PubMed Health⌕ Search

Biomedical subjects

D Kingsley

Publications and source records attributed to D Kingsley.

At least 37 records · Page 2Linked to original sources

Destructive lesions in demyelinating disease.

Three cases are presented in which clinical and radiological features suggested the diagnosis of glioma but surgical biopsy revealed a demyelinating process, with tissue destruction and cyst formation in two. One patient had clinically definite multiple sclerosis. Two had probable acute disseminated encephalomyelitis. Treatment with high dose steroids is appropriate when there is clinical or investigative evidence to suggest the presence of demyelinating disease, before deciding on biopsy.

Adolescent↗

Do bilateral optic nerve sheath meningiomas exist?

All patients examined at The National Hospital for Nervous Diseases, Queen Square, from 1983 to 1987 with radiological evidence of meningiomas involving both optic nerves within the orbits have been reviewed. Their clinical and X-ray computed tomography (CT) features are different from those of patients with unilateral tumours, and they appear to form a separate group, probably representing optic nerve involvement by a primarily retro-orbital meningioma.

Adolescent↗

High-level synthesis of biologically active human plasminogen activator inhibitor type 1 (PAI-1) in Escherichia coli.

Segments of a cDNA encoding human plasminogen activator inhibitor type 1 (PAI-1) were subcloned into a highly regulated and inducible Escherichia coli expression system. A plasmid encoding the mature form of human endothelial PAI-1 produced a functional recombinant molecule, as indicated by its ability to inhibit tissue plasminogen activator's enzymatic activity. In contrast to PAI-1 isolated from human fibrosarcoma cells, the biological activity of the recombinant PAI-1 was not dependent on pretreatment with denaturing agents. A construct encoding a polypeptide lacking the first 80 amino acids of PAI-1 also produced elevated levels of the truncated recombinant protein. However, this truncated product was functionally inactive, indicating that an intact N terminus is required for activity.

Amino Acid Sequence↗

Purification and characterization of recombinant plasminogen activator inhibitor-1 from Escherichia coli.

A recombinant form of plasminogen activator inhibitor-1 (rPAI-1) has been purified from lysates of pCE1200, a bacterial expression vector containing the full length PAI-1 gene, by utilizing sequential anion exchange and cation exchange chromatography on Q-Sepharose and S-Sepharose columns. Approximately 140 mg of rPAI-1, estimated at 98% purity on the basis of analytical high performance liquid chromatography, could be obtained from 200 g wet weight of cells. The purified protein exhibited a single Coomassie Blue-stainable band at the region of Mr = 42,000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and an NH2-terminal amino acid sequence consistent with the expected translation product of the pCE1200 PAI-1 insert. The rPAI-1 rapidly inhibited single- and two-chain tissue plasminogen activators, as well as urokinase, with apparent second order rate constants in the range of 2-5 x 10(7) M-1 s-1. A specific activity measurement of 250,000 units/mg was calculated for the rPAI-1 based on its ability to inhibit the enzymatic activity of a single-chain tissue plasminogen activator. Stability studies showed that the activity of the rPAI-1 was very stable when stored at temperatures of 25 degrees C or lower, but decayed within hours when stored at 37 degrees C. Sodium dodecyl sulfate treatment, which partially activates the latent form of natural PAI-1, inactivated rPAI-1. These results show that the purified rPAI-1 produced from pCE1200 displays many of the properties associated with the biologically active form of natural PAI-1.

Amino Acid Sequence↗

Joubert syndrome: a clinico-radiological study.

A characteristic malformation of the cerebellum, including dysgenesis of the vermis and enlargement of the fourth ventricle was observed on computed tomography (CT) in 16 children on review of our consecutive material. Seven of these children underwent magnetic resonance imaging (MRI) which showed hypoplasia of the brainstem in addition to cerebellar vermian dysgenesis. One child had, in addition, dysgenesis of the corpus callosum. All these children were developmentally delayed, and many had neonatal breathing abnormalities, congenital retinal dystrophy and supranuclear ocular motor abnormalities. Joubert's syndrome should be suspected in children in whom dysgenesis of the cerebellar vermis and hypoplasia of the brainstem is shown on CT or MRI.

Brain Stem↗

Acute disseminated encephalomyelitis. MRI findings and the distinction from multiple sclerosis.

Brain MRI was performed on 12 patients with acute disseminated encephalomyelitis (ADEM). Multifocal white matter lesions indistinguishable from those seen in multiple sclerosis (MS) were found in 10. In 5 there were rather extensive symmetric abnormalities in the cerebral (2) or cerebellar white matter (2), or basal ganglia (1). Follow-up MRI after intervals of 2 wks to 18 months demonstrated partial resolution of the abnormalities, but some persisting lesions. New MRI lesions were found at follow-up in only 1 case after an interval of 2 wks. Serial MRI makes a useful contribution to the distinction between MS and ADEM.

Acute Disease↗

Value of CT and NMR imaging in diagnosing of chordomas.

Chordomas usually occur in the axial skeleton and they arise from the remnants of notochord. Their growth is slow and they often give metastases. Such cases are mainly observed among people above 40 years of age. Most frequently chordomas are situated in sacral bone (50%), in spheno-occipital region of the skull base (35%), and in the cervical, dorsal and lumbar spine (15%). Very rarely chordomas are found within sella, paranasal sinuses and nasopharynx, and in the forms of ectopic foci in the pons and spinal canal. Such tumour situated within spine destroys vertebral bodies and arches and can bulge into subdural space causing impression of the dural sac. Despite osteolytic destruction, chordomas cause visible reactive sclerotization and characteristic granular calcifications or ossifications. Intracranial chordomas destroy bony base of skull, specially clivus, pyramids and sphenoid sinuses.

Adolescent↗

MRI and hydrocephalus in childhood.

In six young patients presenting with raised intracranial pressure during the period of a year, CT revealed the presence of hydrocephalus, but not the cause. Magnetic Resonance Imaging not only showed the site and nature of the obstructing lesion, but also detected additional clinically silent spinal cord tumors in five of the patients. The place of MRI in the diagnosis of diseases involving the region of the cranio-cervical junction and in the elucidation of "unexplained hydrocephalus" is considered.

Child↗

Use of a mutant cell line to study the kinetics and function of O-linked glycosylation of low density lipoprotein receptors.

A rapidly reversible defect in protein O-glycosylation exhibited by a line of mutant Chinese hamster ovary (CHO) cells was used to study the kinetics and function of O-glycosylation of the low density lipoprotein (LDL) receptor. The mutant line, genotype LDLD, cannot synthesize UDP-N-acetylgalactosamine under normal culture conditions and, therefore, cannot add mucin-type O-linked oligosaccharides to proteins. The UDP-N-acetylgalactosamine pools in LDLD cells can be filled rapidly when N-acetylgalactosamine is added to the culture medium, thus restoring normal synthesis of O-linked carbohydrates. Pulse-chase metabolic labeling experiments were used to show that (i) the first step in the O-glycosylation of LDL receptors can occur posttranslationally; (ii) after O-linked sugar-deficient LDL receptors reach the cell surface, they are not subject to subsequent O-linked sugar addition, suggesting that they do not return to compartments in which O-glycosylation takes place; (iii) O-linked carbohydrate chains on the LDL receptor itself are required for normal stability and function; and (iv) the instability of the O-linked sugar-deficient LDL receptor is due to proteolytic cleavage and the release into the medium of the bulk of the NH2-terminal extracellular domain of the receptor. It appears that O-glycosylation of the LDL receptor and several other cell surface glycoproteins permits stable cell-surface expression by preventing proteolytic cleavage of the extracellular domains of these proteins.

Animals↗

Applications of a computerized adjustable brain atlas in positron emission tomography.

A computerized brain atlas, adjustable to the patient's anatomy, has been developed. It is primarily intended for use in positron emission tomography (PET), but may also be employed in other fields utilizing neuro-imaging, such as stereotactic surgery. The atlas is based on anatomic information obtained from digitized cryosectioned cadaver brains. It can be adjusted to fit a wide range of individual brains with reasonable accuracy. The corresponding transformation is chosen so that the modified atlas agrees with a set of CT or MR images of the patient. The computerized atlas can be used to facilitate and improve the quantification and evaluation of PET data by: enabling the merging and comparison of results from different individuals or groups of individuals; serving as a vehicle in the comparison of different examinations of the same patient, thus reducing the need of reproducible fixation systems; supplying external information to be used in the image reconstruction, such as proper three-dimensional regions of interest; improving the attenuation and scatter corrections; helping to select suitable patient orientation during the PET study. By applying the inverse atlas transformation to the PET data volume it is possible to relate the PET information to the anatomy of the reference atlas. Reformatted PET data from different patients can thus be averaged, and averages from different categories of patients can be compared. The method will facilitate the identification of statistically significant differences in the PET information from different groups of patients.

Brain↗

Amphotericin B selection of mutant Chinese hamster cells with defects in the receptor-mediated endocytosis of low density lipoprotein and cholesterol biosynthesis.

This paper describes a rapid and efficient two-step procedure for the isolation of mutant cells with defects in receptor-mediated endocytosis. The procedure takes advantage of two fungal metabolites, compactin (ML236B), a potent inhibitor of cholesterol biosynthesis, and amphotericin B, a polyene antibiotic that forms toxic complexes with sterols in membranes. Mutagen-treated Chinese hamster ovary cells were preincubated overnight in a medium containing mevalonate, low density lipoprotein (LDL), and compactin (Mev/LDL/Com). At the end of the preincubation period, wild-type cells were cholesterol replete while mutant cells that could not utilize the cholesterol in LDL were cholesterol deficient. Subsequent incubation with amphotericin B for 6 hr killed most of the wild-type cells. After a second round of Mev/LDL/Com-amphotericin B selection, endocytosis-defective clones appeared at a frequency of approximately equal to 2.6 X 10(-5). Some of these clones expressed LDL receptor-defective phenotypes and fell into one of two previously defined classes of mutation. Sensitivity of the mutants to infection by vesicular stomatitis virus suggested that the mutations do not disrupt the coated pit-coated vesicle pathway of endocytosis. Minor modifications in the Mev/LDL/Com-amphotericin B selection permit the isolation of cholesterol auxotrophs and might allow the isolation of conditional-lethal mutations. Because LDL can be coupled to ligands that bind to receptors other than the LDL receptor, Mev/LDL/Com-amphotericin B selection may permit the isolation of mutant cells with defects that specifically disrupt other endocytic pathways.

Amphotericin B↗

Head fixation system for integration of radiodiagnostic and therapeutic procedures.

A head fixation system is described enabling exact transfer of positions between neuroradiological and therapeutic procedures. The key item of the system is a base plate that is rigidly attached to the patient's head, either by a plastic mould or screws onto the calvarium. The base plate may easily and accurately be attached to diagnostic or therapeutic units. Coordinates of target points in the various units are directly related through the exact application of the base plate. Procedures for the exact comparison of spatial information have been worked out. The system has been used for diagnostic procedures such as plain skull radiography, cerebral angiography, CT scanning, position emission tomography, and gamma camera examinations, as well as for therapeutic procedures such as stereotaxic biopsy and radiation treatment.

Head↗

Receiver operating characteristic curves in the evaluation of hard copies of computed tomography scans.

Receiver operating characteristic curves have been used to compare a variety of pictures derived from a number of hard copy devices used with EMI computed tomography scanners. The pictures examined were obtained from (a) a Shackman camera with bromide paper, (b) a Polaroid camera and Polaroid film, (c) a Shackman backed camera with radiographic film, and (d) an EMI multiformat imager. The results show no significant difference in detectability of an experimental object close to noise values using the various hard copies. It is concluded that the choice of a hard copy device might be based on considerations other than its physical performance.

Data Display↗

The value of computed tomography in the evaluation of the enlarged head.

The contribution of computed tomography (CT) in the assessment of macrocrania has been examined with reference to a consecutive series of 93 cases. In the great majority a definitive diagnosis could be made without resorting to more noxious procedures. Hydrocephalus was present in 46% of this group. The incidence of macrocrania with childhood hydrocephalus and its relationship to the aetiology and other CT features was examined with reference to 109 consecutive cases with hydrocephalus shown on CT. Macrocrania was present in only 11% of cases with an underlying tumour, but in 71% with other obstructing lesions.

Arachnoid↗

Growing fractures of the skull.

Tne cases of growing fractures seen in the last 10 years are presented. Six of the patients sustained their injury within the first six months of life. The defects formed rapidly, several within two or three months after injury. There was enlargement of the defect in only one case after the date of discovery. Although the defects involved the parietal bone most commonly, in four out of 10 the lesion crossed either the coronal or the lambdoid suture. The edges of the defects were usually thickened; in some areas they were saucer-shaped but in two cases there was erosion of the outer table of the skull at a distance from the margin of the defect, the erosion being related to an extracranial fluid-filled cavity in continuity with a porencephalic cyst. The ipsilateral ventricle was usually dilated and in a number of cases was associated with a porencephalic cyst. In no case was a "leptomeningeal cyst" found beneath the defect at operation. A detailed review confirms many of the findings previously described but suggests that the pathology of the condition is still not fully understood. Computed tomography, undertaken in one case, appears to be the examination of choice. Further light may be thrown on the pathogenesis of this condition by the use of intracystic, intrathecal, and intraventricular water-soluble contrast media.

Arachnoid↗