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Biomedical subjects

M H Moore

Publications and source records attributed to M H Moore.

At least 37 records · Page 2Linked to original sources
PubMed1997

Imaging of the Apert syndrome hand using three-dimensional CT and MRI.

Imaging of the Apert syndrome hand is usually done with plain x-rays. This gives only a limited assessment of the grossly abnormal anatomy. Computed tomography (CT) and magnetic resonance imaging (MRI) have the ability to comprehensively demonstrate the spatial arrangement of the bones as well as the anatomy of the soft-tissue structures. This paper demonstrates the use of these two imaging modalities in the complex Apert syndrome hand to improve surgical planning and treatment.

Acrocephalosyndactylia↗
PubMed1996

Factors affecting DNA sequence selectivity of nogalamycin intercalation: the crystal structure of d(TGTACA)2-nogalamycin2.

As part of an investigation into the sequence selectivity of the nogalamycin-DNA interaction, the 1.58 A structure of nogalamycin complexed with d5'(TGTACA)2 has been determined by single-crystal X-ray analysis. The complex crystallised in the orthorhombic space group P2(1)2(1)2(1) with cell dimensions a = 26.3 A, b = 52.0 A and c = 67.1 A, incorporating two B-DNA duplexes and four nogalamycin molecules in the asymmetric unit. The final refined structure included 97 water molecules, one spermine molecule, two acetate ions and one sodium ion, yielding an overall R factor of 19.2% (calculated using all 12,358 reflections in the resolution range 10.7 to 1.6 A) and an Rtree of 23.7% (using 1229 test reflections). The d5'(TGTACA)2 sequence was designed to include the d5'(TpG) pyrimidine-purine base step that has been ascertained as a preferential intercalation site. The complexes in the asymmetric unit are globally similar; one nogalamycin molecule intercalates between each d5'(TpG) step in each duplex. The DNA of each complex exists as a distorted B-DNA duplex displaying some Z-DNA character in the form of C3' endo sugars at some residues. Structural comparisons between the d5'(TGTACA)2-nogalamycin2 complex and the complexes of this drug with the sequences d5'(TGATCA)2 and d5'(5MeCGT(pS)A5MeCG)2 highlight differences in binding interactions between nogalamycin and these various triplet DNA binding sites, with regards to the stability of drug intercalation, which in turn is correlated to effective levels of cytotoxicity towards tumour cells. The number of both direct and water-mediated hydrogen bonds and van der Waal's interactions between substituents of nogalamycin and the d5'(TGTACA)2 and d5'(5MeCGT(pS)A5MeCG)2 sequences are significantly greater than those made with the d5'(TGATCA)2 sequence, suggesting that the central d5'(TpA) in the former confers additional stability to the complex once the drug has bound.

Crystallography, X-Ray↗
PubMed1996

DNA-drug refinement: a comparison of the programs NUCLSQ, PROLSQ, SHELXL93 and X-PLOR, using the low-temperature d(TGATCA)-nogalamycin structure.

In an earlier study [Smith, Davies, Dodson & Moore (1995). Biochemistry, 34, 415-425] the crystal structure of the d(TGATCA)-nogalamycin complex was determined to 1.8 A and refined with PROLSQ to R = 19.5% against 4767 reflections with F> 1sigma(F). A low-temperature crystallographic study on this complex has now been performed. Native data collection at liquid-nitrogen temperature (120 K) improved the resolution to 1.4 A. The structure has now been refined against these new diffraction data in the resolution range 8-1.4 A using NUCLSQ, PROLSQ, SHELXL93 and X-PLOR, in order to determine to what extent the resulting DNA conformation and associated solvent structure would differ and to examine the suitability of these programs for the refinement of oligonucleotide structures. With the advent of more DNA-protein structure determinations, it is of interest to see how well the protein-refinement packages, PROLSQ and X-PLOR, and the small-molecule program, SHELXL93, are able to accommodate DNA. Comparisons are made between the dictionaries, weights and restraints used and the final models obtained from each program. Although the final R values, using all data in the resolution range 8.0-1.4 A, from PROLSQ (22.8%), SHELXL93 (R1 =21.7% after isotropic refinement) and X-PLOR (24.4%) are higher than the R value from the NUCLSQ refinement (21.2%), the root-mean-square deviations between the four final models are very small. Using this high-quality 8.0-1.4 A data set neither the dictionary nor the refinement program leave an imprint on the final fully refined complex. Likewise, the helical parameters and backbone conformation including sugar-puckering modes are not influenced by the refinement procedure used. Although a different number of water molecules is found in each refinement, varying from 62 (X-PLOR) to 86 (NUCLSQ), the first hydration sphere is well conserved in all four models.

Journal Article↗
PubMed1996

Structure determination and refinement of the Humicola insolens endoglucanase V at 1.5 A resolution.

The structure of the catalytic core of the endoglucanase V (EGV) from Humicola insolens has been determined by the method of multiple isomorphous replacement at 1.5 A resolution. The final model, refined with X-PLOR and PROLSQ, has a crystallographic R factor of 0.163 (R(free) = 0.240) with deviations from stereochemical target values of 0.012 A and 0.037 degrees for bonds and angles, respectively. The model was further refined with SHELXL, including anisotropic modelling of the protein-atom temperature factors, to give a final model with an R factor of 0.105 and an R(free) of 0.154. The initial isomorphous replacement electron-density map was poor and uninterpretable but was improved by the use of synchrotron data collected at a wavelength chosen so as to optimize the f" contribution of the anomalous scattering from the heavy atoms. The structure of H. insolens EGV consists of a six-stranded beta-barrel domain, similar to that found in a family of plant defence proteins, linked by a number of disulfide-bonded loop regions. A long open groove runs across the surface of the enzyme either side of which lie the catalytic aspartate residues. The 9 A separation of the catalytic carboxylate groups is consistent with the observation that EGV catalyzes the hydrolysis of the cellulose, beta(1-->4) links with inversion of configuration at the anomeric C1 atom. This structure is the first representative from the glycosyl hydrolase family 45.

Journal Article↗
PubMed1996

Cerebrospinal fluid spaces before and after infant fronto-orbital advancement in unilateral coronal craniosynostosis.

Computed tomographic scan-based examination of the cerebrospinal fluid-filled spaces before and after fronto-orbital advancement in infants with unilateral coronal synostosis was performed. In infants who had not undergone surgery, pronounced compression of the ipsilateral frontal brain substance, frontal subarachnoid space, and frontal horn of the lateral ventricle were evident, with deviation of the interhemisphere fissure. After infant fronto-orbital advancement, frontal dead-space is obliterated early by expansion of the frontal subarachnoid space. Asymmetries interhemispheric fissure are slower to adapt and may be persistent some years later.

Brain↗
PubMed1996

Cranial suture disease in the Apert's syndrome infant.

The histologic findings from sutural specimens remove during early cranial surgery in Apert's syndrome infants have been reviewed. Coronal sutures are uniformly fused histologically in their inferolateral extent, showing a progression to lesser changes at the superior margin. These findings correspond with radiographic changes. The lambdoid sutures occasionally show histologic evidence of fusion, with the same pattern of inferior to superior progression, but a lack of objective radiographic changes.

Acrocephalosyndactylia↗
PubMed1996

Rare craniofacial clefts.

I present a review of the pattern of rare craniofacial clefting in patients presenting to a tertiary referral craniofacial unit. Patients with an isolated rare cleft were uncommon; most had multiple axes of disruption. Midline and paramedian facial clefts, although occasionally occurring alone, often overlap with adjacent facial clefts and extend along an upward cranial axis. The corresponding midline and paramedian facial clefts were never seen in isolation but were almost always seen with their axial downward cleft. Lateral nasal, oro-ocular, and lateral forehead clefts showed diffuse and often poorly defined regions of disruption, resulting in a multiplicity in clefts. The small subgroup of patients with features of the amniotic band sequence had more and differently distributed clefts compared with the larger nonamniotic band group.

Amniotic Band Syndrome↗
PubMed1996

Extradural deadspace after infant fronto-orbital advancement in Apert syndrome.

Infant fronto-orbital advancement is presently a management cornerstone of the craniosynostosis in Apert syndrome. This procedure is based on the premise that the expanding brain rapidly advances in support of, and to remodel, the new frontal facade. This series of infant patients with Apert syndrome undergoing fronto-orbital advancement with early postoperative computerized tomography assessment reveals a large extradural deadspace persistent through the first postoperative week, not obliterated consistently until the fourth week. Early deadspace effacement results from expansion of the prefrontal subarachnoid space, without any significant change in size or shape of the frontal brain substance or ventricles. Brain growth or expansion was particularly slow with brain shape distortions still evident at late follow-up.

Acrocephalosyndactylia↗
PubMed1996

The future of the juvenile court: a theoretical framework that fits.

The juvenile court has been subject to increasing criticism over the years, particularly with regard to its handling of delinquency cases. This is in part the result of an inaccurate view of the court as primarily a criminal court that adjudicates crimes committed by children. This article proposes an alternative model for the court, one that encompasses its jurisdiction over dependency and status offense cases, as well as delinquency cases. In describing this new conception of the juvenile court, an analogy is made to a "bankruptcy" court that intervenes when family members violate the laws regulating their relationships to one another. This new juvenile court would not take direct responsibility for the rehabilitation of child or family. Instead, it would use its power to hold private and public caretakers accountable for fulfilling their roles as supervisors and habilitators of children. The article concludes by exploring the advantages and potential disadvantages of this new vision of the juvenile court.

Adolescent↗
PubMed1995

Direct observation of two base-pairing modes of a cytosine-thymine analogue with guanine in a DNA Z-form duplex: significance for base analogue mutagenesis.

The pyrimidine nucleobase analogue 6H,8H-3,4-dihydropyrimido[4,5-c]- [1,2]oxazin-7-one (P) is a mimic both of cytosine and thymine, since it can form stable hydrogen-bonded base-pairs with either guanine or adenine. To investigate the geometric properties of pairing with guanine in a DNA double helix, the structure of d(CGCGPG)2 has been determined by single crystal X-ray analysis. The oligonucleotide crystallised as a left-handed Z-DNA duplex in the orthorhombic space group P2(1)2(1)2(1) with cell dimensions a = 18.23 A, b = 30.63 A, c = 43.78 A. Refinement using NUCLSQ with 51 water molecules included in the final model converged at R = 0.179 (Rw = 0.159) for 2798 reflections (F > 2 sigma (F)) in the range 8 A to 1.7 A. Remarkably, the two P.G pairs in the hexamer duplex are different: Watson-Crick and wobble types separately illustrate both cytosine-like and thymine-like behaviour. The result suggests that mutagenesis experiments involving P and other analogues which display pronounced base-pairing ambivalence can be used to examine the structural basis of substrate discrimination by polymerases that is essential to accurate genetic replication.

Base Composition↗
PubMed1995

DNA-nogalamycin interactions: the crystal structure of d(TGATCA) complexed with nogalamycin.

The structure of the self-complementary deoxyoligonucleotide d5'(TGATCA) complexed with nogalamycin, an antitumor anthracycline, has been solved to 1.8 A resolution using X-ray crystallographic methods. The technique of single isomorphous replacement, utilizing the anomalous signal of bromine in derivative data collected at three different wavelengths, Cu K alpha, Mo K alpha, and 0.91 A synchroton radiation, was used. The complex crystallized in space group P4(1)2(1)2 with unit cell dimensions a = 37.2 A and c = 70.1 A. The final structure including 116 water molecules has an overall R factor of 19.5% for the 4767 reflections with F > or = 1 sigma F in the resolution range 10.0-1.8 A. One nogalamycin molecule intercalates between each of the d5'(TpG) steps at both ends of a distorted B DNA double helix. This structure provides the first three-dimensional picture of nogalamycin bound to the triplet sequence d5'(TGA), one of its favorable natural binding sites. The drug exhibits a strict requirement for binding to the 3' side of a pyrimidine and the 5' side of a purine. Nogalamycin has bulky sugar groups at either end of a planar aglycon chromophore; therefore, in order for intercalation to occur, the DNA must either transiently open or flex along the helix axis to allow insertion of the chromophore between the base pairs. Conformational change in nogalamycin is observed in the drug-DNA complex with respect to free nogalamycin. Nogalamycin binding to DNA induces severe deformation to the intercalation site base pairs. In comparison to previously reported anthracycline-DNA structures significant differences in base-pair geometry, drug hydrogen-bonding patterns, and the extent of hydration are observed. The position of the drug in this complex is stabilized by a number of nonbonded forces including van der Waals interactions and extensive direct and solvent-mediated hydrogen bonds to the DNA duplex.

Crystallography, X-Ray↗
PubMed1995

Massive craniofacial osteolysis.

Involvement of the craniofacial skeleton by the process of massive osteolysis has been infrequently recorded. We describe a patient whose extent of craniomaxillofacial bony loss defied combined reconstruction by combined autogenous tissue and alloplastic materials. The clinical and radiographic features and management approaches to massive osteolysis are reviewed.

Adult↗
PubMed1995

Central nervous system imaging in Crouzon's syndrome.

Although the need to prevent the secondary effects of craniosynostosis on the central nervous system is fundamental to the practice of craniofacial surgery, the detailed structural anatomy of the central nervous system in the syndromal craniosynostoses has become the subject of recent interest. A clinical and radiographic review of a population of 59 patients with Crouzon's syndrome determined the frequency of central nervous system deformities. Twelve percent of patients had evidence of decreased mental function. Ventriculomegaly on computed tomographic scan was present in 51% and found to be of three grades: mild, moderate, and severe (hydrocephalus). This was nonprogressive in 7 of the 11 patients with follow-up computed tomographic scans. Ten patients underwent surgical release to increase intracranial space; however, 6 of these patients showed no progression in ventricular size. Nonventricular anomalies were found less frequently (14%). Central nervous system findings show fewer nonventricular anomalies than in Apert's syndrome patients, with a corresponding higher mental function. The principal anomaly of ventriculomegaly is not directly related to suture defect and may represent a primary brain abnormality. Recommendations are made for the assessment and management of patients with Crouzon's syndrome with reference to these areas.

Adolescent↗
PubMed1995

The infant skull in Pfeiffer's syndrome.

A review of Pfeiffer's syndrome patients presenting in infancy identifies characteristic patterns of onset and progression of premature sutural fusion. Classic Pfeiffer's syndrome manifests symmetrical bicoronal synostosis; all other sutures are normal. The remaining patients, with a more extreme phenotypic expression, have superimposed on bicoronal synostosis progressive involvement of other cranial sutures, frequent hydrocephalus and craniolacunae, suggesting craniostenosis and intracranial hypertension. Although similar in clinical features and outcome, these patients have been subgrouped according to the presence or absence of a cloverleaf skull anomaly.

Acrocephalosyndactylia↗
PubMed1995

Pfeiffer syndrome: a clinical review.

The combination of bicoronal craniosynostosis, broad thumbs and great toes, and partial variable soft tissue syndactyly of the hands and feet (i.e., Pfeiffer syndrome) classically followed a benign clinical course. A review of the clinical features of those Pfeiffer syndrome patients presenting to our unit confirm another subgroup in whom the craniofacial and associated manifestations are more extreme, with a significant risk of early demise. The early aggressive surgical management of craniostenosis, hydrocephalus, exorbitism, faciostenosis, and upper airway obstruction has provided the potential for prolonged useful survival in these cases.

Acrocephalosyndactylia↗
PubMed1995

Spinal anomalies in Pfeiffer syndrome.

Review of the spinal radiographs of a consecutive series of 11 patients with Pfeiffer syndrome presenting to the Australian Craniofacial Unit was performed. The prevalence of cervical spine fusions was high, and the pattern of fusion complex. Isolated anomalies were evident at lower levels, including two cases of sacrococcygeal eversion. Spinal anomalies occur more frequently in the more severely involved cases of Pfeiffer syndrome emphasizing the generalized dysostotic nature of this condition.

Acrocephalosyndactylia↗
PubMed1995

A homology model of the three-dimensional structure of human O6-alkylguanine-DNA alkyltransferase based on the crystal structure of the C-terminal domain of the Ada protein from Escherichia coli.

O6-Alkylguanine-DNA alkyltransferase (EC 2.1.1.63) repairs O6-alkylguanine lesions in DNA. A homology model of the human protein (hAT) was built, based on the crystal structure of the C-terminal domain of the Ada protein, which carries out a similar repair in Escherichia coli. Sequence alignments of known O6-alkylguanine-DNA alkyltransferases were used to aid the model building using QUANTA and CHARMm software. Despite low homology in the N-terminal half (hAT residues 1-85), a well-defined topology over this region in Ada permitted successful modelling. The C-terminal half of hAT (residues 92-207) was modelled almost entirely by residue-for-residue superposition onto the Ada structure up to residue hAT175. The model was solvated to a residue radius of 8.0 A [corrected] and then minimized using CHARMm. This structural model was used to rationalize findings from site-directed mutagenesis experiments on hAT, to make further predictions on the relationship between structure and function for the alkyltransferase family of proteins, and to explain the specificity towards known small-molecule inhibitors of the protein.

Amino Acid Sequence↗