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Biomedical subjects

D Adam

Publications and source records attributed to D Adam.

At least 91 records · Page 5Linked to original sources
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

[Empirical antimicrobial therapy in neutropenic patients. Results of a multicenter study by the Infections in Hematology Study Group of the Paul Ehrlich Society].

BACKGROUND: Severe infections are the predominant cause of treatment failure in patients with high grade malignant hematological disorders undergoing intensive chemotherapy. PATIENTS AND METHODS: In a multicenter trial of the Paul Ehrlich Society (PEG) study group, febrile neutropenic patients with acute leukemias or other high grade hematological malignancies were randomized for a three phase sequential antimicrobial intervention comparing different widely applied regimes for empirical therapy. Patients with clinically documented infections were treated according to a modification depending on the respective source of infection, whereas in patients with microbiologically documented infections, treatment could be adapted to the sesceptibility patterns of detected pathogens. Criteria for evaluation as well as time points for response assessment and treatment escalation were strictly prescribed by the study protocol. RESULTS: Of 1573 evaluable patients, 50.9% had fever of unknown origin (FUO) throughout the study period, 17.1% had lung infiltrates, 14.1% primary bacteremia or fungemia (B/F), 12.6% other clinically documented (CDI) and 5.3% other clinically as well as microbiologically documented infections (CMDI). Cumulative response rate (CR) in patients with FUO was 91.3%, a significant difference between various regimens could not be detected in either of the three treatment phases. Patients with lung infiltrates had a significantly worse treatment outcome as compared to patients with other documented infections or with FUO (61.3% vs 82.9% vs 91.3%). Gram-positive pathogens dominated in case of microbiologically documented infections (MDI), whereas the proportion of fungal infections increased dramatically in MDI with pathogens detected only after more than six days under study. Of numerous prognostic factors analyzed, only the trend in white blood cell counts had a significant impact on treatment outcome. CONCLUSION: Infection-related mortality in neutropenic patients with high grade hematological malignancies can be markedly reduced by a systematically escalating interventional antimicrobial therapy. Early systemic antifungal treatment, especially in patients with lung infiltrates, might further improve treatment results.

Adolescent↗
PubMed1994

Interventional antimicrobial therapy in febrile neutropenic patients. Study Group of the Paul Ehrlich Society for Chemotherapy.

In this prospective multicenter trial, treatment strategies for 1573 patients with neutropenia < 1000/microliters and fever > or = 38.5 degrees C after cytotoxic chemotherapy were compared. Patients with unexplained fever were randomized to a three-phase sequential study for different established drug regimens. If an infection could be defined microbiologically or clinically, treatment modifications were determined. In phase I, treatment for all patients consisted of acylaminopenicillin (PEN) plus aminoglycoside (AMG); or third-generation cephalosporin (CEPH) plus AMG; or PEN plus CEPH. In 800 patients with unexplained fever the response rates were: PEN/AMG (n = 258): 74.4%, CEPH/AMG (n = 252): 73.4%; PEN/CEPH (n = 290): 70.0%. Total response rate was 72.5%. In phase II, patients not responding after 3 days received PEN/CEPH/vancomycin (n = 70) or PEN/CEPH/AMG (n = 74). The respective response rates were 52.9% and 55.4%, total 54.2%. If fever did not resolve, the patients received either PEN/CEPH (n = 40) or imipenem/cilastatin (n = 59) both in combination with amphotericin-B/5-flucytosin/rifampin. The response rates were 62.5% and 79.7%, respectively (p = 0.07), total 72.7%. No significant differences between the treatment modalities compared were found. Analyzing all three phases together, 91.3% of patients with unexplained fever were cured. The response rate was also analyzed according to patients with gram-positive bacteremia (n = 183), response rate = 82.5%; gram-negative organisms (n = 145) 78.6%; fungemia (n = 51) 43.1% (p < 0.001); lung infiltrates (n = 269) 61.3% (p < 0.001); clinically documented infections (n = 198) 84.4%; and clinically and microbiologically documented infections (n = 84) 82.1%. If infections were diagnosed after at least 5 febrile days, more lung infiltrates and fungal infections occurred (p < 0.001). Leukocytes rising above 500/mu during the infection predicted better response rates (p < 0.001): in unexplained fever 97.8% vs 86.5% and lower death rates 1.5% vs 8.5%. In documented infections the response rates were then 89.9% vs 62.3% and the death rates 7.0% vs 20.5%. Therapy of neutropenic fever and infections must be adapted according to risk factors and should include early empiric antifungal therapy. The therapeutic and prophylactic use of hematopoietic growth factors to overcome neutropenia should be evaluated.

Adolescent↗
PubMed1994

Treatment of fever in childhood.

Although the need for routine antipyretic therapy in children has often been questioned, there are no data to contra-indicate this. Not all fevers need to be treated but many physicians do so to relieve parental concern. The most commonly used antipyretic drugs are acetylsalicylic acid (ASA), paracetamol (acetaminophen) and dipyrone (metamizol). Paracetamol and ASA have been extensively evaluated but there are few clinical trials on dipyrone. In the last decade a strong statistical association has been observed between salicylates and Reye syndrome. Paracetamol is the most common cause of acute hepatic failure. Dipyrone has been associated with agranulocytosis. In the light of these findings the extensive use of antipyretics drugs has been seriously questioned.

Acetaminophen↗
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↗
PubMed1993

Signal transduction through a biomolecular receptor tyrosine protein kinase composed of a platelet-derived growth factor receptor-CD4 chimera and the nonreceptor tyrosine protein kinase Lck.

We have generated a novel "receptor tyrosine kinase" by fusing the extracellular and transmembrane domain of the mouse platelet-derived growth factor receptor (PDGFR) to the cytoplasmic domain of CD4 and coexpressing the construct with the murine cytoplasmic tyrosine protein kinase p56lck. NMuMG cells, which are mouse mammary gland epithelial cells that lack endogenous platelet-derived growth factor (PDGF) receptor expression, were stably transfected with both PDGFR-CD4 and p56lck. The PDGFR-CD4 chimeric protein was expressed at the cell surface and formed a complex with p56lck. Addition of PDGF to these cells led to increased tyrosine phosphorylation of a 56-kDa protein likely to be p56lck and several unidentified cellular proteins. The enzymatic activity of p56lck was increased after treatment with PDGF, indicating that dimerization (or oligomerization) mediated by ligand binding at the cell surface is capable of inducing the activation not only of receptor tyrosine kinases but nonreceptor tyrosine kinases as well. However, the PDGFR-CD4.p56lck complex was, in contrast to the wild type PDGF receptor, not able to induce a PDGF-dependent mitogenic response or DNA synthesis in NMuMG cells. Analysis of several known substrates of the PDGFR-signaling pathway indicates an early block in the transduction of the signal generated by p56lck.

Amino Acid Sequence↗
PubMed1993

Tumor suppression in Xiphophorus by an accidentally acquired promoter.

Melanoma formation in the teleost Xiphophorus is caused by a dominant genetic locus, Tu. This locus includes the Xmrk oncogene, which encodes a receptor tyrosine kinase. Tumor induction is suppressed in wild-type fish by a tumor suppressor locus, R. Molecular genetic analyses revealed that the Tu locus emerged by nonhomologous recombination of the Xmrk proto-oncogene with a previously uncharacterized sequence, D. This event generated an additional copy of Xmrk with a new promoter. Suppression of the new Xmrk promoter by R in parental fish and its deregulation in hybrids explain the genetics of melanoma formation in Xiphophorus.

Amino Acid Sequence↗
PubMed1993

Cefprozil versus penicillin V in treatment of streptococcal tonsillopharyngitis.

In a randomized multicenter study, the efficacy and safety of cefprozil were compared with those of penicillin in the treatment of group A streptococcal tonsillopharyngitis in children. Of the 409 patients enrolled, 323 were evaluable for their clinical and bacteriological responses; of these 323 children, 172 received cefprozil and 151 received penicillin V. The clinical responses in patients treated with cefprozil were significantly better than those in patients who received penicillin (95.3 versus 88.1%; P = 0.023). Eradication of the original serotype of group A streptococci was achieved in 91.3% of patients treated with cefprozil and 87.4% of patients treated with penicillin, the difference not being statistically significant (P = 0.125). However, there were significantly more symptomatic patients among the bacteriological failures in the penicillin group (68.4%) than in the cefprozil group (26.7%). beta-Lactamase-producing Staphylococcus aureus was more frequently isolated from the throat flora during penicillin therapy than during cefprozil treatment. No difference in the incidence of adverse events probably related or of unknown relationship to the study drugs was observed in the two treatment groups (5.2% of those treated with cefprozil and 6.0% of those treated with penicillin). Cefprozil can be considered a safe and reliable drug for the treatment of streptococcal pharyngitis in children.

Cephalosporins↗
PubMed1993

Molecular cloning and analysis of cDNA encoding the murine c-yes tyrosine protein kinase.

The cellular yes (c-yes) gene is a member of the class of proto-oncogenes that encode non-receptor tyrosine protein kinases. In this report we describe the isolation of cDNAs that encode the murine c-yes gene product and analysis of the nucleotide sequence of the murine c-yes cDNA clones. The reading frame encodes a protein of 541 amino acids with a calculated molecular mass of 60.63 kDa that is reactive with anti-Yes antisera and possesses protein kinase activity.

Amino Acid Sequence↗
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↗