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Biomedical subjects

G Harrison

Publications and source records attributed to G Harrison.

At least 19 recordsLinked to original sources

The Ty1-copia group retrotransposons in Vicia species: copy number, sequence heterogeneity and chromosomal localisation.

We present an in-depth study of the Ty1-copia group of retrotransposons within the plant genus Vicia, which contains species with widely differing genome sizes. We have compared the numbers and sequence heterogeneities of these genetic elements in three diploid Vicia species chosen to represent large (V. faba, 1C = 13.3 pg), medium (V. melanops, 1C = 11.5 pg) and small (V. sativa, 1C = 2.3 pg) genomes within the genus. The copy numbers of the retrotransposons are all high but vary greatly, with V. faba containing approximately 10(6) copies, V. melanops about 1000 copies and V. sativa 5000 copies. The degree of sequence heterogeneity of Ty1-copia group elements correlates with their copy number within each genome, but neither heterogeneity nor copy number are related to the genome size of the host. In situ hybridization to metaphase chromosomes shows that the retrotransposons in V.faba are distributed throughout all chromosomes but are much less abundant in certain heterochromatic regions. These results are discussed in the context of plant retrotransposon evolution.

Amino Acid Sequence

Variability of post-void residual urine volume in the elderly.

Residual urine volume, though clinically important as a diagnostic tool, is reported to be variable and unreliable. Variability was examined among 14 geriatric patients, mean age 77 years. Residual urine was measured by ultrasound at three different times of day on each of two visits separated by 2-4 weeks. Results were examined by analysis of variance. Mean residual urine was 154 ml. Between-patient variability was large [standard deviation (SD) 246 ml]. There was no significant difference between values in men and women, nor between visits. Within-patient variability was large because of a large systematic variation with time of day (SD 128 ml), with greatest volumes in the early morning. The inherent, random variability of the measurement was much smaller than this (SD 44 ml). If the physiological factors causing the temporal variation could be controlled, more reproducible measurements would be possible.

Aged

Long-term follow-up of schizophrenia in 16 countries. A description of the International Study of Schizophrenia conducted by the World Health Organization.

An unexpected finding of the International Pilot Study of Schizophrenia, launched by the World Health Organization (WHO) in 1967, was that patients in countries outside Europe and the United States have a more favourable short- and medium-term course of the disease than those seen in developed countries. Since then, WHO has intensified its schizophrenia research programme and has initiated a set of international studies that have confirmed these initial findings and explored possible reasons for such differences in the course and outcome of schizophrenia. While such work has provided important findings and has generated additional pertinent hypotheses, it did not explain the differences in outcome. The present paper describes a new initiative in which approximately 2500 subjects involved in previous WHO multicentre schizophrenia studies are being followed up for between 15 and 25 years after initial examination. Nineteen research centres in 16 countries are taking part in this work. The research methodology is described.

Adult

The Ty1-copia group retrotransposons of Allium cepa are distributed throughout the chromosomes but are enriched in the terminal heterochromatin.

The genomic organization and diversity of the Ty1-copia group retrotransposons has been investigated in a monocotyledonous plant, Allium cepa. We used the polymerase chain reaction (PCR) to generate sequences corresponding to a conserved domain of the reverse transcriptase gene of Ty1-copia retrotransposons in this plant. Sequence analysis of 27 of these PCR products shows that they are a highly heterogeneous population, a feature which is common in plants but not in yeast and Drosophila. Slot-blot analysis shows there are 100,000-200,000 copies of Ty1-copia group retrotransposons within the A. cepa genome (2C = 31.7 pg), indicating that they are a significant component of the genome of this plant. In situ hybridization to metaphase chromosomes reveals that Ty1-copia retrotransposons are distributed throughout the euchromatin of all chromosomes of A. cepa but are enriched in the terminal heterochromatic regions, which contain tandem arrays of satellite sequences. This is the first clear evidence for the presence of Ty1-copia retrotransposons in the terminal heterochromatin of plants and contrasts with the distribution of these elements in other plant species.

Allium

Predicting the long-term outcome of schizophrenia.

Predictors of long-term (13 year) outcome of schizophrenia are reported for a representative cohort of 'treated incidence' patients ascertained on their first contact with Nottingham psychiatric services between 1978-80. An initial (baseline) model including previously reported predictors of 2-year outcome (age, gender, ever married, acuteness of onset) and length of untreated illness was used to predict a range of outcome measures covering the domains of disability, psychopathology, hospitalization, employment, social activity, and global outcome. This model demonstrated significant prognostic ability across all non-hospitalization outcomes under both ICD-10 and ICD-9 diagnoses of schizophrenia, but was attenuated under broad (ICD-9 and CATEGO S, P or O) and restrictive (S+) diagnostic classifications. Female gender predicted more favourable outcome under all diagnostic classifications except S+. In an extended analysis, the addition of initial 2-year course type substantially increased the prognostic ability of the model under all diagnostic classifications and enabled over 30% of the variance in global ratings of disability and symptoms to be predicted. In this extended model female gender predicted more favourable outcome over and above the effect of course type, across most domains under ICD-10, and for disability and psychopathology under other diagnostic classifications. The inclusion of measures of psychopathology at the time of first assessment, pre-morbid functioning, and duration of index admission conferred only marginal additional predictive ability for respective outcomes in the domains of psychopathology, social activity, employment and hospitalization. Hospitalization during the past year was the most difficult outcome to predict under any model suggesting that resource utilization represents the 'administrative outcome' of schizophrenia and serves as a poor proxy for broader concerns in the era of community care. These data demonstrate that key demographic variables and the mode of onset influence the long-term course of schizophrenia, but that early course type is a particularly strong predictor.

Adult

The course of schizophrenia over 13 years. A report from the International Study on Schizophrenia (ISoS) coordinated by the World Health Organization.

BACKGROUND: This paper describes the 13 year course of illness in an epidemiologically defined and representative cohort of patients selected when they were experiencing their first episode of schizophrenia. METHOD: In a 13-year follow-up study of 67 patients with ICD-9 schizophrenia, identified in Nottingham in 1978-80, the course of illness (symptoms, disability and hospitalisation) was assessed using standardised instruments, applied at onset, 1,2, and 13 years. Time to first relapse and first readmission were calculated and plotted as survival curves and patients were assigned to the course types described by Ciompi. RESULTS: The survival curves show that first relapses and first readmissions occur during the first five years. The amount of time spent in psychotic episodes and in hospital is greatest in the first year of follow-up, but stable thereafter. Social adjustment improves from entry to the study to the first follow-up year, but there is a small deterioration in social adjustment between 2 and 13 years. CONCLUSIONS: The findings reported suggest that after the initial episode the course of schizophrenia is relatively stable. The data support neither concepts of progressive deterioration nor progressive amelioration. There was no evidence of a "late recovery'.

Adolescent

The phosphatidylinositol-glycolipid anchor on alkaline phosphatase facilitates mineralization initiation in vitro.

Alkaline phosphatase (AP) is required for the proper mineralization of cartilage and bone. The enzyme is localized to the outer surface of cells through a phosphatidylinositol-glycolipid anchor, which is covalently attached to the carboxyl terminus of the protein. In calcifying cartilage, AP-rich matrix vesicles (MVs) are released into the matrix from chondrocytes, and apatite formation is initiated within and around these particles. In this paper we examine the role of the AP glycolipid anchor using an in vitro mineralization assay system. AP was purified to homogeneity, and the purified enzyme was used to drive mineral formation in vitro with and without the anchor. Mineral formation was initiated through phosphate release from beta-glycerol phosphate (beta-GP). The amount of PO4(-3) released was similar whether the anchor was present or absent. However, SEM and X-ray microanalysis revealed that the mineral produced by anchored AP was indistinguishable from that produced by MVs and that both of those minerals were more apatite-like than mineral formed by soluble AP or through spontaneous precipitation. Taken together, the data suggest that in addition to providing PO4(-3) to drive mineralization, AP influences the nature of the mineral formed. Further, AP containing its glycolipid anchor produces mineral comparable with that formed by tissue-derived MVs. Thus, in the absence of extracellular matrix, MV mineralization in vitro can be emulated by glycolipid-anchor containing AP.

Alkaline Phosphatase

Characteristics of outcome in schizophrenia at 13 years.

BACKGROUND: This paper describes the 13-year outcome of an epidemiologically defined and representative cohort of patients selected when they were experiencing their first episode of schizophrenia. METHOD: In a 13-year follow-up study of a cohort identified in Nottingham in 1978-80, the outcome (symptoms, disability, residence and treatment) was assessed using standardised instruments. RESULTS: Four of the original 67 patients with ICD-9 schizophrenia were lost to follow-up and five were dead: 52% were without psychotic symptoms in the last two years of follow-up, 52% were without negative symptoms and 55% showed good/fair social functioning. However, only 17% were alive at follow-up, without symptoms and disability, and receiving no treatment. CONCLUSIONS: The findings reported are similar to those of other long-term follow-up studies of schizophrenia and also to 5-year follow-up studies. Kraepelin's emphasis on the longitudinal implications of a diagnosis of schizophrenia are supported, but may be over-pessimistic.

Adolescent

Psychological consequences of the Kegworth air disaster.

BACKGROUND: The study sought to quantify psychiatric morbidity among survivors of a major air crash and to identify aetiological factors linked with post-traumatic stress disorder (PTSD). METHOD: Sixty-eight of the 79 survivors (86%) were assessed at a clinical interview within one year of the disaster. The majority also completed the General Health Questionnaire, the Impact of Events Scale (IES) and the Zung Anxiety and Depression Scales. RESULTS: Fifty-four of the study group (79%) met DSM-III-R criteria for a psychiatric disorder within one year of the disaster, of whom 27 (50%) had PTSD. Those who saw injured or dead people at the scene, or had sustained less severe injuries as measured by their Injury Severity Scores, or were under 35 years old, were significantly more likely to develop PTSD. CONCLUSIONS: High rates of psychiatric morbidity are found in survivors of transportation disasters. Further studies are needed to identify those at most risk and to evaluate the benefits of psychological intervention.

Adult

Residence of incident cohort of psychotic patients after 13 years of follow up.

OBJECTIVE: To establish the residential history of an incident cohort of psychotic patients 13 years after their first contact with the psychiatric services. DESIGN: Tracing of all patients admitted to the WHO study on determinants of outcome of severe mental disorders in Nottingham between 1978 and 1980. Patients were assessed using standardised and comparable instruments, and extra information was obtained from key informants and medical records. SETTING: Catchment area of Nottingham psychiatric services. MAIN OUTCOME MEASURES: Main place of residence over the previous two years and residential history over 13 years in terms of homelessness, imprisonment, and use of high dependency psychiatric facilities. RESULTS: 95 patients were traced. At the point of follow up no patients were in long stay psychiatric wards, two were in supervised residence, none was homeless, and none was in prison or a high security hospital. 85 patients were living either independently alone or with their family or friends in the community. Of these, 44 had had no contact with the psychiatric services at the point of follow up. CONCLUSIONS: Although many patients experienced a difficult early course of illness, the longer term outcome of the disorder was associated with remarkably low periods of homelessness and imprisonment and low use of intensive care facilities. These findings offer some reassurance, given the concerns about the effectiveness of community oriented care for this potentially most vulnerable group of psychiatric patients.

Adult

Flow cytometric analysis of the cytotoxic effects of Actinobacillus actinomycetemcomitans leukotoxin on human natural killer cells.

The goal of this investigation was to determine if human natural killer (NK) cells were susceptible to the cytolytic effects of the Actinobacillus actinomycetemcomitans leukotoxin (LTX). Following treatment with LTX (0-200 ng/ml), NK cell activation by interleukin-2 (IL-2) was evaluated. LTX inhibited the IL-2-induced expression of both CD69 and the IL-2 receptor. Furthermore, the up-regulation of CD56 was also impaired. To determine whether the observed functional deficits were the result of cell death, NK cell viability was evaluated by flow cytometry. Changes in forward and side light scatter patterns consistent with cell death were observed within 60 min. Direct analysis of cell viability by measuring propidium iodide exclusion, however, indicated little change in the viability of LTX-treated NK cells. Electron microscopic analysis of NK cells exposed to LTX revealed early nuclear alterations characterized by hyperchromaticity, nuclear fragmentation, and condensation of nucleoplasm. However, no change in membrane integrity was initially noted. Finally, LTX caused a rapid and sustained elevation in the intracellular levels of Ca2+. These morphological and biochemical changes are consistent with the notion of programmed cell death.

Aggregatibacter actinomycetemcomitans

Long-term changes in urodynamic studies of voiding in the elderly.

Urodynamic studies were conducted in 80 incontinent elderly patients (27 men and 53 women; mean age, 77 years) and repeated 2-4 weeks later after patients had been subject to interventions. Interpretable voiding studies were performed in 84% of sessions. Interpretable initial and repeat studies were performed in 74% of patients. For detrusor pressure at maximum flow the intra-individual, between-sessions variability was +/- 11.7 cm H2O (SD) and the initial-repeat correlation coefficient was 0.61. For maximum flow rate the corresponding figures were +/- 4.7 ml/s and 0.44. Mean residual urine volume was 195 ml, with a between-sessions variability of +/- 113 ml (SD). These results suggest that there is substantial long-term variability in voiding function, including urethral resistance. Of the mean, 5% showed a change in obstruction classification (unobstructed/obstructed) between sessions. This variability and the modest proportion of interpretable studies should be taken into account when assessing urethral obstruction and designing clinical trials.

Aged

Dentin ablation by Ho: YAG laser: correlation of energy versus volume using stereophotogrammetry.

The future use of lasers in endodontics is dependent upon predictable and consistent ablation of dentin. In this pilot study we used an Ho:YAG laser fiberoptic delivery system to apply laser energy to prepared tooth sections in vitro. Longitudinally sectioned single-rooted human teeth were subjected to single-energy pulses varying from 25 to 1750 mJ at a focal length of 1 mm. At different energy levels we observed changes in the dentin surface ranging from minute surface pitting to the formation of large craters. Scanning electron microscopy and stereophotogrammetry were used to determine the relationship between the amount of energy applied to dentin and the extent of dentin ablation. Dentin crater formation was quantified by determining surface area, depth, and volume of craters produced. Increases in laser energy were compared with increases in surface area, depth, and volume of craters produced within the range of 150 to 1200 mJ. The Ho:YAG laser fiberoptic delivery system used in this study provides an effective means of ablating dentin. Three-dimensional stereophotogrammetry may prove to be a useful method for further studies on the effects of laser energy on mineralized tissues.

Dentin

Premorbid personality in first-onset psychosis.

The data presented are those from a two-year prospective study of 69 patients identified in the Nottingham field centre of the WHO Study of Determinants of Outcome of Severe Mental Disorders. Premorbid personality, childhood adjustment and adolescent adjustment were assessed at the patients' first presentation to psychiatric services with a psychotic illness. Ratings were made blind to diagnosis. Premorbid explosive and paranoid traits were commoner in patients with schizophrenia than in patients with other non-organic psychoses, and these traits were associated with later onset of schizophrenia. Premorbid schizoid traits were significantly commoner in patients with schizophrenia compared to patients with other psychoses, but only in those patients for whom a parent was the informant. Schizoid traits were no commoner in men with schizophrenia than in women, and were not associated with earlier age of onset. The findings suggest that premorbid personality, in men and women, may shape the expression of symptoms produced during an illness episode.

Adolescent

Helicobacter pylori eradication in patients with peptic ulcer disease: clinical consequences and financial implications.

We assessed clinical consequences and financial implications of Helicobacter pylori eradication in 175 patients with peptic ulceration, of whom 106 had been free from H. pylori infection for a mean of 3.2 years, while 69 remained infected. We used quarterly questionnaires to examine consumption of ulcer-healing medication and antacids. In the 106 successfully treated patients, gastrointestinal haemorrhage as a complication of peptic ulcer complications during the 344 patient years after eradication (0.003 per patient year) was 18-fold lower than during the 912 patient years before eradication (0.056 per patient year). Of the H. pylori-negative patients, 12-18% used ulcer-healing medication during any one of the three-month periods of the survey, compared with 34-51% of the patients with residual H. pylori infection. The average cost of the ulcer-healing drugs consumed by the H. pylori-negative patients was 30.59 pounds during the 12 months of the survey, compared with 99.05 pounds for H. pylori-positive patients. Consumption of antacids was also lower in the H. pylori-negative group. Successful eradication of H. pylori significantly reduced the annual cost of ulcer-healing drugs consumed by the patients with ulcer disease. Maintenance of ulcer remission following successful eradication of H. pylori also significantly reduced ulcer complications.

Antacids