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Biomedical subjects

D Castle

Publications and source records attributed to D Castle.

At least 37 records · Page 2Linked to original sources
PubMed1998

Intracellular transport and secretion of salivary proteins.

Intracellular transport and secretion of salivary proteins are major activities of salivary acinar cells. While the major intracellular pathway followed by salivary proteins following their synthesis has been described previously, there is only limited understanding of how this process is regulated at the molecular level. Studies of salivary proteins, especially proline-rich proteins, expressed in an endocrine cell line have begun to provide insight regarding intermolecular interactions during transport and the role played by structural signals during intracellular sorting. Analysis of the secretion of newly synthesized salivary proteins in parotid tissue has shown that there are multiple pathways of discharge from acinar cells. While granule exocytosis is the major pathway, at least two other pathways that export salivary proteins have been found to originate from maturing secretion granules. These pathways may contribute to other acinar cell functions, including secretion of proteins in the absence of acute stimulation and support of the secretory process for fluid and electrolytes.

Animals↗
PubMed1997

Influenza epidemics and incidence of schizophrenia, affective disorders and mental retardation in Western Australia: no evidence of a major effect.

In-utero exposure to influenza has been implicated as a risk factor for developmental CNS damage. This study tests the hypothesis that in-utero exposure to influenza: (1) in the second gestational trimester is associated with an increased risk of schizophrenia and affective psychoses; and (2) in the first gestational trimester is associated with an increased risk of mental retardation. Analysis was confined to 1852 cases on the Western Australian psychiatric case register with ICD-9 diagnoses of schizophrenia, affective psychoses, or neurotic depression (comparison group), and 804 cases on the Intellectual Handicap Register with mental retardation that were related to 82,963 'exposed' and 32,462 'non-exposed' births between 1950 and 1960 in the total population of Western Australia. The data were examined for effects associated with six influenza epidemics in the period 1950-1960. Using relative risk ratios for individual epidemics as well as Poisson regression and a proportional hazards model to examine systematic effects for the whole period, no major effect could be identified for maternal influenza on the incidence of schizophrenia, affective psychoses and neurotic depression, despite sufficient statistical power to detect an effect. However, a possible effect was found for mental retardation in males exposed in the first and second gestational trimester.

Adolescent↗
PubMed1995

Evidence for a genetic association between alleles of monoamine oxidase A gene and bipolar affective disorder.

We present evidence of a genetic association between bipolar disorder and alleles at 3 monoamine oxidase A (MAOA) markers, but not with alleles of a monoamine oxidase B (MAOB) polymorphism. The 3 MAOA markers, including one associated with low MAOA activity, show strong allelic association with each other but surprisingly not with MAOB. Our results are significant only for females, though the number of males in our sample is too small to draw any definite conclusions. Our data is consistent with recent reports of reduced MAOA activity in patients with abnormal behavioral phenotypes. The strength of the association is weak, but significant, which suggests that alleles at the MAOA locus contribute to susceptibility to bipolar disorder rather than being a major determinant.

Alleles↗
PubMed1995

Genetic association between alleles of pancreatic phospholipase A2 gene and bipolar affective disorder.

Chromosome 12q is a region of interest for the genetics of bipolar affective disorder because of reports of apparent cosegregation between this disorder and Darier's disease in a small number of families. Findings from a recent linkage study suggest that this chromosomal region may contain a susceptibility gene for bipolar affective disorder. We have found evidence of an allelic association between bipolar disorder and a marker at the pancreatic phospholipase A2 gene (PLA2A) in this region (p < or = 0.01). These results are consistent with the linkage study, and warrant additional investigations.

Alleles↗
PubMed1995

Does influenza cause schizophrenia? A five year review.

Over the last five years a body of literature has been generated concerning whether or not prenatal exposure to influenza results in an increased risk of developing schizophrenia in the exposed offspring. The studies are reviewed with respect to the traditional epidemiological criteria that help to define causality. There is a modest degree of consistency in support of an association between the 1957 influenza epidemic--and less so, for influenza epidemics in general--and later schizophrenia. Two cohort studies examining the 1957 epidemic do not support an association. The strength and specificity of the association remain weak. The proposed association draws coherence from the neurodevelopmental hypothesis of schizophrenia. Suggestions are made for future research that could add to our understanding of the putative association between influenza and schizophrenia.

Australia↗
PubMed1994

No evidence of association between dopamine D4 receptor variants and bipolar affective disorder.

Disturbance in the dopamine neurotransmitter system has been implicated in the pathogenesis of affective disorder. In this study, we examine the possibility that functional variants of the recently cloned dopamine D4 receptor gene contribute to the genetic component of manic depression. The polymorphism, a 48 bp tandem repeat coding for part of the third cytoplasmic loop, was detected using a PCR based method. In a first sample of 57 patients and 59 controls, we found allele 7 to be in excess in the patients. In contrast, allele 3 was less frequent in patients. A second, larger sample of 90 patients and 91 controls was utilized to test these hypotheses. Data from the two samples were then pooled together for further analyses. We calculated the power of our samples, and if the frequency of 7 repeat allele obtained from sample 1 is true, i.e., 25% (28/114) for patients and 14% (16/118) for controls, then the power of the combined sample is 62% at 5% (two-tailed) significance level. However, both observations were not replicated; we therefore conclude that variations in this repeat at the DRD4 gene do not contribute to the genetic component of manic depression.

Alleles↗
PubMed1994

The criminal careers of incident cases of schizophrenia.

We present a population-based, longitudinal study of all incident cases (N = 538) of schizophrenia in the London Borough of Camberwell between 1964 and 1984. Cases were selected from the Camberwell Cumulative Psychiatric Case Register. Case-notes were obtained, and further classified using a computerized operational check list for rating psychotic illness. Cases are not restricted to hospital discharges, as in previous studies, and account is taken of time at liberty to offend. In order to test the hypothesis that schizophrenia makes an independent contribution to criminality over other mental disorders, controls were chosen to be representative of nonschizophrenic mental disorders matched for age, sex and period. The rate of conviction is increased in women with schizophrenia compared to other mental disorders for most offence categories (rate ratio = 3.3). In men overall rates do not differ (rate ratio = 1.03), although there is an interaction between gender, schizophrenia and ethnicity, with young black men with schizophrenia being most at risk. The rate ratio for violent offences in men with schizophrenia is 3.8, confirming recent studies from Sweden. Subjects with schizophrenia were more likely to acquire any criminal record than those with other mental disorders. The rate of lifetime conviction was greater in those with schizophrenia than either a sample of working-class boys from the same area followed by Farrington & West, or National data. The risk of first conviction is increased by schizophrenia, unemployment, ethnic group, substance abuse and low social class, and decreased by being employed, married, female and older age of onset. Adjustment using survival analysis showed that schizophrenia made a small independent contribution to the risk of acquiring a criminal record (hazard ratio = 1.4) but gender, substance abuse, ethnicity and age of onset were more substantial. Previous criminality was the strongest independent association of post-illness conviction, with schizophrenia only a trend. Although subjects with schizophrenia were more likely to acquire a criminal record, criminal careers began later and were shorter than those of the controls. The risk of criminality increased throughout the study period, but suggestions of a specific increase in those with schizophrenia as a result of changes in community care were not confirmed. These results confirm that women with schizophrenia are at increased risk of acquiring a criminal record, but the effect in men is for violent convictions only. The strongest associations of criminal conviction remain those recognized in non-schizophrenic subjects.

Adolescent↗
PubMed1994

Association and haplotype analysis at the tyrosine hydroxylase locus in a combined German-British sample of manic depressive patients and controls.

Tyrosine hydroxylase (TH) is the key enzyme in the synthesis of catecholamines and may therefore be of aetiological relevance in the development of psychiatric illness. Hipolar affective disorder association studies, with restriction fragment length polymorphisms located in flanking regions of the TH gene, have shown conflicting results. Alleles of a tetranucleotide repeat polymorphism (TH4) located in intron 1 of the gene were tested for association with bipolar affective disorder in a combined German and British sample of 183 bipolar patients and 209 healthy control probands. No differences in TH4 allele frequencies were found in the two groups. A subset of patients and controls was typed with the flanking markers Ty7/BglII and pJ4.7/TaqI and frequencies of two-locus haplotypes were estimated. Linkage disequilibrium was found between TH4-Ty7 and TH4-pJ4.7. Haplotype frequencies did not differ between patients and controls.

Alleles↗
PubMed1993

Activation of the mitogen-activated protein kinase pathway in Triton X-100 disrupted NIH-3T3 cells by p21 ras and in vitro by plasma membranes from NIH 3T3 cells.

We describe a novel Triton-disrupted mammalian cell system wherein the pathways for activation of mitogen-activated protein (MAP) kinases (MAPKs) are capable of direct biochemical manipulation in vitro. MAPKs p42mapk and p44mapk are activated in signal transduction cascade(s) initiated by occupancy of plasma membrane receptors for peptide growth factors, hormones, and neurotransmitters. One likely activation pathway for MAPKs consists of sequential activations of c-ras, c-raf-1, and a protein-tyrosine/threonine kinase, MAP kinase kinase. Triton-disrupted cells retained capacity for activation of the pathway by both peptide growth factors and by addition of GTP-loaded p21 rasVal12. Incubation of disrupted cells with an antibody that neutralized the function of c-ras (Y13-259) abolished receptor-mediated stimulation of MAPK as did acute addition of 200 microM azatyrosine. Activation of the pathway was reconstituted in a cell-free system using high-speed supernatants generated from Triton-disrupted cells together with purified plasma membranes from parental cells and as a heterogeneous system using purified plasma membranes from v-ras-transformed cells. These systems will allow biochemical dissection in vitro of the interaction(s) between c-ras and the MAPK pathway in mammalian cells.

3T3 Cells↗
PubMed1993

The dopamine D3 receptor gene: no association with bipolar affective disorder.

Bipolar affective disorder and schizophrenia share many clinical and genetic characteristics, and are thought by some to be different expressions of the same underlying disorder. A recent study showed an excess of homozygosity at a BalI polymorphism in the dopamine D3 receptor gene in schizophrenic patients compared with controls, from two independent centres. We have found no evidence of such an excess in a comparable sample of patients with bipolar affective disorder compared with matched controls. If these findings are confirmed then at least one genetic distinction between these two disorders will have been ascertained and doubt cast upon theories of a common genetic aetiology.

Alleles↗
PubMed1993

A comparative study of 470 cases of early-onset and late-onset schizophrenia.

The presence or absence of 22 schizophrenic symptoms was recorded with the age at onset of illness in 470 patients with non-affective, non-organic psychoses. Positive and negative formal thought disorder, affective symptoms, inappropriate affect, delusions of grandiosity or passivity, primary delusions other than delusional perception, and thought insertion and withdrawal were all more common in early-onset cases (age at onset 44 years or less; n = 336). Persecutory delusions with and without hallucinations, organised delusions, and third-person, running commentary and accusatory or abusive auditory hallucinations were all more common in late-onset cases (age at onset 45 years or more; n = 134). There was no difference between cases of early and late onset in the prevalence of delusions of reference, bizarre delusions, delusional perception, or lack of insight. We conclude that although there are clinical similarities between cases of schizophrenia with early and late onset, there are sufficient differences between them to suggest that they are not phenotypically homogeneous.

Adolescent↗
PubMed1992

Protein sorting and secretion granule formation in regulated secretory cells.

Formation of secretion granules in regulated secretory cells involves packaging a subject of proteins undergoing intracellular transport into specific vesicular carriers that function in stimulus-dependent exocytosis. Recent findings suggest that immature granules are a site of passive sorting, involving condensation of regulated secretory proteins. Proteins that are not condensed are stored to a lesser degree and are enriched in unstimulated, constitutive-like secretion. While these observations have helped to distinguish possible mechanisms of secretory protein sorting, there are only recent hints about the sorting processes that may be required to create the regulated secretory carrier membranes.

Journal Article↗
PubMed1992

Hereditary motor and sensory neuropathy type I, associated with aplasia cutis congenita: possible X-linked inheritance.

We report a family with possible X-linked recessive HMSN I with minor signs of the disease and abnormal sensory conduction studies evident in female carriers. There is a previously undescribed association with aplasia cutis congenita in both affected males, and a history of a severe skull defect in a third male child, who died at birth. The latter defect usually shows an autosomal dominant pattern of inheritance.

Adolescent↗