Biomedical subjects
C Dean
Publications and source records attributed to C Dean.
Self-neglect in adult life.
Two cases of self-neglect in adult patients with no psychiatric diagnosis are reported. The presentation included domestic squalor and hoarding of rubbish, with the patients living alone and having a history of schizoid and paranoid personality traits. Both refused all recommended help. A move to more protected accommodation was the only practical measure that led to a degree of improvement.
Controlling cardiovascular disease: the role of the local health department.
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One hundred consecutive laparoscopic cholecystectomies performed in a rural hospital.
Laparoscopic cholecystectomy has quickly become the treatment of choice by most surgeons for the treatment of gallstone disease. The authors reviewed their first 100 consecutive patients undergoing laparoscopic cholecystectomy at a rural hospital. Twenty-three patients had previous abdominal procedures. The open insufflation technique was used on all patients with previous abdominal operations, with the exception of those who had an appendectomy only. Operative cholangiography was performed routinely and successfully on all patients, with the exception of the first seven because of nonavailability of a cholangiocath. In 54 percent of the first two-thirds of these patients, the operation was completed in less than 1.5 hours. In contrast, 88 percent of the last one-third of the patients were operated on within the same time period. All but 9 of the 100 patients were discharged within 24 hours of their surgery. Laparoscopic cholecystectomy can be performed safely and routinely in the rural hospital setting with results similar to those expected in larger metropolitan centers.
The effect of circulating antigen and radiolabel stability on the biodistribution of an indium labelled antibody.
This study has investigated two of the main problems with radiolabelled antibody imaging, the formation of circulating immune complexes (I.C.) and the non specific binding of radiolabel to the antibody molecule. Patients undergoing immunoscintigraphy with 111In labelled monoclonal antibody ICR2 were divided into three groups who received either the radiolabelled antibody alone (control, n = 12), the radiolabelled antibody which was incubated with the chelating agent diethylene triamine pentacetic acid (DTPA) prior to size exclusion chromatography (n = 6) or whose injectate was treated with DTPA and cold MAb administered intravenously prior to radiolabelled MAb administration (n = 6). Radiolabelled antibody uptake in abdominal organs was measured by region of interest analysis using a gamma camera with online computer and that in tumour and normal tissues by gamma well counting of biopsies. Circulating antigen and immune complex was measured by high pressure liquid chromatography (HPLC). The sensitivity of tumour imaging and the tumour uptake of radiolabelled antibody was not significantly different between the groups. Patients with high circulating antigen levels developed high levels of circulating immune complex but also had high tumour uptakes of radiolabelled antibody. Administration of cold MAb increased the splenic, but did not effect the tumour uptake of radiolabelled antibody and only minimally reduced levels of circulating immune complex. Chelate administration reduced the urinary excretion of radioactivity but increased the liver uptake of radioactivity. These results have shown that successful antibody imaging can be carried out despite high levels of circulating antigen, that large doses of unlabelled antibody are required to prevent immune complex formation and that removal of non specifically bound 111In does not reduce the liver uptake of radioactivity.
Identification and map position of YAC clones comprising one-third of the Arabidopsis genome.
YAC clones corresponding to 125 Arabidopsis thaliana RFLP markers have been identified. At least one YAC clone has been isolated for each of the RFLP markers tested. Based on CHEF gel analysis of 196 clones, the mean insert size of the available Arabidopsis YAC libraries is approximately 160 kb. The YACs of known genetic map location encompass about 30% of the Arabidopsis genome. The results presented here represent a first step towards assembly of an overlapping YAC library of the A. thaliana genome.
Gender, parity and the prevalence of minor affective disorder.
Data from a two-stage survey of the general population were used to test the proposition that the over-representation of minor affective disorders among women was restricted to those who had had children, independently of current involvement in childcare. Initial analyses supported this proposition strongly. Subsequent linear logistic analyses were largely in favour of an effect of marriage rather than of parity, but it remains possible that part of the gender differences in rates of depression arises because of the effect of parity in raising female prevalence. If substantiated, the parity effect could operate through social or biological mechanisms; although its nature is unclear, it merits further investigation.
The Fregoli syndrome and puerperal psychosis.
Four cases of the Fregoli syndrome occurring in the setting of puerperal psychosis are described. They are discussed in relation to previously reported cases and it is proposed that the acute onset of the psychosis and ambivalence arising with childbirth are important factors in the pathogenesis.
Development of an efficient transposon tagging system in Arabidopsis thaliana.
We are currently developing a transposon tagging system in Arabidopsis thaliana using the maize transposable elements Ac and Ds. In order to make the system as efficient as possible, four different antibiotic resistance markers have been tested for their usefulness in monitoring excision and reinsertion of transposons in the Arabidopsis genome. Owing to the low transposition frequency of wild-type Ac in Arabidopsis we have also tested a number of modifications to the Ac element. Deletion of the CpG-rich region in the transposase 5' untranslated leader was found to significantly increase the activity of Ac in Arabidopsis. In our first non-targeted tagging experiment, 200 individuals with an inherited transposed Ac element have been collected and their progeny are being screened in families of twelve for segregation of mutant phenotypes. A two-element system, using Ac and Ds, is also being developed and a way of stabilising the Ds-induced mutations by counter selecting plants carrying the transposase source is being investigated. The Agrobacterium T-DNA insertions carrying the different transposons are currently being mapped onto the Arabidopsis RFLP map. Inverse polymerase chain reaction (IPCR) is being used to generate flanking DNA probes, that will be used on the RFLP blots to map the T-DNA relative to the other known markers. Once the first few have been mapped the first targeted tagging experiment will be initiated.
Home treatment for acute psychiatric illness.
OBJECTIVE: To determine the factors influencing the successful outcome of community treatment for severe acute psychiatric illnesses that are traditionally treated in hospital. DESIGN: All patients from a single electoral ward who were either admitted to hospital or treated at home over a two year period (1 October 1987 to 30 September 1989) were included in the study and their case notes audited. The second year of the study is reported. SETTING: Electoral ward of Sparkbrook, Birmingham. SUBJECTS: 99 Patients aged 16-65 with severe acute psychiatric illness. RESULTS: 65 Patients were managed by home treatment alone; 34 required admission to hospital. The location of treatment was significantly (all p less than 0.05) influenced by social characteristics of the patients (marital state, age (in men), ethnicity, and living alone) and by characteristics of the referral (occurring out of hours; assessment taking place at hospital or police station). DSM-III-R diagnosis was more weakly associated with outcome. Violence during the episode was significantly related to admission, although deliberate self harm was not. CONCLUSIONS: Home treatment is feasible for most patients with acute psychiatric illness. A 24 hour on call assessment service increases the likelihood of success because admission is determined more strongly by social characteristics of the patient and the referral than by illness factors. Admission will still be required for some patients. A locally based mental health resource centre, a 24 hour on call service, an open referral system, and an active follow up policy increase the effectiveness of a home treatment service.
Genes for two herbicide-inducible cytochromes P-450 from Streptomyces griseolus.
Streptomyces griseolus ATCC 11796 contains two inducible, herbicide-metabolizing cytochromes P-450 previously designated P-450SU1 and P-450SU2 (P-450CVA1 and P-450CVB1, respectively, using nomenclature of Nebert et al. [D. W. Nebert, M. Adesnik, M. J. Coon, R. W. Estabrook, F. J. Gonzalez, F. P. Guengerich, I. C. Gunsalus, E. F. Johnson, B. Kemper, W. Levin, I. R. Phillips, R. Sato, and M. R. Waterman, DNA 6:1-11, 1987]). Using antibodies directed against cytochrome P-450SU1, its N-terminal amino acid sequence, and amino acid composition, we cloned the suaC gene encoding cytochrome P-450SU1. Similar information about the cytochrome P-450SU2 protein confirmed that a gene cloned by cross-hybridization to the suaC gene was the subC gene encoding cytochrome P-450SU2. The suaC and subC genes were expressed in Escherichia coli, DNA for both genes was sequenced, and the deduced amino acid sequences were compared with that of the well-characterized cytochrome P-450CAM from Pseudomonas putida. Both cytochromes P-450SU1 and P-450SU2 contain several regions of strong similarity with the amino acid sequence of P-450CAM, primarily in regions of the protein responsible for attachment and coordination of the heme prosthetic group.
Firing characteristics of single-fiber carotid sinus baroreceptors.
This study examined firing patterns of single-fiber carotid baroreceptors in response to slow ramp increases in carotid sinus pressure (1-2 mm Hg/sec) in vascularly isolated carotid sinus preparations in thiopental-anesthetized dogs (25 mg/kg, plus 10 mg/kg/hr). Two general types of baroreceptor discharge patterns were obtained: 1) type I, a discontinuous, hyperbolic pattern characterized by a sudden onset of discharge at threshold pressure with a relatively high threshold frequency, which gradually increased to a higher saturation firing rate and 2) type II, a continuous, sigmoidal pattern characterized by a gradual increase in discharge above threshold pressure and a relatively low threshold frequency and saturation firing rate. Type II baroreceptor curves typically showed spontaneous discharge below threshold pressure and significantly lower sensitivities, threshold frequency, saturation firing rate, and threshold pressure than those of type I receptors. However, the saturation pressures and operating ranges of the type II receptors were greater than those of type I receptors, and the pressure at which type II receptors had their greatest sensitivity was greater than that for type I receptors. Type I baroreceptors generally had large myelinated afferent A fibers; type II baroreceptors generally had smaller A and unmyelinated C fibers, based on conduction velocities. The presence of spontaneous activity with type II baroreceptors, combined with significantly lower sensitivities and wider pressure operating ranges seen relative to type I baroreceptors, suggests that these receptors may primarily serve to provide information on tonic, or baseline, levels of arterial blood pressure to the central cardiovascular centers. The sudden onset of discharge, higher sensitivities, and narrower operating ranges of type I baroreceptors suggest that their primary role may be to provide information on dynamic, sudden changes in arterial pressure.
Experimental and modeling study of the excitability of carotid sinus baroreceptors.
In this study we examined the effects of blockade of a transient K+ current with 4-aminopyridine (4-AP) on the static stimulus-response relation of myelinated carotid sinus baroreceptors (n = 8), using a vascularly isolated sinus preparation in sodium thiopental-anesthetized dogs. In one class of baroreceptors (type I), which did not fire spontaneously below the pressure threshold (Pth), 4-AP (10(-5) to 10(-4) M) decreased Pth in a dose-dependent manner and transformed the stimulus-response relation from a discontinuous, hyperbolic shape to a sigmoidal, continuous curve. After exposure to 10(-4) M of 4-AP, baroreceptors were spontaneously active below Pth. These effects of 4-AP were more pronounced in baroreceptors with a high control Pth and were independent of enhanced neurotransmitter release or changes in carotid sinus distensibility. In contrast, 4-AP had relatively little effect on type II baroreceptors, which under control conditions are characterized by a continuous, sigmoidal stimulus-response curve. We believe that these effects of 4-AP on baroreceptor discharge were mediated by blockade of a transient K+ conductance that was present at the receptor spike-initiation zone. This hypothesis was examined using a mathematical model based on the Hodgkin-Huxley axon, but modified to include the transient K+ conductance. The modeling results showed that the minimum current necessary to elicit action potential firing is an extremely sensitive function of the magnitude of this K+ conductance, supporting our experimental results obtained with 4-AP. Our findings suggest that a transient K+ conductance might play a role in the determination of Pth and that differences between type I and II receptors could be the result of differences in the effectiveness of this conductance in controlling spike-initiation zone excitability.
Symptomatic trans-sexualism.
A 24-year-old male schizophrenic had a delusion that he was female and had lived his life as a woman for almost two years. Unlike the only other reported case, his 'symptomatic trans-sexualism' responded to the effective treatment of his schizophrenia.
The t complex polypeptide 1 (TCP-1) is associated with the cytoplasmic aspect of Golgi membranes.
The t complex polypeptide 1 (TCP-1) is a protein of unknown function expressed in large amounts during spermatogenesis. Rat monoclonal antibodies recognizing TCP-1 have been prepared and used to immunoprecipitate and Western blot a 57 kd protein from germ cell and tissue culture cell extracts. In tissue culture cells, indirect immunofluorescent localization of antigen indicated a perinuclear distribution similar to that of the Golgi apparatus. Analysis of the TCP-1 distribution in tissue culture cells showed that the polypeptide was associated with the cytoplasmic aspect of membranes of the trans-Golgi network (TGN). The distribution in spermatids suggested that TCP-1 was localized to structures often associated with the developing acrosome. The TCP-1 antigenic epitopes are highly conserved, allowing the protein to be identified in cells across a wide variety of vertebrate species and tissues. These experiments suggest that TCP-1 may be essential for transport of proteins through the exocytic pathway in all cells and required in large amounts for acrosome formation in developing spermatids.
Problem child. Interview by Daloni Carlisle.
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Expression of a C3 plant Rubisco SSU gene in regenerated C4 Flaveria plants.
We report the successful transformation, via Agrobacterium tumefaciens infection, and regeneration of two species of the genus Flaveria: F. brownii and F. palmeri. We document the expression of a C3 plant gene, an abundantly expressed ribulose 1,5-bisphosphate carboxylase/oxygenase small subunit gene isolated from petunia, in these C4 plants. The organ-specific expression of this petunia gene in Flaveria brownii is qualitatively identical to its endogenous pattern of expression.
Do psychological factors predict survival in breast cancer?
One hundred and twenty-two women with primary operable breast cancer were interviewed before and three months after mastectomy. The outcome of 121 of the women was assessed 6-8 years after operation. Women who were regarded as having enough symptoms to fulfil the criteria for a psychiatric illness (according to Research Diagnostic Criteria (RDC) and the General Health Questionnaire (GHQ) before operation were less likely to have a recurrence during the follow-up. Those who were assessed three months after operation as coping by using a strategy of denial had a better chance of remaining recurrence-free than those women employing other coping strategies; this finding must be viewed with reservation because of the inherent difficulties in measuring coping strategies. These psychological measures improved the prediction of recurrence-free survival beyond that achieved by other variables (e.g. histological node status, tumour size and treatment).