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J F Geddes

Publications and source records attributed to J F Geddes.

At least 55 records · Page 3Linked to original sources
PubMed1996

Plectin deficiency results in muscular dystrophy with epidermolysis bullosa.

We report that mutation in the gene for plectin, a cytoskeleton-membrane anchorage protein, is a cause of autosomal recessive muscular dystrophy associated with skin blistering (epidermolysis bullosa simplex). The evidence comes from absence of plectin by antibody staining in affected individuals from four families, supportive genetic analysis (localization of the human plectin gene to chromosome 8q24.13-qter and evidence for disease segregation with markers in this region) and finally the identification of a homozygous frameshift mutation detected in plectin cDNA. Absence of the large multifunctional cytoskeleton protein plectin can simultaneously account for structural failure in both muscle and skin.

Amino Acid Sequence↗
PubMed1996

Granular cell change in astrocytic tumors.

Intracerebral granular cell neoplasms are uncommon. We report five hemispheric astrocytomas, all of which showed the distinctive features of granular cell change, being composed exclusively or predominantly of rounded cells with coarse granular eosinophilic cytoplasm and eccentrically placed nuclei. Four showed clear foci of transition from an anaplastic astrocytoma and contained lipidized as well as granular cells. In all tumors, the cytoplasmic granules were positive for periodic acid Schiff and resistant to diastase digestion, and there was focal glial fibrillary acidic protein expression. In addition, diffuse cytoplasmic positivity with epithelial membrane antigen antiserum was present, but in no case was there true membrane staining. Ultrastructural appearances were similar in four cases, showing the cytoplasm of tumor cells to be filled with membrane-bound autophagic vacuoles; bundles of intermediate filaments were also seen in some cells. Despite earlier controversy over the histogenesis of granular cell tumors, it is now clear that granular change is a degenerative phenomenon that, like lipidization, can occur in tumors of different cell types, including--rarely--astrocytic neoplasms. It is important that this histologic variant be recognized, as on a small biopsy sample diagnostic confusion with an infarct, demyelinating disease or a secondary carcinoma is a real possibility.

Aged↗
PubMed1996

Neurofibrillary tangles, but not Alzheimer-type pathology, in a young boxer.

The chronic neurological sequelae of boxing are well described, but there have been few neuropathological studies of boxers dying early in their career. We report the case of a 23-year-old boxer, whose brain showed neurofibrillary tangles in all neocortical areas, but remarkable sparing of medial temporal lobe structures. These tangles, assumed to be the result of repetitive head injury, were the only detectable abnormality: none of the other changes previously described in the brains of retired boxers were seen. The distribution and features of the neuropathological findings in this case suggest that the mechanism of tangle formation induced by repetitive head trauma may be different from that in Alzheimer's disease.

Adult↗
PubMed1995

Focal myositis: a clinicopathological study.

Focal myositis is a rare, benign inflammatory condition that may clinically simulate a soft tissue sarcoma. It was first described in 1977 and around 30 cases have been reported to date. We report two further cases on which we have performed immunocytochemistry and electron microscopy. Histology of both lesions was identical, showing a destructive inflammatory myopathy with evidence of regeneration. Stains for micro-organisms were negative and no viral particles were seen on electron microscopy. The immunocytochemical profile of our two cases differed from that of polymyositis: with a panel of T- and B-cell markers the cellular infiltrate was found to be composed of T-lymphocytes and variable numbers of macrophages: sub-typing in one case revealed the T-cells to be predominantly CD4+ cells. Use of antibodies to MHC class 1 and 2 antigens showed occasional positive inflammatory cells only. Clinicopathological correlations and the differential diagnosis are discussed.

Aged↗
PubMed1995

Loss of heterozygosity for DNA polymorphisms mapping to chromosomes 10 and 17 and prognosis in patients with gliomas.

Twenty nine patients with gliomas were investigated for loss of heterozygosity for 40 DNA polymorphisms in tumour DNA, particularly concentrating on those mapping to chromosomes 10 and 17. Eight of 18 grade IV gliomas showed loss of sequences from chromosomes 10, 17, or both. The data suggested total loss of one copy of chromosome 10, but there were interstitial deletions of the short arm of chromosome 17 in three of five tumours. Heterogeneous interstitial deletions of chromosome 17 were also found in two lower grade astrocytomas and one benign oligodendroglioma. The striking finding of this study was that patients with high grade gliomas whose tumours exhibited loss of heterozygosity for chromosomes 10, 17, or both survived significantly longer after surgery (median 17.4 months) than those whose tumours did not show loss of these chromosomes (median 6.7 months). These findings suggest that there is a subset of particularly aggressive high grade gliomas with no currently known molecular genetic abnormalities.

Adult↗
PubMed1995

Glycoprotein hormone alpha-subunit production and plurihormonality in human corticotroph tumours--an in vitro and immunohistochemical study.

Glycoprotein hormone alpha-subunit (alpha SU) is a recognized product of clinically non-functioning, glycoprotein hormone-secreting and somatotroph adenomas but has not been studied systematically in corticotroph tumours. We have performed immunohistochemistry for alpha SU in a consecutive series of four corticotroph tumours causing Nelson's syndrome, three corticotroph macroadenomas, 12 corticotroph microadenomas and one adrenocorticotrophin-secreting bronchial carcinoid tumour. In addition we have assessed alpha SU secretion in vitro in corticotroph adenomas from two subjects with Cushing's disease and two subjects with Nelson's syndrome. Immunohistochemistry, performed after microwave treatment of sections to enhance antigen retrieval, demonstrated alpha SU positivity in 3/4 Nelson's tumours, 2/3 corticotroph macroadenomas, 7/12 microadenomas and one bronchial carcinoid. Eight of the 13 tumours positive for alpha SU were also immunostained after microwave pretreatment of sections for thyrotrophin (six positive), follicle-stimulating hormone (four positive), luteinizing hormone (three positive), beta-chorionic gonadotrophin (five positive), growth hormone (three positive) and prolactin (two positive) immunoreactivity. In vitro cell cultures of all four tumours studied secreted adrenocorticotrophin and three secreted alpha SU, with the variable presence of luteinizing hormone, follicle-stimulating hormone, thyrotrophin, growth hormone and prolactin, in basal culture. The alpha SU secretion was augmented by phorbol ester (160 +/- 15%, SEM, n = 3 wells; p < 0.01) and 8-bromo-cAMP (138 +/- 8%; p < 0.05) in one tumour. These data indicate that plurihormonality and, in particular, alpha SU elaboration and secretion by corticotroph tumours is more common than hitherto recognized. Possible mechanisms include abnormal or deregulated gene expression, autocrine or paracrine effects or a stem cell origin of tumour.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma↗
PubMed1994

Detection of multidrug resistance gene product (P-glycoprotein) expression in ependymomas.

A neurosurgical series of 33 ependymal tumours was examined for expression of the membrane transport molecule P-glycoprotein, which is linked with the development of multidrug resistance in many human tumours. We employed the monoclonal antibodies JSB1 and C219, raised to two different epitopes of the P-glycoprotein molecule, and found P-glycoprotein expression both in normal ependyma and in 29 of the tumours. This is the first time that ependymal tumours have been demonstrated to express the protein, and we conclude that its expression may contribute to the reported failure of adjuvant chemotherapy to improve outcome in ependymomas.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1994

Effects of pituitary adenylate cyclase-activating polypeptide on hormone secretion by human pituitary adenomas in vitro.

Hormone release in culture in response to pituitary adenylate cyclase-activating polypeptide (PACAP) was examined in 28 human pituitary adenomas: 10 null cell adenomas, 4 gonadotropin-, 6 GH-, 6 ACTH-, and 2 PRL-producing adenomas. The effects of PACAP38 were compared with those of the classical hypothalamic releasing hormones and other activators of intracellular signaling pathways. PACAP38 significantly stimulated GH release from 1 somatotrope tumor (125 +/- 3% of control; P < 0.05) and ACTH release from 3 corticotrope tumors (134 +/- 6%, 136 +/- 7%, and 137 +/- 9% of control; P < 0.05). The effects of PACAP38 were less potent than either GHRH on GH release in the somatotrope tumor or CRH on ACTH release in the corticotrope tumors but similar to the responses seen with the cAMP analog 8-bromo-cAMP (8-Br-cAMP). No detectable effects of PACAP38 on hormone release from null cell, gonadotropin-, or PRL-producing adenomas were observed. Of the 5 somatotrope tumors that failed to respond to PACAP38, all also failed to respond to either 8-Br-cAMP, TRH, or GHRH. Of the corticotrope tumors that failed to respond, 2 of the 3 also failed to respond to CRH. In addition to eliciting hormone release appropriate to the tumor type, PACAP38 also stimulated glycoprotein hormone alpha-subunit (alpha SU) release from one somatotrope tumor (229 +/- 35% of control, P < 0.01) and one corticotrope tumor (149 +/- 4% of control; P < 0.01). This response was not mimicked by 8-Br-cAMP in the somatotrope tumor, but in the corticotrope tumor a significant alpha SU release was also seen after stimulation with the protein kinase C activator 12-O-tetradecanoyl-phorbol-13-acetate and 8-Br-cAMP. These results suggest that the novel hypothalamic peptide PACAP38 has a modest role in the regulation of GH, ACTH, and alpha SU secretion from some human tumourous pituitary corticotropes and somatotropes. Further studies are needed to elucidate the intracellular signaling pathways that mediate the effects of PACAP on hormone secretion by these tumor types.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1993

Pathological overlap in cases of parkinsonism associated with neurofibrillary tangles. A study of recent cases of postencephalitic parkinsonism and comparison with progressive supranuclear palsy and Guamanian parkinsonism-dementia complex.

In recent years a number of patients suffering from long-standing postencephalitic parkinsonism have donated their brains to the United Kingdom Parkinson's Disease Society Brain Bank, in London. In view of the paucity of detailed neuropathological reports of the disease since the 1940s, we have carried out a clinicopathological study of eight recent cases. A spectrum of pathological change was seen, with highly variable involvement of cortical, subcortical and brainstem structures. There was no correlation between severity of disease and severity of pathology. The anatomical distribution of lesions was compared with that seen in progressive supranuclear palsy and Guamanian Parkinson-dementia complex. No definite histological features were identified that could distinguish any of the three disease entities. While the pathogenesis of postencephalitic parkinsonism, progressive supranuclear palsy and Guamanian Parkinson-dementia complex remains unknown, the presence of similar pathologies in these conditions suggests a common disease mechanism, despite the distinctive clinical features.

Aged↗
PubMed1993

Neuropathology of the brainstem and spinal cord in end stage rheumatoid arthritis: implications for treatment.

OBJECTIVE: To study the detailed histopathological changes in the brainstem and spinal cord in nine patients with severe end stage rheumatoid arthritis, all with clinical myelopathy and craniocervical compression. METHODS: At necropsy the sites of bony pathology were related exactly to cord segments and histological changes, and correlated with clinical and radiological findings. RESULTS: Cranial nerve and brainstem pathology was rare. In addition to the obvious craniocervical compression, there were widespread subaxial changes in the spinal cord. Pathology was localised primarily to the dorsal white matter and there was no evidence of vasculitis or ischaemic changes. CONCLUSIONS: Myelopathy in rheumatoid arthritis is probably caused by the effects of compression, stretch, and movement, not ischaemia. The additional subaxial compression may be an important component in the clinical picture, and may explain why craniocervical decompression alone may not alleviate neurological signs.

Aged↗
PubMed1992

Primary cerebral lymphoma: a study of 47 cases probed for Epstein-Barr virus genome.

AIMS: To determine the prevalence of Epstein-Barr virus genome in primary cerebral lymphomas occurring in the absence of immune suppression. METHODS: Forty eight consecutive patients with lymphomas restricted to the central nervous system were identified, all of whom had had neurosurgical biopsies performed at the National Hospitals for Neurology and Neurosurgery, London. Only five patients had some form of underlying immune deficiency; 43 were apparently normal. The tumours were studied with immunohistochemical markers and by in situ hybridisation, using a biotinylated probe to the internal repeat region of Epstein-Barr virus. RESULTS: All the lymphomas were B cell in origin. Tumours from the five immunosuppressed patients all showed hybridisation, as did two of the "spontaneous" tumours. CONCLUSIONS: This is the largest series of cerebral lymphomas so far probed for Epstein-Barr virus genome: as more are examined, it is suggested that a small proportion of the tumours from immunocompetent patients will also contain the virus.

B-Lymphocytes↗
PubMed1991

Examination of spinal cord in diseases of the craniocervical junction and high cervical spine.

A simple necropsy technique for the removal of the craniocervical junction was devised: a relatively small specimen comprising part of the clivus, the foramen magnum, and cervical vertebral canal is removed in one piece with the medulla and spinal cord inside, and examined systematically after fixation. This method, used in a series of patients with chronic craniocervical instability, allows both good clinicopathological correlations to be made and histological changes in the lower medulla or upper cervical cord segments to be related to sites of extrinsic compression.

Atlanto-Axial Joint↗
PubMed1991

Damaged ligaments at the craniocervical junction presenting as an extradural tumour: a differential diagnosis in the elderly.

An extradural mass at the craniocervical junction causing progressive neurological disability in five elderly patients is described. The lesion, which might be confused with a meningioma or other tumour, is composed of amorphous degenerate fibrocartilaginous material and could be due to degeneration of the ligaments responsible for atlanto-axial stability. Recognition of the condition early is important as the patient's clinical condition will deteriorate without decompression. Anterior transoral removal is relatively simple, unlike surgery for tumours in the area, and will not destabilise the craniovertebral junction. It is likely that a proportion of these lesions are undetected, misdiagnosed or untreated to the detriment of the patient.

Aged↗
PubMed1987

The incidence of multifocal cerebral gliomas. A histologic study of large hemisphere sections.

A series of 241 gliomas (astrocytomas, oligodendrogliomas, glioblastomas, and subependymal giant-cell astrocytomas) was studied. This represents all the gliomas examined post mortem over 25 years at one hospital. Two hundred and one cases (85%) were apparently solitary tumors; of the 40 cases with multiple tumor foci, 23 (9.5%) were true multicentric gliomas. After excluding cases in which there was concomitant disease (neurofibromatosis, tuberose sclerosis, or multiple sclerosis), 18 cases of multicentric tumor (7.5%) remained. Multicentric tumors with different histologic appearances accounted for 2.9% of the series. Celloidin-embedded whole brain sections proved invaluable for the detection of microscopic neoplastic foci and unsuspected diffuse spread. The estimated incidence of multiplicity in gliomas is higher than in most series, but the findings suggest that detection of multifocal neoplastic change in these tumors is directly related to the extent to which the brain is sampled, and that figures obtained in this study may well underestimate the true incidence.

Adolescent↗