Role of genetics in medical education in North America.
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Biological Evolution↗
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A prospective study of painful symptoms, small-fibre function and peripheral vascular disease in chronic painful diabetic neuropathy.
Fifty diabetic patients with chronic painful sensorimotor neuropathy were studied prospectively to clarify the natural history of this condition and the roles of small-fibre damage and concomitant peripheral vascular disease (PVD). Initially, 30 patients had no significant PVD (ankle:brachial Doppler ratio > 1.0). Pain was assessed using a visual analogue scale (0-10 cm), and small-fibre function by thermal limen (TL), heat-pain threshold (HPT), and weighted pinprick threshold (PPT). At follow-up, on average 3.6 years later (range 3.0-4.1), 11 patients had died (6 with PVD) and contact had been lost with 6. Pain scores fell in subjects without PVD (n = 24; median (range), from 4.8 (0.5-10.0) to 2.0 (0.0-9.2) cm, p < 0.001) and also in those with PVD (n = 9; from 5.1 (2.0-8.2) to 2.1 (0.0-8.0) cm, p < 0.05). Seven patients (5 without PVD) became painfree; at presentation, these 7 patients had experienced pain for a shorter period of time. Despite this symptomatic improvement, small-fibre function generally deteriorated in both groups, with significant worsening (p < 0.05) of HPT and PPT in patients without PVD, and in HPT and TL in patients with PVD. Neuropathic pain therefore tends to improve with time and can resolve completely. By contrast, small-fibre function continues to deteriorate, indicating that these peripheral measures do not predict the evolution of painful symptoms. The presence or absence of PVD does not appear to affect the natural history of neuropathic pain or its symptomatology.
Adult↗
Effects of membrane potential and sphingolipid structures on fusion of Semliki Forest virus.
Cells expressing the E1 and E2 envelope proteins of Semliki Forest virus (SFV) were fused to voltage-clamped planar lipid bilayer membranes at low pH. Formation and evolution of fusion pores were electrically monitored by capacitance measurements, and membrane continuity was tracked by video fluorescence microscopy by including rhodamine-phosphatidylethanolamine in the bilayer. Fusion occurred without leakage for a negative potential applied to the trans side of the planar membrane. When a positive potential was applied, leakage was severe, obscuring the observation of any fusion. E1-mediated cell-cell fusion occurred without leakage for negative intracellular potentials but with substantial leakage for zero membrane potential. Thus, negative membrane potentials are generally required for nonleaky fusion. With planar bilayers as the target, the first fusion pore that formed almost always enlarged; pore flickering was a rare event. Similar to other target membranes, fusion required cholesterol and sphingolipids in the planar membrane. Sphingosine did not support fusion, but both ceramide, with even a minimal acyl chain (C(2)-ceramide), and lysosphingomyelin (lyso-SM) promoted fusion with the same kinetics. Thus, unrelated modifications to different parts of sphingosine yielded sphingolipids that supported fusion to the same degree. Fusion studies of pyrene-labeled SFV with cholesterol-containing liposomes showed that C(2)-ceramide supported fusion while lyso-SM did not, apparently due to its positive curvature effects. A model is proposed in which the hydroxyls of C-1 and C-3 as well as N of C-2 of the sphingosine backbone must orient so as to form multiple hydrogen bonds to amino acids of SFV E1 for fusion to proceed.
Hydrogen Bonding↗
The evolutionary dynamics of human endogenous retroviral families.
The capacity to integrate into the chromosomal DNA of germ-line cells has endowed retroviruses with the potential to be vertically transmitted from generation to generation and eventually become fixed in the genomes of the entire population. This has been independently accomplished by several ancient retroviruses that invaded the genomes of our early and more recent primate and hominoid ancestors. Some of the inherited elements then proliferated in the genome, resulting in a number of lineages with complex phylogenetic patterns. Although the vast majority of chromosomally integrated retroelements have suffered inactivating mutations and deletions, a significant impact on various aspects of human biology has been recently revealed and evidence for the present activity of at least one human endogenous retrovirus family continues to accumulate.
Biological Evolution↗
Multicolor FISH used for the characterization of small supernumerary marker chromosomes (sSMC) in commercially available immortalized cell lines.
There are only about 30 commercially available cell lines which include small supernumerary marker chromosomes (sSMC). As approximately 2.5 million people worldwide are carriers of an sSMC, this small number of immortalized cell lines is hard to understand. sSMC cell lines provide practically unlimited material for continuing studies e.g. to learn more about marker chromosome formation, or karyotypic evolution. To obtain information about their genetic content, in the present study we analyzed by FISH and multicolor-FISH approaches 19 sSMC cell lines obtained from the European Collection of Cell Cultures (ECACC). Microdissection and reverse painting, (sub-) centromere-specific multicolor-FISH (sub-)cenM-FISH, multicolor banding (MCB) and selected locus-specific FISH probes were applied. Thus, we were able to characterize comprehensively 14 out of 19 sSMC carrying cell lines; in the remaining five cases an sSMC could not be detected. Surprisingly, in six of the nine cell lines with sSMC previously characterized for their chromosomal origin by others, those results had to be revised. This has impact on the conclusions of previous studies, e.g. for uniparental disomy (UPD) in connection with sSMC.
Cell Line↗
A study of the simulated evolution of the spectral sensitivity of visual agent receptors.
In this article we study a model for the evolution of the spectral sensitivity of visual receptors for agents in a continuous virtual environment. The model uses a genetic algorithm (GA) to evolve the agent sensors along with the control of the agents by requiring the agents to solve certain tasks in the simulation environment. The properties of the evolved sensors are analyzed for different scenarios. In particular, it is shown that the GA is able to find a balance between sensor costs and agent performance in such a way that the spectral sensor sensitivity reflects the emission spectrum of the target objects and that the capability of the sensors to evolve can help the agents significantly in adapting to their task.
Algorithms↗
SIAMESE, a gene controlling the endoreduplication cell cycle in Arabidopsis thaliana trichomes.
Cell differentiation is generally tightly coordinated with the cell cycle, typically resulting in a nondividing cell with a unique differentiated morphology. The unicellular trichomes of Arabidopsis are a well-established model for the study of plant cell differentiation. Here, we describe a new genetic locus, SIAMESE (SIM), required for coordinating cell division and cell differentiation during the development of Arabidopsis trichomes (epidermal hairs). A recessive mutation in the sim locus on chromosome 5 results in clusters of adjacent trichomes that appeared to be morphologically identical 'twins'. Upon closer inspection, the sim mutant was found to produce multicellular trichomes in contrast to the unicellular trichomes produced by wild-type (WT) plants. Mutant trichomes consisting of up to 15 cells have been observed. Scanning electron microscopy of developing sim trichomes suggests that the cell divisions occur very early in the development of mutant trichomes. WT trichome nuclei continue to replicate their DNA after mitosis and cytokinesis have ceased, and as a consequence have a DNA content much greater than 2C. This phenomenon is known as endoreduplication. Individual nuclei of sim trichomes have a reduced level of endoreduplication relative to WT trichome nuclei. Endoreduplication is also reduced in dark-grown sim hypocotyls relative to WT, but not in light-grown hypocotyls. Double mutants of sim with either of two other mutants affecting endoreduplication, triptychon (try) and glabra3 (gl3) are consistent with a function for SIM in endoreduplication. SIM may function as a repressor of mitosis in the endoreduplication cell cycle. Additionally, the relatively normal morphology of multicellular sim trichomes indicates that trichome morphogenesis can occur relatively normally even when the trichome precursor cell continues to divide. The sim mutant phenotype also has implications for the evolution of multicellular trichomes.
Arabidopsis↗
Text mining neuroscience journal articles to populate neuroscience databases.
We have developed a program NeuroText to populate the neuroscience databases in SenseLab (http://senselab.med.yale.edu/senselab) by mining the natural language text of neuroscience articles. NeuroText uses a two-step approach to identify relevant articles. The first step (pre-processing), aimed at 100% sensitivity, identifies abstracts containing database keywords. In the second step, potentially relevant abstracts identified in the first step are processed for specificity dictated by database architecture, and neuroscience, lexical and semantic contexts. NeuroText results were presented to the experts for validation using a dynamically generated interface that also allows expert-validated articles to be automatically deposited into the databases. Of the test set of 912 articles, 735 were rejected at the pre-processing step. For the remaining articles, the accuracy of predicting database-relevant articles was 85%. Twenty-two articles were erroneously identified. NeuroText deferred decisions on 29 articles to the expert. A comparison of NeuroText results versus the experts' analyses revealed that the program failed to correctly identify articles' relevance due to concepts that did not yet exist in the knowledgebase or due to vaguely presented information in the abstracts. NeuroText uses two "evolution" techniques (supervised and unsupervised) that play an important role in the continual improvement of the retrieval results. Software that uses the NeuroText approach can facilitate the creation of curated, special-interest, bibliography databases.
Abstracting and Indexing↗
Rheumatic carditis treated with high doses of pulsetherapy methylprednisolone. Results in 70 children over 12 years.
PURPOSE: To report the result of patients treated with IV methylprednisolone divided into three groups and compare their follow-up during the last 12 years. METHODS: Seventy children with active rheumatic carditis (76 episodes) in heart failure Class III and IV (NYHA) were studied. The diagnosis was based on modified Jones' criteria. After ruling out infections and strongyloidiasis, treatment with IV methylprednisolone bolus was started three times a week until the laboratory tests became negative. Patients were divided into 3 groups, according to the time of hospital admittance: Groups 1, 2 and 3, comprising of 40, 18 and 12 children, respectively. RESULTS: Eighteen children in Group 1 (45%) were in their 1st attack: 2 series of pulsetherapy were used in 10 (25%), 3 in 9 (23%) and 4 in 21 (52%). In Group 2, 14 cases (77%) were in their 1st attack: 2 series were used in 7 (39%), 4 in 9 (50%) and 5 in 2 (11%). The echocardiogram showed a flail mitral valve in 12 (66%) of these patients (1 death occurred after mitral valvoplasty). In Group 3, 6 patients needed 5 or more series of pulsetherapy and a flail mitral valve was present in 5 (41%). One child underwent mitral valve replacement while still in the active phase, after 8 series of pulsetherapy, and another died. The number of patients who needed 5 or more series was significantly higher in Group 3. CONCLUSION: There were variations in the presentation and evolution of the cases during these 12 year. The established pulsetherapy protocol continues to be useful to treat severe cases.
Adolescent↗
Clinical pharmacy in primary care and community pharmacy.
The role of the community pharmacist involved in primary care has been undergoing change. In the late 1970s and early 1980s, developments in computerized medication surveillance within the Netherlands enabled pharmacists to react to prescriptions and detect inappropriate pharmacotherapy in community pharmacy sites. This activity became more clinically or patient-oriented in the late 1980s. In the early 1990s, pharmaceutical care was introduced in community pharmacy practice, and emphasis was given to providing patient-centered care and documenting cognitive services. The key features of pharmaceutical care provided in the primary care setting are described based on a review of the literature and on experiences in the Netherlands. Patient outcomes have yet to be shown to be improved by community pharmacy practice; methods for measuring performance are still lacking. Methods to evaluate the extent of integration of community pharmacy services into the clinical team are also lacking but are needed in order to define the future role of community pharmacists in the primary care setting. Integrated care needs to be developed in the Netherlands in order to present the next phase in the process of the "pharmaceutical evolution."
Community Pharmacy Services↗
Kinetic and dynamic models of diving gases in decompression sickness prevention.
Decompression sickness is a complex phenomenon involving gas exchange, bubble dynamics and tissue response. Relatively simple deterministic compartmental models using empirically derived parameters have been the mainstay of the practice for preventing decompression sickness since the early 1900s. Decades of research have improved our understanding of decompression physiology, and the insights incorporated in decompression models have allowed people to dive deeper into the ocean. However, these efforts have not yet, and are unlikely in the near future, to result in a 'universal' deterministic model that can predict when decompression sickness will occur. Divers using current recreational dive computers need to be aware of their limitations. Probabilistic models based on the estimation of parameters using modern statistical methods from large databases of dives offer a new approach and can provide a means of standardisation of deterministic models. Future improvements in decompression practice will depend on continued improvement in understanding the kinetics and dynamics of gas exchange, bubble evolution and tissue response, and the incorporation of this knowledge in risk models whose parameters can be estimated from large databases of human and animal data.
Decompression Sickness↗
Human recombinant erythropoietin in the prevention and treatment of anemia of prematurity.
Human recombinant erythropoietin has been studied extensively as treatment for a variety of anemias. Since in vitro studies showed the primary etiology of the anemia of prematurity to be insufficient serum erythropoietin concentrations, clinical trials have evaluated the administration of human recombinant erythropoietin to preterm infants to treat this indication. These studies were followed by pharmacokinetic determinations in animal models and preterm infants, which revealed that preterm infants required greater doses of human recombinant erythropoietin because of a more rapid clearance and greater volume of distribution. Recent studies have focused on the administration of human recombinant erythropoietin in the first weeks of life to alleviate the anemia caused by excessive phlebotomy losses, and to prevent the anemia of prematurity. In addition, human recombinant erythropoietin has been tried clinically in a variety of neonatal populations in an attempt to decrease or eliminate transfusions. Although much information has been accumulated about the clinical use of human recombinant erythropoietin in preterm infants over the last 15 years, many questions remain unanswered. The evolution of clinical practice in the care of extremely low birthweight infants continues to affect the number of transfusions. It is likely that human recombinant erythropoietin administration in combination with instituting rigorous transfusion guidelines and decreasing phlebotomy losses will have the greatest impact in decreasing transfusion requirements in all preterm and term neonates, regardless of the etiology of their anemia.
Anemia, Neonatal↗
[Insight into Crohn's disease].
After noting that Cohn's disease has a long history behind it, the authors show a real increase in the frequency of the disease, apparently more marked in the Anglo-Saxon countries than in France. The etiopathogenesis of the disease is completely unknown. It seems that subjects suffering from Crohn's disease present an exacerbated xenic reaction. There are strong arguments in favour of a genetic contribution. The association with ankylosing spondylarthritis and thus the HLA system is particularly interesting. Following a breif review of the clinical signs and of the complications of the disease, the authors emphasize the diagnostic value of a scoring system. The evolution is very variable: quiescence which does not mean cure, progressive and continuous aggravation, alternation of outbreaks and remissions. Symptomatic, medical therapy is certainly effective but is efficacy is limited. Medical therapy aimed at the etiopathogenic factors is without foundation. Surgical intervention, sometimes immediately beneficial, is accompanied by a 50% frequency of recurrences in a ten-year period. Crohn's disease, fatal in 5% of cases, sometimes handicapping severely the development of the individual, is worthy of further rheumatological study.
Consanguinity↗
[Supranuclear gaze palsy following extracorporeal surgery with induced hypothermia. Report of two cases].
Although up to 5-20% of the patients who underwent surgery with hypothermia and cardiac arrest may present neurological complications, just a few cases of ocularmotor disorders have been described. Acquired supranuclear ocular motor paresis (ASOMP) is a rare disorder characterized by impairment in volitional and reflex saccades and smooth pursuit in one or more directions of gaze with intact extraocular movements in response to vestibular estimulation. We present two cases of acquired supranuclear ocular motor paresis associated with a peculiar gait disorder. Although a partial improvement was observed, both patients continue with ocular motor paresis in vertical direction after one year of evolution. A selective vulnerability of certain brainstem neuronal groups would explain the pathophysiology of these symptoms.
Adult↗
[Genetic diagnosis of leukemia: diagnosis of relapse and complete remission, and prediction of leukemia onset].
Wilms' tumor gene WT1 mRNA is a new marker of leukemic blast cells for AML, ALL, and CML. Minimal residual disease(MRD) of leukemia can be detected at frequencies as low as 1 in 10(3) to 10(4) normal bone marrow cells and 1 in 10(5) normal peripheral blood mononuclear cells by means of the quantitation of WT1 mRNA(WT1 assay) using reverse transcriptase-polymerase chain reaction. Thus, the WT1 assay makes it possible to rapidly assess the effectiveness of treatment and to evaluate the degree of eradication of leukemic cell in individual leukemia patients. Furthermore, WT1 assay can continuously assess the disease progression of myelodysplastic syndromes(MDS) and predict the evolution of MDS to overt AML within 6 months.
DNA-Binding Proteins↗
Disseminated cutaneous histoplasmosis and AIDS: case report.
Histoplasmosis is caused by the dimorphic fungus Histoplasma capsulatum. It manifests by the presence of fever as the only symptom in most individuals. The disease may present as self-limited pneumonia, or as an hematogenous widespread fungal infection with a potentially fatal outcome in elderly individuals and people with compromised T-cell mediated immunity. Here, we report a case of disseminated cutaneous histoplasmosis in a patient with AIDS. The patient was a 33 year old male homosexual, intravenous drug user, who had been diagnosed with HIV infection 5 years earlier. He was in good health, but had erythematous papules and pustules in the skin of the scalp, face, back, thighs, abdomen, palms, and soles. He was placed on anti-retroviral therapy, fluconazole for mucosal candidiasis, trimethoprim/sulfamethoxazole for pneumocystis prophylaxis, and antibiotics for the skin pustules. The skin lesions improved remarkably within 14 days. He was discharged and soon lost to follow-up. After his discharge, skin biopsy and fungal culture results revealed H. capsulatum. He was seen again 1 year later. The interim history revealed that he had taken fluconazole 100 mg/day for 1 month and fluconazole 150 mg/week for 7 months. He had not continued anti-retroviral therapy, nor taken other antifungal drugs. The clinical evolution of the disease was exceptional in that there was disappearance of all the skin lesions attributed to histoplasmosis with fluconazole. Although itraconazole remains the drug of choice for histoplasmosis. Cutaneous histoplasmosis should be considered in the differential diagnosis of atypical cutaneous lesions in individuals infected with HIV.
AIDS-Related Opportunistic Infections↗
[BIOME 6000 Project: latest advances of reconstructing palaeobiome].
Global change research needs the data about the past states of the Earth system, e.g., the pollen and plant macrofossil records for specified time slices (for example, the mid-Holocene interval, ca 6,000 aBP, and the last glacial maximun, LGM, ca 18,000 aBP). In the past, the utilization of these palaeoecological data is mostly scattered and point-fixed, and the reconstruction of palaeovegetation is often qualitatively descriptive. The establishment of international collaboration project BIOME 6000 (a global palaeovegetation mapping program) of the International Geosphere-Biosphere Project (IGBP) breaks a new approach for the synthesis and quantitative study of palaeoecological data. In the projescts The methodology of biomization for assigning palaeoeclogical records to biomes is emphasized, in which, plant pollen taxa are assigned to one or more plant functional types (PFTs) by collecting widely global palaeoecological records which have quality assurance, and by using PFT definition based on the principles of modern ecology. Through combining PFTs into biome types, the global synthesis of biomes reconstructed by using palaeoecological data can be realized. The biomization method might provide a benchmark for coupled atmosphere-biosphere. This trend will facilitate biome mapping for other time slices, and co-evolution of atmosphere-biosphere modeling and palaeodata synthesis and analysis will continue.
Ecology↗
Advances in myotonic dystrophy: a clinical and genetic perspective.
The recent identification of the gene responsible for myotonic dystrophy and the recognition of an expanding unstable repeat sequence as the specific molecular defect, have resulted in rapid changes in clinical practice as well as in our understanding of the disorder. Against such a framework, this review traces the evolution of clinical and genetic knowledge of the disorder and emphasizes the continuing central role of thorough clinical investigation of those at risk for carrying the gene as an essential element of predictive testing for myotonic dystrophy.
Chromosomes, Human, Pair 19↗