Biomedical subjects
S Peters
Publications and source records attributed to S Peters.
Nurse practitioner education in the new century.
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Condom sense. Reducing common mistakes.
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Sequence and analysis of chromosome 4 of the plant Arabidopsis thaliana.
The higher plant Arabidopsis thaliana (Arabidopsis) is an important model for identifying plant genes and determining their function. To assist biological investigations and to define chromosome structure, a coordinated effort to sequence the Arabidopsis genome was initiated in late 1996. Here we report one of the first milestones of this project, the sequence of chromosome 4. Analysis of 17.38 megabases of unique sequence, representing about 17% of the genome, reveals 3,744 protein coding genes, 81 transfer RNAs and numerous repeat elements. Heterochromatic regions surrounding the putative centromere, which has not yet been completely sequenced, are characterized by an increased frequency of a variety of repeats, new repeats, reduced recombination, lowered gene density and lowered gene expression. Roughly 60% of the predicted protein-coding genes have been functionally characterized on the basis of their homology to known genes. Many genes encode predicted proteins that are homologous to human and Caenorhabditis elegans proteins.
Risk stratification of sudden cardiac death and malignant ventricular arrhythmias in right ventricular dysplasia-cardiomyopathy.
UNLABELLED: Arrhythmogenic right ventricular dysplasia-cardiomyopathy is in most cases a benign cause of ventricular arrhythmias in young patients. The major reason of mortality is sudden arrhythmic death with an annual rate of 2-3% as the first manifestation of the disease in most cases. Little is known about risk factors of sudden arrhythmic death so far. The purpose of the retrospective study was to classify risk factors from invasive and non-invasive examinations. METHODS: In a cohort of 121 consecutive patients sampled from 1986 to 1998 the value of right ventricular dilatation, left ventricular involvement analysed by angiocardiography or echocardiography and standard ECG parameters such as precordial T wave inversions, right precordial ST elevation, precordial QRS dispersion, left precordial JT interval prolongation and complete right bundle branch block were determined. The whole cohort of patients were divided into two groups with high arrhythmic risk (aborted or non-aborted sudden death, recurrent ventricular tachycardia despite medical treatment, recurrent syncopes) and low risk (frequent ventricular premature beats, non sustained ventricular tachycardia, uneventful course under medical therapy). RESULTS: From angiocardiography or echocardiography in a quantitative approach right ventricular dilatation (p<0.0001) and additional left ventricular abnormalities (p<0.0001) could be identified as major risk factors. From an ECG point of view increased precordial QRS dispersion > or =50 ms (p<0.01) with complete right bundle branch block and right ventricular dilatation in most cases and precordial T wave inversions beyond V3 (p<0.0001) and the phenomenon of left precordial JT interval prolongation (JT dispersion > or =30 ms) in cases of additional left ventricular abnormalities represented non-invasive predictors of recurrent arrhythmic events. Right precordial ST segment elevation could be excluded as risk factor of sudden arrhythmic death. CONCLUSIONS: Right ventricular dilatation with ECG depolarisation abnormalities and additional left ventricular involvement with striking ECG repolarisation abnormalities could be identified as strong risk factors of recurrent arrhythmic events in ARVD with unfavorable prognosis.
Heart failure in arrhythmogenic right ventricular dysplasia-cardiomyopathy.
UNLABELLED: Sudden arrhythmic death and heart failure are essential factors influencing the prognosis of arrhythmogenic right ventricular dysplasia-cardiomyopathy. Heart failure is a rare, but often lethargic event although little is known about morphology, time course and non-invasive predictors. METHOD: In a retrospective study of a consecutive cohort of 121 patients with ARVD over a follow-up period of up to 12 years morphological features of heart failure, time course from the initial diagnosis and standard 12-lead ECG as a non-invasive predictor of developing heart failure were analysed. RESULTS: Heart failure occurred in 13 patients (11%) with isolated right ventricular dilatation and loss of function in 10 cases (77%) and biventricular failure in three cases (23%). Patients developed NYHA class IV in four cases, class III-IV in two cases and class II in seven cases in 4-8 years. In standard ECG of 12 patients (92%) complete right bundle branch block was present at the time of initial diagnosis (n=6) or in a time interval of 4 years (n=6). Morphological distinction of isolated right and biventricular heart failure could be achieved not only by imaging techniques such as echocardiography or cardioangiography, but also by standard ECG with right atrial hypertrophy and an increased mean precordial QRS dispersion of 47.1+/-18.9 ms in cases of right heart failure and biatrial hypertrophy and a reduced precordial QRS dispersion of 33.0+/-23.1 ms in cases of biventricular heart failure. CONCLUSIONS: Heart failure in ARVD consists of isolated right ventricular and biventricular dilatation and pump failure in a time course of 4-8 years after developing complete right bundle branch block as a strong non-invasive predictor from standard 12-lead ECG.
Lymphohematopoietic stem cell engraftment.
Traditional dogma has stated that space needs to be opened by cytoxic myeloablative therapy in order for marrow stem cells to engraft. Recent work in murine transplant models, however, indicates that engraftment is determined by the ratio of donor to host stem cells, i.e., stem cell competition. One hundred centigray whole body irradiation is stem cell toxic and nonmyelotoxic, thus allowing for higher donor chimerism in a murine syngeneic transplant setting. This nontoxic stem cell transplantation can be applied to allogeneic transplant with the addition of a tolerizing step; in this case presensitization with donor spleen cells and administration of CD40 ligand antibody to block costimulation. The stem cells that engraft in the nonmyeloablated are in G0, but are rapidly induced (by 12 hours) to enter the S phase after in vivo engraftment. Exposure of murine marrow to cytokines (IL-3, IL-6, IL-11 and steel factor) expands progenitor clones, induces stem cells into cell cycle, and causes a fluctuating engraftment phenotype tied to phase of cell cycle. These data indicate that the concepts of stem cell competition and fluctuation of stem cell phenotype with cell cycle transit should underlie any new stem cell engraftment strategy.
Counteractive effects of a partial (sabcomeline) and a full (RS86) muscarinic receptor agonist on deficits in radial maze performance induced by S-AMPA lesions of the basal forebrain and medial septal area.
After S-AMPA (8.0 mM) lesions to the nucleus basalis and medial septal regions, at the source of the cortical and hippocampal branches of the forebrain cholinergic projection system, rats displayed long-lasting and relatively stable impairment in long-term reference and short-term working memory in both spatial (place) and associative (cue) radial maze tasks. Treatment with four doses of the partial agonist at the M1 cholinergic muscarinic receptor, sabcomeline (formerly known as SB 202026: 0.01-0.156 mg/kg), substantially reduced working and reference memory errors in both tasks in lesioned rats, in a mainly dose-related manner. These effects were more consistent than those found with the direct muscarinic agonist RS86 (0.05-0.781 mg/kg). The performance of non-lesioned controls was largely unaffected by either treatment. These findings are consistent with previous evidence for cholinergic participation in the radial maze deficits induced by excitotoxic lesions to the forebrain cholinergic projection system. They show that with a relatively selective lesion, which respectively, reduced choline acetyltransferase activity to 36.5 and 22.5% of control level in frontal and dorsolateral cortex, and to 61.8 and 69.2% of control level in dorsal and ventral hippocampus, lesioned rats were responsive to pharmacological treatments aimed to enhance cholinergic function by full or partial agonist activity at M1 receptors. Findings that nicotine (0.1 mg/kg) also reduced radial maze errors in the lesioned animals supports the suggestion that lesion-induced deficits in radial maze performance were amenable to improvement by cholinergic receptor manipulation. However, given the potential adverse side effects of full receptor agonists, which nonselectively target cholinergic receptors throughout the organism, the functional efficacy of sabcomeline, which shows regional selectivity for the central M1 receptor subtypes, suggests that deleterious effects of cholinergic depletion on cognition can be counteracted without incurring the risk of unwanted side effects.
Patients' perceptions of medical explanations for somatisation disorders: qualitative analysis.
OBJECTIVES: To describe, from the perspective of patients, distinguishing features of doctors' attempts to explain the symptoms of somatisation disorders. DESIGN: Qualitative analysis of verbatim records of interviews in which patients recounted doctors' explanations of their symptoms. SETTING: Patients with persistent somatising symptoms referred from general practices in Liverpool and St Helens and Knowsley were interviewed before entry into a treatment programme. SUBJECTS: 228 of 324 patients referred were interviewed. Initial interviews were used to develop the process and technique, and the final analysis was based on a subsample of 68 records, randomly chosen from the transcripts of 188 subjects who were interviewed subsequently. RESULTS: Doctors' explanations were often at odds with the patients' own thinking. Analysis showed that medical explanations could be grouped into one of three categories, defined by the patients' perceptions. Most explanations were experienced as rejecting the reality of the symptoms. An intermediate category comprised explanations that were viewed as colluding, in which the doctor acquiesced with the patients' own biomedical theories. However, a few explanations were perceived by patients as tangible, exculpating, and involving. These explanations were experienced by patients as satisfying and empowering. CONCLUSIONS: Patients with somatisation disorders feel satisfied and empowered by medical explanations that are tangible, exculpating, and involving. Empowering explanations could improve these patients' wellbeing and help to reduce the high demands they make on health services.
The development of within-song type variation in song sparrows.
We investigated the development of within-song type variation in song sparrows, Melospiza melodia, with two experiments designed to determine how exposure to within-type variation influences the song-learning process and whether within-type variation itself is a learned trait. In the first experiment, we compared learning between two groups of males, one group tutored exclusively with song models presented with no variation, and the other group tutored exclusively with song models presented with a range of within-type variation that is normally produced by birds in the field. The two groups in this experiment did not differ significantly in any measure of how well they learned, suggesting that exposure to within-type variation has no measurable influence on the learning process overall. Nor did the groups differ in the expression of within-song type variation in their own adult songs, demonstrating that within-type variation is not a learned feature of song sparrow song. In the second experiment, we tutored a single group of birds with both invariant and variable models, allowing us to ask how within-type variability affects learning preferences. Young birds preferentially copied song type models presented with variation significantly more than invariant models. Taken together, these experiments provide insight into the evolution of within-song type variation in song sparrows, although the functional significance of this level of variation and learning preferences based on variation remain enigmatic. Copyright 1999 The Association for the Study of Animal Behaviour.
Song types as fundamental units in vocal repertoires.
We investigated whether song types function as fundamental units of song variation in song sparrows, Melospiza melodia. As the size of a male song sparrow's repertoire increases, so does the mean similarity of his song types, as measured by the sharing of minimal units of production (MUPs). It follows that if MUP similarity is important perceptually, then small repertoires (of dissimilar song types) may be functionally equivalent to large repertoires (of similar song types). We performed two experiments to test whether MUP similarity is important perceptually to male song sparrows. Both experiments used a habituation/recovery design, in which recovery in response at a switch in stimuli is used to gauge the subject's perception of the similarity of the stimuli. The results of both experiments indicate that the level of perceived similarity between pairs of songs does not depend on their level of MUP similarity, within the range of MUP similarities found between song types. Songs with high enough MUP similarity to be judged as variants of the same song type are, however, perceived to be much more similar than are any two song types. The results are compatible with a categorical model of song type perception. Copyright 1999 The Association for the Study of Animal Behaviour.
Permissiveness in the learning and development of song syntax in swamp sparrows.
Vocal learning in swamp sparrows, Melospiza georgiana, is subject to a host of sensory and motor limitations. One such limitation is that young swamp sparrows almost invariably crystallize their songs with a simple trilled syntax, irrespective of the syntax of vocal models from which they learn. A striking exception to this pattern was recently identified by Podos (1996, Animal Behaviour, 51, 1061-1070), who found that large-scale organizational changes in vocal syntax, including the production of an intermittent or 'broken' syntax, were produced when birds faced limits on vocal performance capacities during motor ontogeny. Our goal in the present study was to determine whether song models with broken syntax could serve as suitable training models for young swamp sparrows, and, if so, if broken syntax could be faithfully reproduced. We hand-reared 10 male swamp sparrows and exposed them to control, rapid and broken song models. Control song models were copied with a high degree of accuracy, as in previous studies. Rapid song models were copied with deficiencies that suggested performance limits on vocal production; such deficiencies included the production of songs with broken syntax and the production of songs in which notes were dropped out as songs progressed. Broken songs proved suitable as training models. Furthermore, copies of broken song models were crystallized either with normal or with broken syntax. These data identify an unexpected direction of permissiveness in the types of songs swamp sparrows will memorize and accurately reproduce, and also point to a possible proximate basis for syntactical changes in the evolution of sparrow songs. Copyright 1999 The Association for the Study of Animal Behaviour.
Melanin granules of retinal pigment epithelium are connected with the lysosomal degradation pathway.
Melanosomes are closely related to lysosomes and lipofuscin granules. This paper indicates the potential involvement of lysosomal degradation processes in retinal pigment epithelial (RPE) cells. RPE cells cultured on Bruch's membrane and choroid were fed with indigestible latex beads. The RPE cells from this preparation were treated with chloroquine to investigate whether membrane swelling, typical for lysosomes under this condition, can be induced in melanosomes. To investigate the fate of indigestible material associated with rod outer segments (ROS), gold-labeled ROS were injected transsclerally into the subretinal space of Long Evans rats using a 32 gauge Hamilton syringe. The degradation of labeled ROS was observed after 5 and 12 days by electron microscopy. The following results were observed. Latex particles fuse with the melanin granules of the RPE. Following chloroquine treatment, the membranes of melanin granules fused, and formed large clusters and vacuoles. Gold granules were detected inside both early stage melanosomes and mature melanin granules of the RPE cells 5 and 12 days following subretinal injection of the labeled ROS. Higher numbers of gold granules were predominantly found in immature melanosomes containing still melanofilaments and in small fused mature melanin granules. In conclusion the effect of chloroquine clearly demonstrates that the melanosomes possess active proton pumps which is typical for lysosomes. In RPE cells stressed by overload with rod outer segments or by ingestion of undegradable material (latex beads, gold particles), fusion of these phagosomes with melanosomes of different maturity is more a general rule than an exception. Therefore, melanosomes are connected to lysosomal pathways in RPE cells.
[Fatal ventricular rupture after stent implantation in acute myocardial infarct with subsequent stent thrombosis: discussion of reperfusion injury as the cause].
Ventricular rupture due to myocardial infarction is a well-known but rare complication. Since the introduction of thrombolytics or acute PTCA in the management of acute myocardial infarction, the frequency of this complication has further decreased. A case of lethal ventricular rupture in the course of acute stenting for myocardial infarction, acute stent thrombosis 7 hours after successful intervention, and successful reintervention with intracoronary administration of abciximab is reported. Myocardial rupture as a severe form of reperfusion injury is discussed.
Ultrastructural localization of lipid peroxides as benzidine-reactive substances in the albino mouse eye.
BACKGROUND: Lipid peroxidation is considered to be a prominent feature of retinal degeneration and has also been proposed to be involved in the pathogenesis of age-related macular degeneration. Melanin protects against lipid peroxidation and takes part in the detoxification of lipid peroxides (LP). LP can be ultrastructurally detected as benzidine-reactive substances (BRS) using tetramethylbenzidine (TMB). Albino mice lack melanin. In the present study, LP were localized as BRS in the eyes of albino and pigmented mice. METHODS: Eye cups of an albino mouse lineage and of wild-type mice were fixed with 2% glutaraldehyde, incubated with 0.5 mg/ml TMB and embedded for electron microscopy. RESULTS: BRS were detected in the eyes of albino mice, but no reaction product was seen in pigmented eyes. BRS located in the retinal pigment epithelium (RPE) and in the choroid of the albino mouse; no BRS were found in intact rod outer segments (ROS). CONCLUSION: The lack of melanin in albino mice is associated with a higher level of lipid peroxidation in RPE and choroid. Melanin seems to protect against LP in RPE and choroid. A lack of melanin is not associated with lipid peroxidation in intact ROS. The present investigation demonstrates the significance of melanin in protection against LP in RPE and choroid.
Cellular transport of subretinal material into choroidal and scleral blood vessels: an electron microscopic study.
BACKGROUND: The fate of indigestible material injected into the subretinal space of rats was investigated. METHODS: The non-toxic dye Monastral Blue (MB), which cannot be digested within the lysosomal compartment, was injected transsclerally into the subretinal space of Long Evans and Wistar rats. After 5 and 12 days respectively the eyes were enucleated and examined by light and electron microscopy. Cryo sections were made of eyes 5 days after MB injection for the application of immunohistochemical techniques using markers for epithelial cells (cytokeratin) and macrophages (ED 1). RESULTS: Retina, choroid and sclera were not altered in their morphology in the circumference of the MB-containing bubble generated by subretinal injection. After both 5 and 12 days no injected material was found extracellularly in the subretinal space. Especially high amounts of MB were found, in particular 5 days after injection, in lysosomes and melanosomes of RPE cells as well as in cells between choroidal melanocytes. Cells containing MB were seen in contact with choroidal and scleral blood vessels. These MB-containing cells in the choroid and in the sclera were positive for macrophage antibodies. CONCLUSION: Subretinal injection was confirmed as a suitable method for placing fluids into the subretinal space without affecting the morphology of the retina. Subretinal injected material was shown to be incorporated into lysosomes and melanosomes of RPE cells. The injected material was subsequently transported through Bruch's membrane to be finally removed from the eye via choroidal and scleral veins, the process involving macrophages.
Stem cell engraftment and cell cycle phenotype.
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Multisite optical recording of excitability in the enteric nervous system.
A multisite optical recording technique consisting of an array of 464 photodiodes was used to measure dynamic changes in transmembrane potentials (Vm) of guinea-pig and mouse enteric neurones stained with the voltage-sensitive dye Di-8-ANEPPS. Optical recordings of Vm changes in enteric neurones which were evoked by depolarizing current pulses or synaptic activation mirrored the Vm changes measured intracellularly in the same neurone. Action potentials had fractional change in fluorescence of -0.09 +/- 0.06% and their peak to peak noise level was 20 +/- 14% of the action potential amplitude. Optical recordings after electrical stimulation of interganglionic nerve strands revealed slow EPSPs, nicotinergic supra- and subthreshold fast EPSPs as well as propagation of action potentials along interganglionic strands. Local application of acetylcholine onto a single ganglion induced reproducibly and dose dependently action potential discharge demonstrating the feasibility of neuropharmacological studies. The optical mapping made it possible to record action potentials simultaneously in a large number of neurones with high spatiotemporal resolution that is unattainable by conventional techniques. This technique presents a powerful tool to study excitability spread within enteric circuits and to assess differential activation of enteric populations in response to a number of stimuli which modulate neuronal activity directly or through synaptic mechanisms.