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Biomedical subjects

N J Gutowski

Publications and source records attributed to N J Gutowski.

At least 19 recordsLinked to original sources
PubMed2000

Confirmation of linkage of Duane's syndrome and refinement of the disease locus to an 8.8-cM interval on chromosome 2q31.

Duane's syndrome is a congenital abnormality of eye movement, which may be inherited as an autosomal dominant trait but usually occurs sporadically. Genetic mapping in a Mexican family has recently identified a locus for Duane's syndrome within a 17.8-cM region of chromosome 2q31. The region was flanked by the microsatellite markers D2S2330 and D2S364. We performed linkage and haplotype analysis in a four-generation UK family with autosomal dominant transmission of Duane's syndrome. Linkage to 2q31 was confirmed with a maximum logarithm of differences (lod) score of 3.3 at theta = 0. The genetic interval was reduced to an 8.8-cM region between markers D2S326 and D2S364 that includes the candidate homeobox D gene cluster.

Chromosome Mapping↗
PubMed2000

Duane's syndrome.

Duane's syndrome is an unusual congenital form of strabismus where there is paradoxical anomalous lateral rectus innervation of the affected eye due to misdirection of axons destined for the medial rectus. Three types of Duane's syndrome are recognized. Most cases of Duane's syndrome are sporadic but up to 10% are familial, usually with autosomal dominant inheritance. Several autosomal dominant syndromes with dysmorphic features are associated with Duane's syndrome. Chromosomal loci for genes contributing to Duane's syndrome have been suggested at 4q, 8q and 22q. Duane's syndrome is heterogeneous at multiple levels with variations in its ocular manifestations, accompanying systemic manifestations and in the chromosomal loci with which it may be associated. The definition clinically and genetically of the various subgroups of Duane's syndrome will provide a valuable insight into brainstem axonal guidance to the extraocular muscles during human development.

Duane Retraction Syndrome↗
PubMed1999

Oligodendroglial gliomatosis cerebri: (1)H-MRS suggests elevated glycine/inositol levels.

Oligodendroglial gliomatosis cerebri is very rare. We describe 42-year-old woman who had low-grade oligodendroglial gliomatosis cerebri confirmed on stereotactic biopsy. The diffuse nature of the tumour was apparent clinically, neurophysiologically, on MRI and on proton magnetic resonance spectroscopy (MRS). She also had an isolated, false-localising partial seventh nerve palsy. MRS, of which there are no previous reports, suggested elevated glycine/inositol levels. This might be explained by the cell lineage from which the tumour arose.

Adult↗
PubMed1999

Genetic aberrations in glioblastoma multiforme: translocation of chromosome 10 in an O-2A-like cell line.

We have examined the genetic aberrations in two near-diploid glioblastoma multiforme cell lines that appear to have arisen from different glial lineages. One cell line, Hu-O-2A/Gb1, expresses antigens and metabolic profiles characteristic of the oligodendrocyte-type-2 astrocyte (0-2A) lineage of the rat central nervous system. This line generates, in vitro, cells with characteristics of 0-2A progenitor cells, oligodendrocytes and astrocytes. The second cell line, IN1434, is derived from an astrocyte or a precursor cell restricted to astrocytic differentiation. In Hu-O-2A/Gb1 the sole homologue of chromosome 10 is disrupted at band 10p11-12.1 by translocation with chromosomes X and 15. The translocation breakpoint is localized between genetic markers D10S2103 and [D10S637, D10S1962, D10S355]. Other aberrations include a 5;14 translocation, deletion of the long and short arms of chromosome 16 and loss of one copy of the CDKN2 gene. IN1434 cells share some cytogenetic abnormalities with Hu-O-2A/Gb1 cells, despite their apparent derivation from a different biological origin, but also have translocations involving the long and short arms of chromosome 1 and the long arm of chromosome 7, and deletion of chromosome 13 at bands 13q12-21.

Animals↗
PubMed1999

Tenascin-R and C in multiple sclerosis lesions: relevance to extracellular matrix remodelling.

In the present study the distribution of the inhibitory extracellular molecules tenascin-R (TN-R) and tenascin- C (TN-C) was examined by immunocytochemistry during evolution of the multiple sclerosis (MS) lesion, in which astrogliosis is a prominent feature. Sections were cut from five control cases and from 22 blocks containing lesions representing different pathological stages in 18 cases of secondary progressive MS. Widespread expression of TN-R was found in the normal human central nervous system (CNS), while that of TN-C was in general restricted to white matter. In acute MS plaques however, there was a similar striking loss of both TN-R and TN-C up to the edge of the lesion, where the macrophage density is greatest, extending into the apparently normal white matter. In subacute lesions a TN-C and/or TN-R-immunopositive reactive astrocyte subpopulation was prominent, reflecting synthesis of extracellular matrix molecules. Both tenascins were expressed throughout chronic MS plaques at levels similar to those seen in adjacent white matter. The loss of TN-R and TN-C in acute plaques is indicative of enzyme-mediated breakdown of the matrix which may be a marker of blood-brain barrier breakdown and leucocyte extravasation. Subsequent production of tenascins by reactive astrocytes may result in glial scar formation impeding remyelination and axonal repair in MS lesions.

Adult↗
PubMed1997

Early impairment of foveal magno- and parvocellular pathways in juxta chiasmal tumours.

Foveal pathway visual function was assessed in 11 patients having tumours extending into the suprasellar region but without evidence of visual impairment as assessed by visual acuity and Bjerrum screen campimetry. Psychophysical and routine visual evoked potential (VEP) measurements were obtained from the eye ipsilateral to the maximal suprasellar extension. The sensitivity of luminance and chromatic pathways was assessed psychophysically by measuring increment thresholds for white and red flashes of light presented on a white adapting field. Temporal sensitivity was assessed psychophysically by measuring threshold modulation sensitivity for sinusoidally modulating stimuli (de Lange attenuation characteristic). The patient group showed approximately equal significant psychophysical losses in chromatic, luminance and temporal sensitivities relative to normal controls. Midline VEP P100 latencies of the patient group did not significantly differ from those of the normal control group. It is concluded that tumours extending into the suprasellar region can cause foveal pathway dysfunction affecting both magno- and parvocellular pathways, even in the presence of normal visual acuity and fields suggesting a more widespread and insidious abnormality of the visual pathways in this condition than previously thought.

Adenoma↗
PubMed1996

LIM-kinase1 hemizygosity implicated in impaired visuospatial constructive cognition.

To identify genes important for human cognitive development, we studied Williams syndrome (WS), a developmental disorder that includes poor visuospatial constructive cognition. Here we describe two families with a partial WS phenotype; affected members have the specific WS cognitive profile and vascular disease, but lack other WS features. Submicroscopic chromosome 7q11.23 deletions cosegregate with this phenotype in both families. DNA sequence analyses of the region affected by the smallest deletion (83.6 kb) revealed two genes, elastin (ELN) and LIM-kinase1 (LIMK1). The latter encodes a novel protein kinase with LIM domains and is strongly expressed in the brain. Because ELN mutations cause vascular disease but not cognitive abnormalities, these data implicate LIMK1 hemizygosity in imparied visuospatial constructive cognition.

Base Sequence↗
PubMed1995

Limk1 is predominantly expressed in neural tissues and phosphorylates serine, threonine and tyrosine residues in vitro.

We have isolated the murine Limk1 gene, which is a single copy gene located at the distal end of mouse chromosome 5. Limk1 exhibits a 95% homology to the human homologue, LIMK, which contains two LIM domains and a putative protein kinase domain. Although Limk1 and LIMK contain all motifs found in catalytic kinase domains, amino acids previously described to be diagnostic of either serine/threonine- or tyrosine-kinases are not present. It is demonstrated that GST-Limk1-fusion protein can autophosphorylate on serine, tyrosine and threonine residues in vitro and that mutation of residue D460 within the IHRDL motif abolishes kinase activity. Northern blot showed preferential expression of a 3.5 kb message in adult spinal cord and brain. In situ hybridisation confirmed high expression levels in the nervous system, particularly in the spinal cord and the cranial nerve and dorsal root ganglia. Limk1 also contains two tandem LIM-domains. These zinc-finger like domains can mediate protein-protein interactions and have been described in nuclear and cytoskeletal proteins. The combination of LIM- and kinase domains may provide a novel route by which intracellular signalling can be integrated.

Amino Acid Sequence↗
PubMed1993

Transverse myelitis following general anaesthesia.

A 47-year-old woman developed a complete transverse myelitis 2 weeks after an uncomplicated general anaesthetic for total abdominal hysterectomy and bilateral salpingo-oophorectomy. If spinal or epidural anaesthesia had been used, a causal relationship might have been assumed. This case emphasises the danger of attributing all cases of transverse myelitis which have a close temporal relationship to spinal or epidural anaesthesia, to the anaesthetic technique itself.

Anesthesia, General↗
PubMed1993

Recurrent confusion and hypopituitarism.

Three women in late middle age had recurrent episodes of confusion which could not be explained solely on the basis of an associated infection. All three patients had latent hypopituitarism diagnosed on final presentation. Each patient had a previous history of a severe postpartum haemorrhage followed by two further pregnancies. Experienced clinicians had not made a diagnosis of confusional episodes due to hypopituitary encephalopathy because the history was not immediately available in the confused patient, and the significance of deficient axillary and pubic hair was not given due emphasis.

Confusion↗
PubMed1992

Unilateral upper cervical posterior spinal artery syndrome following sneezing.

A 35 year old man experienced severe transitory neck pain following a violent sneeze. This was followed by neurological symptoms and signs indicating a left sided upper cervical cord lesion. MRI showed an infarct at this site in the territory of the left posterior spinal artery. This discrete infarct was probably due to partial left vertebral artery dissection secondary to sneezing.

Adult↗
PubMed1992

Late onset epilepsy in undiagnosed tuberous sclerosis.

A 67 year old woman first developed left-sided sensorimotor seizures postoperatively in association with infection and mild hyponatraemia. She was found to have previously unrecognized tuberous sclerosis, with gross pathognomic features: periungual fibromata, facial angiofibromata, calcified subependymal nodules, cortical tubers and multiple renal angiomyolipomata. Her son who was epileptic was also found to have other mild features of tuberous sclerosis as a result. As far as we are aware our patient is the oldest for the first presentation of tuberous sclerosis.

Abscess↗
PubMed1987

Thalamotomy for movement disorders: a critical appraisal.

Symptomatic and functional assessments have been made on a number of patients with a variety of involuntary movement disorders. Difficulties of assessment and their relevance to outcome are discussed. Almost all groups showed a substantial symptomatic improvement but functional improvement was less pronounced.

Humans↗