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Biomedical subjects

D Adam

Publications and source records attributed to D Adam.

At least 19 recordsLinked to original sources
PubMed1995

Cross-linking of the p55 tumor necrosis factor receptor cytoplasmic domain by a dimeric ligand induces nuclear factor-kappa B and mediates cell death.

We have fused the cytoplasmic domain of the p55 tumor necrosis factor (TNF) receptor to the extracellular and transmembrane domain of the mouse platelet-derived growth factor (PDGF) receptor. Mouse mammary gland epithelial (NMuMG) cells were stably transfected with the PDGFR-TR55 chimeric receptor. These cells lack endogenous PDGF receptor expression and do not respond to PDGF. In the PDGFR-TR55 transfectants, PDGF elicited a cytotoxic response, which is indistinguishable from that induced by the wild type p55 TNF receptor. In addition, PDGF-induced activation of the PDGFR-TR55 chimeric receptor resulted in nuclear translocation of NF-kappa B. The data presented suggest that cross-linking of the p55 TNF receptor cytoplasmic domain by a dimeric ligand such as PDGF is sufficient to generate cellular responses that do not differ from those observed with the trimeric ligand TNF.

Animals↗
PubMed1995

Tumor necrosis factor (TNF)-alpha activates c-raf-1 kinase via the p55 TNF receptor engaging neutral sphingomyelinase.

TNF-alpha mediates proliferation, functional activation and apoptotic death of cells depending upon its concentration and target cell type. The signaling pathways used by TNF-alpha to mount these responses are, at present, not completely understood. We report here that TNF-alpha promotes dose- and time-dependent phosphorylation and activation of the c-raf-1 kinase engaging the type I p55 TNF receptor (TNF-R). c-raf-kinase activation was duplicated by an agonistic monoclonal antibody directed against the p55 TNF-R. Moreover, ectopic expression of the human p55 TNF-R in murine pre-B 70Z/3 cells was sufficient to confer c-raf-1-kinase activation by human TNF-alpha. By inhibiting intracellular activation of acidic sphingomyelinase (SMase) and by using deleted forms of the type I TNF-R it was shown that the neutral, but not the acidic SMase, participated in TNF-alpha-mediated phosphorylation and activation of the c-raf kinase. TNF-alpha-induced transcriptional activation of a heterologous promoter construct harboring the AP-1 binding site was also mediated by the type I p55 TNF-R. In this case the initiation of transcription required the same cytoplasmic domain as that responsible for activation of c-raf-1 kinase and was liberated in the presence of a dominant negative mutant of c-raf-1.

Animals↗
PubMed1995

Modulation of the arterial coronary blood flow by asynchronous activation with ventricular pacing.

UNLABELLED: This study aims to test the assumptions that: (1) coronary arterial flow is attenuated in an early activated region by ventricular pacing; (2) asynchronous mechanical activation caused by ventricular pacing under controlled perfusion pressure and intact coronary tone is associated with reduced coronary flow compared to atrial pacing; and (3) abolishment of vascular tone under controlled perfusion pressure diminishes the expected difference in blood flow between atrial and ventricular pacing. Blood flow velocity (BFV) in the left anterior descending (LAD) and the left circumflex arteries (CFX) and a wall thickening index were measured in 14 open-chest dogs under normal conditions, and constant perfusion pressure. Four pacing sites were used: right atrium (RAp), mid-right ventricle (RVp), mid-left ventricle (LVp), and left ventricular apex (Apexp). Pacing modes were either sequential ventriculoatrial (VA) (protocol A, n = 7), or sequential atrioventricular (AV) (protocol B, n = 7), with a shorter AV difference (30 msec) than normal. RESULTS: BFV was decreased in the LAD during RVp and Apexp pacing by 9.7%-12.9% versus RAp and by 11.6%-14.6% versus LVp (P < 0.05). No BFV variations were observed in the CFX. Flow velocity conductance (FVC = mean blood flow velocity divided by the mean aortic pressure) was higher by 16%-28% in the CFX for the three ventricular pacing sites versus the atrial pacing, and higher by 14.1% +/- 6.1% only in LVp versus RAp pacing in the LAD (P < 0.05). Wall thickening index reduced during ventricular pacing in all three ventricular sites by 50%-64% (P < 0.05) compared to atrial pacing. Under constant perfusion pressure, LAD blood flow decreased with ventricular pacing as compared to right atrial pacing; this was particularly pronounced during the diastolic phase (16.6%-45.5%, P < 0.02). Normalized oscillatory flow amplitude (OFAn) was reduced in RVp pacing compared to RAp and LVp pacing (16.2 +/- 3.5 and 21.7% +/- 4.1%, respectively, P < 0.03). The variations in blood flow and OFAn disappeared with adenosine-mediated maximum vasodilatation. SUMMARY: (1) Mean and phasic flows are reduced in the early activated LAD region by ventricular pacing (RVp, Apexp). (2) Under controlled perfusion pressure and intact vascular tone, ventricular pacing compromises blood flow compared with atrial pacing. (3) This effect disappears when vascular tone is eliminated by intracoronary injection of adenosine, suggesting that the coronary autoregulation is responsible for some of the effects.

Animals↗
PubMed1995

Macrolide antibacterials. Drug interactions of clinical significance.

Macrolide antibiotics can interact adversely with commonly used drugs, usually by altering metabolism due to complex formation and inhibition of cytochrome P-450 IIIA4 (CYP3A4) in the liver and enterocytes. In addition, pharmacokinetic drug interactions with macrolides can result from their antibiotic effect on microorganisms of the enteric flora, and through enhanced gastric emptying due to a motilin-like effect. Macrolides may be classified into 3 different groups according to their affinity for CYP3A4, and thus their propensity to cause pharmacokinetic drug interactions. Troleandomycin, erythromycin and its prodrugs decrease drug metabolism and may produce drug interactions (group 1). Others, including clarithromycin, flurithromycin, midecamycin, midecamycin acetate (miocamycin; ponsinomycin), josamycin and roxithromycin (group 2) rarely cause interactions. Azithromycin, dirithromycin, rikamycin and spiramycin (group 3) do not inactivate CYP3A4 and do not engender these adverse effects. Drug interactions with carbamazepine, cyclosporin, terfenadine, astemizole and theophylline represent the most frequently encountered interactions with macrolide antibiotics. If the combination of a macrolide and one of these compounds cannot be avoided, serum concentrations of concurrently administered drugs should be monitored and patients observed for signs of toxicity. Rare interactions and those of dubious clinical importance are those with alfentanil and sufentanil, antacids and cimetidine, oral anticoagulants, bromocriptine, clozapine, oral contraceptive steroids, digoxin, disopyramide, ergot alkaloids, felodipine, glibenclamide (glyburide), levodopa/carbidopa, lovastatin, methylprednisolone, phenazone (antipyrine), phenytoin, rifabutin and rifampicin (rifampin), triazolam and midazolam, valproic acid (sodium valproate) and zidovudine.

Animals↗
PubMed1994

Ctk: a protein-tyrosine kinase related to Csk that defines an enzyme family.

We used the polymerase chain reaction with degenerate oligonucleotide primers to search for Csk-related kinases. A cDNA coding for a Csk-like protein-tyrosine kinase was cloned from mouse brain and was designated ctk, for csk-type protein-tyrosine kinase. The 1.9-kb ctk mRNA was found to be expressed predominantly in brain and capable of encoding a 52-kDa protein-tyrosine kinase. The amino acid sequence of Ctk was found to possess 53% identity with mouse Csk, shared all the predicted structural features of Csk, and was capable of phosphorylating the carboxyl-terminal conserved tyrosine of Src family members. Our results thereby indicate that ctk represents a gene that defines a family of structurally and functionally related Csk-like protein-tyrosine kinases.

Amino Acid Sequence↗
PubMed1994

Quinolone antibacterials. An update of their pharmacology and therapeutic use.

Quinolones are a class of antibiotics structurally related to nalidixic acid. They exhibit bactericidal activity primarily by inhibiting bacterial DNA gyrase. The early quinolones had a limited spectrum of activity, low potency, high frequency of spontaneous bacterial resistance, low serum drug concentrations and short half-lives, which virtually restricted their use to urinary tract infection. The new fluorinated quinolones differ from their predecessors in their broad antibacterial spectrum, including both Gram-negative and Gram-positive aerobic, and facultative anaerobic bacteria as well as many Mycobacterium spp., Chlamydia spp., Legionella spp. and Mycoplasma spp., in addition to many strains of bacteria that are multiresistant to beta-lactam antibiotics and aminoglycosides. They also exhibit high potency, a low incidence of resistance, high oral bioavailability, extensive tissue penetration, low protein binding and long elimination half-lives. They are generally well tolerated apart from some gastrointestinal disturbance and rashes, including photosensitive eruptions and a propensity to cause central nervous system excitation. Clinically important interactions include those with antacids, theophylline, fenbufen and warfarin. Potential toxic effects include cartilage damage, ocular toxicity, teratogenicity and impairment of spermatogenesis. The role of fluoroquinolones continues to widen, encompassing infections of the urinary tract, respiratory tract, skin and soft tissues, bone and joints, infections in immunocompromised patients, sexually transmitted diseases, infectious diarrhoea, gynaecological infections and surgical prophylaxis. The convenience of oral therapy is an added advantage of the new fluoroquinolones.

4-Quinolones↗
PubMed1992

Cross-linking of surface immunoglobulin activates src-related tyrosine kinases in WEHI 231 cells.

Crosslinking of sIgM on the B cell line WEHI 231 with anti-sIgM antibody induces protein tyrosine phosphorylation, implicating protein tyrosine kinases (PTKs) in sIg-mediated signal transduction. We have analyzed this cell line for members of the src family of PTKs and have evaluated whether these PTKs might be involved in the process of sIgM-mediated signaling. Our results show that Blk, Lyn, Lck, and Hck are detectable in WEHI 231 cells. Addition of antibodies to sIgM were found to variably stimulate the activities of Blk, Lyn, Lck, and Hck as measured by immune-complex protein kinase assays. Autophosphorylation of these src PTKs, as assessed by reaction with anti-phosphotyrosine antibodies, increased over the time course of sIgM-mediated activation. Co-immunoprecipitation studies to investigate the potential physical interaction of src PTKs with the sIgM receptor complex revealed that, under digitonin and Brij 96 lysis conditions Lyn, Lck, Hck, but not Blk associated with sIgM.

Animals↗
PubMed1992

Conservation and characterisation of spatial features in a new method of data compression for body surface potential maps.

Body surface potential maps consist of a huge amount of data represented as a series of three-dimensional maps, which are time consuming to process and expensive to store. In spite of the continuous interest in body surface potential maps, their use has not become common and they are of no practical use in the clinics. This is due to the overwhelming amount of measured data required to generate the maps and the lack of quantitative methods to analyse them. Data compression or reduction may solve these deficiencies. Such a procedure must conserve the fine spatial details of the maps, which are usually extracted from low level surface potentials, as these are reported to be significant in diagnostic electrocardiography. A technique is presented for data reduction, that implements two-level thresholding and conserves the fine significant spatial features of each map. A sequence of annuli thus produced is shown to describe the dynamic nature of the underlying process. This sequence is further processed and characterised by features which quantify its dynamic behaviour: time of annuli sequence appearance, its duration, three-dimensional loci of centres of mass of the annuli, distances between successive centres of mass and cross-correlation coefficients between successive annuli. To test the data reduction procedure and the usefulness of the features, maps from 20 subjects are studied (both normal patients and those with various pathologies). It is found that the use of annuli instead of the whole measured information allows simple storage, display and calculations; the features, which vary in time, represent closely the changes in location of the annuli and their dynamic variations of shape. The features are also found to be grouped together for the maps of the normal patients and for each pathology. Thus, body surface potential maps may become more commonly used in clinics by being represented by a set of features, which conserve their dynamic and spatial nature, and which may serve for classification of cardiac pathologies.

Action Potentials↗
PubMed1992

Classification of pathologies by reduced sequential potential maps.

Body surface potential mapping (BSPM) is an electrocardiographic measuring technique which produces the data as a series of three-dimensional maps. These maps are assumed to contain information which may help classify subjects for diagnostic purposes more effectively than standard ECGs. As quantitative classification of the complete sequences of maps is complex and cumbersome, the present study uses extracted features which characterise the data. The features, which have been presented and evaluated in a recent work, have been extracted after the maps were processed by a compression technique which conserved the spatial details of the maps. The compression by two-level thresholding converted the sequences of maps into sequences of annuli, from which the following features were extracted: time indices, velocity vector magnitude, loci in three-dimensional space of the centres of mass and cross-correlation coefficients between successive annuli in the sequence. Here, three different classification methods are applied to these features: statistical methods, the Fisher linear discriminant method and visual inspection. BSPMs from 54 subjects are used: 25 normal, 11 WPW syndrome and 18 CAD cases. It is found that by applying a decision role which comprises all features, the procedure offers a completely accurate classification of the subjects to their groups. The three-dimensional centre of mass is found to be the single best classifier; successfully categorising 20/25 of the normals 17/18 of the CAD patients and 11/11 of the WPW patients.

Action Potentials↗
PubMed1992

Portable system for acquisition and transmission of ECG parameters.

A simple inexpensive bedside automatic ECG data-collection system is presented. The main parameter measured is the R-R interval length that can be used in the construction of a heart rate variability signal. Another parameter measured is the shape of the T-wave in the ECG signal. The collected data are transferred to a remote host computer through the public telephone network, by means of a modem. The system can function through the whole range of human heart rates. The described solution differs from most existing ones by utilising the existing ECG monitoring equipment in hospitals, which usually does not store any information. This equipment is connected by a portable, independent, special-purpose system to a remote host computer which can further analyse and store the data.

Computer Communication Networks↗
PubMed1992

Clinical use of the new macrolides, azalides, and streptogramins in pediatrics.

Macrolides are the primary drugs of choice for a number of clinically significant infections in children. The clinical aspects of newer macrolides such as roxithromycin, clarithromycin, dirithromycin, flurithromycin, miocamycin, rokitamycin, azithromycin and RP 59500 are discussed in different pediatric infections including streptococcal infections (e.g. pharyngitis, otitis, pneumonia, skin infections), staphylococcus soft tissue infections, mycoplasma pneumonia, chlamydial infections as well as legionellosis and campylobacter enteritis. Also, incidences of adverse events in pediatric patients receiving different macrolides are indicated as well as the dosages in children. The advantages of newer macrolides are: lower dosages, b.i.d. or once daily dosage regimens, good intracellular and tissue penetration, better activity against gram-negative microorganisms (some) and a low rate of adverse reactions.

Adolescent↗
PubMed1992

[An economic comparison between digital luminescence radiography and conventional film processing in intensive care medicine].

The costs of a conventional film-screen radiography daylight-system and storage-phosphor computed radiography (Fuji AC-1) are compared. In 1990, 3841 radiologic procedures (mostly portable chest X-rays) were performed in 3474 patients of a surgical intensive care unit. With conventional film-screen radiography 6.8% retakes were necessary for diagnostic or technical reasons. Comparing the fixed and variable costs of both systems conventional film-screen radiography was more economic under the given conditions of the test. It is concluded that computed radiography in intensive care patients has definite advantages in terms of image quality and reproducibility, however, in order to compete successfully in the economic turf CR has to be implemented in a picture archiving and communication system (PACS).

Costs and Cost Analysis↗
PubMed1992

[A career in nursing sciences?].

A research study was conducted in a francophone high school in Northern Ontario to examine students' perceptions of nursing and the influence of these perceptions on nursing as a career choice. All students in grades 11, 12 and 13 were invited to participate. Fifty-eight percent (n = 268) completed the questionnaire. Results showed that 37 percent of the respondents considered pursuing a career in the health sciences. Only 14% percent were interested in nursing. Respondents' comments suggest that the nurse is viewed favorably but the profession is perceived as a career that does not involve pleasant tasks, good working conditions or opportunities for professional advancement. Reasons advocated for choosing nursing were altruistic rather than career-oriented. Students saw nursing practice as occurring mainly in a hospital setting. Half of the respondents who had chosen nursing as a career opted to enroll in a university program and the other half chose a college program. Results suggest that nursing continues to face an image problem regarding its role in the health care system. In these times of job losses and budget cuts, the profession still needs to attract young recruits. This is the challenge we have to face.

Adolescent↗