Retinal infarcts and haemorrhages due to scurvy.
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Humans↗
Biomedical subjects
C A Bloxham
Publications and source records attributed to C A Bloxham.
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↗
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↗
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↗
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↗
Impairments in the learning and performance of a new manual skill in patients with Parkinson's disease.
Twelve patients with Parkinson's disease learned two novel skills in which they had to track a target by moving a joystick. In task 1 they had to learn to anticipate the movements of a semi predictable target. In task 2 they had to learn a novel control system in which the movements of the joystick were mirror reversed in relation to the computer screen. On each task they performed two sessions of three minutes continuous practice separated by a 10 minute rest. In both tasks the patients performed much worse than the controls, but showed clear evidence of learning, particularly after the ten minute rest. Detailed examination of their performance suggested that the skill was becoming automatic, releasing attention for aspects of the task that could not be learned. The major difference from the controls appeared during the first minute of each practice session when the controls showed a marked improvement in performance while the patients did not. We suggest that this rapid but temporary improvement in performance reflects the acquisition of a motor "set" whereby existing motor programs or skills are modified to suit the task currently in hand. We concluded that patients with Parkinson's disease have difficulty in maintaining such sets.
Adaptation, Psychological↗
Evidence for the early prenatal development of cortical cholinergic afferents from the nucleus of Meynert in the human foetus.
A combined histochemical and biochemical approach has shown that the cholinergic system in the nucleus of Meynert region of the substantia innominata is well defined both histochemically and neurochemically within the first 3 months of gestation in the human foetus. Thus, at between 12 and 22 weeks of development the most intense acetylcholinesterase (AChE) histochemical reactivity was observed in the neuropil, cell bodies and processes in the nucleus of Meynert. AChE-stained fibres were observed which coursed from the nucleus of Meynert towards the cortical mantle and within the mantle AChE-stained fibres were also present. Micropunch samples from within the nucleus of Meynert contained higher levels of choline acetyltransferase (ChAT) activity than any other area examined including the striatum, while in the cortical mantle the level of ChAT activity was comparable to that found in the adult cerebral cortex. These observations suggest that the cholinergic innervation from the nucleus of Meynert--considered to be the major source of cholinergic afferents in the adult cerebral cortex--may play a key role in the early development of the human neocortex.
Acetylcholinesterase↗
Human cerebellar cortex possesses high affinity binding sites for [3H]somatostatin.
Somatostatin binding sites have been identified in the human brain using [4-3H-(Phe6)]-somatostatin-14. In contrast to that of the rat, the human cerebellar cortex possesses a high density of somatostatin binding sites, comparable to that found in either the rat or human cerebral cortex. Autoradiographic localisation of somatostatin binding sites in the human cerebellum reveals that the highest density is associated with the granule cell layer.
Aged↗
Cholinergic correlates of cognitive impairment in Parkinson's disease: comparisons with Alzheimer's disease.
Dementia in Parkinson's disease has previously been attributed to the presence in the cerebral cortex of Alzheimer-type neuropathological abnormalities. New evidence suggests, however, that dementia in this disease usually occurs in the absence of substantial Alzheimer-type changes in the cortex and may be related to abnormalities in the cortical cholinergic system. Thus, in Parkinsonian patients with dementia there were extensive reductions of choline acetyltransferase and less extensive reductions of acetylcholinesterase in all four cortical lobes. Choline acetyltransferase reductions in temporal neocortex correlated with the degree of mental impairment assessed by a test of memory and information but not with the extent of plaque or tangle formation. In Parkinson's but not Alzheimer's disease the decrease in neocortical (particularly temporal) choline acetyltransferase correlated with the number of neurons in the nucleus of Meynert suggesting that primary degeneration of these cholinergic neurons may be related, directly or indirectly, to declining cognitive function in Parkinson's disease.
Acetylcholinesterase↗
Initiation and execution of predictable and unpredictable movements in Parkinson's disease.
Nine patients with Parkinson's disease were compared with aged-matched normal controls on a tracking and a reaction time task. In the tracking task, subjects had to follow a target moving either predictably or unpredictably at various frequencies. There were no differences between the groups on this task. Both groups were able to use the predictable target movements to eliminate the lag between the target movements and their own movements, indicating that they could emit preprogrammed responses which did not depend on visual feedback. The reaction time task also contrasted predictable and unpredictable movements since the subjects were sometimes told in advance which finger they would have to lift in response to the imperative signal. The patients were significantly less able than controls to use this predictability to reduce their reaction times. It is concluded that parkinsonian patients can use prior information to control the form of a preprogrammed movement, but cannot use this information to help initiate such a movement.
Adult↗
Cortical cholinergic deficit in mentally impaired Parkinsonian patients.
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Alzheimer Disease↗
Dopamine D1 receptors in human parathyroid gland: in vitro and in vivo studies.
Dopamine receptors in human parathyroid were studied in vitro using ligand binding techniques. With 3H-piflutixol as ligand, binding characteristic of the dopamine D1 receptor was observed. Administration of apomorphine, flupenthixol or metoclopramide to normal controls or acute schizophrenic patients at doses producing significant alterations in serum prolactin concentrations did not alter serum parathyroid hormone (PTH) concentrations. Whilst D1 binding sites are present in human parathyroid, the measurement of PTH after administration of dopaminergic drugs is unlikely to provide a test of D1 receptor function in man.
Adult↗
An investigation of the effects of intracerebral injection in the marmoset of cytopathic cerebrospinal fluid from patients with schizophrenia or neurological disease.
In experiments designed to investigate transmission, cerebrospinal fluid (CSF) from patients with schizophrenia and neurological disease (huntington's chorea and multiple sclerosis) which had been found to induce cytopathic effects in human embryonic fibroblast cell culture was injected intracerebrally into mice, hamsters and marmosets (small New World primates). No evidence was obtained of transmission to mice or hamsters. A total of 15 marmosets (Callithrix jacchus) was injected intracerebrally with CSF [8 with samples from 4 patients with schizophrenia. 3 with samples from patients with neurological disease (2 with Huntington's chorea and 1 with multiple sclerosis) and 4 with samples from 3 patients without neurological or psychiatric disease] and was observed over a period of 2 1/2 years. Analysis of variance on data obtained from behavioral observations averaged over 6-month periods revealed that animals injected with CSF from patients with schizophrenia and neurological disease became progressively more inactive when compared with animals injected with CSF from control patients. The change detected by behavioural observation was confirmed as a difference 2 and 2 1/2 years after injection by automated activity monitoring. There was an incidence of reproductive anomalies (including two occipital encephalocoeles) in the females in the experimental group, but the numbers are too small to draw firm conclusions from this observation. Many reported differences in biological samples from schizophrenic patients and normal controls have subsequently been found to be due to factors unrelated to the disease state. This may prove to be the case with the changes observed in this experiment. Nevertheless, the fact that marmosets injected with CSF from patients suffering from neuropsychiatric disease, including schizophrenia, subsequently differed in their behaviour from those injected with control CSF warrants further investigation.
Animals↗
Guanfacine: a new centrally-acting antihypertensive agent.
The centrally-acting antihypertensive drug guanfacine was studied in a group of 11 moderate hypertensives. In doses of 2 mg daily, an average reduction in diastolic blood pressure of 10.8 mmHg was achieved. Side-effects were few when doses were maintained below 3 mg daily. The blood pressure reduction was associated with a fall in plasma renin activity and an average weight gain of 1.8 kg. When guanfacine was tried in 6 very severe hypertensives who had proved resistant to other antihypertensive drugs, a similar reduction in diastolic pressure of 7 mmHg was achieved using a dose of 3 mg daily. It is considered that guanfacine is a useful new antihypertensive drug, effective in mild hypertension, and side-effects are few if doses are maintained below 3 mg daily. Above this dose, side-effects became prominent, and these included sedation, dry mouth and constipation.
Adult↗
Malignant hypertension and cigarette smoking.
The smoking habits of 48 patients with malignant hypertension were compared with those of 92 consecutive patients with non-malignant hypertension. Thirty-three of the patients with malignant and 34 of the patients with non-malignant hypertension were smokers when first diagnosed. This difference was significant, and remained so when only men or black and white patients were considered separately. Results suggest that malignant hypertension is yet another disease related to cigarette smoking.
Female↗
The Remler M2000 semi-automatic blood pressure recorder.
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Blood Pressure Determination↗
Self-poisoning by sodium chlorate--some unusual features.
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Adult↗