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Biomedical subjects

D J Clarke

Publications and source records attributed to D J Clarke.

At least 109 records · Page 6Linked to original sources
PubMed1990

Very early onset Huntington's disease: genetic mechanism and risk to siblings.

A study of very early onset Huntington's disease (VEOHD) has shown that at least 38% of gene-carrying sibs also develop symptoms before the age of 10, thus improving the genetic risk for those sibs who remain healthy. The prevalence of VEOHD among sibs shows that mutation during spermatogenesis is most unlikely to account for these uncommon cases. The data suggest that two mechanisms contribute to VEOHD: modification by many genes (individually of small effect), and an epigenetic mechanism occurring when transmission is through a series of males.

Adolescent↗
PubMed1990

Tourette-like disorder in Asperger's syndrome.

An eight-year-old boy with Asperger's syndrome was given haloperidol to control agitation and aggressive outbursts. Withdrawal of the drug after two years was followed by Tourette-like symptoms. Subsequently neither haloperidol nor a second antipsychotic drug altered the core features of Asperger's syndrome, despite suppressing the movement disorder. His first exposure to neuroleptics was in utero.

Adolescent↗
PubMed1990

Klüver-Bucy syndrome and psychiatric illness.

A 52-year-old woman, whose initial psychiatric presentation at the age of 15 was with a disorder resembling schizophrenia, developed symptoms of Klüver-Bucy syndrome, and is now thought to suffer from an organic psychotic disorder. Klüver-Bucy syndrome must be distinguished from symptoms of schizophrenia or affective disorder; its presence suggests an organic process.

Affective Symptoms↗
PubMed1989

Agglutination of Legionella pneumophila by antiserum is accelerated in an ultrasonic standing wave.

The agglutination of Legionella pneumophila (LP) by diluted anti-LP whole rabbit serum has been compared in conventional microwell plates and in capillary containers where the suspension was exposed to a 1 MHz ultrasonic standing wave field. A positive reaction in the standing wave field was detected as a series of cell agglutinates, separated by half an acoustic wavelength (0.75 mm), distributed along the length of the capillary. Agglutination occurred in 60 s or less with ultrasound, while the incubation period for a positive microwell test was often of the order of hours. At a given antiserum concentration, ultrasound-induced agglutination occurred at LP concentrations two-fold lower than those giving a positive result in the microwell plate assays. At cell concentrations near the lower limit for detection of a positive result in the microwell plates a positive reaction was detected in the standing wave field at antiserum concentrations up to 500-fold lower than those forming visible precipitates in the conventional assay.

Agglutination↗
PubMed1989

Restoration of cholinergic circuitry in the hippocampus by foetal grafts.

The pathway from medial septum to hippocampus is one of the major and most well-documented cholinergic connections in the rodent brain. Interruption of this pathway by either direct destruction of the cells of origin in the medial septum or by transection of the fimbria-fornix, the fibre tract along which the septohippocampal axons traverse, results in a virtually complete depletion of cholinergic markers within the hippocampal formation. Previous experiments have shown that grafts of foetal rat septal-diagonal band region placed into the denervated hippocampus can restore acetylcholinesterase (AChE) fibre density to 85-90% of control values (Björklund et al., Acta physiol. scand. Suppl. 522 (1983) 49-58). More recently, it has been demonstrated using the more specific technique of choline acetyltransferase (ChAT) immunocytochemistry in combination with electron microscopy that septal grafts are also able to restore the cholinergic connectivity at the synaptic level in the dorsal hippocampal formation. However, we have demonstrated that this restoration of both AChE and ChAT fibre density represents a specific mechanism and that the source of the foetal cholinergic neurons is crucial to the extent of reinnervation and pattern of connectivity achieved. In aged rats, judged as being behaviourally impaired with respect to their spatial memory, there appears to be an intrinsic denervation of the septohippocampal pathway such that the hippocampus is depleted of cholinergic markers. In these cases, transplantation can again restore cholinergic innervation but without the requirement of prior denervation by a fimbria-fornix transection--grafts are placed into the intact hippocampus. Results show that the grafts survive well in the aged, intact hippocampus and are able to ameliorate the behavioural impairments, perhaps by the formation of substantial numbers of cholinergic synapses between the graft and host brain. In conclusion, therefore, neural grafting of cholinergic neurons of appropriate type and origin is able to reinnervate the hippocampal formation previously denervated either by mechanical transection of the fimbria-fornix or as a result of an age-dependent deterioration.

Acetylcholine↗
PubMed1989

Apparatus for the electrical characterisation of conductive fluids.

Non-invasive and fully automated conductimetric measurements of electrolyte and bacterial samples were achieved in a closed volume test cell, comprising a magnetic field coil and detector. By monitoring field induced currents in sample electrolytes the magnitude of the sample current was shown to vary as the inverse of the sample impedance. The impedance characteristic was shown to be that of an LCR resonant circuit. This characteristic is primarily a function of the applied frequency and the solution/cell properties being dependent on the solution conductivity and dielectric permittivity at any given concentration. Small changes in sample dielectric permittivity in the presence of a large background conductivity are shown to be significant. The apparatus described can provide fixed or swept frequency conductivity measurements in the range 1 kHz to 2.25 MHz with a lower conductivity sensitivity of 0.9 x 10(-3) Scm-1. Bulk impedimetric characteristics of cell suspensions are derived by a two stage measurement.

Bacillus megaterium↗
PubMed1989

Antilibidinal drugs and mental retardation: a review.

A minority of people with mental retardation have sexual behaviour which is socially unacceptable or which brings them into conflict with the law. Such behaviour may be the result of ignorance about sexual matters, often best managed by counselling or by a behavioural approach. There are a small number of men with mental retardation and aberrant sexual behaviour who benefit from the prescription of an antilibidinal drug. Treatment with an antilibidinal drug alone reduces the intensity of sexual drive but does not alter its direction; concurrent sexual counselling or psychotherapy is often indicated. The various antilibidinal medications available are reviewed, with particular attention to reports which have described the treatment of people with mental retardation. Of the antilibidinals currently used, medroxyprogesterone acetate and cyproterone acetate are those for which there is most evidence of efficacy. Cyproterone acetate is preferable because it has a specific antiandrogenic action and fewer adverse effects. There is a need for controlled studies of antilibidinal drugs, with clearly defined inclusion criteria and adequate measures of both behavioural and attitudinal change.

Benperidol↗
PubMed1989

Adults with Prader-Willi syndrome: abnormalities of sleep and behaviour.

A survey of 32 adult females and 31 adult males with Prader-Willi syndrome (PWS) shows that sleep disorders (including excessive day and night time sleep) and behavioural abnormalities, (temper tantrums and deliberate picking of sores) are common. These abnormalities are not related to the degree of obesity or to each other. Speech disorders also occur. Intelligence quotients are often within the normal range.

Adolescent↗
PubMed1989

Familial association of albinism and schizophrenia.

Of three siblings in a family, one brother and one sister have both tyrosinase-negative oculocutaneous albinism and a psychotic disorder indistinguishable from schizophrenia. The two disorders may associate within families through genetic linkage or a failure of neurotransmitter homoeostasis.

Adult↗
PubMed1989

Rapid detection of hepatitis B virus using a haemagglutination assay in an ultrasonic standing wave field.

A haemagglutination test for Hepatitis B virus has been expedited by increasing cell-cell contact through concentrating antibody-coated erythrocytes in an ultrasonic standing wave field. The reactants used were taken from a commercially available Hepatitis B surface antigen screening kit, which is commonly employed in hospital laboratories and blood banks to screen human sera. When performed in microwells, as prescribed in the kit, positive and negative reactions were discernible after 30 min. However, with the ultrasonic technique these reactions can be distinguished within 5 min.

Evaluation Studies as Topic↗
PubMed1988

Comparison of growth and reinnervation properties of cholinergic neurons from different brain regions grafted to the hippocampus.

Grafts of five different types of central cholinergic neurons, from the septal-diagonal band region, the nucleus basalis magnocellularis region (NBM), the striatum, the pontomesencephalic tegmentum of the brainstem, and the spinal cord, were compared with respect to their ability to grow and to reinnervate the cholinergically denervated hippocampal formation of adult rats. The areas were dissected from 14 to 15-day-old rat fetuses, and the same number of viable cells (35 X 10(4) from each of the different regions were stereotaxically injected as cell suspensions into the hippocampus of rats subjected to a transection of the intrinsic septo-hippocampal cholinergic pathways. At 17-19 weeks after transplantation, the various graft types differed considerably in their volume, the total amount of acetylcholinesterase (AChE)-positive fiber outgrowth, and the innervation pattern and morphology of the AChE-positive fibers growing into the host hippocampus. On average the NBM and spinal cord grafts had grown to become three to four times larger than the septal and the brainstem grafts, and 15-20 times larger than the striatal grafts. By contrast, the total ingrowth score of AChE-positive fibers in the host hippocampus from the septal grafts was about twice that of the NBM and brainstem grafts, about five times greater than the striatal grafts, and about six times greater than that of the spinal cord grafts. The large NBM grafts thus exhibited similar fiber outgrowth to the much smaller brainstem grafts, and the AChE-positive neurons of the grafted spinal cord grew very poorly into the hippocampus despite the fact that they survived very well. The innervation pattern and morphological features of the ingrowing AChE-positive fibers in the host hippocampus proper and in the dentate gyrus resembled those of normal rats in animals with grafts from any of the three forebrain regions (i.e., septum, NBM, or striatum), whereas ingrowth from the brainstem and spinal cord grafts were markedly abnormal with respect to both innervation pattern and fiber morphology. These results provide further evidence that the overall survival, growth, and fiber outgrowth of intracerebral neural grafts depend on interactions with the surrounding host tissue. Since the ability to reinnervate the previously denervated host target was greatest for the neuron type normally innervating that area, i.e., the septal-diagonal band neurons, we conclude that neuronal properties beyond the transmitter type are essential for the optimal performance of implanted neurons in intracerebral grafting experiments.

Acetylcholinesterase↗
PubMed1988

Human fetal dopamine neurons grafted in a rat model of Parkinson's disease: immunological aspects, spontaneous and drug-induced behaviour, and dopamine release.

We have used a rat model of Parkinson's disease (PD) to address issues of importance for a future clinical application of dopamine (DA) neuron grafting in patients with PD. Human mesencephalic DA neurons, obtained from 6.5-8 week old fetuses, were found to survive intracerebral cell suspension xenografting to the striatum of rats immunosuppressed with Cyclosporin A. The grafts produced an extensive new DA-containing terminal network in the previously denervated caudate-putamen, and they normalized amphetamine-induced, apomorphine-induced and spontaneous motor asymmetry in rats with unilateral lesions of the mesostriatal DA pathway. Grafts from an 11.5-week old donor exhibited a lower survival rate and smaller functional effects. As assessed with the intracerebral dialysis technique the grafted DA neurons were found to restore spontaneous DA release in the reinnervated host striatum to normal levels. The neurons responded with large increases in extracellular striatal DA levels after the intrastriatal administration of the DA-releasing agent d-amphetamine and the DA-reuptake blocker nomifensine, although not to the same extent as seen in striata with an intact mesostriatal DA system. DA fiber outgrowth from the grafts was dependent on the localization of the graft tissue. Thus, grafts located within the striatum gave rise to an extensive axonal network throughout the whole host striatum, whereas grafted DA neurons localized in the neocortex had their outgrowing fibers confined within the grafts themselves. In contrast to the good graft survival and behavioural effects obtained in immunosuppressed rats, there was no survival, or behavioural effects, of human DA neurons implanted in rats that did not receive immunosuppression. In addition, we found that all the graft recipients were immunized, having formed antibodies against antigens present on human T-cells. This supports the notion that the human neurons grafted to the non-immunosuppressed rats underwent immunological rejection. Based on an estimation of the survival rate and extent of fiber outgrowth from the grafted human fetal DA neurons, we suggest that DA neurons that can be obtained from one fetus may be sufficient to restore significant DA neurotransmission unilaterally, in one putamen, in an immunosuppressed PD patient.

Amphetamine↗
PubMed1988

Human fetal dopamine neurons grafted in a rat model of Parkinson's disease: ultrastructural evidence for synapse formation using tyrosine hydroxylase immunocytochemistry.

Human fetal mesencephalic dopamine (DA) neurons, obtained from 6.5-9 week old aborted fetuses, were grafted to the striatum of immunosuppressed rats with 6-hydroxydopamine lesions of the ascending mesostriatal DA pathway. The effects on amphetamine-induced motor asymmetry were studied at various timepoints after grafting. At eight weeks, functional graft effects were not evident but after 11 weeks small effects on motor asymmetry could be monitored and rats tested 19-21 weeks after grafting exhibited full reversal of the lesion-induced rotational behaviour. Four rats were sacrificed at different timepoints between 8 and 20 weeks and the grafted DA neurons were studied in tyrosine hydroxylase (TH) immunocytochemically stained sections at the light and electronmicroscopic level. The grafts contained a total of 500-700 TH-positive neurons in each rat. In one rat sacrificed 8 weeks after grafting the grafted neurons were TH-positive but exhibited virtually no fiber outgrowth. In another rat, sacrificed after 11 weeks, a sparse TH-positive fiber plexus was seen to extend into the adjacent host neostriatum. Two rats sacrificed after 20 weeks both contained TH-positive neurons that gave rise to a rich fiber network throughout the entire host neostriatum, and this fiber network was also seen to extend into the globus pallidus and nucleus accumbens. Very coarse TH-positive processes, identified as dendrites in the electron microscope, projected up to 1.5-2.0 mm from the graft into the host striatum. Ultrastructural analysis revealed that the grafted neurons had formed no TH-positive synaptic contacts with host striatal neurons after 8 weeks, and at 11 weeks some few TH-positive synapses were identified. Twenty weeks after transplantation, abundant TH-positive synaptic contacts with host neurons were seen throughout the neostriatum, and such contacts were identified in the globus pallidus as well. Thus, the present study provides tentative evidence for a time-link between the development of synaptic contacts and the appearance of functional graft effects. Similar to the normal mesostriatal DA pathway, ingrowing TH-positive axons formed symmetric synapses and were mainly seen to contact dendritic shafts and spines. However, in comparison to the normal rat striatum there was a higher incidence of TH-immunoreactive boutons forming synapses onto neuronal perikarya. The TH-positive dendrites that extended into the host striatum were seen to receive non-TH-immunoreactive synaptic contacts, presumably arising from the host neurons.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1988

Determination of protein size in chromatography column eluants by on-line photon correlation spectroscopy.

The dynamic light scattering technique of photon correlation spectroscopy has been used to determine biomacromolecule hydrodynamic radius in solutions flowing at rates similar to those experienced in liquid chromatographic separation systems. Such analyses can be performed rapidly (less than 5 s). The potential of the technique as an on-line noninvasive monitor for liquid chromatography is discussed.

Light↗
PubMed1988

Striatal grafts in rats with unilateral neostriatal lesions--I. Ultrastructural evidence of afferent synaptic inputs from the host nigrostriatal pathway.

Tyrosine hydroxylase immunocytochemistry, in combination with Golgi impregnation, has been used to study the dopaminergic afferent input to striatal suspension grafts implanted into the previously ibotenic acid-lesioned striatum in adult recipient rats. The rats were perfused for combined light- and electron microscopy at 10-11 months after transplantation, at the end of a series of behavioural experiments and a study of in vivo GABA release, reported in the two accompanying papers. A tyrosine hydroxylase-positive fibre network occurred within the grafts in all eight specimens analysed. The tyrosine hydroxylase-positive fibres had a distinct "patchy" distribution, throughout the graft tissue, and within these patches the terminal density was similar to that of the normal intact striatum. Ultrastructurally, the tyrosine hydroxylase-positive fibres were seen to make abundant synaptic contacts with neuronal elements within the grafts. As in the normal striatum, they were all of the symmetric type and dendritic shafts and spines were the most usual postsynaptic targets. Sections from three of the grafted animals were taken for combined Golgi-impregnation and immunostaining. Only cells of the medium-sized densely spiny type were impregnated in this material. Six of them, which had portions extending into the immunostained neuropil, were drawn using a camera lucida and processed for electron microscopy. Tyrosine hydroxylase-positive boutons were seen to make symmetrical synaptic contacts onto the shafts and spines of the impregnated dendrites, and in one case also with the perikaryon. The results indicate that the medium-sized densely spiny neuron type (which is a predominant target for the dopaminergic afferents in the normal striatum) is abundant in the grafted tissue, and that these neurons represent a synaptic target also for the tyrosine hydroxylase-positive innervation of the striatal grafts.

Animals↗
PubMed1988

Striatal grafts in rats with unilateral neostriatal lesions--II. In vivo monitoring of GABA release in globus pallidus and substantia nigra.

GABA release was recorded in vivo by push-pull perfusion from the globus pallidus and substantia nigra of control rats, rats with unilateral ibotenic acid lesions of the neostriatum, and rats with embryonic striatal tissue grafts implanted in the lesioned striatum. The lesions reduced baseline levels of GABA release to 5% of control levels in the globus pallidus and to 13% of control levels in the substantia nigra pars reticulata. GABA release was substantially restored in both the globus pallidus and substantia nigra of the grafted rats, to 34 and 60%, respectively. Peripheral injection of the dopaminergic stimulant methamphetamine induced a short (lasting approximately 20 min) 4-5 fold increase in GABA release in the intact globus pallidus and a longer (lasting longer than 80 min) increase in the substantia nigra. The stimulatory effect of methamphetamine on GABA release was completely abolished in both sites by the strial lesions, suggesting that the effect was mediated via a direct or indirect dopaminergic action on striatal output neurons. The grafts reinstated methamphetamine-induced stimulation of GABA release in striatal output targets to a level (as a proportion of baseline) that was similar to that seen in the control rats. The results support the view that activation of the dopaminergic inputs to the striatum is functionally excitatory on the major striatal output projections to the globus pallidus and substantia nigra pars reticulata. The results also support the hypothesis that striatal grafts have the capacity to become functionally incorporated by reciprocal graft-host connections into the neural circuitry of the host brain.

Animals↗
PubMed1988

Striatal grafts in rats with unilateral neostriatal lesions--III. Recovery from dopamine-dependent motor asymmetry and deficits in skilled paw reaching.

This study investigated the functional capacity of intrastriatal grafts of embryonic striatal tissue in rats with unilateral ibotenic acid lesions of the neostriatum. The group of grafted rats was compared with lesion-alone and control groups for motor bias, as assessed by tests of rotation induced by dopaminergic, cholinergic and GABAergic drugs, and of skilled paw reaching. Unilateral striatal lesions induced marked ipsilateral turning to apomorphine and methamphetamine, which was substantially ameliorated in the grafted rats. Atropine induced similar rates of moderate (but non-significant) ipsilateral turning in the lesion and graft groups, whereas muscimol and gamma-acetylenic GABA induced no turning bias in any group. The lesioned rats showed a strong bias in their preference to use the paw ipsilateral to the lesion when reaching for food pellets, and a decline in reaching success with both paws. The grafts did not influence the ipsilateral paw preference in this task, but did provide a substantial improvement in the animal's reaching accuracy and ability to retrieve food with either paw. The results indicate that striatal grafts can provide a substantial amelioration of motor impairments induced by striatal lesions. Moreover they suggest that the graft's influence on the host brain is itself under the functional regulation of an afferent dopaminergic input from the host brain.

Alkynes↗