PubMed Health⌕ Search

Biomedical subjects

R O Weller

Publications and source records attributed to R O Weller.

At least 109 records · Page 6Linked to original sources
PubMed1981

Dopaminergic inhibition of growth hormone and prolactin release during continuous in vitro perifusion of normal and adenomatous human pituitary.

An in vitro technique for continuous perifusion of human pituitary has been developed to study the effect of dopamine on hormone release. Pituitary tissue was obtained from 2 patients with prolactinomas, 3 patients with acromegaly and 2 patients with disseminated malignancy whose pituitaries were normal. During perifusion prolactin release was reversibly inhibited from both normal and adenomatous glands, confirming the direct effect of dopamine on the pituitary. Rebound secretion following inhibition suggested that dopamine acted upon hormone release rather than synthesis under these conditions. Growth hormone (GH) release in vivo is stimulated by levodopa in normal subjects but inhibited in acromegaly. In vitro, however, we have demonstrated inhibition of GH release by dopamine, regardless of whether the pituitary was normal or adenomatous. This finding does not support the view that dopamine receptors are acquired by tumour cells as a result of adenomatous dedifferentiation. It is suggested that the paradoxical GH response to levodopa in acromegaly can be explained by a dual action of dopamine at hypothalamic and pituitary levels. According to this hypothesis GH release is stimulated by a hypothalamic effect, whereas inhibition occurs at pituitary level. The net effect of these opposing stimuli in vivo may depend upon the sensitivity of dopamine receptors at the prevailing concentration of GH.

Acromegaly↗
PubMed1980

Mechanisms of uptake and the fate of serum proteins and horseradish peroxidase in cultured human glioma cells. A light- and electron-immunocytochemical study.

Previous studies have shown that serum proteins are taken up from extracellular oedema fluid by reactive astrocytes and by tumour astrocytes. The present investigation was designed to define the mechanism of this protein uptake. Two or 3-week-old explant cultures from 26 astrocytic gliomas, one anaplastic ependymoma, and five non-glial intracranial tumours were treated with either human IgG (12 mg/ml), human serum albumin, (44 mg/ml) or horseradish peroxidase (0.1--4.0 mg/ml) for 4--24 h. Human IgG and albumin were subsequently detected in cultured cells by the indirect peroxidase-antiperoxidase (PAP) method for light microscopy or by direct peroxidase conjugate technique for electron microscopy. Horseradish peroxidase activity was localised by treatment with diaminobenzidine and hydrogen peroxide. Results of the study show that human serum proteins and horseradish peroxidase are taken up by tumour astrocytes and ependymal cells, and by macrophages, but not by non-glial tumour cells nor by mesenchymal elements in the glioma cultures. Electron immunocytochemistry suggests that the serum proteins are taken up by smooth walled micropinocytic vesicles (approximately 80 nm in diameter) which fuse to form larger endocytic vesicles (200--300 nm); these vacuoles in turn fuse with secondary lysosomes to form cytoplasmic bodies 1.2--3 mum in diameter.

Adolescent↗
PubMed1980

Age changes at cerebral artery bifurcations and the pathogenesis of berry aneurysms.

Cerebral artery bifurcations with and without aneurysms were studied in postmortem brains by histology (1-micron resin sections) and by scanning electron microscopy. Specimens were taken from 20 patients without aneurysms with an age range of 1 month--80 years. Gaps in the tunica media at the carina and the lateral wall of the bifurcations were observed in 60% of specimens from arteries at all ages, but they were larger in older patients. A more striking change with age was the development of inelastic pads of intimal thickening in relation to bifurcations. Intimal pads were observed at and distal to the carina of bifurcations, but scanning electron microscopy also revealed intimal pads proximal to bifurcations in 60% of patients over the age of 30 years and in 2 out of 9 (22%) patients under 10 years. Similar pads covered a much wider area of vessel wall proximal to the necks of berry aneurysms in the 15 patients studied. Contralateral bifuractions in these patients showed no difference from non-aneurysm patients. It is suggested that the inelastic intimal pads form as a result of haemodynamic stress and that the presence of such pads may alter the stresses and strains at vessel bifurcations. Together with the presence of a gap in the tunica media, the pattern of inelastic intimal pad formation may be a major predisposing factor in the formation of cerebral artery aneurysms.

Adolescent↗
PubMed1980

Crystalline stromal dystrophy: histochemistry and ultrastructure of the cornea.

A report of a woman in her fifties with Schnyder's crystalline stromal dystrophy is presented. There is no personal or family history of hypercholesterolaemia. A full thickness corneal disc was removed before grafting and examined by polarised light, histochemistry, and electron microscopy. Specific lipid histochemical methods showed deposits of cholesterol and cholesterol ester in the superficial stroma and in Bowman's membrane, but no triglyceride or free fatty acids were detected. Electron microscopy showed disruption of the superficial corneal stroma and Bowman's zone by cholesterol crystals and the presence of extracellular lamellated lipid droplets with a 4-4.5 nm periodicity. The epithelium, endothelium, and Descemet's membrane were virtually unaffected. The role of corneal grafting in crystalline stromal dystrophy is evaluated and the possible mechanisms of lipid accumulation in this disease are discussed.

Cholesterol↗
PubMed1980

Cerebrospinal fluid edema and its sequelae in hydrocephalus.

CSF edema is observed in the periventricular white matter in acute hydrocephalus especially when the intraventricular pressure is elevated; there is usually no detectable disturbance of the blood-brain barrier. Histological and ventricular perfusion studies suggest that CSF flows through the intact or disrupted ependyma into the periventricular white matter when the normal pathways of drainage are occluded. Absorption of fluid into the blood probably occurs through the periventricular blood vessels as an alternative pathway of CSF drainage. There is tissue damage in the edematous periventricular white matter and gliosis ensues. However, the degree of active tissue disruption is reduced in the chronic stages of hydrocephalus when the CSF edema is often reduced.

Acute Disease↗
PubMed1979

Vascular pathology in hypertension.

The pathological changes in blood vessels observed in primary (essential hypertension) are similar to those seen in secondary hypertension due to renal disease or other causes. In benign hypertension, the major changes are in the small arteries and arterioles especially in the kidney. Interlobular arteries exhibit intimal thickening and duplication of the elastic lamina (elastosis) and there is hyaline change in the media of many arterioles. In some respects these changes are an accentuation of vessel ageing. Malignant hypertension usually presents in a younger age group (35--50 years) and is characterized pathologically by fibrous endarteritis in the interlobular arteries of the kidney and fibrinoid necrosis in the walls of a proportion of the efferent glomerular arterioles. Similar vessel changes are seen in other organs but many of the pathological changes in the heart and brain of patients with benign hypertension are related to the accentuation of arterosclerosis. There is an increased mortality from cardiac failure, myocardial infarction, cerebral haemorrhage and subarachnoid haemorrhage due to ruptured berry aneurysms in patients with benign hypertension. Although there is ischaemic damage to the kidneys in benign hypertension, death from renal failure is uncommon. Severe ischaemic damage to renal glomeruli and renal failure does, however, occur in malignant hypertension.

Aging↗
PubMed1978

The effects of cytochalasin B and colchicine on cell motility and ultrastructure in primary cultures of malignant gliomas.

Primary tissue cultures of human gliomas were treated with cytochalasin B (0.5--60 microgram/ml for 90 min). Cell motility was inhibited irreversibly in glial tumour cells, but the effect was reversible on the mesenchymal cells growing in culture in the lower dose range. Cell adhesion was considerably reduced as the dose was increased, as was the capacity for cells to spread on a surface from suspension. Low concentrations of cytochalasin B caused negligible cell death and little disruption of cell ultrastructure. However, increases in dose were accompanied by a greater predominance of rough endoplasmic reticulum and inclusions and aggregation of microfilament bundles. As seen by scanning electron microscopy, cytochalasin B caused the withdrawal of peripheral cell borders, disappearance of ruffles and the breakdown of cytoplasmic lamellae. Charateristic surface blebs and folds appeared in their place. By comparison, colchicine (1--10 microgram/ml) caused a less marked and non-specific reversible reduction in cell motility on both glial and mesenchymal cells. No significant change in cell adhesion or spreading took place even at high doses, although at all concentrations gross disruption of the cell surface took place with changes in ultrastructure characterised by loss of cytoplasmic microtubules and aggregation of 10 nm filaments.

Brain Neoplasms↗
PubMed1978

Scanning electron microscopy of malignant gliomas. A comparative study of glioma cells in smear preparations and in tissue culture.

Smear preparations from 15 malignant gliomas, 2 metastatic carcinomas and from normal brain were examined by scanning electron microscopy. Tissue culture preparations from malignant gliomas were also studied. In the better differentiated areas of gliomas, the cells in smears were stellate with multiple long interweaving processes 0.25--1.3 micrometer in diameter which could be distinguished from myelinated nerve fibers (1.3--5 micrometer) and from fibrin (0.08--0.3 micrometer) by their thickness and arrangement in the tissue. The relationship of glial processes to blood vessels within the tumour was well demonstrated in smears. Metastatic carcinoma cells lacked the processes seen in glioma cell smears and did not show the same relationship to blood vessels. The more anaplastic glioma cells had fewer processes and ovoid cell bodies covered with surface ruffles and microvilli similar to the cell membrane projections in the nuclear regions of glioma cells in culture. The relationship of the surface morphology of glioma cells in smears to the known invasive nature of these tumours is discussed.

Brain Neoplasms↗
PubMed1978

The effects of hydrocephalus upon the developing brain. Histological and quantitative studies of the ependyma and subependyma in hydrocephalic rats.

A suspension of kaolin was injected into the cisterna magna of 44 rats at 2 weeks of age. Animals killed at intervals from 5--19 weeks of age showed varying degrees of hydrocephalus. Light microscopy, scanning and transmission electron microscopy revealed stretching and flattening of the ependymal cells but no significant loss of cilia. Histological evidence of periventricular tissue damage in these chronically hydrocephalic animals was only present when the ventricular dilatation was extensive. A quantitative assessment was made of the ependymal and subependymal cell reactions around the lateral ventricles of the hydrocephalic animals. Although the ependymal cells were clearly stretched around the ventricles, there was no apparent proliferation of these cells. An increase in the total number of subependymal cells was observed in hydrocephalic animals when compared with a series of 39 aged-matched controls. The greatest proliferation was in the dorsal and lateral walls of the ventricles which were the regions most severely stretched by the ventricular dilatation. There is evidence that subependymal cells differentiate into astrocytes and microglia so that proliferation of these cells may be interpreted as a response to continuing and progressive brain damage in chronic hydrocephalus. Such progressive tissue damage could adversely affect the developing brain.

Age Factors↗
PubMed1978

Spinal cord necrosis after intrathecal injection of methylene blue.

A 59 year old man had 6 ml of unbuffered methylene blue injected into the lumbar theca in an attempt to localise the source of cerebrospinal fluid rhinorrhoea. After injection of the dye he became shocked, and within the next few days he developed a mild paraparesis which subsequently progressed to a total paraplegia. The distribution of the spinal cord damage found at necropsy, eight and a half years after injection of the dye, is described and its relationship to the clinical picture discussed.

Cerebrospinal Fluid Otorrhea↗
PubMed1978

Induction of some features of glial differentiation in primary cultures of human gliomas by treatment with dibutyrl cyclic AMP.

Explants from 18 gliomas were cultured for periods up to 7 weeks and studied by light microscopy scanning and transmission electron microscopy. Well-differentiated tumor tissue gave rise to early outgrowths of stellate cells showing process orientation. Poorly-differentiated tissue produced a more haphazard out-growth of pleomorphic cells with few processes and flattened pseudopodia. Mean circadian cell displacement was several times greater in poorly-differentiated cells, but was significantly and reversibly reduced by treatment and dibutyryl cAMP (5 X 10(-4)M) for 48 h. Reduction in motility was directly correlated with a change in cell morphology to a more stellate form. Well-differentiated cells had a smooth surface with ruffling restricted to the ends of processes and highly orientated glial filament and microfilament bundles. The poorly-differentiated cell surface had a microvillous, blebbed appearance and ruffling regularly occurred around the edge of the cytoplasm. Glial filaments and microfilaments were fewer and less well orientated in the poorly-differentiated cells; sites of adhesion to the substratum were fewer than in well-differentiated cells. Treatment of malignant cultures with dibutyryl cAMP resulted in smoothing of the cell surface, retraction of processes into thin pseudopodia and the appearance of microfilament bundles within the cells. These features marked the apparent cyto-differentiation. However, there was a loss of attachment, disappearance of microtubules and loss of glial filaments in the cytoplasm which was not compatible with differentiation. Intracellular recordings of membrane potentials gave a significantly higher mean value for well-differentiated cells. The mean membrane potential and input resistance of poorly-differentiated cells was unchanged by the addition of dibutyryl cAMP. The results of this study suggest that some, but not all, features of mature glia are restored in malignant tumour cells by cAMP treatment.

Brain Neoplasms↗
PubMed1976

Epidemiology of primary tumours of the brain and spinal cord: a regional survey in southern England.

This survey is based upon 894 patients presenting with primary tumours of the brain, spinal cord, and meninges, over a nine year period in the Wessex population of about 1 1/2 million. All patients were 15 years of age or over. Each tumour type is characterized by age, sex, district, social class, and by rural or urban distribution. Standardized morbidity ratios for each tumour type are calculated for each health district. Gliomas are the commonest tumour with an average annual incidence of 3.94 per 100,000; they occur with a lower frequency in large urban areas. Grade 3-4 astrocytomas (glioblastoma multiforme) have a peak annual incidence of 7.53 per 100,000 in the 50-59 years age group and are more common in males. The peak incidence for oligodendrogliomas is also 50-59 years but for grade 1-2 astrocytomas it is 30-39 years. Meningiomas have an average annual incidence of 1.23 per 100,000 with a peak incidence of 2.48 per 100,000 at 60-69 years; they have a female predominance (female 1.76 per 100,000; male of 0.64 per 100,000). Rural districts have a lower incidence of meningiomas than urban areas. There is some variation in the distribution of gliomas, meningiomas, and Schwannomas throughout the Wessex region and there is a suggestion of geographical clustering of ependymomas, acoustic neuromas, and meningiomas. An excess of patients with grade 1-2 astrocytomas and oligodendrogliomas is seen in social classes 1 and 2 and a deficit in classes 4-5; a similar, but less marked, preponderance is seen with meningiomas.

Adolescent↗
PubMed1975

Seasonal nephrotic syndrome. Description and immunological findings.

Three cases are described showing a seasonal exacerbation of their nephrotic syndrome in association with an atopic trait and grass pollen allergy. The first patient has a history of four consecutive seasonal relapses each requiring steroid therapy. Following a course of desensitization injections he has now been free of relapse for 3 consecutive years. The second patient has also had a recurrent steroid-sensitive nephrotic syndrome often associated with the pollen season and allergic rhinitis. In this patient a course of cyclophosphamide has reduced his tendency to relapse. The third patient who has been on continuous prednisone therapy shows a seasonal increase in proteinuria. Serum changes in the first two patients include: a seasonal rise in total and grass pollen specific IgE; the continued presence of grass pollen specific IgG throughout the year but with a reduction during the pollen season in association with a more pronounced fall in the total IgG level; a depression in the C3 level in association with each major relapse; a mild rise in the I-K titre and a positive result in the Clq test for circulating complexes. A renal biopsy performed on the first patient when in relapse showed minor histological changes only and IgG, IgM, IgA, IgD, IgE, C3 and fibrinogen were undetectable by immunofluorescent examination. The probable mechanism for the development of proteinuria in these patients is discussed.

Adolescent↗
PubMed1975

Cerebral biopsy and assessment of brain damage in hydrocephalus.

Needle biopsies of the cerebral mantle were taken from 12 hydrocephalic children aged between 14 days and 3 years. 5 children were biopsied twice or more often during subsequent shunting operations. Histological studies of biopsies embedded in epoxy resin for light and electron microscope examination revealed more useful information than those embedded in paraffin wax. There was evidence of axonal degeneration in the white matter of patients with acute hydrocephalus. Progressive gliosis was seen in more chronic hydrocephalus together with signs of cerebral atrophy. No measurable effect of hydrocephalus on myelination was detected. This histological study of needle biopsies taken at shunt operations could be useful in assessing brain damage and thus in predicting future intellectual development in hydrocephalic children.

Astrocytes↗