Biomedical subjects
Publications and source records attributed to M J Dobson.
This article poses a diagnostic problem commonly encountered in neuroradiology and otolaryngology. The solution and ensuing discussion focus on the anatomy of the posterior cranial fossa (with emphasis on the cerebellopontine angle) and the relevant pathology. Current methods of imaging the posterior cranial fossa are explained and their relative merits discussed.
Lateral chest radiography in the investigation of thoracic lymphoma remains a feature of the current literature. This study assessed what information the lateral chest radiograph (CXR) adds in the follow-up of such patients. Eighty-eight patients with known lymphoma who had a CXR and thoracic CT within the same 4-week period were assessed. Five radiologists scored eight mediastinal and hilar nodal groups and eight extramediastinal regions on the frontal CXR as normal, equivocal or definitely abnormal (denoted 0, 1 and 2, respectively). This was repeated 1 week later with a combination of frontal and lateral films. Results were compared with the findings on CT which were scored similarly using accepted criteria for the presence of lymphadenopathy. Where the lateral CXR caused a change in score at any site, this change was compared with CT to determine the effect on diagnostic accuracy. For four of the five observers, the lateral film made no significant difference in diagnostic accuracy in the assessment of mediastinal lymph nodes. A fifth observer derived a small benefit from the addition of the lateral film, although almost 30 % of this was accounted for by changing from a wrong to an equivocal diagnosis. The lateral film did cause a small increase in the detection of pleuro-parenchymal lung lesions, although none of these were clinically significant. We conclude that routine lateral chest radiography is unhelpful in the follow-up of patients with lymphoma.
PURPOSE: To define the appearance of peripheral vascular malformations at magnetic resonance angiography (MRA) and assess the role of magnetic resonance imaging (MRI) and MRA in the investigation of these lesions. PATIENTS AND METHODS: Fourteen patients (aged 8-51 years) with clinical evidence of a vascular malformation were referred for MRI and MRA, performed on a 0.5T GE Vectra superconducting system (International General Electric, Slough, UK). Multisection T1-weighted spin-echo and T2-weighted fast spin-echo pulse sequences were performed, with an inversion recovery fast spin-echo sequence in two cases. Two-dimensional time of flight (2-D TOF) and/or 2-D phase contrast (PC) MRA was performed in 13 cases. Eleven patients had digital subtraction angiography (DSA) using a Phillips Integris V3000 digital angiographic unit. The findings at MRA and MRI were compared with the catheter angiograms, and the effective diagnostic input of MRA and MRI was determined. RESULTS: MRA demonstrated major feeding vessels and multiple intra-lesional vessels in relation to the high flow lesions, features absent in the low flow lesions. However, small feeding vessels to the AVMs were not clearly identified. MRI gave a clear demonstration of the anatomical extent of all lesions. AVMs (n = 6) and venous malformations (n = 6) were reliably distinguished, the former containing multiple serpentine signal voids on T1- and T2-weighted imaging, the latter being hyperintense to fat on T2-weighted images. Two other high-flow lesions diagnosed clinically as vascular malformations appeared solid on MRI, and were diagnosed histologically as a carotid body tumour and an angiomyolipoma. CONCLUSION: Although 2-D TOF MRA can distinguish AVMs from venous malformations, the technique adds little extra practical information to the diagnostic process, and cannot compete with catheter angiography for the detailed demonstration of AVM feeding vessels. These lesions can also be characterized using spin-echo sequences, though the primary role of MRI is to demonstrate their anatomical extent.
The diagnosis of maxillary sinusitis can be difficult, with clinical signs and symptoms leading to a correct diagnosis in only approximately half of cases. This study compared ultrasound and plain radiography of 50 maxillary antra (25 patients) with clinically suspected maxillary sinusitis. Ultrasound showed 100% concordance with plain radiographs reported as normal, and was abnormal in all cases where plain films were reported as showing complete opacification or an air fluid level, the only reliable plain film indicators of an inflamed antrum. We conclude that ultrasound can provide an alternative to plain radiography in the initial investigation of maxillary sinusitis.
Skin tumors were staged at magnetic resonance (MR) imaging on a 0.5-T (middle-field-strength) system, with use of a 2-cm-diameter receive-only surface coil. T1- and T2-weighted spin-echo (SE), fast SE, or three-dimensional (3D) spoiled gradient-recalled imaging were performed in three volunteers and in 13 patients with skin tumors (nine, basal cell carcinoma). MR findings correlated well with histologic findings in the patients (epidermis, relatively hyper-intense on all images; dermis, hypo-intense with irregular interface with subdermal fat). 3D images had the optimal combination of tissue contrast, signal-to-noise ratio, and spatial resolution. MR imaging depicts depth of skin tumor invasion, and findings are complementary to clinical staging.
We have used polyclonal antibodies against fusion proteins produced from cDNA fragments of a meiotic chromosome core protein, Cor1, and a protein present only in the synapsed portions of the cores, Syn1, to detect the occurrence and the locations of these proteins in rodent meiotic prophase chromosomes. The 234 amino acid Cor1 protein is present in early unpaired cores, in the lateral domains of the synaptonemal complex and in the chromosome cores when they separate at diplotene. A novel observation showed the presence of Cor1 axial to the metaphase I chromosomes and substantial amounts of Cor1 in association with pairs of sister centromeres. The centromere-associated Cor1 protein becomes dissociated from the centromeres at anaphase II and it is not found in mitotic metaphase centromeres. The extended presence of Cor1 suggests that it may have a role in chromosome disjunction by fastening chiasmata at metaphase I and by joining sister kinetochores, which ensures co-segregation at anaphase I. Two-colour immunofluorescence of Cor1 and Syn1 demonstrates that synapsis between homologous cores is initiated at few sites but advances rapidly relative to the establishment of new initiation sites. If the rapid advance of synapsis deters additional initiation sites between pairs of homologues, it may provide a mechanism for positive recombination interference. Immunogold epitope mapping of antibodies to four Syn1 fusion proteins places the amino terminus of Syn1 towards the centre of the synaptonemal complex while the carboxyl terminus extends well into the lateral domain of the synaptonemal complex. The Syn1 fusion proteins have a non-specific DNA binding capacity. Immunogold labelling of Cor1 antigens indicates that the lateral domain of the synaptonemal complex is about twice as wide as the apparent width of lateral elements when stained with electron-dense metal ions. Electron microscopy of shadow-cast surface-spread SCs confirms the greater width of the lateral domain. The implication of these dimensions is that the proteins that comprise the synaptic domain overlap with the protein constituents of the lateral domains of the synaptonemal complex more than was apparent from earlier observations. This arrangement suggests that direct interactions might be expected between some of the synaptonemal complex proteins.
The marshlands of coastal southern and eastern England had unusually high levels of mortality from the sixteenth to the nineteenth century. The unhealthiness of the environment aroused frequent comment during this period and it was attributed to an endemic disease known as "marsh fever" or "ague". Marsh parishes were perceived both as a danger to the local inhabitants and as a deterrent to potential settlers. This paper traces the geography and history of the "marsh fever" in England and shows that the disease was, in fact, malaria transmitted by anopheline mosquitoes. Malaria, once endemic in the coastal marshes of England, had a striking impact on local patterns of disease and death. Yet this study also suggests that the species of malaria endemic in England were vivax and malariae and not the tropical strains of P. falciparum. The paper outlines a number of ways in which "benign" forms of malaria, acting either directly or indirectly, as well as in conjunction with other factors, could have given rise to the unusually high death rates experienced in early modern marshland England. The discussion concludes with an examination of the reasons for the clinical disappearance of malaria during the nineteenth century, its reappearance after the First and Second World Wars and the problem of imported malaria in Britain today.
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We have analyzed the DNA sequences associated with four different human telomeres. Two are members of distinct repeated sequence families which are located mainly but not exclusively at telomeres. Two are unique in the genome, one deriving from the long arm telomere of chromosome 7 and the other from the pseudoautosomal telomere. One telomere-associated repeated sequence has a polymorphic distribution among the chromosome ends, being present at a different combination of ends in different individuals. These data thus identify a new source of human genetic variation and indicate that the canonical features of the organization of telomere-associated DNA are widely conserved in evolution.
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Total RNA was extracted daily from the beta-lactam antibiotic producing fungus A. chrysogenum strain CO728 during a 7 day cephalosporin C fermentation. IPNS mRNA species, with a size of about 1.5 kb, were detected by Northern blotting at high levels between days 2 and 4. The rapid appearance of IPNS mRNA in mycelial extracts up to day 2 suggests that IPNS is regulated at the transcriptional level. Primer extension and S1 endonuclease mapping studies indicate the existence of two major and at least two minor transcription initiation start sites. There was no change in the relative levels of the four transcripts during the period they could be detected. A region upstream of the IPNS structural gene (pcbC) has been sequenced and the transcription initiation sites appear as major and minor pairs on either side of one of the pyrimidine-rich blocks that punctuate the promoter sequence.
Although eucaryotic chromosomes vary in size over five orders of magnitude and are constituents of diverse genetic systems the fundamental features of their telomeres appear to be almost completely conserved. This can be exploited to enable molecular cloning of human telomeres in yeast and suggests that many of the ideas that will arise from studies of telomeres in the experimentally tractable ciliates and yeasts will hold true of mammalian telomeres. The particular value of cloned mammalian telomeres is that they contribute reagents for mapping mammalian chromosomes and that they provide one set of elements for the construction of artificial mammalian chromosomes.
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The effect of the yeast 2 micron circle encoded REP1 and REP2 gene products on plasmid partitioning and copy number control was analyzed by removing the open reading frames from their normal sequence context and transcriptional control regions and directing their expression using heterologous promoters in [cir0] host strains. Both the REP1 and REP2 gene products are directly required at appropriate levels of expression to reconstitute the 2 microns circle partitioning system in conjunction with REP3 and the origin of replication. The level of expression of REP2 appears to be critical to re-establishing proper partitioning and may also play a role in monitoring and thereby regulating the plasmid copy number. Constitutive expression of the REP1 and REP2 open reading frames using heterologous expression signals can be used to reconstruct efficient plasmid partitioning even in the absence of FLP-mediated plasmid amplification and a functional D open reading frame.