Search PubMed⌕ Search

Biomedical subjects

T Peters

Publications and source records attributed to T Peters.

At least 37 records · Page 2Linked to original sources
PubMed2001

Gene and cluster-specific expression of the Iroquois family members during mouse development.

Mammalian homologues of the Drosophila Iroquois homeobox gene complex, involved in patterning and regionalization of differentiation, have recently been identified (Mech. Dev., 69 (1997) 169; Dev. Biol., 217 (2000) 266; Dev. Dyn., 218 (2000) 160; Mech. Dev., 91 (2000) 317; Dev. Biol., 224 (2000) 263; Genome Res., 10 (2000) 1453; Mech. Dev., 103 (2001) 193). The six members of the murine family were found to be organized in two cognate clusters of three genes each, Irx1, -2, -4 and Irx3, -5, -6, respectively (Peters et al., 2000). As a basis for further study of their regulation and function we performed a comparative analysis of the genomic organization and of the expression patterns of all six Irx genes. The genes are expressed in highly specific and regionalized patterns of ectoderm, mesoderm and endoderm derived tissues. In most tissues the pattern of expression of the clustered genes, especially of Irx1 and -2 and of Irx3 and -5, respectively, closely resembled each other while those of Irx4 and -6 were very divergent. Interestingly, the expression of cognate genes was found to be mutually exclusive in adjacent and interacting tissues of limb, heart and the laryncho-pharyncheal region. The results indicate that the Irx genes are coordinately regulated at the level of the cluster.

Animals↗
PubMed2001

[Automated swinging flashlight test in patients with optic nerve diseases].

AIM OF THE STUDY: The swinging flashlight test is an objective method to diagnose a lesion of the anterior visual pathways. However, errors and faults may easily alter the test's results. Hence, the value of the swinging flashlight test depends highly on the examiner's skills. Therefore an automated and objective procedure was developed which is independent from the examiner. METHODS: A binocularly measuring instrument adapted for video pupillography was supplied with two arrays of light emitting diodes in front of each eye of the subject. By means of this illumination, pupillary light reflexes are elicited alternately. Pupil size is registered continuously, and after artifact elimination, the response amplitudes of the pupils are determined as a mean of right and left pupil. Responses elicited via right and left eye are compared. By varying the stimulus intensity it is possible to measure the amount of the relative afferent pupillary defect. The procedure was tested in 31 patients with optic nerve disorders. RESULTS: The measurements were easily feasible, stable and reliable. Correlation between the relative afferent pupillary defect detected manually by grey filter compensating and with the automated procedure proved to be high. Both variables correlated highly significant with a Spearman rank coefficient of 0.65. If the clinical test is regarded as the golden standard, the automated swinging flashlight test is able to detect 85% of the relative afferent pupillary defects > or = 0.3 logE and 94% of the defects > or = 0.6 logE. CONCLUSION: The automated swinging flashlight test can be recommended to exclude influences by the examiner or if the exact amount of the relative afferent pupillary defect is desired, e.g. when monitoring therapeutic effects in optic nerve diseases. Furthermore, an automated swinging flashlight test could serve as a screening test.

Adult↗
PubMed2001

Pharmacokinetic/pharmacodynamic evaluation of the NHE inhibitor eniporide.

The aim of this study was to investigate the pharmacokinetics and pharmacodynamics of the new cardioprotective sodium/proton exchange (NHE-1) inhibitor eniporide in humans. Eniporide was administered intravenously to healthy volunteers in doses between 2.5 and 100 mg. Concentrations of parent drug and its metabolite were measured by HPLC, and the data were analyzed by noncompartmental and compartmental pharmacokinetic methods. Platelet-swelling time was determined in each subject as a biomarker to assess pharmacodynamic activity. Eniporide showed linear pharmacokinetics with an average half-life of approximately 2 hours. The mean total body clearance was 34.4 L/h. The mean volume of distribution (Vdss) was 77.5 L, and the mean residence time was 2.3 hours. An average of 43% of the dose was recovered unchanged from urine. A pharmacokinetic two-compartment model was found suitable to provide excellent curve fits of the measured plasma concentration profiles. Plasma concentrations of the major metabolite were lower than that of the parent drug. An average of 27% of the dose was found in urine as that metabolite. The effect on platelet swelling could be well characterized by a direct Emax model. The average concentration for half-maximum effect (IC50) was 12 ng/mL. Eniporide was found to have predictable linear pharmacokinetics in the investigated dose range. Platelet-swelling time was shown to be a reproducible individual biomarker for pharmacodynamic activity, with great potential for a surrogate that predicts clinical outcome, since this effect is mediated through the same mechanism of action (NHE-1 inhibition) as the desired cardioprotective activity. Pharmacokinetic/pharmacodynamic modeling allowed a first estimate of the degree of NHE inhibition in the investigated dose range.

Adolescent↗
PubMed2001

Guidelines and educational outreach visits from community pharmacists to improve prescribing in general practice: a randomised controlled trial.

OBJECTIVES: To evaluate the effectiveness of guidelines with or without one-to-one educational outreach visits by community pharmacists in improving general practice prescribing for non-steroidal anti-inflammatory drugs (NSAIDs). METHODS: Cluster randomised trial of 20 general practices within Avon, England. Practices were randomised to three groups: control; mailed guidelines; mailed guidelines plus educational outreach visits. General practitioners (GPs) in the latter group received two one-to-one outreach visits from community pharmacists. Changes in prescribing were measured using outcomes derived from prescribing analysis and cost (PACT) data. The primary outcome measure was change in the volume of prescribing for ibuprofen, diclofenac and naproxen as a percentage of total NSAID prescribing. Six secondary outcomes included other measures of prescribing quality and volume. A cost-benefit analysis was performed. RESULTS: No significant differences were observed for the primary outcome measure: practices receiving outreach visits prescribed only 2.1% [95% confidence interval (CI): -0.8 to 5.0] more of the three recommended NSAIDs than the control practices did and 1.6% (95% CI: -1.4 to 4.7) more than practices that received guidelines only. Following adjustment for multiple comparisons, only one secondary outcome showed a statistically significant difference between the groups: the proportion of prescribing of the five most frequently used drugs was 2.2% (95% CI: 0.9 to 3.6) higher in the educational outreach group compared with the control group. A net increase in costs was shown with both interventions. CONCLUSIONS: Although good prescribing at baseline in the participating practices limited the capacity for improvement, this trial provides no evidence that guidelines with or without educational outreach visits from community pharmacists lead to substantial improvements in prescribing behaviour.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2001

Day in, day out: the everyday therapy of community clinics.

This paper describes the timing and nature of therapy provided within a recent randomised controlled trial (RCT) of preschool speech and language therapy services. There is literature that describes and evaluates speech and language therapy but there is little indication of how this is translated into everyday practice. The study collected data from 21 speech and language therapists (SLTs) in 16 community clinics. The areas targeted, goals, approaches used, the frequency and timing of contact for the 68 children who received treatment were documented. The data show that several aspects of therapy were frequently targeted simultaneously, that approaches were combined and that the frequency of therapy did not vary with severity. The discussion will consider the gap between published programmes and everyday practice and the implications for effectiveness.

Child, Preschool↗
PubMed2001

Who's afraid of the randomised controlled trial? Parents' views of an SLT research study.

Evidence-based health care is now a reality within the national health service (NHS) and the randomised controlled trial (RCT) is the linchpin of this movement. In modern health care, there has also been a shift towards understanding client perspectives. With regard to clients' participation in research, much consideration has been given to ethical issues and barriers to participation. However, less attention has been paid to the participants' views of clinical trials and understanding how they construe the research. This paper reports a study of the attitudes of parents whose children took part in an RCT. Data were collected from the parents of 20 children, using qualitative in-depth interviews. Parents talked about the meaning of their participation, their motivation for taking part and their understanding of the nature of the trial. The implications of the findings for future research will be considered.

Attitude↗
PubMed2000

Mapping the binding of synthetic disaccharides representing epitopes of chlamydial lipopolysaccharide to antibodies with NMR.

A NMR study of the binding of the synthetic disaccharides alpha-Kdo-(2-->4)-alpha-Kdo-(2-->O)-allyl 1 (Kdo, 3-deoxy-D-manno-oct-2-ulopyranosonic acid) and alpha-Kdo-(2-->8)-alpha-Kdo-(2-->O)-allyl 2, representing partial structures of the lipopolysaccharide epitope of the intracellular bacteria Chlamydia, to corresponding monoclonal antibodies (mAbs) S23-24, S25-39, and S25-2 is presented. The conformations of 1 bound to mAbs S25-39 and of 2 bound to mAbs S23-24 and S25-39 were analyzed by employing transfer-NOESY (trNOESY) and QUIET-trNOESY experiments. A quantitative analysis of QUIET-trNOESY buildup curves clearly showed that S25-39 recognized a conformation of 1 that was similar to the global energy minimum of 1, and significantly deviated from the conformation of 1 bound to mAb S25-2. For disaccharide 2, only a qualitative analysis was possible because of severe spectral overlap. Nevertheless, the analysis showed that all mAbs most likely bound to only one conformational family of 2. Saturation transfer difference (STD) NMR experiments were then employed to analyze the binding epitopes of the disaccharide ligands 1 and 2 when binding to mAbs S23-24, S25-39, and S25-2. It was found that the nonreducing pyranose unit was the major binding epitope, irrespective of the mAb and the disaccharide that were employed. Individual differences were related to the engagement of other portions of the disaccharide ligands.

Animals↗
PubMed2000

Application of 3D-TOCSY-trNOESY for the Assignment of Bioactive Ligands from Mixtures This work was supported from the BMBF (FKZ 031161) and from the German Research Council (DFG, Sonderforschungsbereich 470, Teilprojekt B3). We thank the Fonds der Chemischen Industrie for generous support. We also thank Dr. T. Keller and Dr. G. Wolff (Bruker Analytik GmbH, Germany) for excellent support. Dr. Yasmin Karimi-Nejad (Solvay Pharmaceuticals, Netherlands) is thanked for helpful discussions.

Explore the source record for details and available documents.

Journal Article↗
PubMed2000

Isolation, characterization and biological significance of hepatitis B virus mutants from serum of a patient with immunologically negative HBV infection.

BACKGROUND/AIM: A low-titered hepatitis B virus infection without immunological markers was identified in a prospective study in the serum of a kidney transplant recipient by PCR. The aim of this study was to analyze HBV genomes and their biological significance. METHODS: The genome was amplified in two overlapping fragments A and B. Sequencing of 22 clones of the A- and 12 clones of the B-fragment revealed a heterogeneous virus population. A consensus and a mutant sequence were computed, representing the complete sequence of the virus population. The two sequences were compared with 41 published genomes of the different HBV geno- and serotypes. RESULTS: Ninety-five point mutations and two deletions were identified. Two mutations were observed in all clones and 17 other mutations in three or more clones. The deletions were found in ten and seven of 22 clones. They were located in the C-gene and led to stop codons yielding truncated e- and/or core proteins. In vitro transfection of DNA constructs containing these deletions demonstrated a stop of HBV replication and of HBeAg expression. Cotransfection experiments demonstrated a dominant negative effect of the mutants containing the deletions. In addition, we describe new variants of naturally occurring HBsAg mutants that may cause HBV infection less detectable by standard HBsAg measurement assays. They were characterized by two point mutations which were observed in 9 of 12 and 13 of 22 clones of the S-gene. They significantly reduced the HBsAg expression in in vitro transfection experiments. CONCLUSION: We found a patient with low-titered HBV infection, with mutations of the 'a' epitope of the Santigen as well as with mutations leading to truncated core proteins which may cause a dominant negative effect.

Amino Acid Sequence↗
PubMed2000

Clinical, virological and histopathological features: long-term follow-up in patients with chronic hepatitis C co-infected with S. mansoni.

BACKGROUND/AIMS: Infection with Schistosoma mansoni is endemic in Egypt leading to hepatic schistosomiasis and eventually portal hypertension. The prevalence of antibodies against hepatitis virus C among Egyptians is 14-51%. The aim of the present study was to investigate the influence of schistosomiasis on chronic hepatitis C with respect to the natural course of the disease, immunology, virology and histology. PATIENTS AND METHODS: One hundred and twenty-six Egyptian patients classified into three groups: group A: chronic hepatitis C (n=33); group B: chronic schistosomiasis (n=30) and group C: chronic hepatitis C and chronic schistosomiasis (n=63) were enrolled and prospectively followed for 62.7 +/- 22 months. Patients infected with other hepatic viruses and/or parasites were excluded. Detailed history, clinical examination, CD4+ and CD8+ lymphocyte counts in blood, hematological and blood chemical values, abdominal ultrasonography, upper endoscopy, HCV RNA titer by RT/PCR, genotype and histological activity index in the liver biopsy were determined. RESULTS: Thirty patients (48%) with HCV and schistosomiasis had liver cirrhosis and Child-Pugh class C vs. five (15%) in HCV patients and none in the schistosomal group. HCV RNA levels ranged between 0.07 and 13 x 10(5) copies/ml in group A, and between 1 and 25 x 10(5) copies/ml in group C. HCV genotype 4 was detected in 58 patients with co-infection (92%) and 21 patients with HCV alone (64%). Patients with coinfection showed higher grading and staging scores in their liver biopsies. Hepatocellular carcinoma was detected only in patients with coinfection. During follow-up, the mortality rate was 12%, 3% and 48% in group A, B and C, respectively. CONCLUSIONS: Patients with concomitant HCV and schistosomiasis infection were characterized by more advanced liver disease, higher HCV RNA titers, predominance of HCV genotype 4, higher histologic activity, higher incidence of cirrhosis and hepatocellular carcinoma as well as a much higher mortality rate.

Adult↗
PubMed2000

Organization of mouse Iroquois homeobox genes in two clusters suggests a conserved regulation and function in vertebrate development.

Iroquois proteins comprise a conserved family of homeodomain-containing transcription factors involved in patterning and regionalization of embryonic tissues in both vertebrates and invertebrates. Earlier studies identified four murine Iroquois (Irx) genes. Here we report the isolation of two additional members of the murine gene family, Irx5 and Irx6. Phylogenetic analysis of the Irx gene family revealed distinct clades for fly and vertebrate genes, and vertebrate members themselves were classified into three pairs of cognate genes. Mapping of the murine Irx genes identified two gene clusters located on mouse chromosomes 8 and 13, respectively. Each gene cluster is represented by three Irx genes whose relative positions within both clusters are strictly conserved. Combined results from phylogenetic, linkage, and physical mapping studies provide evidence for the evolution of two Irx gene clusters by duplication of a larger chromosomal region and dispersion to two chromosomal locations. The maintenance of two cognate Irx gene clusters during vertebrate evolution suggests that their genomic organization is important for the regulation, expression, and function of Irx genes during embryonic development.

Amino Acid Sequence↗