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J R Bonham

Publications and source records attributed to J R Bonham.

54 records · Page 3Linked to original sources
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↗
PubMed1987

Molecular forms of butyrylcholinesterase in the human neocortex during development and degeneration of the cortical cholinergic system.

The total levels of butyrylcholinesterase (BChE) activity and, more specifically, the distribution of BChE molecular forms were measured in the human neocortex during fetal development. Both the amount of total activity and the abundance of the different molecular forms (G1 and G4) remained relatively constant between gestational ages of 8-22 weeks and were similar to those observed in samples of cortex from aged brain. In addition, in both Alzheimer-type and parkinsonian dementia, the levels of total BChE activity as well as the relative abundance of the G1 and G4 molecular forms were similar to those observed in control tissue. Hence, both the levels of total activity and the distribution of molecular forms did not change significantly either during fetal development or in the neurodegenerative disorders of Alzheimer-type and parkinsonian dementias. Because these situations are accompanied by changes in the cortical cholinergic system (including an increase and decrease in levels of the G4 form of acetylcholinesterase, respectively), it is concluded that, at least in the human neocortex, BChE is unrelated to cholinergic neurotransmission associated with subcortical cholinergic projection fibres.

Aged↗
PubMed1987

Molecular forms of acetylcholinesterase and butyrylcholinesterase in human plasma and cerebrospinal fluid.

The measurement of cholinesterase activities in either plasma or cerebrospinal fluid (CSF) may ultimately prove to be relevant in the diagnosis of neurological and neuropsychiatric disorders. However, studies to date have examined only total enzyme activities. Therefore in the present study we have examined the distribution of the individual molecular forms of both acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) in plasma and CSF using sucrose density gradient centrifugation. Although the total activities of AChE were of the same order of magnitude in plasma and CSF, there was a considerable difference (120-500-fold) between total BChE activity in the CSF and the BChE-rich plasma. The analysis of the individual molecular forms revealed that the predominant molecular species of AChE and BChE in the CSF--both lumbar and ventricular--was the G4 form. The G4 form also constituted the majority of the plasma BChE activity and, on average, over half (56%) of the plasma AChE activity. The significance of the AChE and BChE molecular form compositions of both plasma and CSF and their possible relationship to pathological states are discussed.

Acetylcholinesterase↗
PubMed1986

Molecular forms of acetylcholinesterase and butyrylcholinesterase in the aged human central nervous system.

The distribution of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) molecular forms and their solubility characteristics were examined, using density gradient centrifugation, in various regions of the postmortem human CNS. Total AChE activity varied extensively (50-fold) among the regions investigated, being highest in the telencephalic subcortical structures (caudate nucleus and nucleus of Meynert); intermediate in the substantia nigra, cerebellum, and spinal cord; and least in the fornix and cortical regions (hippocampus and temporal and parietal cortex). Total BChE activity was, in contrast, much more evenly distributed, with only a threefold variation between the regions studied. Although the patterns of molecular forms of each enzyme were broadly similar among the different areas, regional variations in the distribution and abundance of the various forms of AChE were much greater than those of BChE. Thus, although the tetrameric G4 form of AChE constituted the majority of the total AChE activity in all regions examined, the ratio of the G4 form to the monomeric G1 form, the latter of which constituted the majority of the remaining activity, varied markedly, ranging from 21 in the caudate nucleus to 1.7 in the temporal cortex. In addition to the G4 and G1 forms of AChE, the dimeric G2 form was observed in the nucleus of Meynert and a fast-sedimenting (16S) species was found in samples of both the parietal cortex and spinal cord. In contrast, the G4 and G1 forms of BChE were the only molecular species observed in the different areas and the G4:G1 ratio varied from 3.3 in the substantia nigra to 0.9 in the temporal cortex. Regarding the solubility characteristics of the individual AChE and BChE molecular forms, the majority of the G4 form of AChE was extractable only in the presence of detergent, indicating a predominantly membrane-bound localization of this species. The smaller AChE forms (G1 and G2) and both the G1 and G4 forms of BChE were all relatively evenly distributed between soluble and membrane-bound species. These findings are discussed in relation to neurochemical and neuroanatomical, particularly cholinergic, features of the regions examined.

Acetylcholinesterase↗
PubMed1985

Molecular forms of acetylcholinesterase in Hirschsprung's disease.

We describe changes in the levels of different molecular forms of acetylcholinesterase in four cases of Hirschsprung's disease linked to the transition from aganglionic to normal bowel. In addition changes in a control case with histologically normal bowel is reported. In all patients with Hirschsprung's disease there is a marked increase in the level of the tetrameric form of the enzyme in the aganglionic region. The changing level of this form of the enzyme correlates well with the histochemical appearance suggesting that quantitative measurement of this molecular species might form the basis of an improved diagnostic test for the disease.

Acetylcholinesterase↗
PubMed1983

Molecular forms of acetylcholinesterase in senile dementia of Alzheimer type: selective loss of the intermediate (10S) form.

Using density gradient centrifugation, three molecular forms of acetylcholinesterase have been distinguished in both normal and senile dementia of Alzheimer-type (SDAT) postmortem neocortex. Whilst the levels of the light and heavy forms were unaltered in SDAT there was a selective and extensive loss of the intermediate form. This form is predominantly hydrophobic and its loss from the cerebral cortex in SDAT may reflect degeneration of cholinergic axonal processes. This is the first report of an altered distribution of acetylcholinesterase molecular forms in a disease of the central nervous system.

Acetylcholinesterase↗
PubMed1981

Acetylcholinesterase and butyrylcholinesterase measurement in the pre-natal detection of neural tube defects and other fetal malformations.

Acetylcholinesterase activity in amniotic fluid was measured at 30 degree C by a reaction rate method employing acetyl-beta-methyl thiocholine as substrate and ethopropazine as a selective inhibitor of butyrylcholinesterase. This assay proved more specific than previously reported methods. Activity was greater in five cases of anencephaly (4.8-9.7 U/l) and nine cases of spinal bifida (5.1-8.6 U/l) than in 50 pregnancies with normal outcome (mean activity 2.0 +/- 0.9 (S.D.) U/l). There was no overlap between results from normal and neural-tube-defect groups, and the results showed no significant correlation with gestational age. Butyrylcholinesterase activity in amniotic fluid was measured using butyrylthiocholine as substrate. In accordance with previous reports, levels were elevated in pregnancies affected by neural tube defects. The ratio butyrylcholinesterase/acetylcholinesterase activity showed similar values for anencephalic, spina bifida and normal pregnancies; however, the two cases of exomphalos investigated could be clearly distinguished from all other groups on this basis.

Acetylcholinesterase↗
PubMed1981

Diagnosis of neural tube defects by estimation of amniotic fluid acetylcholinesterase.

Acetylcholinesterase (AChE) activity in amniotic fluid was assayed directly by a reaction rate method at 30 degrees C using acetylthiocholine iodide as substrate and ethopropazine as a safe 'pseudo' cholinesterase inhibitor. Fresh samples from 101 normal pregnancies of 14-24 weeks gestation had a mean AChE activity of 2.56 u/l (SD 1.10). Elevated levels of AChE were found in association with open spina bifida (5.5-20.4 u/l), anencephaly (10.2-19.5 u/l), exomphalos (2.7-15.6 u/l), intrauterine death (30.2-59.3 u/l) and Turner's syndrome (36.4 u/l) but not with closed spina bifida or rhesus isoimmunisation. When AChE activity was expressed as a percentage of the total cholinesterase activity ('percentage AChE'), there was a good correlation between AChE activity and 'percentage AChE' in normal pregnancies and the values associated with the 37 pregnancies affected by open neural tube defects (NTD) fell outside the 99.9 per cent confidence limits of the normal group. Qualitative differences in cholinesterase activity could be demonstrated between the groups with exomphalos and open NTD. It is suggested that the assay might be used satisfactorily to demonstrate the presence of open NTD in affected pregnancies.

Acetylcholinesterase↗
PubMed1979

Diagnostic value of rectal mucosal acetylcholinesterase levels in Hirschsprung's disease.

Acetylcholinesterase (AChE) activity was measured in rectal biopsy specimens obtained from 68 children aged between 2 days and 14 1/2 years in whom Hirschsprung's disease was suspected. The diagnosis was subsequently established in 12; in these, the mean AChE activity was found to be 30.5 X 10(-7) units/g tissue (range 16.9 to 63.0). The 56 non-Hirschsprung cases had a mean of 5.0 X 10(-7) units/g tissue (S.D. 2.2), the highest value in this group being 10.9. The results were unaffected by age, sex, nature of biopsy procedure, or the presence of blood. It is suggested that the assay of AChE activity in rectal biopsy material is a simple and quick procedure that is useful in the diagnosis of Hirschsprung's disease.

Acetylcholinesterase↗
PubMed1977

An improved method for the determination of acetylcholinesterase activity in rectal biopsy tissue from patients with Hirschsprung's disease.

A method is described for the assay of acetylcholinesterase in tissue samples using the selective cholinesterase inhibitor, lysivane (10-(alpha-diethylaminopropyl) phenothiazine hydrochloride). Significantly increased enzyme activity is found in rectal biopsy specimens from patients with Hirschsprung's disease (p less than 0.001) indicating the diagnostic usefulness of the assay.

Acetylcholinesterase↗