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Biomedical subjects

R S Kerr

Publications and source records attributed to R S Kerr.

18 recordsLinked to original sources

Isolation and characterization of chondroitin sulfate proteoglycans from embryonic quail that influence neural crest cell behavior.

The movement of neural crest cells is controlled in part by extracellular matrix. Aggrecan, the chondroitin sulfate proteoglycan from adult cartilage, curtails the ability of neural crest cells to adhere, spread, and move across otherwise favorable matrix substrates in vitro. Our aim was to isolate, characterize, and compare the structure and effect on neural crest cells of aggrecan and proteoglycans purified from the tissues through which neural crest cells migrate. We metabolically radiolabeled proteoglycans in E2.5 quail embryos and isolated and characterized proteoglycans from E3.3 quail trunk and limb bud. The major labeled proteoglycan was highly negatively charged, similar in hydrodynamic size to chick limb bud versican/PG-M, smaller than adult cartilage aggrecan but larger than reported for embryonic sternal cartilage aggrecan. The molecular weight of the iodinated core protein was about 400 kDa, which is more than reported for aggrecan but less than that of chick versican/PG-M. The proteoglycan bore chondroitin sulfate glycosaminoglycan chains of 45 kDa, which is larger than those of aggrecan. It lacked dermatan sulfate, heparan sulfate, or keratan sulfate chains. It bound to collagen type I, like aggrecan, but not to fibronectin (unlike versican/PG-M), collagen type IV, or laminin-1 in solid-phase assays and it bound to hyaluronate in gel-shift assays. When added at concentrations between 10 and 30 microg/ml to substrates of fibronectin, trunk proteoglycan inhibited neural crest cell spreading and migration. Attenuation of cell spreading was shown to be the most sensitive and titratable measure of the effect on neural crest cells. This effect was sensitive to digestion with chondroitinase ABC. Similar cell behavior was also produced by aggrecan and the small dermatan sulfate proteoglycan decorin; however, 30-fold more aggrecan was required to produce an effect of similar magnitude. When added in solution to neural crest cells which were already spread and migrating on fibronectin, the embryonic proteoglycan rapidly and reversibly caused complete rounding of the cells, being at least 30-fold more potent than aggrecan in this activity.

Aggrecans↗

Changes in cell adhesion and extracellular matrix molecules in spontaneous spinal neural tube defects in avian embryos.

Quail embryos (embryonic days 2-2.5) with spontaneous neural tube defects (NTDs), along with age-matched normal embryos, were examined immunocytochemically for the extracellular matrix (ECM) molecules laminin, fibronectin, and chondroitin sulfate proteoglycan, the cell adhesion molecules (CAMs) E- and N-cadherin and neural CAM (NCAM), and the neural crest marker HNK-1. The embryos with NTDs were at the lower limit of the normal stage range and the affected region was about 25% shorter than in normal embryos. Open NTDs occurred in cervical and upper thoracic level, although often the ventral neural tube was morphologically normal. Widened, irregular but closed neural tubes (lower thoracic to sacral levels) showed disorganized mesenchyme-like cells centrally and often multiple lumens. Finger-like tabs projecting from the ectoderm over the neural tube also occurred at lower thoracic to sacral levels. In open NTDs, the E-cadherin-labeled epidermis was incomplete dorsally, and was continuous with the N-cadherin-labeled neural tissue, with a sharp demarcation between E- and N-cadherin-expressing regions, as in the early stages of normal primary neurulation. A sharp inverted peak of epidermis extended ventrally, closely applied to the side of the neural tissue. The intervening matrix labeled less intensely for chondroitin sulfate proteoglycan relative to laminin and fibronectin, in comparison to control embryos. In closed NTDs, the dorsal superficial cell layer (i.e., positionally epidermis) was not separated from the underlying neural tissue by a band of matrix as in control embryos. In addition, this layer expressed E-cadherin (as in normal embryos), but coexpressed N-cadherin and NCAM, which are not normally found here at this stage. This overlap region resembled the mid-dorsal tissue at earlier stages in normal secondary neurulation in the tail-bud. The tabs of tissue appeared to be localized hypertrophy of the epidermal and neural ectoderm, and also showed codistribution of E- and N-cadherin. In all these defects, matrix molecules occurred within (rather than around) the neural and epidermal epithelia. HNK-1-labeled neural crest cells were frequently absent in regions of NTDs, in contrast to control embryos. These results show that matrix and cell adhesion molecules are disturbed in spontaneous NTDs at the time of neurulation, and therefore could be involved in the generation of the defects by altering cell adhesion-dependent morphogenetic events.

Animals↗

Benign intracerebral cysts with ependymal lining: pathological and radiological features.

Cerebral intraparenchymal cysts without communication with the ventricles are very rare. We report four such cases with no relevant past history or evidence of infection, haemorrhage, trauma, tumour or congenital neural tube defect. At operation smooth wailed cysts with an ependymal-type lining were found. To the best of our knowledge, we present the first correlation of their pathological and radiological features (including magnetic resonance imaging). We also review the literature on these cysts.

Adult↗

Endosaccular treatment of inoperable intracranial aneurysms with platinum coils.

Endosaccular packing of inoperable aneurysms with electrolytic platinum coils was performed in 50 patients. Complete embolization of the aneurysms was achieved in 100% of small, 95% of large and 85% of giant aneurysms, with combined procedural and periprocedural morbidity and mortality rates of 6 and 4%, respectively. Follow-up angiography of 42 aneurysms demonstrated some degree of refilling in 17% of small, 19% of large and 50% of giant aneurysms. The risks associated with the procedure were similar in aneurysms of the carotid and vertebrobasilar circulations. This treatment should therefore be considered for all inoperable aneurysms and particularly for aneurysms involving the posterior circulation. Its long-term efficacy remains uncertain.

Adult↗

Effect of a new computed tomographic image transfer system on management of referrals to a regional neurosurgical service.

A computed tomographic image transfer system ('Image Link') was used to link scanners within the Oxford region, UK, to the regional neurosurgical service. 100 consecutive neurosurgical referrals were examined by this system; 43% of the emergency referrals did not require transfer, 31% were transferred electively, and 26% urgently. Most of the patients defined as potentially hazardous for transfer (10/11) did not require neurosurgical intervention. The delay by the use of the system was negligible and early detection of intracranial haematoma contributed to good outcome in some head injured patients. Overall, 3,170 miles of ambulance journey were avoided. Use of image link has led to substantial improvements in management of neurosurgical emergency referrals, cost-effectiveness of neurosurgical and ambulance facilities, and interhospital communication between doctors.

Adolescent↗

Pasteurella multocida: a rare case of shunt infection.

Pasteurella multocida, the major pathogen following an animal bite, is a rare cause of intracranial infection. This report documents the first case of ventriculo-peritoneal shunt infection with Pasteurella multocida.

Adult↗

Persistent CSF leucocytosis associated with intrathecal gentamycin.

A case where the administration of intrathecal gentamycin, used to treat a ventriculitis consequent upon a ventriculoperitoneal shunt infection, with a persistent elevation of the CSF leucocyte count is described. In a situation where the number of white cells in the CSF is taken to indicate resolution of infection, it is important to recognise that apparent failure of resolution of infection may be due to the gentamycin itself and not persistent infection.

Brain Diseases↗

A quantitative assessment by flow cytometry of the preservation of the Thy-1 antigen by various fixation procedures.

A quantitative assessment of the effects of various fixatives upon the preservation of the Thy-1 surface antigen has been undertaken. A panel of 5 monoclonal antibodies (MAbs) have been reacted with mouse lymphocytes treated with various fixatives, and their binding analysed by flow cytometry using a fluorescence activated cell sorter. It was found that 2% paraformaldehyde (PFA) provided the best antigenic preservation, as detected by both the anti Thy-1.1 and anti Thy-1.2 MAbs. The effectiveness of 2% PFA fixation is further demonstrated by the immunohistochemical identification of the Thy-1 antigen in sections of mouse cerebellar cortex.

Animals↗

The value of accurate clinical assessment in the surgical management of the lumbar disc protrusion.

One hundred patients with lumbar disc protrusions were studied. Thirty six "control" patients were admitted in the same time period with low back pain and sciatica but with subsequently "normal" myelograms and no surgery. The aim of this paper was to relate history and clinical signs to the myelograms and surgical findings. Ninety nine per cent of our patients presented with sciatica (controls 94%). The most frequently found sign in patients with a disc protrusion was reduction of ipsilateral straight leg raising (98%). However, 55% of controls also showed this sign. There were three signs that, when present, particularly indicated a disc protrusion; "crossed straight leg raising" (pain on contralateral straight leg raising), measured calf wasting and impaired ankle reflex: the latter being especially indicative of an L5-S1 disc protrusion. There were two further important signs, weakness of dorsiflexion of the foot and scoliosis of the lumbar spine. However, such signs occurred in about half the patients and so clinical diagnosis in the remaining half depended on obtaining a good history of sciatica, and paying due regard to severity of the pain, the mobility of the patient, the ability and desire to work and the overall personality. Satisfactory results of surgery simply depend on finding and removing a definite disc protrusion. Using these methods of selection, 98% have returned to their original employment, 86% within 3 months of the operation. For a patient with no abnormal signs and a normal myelogram, surgical treatment should not be advised.

Adult↗

Lymphomatoid granulomatosis apparently confined to one temporal lobe. Case report.

Lymphomatoid granulomatosis is of uncertain etiology and poses problems with diagnosis and treatment. A case with involvement of the right temporal lobe, but associated with cystoid macular edema of the retina, is described. The unusual mode of presentation, the radiographic, operative, and pathological findings, the response to surgery and radiotherapy, and the possible etiology are discussed.

Adult↗