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Biomedical subjects

S Jablonski

Publications and source records attributed to S Jablonski.

9 recordsLinked to original sources

Re-expression of the tumor suppressor NF2/merlin inhibits invasiveness in mesothelioma cells and negatively regulates FAK.

The neurofibromatosis type 2 NF2 gene product, merlin, is a tumor suppressor frequently inactivated in malignant mesothelioma (MM). To investigate a possible correlation between merlin inactivation and MM invasiveness, we restored merlin expression in NF2-deficient MM cells. Re-expression of merlin markedly inhibited cell motility, spreading and invasiveness, properties connected with the malignant phenotype of MM cells. To test directly whether merlin inactivation promotes invasion in a nonmalignant system, we used small interfering RNA to silence Nf2 in mouse embryonic fibroblasts (MEFs) and found that downregulation of merlin resulted in enhanced cell spreading and invasion. To delineate signaling events connected with this phenotype, we investigated the effect of merlin expression on focal adhesion kinase (FAK), a key component of cellular pathways affecting migration and invasion. Expression of merlin attenuated FAK phosphorylation at the critical phosphorylation site Tyr397 and disrupted the interaction of FAK with its binding partners Src and p85, the regulatory subunit of phosphatidylinositol-3-kinase. In addition, NF2-null MM cells stably overexpressing FAK showed increased invasiveness, which decreased significantly when merlin expression was restored. Collectively, these findings suggest that merlin inactivation is a critical step in MM pathogenesis and is related, at least in part, with upregulation of FAK activity.

Animals↗

Standardized exchange of clinical documents--towards a shared care paradigm in glaucoma treatment.

OBJECTIVES: The exchange of medical data from research and clinical routine across institutional borders is essential to establish an integrated healthcare platform. In this project we want to realize the standardized exchange of medical data between different healthcare institutions to implement an integrated and interoperable information system supporting clinical treatment and research of glaucoma. METHODS: The central point of our concept is a standardized communication model based on the Clinical Document Architecture (CDA). Further, a communication concept between different health care institutions applying the developed document model has been defined. RESULTS: With our project we have been able to prove that standardized communication between an Electronic Medical Record (EMR), an Electronic Health Record (EHR) and the Erlanger Glaucoma Register (EGR) based on the established conceptual models, which rely on CDA rel.1 level 1 and SCIPHOX, could be implemented. The HL7-tool-based deduction of a suitable CDA rel.2 compliant schema showed significant differences when compared with the manually created schema. Finally fundamental requirements, which have to be implemented for an integrated health care platform, have been identified. CONCLUSIONS: An interoperable information system can enhance both clinical treatment and research projects. By automatically transferring screening findings from a glaucoma research project to the electronic medical record of our ophthalmology clinic, clinicians could benefit from the availability of a longitudinal patient record. The CDA as a standard for exchanging clinical documents has demonstrated its potential to enhance interoperability within a future shared care paradigm.

Computer Communication Networks↗

Human immunodeficiency virus type-1 reverse transcriptase. Contribution of Met-184 to binding of nucleoside 5'-triphosphate.

Mutations were made in recombinant human immunodeficiency virus type-1 reverse transcriptase (RT) by substituting methionine 184 with alanine (M184A) or valine (M184V), and steady-state and pre-steady-state kinetic constants were determined. The Km values of M184A RT for dNTPs were larger than those of wt RT for RNA-directed synthesis; the kcat values of M184A RT for processive or distributive synthesis were similar. In contrast to M184A RT, the Km and kcat values of M184V RT for dNTP substrates were similar to those of wt RT. The Ki values of M184V RT for 1-beta-L-nucleoside analogs were increased 30-500-fold relative to wt RT for both RNA- and DNA-directed synthesis. The Kd and kp values of wt RT and M184V RT for dCTP and cis-5-fluoro-1-[2-(hydroxymethyl)-1, 3-oxathiolan-5-yl]cytosine 5'-triphosphate (1-beta-L-FTCTP) were estimated from pre-steady-state kinetics for single nucleotide incorporation. The Kd value of M184V RT for 1-beta-L-FTCTP was 19-fold greater than that of wt RT; the kpvalues of the two enzymes were similar. These results support the hypothesis that methionine 184 in the highly conserved YMDD region of wt RT participates in the binding of the nucleoside (analog) 5'-triphosphate.

Amino Acid Sequence↗

Peripheral artery recanalization in humans using balloon and laser angioplasty.

The treatment of patients with complex peripheral arterial disease and those who have had previous unsuccessful attempted revascularization procedures can be clinically challenging. Initial treatment was begun using therapy by percutaneous balloon and laser angioplasty, then proceeding to bypass surgery if severe ischemia persisted. Both percutaneous and cut-down approaches were used to access totally occluded arteries. An attempt was made to cross the occlusion mechanically with either a guide wire or an activated laser probe. If laser recanalization was not successful, the patient underwent bypass surgery or was managed with medication unless an amputation was necessary. Following initial screening of 381 patients, 115 procedures were performed on 103 patients. In 31 procedures (28 patients), only balloon angioplasty was performed. In 84 procedures (75 patients), laser recanalization was attempted: 55 percutaneously and 29 by cut-down. Overall technical success (crossing the obstruction without perforation) was 86/115 (75%). Technically successful procedures were characterized by shorter arterial occlusions than were technical failures (8.4 +/- 1 cm vs. 14.3 +/- 1.9 cm; p < 0.004). Clinical success (residual stenosis < 50%, symptom relief, improved ankle brachial index > or = 0.15, and no complications) was achieved in 22/31 (71%) of balloon angioplasty procedures alone. The stenoses decreased from 98 +/- 4% to 31 +/- 24%, p < 0.00001. Combined percutaneous laser and balloon angioplasty had a technical success of 36/55 (65%). Stenoses were reduced from 99 +/- 2% to 56 +/- 14% after laser angioplasty, to 30 +/- 15% after balloon angioplasty, p < 0.0001. Laser angioplasty performed via a cut-down had a clinical success of 9/29 (31%). However, major complications were rare. Device staging for treatment of peripheral vascular disease provides additional options for patients who are at high surgical risk and/or in whom standard therapy has failed.

Adult↗

Syndrome--a changing concept.

Syndrome is one of the oldest terms in the medical vocabulary. Traditionally, the term has been used mainly as a designation for complex medical entities, such as multiple abnormalities, that are characterized by clusters of concurring symptoms, usually three or more. During the mid-twentieth century, the meaning and the use of the term were altered. First to take place was an attempt to eliminate physicians' names from syndrome nomenclature, resulting in a significant increase in the use of descriptive designations in proportion to eponyms. But the trend was counterbalanced by the creation of new classes of eponyms. Eponymous syndrome nomenclature now includes the names of literary characters, patients' surnames, subjects of famous paintings, famous persons, geographic locations, institutions, biblical figures, and mythological characters. This was followed by a relaxation in the scope of the definition of syndrome, wherein the term could also be used as a modifier indicating a special (sometimes unspecified) complexity of an already named pathological condition. Eventually syndrome changed from its original use as an exclusively medical term and came to mean anything unusual, abnormal, bizarre, or humorous, whether medical, social, behavioral, or cultural. This unrestrained use of the term is the principal cause of an enormous volume of the sometimes irrelevant syndrome literature cluttering databases in the MEDLARS system and of the deterioration of "SYNDROME" as a specific MeSH term and a useful search parameter.

Abstracting and Indexing↗

Syndrome: le mot de jour.

Syndrome is one of the oldest terms in the medical vocabulary. It has been used as a designation for those disorders that were marked by etiologically nonspecific similar groups of manifestations up to the time of Syndenham. His contention that the terms syndrome and disease were in fact synonymous explains in part infrequent use of syndrome in the literature until the latter part of the 19th century. Redefinition of syndrome early in the 20th century as a disorder characterized by the concurrence of symptoms which are causally related, and further refinement of the definition as a condition marked by a cluster of symptoms occurring together coincidentally, gradually restored the popularity of the term to where syndrome is now one of the most frequently used designations of morbid states in the literature. There are numerous definitions of syndrome currently in use. One which is accepted by most dysmorphologists, geneticists, and some clinicians states that syndrome is an etiologically defined entity of unknown pathogenesis. However, most writers use the term randomly to denote any abnormal condition, whether medical, social, or behavioral, when a more satisfactory designation cannot be found or created, or to emphasize special complexity (syndromic qualities?) of already named diseases, or merely to be amusing. The post-Sydenham custom of naming of syndromes after physicians gave way in the mid-20th century to methods wherein syndrome names incorporate clinical, etiological, genetic, and other significant characteristics. Other methods used in designating syndromes include using the names of the first patient known to be affected, acronyms and abbreviations, personal names of all kinds, and the like.(ABSTRACT TRUNCATED AT 250 WORDS)

Eponyms↗

The preconstructed vocabulary: a Procrustean bed.

The mechanization of bibliographic services has imposed a change from the retrospective to the prospective approach to vocabulary development. This results in vocabularies rigidly structured to serve a variety of purposes which are not always mutually compatible. The user suffers from the inflexibility of the basic framework, the dearth of cross-references, and the overspecificity of many subject headings. Computer technology and our knowledge of its application have advanced to the point that we should begin to reclaim some of the bibliographic conveniences which no longer have to be sacrificed.

Information Systems↗

The biomedical information explosion: from the index-catalogue to MEDLARS.

This study demonstrates the growth of medical periodical literature by means of the increase of titles indexed in the Index-Catalogue and in Index Medicus, with reference to other biomedical-related titles not covered in these publications. Stress is laid on the fact that information outside the biomedical area is needed by the researcher. Problems of information retrieval, with the specific needs of the user in mind, are discussed, together with the particular problems of indexing which this specificity raises.

Abstracting and Indexing↗