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Biomedical subjects

N Hunt

Publications and source records attributed to N Hunt.

At least 73 records · Page 4Linked to original sources

Identification of an inhibitory element within the human 68-kDa (U1) ribonucleoprotein antigen.

Various nuclear proteins are the major targets of autoimmune responses in various rheumatic disorders. In particular, autoantibodies directed against a 68-kDa protein associated with the (U1) RNA-containing small nuclear ribonucleoprotein complexes typically occur in sera of patients with mixed connective tissue disease and related rheumatic disorders, such as systemic lupus erythematosus, and therefore are very useful as a serological marker. For establishing powerful immunoassays, it was necessary to generate recombinant human P68 antigen as the antigenic target. In this study we demonstrated that the cDNA coding for the full-length human P68 antigen could not be expressed by a traditional bacterial vector system due to a putative inhibitory sequence designated as inhibitory sequence X which is located between the autoreactive domains C' and D' of the human P68 antigen. The construction of corresponding hybrid plasmids carrying two functional and independent gene blocks indicated the trans-active function of the inhibitory sequence X, which could be localized by expression studies of various deletion constructs. Comparable Northern blot analysis clearly demonstrated that the inhibitory sequence X could act on the translation of the P68 mRNA. After excision of the inhibitory sequence X a dramatic increase in the production of recombinant human P68 antigen was observed.

Amino Acid Sequence↗

Corrosion of intra-oral magnets in the presence and absence of biofilms of Streptococcus sanguis.

Intra-oral magnets are used in dentistry for a variety of purposes, and their susceptibility to corrosion is of great clinical importance. Although a number of in vitro models have been developed to study corrosion of intra-oral magnets, none have attempted to determine the possible contribution to corrosion made by oral bacteria, which are known to form a biofilm on intra-oral appliances. We have exposed demagnetized neodymium/iron/boron (Nd2Fe14B) magnets to an artificial saliva in the presence and absence of a biofilm of Streptococcus sanguils, one of the predominant organisms in the oral cavity. Over a 21-d period, a 3.2% decrease in the mass of the magnets was observed when S. sanguis was present, while in the absence of the organism the decrease in mass was 1.4%. We also examined the ability of poly(para-xylylene), a commonly-used coating, to protect the magnets against corrosion. No decrease in the mass of magnets coated with poly(para-xylylene) was detected over a 21-d period in the presence of S. sanguis. This study has shown that biofilms of S. sanguis cause appreciable corrosion of Nd2Fe14B magnets which is greater than that occurring in the absence of the organism, and that a coating of poly(para-xylylene) provides protection against such corrosion.

Biofilms↗

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↗

Is there a seasonal pattern of relapse in bipolar affective disorders? A dual northern and southern hemisphere cohort study.

BACKGROUND: Admission statistics for mania frequently show an increase in the summer. The present two-centre study was designed to test the hypothesis, in a representative sample of bipolar patients, that manic and depressive relapses show a seasonal pattern. METHOD: Two cohorts of bipolar I patients, one in London, England (n = 86), the other in Dunedin, New Zealand (n = 58), were tracked retrospectively during 1985-88 and prospectively during 1989-91, with the onset of all relapses being carefully dated. RESULTS: In the London cohort there were 221 episodes of mania and 76 of depression; in the Dunedin cohort there were 201 of mania and 61 of depression. No consistent seasonal pattern of mania was detected in either centre. There was an autumn preponderance of depressive episodes in both centres. CONCLUSIONS: Relapse of bipolar depression, but not of mania, appears to be determined in part by seasonal factors.

Adult↗

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↗

A strategy for trauma debriefing after railway suicides.

Following an increase in the incidence of railway suicide from an average of four events a year up to 1989 to 12 in 1990 an initiative was developed between the District Department of Clinical and Community Psychology, Exeter Health Authority and British Rail, Western Region. Traincrew leaders and management had become increasingly aware of the severity of the short- and long-term effects on drivers of experiencing a suicide. Although a management strategy had been developed over time to deal with what had been a rare phenomenon it was clear that such a dramatic increase in suicides warranted a more professional approach to debriefing and trauma counselling. This paper describes the strategies adopted by psychologists in developing an understanding of the stresses of experiencing suicides and other major incidents. The outcome of small group sessions with affected drivers is outlined. An account of the strategy developed through workshops with traincrew leaders is detailed and a three-stage debriefing (shock, search, adjustment) and follow-up protocol is discussed. This process is proposed for adoption as normal procedure following suicides or similar traumas for drivers and line managers.

Adaptation, Psychological↗

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↗

'Alarming but very necessary': working with staff groups around the sexual abuse of adults with learning disabilities.

This study focused on the knowledge of front line staff, as individuals and in groups, in relation to the sexual abuse of adults with learning disabilities and was designed to inform staff training and policy initiatives and to explore gender dynamics. It showed that front line staff were alert to the possibility of sexual abuse but unclear about their roles and responsibilities making this an area of great concern to them. One third knew of people who had been abused but these had been dealt with haphazardly, leaving front line staff holding disproportionate anxiety on behalf of the service as a whole.

Adult↗

Selectable retrovirus vectors encoding Friend virus gp55 or erythropoietin induce polycythemia with different phenotypic expression and disease progression.

The Friend spleen focus-forming virus induces a massive expansion of erythroid progenitor cells resulting in polycythemia and splenomegaly. The pathogenic agent is the membrane glycoprotein gp55, encoded by the env gene. Recent evidence indicates that gp55 binds to and activates the erythropoietin (Epo) receptor. It is not clear, however, whether gp55 completely mimics the natural receptor ligand (Epo). To directly compare both effectors, we constructed selectable retroviral vectors which carry either the env or the Epo gene. The selection marker allowed for clonal analysis of infected cells. After infection of DBA/2J mice, the spleen weight, hematological indices, and Epo titer of peripheral blood were monitored. Although both viruses induced an acute erythrocytosis, there were significant differences in disease phenotype and progression. The Epo virus caused an enhanced increase of hematocrit and erythrocytes, whereas with the env virus the pool of late progenitors (CFU-erythroid) was dramatically expanded, resulting in a more severe splenomegaly. The distribution of cytologically recognizable erythroid precursors was shifted towards immature cell types by the env vector compared with Epo. These data suggest that Epo and gp55 differentially affect proliferation and differentiation. Gp55 appears to promote proliferation over differentiation, whereas Epo preferentially drives differentiation.

Animals↗

The incidence of mania in two areas in the United Kingdom.

The incidence of mania in an inner-city area was estimated by both a casenote search with later interview and a prospective interview method. The incidence was found to be twice as high as that in a more rural area, as estimated by the casenote-based method. Though a high proportion of the inner-city population were from ethnic minorities, particularly Afro-Caribbean, this could not explain the discrepancy. It is suggested that the incidence of mania is related to the mobility of the local population.

Adult↗

Graves' autoimmune serum inhibits gonadal steroidogenesis: development of a Leydig cell bioassay to identify broad spectrum anti-endocrine autoantibodies.

In order to establish an assay for the detection of autoimmune sera with broad spectrum activity, we have investigated the effect of unselected normal and Graves' disease sera upon steroidogenesis by gonadal cells. Steroidogenesis was enhanced by the addition of normal serum in a 3-h primary Leydig cell bioassay, but was inhibited by the majority of Graves' sera. The inhibition was not related to clinical thyroid parameters, such as the severity of the TSH-binding inhibition index, and was not overcome by other agonists or second messenger supplements. Although pituitary TSH preparations bound to and stimulated Leydig cells, TSH receptor mRNA was not detectable and pure recombinant TSH failed to bind or stimulate, indicating contamination of pituitary TSH with LH. The binding of hCG to the Leydig cell luteinizing hormone receptor was not perturbed by the Graves' autoimmune sera, indicating that cross-reactive anti-TSH receptor antibodies were not responsible for the inhibition. By use of intermediates in the stimulatory pathway, the site of Graves' serum inhibition was identified to be distal to hormone receptor/adenylate cyclase coupled responses and proximal to supply of cholesterol for steroidogenesis.

Animals↗

Maternal/congenital syphilis in a large tertiary-care urban hospital.

Among the women delivering a total of 9,591 infants in 1990 at Hutzel Hospital in Detroit, 148 had positive results in the rapid plasma reagin (RPR) and fluorescent treponemal antibody-absorption tests for syphilis. This group included primarily young, black, multigravid women with a history of crack cocaine use. RPR titers ranged from 1:1 to 1:256 among the 103 mothers not treated or inadequately treated for syphilis. Two mothers with very low RPR titers (1:2) delivered a stillborn infant and an infant with a reaction in the cerebrospinal fluid Venereal Disease Research Laboratory (CSF-VDRL) test, respectively. Seventy-five percent of the infants born to untreated or inadequately treated women had asymptomatic congenital syphilis. The remaining 25% were stillborn (6 infants) or had clinical features of congenital syphilis (3 infants), a reactive CSF-VDRL test (11 infants), or radiological evidence of periostitis or metaphysitis (6 infants). Abnormalities were documented in the placentas from 11 live births and one stillbirth. The resurgence of congenital syphilis highlights the need for better diagnostic tests and for studies that will determine optimal therapy for mother and infant.

Adult↗

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↗