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At least 217 records · Page 12Linked to original sources
PubMed2004

Human retroviral gag- and gag-pol-like proteins interact with the transforming growth factor-beta receptor activin receptor-like kinase 1.

Mutations in activin receptor-like kinase 1 (ALK1), a transforming growth factor (TGF)-beta type I receptor, lead to the vascular disorder hereditary hemorrhagic telangiectasia caused by abnormal vascular remodeling. The underlying molecular cause of this disease is not well understood. Identifying binding partners for ALK1 will help to understand its cellular function. Using the two-hybrid system, we identified an ALK1-binding protein encoded by an ancient retroviral/retrotransposon element integrated as a single copy gene known as PEG10 on human chromosome 7q21. PEG10 contains two overlapping reading frames from which two proteins, PEG10-RF1 and PEG10-RF1/2, are translated by a typical retroviral -1 ribosomal frameshift mechanism. Reverse transcription-PCR and Northern blot analysis showed a broad range of PEG10 expression in different tissues and cell types, i.e. human placenta, brain, kidney, endothelial cells, lymphoblasts, and HepG2 and HEK293 cells. However, endogenous PEG10-RF1 and PEG10-RF1/2 proteins were only detected in HepG2 and HEK293 cells. PEG10-RF1, which is the major PEG10 protein product, represents a gag-like protein, and PEG10-RF1/2 represents a gag-pol-like protein. PEG10-RF1 also interacts with different members of TGF-beta superfamily type I and II receptors. PEG10-RF1 binding to ALK1 is mediated by a 200-amino acid domain with no recognized motif. PEG10-RF1 inhibits ALK1 as well as ALK5 signaling. Co-expression of ALK1 and PEG10-RF1 in different cell types induced morphological changes reminiscent of neuronal cells or sprouting cells. This is the first report of a human retroviral-like protein interacting with members of the TGF-beta receptor family.

Activin Receptors, Type I↗
PubMed1999

Parathyroid biopsy to facilitate the preservation of functional parathyroid tissue during thyroidectomy.

BACKGROUND: The preservation of viable parathyroid tissue, either by preserving parathyroid glands in situ with an intact blood supply or by autotransplantation, is an integral element of thyroid surgery. There is a general impression that nonviable parathyroid glands can be recognized on the basis of black or purple-black discoloration of the gland. We came to believe that this is not a reliable way to assess the viability of parathyroid glands because we observed that when we excised parathyroid glands (with the intention of reimplanting them) in situations where it was not feasible to preserve their blood supply, they did not become discolored. METHODS: To assess the status of the parathyroid blood supply, we performed incisional biopsies of suspected parathyroid glands during 14 consecutive thyroid operations (9 hemithyroidectomies, 1 completion thyroidectomy, 4 total thyroidectomies), and observed the biopsy site for evidence of active bleeding. RESULTS: Thirty-four of 36 possible parathyroid glands were histologically confirmed. Seventeen bled actively from the biopsy site and were preserved in situ. The other 17 were felt to be nonviable: 5 were severely discolored (black) and either no bleeding or minor venous oozing was seen when they were biopsied; 12 with normal coloration (3 were harvested prior to biopsy), did not bleed actively following an incisional biopsy. Parathyroid glands that were judged to be devascularized were autotransplanted into the sternocleidomastoid muscle. CONCLUSIONS: The absence of discoloration is not a reliable way to determine whether the parathyroid blood supply is intact. Biopsy of the parathyroid glands during thyroid surgery facilitates the identification of devascularized parathyroid glands that can be salvaged with autotransplantation.

Adult↗
PubMed2000

The concept of social class: the contribution of Everett Hughes.

In French Canada in Transition (1943) and a set of related essays written between 1933 and 1941, Everett Hughes, a key figure in the "Second Chicago School" of sociology developed a novel and noteworthy conceptualization of social class. This contribution, which was not recognized outside of French-language sociology in Quebec, was an integral element of Hughes's "interpretive institutional ecology" theoretical frame of reference. It combined elements of the classical ecological theory of class (human ecology, functionalism, Simmel), aspects of a Weber-inspired analysis of class, status, and political power, and elements of a proto-dependency analysis of Quebec's industrialization in the 1930s.

Canada↗
PubMed2000

Neurotrophins and development of the rod pathway: an elementary deduction.

The rodent retina is a particularly attractive model for the study of neuronal developmental processes since considerable neurogenesis, cellular migration, phenotypic differentiation of retinal cell types and synaptogenesis occurs postnatally. In addition, the retina is readily accessible to surgical intervention, pharmacological manipulation, and local suppression of gene expression-tools that can be utilized to study mechanisms underlying the development of retinal neurons and their interconnections that form distinct functional circuits. Here, I review our studies describing the ontogeny of a specific retinal interneuron, the AII amacrine cell, an integral element in the rod (scotopic) pathway. Specifically, we used a number of approaches to examine the potential role of neurotrophic factors on the morphological and neurochemical differentiation of the AII.

Animals↗
PubMed1988

The mouse protein synthesis initiation factor 4A gene family includes two related functional genes which are differentially expressed.

We have cloned and characterized a family of mouse genomic sequences hybridizing to mouse cDNA probes coding for eIF-4A, one of the protein synthesis initiation factors involved in the binding of mRNA to the ribosome. We estimate that there is a total of approximately 9-13 eIF-4A pseudogenes. We also found an eIF-4A intronless retroposon which, when compared to the cDNA, contains a single nucleotide difference. This possibly functional gene contains a mouse repetitive B1 element integrated in the promoter region. Furthermore, we have cloned two intron-containing eIF-4A genes (termed eIF-4AI and eIF-4AII). The eIF-4AII gene codes for a previously unknown form of eIF-4A. Northern blot hybridization with RNA from several mouse organs shows a variation in eIF-4AI expression within a factor of 7. In contrast, relative to liver, eIF-4AII expression is 20- to 30-times higher in brain and kidney, 10- to 17-fold higher in lung and heart, and is about equally abundant in liver, spleen and thymus. These data suggest that the relative efficiency of protein synthesis initiation for different mRNAs, as reflected by discrimination in messenger 5'-terminal cap recognition and binding to ribosomes, varies in different tissues.

Amino Acid Sequence↗
PubMed1997

Apolar, Polar, and Electrostatic Interactions of Spherical Particles in Cylindrical Pores

A new Surface Element Integration (SEI) technique is developed for determination of the interaction energy of a spherical particle in a cylindrical pore based on the knowledge of the corresponding interaction energy per unit area between plane-parallel half spaces. Like the celebrated Deryaguin's approximation, the SEI can be used for any component of the interaction energy (e.g., apolar Lifshitz-van der Waals, electrostatic, polar) whenever interaction between corresponding half-spaces is known theoretically or experimentally. Accuracy of the SEI is assessed based on its comparison with the exact results for the van der Waals interaction energy. Results of the SEI are also compared with the approximate series solution for the electrostatic interaction in the Debye-Huckel approximation. While Deryaguin's approximation fails for the particle-pore geometry for small pores (<10 nm), the SEI is accurate for all realistic combinations of particle and pore radii, radial position of the particle, and decay length of interactions. Based on the SEI, the role of polar repulsion (hydration pressure) on the partitioning behavior of macromolecules across small pores is also studied. The hydration force in aqueous hydrophilic systems can lead to a significant lowering of the distribution coefficient in small pores characteristic of ultrafiltration.

Journal Article↗
PubMed2001

Transfer region of a bacteroides conjugative transposon, CTnDOT.

Bacteroides species harbor large self-transmissible integrated elements called conjugative transposons (CTns). In this paper, we report the first complete sequence analysis of the transfer region of a Bacteroides CTn. The transfer region contained 17 genes (designated orfA-orfQ). Only 2 of the genes shared sequence similarity with genes in the databases and only 1 of these genes was associated with self-transmissible elements.

Amino Acid Sequence↗
PubMed1995

A protein is involved in accessibility of the inhibitor acetazolamide to the carbonic anhydrase(s) in the cyanobacterium Synechocystis PCC 6803.

A gene, zam (for resistance to acetazolamide), controlling resistance to the carbonic anhydrase inhibitor acetazolamide, is described. It has been cloned from a spontaneous mutant, AZAr-5b, isolated from the cyanobacterium Synechocystis PCC 6803, for its resistance to this drug (Bédu et al., Plant Physiol 93: 1312-1315, 1990). This mutant, besides its resistance to acetazolamide, displayed an absence of catalysed oxygen exchange activity on whole cells, suggestive of a deficiency in carbonic anhydrase activity. The gene was isolated by screening a genomic library of AZAr-5b, and selecting for the capacity to transfer the AZAr phenotype to wild-type cells. A system leading to forced homologous recombination in the host chromosome, using a platform vector, was devised in order to bypass direct selection difficulties. The putative encoded protein, 782 amino acids long, showed some homology with four eukaryotic and prokaryotic proteins involved in different cellular processes, one of them suppressing a phosphatase deficiency. The mutated allele of AZAr-5b showed an in-frame 12 nucleotide duplication, which should not interfere with translation, and might result from transposition of a mobile element. Integration into a wild-type genome of either the spontaneous mutated allele or one inactivated by insertional mutagenesis conferred the character of resistance, but not the deficiency in oxygen exchange, indicating that the two phenotypic aspects of AZAr-5b corresponded to two independent mutations. A working hypothesis explaining the phenotypes of the mutants is that the presence of the Zam protein would be necessary for the inhibitor to reach (one of) the two carbonic anhydrases present in this strain. This, however, would be a secondary action, the physiological role of the protein still being cryptic.

Acetazolamide↗
PubMed1981

A new type of IS1-mediated deletion.

Genetical tests and DNA sequence analysis revealed that the mechanism of formation of IS1-induced type I and type II deletions differs. IS1-mediated type II deletions occur at the termini of the integrated element and do not remove the element. This process is independent of the cellular recA system and does not involve DNA sequence homology. Conversely, the formation of IS1-induced type I deletions differs substantially. They require recA gene product, small DNA sequence duplications and a topological arrangement of the DNA molecule to allow alignment of duplications.

Base Sequence↗
PubMed1988

Neural control of ventilation in the shore crab, Carcinus maenas. II. Frequency-modulating interneurons.

1. We have identified a class of nonspiking interneurons which can control the frequency of ventilation in a graded manner. These frequency modulating interneurons (FMis) also receive synaptic inputs in-phase with the ventilatory motor output providing a functional positive feedback loop in the ventilatory system. The class of FMis is composed of three morphologically and physiologically distinct interneurons, FMi1, FMi2 and FMi3. 2. Depolarization of FMi1 increases the rate of ventilation, while hyperpolarization decreases the rate (Fig. 1). This control is restricted to a single ventilatory central pattern generator (CPG), (Fig. 2), although FMi1 sends processes into the neuropils of both hemiganglionic CPGs (Fig. 3). 3. Hyperpolarization of FMi2 increases the rate of both ventilatory CPGs while depolarization of this cell slows and eventually arrests the rhythm (Figs. 5 and 6). FMi2 receives a synaptic input correlated with the motor output of each of the ventilatory CPGs (Fig. 4). During periods of reversed ventilation, this cell is abruptly hyperpolarized and continues to be driven in-phase with the ventilatory motor output (Fig. 7). 4. Hyperpolarization of FMi3 increases the rate of ventilation and depolarization decreases the rate of ventilation produced by both CPGs (Fig. 10). This control of the ventilatory rate by FMi3 is graded (Fig. 11). There is no apparent change in the membrane potential of FMi3 during reversed ventilation and it is morphologically distinct from FMi2. 5. FMi2 and FMi3 may be involved in the switch in ventilatory motor pattern from forward to reversed ventilation. Hyperpolarization of FMi2 and depolarization of FMi3 can elicit bouts of reversed ventilation from both CPGs (Fig. 13). 6. These results suggest that the FM interneurons act in parallel to control the frequency of ventilation and may act as integrating elements between spiking 'command' fibers in the circumesophageal connectives and the nonspiking interneurons of the ventilatory CPG.

Animals↗
PubMedDate not supplied

Bilateral influences from the motor cortex on lumbar ventral horn interneurons.

Microelectrode recordings were made of discharges of ventral horn interneurons (VHIN) in segments L6-7 of the spinal cord during bilateral stimulation of the motor cortex in cats. The overwhelming majority of VHIN was shown to be activated by influences from the contralateral cortex, and about half of them also by ipsilateral influences. Clear correlation was established between convergence of afferent and cortical influences: Neurons with inputs from ipsilateral afferents only were activated, irrespective of their other characteristics, by descending influences from the contralateral cortex only, whereas bilateral cortical influences converged on cells with bilateral afferent connections. It is suggested that VHIN with bilateral segmental and supraspinal connections are important integrative elements in the mechanism of bilateral coordination of motor responses of different degrees of complexity.

Afferent Pathways↗
PubMed1986

The multiple origins of human Alu sequences.

I have analyzed a collection of published human Alu sequences. The compiled sequences show several unexpected features, including a uniform pattern of divergence from their consensus sequence, a mutual divergence that is not correlated with their age, and common features in the genomic DNA flanking the 5' ends of the elements. I suggest that the Alu family of sequences derives from a large pool of precursors and not from a single precursor similar to the family consensus sequence, and that new elements integrate into the genome selectively at oligo-A-rich sites.

Base Sequence↗
PubMed2002

[Risk Management: concepts and chances for public health].

BACKGROUND: Errors are a common problem in medicine and occur as a result of a complex process involving many contributing factors. Medical errors significantly reduce the safety margin for the patient and contribute additional costs in health care delivery. SYSTEM APPROACH: In most cases adverse events cannot be attributed to a single underlying cause. Therefore an effective risk management strategy must follow a system approach, which is based on counting and analysis of near misses. The development of defenses against the undesired effects of errors should be the main focus rather than asking the question "Who blundered?". Analysis of near misses (which in this context can be compared to indicators) offers several methodological advantages as compared to the analysis of errors and adverse events. Risk management is an integral element of quality management.

Computer Simulation↗
PubMed2003

[Basic ethical aspects of living organ donation].

A characteristic feature of transplanting organs from living donors is that not only patients in need for treatment but also healthy individuals are submitted to medical interventions. Ethical considerations in this field have to deal with the question of property attributes of the human body and conflicts with traditional medical principles. Altruistic organ donation, appreciated by Christianity as a sign of charity, is indeed contradictory to the classic maxim of medical ethics "primum nihil nocere, " meaning "first of all, do not harm." The autonomous choice of a potential donor has to be balanced thoroughly against his personal physical and psychological risks. Apart from organ donation with altruistic motives, commercial incentives or payment for organ donation, which are increasingly under discussion in many nations, need profound ethical reflection. Organ selling does not lead to long-term economic benefit for individual donors in developing countries and is associated with a decline in health. A market system of organ sales would foster exploitation of the poor, and it is substantially doubtful whether autonomy and self determination are valid under circumstances of poverty and coercion. Commodification of the human body risks viewing persons as marketable objects. The human body,however, is an integral element of an individual's personality and not a resource to be removed. It is therefore fundamental that the social good of altruism is preserved as the major principle in organ donation.

Altruism↗
PubMed2006

Broadening perspectives on clinical performance assessment: rethinking the nature of in-training assessment.

CONTEXT: In-training assessment (ITA), defined as multiple assessments of performance in the setting of day-to-day practice, is an invaluable tool in assessment programmes which aim to assess professional competence in a comprehensive and valid way. Research on clinical performance ratings, however, consistently shows weaknesses concerning accuracy, reliability and validity. Attempts to improve the psychometric characteristics of ITA focusing on standardisation and objectivity of measurement thus far result in limited improvement of ITA-practices. PURPOSE: The aim of the paper is to demonstrate that the psychometric framework may limit more meaningful educational approaches to performance assessment, because it does not take into account key issues in the mechanics of the assessment process. Based on insights from other disciplines, we propose an approach to ITA that takes a constructivist, social-psychological perspective and integrates elements of theories of cognition, motivation and decision making. A central assumption in the proposed framework is that performance assessment is a judgment and decision making process, in which rating outcomes are influenced by interactions between individuals and the social context in which assessment occurs. DISCUSSION: The issues raised in the article and the proposed assessment framework bring forward a number of implications for current performance assessment practice. It is argued that focusing on the context of performance assessment may be more effective in improving ITA practices than focusing strictly on raters and rating instruments. Furthermore, the constructivist approach towards assessment has important implications for assessment procedures as well as the evaluation of assessment quality. Finally, it is argued that further research into performance assessment should contribute towards a better understanding of the factors that influence rating outcomes, such as rater motivation, assessment procedures and other contextual variables.

Clinical Competence↗
PubMed1992

In vitro interactions of the histone-like protein IHF with the algD promoter, a critical site for control of mucoidy in Pseudomonas aeruginosa.

The ability of the histone-like element Integration Host Factor (IHF) to interact with the algD promoter was investigated. IHF from Escherichia coli was found to bind to the algD promoter and to form multiple protein-DNA complexes in gel mobility shift DNA binding assay. The highest affinity binding site for IHF was mapped by DNaseI footprinting analysis. This site spanned nucleotides -50 to -85 relative to the algD mRNA start site and overlapped a sequence matching the IHF consensus sequence WATCAANNNNTTR in 12 out of 13 base pairs. Previous studies have shown that deletion of sequences including a portion of this site adversely affects algD promoter activity. IHF binding to the algD promoter induced DNA bending. Western blot analysis with antibodies against E. coli IHF detected a cross-reactive protein of a similar molecular mass in Pseudomonas aeruginosa, suggesting the presence of an analogous factor in this organism.

Amino Acid Sequence↗
PubMed1993

Antinociceptive activity of intrathecal ketorolac is blocked by the kappa-opioid receptor antagonist, nor-binaltorphimine.

Systemic and intrathecally administered ketorolac produced antinociception in the p-phenylquinone test, but not in the tail-flick or hot-plate tests. Antagonists of the subtypes of opioid receptors were used to evaluate the interaction of ketorolac with these receptors. Intrathecally administered kappa-opioid receptor antagonist nor-binaltorphimine dihydrochloride blocked the antinociceptive effects of systemic ketorolac and intrathecally administered ketorolac. Naloxone and ICI 174,864 failed to block the effects of ketorolac. Activation of nor-binaltorphimine-sensitive receptors appears to be an integral element in the mechanism of antinociception of ketorolac at the spinal level. Ketorolac did not precipitate withdrawal jumping in morphine-tolerant mice demonstrating that ketorolac does not act as a mixed agonist-antagonist at the opioid receptor. We suggest that neuraxial placement of ketorolac may prove useful in the clinical setting for the management of acute pain in humans.

Analgesics↗
PubMed1992

Thoracic spine trauma.

Thoracic spine fractures are most commonly flexion injuries resulting from vehicular accidents or falls. The initial evaluation of any multiple trauma victim should include AP and cross-table lateral radiographs of the thoracic spine. Conventional and computed axial tomography can add additional information regarding posterior element integrity and spinal canal encroachment. MRI can also be useful in that it directly images the effects of fractures on the spinal cord.

Humans↗