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Biomedical subjects

C A Bloxham

Publications and source records attributed to C A Bloxham.

At least 19 recordsLinked to original sources
PubMed1992

Iron and aluminium in relation to brain ferritin in normal individuals and Alzheimer's-disease and chronic renal-dialysis patients.

Ferritin has been isolated and its subunit composition, iron and aluminium content determined in the cerebral cortex and cerebellum of normal individuals and in the cerebral cortex of Alzheimer's-disease and renal-dialysis patients. An e.l.i.s.a. for ferritin has been developed and the ferritin, non-haem iron and aluminium content of the parietal cortex were determined in normal individuals and Alzheimer's-disease patients. It was found that ferritin from the cerebral cortex and cerebellum of normal individuals had a high H-subunit content, similar to that of heart ferritin. The subunit composition of ferritin isolated from the cerebral cortex was not significantly altered in Alzheimer's-disease or renal-dialysis patients. Ferritin from the cerebral cortex of normal individuals had only approx. 1500 atoms of iron per molecule and the iron content of ferritin was not significantly changed in Alzheimer's-disease or renal-dialysis patients. Ferritin isolated from the cerebral cortex of normal, Alzheimer's-disease and renal-dialysis patients had less than 9 atoms of aluminium per molecule. The failure to find increased concentrations of aluminium associated with ferritin in dialysis patients, who had markedly increased concentrations of aluminium in the cerebral cortex, shows that aluminium does not accumulate in ferritin in vivo. This has important implications for the toxicity of aluminium, since it implies that cells are unable to detoxify aluminium by the same mechanism as that available for iron. Comparison of the concentrations of ferritin, aluminium and iron in the parietal cortex from normal and Alzheimer's-disease patients showed that, whereas the concentration of aluminium was not increased, both ferritin and iron were significantly increased in Alzheimer's disease.

Aged↗
PubMed1992

Angiodysgenetic necrotising encephalopathy: presentation as an intrauterine death.

The various morphological manifestations of intracranial vascular anomalies include the rare diffuse meningo-cerebral angiomatosis, sometimes termed "angiodysgenetic necrotising encephalopathy" on account of the severe associated hypoxic damage to the cerebral cortex and white matter. It may occur in any age group and displays both sporadic and familial forms. A further case is reported which is apparently unique in presenting as an intrauterine death with extensive subarachnoid haemorrhage. Associated pathological abnormalities of the adrenal glands indicate that cerebral damage may have commenced from as early as the 20th week of pregnancy. Possible relationships of this entity to other central nervous system vascular malformations are discussed.

Adult↗
PubMed1992

Platyspondylic lethal osteochondrodysplasia: Shiraz type with radiological-pathological correlation.

We report two cases of a platyspondylic lethal osteochondrodysplasia in siblings. The condition affects predominantly the metaphyses of the axial skeleton associated with limb shortening and mild platyspondyly. The radiological and pathological features correlate very closely with Sedaghatian's lethal metaphyseal chondrodysplasia, which has previously been described only in Iranian Nationals. Both the radiological and pathological appearances will be described, together with a discussion of the differential diagnosis, the genetical implications and a review of literature.

Female↗
PubMed1992

Distribution of transferrin receptors in relation to cytochrome oxidase activity in the human spinal cord, lower brainstem and cerebellum.

Neuronal activity and oxidative energy metabolism are tightly coupled. There is evidence that cytochrome oxidase, the terminal enzyme of the electron transport chain, can serve as a metabolic marker of neuronal activity. All the respiratory chain enzymes have iron containing prosthetic groups and therefore represent an important component of iron utilisation. Since iron entry into cells is mediated by the transferrin receptor, this receptor may also serve as marker of neuronal activity. The histochemical distribution of cytochrome oxidase has therefore been compared with the autoradiographic distribution of the transferrin receptor in the human spinal cord, brainstem and cerebellum. Cytochrome oxidase activity showed a very similar pattern of distribution to the transferrin receptor in the spinal cord, brainstem and cerebellum. The highest levels of cytochrome oxidase activity and transferrin receptor binding were associated with; in the spinal cord, the substantia gelatinosa, laminae II and III and the motor neurones; in the medulla and pons, the spinal trigeminal nucleus, hypoglossal nucleus, dorsal motor nucleus of the vagus, inferior and superior olives, nucleus praepositus, nucleus paramedianus, central grey, superior central nuclei and locus coeruleus; in the cerebellum, the molecular layer. The results suggest that the transferrin receptor may provide a useful marker of total neuronal respiratory activity.

Aged↗
PubMed1992

Immunocytochemical localisation of transferrin in the human brain.

Immunocytochemical studies on the adult human brain have shown that transferrin is localized within three main compartments in the adult human brain. Oligodendrocytes and some astrocytes together with cells of the choroid plexus showed the highest intensity of staining. Neuronal staining occurred mainly within pyramidal or large polygonal cells, but this showed considerable regional variation being most marked in areas such as the cerebral cortex, amygdala, hippocampus, brainstem and cerebellar Purkinje cells. Small neurones such as caudate interneurones and granule cells showed relatively low activity. Diffuse immunostaining of the neuropil was evident, particularly where heavy neuronal or glial staining occurred. Immunostaining was also observed in white-matter fibre tracts. This pattern of distribution helps to provide a model for the mechanisms responsible for iron homeostasis in the normal brain.

Astrocytes↗
PubMed1992

Histochemical distribution of non-haem iron in the human brain.

The detailed anatomical distribution of iron in the post-mortem human brain has been studied using Perl's and Turnbull's methods with the diaminobenzidine intensification procedure for the demonstration of non-haem Fe3+ and Fe2+, respectively. Attention to methodological procedures has revealed that even brief immersion of tissue in routinely used fixatives causes a reduction of staining intensity in areas of high iron content and, often, loss of staining in areas of low iron content. Optimal staining is obtained using frozen section briefly fixed for 5 min in 4% formalin and Perl's stain (Fe3+) with diaminobenzidine intensification. Highest levels of stainable iron were found in the extrapyramidal system with the globus pallidus, substantia nigra zona reticulata, red nucleus and myelinated fibres of the putamen showing highest staining reactivity. Moderate staining intensity with Perl's technique was found in the majority of forebrain, midbrain and cerebellar structures with the striatum, thalamus, cortex and deep white matter, substantia nigra zona compacta, and cerebellar cortex showing consistent staining patterns with intensification of Perl's stain. The brain-stem and spinal cord generally only showed staining with the intensification procedure and even this was of low intensity. Microscopically the non-heam iron appears to be found predominantly in glial cells as fine cytoplasmic granules which in heavily stained areas coalesce to fill the entire cell. Iron-positive granules appear to be free in the neuropil and also around blood vessels in the globus pallidus, striatum and substantia nigra. The neuropil shows a fibrous impregnation when stained for iron which is, in part, derived from glial processes, myelinated fibres and fibre bundles. Neurones, in general, show only very low reactivity for iron, and this is difficult to discern due, often, to the higher reactivity of the surrounding neuropil. In the globus pallidus and substantia nigra zona reticulata, neurones with highly stainable iron content are found with granular cytoplasmic iron reactivity similar to that seen in the local glial cells. Our results are comparable with those of early workers, but with the use of intensification extend the distribution of non-haem iron to areas previously reported as negative. No apparent correlation of iron staining with known neurotransmitter systems is seen and the predilection for the extrapyramidal system is not easily explained, though the non-haem iron in the brain appears to be as a storage form in the iron storage protein ferritin. The localization of iron in the brain provides a foundation for the study of iron in certain neurodegenerative diseases such as Parkinson's disease, where iron has been implicated in the pathogenesis.

Aged↗
PubMed1991

Halo eczema--resolution after excision of the central naevus alone.

We describe a patient with halo eczema around a benign pigmented compound naevus. The eczema resolved after excision of the central naevus alone; this allowed histological assessment of the naevus without the need for a large excision or for additional topical therapy.

Adult↗
PubMed1990

Disseminated zygomycosis and systemic lupus erythematosus.

A young woman with long-standing systemic lupus erythematosus and rheumatic fever presented with deteriorating renal function. She had severe gastritis treated with cimetidine and received methylprednisolone when her blood cultures were repeatedly negative. She developed spontaneous bruising and bleeding from venepuncture sites, leading to clotting studies and a diagnosis of thrombotic thrombocytopenic purpura. At post-mortem, extensive evidence of disseminated zygomycosis was found. The likely portal of entry was the gastric route.

Adult↗
PubMed1990

Bladder carcinosarcomas: three cases with diverse histogenesis.

Carcinosarcomas of the bladder are rare. We describe three such tumours, including an apparently unique case in which the components comprised liposarcoma and poorly-differentiated transitional cell elements. A second example included chondrosarcomatous elements. These two tumours showed architectural and immunocytochemical features which suggested that they had originated as carcinomas but had subsequently differentiated along both epithelial and mesenchymal pathways. The third tumour contained both carcinoma and osteosarcoma and may represent a collision tumour.

Aged↗
PubMed1989

Comparison of the regional distribution of transferrin receptors and aluminium in the forebrain of chronic renal dialysis patients.

Recent studies have emphasised the potential neurotoxicity of aluminium in dialysis encephalopathy and it has also been suggested that this element may have a role in the pathogenesis of Alzheimer's disease. Aluminium is known to be transported by the iron transport protein transferrin. In this study using receptor autoradiography we have demonstrated the presence of transferrin binding sites in the human forebrain and shown a pattern similar to that found in other species. Imaging secondary ion mass spectrometry has demonstrated the distribution of aluminium-containing cell-like profiles in the brains of chronic renal dialysis patients who have raised levels of brain aluminium (greater than 4 micrograms/g dry weight) and even in dialysis patients where the gross level of aluminium was within the normal range. The density of these profiles corresponded to the regions of high transferrin receptor density. In contrast, the distribution of iron in the brain showed an inverse correlation with transferrin receptor density with highest iron levels present in the globus pallidus, an area of low transferrin receptor density. These results suggest that the regional distribution of neuropathological changes seen in dialysis encephalopathy patients and also Alzheimer's disease may reflect the distribution of transferrin receptors. The discrepancy between iron distribution and transferrin receptor distribution suggests that further, as yet uncharacterized mechanisms, govern the distribution of brain iron.

Adult↗
PubMed1989

Dural punctures.

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Dura Mater↗
PubMed1987

Raised thyrotrophin-releasing hormone, pyroglutamylamino peptidase, and proline endopeptidase are present in the spinal cord of wobbler mice but not in human motor neurone disease.

The Wobbler mouse (wr) is a mutant that exhibits loss of anterior horn cells in the spinal cord and brainstem and subsequent muscle wasting, particularly of the forelimbs and neck. The wr mice, 2-3 months of age, were found to have increased levels of immunoreactive-thyrotrophin-releasing hormone (ir-TRH) in the spinal cord and pons and medulla, but not in other CNS areas. This increase was observed in dorsal and ventral cord and at cervical, thoracic, and lumbar levels and was confirmed by HPLC to be authentic TRH. The levels of immunoreactive-somatostatin, -neurotensin, and -substance P were not raised in the CNS of wr mice. The activities of two peptidases capable of degrading TRH, pyroglutamylaminopeptidase (PGAP, EC 3.4.11.8) and proline endopeptidase (PEP, EC 3.4.21.26), and the level of 5-hydroxyindoleacetic acid were also raised in the spinal cord of 2-3-month-old wr mice although the activities of alanine aminopeptidase and lactate dehydrogenase and the level of 5-hydroxytryptamine were not. Increased spinal cord levels of ir-TRH and PGAP and PEP activities were not observed in the 1-month-old wr mice. In addition, a pilot study using spinal cord obtained at autopsy from three patients with motor neurone disease and 12 control subjects indicated no increase in spinal cord ir-TRH, PGAP, or PEP in human motor neurone disease.

Aminopeptidases↗
PubMed1987

Reaction times and attention in Parkinson's disease.

Ten patients with Parkinson's disease performed a simple reaction time task in which, on hearing a tone, they pressed a button with the left thumb. In the first experiment tones sometimes occurred unannounced and at other times were preceded (by between 0 and 3200 ms) by a warning signal. The second experiment was identical to the first except that the subject had simultaneously to perform a simple continuous task with his right hand. Patients had slower reaction times than controls under all circumstances. In general, however, the effect of a warning signal and the effect of a second task were the same for both groups. In the control group the effect of a warning signal depended on whether or not a second task was being performed. Specifically, the advantage of a warning signal for reaction time was lost after long intervals (greater than 200 ms) when a second task was being performed. Parkinson's disease patients lost this advantage even when they were not performing a second task. Animal studies have suggested that dopamine deficiency results in an increase in neural "noise" in the basal ganglia. The behavioural consequences of this may be that Parkinson's disease patients always perform as if they were carrying out another task at the same time. In contrast, their ability to benefit from a warning signal and to allocate attentional resources are unimpaired.

Adult↗
PubMed1986

Regional distribution of high-affinity [3H]somatostatin binding sites in the human brain.

The distribution of high-affinity binding sites for [3H]somatostatin has been studied in membrane preparations from a number of regions of normal human brain. The highest densities of binding sites (greater than 48 fmol/mg protein) were found in the cerebral and cerebellar cortices and the hippocampus, with intermediate binding densities (30-46 fmol/mg protein) being present in the basal ganglia, amygdala, septum and claustrum. The lowest densities of binding sites (less than 14 fmol/mg protein) were observed in the hypothalamus, thalamus and substantia nigra. The binding of [3H]somatostatin in both the frontal cortex and cerebellar cortex demonstrated pharmacological specificity, since somatostatin-28, but not somatostatin-28(1-12) or Des AA1,2,4,5,12,13, D-Trp8-somatostatin, competed for the binding sites. Scatchard analysis of the binding in both frontal cortex and cerebellar cortex revealed the presence of two classes of high-affinity binding sites.

Aged↗