Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Subcutaneous injection of adrenaline into normal male volunteer subjects caused large increases of plasma non-esterified fatty acids and free tryptophan, but plasma total tryptophan fell considerably. Therefore increases of the percentage of plasma tryptophan in the free state were more marked than absolute increases of free tryptophan. 2. Plasma tyrosine fell slightly and plasma phenylalanine and cortisol were unaffected. 3. It is suggested that catecholamine release could lead to abnormalities of tryptophan disposition in stress and psychiatric illness.
Clin Sci Mol Med 1977 Sep
PMID:Effects of adrenaline injection on human plasma tryptophan and non-esterified fatty acids. 91 45

Cells from the olfactory epithelium of adult human cadavers have been propagated in primary culture and subsequently cloned. These cells exhibit neuronal properties including: neuron-specific enolase, olfactory marker protein, neurofilaments, and growth-associated protein 43. Simultaneously, the cells exhibit nonneuronal properties such as glial fibrillary acidic protein and keratin, the latter suggesting properties of neuroblasts or stem cells. These clonal cultures contain 5-10% of cells sufficiently differentiated to show odorant-dependent cyclic adenosine 3',5'-monophosphate (cAMP) or calcium-release responses when challenged with submicromolar concentrations of odorants. The potential of culturing neuronal cells from patients with neuropsychiatric disorders, such as Alzheimer's disease or schizophrenia, could enable the study of the pathophysiology of these neurons in the culture dish and allow new approaches to the study of mental illness.
J Mol Neurosci 1992
PMID:Continuous culture of neuronal cells from adult human olfactory epithelium. 132 Sep 21

Adrenoleukodystrophy (ALD) is a progressive X-linked disorder that produces pathological changes, mainly in the adrenal cortex and the white matter of the central nervous system. The main biochemical abnormality is the accumulation of saturated unbranched fatty acids with a chain length of 24 or more, referred to as very-long-chain fatty acids (VLCFA). Affected children develop large zones of demyelination associated with perivascular lymphoctyic infiltrations resembling those seen in multiple sclerosis. Adults show a more chronic form of the disease, referred to as adrenomyeloneuropathy (AMN). AMN mainly involves the spinal cord ad peripheral nerves, although the cerebral hemispheres may also be affected. Approximately 15% of female carriers have nervous-system involvement that resembles AMN. It is well known that ALD may initially appear as a psychiatric disorder. In the present study, we have assessed the prevalence of cognitive impairment in a group of AMN patients and neurologically symptomatic ALD heterozygotes initially presenting primarily physical complaints. Sixty percent of these patients demonstrated significant neuropsychological impairment, most commonly a pattern of spared and impaired functions typical of a subcortical dementia. We suggest that this progressive cognitive impairment may underlie other behavioral deficits, affirming the significance of the psychological features of this genetically determined disorder.
Mol Chem Neuropathol 1990 Jun
PMID:Cognitive impairment in adult-onset adrenoleukodystrophy. 209 65

We report a null mutation in the first exon of the human dopamine D4 receptor (DRD4) gene. The mutation is predicted to result in a truncated non-functional protein and is the first natural nonsense mutation found in a human dopamine receptor gene. It occurs with a frequency of about 2% in the general population. The distribution of the mutation was found to be similar in healthy controls and patients suffering from psychiatric diseases which included schizophrenia, bipolar affective disorder and Tourette's syndrome, indicating that heterozygosity for this mutation in the DRD4 gene is not causally related to major psychiatric diseases. We also identified an adult male who is homozygous for this mutation. He shows no symptoms of major psychiatric illness, but he displays somatic ailments including acousticous neurinoma, obesity and some disturbances of the autonomic nervous system. Some of these symptoms might be related to the absence of functional DRD4 protein.
Hum Mol Genet 1994 Dec
PMID:Human dopamine D4 receptor gene: frequent occurrence of a null allele and observation of homozygosity. 788 21

1. The topical distribution of tritiated dexamethasone (DEX), a potent synthetic glucocorticoid of widespread use in the diagnosis and assessment of mental illness, was studied in rat CNS by autoradiography to obtain information on potential target sites for feedback and other centrally mediated effects of glucocorticoids. 2. The cells of the arcuate nucleus of the hypothalamus and the lateral thalamic nuclei displayed the most concentrated nuclear accumulation of silver grains. 3. Significant accumulation, exceeding that found in the hippocampal formation, also occurred in the cells of the ventromedial, periventricular, and paraventricular nuclei of the hypothalamus, the locus ceruleus, the nucleus tractus solitarii, and the area postrema, none of which are targeted by corticosterone, the native glucocorticoid of the rat. 4. Nuclear accumulation of silver grains was prominent in neural and glial cells of the cerebral cortex, the olfactory nucleus, the dorsolateral septum, the amygdala, the subfornical organ, the lateral parabrachial, medial trapezoid, and dorsal reticular nuclei, the nucleus centralis of the raphe, the cerebellum, and vascular tissues. 5. The localization of DEX in hypothalamic and brain-stem nuclei coincided with that of the glucocorticoid receptor, possibly implicating these sites in direct or modulating effects of glucocorticoids in various forms of mental disturbance, including depression, anxiety, panic disorders, and alcohol withdrawal. 6. The extent to which various CNS regions targeted by DEX feature in negative feedback control of adrenocortical secretion remains to be defined, as does the site of impaired feedback disclosed by the dexamethasone suppression test in psychiatric patients.
Cell Mol Neurobiol 1993 Aug
PMID:Dexamethasone target sites in the central nervous system and their potential relevance to mental illness. 825 8

Schizophrenia is a serious psychiatric illness with a life-time risk of approximately one percent. Many of the patients, but not all, benefit from treatment with anti-psychotic drugs known to block dopamine D2-like receptors. The use of conventional neuroleptics is, however, hampered by the risk of extrapyramidal side-effects. Tardive dyskinesia (TD) is usually regarded as the most serious of these drug-induced movement disorders due to its high prevalence and potentially irreversible nature. In this study, we have investigated the genetic variation of the dopamine D3 receptor gene (DRD3) as a putative risk factor for TD in schizophrenic patients receiving long-term anti-psychotic drug therapy. We found a high frequency (22-24%) of homozygosity for the Ser9Gly variant (allele 2) of the DRD3 gene among subjects with TD in both a cross-sectional and a longitudinal evaluation, as compared with the relative under-representation (4-6%) of this genotype in patients with no or fluctuating TD. This result indicates that autosomal inheritance of two polymorphic Ser9Gly alleles (2-2 genotype), but not homozygosity for the wild-type allele (1-1 genotype), is a susceptibility factor for the development of TD, an observation which may improve the understanding of the pathophysiological mechanisms of TD and influence the design and choice of future anti-psychotic drugs. The correlation between a serious motor side-effect and a genetic marker could lead to selection bias in the sampling of schizophrenic patients for genetic studies, and may therefore explain the apparent association reported between susceptibility for schizophrenia per se and homozygosity for the DRD3 gene.
Mol Psychiatry 1997 Mar
PMID:Dopamine D3-receptor gene variant and susceptibility to tardive dyskinesia in schizophrenic patients. 910 22

The majority of common psychiatric disorders pose problems for geneticists because of their complex and non-Mendelian modes of inheritance. Early attempts to map genes for mental illness have so far largely overlooked this and sought genes of major effect in multiplex families using the lod score method of linkage analysis. However it seems that major genes are likely to be at best rare causes of common mental disorders, and the majority of cases probably reflect the interaction of several and perhaps many genes of comparatively small effect. There are two complementary sets of strategies that allow such genes to be identified. The first is to perform linkage analysis based on allele sharing in pairs of affected relatives. The second is to carry out association studies on samples of unrelated individuals. These methods and their applicability to psychiatric disorders are described. Psychiatric genetics has traditionally focussed on categorical phenotypes, but if valid continuous measures can be developed, powerful quantitative trait loci (QTL) approaches may also become feasible. Another important area is likely to be the study of relevant models in animals such as rodents in which genetic studies have many advantages. Finally we should not overlook the possibility that there are molecular explanations for irregular patterns of transmission such as mitochondrial inheritance, genomic imprinting and dynamic mutations.
Mol Psychiatry 1996 Mar
PMID:Modern molecular genetic approaches to complex traits: implications for psychiatric disorders. 911 8

Postmortem brain tissue was used to measure expression of serotonin transporter mRNA in the left frontal and left temporal cortex from schizophrenics (n = 24) and from normal control individuals with no history of psychiatric illness (n = 10). There was an approximately four-fold increase of serotonin transporter mRNA in Brodmann's area 9 and a two-fold decrease in Brodmann's areas 21 and 22. The changes in serotonin transporter mRNA were more prominent in schizophrenics who had received neuroleptic drugs within 1 week prior to death than in schizophrenics who were neuroleptic-free for more than 2 weeks prior to death, suggesting that the changes may be related to neuroleptic treatment. There was no correlation between serotonin transporter mRNA levels and the sex or age of schizophrenic and control cases or the postmortem delay intervals. These results support the hypothesis that region-specific changes in serotonin transporter expression occur in brains of some schizophrenics. Future studies are necessary to determine whether the changes in serotonin transporter expression are drug-related or are associated with the illness itself.
Mol Psychiatry 1997 Jan
PMID:Abnormal expression of serotonin transporter mRNA in the frontal and temporal cortex of schizophrenics. 939 85

In the present study, we evaluated the possible contribution of genetic variation of the serotonin 5-HT7 receptor to the development of schizophrenia and bipolar affective disorder. Cloning and characterization of exon-flanking intronic sequences enabled us to investigate the whole coding region and the exon-intron boundaries of the human 5-HT7 receptor gene. Using single-strand conformational analysis, we screened for presence of DNA sequence variation in a sample of 137 unrelated individuals including 45 schizophrenic and 46 bipolar affective patients, as well as 46 healthy controls. We detected two rare naturally occurring receptor variants (Pro-279-Leu, Thr-92-Lys) and a silent nucleotide substitution (A-->G) at position +1233. The occurrence of the Pro-279-Leu and Thr-92-Lys substitutions was studied in an extended sample of patients (n = 462) and controls (n = 335). The Leu-279 variant was found in similar frequency in all groups, indicating that presence of this variant is not causally related to the development of schizophrenia or bipolar affective disorder. The Lys-92 variant was found in a single individual who suffered from bipolar affective disorder. Investigation of the patient's family revealed independent segregation between the Lys-92 variant and psychiatric illness. Our data suggests that genetic variation of the 5-HT7 receptor does not play a major role in the development of bipolar affective disorder and schizophrenia.
Mol Psychiatry 1996 Nov
PMID:The human serotonin 7 (5-HT7) receptor gene: genomic organization and systematic mutation screening in schizophrenia and bipolar affective disorder. 915 33

Seventy-two adults with phenylketonuria were evaluated to investigate the genotypic relationship to phenotype. Patient data were collected by chart review and medical follow-up as well as current psychological evaluation. Nineteen diagnosed neonatally had remained on a phenylalanine-restricted diet all their lives, whereas 34 who were also diagnosed on newborn screening had discontinued dietary restriction during childhood. Nineteen others who were born prior to newborn screening were diagnosed later than the newborn period on clinical grounds but have remained on dietary restriction. Comparison between intellectual ability, academic achievement, and mental illness was made with degree of diet control as defined by range of blood phenylalanine levels over time. Diet discontinuation in childhood did not significantly lower IQ per se but appeared to diminish academic achievement. The lowest IQ scores were associated with poor dietary restriction of phenylalanine in the diet during childhood. While there appears to be a strong genotypic relationship to phenotypic metabolic parameters in phenylketonuria, there does not seem to be a similar relationship to intellectual ability in adults. Mutation R408W was not strongly related to the occurrence of mental illness in this sample. We conclude that dietary restriction of phenylalanine neonatally and good control contributed to normal intellectual development. Continuation of dietary treatment into adulthood appeared to improve academic achievement in patients with severe phenylalanine hydroxylase mutations.
Biochem Mol Med 1997 Apr
PMID:The relationship of genotype to phenotype in phenylalanine hydroxylase deficiency. 916 88


1 2 3 4 5 6 7 8 9 10 Next >>