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Biomedical subjects

H F Baker

Publications and source records attributed to H F Baker.

119 records · Page 7Linked to original sources
PubMed1979

Monoamine mechanisms in chronic schizophrenia: post-mortem neurochemical findings.

Dopamine and its metabolites homovanillic acid and dihydroxyphenylacetic acid, noradrenaline, serotonin and its metabolite 5-hydroxyindoleacetic acid, and tryptophan and its metabolite kynurenine have been assayed in 9 schizophrenic and 10 control brains, together with the monoamine-related enzymes tyrosine hydroxylase monoamine oxidase, dopamine-beta-hydroxylase, and catechol-o-methyl-transferase. In schizophrenic brains dopamine, noradrenaline and serotonin were significantly increased in some areas of corpus striatum, but there were no significant changes in enzyme activity or monoamine metabolite concentrations in any of the brain areas examined. The findings are not consistent with theories that serotonin or noradrenaline stores are grossly depleted or noradrenaline neurones have degenerated, or that monoamine oxidase activity is abnormal, in schizophrenia, and provide no direct support for the hypothesis that dopamine neurones are overactive.

Aged↗
PubMed1979

The time course of the behavioral effects of amphetamine and their reversal by haloperidol in a primate species.

A group of six marmosets was administered amphetamine (Phase I), amphetamine plus haloperidol (Phase II), and then amphetamine alone (Phase III) over consecutive periods of 27, 51, and 33 days after which drug treatment was terminated (Phase IV). The animals' behavior was monitored during these periods and during a predrug treatment control period. Five mutually exclusive categories of behavior were assessed during the experiment. Social contact between animals was significantly suppressed and inactivity was increased throughout Phases I--III but both measures returned to normal values during Phase IV. Locomotion was significantly decreased towards the end of Phase I and initially during Phase II. Rapid head movements (termed checking) were significantly increased at the beginning of Phase I and again when the haloperidol was withdrawn at the beginning of Phase III. Towards the end of Phase I the animals developed destructive self-grooming habits. The time course of the effects of amphetamine and haloperidol on the different behavioral categories suggests that different mechanisms may be involved in each case. Viewed as a model of schizophrenia, the time course of haloperidol in reversing amphetamine-induced suppression of locomotion most closely resembles the time course of the antipsychotic effect of neuroleptics in man. Some effects of amphetamine (e.g., suppression of social interaction) are not reversed by haloperidol, and some effects of withdrawal of haloperidol (e.g., precipitation of checking movements not present when haloperidol was commenced) do not have an obvious counterpart in the clinical situation.

Amphetamine↗
PubMed1977

Platelet serotonin concentration and monoamine oxidase activity in unmedicated chronic schizophrenic and in schizoaffective patients.

Elevated blood serotonin, perhaps secondary to reduced platelet MAO, has been reported in a group of chronic schizophrenic patients. We have failed to find elevated platelet serotonin, or any relationship between platelet serotonin and MAO either in a group of unmedicated chronic schizophrenic patients or in a group of schizoaffective patients. Possible reasons for these discrepancies are discussed.

Adult↗
PubMed1976

Determination of 3-methoxy-4-hydroxyphenylglycol conjugates in urine. Application to the study of central noradrenaline metabolism in unmedicated chronic schizophrenic patients.

On the basis of post-mortem studies it has been proposed that the central deficit in schizophrenia may be in noradrenergic transmission. It has also been proposed that there is a substantial central contribution to the excretion of the noradrenaline metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG) and more particularly of its sulphate conjugate in man. There is throught to be a lesser central contribution to the excretion of the other major noradrenaline metabolites, vanillylmandelic acid (VMA) and the glucuronide conjugate of MHPG. A strong negative correlation was found between severity of illness in a group of 18 unmedicated chronic schizophrenic patients and their 24-h excretion of MHPG-sulphate but not of MHPG-glucuronide or VMA. However there was no significant difference in the mean excretion of MHPG conjugates or of VMA between the schizophrenic group and an institutional control group. This supports the idea of a relation between MHPG-sulphate excretion and central noradrenergic activity, but suggests that reduced brain noradrenaline turnover is neither necessary nor sufficient for schizophrenia to occur. One possible explanation is that reduced turnover pre-disposes towards a more severe illness in schizophrenics.

Brain↗
PubMed1976

The determination of 5-hydroxytryptophan and its metabolites in plasma following administration to man.

The estimation of 5-hydroxytryptophan and its metabolites 5-hydroxytryptamine and 5-hydroxyindoleacetic acid in plasma is described. The method is based on solvent extraction and the use of a liquid cation exchange reagent to separate 5-hydroxytryptamine and 5-hydroxytryptophan. The 5-hydroxyindoles are determined fluorimetrically following derivatisation with o-phthalaldehyde in strong acid. Data on the specificity and linearity of the method are presented. The time course of plasma 5-hydroxyindoles after oral administration of 5-hydroxytryptophan is studied in two subjects as an example of the application of the method and of its possible role in monitoring the plasma levels in therapy or in provocative tests.

5-Hydroxytryptophan↗
PubMedDate not supplied

Behavioral assessment of the ability of intracerebral embryonic neural tissue grafts to ameliorate the effects of brain damage in marmosets.

The transplantation of neuronal tissue into the brains of patients with Parkinson's disease is already being assessed as an experimental treatment for the symptoms of this disease, and the possibility of using similar graft tissue to ameliorate the symptoms of other neurodegenerative diseases is being considered. In this context, a small number of transplant experiments have been carried out in monkeys with lesions of the central dopamine and cholinergic systems. These experiments make it possible to determine the optimum methods of transplantation in an animal whose brain is structurally more closely related to the human than that of the rat and to assess the behavioral consequences of transplantation on symptoms that either resemble very closely the symptoms seen in patients, or are of a complex cognitive nature and are therefore more difficult to measure in the rat. It is intended that these experiments will contribute to the development of better treatments for the neurodegenerative diseases, either by the use of transplantation as a clinical treatment, or by contributing to a better understanding of the mechanisms that normally maintain neuronal function and that fail in these diseases.

Animals↗
PubMedDate not supplied

A critical evaluation of monkey models of amnesia and dementia.

In this review we consider various models of amnesia and dementia in monkeys and examine the validity of such models. In Section 2 we describe the various types of memory tests (tasks) available for use with monkeys and discuss the extent to which these tasks assess different facets of memory according to present theories of human memory. We argue that the rules which govern correct task performance are best regarded as a form of semantic rather than procedural memory, and that when information about stimulus attributes or reward associations is stored long-term then that knowledge is semantic. The demonstration of episodic memory in monkeys is problematic and the term recognition memory has been used too loosely. In particular, it is difficult to dissociate episodic memory for stimulus events from the use of semantic memory for the rule of the task, since dysfunction of either can produce impairment on performance of the same task. Tasks can also be divided into those which assess memory for stimulus-reward associations (evaluative memory) and those which tax stimulus-response associations including spatial and conditional responding (non-evaluative memory). This dissociation cuts across the distinction between semantic and episodic memory. In Section 3 we examine the usefulness of the classification of tasks described in Section 2 in clarifying our understanding of the contribution of the temporal lobes and the cholinergic system to memory. We conclude that evaluative and non-evaluative memory are mediated by separate parallel systems involving the amygdala and hippocampus, respectively.

Amnesia↗
PubMedDate not supplied

Variable expression in the functional psychoses. A comparison with Huntington's disease.

The variability in presentation and the interaction between age of onset, symptomatology and the calculation of penetrance in Huntington's disease is used as a framework within which to consider whether the various presentations of the functional psychoses could be different manifestations of the effects of a single gene. The phenomenon of the biotype, i.e., the tendency for family members to resemble each other in symptomatology in a manner which is too variable within families to be explained by either genetic or allelic heterogeneity but which is too stable within families to be explained by random variation, is clearly demonstrable in Huntington's disease. In families with multiple cases of psychosis, the tendency for the diagnosis in the proband to prevail in other affected individuals together with the possible occurrence in yet other individuals of different diagnostic categories at above chance levels may also be an example of the biotype phenomenon. While genetic heterogeneity in the functional psychoses probably also occurs, the possible variation in expression of single genes predicts that the correspondence between different genes and diagnostic subtypes would be limited.

Bipolar Disorder↗
PubMedDate not supplied

Survival of nigral grafts within the striatum of marmosets with 6-OHDA lesions depends critically on donor embryo age.

The study examined the importance of embryonic donor age for the survival of nigral grafts in 6-OHDA-lesioned marmosets. The issue as to whether donor age is critical for the survival of nigral grafts in primates is controversial, because several early reports suggested that relatively old tissue could survive transplantation and produce functional benefits in monkeys, in contrast to the restrictive time dependence observed in rodents. Embryonic marmoset donors embryos of three different ages were employed: 1) E74 (Carnegie stage 18-19); 2) E83-84 (Carnegie stage 23+); 3) E92-93 (foetal period). The nigral neurons derived from the ventral mesencephalon in the two older donor age groups did not survive well when grafted to the striatum of adult marmosets with unilateral 6-OHDA lesions. Although a few tyrosine hydroxylase (TH+) neurons could be identified by immunohistochemistry at graft sites in all recipients in older donor age groups, the numbers of surviving neurons in these were small, on average typically less than 100 TH+ cells. These small grafts were not sufficient to affect amphetamine-induced rotation. In contrast, many more TH+ cells typically survived transplantation in the recipients of graft tissue derived from the youngest donors and amphetamine-induced rotation was significantly reduced in this group alone. The time course and extent of the reduction in rotation was remarkably similar to that observed in previous marmoset nigral graft studies, confirming the utility of amphetamine-induced rotation as a sensitive and reliable indicator of nigral graft function in this species. Considering these results and other recent evidence from monkey to monkey, human to rat, and human to human graft studies, the survival of embryonic nigral tissues derived from primate donors transplanted into the striatum does appear to be critically dependent on the age of the donor tissue.

Animals↗