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Biomedical subjects

J Zhao

Publications and source records attributed to J Zhao.

At least 559 records · Page 31Linked to original sources
PubMed1996

Phosphorylation-dependent block of cystic fibrosis transmembrane conductance regulator chloride channel by exogenous R domain protein.

The cystic fibrosis transmembrane conductance regulator (CFTR) constitutes a linear conductance chloride channel, which is regulated by cAMP-dependent protein kinase phosphorylation at multiple sites located in the intracellular regulatory (R) domain. Studies in a lipid bilayer system, reported here, provide evidence for the control of CFTR chloride channel by its R domain. The exogenous R domain protein (encoded by exon 13 plus 85 base pairs of exon 14) interacted specifically with the CFTR molecule and inhibited the chloride conductance in a phosphorylation-dependent manner. Only the unphosphorylated R domain protein blocked the CFTR channel. Such functional interaction suggests that the putative gating particle of the CFTR chloride channel resides in the R domain.

Base Sequence↗
PubMed1996

The regulatory light chains of myosin modulate cross-bridge cycling in skeletal muscle.

We investigated the kinetics of Ca2+ activation of skeletal muscle contraction elicited by the photolysis of caged Ca2+. Previously we showed that partial extraction of the 18-kDa regulatory light chains (RLCs) of myosin decreased the rate of force development and was subsequently increased by approximately 20% following reconstitution with RLCs (Potter, J. D., Zhao, J. and Pan, B. S. (1992) FASEB J. 6, A1240). We extend here the RLC-extraction study to the complete removal of the RLCs. The complete removal of RLCs was achieved by a combination of 5,5'-dithiobis-(2-nitrobenzoic acid) and EDTA treatment followed by reduction of oxidized sulfydryl groups by dithiothreitol. Under these conditions the complete extraction of RLCs was accompanied by the extraction of endogenous troponin C, resulting in the loss of isometric tension. Steady state force was restored to 65-75% following troponin C reconstitution and increased to 75-85% as a result of RLC reincorporation into the fibers. The rates of force transients generated by UV-flash photolysis of 1-(2-nitro-4,5-dimethoxyphenyl)-N,N,N',N' -tetrakis[(oxycarbonyl)methyl]-1,2-ethanediamine) or nitrophenyl-EGTA, photoliberating bound Ca2+, decreased 2-fold after RLC extraction and troponin C reconstitution and then increased to the values of intact fibers after RLC reconstitution. These results support our earlier findings that the regulatory light chains of myosin play an important role in the kinetics of cross-bridge cycling.

Animals↗
PubMed1996

A cell type-specific enhancer in the human B7.1 gene regulated by NF-kappaB.

The costimulatory molecule B7.1 provides a second signal critical for T cell activation. The distribution of this integral membrane protein is restricted to certain tissues where its level of expression is modulated by multiple exogenous stimuli. To identify the molecular basis for specificity and inducibility, the chromatin configuration of the human B7.1 gene was examined in intact nuclei from various cell types. The identification of a tissue-specific deoxyribonuclease I hypersensitive site approximately 3kb upstream of the transcription start site led to the characterization of a cell type-specific enhancer region. This 183-bp region was both cell type specific and responsive to two distinct stimuli, lipopolysaccharide and dibutyryl cAMP, known to regulate B7.1 expression. Deletional and site-directed mutagenesis revealed the presence of multiple functionally critical cis elements within this region, one of which was a nuclear factor (NF)-kappaB consensus sequence. In B7.1-positive B cells, this element bound several members of the NF-kappaB family, transcription factors already implicated in signal transduction pathways relevant to B7.1 expression. This is the first description, to our knowledge, of regulatory elements that control expression of a gene encoding a B7 costimulatory molecule.

Antigens, CD↗
PubMed1996

Interaction between photosystem I and flavodoxin from the cyanobacterium Synechococcus sp. PCC 7002 as revealed by chemical cross-linking.

The interaction between photosystem I (PS I) and flavodoxin from the cyanobacterium Synechococcus sp. PCC 7002 was investigated by covalent cross-linking in the presence of a hydrophilic cross-linker, N- ethyl-3-(3-diaminopropyl)carbodiimide. Under the experimental conditions employed, five distinct cross-linking products of flavodoxin and PS I subunits are formed. Immunoblot analyses show that these species are the result of cross-linking of flavodoxin to PsaC, PsaD, an unidentified low-molecular-mass PS I polypeptide, and a 15-kDa subunit. The latter has been indirectly identified as the PsaF subunit. Analysis of the interaction of flavodoxin with PS I from a psaE mutant indicates that the PsaE subunit is required for correct complex formation between flavodoxin and PS I, although this subunit is not directly cross-linked to flavodoxin. In addition, the cross-linking products of PsaD with PsaC and PsaL, and PsaE with PsaF, are observed. The covalent complex of flavodoxin and PS I is shown to be fully inhibited with respect to electron transfer to soluble flavodoxin, ferredoxin or ferredoxin:NADP+ oxidoreductase.

Binding Sites↗
PubMed1996

Structure-function relationships of the complement regulatory protein, CD59.

CD59 (membrane inhibitor of reactive lysis, protectin) is a membrane protein whose functions include the inhibition of the insertion of the ninth component of complement into the target membrane. It belongs to a superfamily of proteins including Ly-6, elapid snake venom toxins, and urokinase receptor (UPAR); the members of the superfamily have a similar structure that includes four (in mammals five) disulfide bridges that maintain a three-dimensional conformation consisting of a central core, three finger-like "loops" extending from it and a small loop near the coboxyl end. We have used site directed mutagenesis to explore three aspects of the structure of CD59: 1) the role of the disulfide bridges in expression and function of the molecule; 2) the location of epitopes reacting with monoclonal antibodies to the molecule; and 3) the parts of the molecule that are critical to its function in inhibiting complement lysis. Mutant molecules in which the disulfides maintaining the finger-like loops (Cys3-Cys26, Cys19-Cys39, and Cys45-Cys63) were removed were not expressed on the cell surface. The mutation of the disulfide (Cys6-Cys13) resulted in no change in expression or function. The mutation of Cys64-Cys69 maintaining the small loop resulted in an expressed molecule with increased functional activity. The major epitope for 6 of 7 monoclonal antibodies was centered on Arg53 as the mutation 53Arg-->Ser resulted in a loss of interaction with these antibodies, as did the deletion of four nearby residues (Leu54-Asn57). The alteration 55Arg-->Ser resulted in loss of reactivity for some but not other antibodies. The reactivity with one monoclonal antibody, H19, was abrogated by the mutations 61Tyr-->Gly and 61Tyr-->Ala. Functional activity of the molecule was not adversely altered by mutations in the first and second loops; however, the 61Tyr-->Gly mutation was non-functional. The mutation of 61Tyr-->His diminished function but changes 61Tyr-->Ala and 61Tyr-->Phe had no effect on function. We conclude that the functional site of CD59 is located in this region of the molecule.

Animals↗
PubMed1996

Functional expression of the dihydrofolate reductase domain of Leishmania major dihydrofolate reductase-thymidylate synthase bifunctional protein.

The dihydrofolate reductase (DHFR) domain of the bifunctional dihydrofolate reductase-thymidylate synthase from Leishmania major has been subcloned and expressed as a soluble protein in Escherichia coli strain PA414 harboring plasmid pLMDHFR. Homogeneous L. major DHFR was obtained by chromatography on methotrexate-Sepharose followed by DE52. The purified enzyme migrated as a single 25-kDa protein on SDS-PAGE. The native molecular weight was determined to be 26 kDa, indicating that the isolated domain is a monomer. N-terminal sequence analysis revealed that serine, the second amino acid in the coding sequence, was the N-terminal amino acid of the protein. The enzyme showed a pH optimum similar to that of the bifunctional protein. For purified DHFR, the Km values were <1.0 microM for H2folate and <1.0 microM for NADPH. The kcat of the most active DHFR preparation was 5 s-1. The Km and kcat values were similar to those of the bifunctional enzyme.

Amino Acid Sequence↗
PubMed1996

Effects of low-dose long-term sodium fluoride preventive treatment on rat bone mass and biomechanical properties.

Effects of fluoride on bone strength and cortical bone mass remain controversial. We compared 9-month, low-dose sodium fluoride (NaF) treatment with estrogen replacement therapy. Female Wistar rats 4.5 months old were divided into baseline, sham-operated (sham), sham-treated with NaF at 0.5 mg NaF/kg/day in drinking water, and ovariectomy (OVX), OVX treated with NaF and with estrogen. Bone mass was measured by dual X-ray absorptiometry (DXA) in vitro. Dimensions of the first lumbar vertebral body (L1) were determined by radiogrammetry. The right femur was processed undecalcified to obtain a midshaft cross-section to determine cross-sectional moments of inertia (CSMIs). L1 compressive test and left femoral torsional test were performed. OVX induced significant bone loss in L1 and femoral midshaft. Bone mass was increased to a greater extent in NaF-treated rats than in rats receiving estrogen replacement therapy. Femoral CSMIs in OVX rats, both L1 sizes and femoral CSMIs in NaF-treated rats, were significantly increased. Estrogen treatment had the least dimension expansion. OVX significantly decreased L1 compressive variables. There was no statistical difference in compressive parameters between NaF-treated groups and controls. OVX significantly increased femoral torsional strength but NaF treatment did not. Bone fluoride content was significantly increased after treatment with NaF. No significant difference in bone mineralization degree (ash and calcium) was found between treated and control rats. The discrepancy that an increase in bone mass and geometric properties in both trabecular and cortical bones by low-dose, long-term NaF treatment did not increase vertebral strength nor proportionally improve femoral strength indicated that the bone intrinsic biomechanical properties could be changed by NaF treatment.

Animals↗
PubMed1996

Cimicifuga and Melbrosia lack oestrogenic effects in mice and rats.

OBJECTIVES: The natural medicines, Cimicifuga and Melbrosia, are widely sold. Cimicifuga is an extract of Cimicifuga racemosa (L.), and Melbrosia is a mixture of Gelée Royale, perga-pollen and pollen. Cimicifuga and Melbrosia are used through self-medication to relieve symptoms of hot flushes and other menstrual or menopausal discomfort in many of the Danish women consulting private gynaecologists. A gynaecologist tends to treat these symptoms with oestrogen, so the present experiments were therefore made to investigate whether Cimicifuga and Melbrosia have oestrogenic effects as defined by the classical biological methods: uterine growth in immature mice and vaginal cornification in ovariectomized rats. METHODS: Vehicle, 6, 60 or 600 mg/kg Cimicifuga or 30, 300 or 3000 mg/kg Melbrosia was administered orally for 3 days to groups of 10 immature mice and the uterus weight measured on the fourth day. Similarly, vehicle, 6, 60, 600 mg/kg Cimicifuga or 3, 30, 300 mg/kg Melbrosia was injected subcutaneously in groups of 12 ovariectomized rats for 3 days and vaginal smears investigated for signs of cornified cells. All experiments were repeated once. RESULTS: No signs of an oestrogenic effect connected with the preparations were found in any of the experiments. CONCLUSIONS: It can be concluded that the eventual beneficial effects on menstrual or menopausal discomfort connected with Cimicifuga and Melbrosia self-medication cannot be explained as a traditional oestrogenic effect as measured in biological experiments.

Animals↗
PubMed1996

Enhancement of antiproliferative activity of 1alpha,25-dihydroxyvitamin D3 (analogs) by cytochrome P450 enzyme inhibitors is compound- and cell-type specific.

Ketoconazole (keto) or liarozole (liaro), inhibitors of the cytochrome P450 enzymes that mediate vitamin D and A hydroxylations, could potentiate the antiproliferative effects of 1alpha,25-dihydroxyvitamin D3 [1alpha,25(OH)2D3] and its analogs. Proliferation of MCF-7 and T47-D human breast cancer cells, MG-63 human osteosarcoma cells and HL-60 human promyeloid leukemia cells was concentration dependently inhibited by 1alpha,25(OH)2D3. The vitamin D analogs KH 1060 [20-epi-22-oxa-24,26,27-trihomo-1alpha,25(OH)2D3], RO 23-6010 [16-ene-23-yne-26-trifluoro-1,25(OH)2D2D3], ZXY 835 [20-epi-23-yne-25,26-epoxy-1alpha(OH)D3], and CD 99 [11alpha-methyl-1alpha,25(OH)2D3] were 150-,58-,16- and 7-fold more potent than 1alpha,25(OH)2D3 in inhibiting the proliferation of MCF-7 cells, respectively. A similar rank order of potency was observed in other cell lines. The antiproliferative effects of the vitamin D hormone and analogs was enhanced in MCF-7 cells when coincubated with 1 microM keto (7-, 10-, 5-, 25- and 1.3-fold more potent than in the absence of keto), respectively. The antiproliferative effect was less enhanced when 1alpha,25(OH)2D3 or its analogs KH 1060, ZXY 835 and RO 23-6010 were combined with liaro (3-, 7-, 2- and 3-fold, respectively). Keto and liaro did not markedly potentiate the activity of 1alpha,25(OH)2D3 or its analogs in MG-63 or HL-60 cells. These results suggest that differences in cellular metabolism can at least partially explain the different potency of vitamin D analogs. Moreover, the metabolism of vitamin D analogs is cell-type specific.

Calcitriol↗
PubMed1996

Rectification of cystic fibrosis transmembrane conductance regulator chloride channel mediated by extracellular divalent cations.

We report here distinct rectification of the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel reconstituted in lipid bilayer membranes. Under the symmetrical ionic condition of 200 mM KCl (with 1 mM MgCl2 in cis intracellular and 0 MgCl2 in trans extracellular solutions, pH in both solutions buffered at 7.4 with 10 mM HEPES), the inward currents (intracellular-->extracellular chloride movement) through a single CFTR channel were approximately 20% larger than the outward currents. This inward rectification of the CFTR channel was mediated by extracellular divalent cations, as the linear current-voltage relationship of the channel could be restored through the addition of millimolar concentrations of MgCl2 or CaCl2 to the trans solution. The dose responses for [Mg]zero and [Ca]zero had half-dissociation constants of 152 +/- 72 microM and 172 +/- 40 microM, respectively. Changing the pH buffer from HEPES to N-tris-(hydroxymethyl)methyl-2-aminoethanesulfonic acid did not alter rectification of the CFTR channel. The nonlinear conductance property of the CFTR channel seemed to be due to negative surface charges on the CFTR protein, because in pure neutral phospholipid bilayers, clear rectification of the channel was also observed when the extracellular solution did not contain divalent cations. The CFTR protein contains clusters of negatively charged amino acids on several extracellular loops joining the transmembrane segments, which could constitute the putative binding sites for Ca and Mg.

Buffers↗
PubMed1996

Human epithelial cystic fibrosis transmembrane conductance regulator without exon 5 maintains partial chloride channel function in intracellular membranes.

The cardiac isoform of the cystic fibrosis transmembrane conductance regulator (CFTR) is a splice variant of the epithelial CFTR, with lacks 30 amino acids encoded by exon 5 in the first intracellular loop. For examination of the role of exon 5 in CFTR channel function, a CFTR deletion mutant, in which exon 5 was removed from the human epithelial CFTR, was constructed. The wild type and delta exon5 CFTR were expressed in a human embryonic kidney cell line (293 HEK). Fully mature glycosylated CFTR (approximately 170 kDa) was immunoprecipitated from cells transfected with wild type CFTR cDNA, whereas cells transfected with delta exon5 CFTR express only a core-glycosylated from (approximately 140 kDa). The Western blot test performed on subcellular membrane fractions showed that delta exon5 CFTR was located in the intracellular membranes. Neither incubation at lower temperature (26 degrees C) nor stimulation of 293 HEK cells with forskolin or CPT-cAMP caused improvement in glycosylation and processing of delta exon5 CFTR proteins, indicating that the human epithelial CFTR lacking exon5 did not process properly in 293 HEK cells. On incorporation of intracellular membrane vesicles containing the delta exon5 CFTR proteins into the lipid bilayer membrane, functional phosphorylation- and ATP-dependent chloride channels were identified. CFTR channels with an 8-pS full-conductance state were observed in 14% of the experiments. The channel had an average open probability (Po) of 0.098 +/- 0.022, significantly less than that of the wild type CFTR (Po = 0.318 +/- 0.028). More frequently, the delta exon5 CFTR formed chloride channels with lower conductance states of approximately 2-3 and approximately 4-6 pS. These subconductance states were also observed with wild type CFTR but to a much lesser extent. Average Po for the 2-3-pS subconductance state, estimated from the area under the curve on an amplitude histogram, was 0.461 +/- 0.194 for delta exon5 CFTR and 0.332 +/- 0.142 for wild type (p = 0.073). The data obtained indicate that deleting 30 amino acids from the first intracellular loop of CFTR affects both processing and function of the CFTR chloride channel.

Blotting, Western↗
PubMed1996

Slow conversions among subconductance states of cystic fibrosis transmembrane conductance regulator chloride channel.

The cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel exhibits multiple subconductance states. To study the regulation of conductance states of the CFTR channel, we expressed the wild-type CFTR protein in HEK 293 cells, and isolated microsomal membrane vesicles for reconstitution studies in lipid bilayer membranes. A single CFTR channel had a dominant conductance of 7.8 pS (H), plus two sub-open states with conductances of approximately 6 pS (M) and 2.7 pS (L) in 200 mM KCl with 1 mM MgCl2 (intracellular) and 50 mM KCl with no MgCl2 (extracellular), with pH maintained at 7.4 by 10 mM HEPES-Tris on both sides of the channel. In 200 mM KCl, both H and L states could be measured in stable single-channel recordings, whereas M could not. Spontaneous transitions between H and L were slow; it took 4.5 min for L-->H, and 3.2 min for H-->L. These slow conversions among subconductance states of the CFTR channel were affected by extracellular Mg; in the presence of millimolar Mg, the channel remained stable in the H state. Similar phenomena were also observed with endogenous CFTR channels in T84 cells. In high-salt conditions (1.5 M KCl), all three conductance states of the expressed CFTR channel, 12.1 pS, 8.2 pS, and 3.6 pS, became stable and seemed to gate independently from each other. The existence of multiple stable conductance states associated with the CFTR channel suggests two possibilities: either a single CFTR molecule can exist in multiple configurations with different conductance values, or the CFTR channel may contain multimers of the 170-kDa CFTR protein, and different conductance states are due to different aggregation states of the CFTR protein.

Adenosine Triphosphate↗
PubMed1996

Expression of recombinant CD59 with an N-terminal peptide epitope facilitates analysis of residues contributing to its complement-inhibitory function.

CD59 is a plasma membrane-anchored glycoprotein that serves to protect human cells from lysis by the C5b-9 complex of complement. The immunodominant epitopes of CD59 are known to be sensitive to disruption of native tertiary structure, complicating immunological measurement of expressed mutant constructs for structure function analysis. In order to quantify cell-surface expression of wild-type and mutant forms of this complement inhibitor, independent of CD59 antigen, an 11-residue peptide (TAG) recognized by monoclonal antibody (mAb) 9E10 was inserted before the N-terminal codon (L1) of mature CD59, in a pcDNA3 expression plasmid. SV-T2 cells were transfected with this plasmid, yielding cell lines expressing 0 to > 10(5) CD59/cell. The TAG-CD59 fusion protein was confirmed to be GPI-anchored, N-glycosylated and showed identical complement-inhibitory function to wild-type CD59, lacking the TAG peptide sequence. Using this construct, the contribution of each of four surface-localized aromatic residues (4Y, 47F, 61Y, and 62Y) to CD59's complement-inhibitory function was examined. These assays revealed normal surface expression with complete loss of complement-inhibitory function in the 4Y --> S, 47F --> G and 61Y --> S mutants. By contrast, 62Y --> S mutants retained approximately 40% of function of wild-type CD59. These studies confirmed the utility of the TAG-CD59 construct for quantifying CD59 surface expression and activity, and implicate surface aromatic residues 4Y, 47F, 61Y and 62Y as essential to maintenance of CD59's normal complement-regulatory function.

Antibodies, Monoclonal↗
PubMed1996

Polyenylphosphatidylcholine attenuates non-alcoholic hepatic fibrosis and accelerates its regression.

BACKGROUND/AIMS: Polyenylphosphatidylcholine protects against alcoholic cirrhosis in the baboon. This study assesses whether the antifibrotic effect also pertains to a species other than the baboon and to agents other than alcohol. METHODS: Rats were injected with either CC14 in peanut oil or peanut oil alone, and pair-fed nutritionally adequate liquid diets, with or without polyenylphosphatidylcholine. Other rats were injected with heterologous albumin instead of CC14. To assess whether polyenylphosphatidylcholine is active on established fibrosis, rats were also given CC14 for 8 weeks, and then divided into two groups and pair-fed a diet with or without polyenylphosphatidylcholine. RESULTS: After 8 weeks of CC14, the animals were sacrificed; chromotrope aniline blue and Sirius red stains of liver revealed fibrosis or cirrhosis in animals given CC14 alone, whereas the effect was attenuated in the polyenylphosphatidylcholine-supplemented animals. Hepatic collagen content was decreased by 25 to 32% (p < 0.05) and serum ALT and AST were significantly less increased. The expression of liver collagen type I mRNA was significantly increased in CC14 treated rats and was not significantly affected by polyenylphosphatidylcholine although there was a trend towards a lesser increase polyenylphosphatidylcholine also attenuated liver fibrosis produced by the injection of heterologous albumin. CC14-induced liver fibrosis regressed more rapidly in polyenylphosphatidylcholine-treated animals than controls, both histologically and by measurement of collagen (p < 0.05). CONCLUSIONS: Polyenylphosphatidylcholine (a) attenuates hepatic fibrosis induced by CC14 or human albumin in rats; and (b) accelerates the regression of pre-existing fibrosis.

Animals↗
PubMed1996

Genomic individuality and its biological implications.

It is a widely accepted fundamental concept that all somatic genomes of a human individual are identical to each other. The theoretical basis of this concept is that all of these somatic genomes are the descendants of the genome of a single fertilized cell as well as the simple replicated products of asexual reproduction, thus not forming any new recombined genomes. The question here is whether such a concept might only represent one side of somatic genome biology and, even worse, whether it has perhaps already led to a very prevalent misconception that within the organism body, there exists no variability among individual somatic genomes. A hypothesis, called genomic individuality, is proposed, simply saying that every individual somatic genome, perhaps with rare exceptions, has its own unique or individual 'genetic identity' or 'fingerprint', which is characterized by its distinctive sequences or patterns of deoxyribonucleic acid molecules, or both. Thus, no two somatic genomes can be identical to each other in every or all aspects, and consequently, there must be a great deal of genomic variation present within the body of any multicellular organism. The concept or hypothesis of genomic individuality would not only provide a more complete understanding of genome biology, but also suggest a new insight into the studies of the biology of cells and organisms.

Adult↗
PubMed1996

Matrix Gla protein gene expression is elevated during postnatal development.

Matrix Gla protein (MGP) is a vitamin K-dependent extracellular matrix protein with a wide tissue distribution. Developmental expression of the MGP gene is characterized by competitive RT-PCR in kidney and calvaria. High levels of MGP mRNA were observed in kidneys and calvaria from 19-day-old embryos to 1-month-old rats. There was a peak in MGP mRNA at 7 days in both tissues. MGP mRNA expression was very low or undetectable in 3-, 5- and 7- month-old kidneys. Similar observations were seen in lung, heart and spleen. However, in connective tissues like calvaria, tibia and trachea, low levels of MGP mRNA are maintained throughout life. Kidney MGP protein was present from birth to 15 days, with the highest MGP protein level at 7 days. Calvarial MGP protein was present throughout development and maturation but peaked at 7 days. The highest MGP protein levels were coincident with peak levels of MGP mRNA. Thus, MGP protein level correlated with mRNA level during rat development. In situ hybridization revealed that MGP staining was most intense in the straight tubules of the developing kidney medulla at 7 days. Staining was absent in stromal cells and in mature nephrons. Taken together, our finding of high MGP mRNA and its intense in situ staining during the postnatal growth phase prove that increased MGP synthesis occurs at a specific time and place during development and maturation.

Animals↗
PubMed1996

Development and preliminary evaluation of VISLAN, a surgical planning and guidance system using intra-operative video imaging.

VISLAN is an integrated neurosurgical planning and guidance system. New segmentation and rendering techniques have been incorporated. A stereo video system is used intra-operatively and fulfils four roles. First, the video display is overlaid with graphical outlines showing the position of the planned craniotomy or the target (enhanced reality displays). Second, a skin surface patch is reconstructed from the stereo video images using patterned light (mean errors of surface point location are < 0.15 mm). Third, a freely mobile, hand-held localizer is tracked in real time (position errors are < 0.5 mm and with improved calibration < 0.2 mm), with its position superimposed on the pre-operative patient representation to assist surgical guidance. Fourth, markers fixed to the skull bone next to the cranial opening are used to detect intra-operative movement and to update registration. Initial results from phantom experiments show an overall system accuracy of better than 0.9 mm for intra-operative localization of features defined in pre-operative images. The prototype system has been tested during six neurosurgical operations with very good results.

Astrocytoma↗