clinical examination revealed mild weakness in the right lower extremity, a loss of thermoalgic discrimination, and a forward imbalance. A CT scan revealed at T8 and T10 that the right pedicle screws were misplaced by 4 mm in the spinal canal. At the time of the revision surgery the somatosensory evoked potentials (SSEP) returned to normal after screw removal. The clinical symptoms resolved 1 month after the revision. The authors conclude that after pedicle instrumentation at the thoracic level a spinal cord compression should be looked for in case of subtle neurologic findings such as persistent abdominal pain, mild lower extremity weakness, tremor at rest, thermoalgic discrimination loss, or unexplained imbalance.

Abdominal Pain↗
PubMed1999

The 'MW' sacropelvic construct: an enhanced fixation of the lumbosacral junction in neuromuscular pelvic obliquity.

Fixation to the lumbosacral spine to correct pelvic obliquity in neuromuscular scoliosis has always remained a surgical challenge. The strongest fixation of the lumbosacral junction has been achieved with either a Galveston technique with rods or screws or with iliosacral screws. We have devised a new fixation system, in which iliosacral screws are combined with iliac screws. This is made possible by using the AO Universal Spine System with side opening hooks above and below the iliosacral screws and iliac screws below it. The whole sacropelvis is thus encompassed by a maximum width (MW) fixation, which gives an 'M' appearance on the pelvic radiographs and a 'W' appearance in the axial plane. We report on our surgical technique and the early results where such a technique was used. We feel that this new means of fixation (by combining the strongest fixation systems) is extremely solid and should be included in the wide armamentarium of sacropelvic fixation.

Adult↗
PubMed1999

Adolescent idiopathic thoracic scoliosis: apical correction with specialized pedicle hooks.

Forty-one patients with thoracic adolescent idiopathic scoliosis (AIS) treated with only a posterior spine fusion using specialized pedicle hooks (SPH) (hooks augmented with 3.2-mm screws) at the apex of the curve were reviewed in order to assess the effectiveness of this correction method. Inclusion in the study group required a minimum of 2 years' follow-up and the same strategy of correction where the apical vertebrae (3 or 4 vertebrae on the concave side) were instrumented with SPH. The mean preoperative Cobb angle was corrected from 55 degrees (42 degrees -80 degrees) to 18 degrees (67%) postoperatively and to 23 degrees (58%) at the last follow-up (28-50 months) for a flexibility index of 46%. Apical vertebral translation was corrected to 70% at the last follow-up. Thoracic kyphosis remained unchanged, from 23 degrees to 26 degrees, and the lumbar lordosis went from -53 degrees to -59 degrees. The lumbar curve was corrected from 38 degrees to 18 degrees. Coronal balance improved from 10 to 1 mm; shoulder balance was improved from 15 to 5 mm. The rib hump was improved from an average of 30 mm preoperatively to 15 mm postoperatively, but only to 25 mm at the last follow-up (17% of correction). One case of a spastic bladder was observed postoperatively, which resolved completely after 8 months. Three patients had to have their instrumentation removed because of pain. There was no complication related to the use of the SPH. The authors conclude that apical correction with SPH allows effective scoliosis correction without spinal distraction and does not require supra- or infralaminar hook in the spinal canal.

Adolescent↗
PubMed1999

Motor conduction alterations in patients with lumbar spinal stenosis following the onset of neurogenic claudication.

The pathogenesis of neurogenic claudication is thought to lie in relative ischemia of cauda equina roots during exercise. In this study we will evaluate the effect of the transient ischemia brought on by exercise on motor conduction in patients suffering from lumbar spinal stenosis (LSS). We will also evaluate the sensitivity of motor evoked potentials (MEPs) in detecting motor conduction abnormalities before and after the onset of neurogenic claudication. Thirty patients with LSS and 19 healthy volunteers were enrolled in the study. All LSS patients had a history of neurogenic claudication and the diagnosis was confirmed with a CT myelogram. Both groups underwent a complete electrophysiological evaluation of the lower extremities. The motor evoked potential latency time (MEPLT) and the peripheral motor conduction time (PMCT) were measured. The subjects were asked to walk on a flat surface until their symptoms were reproduced. A new set of electrophysiological tests was then performed. Exercise did not produce claudication in any of the control group subjects. Twenty-seven patients did have claudication. The pre-exercise MEPLT and nerve conduction studies in the control group fell within the normal range. In the patient group, 19 patients had increased baseline values for MEPLT to at least one muscle. There was a significant difference between the MEPLT and the PMCT values measured before and after exercise in the patients with signs of neurological deficit. This difference was not found to be significant in patients without neurological deficits (t-test P < 0. 05). It may be concluded that exercise increases the sensitivity of MEPs in detecting the roots under functional compression in LSS.

Adult↗
PubMed1999

Rapid isolation of genes from an indexed genomic library of C. cinereus in a novel pab1+ cosmid.

In this study we present an indexed genomic library of homokaryon AmutBmut constructed within a novel cosmid carrying pab1+ as a selectable Coprinus marker. The average insert size per cosmid comprises 41 kb. We screened the library and detected copies of known (a1-2, beta-tub, cgl1, ras, trp1) and of new Coprinus genes (cac, lac1, lac2, lac3). Screening was performed either by Southern blot hybridisation or more efficiently by non-radioactive PCR amplification. We successfully applied PCR with specific and with degenerate primers, multiplex PCR and colony PCR in library screening. Our results suggest a new, more efficient pooling strategy for future high throughput screenings to be used in PCR with pooled cosmid DNAs, or in a less laborious approach using pooled Escherichia coli colonies for PCR.

Amino Acid Sequence↗
PubMed1999

Management of an unstable lumbar fracture with a laminar split.

This is a case report describing the injury sustained by a 36-year-old man injured in a motorcycle crash who sustained a fracture dislocation of L2 upon L3, associated with a split in the lamina of L3. His neurologic lesion was T12 ASIA B: with a motor score of 52 but with preservation of sensory function (sensory score 96) in most parts of his lower extremities. He also suffered a lower extremity fracture. Imaging of the spine is presented showing a multiplanar fracture associated with translation and with a defect in the lamina that may be seen in certain AO type B or type C fractures, that may entrap the lumbar spinal nerve roots. Discussants of this case comment on the classification and clinical significance of this fracture pattern. and present their operative approaches, both for management of this particular fracture pattern and for any associated dural tear. The issues of steroid use and the place of rehabilitation are also discussed.

Accidents, Traffic↗
PubMed1999

The Saccharomyces cerevisiae CWH8 gene is required for full levels of dolichol-linked oligosaccharides in the endoplasmic reticulum and for efficient N-glycosylation.

The Saccharomyces cerevisiae mutant cwh8 was previously found to have an anomalous cell wall. Here we show that the cwh8 mutant has an N -glycosylation defect. We found that cwh8 cells were resistant to vanadate and sensitive to hygromycin B, and produced glycoforms of invertase and carboxypeptidase Y with a reduced number of N -chains. We have cloned the CWH8 gene. We found that it was nonessential and encoded a putative transmembrane protein of 239 amino acids. Comparison of the in vitro oligosaccharyl transferase activities of membrane preparations from wild type or cwh8 Delta cells revealed no differences in enzyme kinetic properties indicating that the oligosaccharyl transferase complex of mutant cells was not affected. cwh8 Delta cells also produced normal dolichols and dolichol-linked oligosaccharide intermediates including the full-length form Glc3Man9GlcNAc2. The level of dolichol-linked oligosaccharides in cwh8 Delta cells was, however, reduced to about 20% of the wild type. We propose that inefficient N -glycosylation of secretory proteins in cwh8 Delta cells is caused by an insufficient supply of dolichol-linked oligosaccharide substrate.

Amino Acid Sequence↗
PubMed1999

Ordered assembly of the asymmetrically branched lipid-linked oligosaccharide in the endoplasmic reticulum is ensured by the substrate specificity of the individual glycosyltransferases.

The assembly of the lipid-linked core oligosaccharide Glc3Man9GlcNAc2, the substrate for N-linked glycosylation of proteins in the endoplasmic reticulum (ER), is catalyzed by different glycosyltransferases located at the membrane of the ER. We report on the identification and characterization of the ALG12 locus encoding a novel mannosyltransferase responsible for the addition of the alpha-1,6 mannose to dolichol-linked Man7GlcNAc2. The biosynthesis of the highly branched oligosaccharide follows an ordered pathway which ensures that only completely assembled oligosaccharide is transferred from the lipid anchor to proteins. Using the combination of mutant strains affected in the assembly pathway of lipid-linked oligosaccharides and overexpression of distinct glycosyltransferases, we were able to define the substrate specificities of the transferases that are critical for branching. Our results demonstrate that branched oligosaccharide structures can be specifically recognized by the ER glycosyltransferases. This substrate specificity of the different transferases explains the ordered assembly of the complex structure of lipid-linked Glc3Man9GlcNAc2 in the endoplasmic reticulum.

Base Sequence↗
PubMed1999

The MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay is a fast and reliable method for colorimetric determination of fungal cell densities.

The entomopathogenic fungus Neozygites parvispora (Entomophthorales: Zygomycetes) grows in vitro as irregularly rod-shaped hyphal bodies in a complex medium. In order to simplify the medium composition and determine growth-promoting compounds for the cultivation of this fungus, we were looking for a rapid and quantitative method to estimate the number of living cells in small volumes of liquid culture. A colorimetric method for the determination of cell densities using MTT [3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide] proved to be more accurate and timesaving than conventional hemocytometer counting.

Colony Count, Microbial↗
PubMed1999

Anterior cervical interbody fusion with plate fixation for chronic spondylotic radiculopathy: a 2- to 8-year follow-up.

In retrospectively analyzing 35 consecutive patients with chronic spondylotic radiculopathy treated by nerve root decompression, interbody fusion (Robinson technique), and plating, we studied the perioperative complication rate as well as the long-term clinical and radiologic outcomes of an additional plate fixation in degenerative cervical disorders. After an average of 54 months (range 24-102 months), all cases were reviewed for the purpose of this study. There were no perioperative or postoperative complications related to the plate fixation. In particular, there was no infection, graft extrusion, or neurologic deterioration. A solid fusion was obtained in all cases with a single-level fusion and in 87% of the cases with a multilevel fusion. The overall fusion rate was 94%. The clinical outcome of the patients with chronic radiculopathy was comparable with that in the literature, with only three patients (8.6%) having a poor result. This study demonstrated that plate fixation can be a useful adjunct in patients undergoing interbody fusion for cervical spondylotic radiculopathy. Plate fixation seems to reduce the rate of nonunion without additional hazards for the patient. This report should form the basis for a prospective randomized trial to answer the question more conclusively of whether an additional plate fixation is superior to uninstrumented cervical fusion in degenerative disorders.

Adult↗