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Biomedical subjects

J R Bonham

Publications and source records attributed to J R Bonham.

At least 19 recordsLinked to original sources
PubMed1992

Complete recovery from hemorrhagic shock and encephalopathy.

We describe three infants (aged 9 weeks to 4 months) with the classic features of hemorrhagic shock and encephalopathy syndrome, including sudden onset of shock, neurologic disturbance, bleeding, disseminated intravascular coagulation, and impaired hepatic and renal function. Unlike the cases previously described, all three children recovered rapidly without evidence of long-term neurologic damage. These findings may modify the perception that this disorder has a uniformly bad outcome.

Brain Diseases↗
PubMed1992

Metabolic deficiencies and SIDS.

The role of inherited metabolic defects in SIDS is controversial: some workers think that they may account for the cause of death in about 10% of cases. Many maintain that this is a gross overestimate, but it cannot be denied that the sudden onset and rapid deterioration known to occur in some metabolic disorders during the first year of life can mimic SIDS. This may remain undetected unless postmortem material is examined in specialist centres with individual metabolic disorders in mind. Defects in energy metabolism and the maintenance of glucose homeostasis frequently show this pattern of presentation precipitated by minor clinical infection. These disorders include the glycogen storage disorders, gluconeogenic enzyme defects, and the defects of fatty acid oxidation. Several reports have appeared since 1984 linking fatty acid oxidation defects with SIDS. Estimates of their prevalence vary, due partly to methodological heterogeneity and partly to the limited size of individual studies which have not permitted adequate statistical analysis. Nevertheless, the lack of adequate information has not precluded a great deal of debate. Over the past seven years a group in Sheffield has studied the occurrence of these defects in SIDS using three distinct approaches: retrospective analysis of SIDS cases, prospective analysis of SIDS cases, prospective analysis of urine obtained from siblings of SIDS cases during the first week of life. The result of these studies would suggest that the contribution to SIDS made by medium chain acyl CoA dehydrogenase deficiency may be in the region of 1%. Additional related metabolic disorders may account for a further as yet undefined small percentage. The eventual resolution of some of these uncertainties may be provided by harmonizing the results of existing studies and by DNA analysis of materials obtained at necropsy in SIDS cases.

Fatty Acids↗
PubMed1991

Nerve cell loss in the thalamus in Alzheimer's disease and Parkinson's disease.

Serial sections through the thalamus from the fixed right cerebral hemispheres of 15 cases (5 Parkinson's disease, 5 Alzheimer's disease (AD) and 5 controls) were used to obtain quantitative estimates of neuronal loss, neurofibrillary tangle formation and Lewy body inclusions within individual thalamic nuclei. Severe neuronal loss and tangle formation were evident in the anterodorsal nucleus from the AD cases. Nerve cell damage was also present in the centromedian nucleus but was not associated with tangle formation and occurred in all but 2 of the brains examined. It is likely that the anterodorsal neurons are damaged locally by the Alzheimer's disease process whereas the changes in the centromedian nucleus may be related to ageing.

Aged↗
PubMed1990

Parameters of cholinergic neurotransmission in the thalamus in Parkinson's disease and Alzheimer's disease.

Loss of cholinergic cells in the basal forebrain is associated with commensurate reductions in cortical acetylcholine-related enzyme activities in both Alzheimer's disease (AD) and Parkinson's disease (PD). Nerve cell loss from the cholinergic pontine tegmental nuclei also occurs. As the latter nuclei project to the diencephalon, we used frozen tissue from 5 controls, 5 PD and 5 AD cases to study the distribution of ChAT, AChE and [3H]nicotine binding in the thalamus and subthalamic nucleus. The anterior nuclear group and the mediodorsal nucleus showed high activities of ChAT and AChE together with relatively high levels of [3H]nicotine binding. The centromedian nucleus and subthalamic nucleus contained equally high levels of ChAT but negligible levels of [3H]nicotine binding. There were no significant changes in the levels of ChAT, AChE and nicotine binding in the PD and AD groups indicating that involvement of the pedunculopontine tegmental nucleus is likely to be a secondary retrograde phenomenon rather than part of a systematic cholinergic fibre degeneration.

Acetylcholine↗
PubMed1990

Abnormalities of carbohydrate metabolism and of OCT gene function in the Rett syndrome.

The pathogenetic basis of the Rett syndrome (RS) is unknown: an X-linked dominant, male-lethal gene defect is thought likely. We present a girl with RS who has defects both of the urea cycle and of carbohydrate metabolism resulting in fasting hypoglycaemia, post-prandial hyperlactataemia and excess urinary orotic acid excretion after alanine load. Her sister has a similar clinical picture, but less marked metabolic anomalies. The mother of these sisters has abnormal urinary orotic acid excretion; she transmitted opposite ornithine carbomoyltransferase (OCT) alleles to the two girls. Another girl with RS has similar metabolic responses to fasting and to carbohydrate load. We conclude that RS may be an aetiologically homogeneous condition, but that it includes a variable pattern of metabolic anomalies, and that the gene defect is distinct from the OCT locus.

Adolescent↗
PubMed1990

Distribution of neurofibrillary tangle formation and [3H]-D-aspartate receptor binding in the thalamus in the normal elderly brain, in Alzheimer's disease and in Parkinson's disease.

The overactivity of glutamatergic neurons may underlie some neurodegenerative disorders, including Alzheimer's disease (AD). We explored the relationship between glutamatergic transmission and neurofibrillary tangle formation by measuring [3H]-D-aspartate binding activity and the proportion of neurons containing tangles within individual thalamic nuclei in five AD cases. Five elderly normal and five Parkinson's disease (PD) cases were used as controls. A highly significant correlation between [3H]-D-aspartate binding and tangle counts in Alzheimer's disease suggests that those thalamic nuclei which normally receive a relatively dense glutamatergic afferent input are predisposed to tangle formation. There were no significant differences in individual thalamic nuclear [3H]-D-aspartate binding between controls and the AD and PD groups.

Aged↗
PubMed1990

D(+)-glyceric aciduria: etiology and clinical consequences.

A family comprising mother, father, and five children is described. Four of the children were found to excrete massive amounts of D(+)-glyceric acid in their urine. This was verified by gas chromatography-mass spectrometry and the configuration determined by capillary gas chromatography of O-acetylated menthyl esters. The excretion ranged from 10.8 to 19.9 mmol/24 h. The remaining child and the parents showed no evidence of this unusual metabolite. The virtual absence of clinical manifestations in this family was particularly interesting. Only two of the children showed any clinical abnormality and this was limited to mild microcephaly and speech delay; the other two children found to excrete large amounts of D(+)-glycerate were healthy and developmentally normal at 7 y and 9 y of age. There was a marked increase in the excretion rate of D(+)-glycerate in response to both oral fructose and serine loading. These results are consistent with a deficiency of D(+)-glycerate kinase and indicate the potentially benign nature of this disorder.

Administration, Oral↗
PubMed1988

Interaction of 9-amino-1,2,3,4-tetrahydroaminoacridine (THA) with human cortical nicotinic and muscarinic receptor binding in vitro.

Tetrahydroaminoacridine (THA) has recently been reported to be more useful in the treatment of Alzheimer's disease than physostigmine. A comparison of the effects of these two anticholinesterase agents on in vitro enzyme and receptor activities of human cerebral cortex (obtained at autopsy) revealed similarities in their interactions with acetylcholinesterase (AChE) but striking differences in their ability to displace both nicotinic and muscarinic radioligands from membrane preparations. IC50 values (the concentration required to reduce enzyme activity by 50%) for the inhibition of total tissue AChE were 7.9 x 10(-7) M and 4.5 x 10(-8) M for THA and physostigmine, respectively, and similar values were also obtained for individual molecular forms of AChE (monomer G1, dimer G2 and tetramer G4) separated by sucrose density gradient centrifugation. In contrast, IC50 values for [3H]nicotine displacement (a measure of nicotinic cholinergic receptor binding) differed 1000-fold for THA (2 x 10(-5) M) and physostigmine (2 x 10(-2) M) and 100-fold for [3H]N-methylscopolamine displacement (a measure of muscarinic cholinergic receptor binding). Differences were also noted in the inhibition of carbachol stimulated polyphosphoinositide (PI) hydrolysis (a measure of muscarinic receptor induced second messenger activity) in isolated rat cortical miniprisms. It is suggested that variations in clinical efficacy of THA and physostigmine may be related less to their anticholinesterase properties and more to their interactions with other activities such as cholinergic receptors.

Acetylcholinesterase↗
PubMed1988

The characterisation of molecular forms of acetylcholinesterase in Hirschsprung's disease.

Aganglionic rectal tissue from patients with Hirschsprung's disease contains four forms of acetylcholinesterase; the major component has a sedimentation coefficient in the region of 10.0S. Results from gel filtration confirm these findings and, when used in conjunction with the sedimentation data, allow the determination of the molecular mass of these forms. The four species of acetylcholinesterase include: monomer, G1, 74 kDa dimer, G2, 131 kDa; tetramer G4, 275 kDa and an asymmetric form, A12, 811 kDa. Evidence is provided which shows that the major form, G4 interacts with the detergent Triton X-100. Selective measurement of G4-AChE using a suitable assay may provide the basis for improving the existing means of diagnosis of Hirschsprung's disease.

Acetylcholinesterase↗
PubMed1988

Muscarinic cholinergic receptor subtypes in hippocampus in human cognitive disorders.

Total muscarinic receptor levels, the levels of the subtypes exhibiting high and low affinity for pirenzepine, and the high- and low-affinity agonist states of the receptor were investigated in hippocampal tissue obtained at autopsy from mentally normal individuals and the following pathological groups: Alzheimer's disease, Parkinson's disease, Down's syndrome, alcoholic dementia, Huntington's chorea, and motor-neurone disease. A moderate decrease in the density of both high-affinity pirenzepine and high-affinity agonist subtypes was found in Alzheimer's disease, whereas a trend towards an increase in the overall muscarinic receptor density was apparent in the parkinsonian patients without dementia, mainly due to an increase in the low-affinity agonist state; the differences between the Alzheimer's disease and nondemented parkinsonian cases were highly significant. As previously reported, the levels of both choline acetyltransferase and acetylcholinesterase were markedly reduced in both Alzheimer's disease and Parkinson's disease--with a greater loss of both enzymes in the demented subgroup of parkinsonian patients. Activities of the cholinergic enzymes were also extensively reduced in Down's syndrome, accompanied by a loss of high-affinity pirenzepine binding. There were no significant receptor or enzyme alterations in the other groups studied. These observations suggest that in the human brain, extensive degeneration of cholinergic axons to the hippocampus, as indicated by a loss of cholinergic enzymes, is not necessarily accompanied by extensive muscarinic receptor abnormalities (as might be expected if a major subpopulation were presynaptic). Moreover, the opposite changes in muscarinic binding in Parkinson's and Alzheimer's diseases may be related to the greater severity of dementia in the latter disease.

Acetylcholinesterase↗
PubMed1987

Neural tube defect-specific acetylcholinesterase: its properties and quantitation in the detection of anencephaly and spina bifida.

Amniotic fluid from neural tube defect-affected pregnancies (NTD) contains three forms of acetylcholinesterase (AChE), the major species of which is present only in trace amounts in normal pregnancies or those associated with a non-NTD fetal malformation. The activity of this 'specific' AChE is increased 62-fold in the presence of NTD and its measurement provides a sensitive and specific test for the biochemical detection of this disorder. The sedimentation coefficient of 'NTD specific' AChE (10.3S) indicates that it is a tetrameric species, and that the two additional forms present, (4.0S and 5.5S) are monomer and dimer, respectively. Gel filtration studies also support these findings. Combining these data, the molecular masses of monomer, dimer and tetramer are shown to be 78, 126 and 256 kDa (+/- 10%). 'NTD-Specific' AChE does not react with the detergent Triton X-100, indicating that it is a soluble, and probably secreted, species without membrane associating properties.

Acetylcholinesterase↗
PubMed1987

Loss and recovery of acetylcholinesterase molecular forms in the fornix-lesioned rat hippocampus.

The loss and recovery of hippocampal acetylcholinesterase (AChE) molecular forms was studied following fornix lesions. Two weeks after lesioning, the G4 form, which constituted the majority (91%) of AChE activity in the unlesioned hippocampus, was significantly reduced (P less than 0.01) to levels 21% of those in the unlesioned hippocampus, suggesting that this form is probably presynaptic. Thirteen weeks after lesioning total hippocampal AChE activity had increased 3-fold relative to 2-week animals, with the majority of the recovery in total AChE activity being due to a significant (P less than 0.05) increase in the abundance of the G4 form to levels 340% of those at 2 weeks. The increase in the abundance of the G4 form, which appears to be a functionally important molecular form of AChE within the CNS, serves as a marker of the integrity of the newly formed hippocampal cholinergic synapses.

Acetylcholinesterase↗
PubMed1987

A 7-year study of the diagnostic value of rectal mucosal acetylcholinesterase measurement in Hirschsprung's disease.

Over a 7-year period, 213 children were investigated for failure to pass meconium or for chronic constipation. Of these, 45 were confirmed to have Hirschsprung's disease; in this group the acetylcholinesterase activity in rectal biopsy tissue was significantly increased (P less than .001; mean 34.2, 95% confidence limits, 8.6 to 95.2) units g-1 when compared with the non-Hirschsprung's group (mean 6.6, 95% confidence limits, 2.0 to 15.9 units g-1). By expressing the acetylcholinesterase activity as a percentage of the total cholinesterase activity it is possible to compensate for evaporative weight loss and the combination of these two measurements improves the overall diagnostic value of the test. There were no false-positive and only two false-negative results.

Acetylcholinesterase↗