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Biomedical subjects

T Link

Publications and source records attributed to T Link.

28 records · Page 2Linked to original sources
PubMed1995

Ewing's sarcoma of the ribs. A report from the cooperative Ewing's sarcoma study.

31 patients with primary Ewing's sarcoma of the ribs were treated according to the protocols of CESS 81, CESS 86P and CESS 86. The results of treatment were reviewed and analysed. 24 patients presented with localised disease and 7 with regional disease. 20 of 24 localised cases and 6 of 7 regional cases underwent tumour resection. All but 2 localised cases received irradiation. The cumulative relapse-free survival (RFS) rate of 31 patients was 61% at 12.8 years. Patients with poor prognosis had tumour of the upper ribs (P = 0.0338), the posterior component of the ribs (P = 0.0597), or regional disease (P = 0.0001). Tumour size, existence of pleural effusion, type of the surgical margin and response to chemotherapy were not significant prognostic factors. Most of the localised cases could be controlled by combined treatment, but in regional cases prognosis remained poor.

Adolescent↗
PubMed1991

The structure of the dihaem cytochrome b of fumarate reductase in Wolinella succinogenes: circular dichroism and sequence analysis studies.

The fumarate reductase from Wolinella succinogenes contains two haem groups with markedly different midpoint potentials (-20 mV and -200 mV). The enzyme is made up of three subunits, the lipophilic one of which (cytochrome b) ligates the haems. Circular dichroism (CD) spectroscopy has been applied to the reductase in order to obtain information on the structure of the haems and of their environment. This approach is integrated with amino acid sequence comparison of the cytochrome b with other quinone-reacting membrane haemoproteins for predicting the axial ligands of the haems as well as their location relative to the membrane. The following results have been obtained: (1) the CD spectra in the Soret region show exciton coupling indicating haem-haem interaction, which is particularly evident in the reduced state and disappears upon denaturation of the enzyme; (2) The apoprotein of cytochrome b is predicted to consist of five hydrophobic helices (helices A-D and cd), four of which should span the membrane. Helices A, B, C and cd contain a histidine residue each which possibly forms one of the ligands of the haems. It is proposed that haem b (-20 mV) is ligated by H44 and H93, and haem b (-200 mV) by H143 and H182.

Amino Acid Sequence↗
PubMed1987

Orientation of gingival fibroblasts in simulated periodontal spaces in vitro containing collagen gels.

The present study examined the orientation of cultured human gingival fibroblasts in simulated periodontal spaces in vitro containing three dimensional hydrated collagen gels. Extracted human teeth were root planed followed by root resection and root canal instrumentation. The middle and cervical thirds of each root were cut transversely to create 600-micron thick sections. Cortical bovine bone was cut, sectioned, and contoured to create bone rings 600 micron thick with an internal diameter large enough to accommodate a root slice leaving a circumferential space varying from approximately 0.1 to 1.0 mm. Root slices and bone rings were incubated in an enzyme solution to remove all remaining soft tissues and then completely demineralized in EDTA (18%) for 72 hours. Human gingival fibroblasts (HGF) were plated to confluency in tissue culture dishes. The dentin slices were then gently placed over the HGF monolayer along with bone rings around them to create simulated periodontal spaces. Five days later, when initial cell attachment to the dentin and root slices had occurred, a collagen gel was poured in the space. The cultures were maintained for six weeks and were then processed for transmission electron microscopy. The HGF appeared to have formed multilayered cell sheets extending from the periphery of the root slices to the inner surface of bone rings. The HGF had apparently attached to both the bone and root surfaces. There was a close interaction of cells with the matrix fibrils of the gel. The cells and matrix fibrils were oriented parallel to each other.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Adhesion↗
PubMedDate not supplied

A hypothesis to explain the substrate reactivity of ribosomal and stem-loop RNA with ricin A-chain.

A hypothesis is proposed which explains the low catalytic efficiency of ricin A-chain on artifical stem-loop RNA substrates, relative to the high catalytic efficiency found on intact mammalian ribosomes. The enzymatic binding energy required to reach the transition state is greater than that to stabilize the stem structure of stem-loop RNA molecules. When artifical stem-loop complexes bind, the base-pairing of the stem is lost rapidly relative to catalysis. Loss of secondary structure causes movement of the susceptible adenine to a catalytically unfavorable geometry and most of the enzyme-substrate complexes dissociate without catalysis. The protein architecture of intact ribosomes, when bound to ricin A-chain, is proposed to stabilize the stem-loop structure to maintain adenine 4324 in a configuration external to the RNA phosphodiester backbone. The slow catalysis observed with small stem-loop structures is a consequence of the relative probabilities for stem-melting induced by the enzyme and for reaching the transition state. Catalysis with a ten-base stem-loop RNA shows product formation at a rate of up to 0.02 hr-1, but fails to achieve a full catalytic turnover with long incubations. The substoichiometry of product formation with small stem-loops is proposed to be a consequence of the competing rates of catalysis and enzyme denaturation under in vitro assay conditions. Rates for these processes are estimated from the kinetic parameters for ricin A-chain hydrolysis of ribosomes and stem-loop structures.

Humans↗
PubMedDate not supplied

[Axial compressive strength of thoraco-lumbar vertebrae--an experimental biomechanical study].

PURPOSE: This study analyzed the correlation between the compressive strength of human thoracolumbar vertebrae, bone density and endplate area (measured by SE-QCT). METHOD: The compressive strength of 110 human vertebral specimens (D11-L5) was measured. In order to determine standard values for human vertebral specimens from each level and different female and male age groups were examined. Before biomechanical testing the specimens were examined using SE-QCT with 1.5 and 10 mm slice thickness. Three different slice locations (mid-vertebral and adjacent to both endplates) and 6 regions of interest (ROI) were chosen to assess BMD. The area of the vertebral endplates was measured by CT. RESULTS: Highest correlations between BMD and compressive strength were found for the 10 mm thick midvertebral slices with a small ellipsoid ROI. Cancellous and cortical bone contributed to the compressive strength to the same amount. Compressive strength and endplate area increased in the cranio-caudal direction, bone density was constant throughout thoracolumbar spine. Bone density and compressive strength depended on age and sex. Compressive strength of human thoracolumbar vertebrae increased with bone density as well as the size of the endplates. CONCLUSIONS: Using bone density and endplate area (SE-QCT) of human thoracolumbar vertebrae (D11-L5) a prediction of compressive strength is possible with an error of estimation of 1.17 kN and a correlation factor of 0.85. The prediction of the compressive strength allows an estimation of the risk of vertebral fracture, i.e. in patients with osteoporosis or in individuals with intensive physical activities. The standard values of the human thoracolumbar vertebrae together with biomechanical examinations of vertebral metastases can be used to estimate the compressive strength of osteolytic and osteoplastic spinal metastases.

Adult↗
PubMedDate not supplied

[Computerized tomography monitoring of the position of pedicle screws in scoliosis surgery].

With the increasing use of pedicle screws in instrumented spine surgery the neurological risk must be evaluated critically. Studies, which evaluated the accuracy of pedicle screw placement in scoliosis surgery, have not been published up to date to our knowledge. In 25 consecutive patients with idiopathic scoliosis, who underwent posterior instrumented curve correction and stabilization, the accuracy of pedicle screw placement was evaluated using axial computed tomography. There was a total of 178 screws between T5 and L4. The preoperative Cobb angle of the curve averaged 60.7 degrees, the mean rotation of the instrumented vertebrae was 19.1 degrees according to Perdriolle. 145 pedicle screws (81.5%) were placed correctly within the pedicles, of which 4 screws (4.5%) penetrated the anterior aspect of the vertebral body with a mean of 0.9 mm. 22 screws (12.4%) showed lateral penetration of the pedicle with a mean of 1.9 mm, of which one screw was placed completely lateral of the pedicle. 8 screws (4.5%) penetrated the medial wall of the pedicle by 1.3 mm on average. One screw each penetrated the cranial and caudal border of the pedicle. Statistical analysis did not reveal any significant relationships between pedicle screw misplacement and grade of vertebral rotation or site of instrumentation. Neurological complications were not noted in any of the cases. In our mind the risk of pedicle screw threaded curve correction and fusion in scoliosis surgery in the hands of an experienced spine surgeon is calculated acceptably low.

Bone Screws↗
PubMedDate not supplied

Studies on the mechanism of action of the antiparkinsonian drugs memantine and amantadine: no evidence for direct dopaminomimetic or antimuscarinic properties.

The effects of the antiparkinsonian drugs amantadine and memantine and of the noncompetitive NMDA receptor antagonist MK-801 were studied in the model of the electrically evoked release of [3H]dopamine and [3H]acetylcholine in slices of the rabbit caudate nucleus in vitro. In the [3H]dopamine release model, high concentrations (> 10 microM) of the drugs investigated showed a marked increase in spontaneous 3H-efflux, with the following order of potency: memantine > MK-801 > amantadine. The spontaneous 3H-efflux induced by 50 microM memantine was diminished by pargyline (10 microM), but was insensitive to the presence of tetrodotoxin (0.3 microM), or nomifensine (1 microM), or to the omission of Ca2+ in the superfusion medium; in the absence of nomifensine it consisted mainly of 3H-metabolites of dopamine. The latter findings indicate that the memantine-induced spontaneous 3H-efflux is unrelated to the firing of striatal interneurons but point to a direct releasing effect of memantine on dopaminergic storage granules. On the other hand, the electrically evoked release of [3H]dopamine seemed to be unaffected by memantine, was only slightly reduced by amantadine but significantly inhibited by MK-801. In the model of the electrically evoked release of [3H]acetylcholine, only MK-801 (> 50 microM) showed significant inhibitory effects, both on spontaneous and evoked overflow of [3H]acetylcholine; the effects of memantine and amantadine were negligible. Since only high concentrations of amantadine and memantine (exceeding those which, according to the literature, may be reached in vivo) showed effects in the present in vitro dopamine and acetylcholine release models, it is concluded that the clinical efficacy of these antiparkinsonian drugs is most probably unrelated to an enhancement of dopaminergic transmission as suggested from earlier in vitro and in vivo findings. The higher activity of MK-801 in the present model and the recent observation that both memantine and amantadine bind--although with lower affinity--to an MK-801 binding site in the NMDA receptor-linked ion channel, suggest a possible involvement of striatal NMDA receptors in the antiparkinsonian effects of these drugs.

Acetylcholine↗