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Biomedical subjects

M Peters

Publications and source records attributed to M Peters.

At least 181 records · Page 10Linked to original sources
PubMed1998

In vivo and in vitro activities of the gp130-stimulating designer cytokine Hyper-IL-6.

IL-6 is a multifactorial cytokine mediating acute inflammatory responses in the liver. When IL-6 binds to a specific receptor (IL-6R), the IL-6/IL-6R complex associates with the signal transducer gp130, initiating intracellular signaling. A soluble form of the IL-6R (sIL-6R) renders target cells sensitive to IL-6 that do not express the IL-6R on their surfaces. A designer cytokine, termed Hyper-IL-6, consisting of IL-6 covalently linked to the sIL-6R was fully active on gp130-expressing cells at 100- to 1000-fold lower concentrations than unlinked IL-6 and IL-6R. Mice were injected i.p. with Hyper-IL-6 or IL-6. Upon injection of Hyper-IL-6 into mice, the acute phase response, as measured by haptoglobin mRNA expression in the liver, was markedly increased and lasted significantly longer compared with that in mice injected with a 10-fold higher dose of IL-6 alone. On human hepatoma cells, Hyper-IL-6 caused similar effects, indicating that the longer lasting response to the fusion protein could not only be explained by the longer plasma half-life of the fusion protein. Experiments using iodinated IL-6 and Hyper-IL-6 revealed that Hyper-IL-6 bound with high affinity to gp130 and was less efficiently internalized. This effect might explain the longer lasting activity of this protein on cells. The highly active IL-6/sIL-6R designer protein might be of significant clinical importance for the stimulation of cells that are more responsive to the IL-6/sIL-6R complex than to IL-6 alone. Such cells include hemopoietic progenitor cells and hepatocytes.

Acute-Phase Reaction↗
PubMed1998

Increased serum neopterin levels in acutely ill and recovered schizophrenic patients.

Twenty-nine in-patients with acute schizophrenia were examined to assess serum neopterin levels by ELISA at two points of time: during the state of acute symptoms and after clinical recovery at the point of discharge (at an interval of 30.84 +/- 15.22 days). Patients showed significantly higher levels of neopterin than controls. Moreover, the neopterin levels were significantly higher in patients after clinical improvement than in acutely ill patients. Neopterin levels in patients after clinical recovery were negatively correlated to scores of psychopathological symptoms, and positively to neuroleptic medication at the acute stage of the disease. The increase of serum neopterin during treatment of schizophrenia may reflect an up-regulation of dopamine turnover, rather than immunological activity.

Acute Disease↗
PubMed1998

A human alloantibody interferes with binding of factor IXa to the factor VIII light chain.

Inhibitory antibodies directed against factor VIII develop in a substantial number of patients with hemophilia A as a consequence of factor VIII replacement therapy. These antibodies usually recognize discrete epitopes within the A2 and/or the C2 domains of factor VIII. Here, we have characterized the antibodies present in the plasma of a patient affected by severe hemophilia A. The antibodies reacted readily with the metabolically labeled factor VIII light chain and fragments thereof when analyzed by immunoprecipitation. The inhibitory activity could be neutralized by the complete light chain, whereas only slight neutralization occurred with a fragment comprising the isolated C2 domain. Binding of the majority of antibodies to in vitro synthesized factor VIII fragments was dependent on the presence of amino acid residues Gln1778-Met1823, a region known to contain a factor IXa binding site. Functional characterization showed that purified IgG from the patient's serum inhibited binding of factor IXa to immobilized factor VIII light chain in a dose-dependent manner. These data indicate that human alloantibodies may inhibit factor VIII activity by interfering with factor IXa-factor VIIIa complex assembly.

Binding Sites↗
PubMed1998

Unsolved problems in comparing brain sizes in Homo sapiens.

When brain size is compared across taxonomic levels, there is a clear relation between body parameters and brain size. It is generally stated that the correlation between brain size and body parameters becomes very small at the species level (Aboitiz, 1996), but this is not the case for Homo sapiens where there is a strong correlation between brain size and body size across racial groups that differ in body size. The control for body size across racial groups (and sexes) is rendered difficult because bodies do not just differ only in height and weight. Within groups different studies show weak and inconsistent brain size/body height correlations. A better understanding of brain size/body height relations must await better quality data and a better understanding of how exactly body parameters should be scaled between groups and sexes. We attribute the clear between-group and weak within-group correlations to the large variety of body sizes and body types in our species, a variety which is only equalled in selectively bred species of animals. At present, there is no meaningful basis for the comparison of brain sizes within and between racial groups and sexes.

Adult↗
PubMed1998

Simple bone cysts treated with aspiration and a single bone marrow injection. A preliminary report.

The results of a single percutaneous aspiration and injection of marrow into active, simple bone cysts are reported in 8 cases. Slow regression of the cyst was consistently observed except in one lesion in the distal tibia. All the patients have been free of symptoms after this treatment after a mean follow up of 31 months. The evolution of the cysts was monitored by a cyst index, cyst diameter measurements and computer assisted densitometric image analysis of serial radiographs.

Bone Cysts↗
PubMed1998

Hepatocellular hyperplasia, plasmacytoma formation, and extramedullary hematopoiesis in interleukin (IL)-6/soluble IL-6 receptor double-transgenic mice.

Cytokines interact not only with membrane anchored receptors, but also with specific soluble receptors which circulate in the bloodstream. In general, soluble cytokine receptors such as soluble tumor necrosis factor receptor, soluble interleukin 1 receptor, and soluble interleukin 4 receptor compete with their membrane-bound counterparts for the ligands and therefore act as antagonists. In contrast, soluble receptors for cytokines of the interleukin-6 (IL-6) family complex with their ligands act agonistically. Interestingly, the complex of IL-6 and the soluble interleukin 6 receptor (sIL-6R) activates target cells that do not express the membrane-bound IL-6R and therefore cannot respond to IL-6. To identify cellular responses that are due to IL-6/sIL-6R but not to IL-6 alone, IL-6/sIL-6R double-transgenic mice were generated and compared with IL-6 single-transgenic mice. IL-6/sIL-6R transgenic mice develop a severe phenotype showing 1) marked hepatocellular hyperplasia frequently surrounded by peliosis and necrosis, 2) significant acceleration and aggravation of plasmacytoma formation, and 3) excessive activation of extramedullary hematopoiesis in spleen and liver followed by a subsequent increase of all cellular components in the peripheral blood. These in vivo data suggest that the sIL-6R recruits primarily unresponsive cell populations such as hematopoietic progenitor cells and hepatocytes to IL-6-induced proliferation, but also enhances the known mitogenic effect of IL-6 on plasma cells and thereby contributes to plasmacytoma formation.

Animals↗
PubMed1998

Post-movement beta oscillations studied with linear estimation.

The application of surface laplacian and linear estimation methods to single trial EEG data was studied. EEG was recorded in 3 subjects during voluntary, self-paced extensions and flexions of the index finger. In each subject a post-movement beta synchronisation was found in specific frequency bands. The surface laplacian estimates were calculated using spherical splines and cortical current distributions were constructed using the linear estimation method. Both methods yield similar results and reveal a maximal event-related synchronisation over the left sensorimotor area approximately 500-750 ms after termination of movement.

Adult↗
PubMed1998

The microlaparoscope should be used routinely for diagnostic laparoscopy.

OBJECTIVE: To describe the experience of changing from the use of the 10-mm standard laparoscope to the use of the 2-mm microlaparoscope (MicroLap, Imagyn Medical Inc., Laguna Niguel, CA) and to compare the amount of postoperative pain and requirement for analgesics after each technique. DESIGN: Prospective study. SETTING: Day surgery unit in an academic reproductive medicine unit. PATIENT(S): One hundred thirty-five women undergoing diagnostic microlaparoscopy. INTERVENTION(S): Diagnostic laparoscopy with a 2-mm instrument. Recording of postoperative pain on an analog scale. MAIN OUTCOME MEASURE(S): Ability to complete the procedure satisfactorily with the microlaparoscope, pain scores, and use of analgesics. RESULT(S): All diagnostic procedures were performed satisfactorily with the use of the MicroLap. Patients who underwent MicroLap procedures had significantly less abdominal pain postoperatively, but there was no difference in shoulder tip (gas-related) pain. Less analgesia was required after the microlaparoscopy. CONCLUSION(S): In most situations, the microlaparoscope is the instrument of choice for initial diagnostic laparoscopy. The 10-mm laparoscope should be used only as a secondary instrument after microlaparoscopy, if indicated.

Abdominal Pain↗
PubMed1998

Differential magnetic resonance signal change in human sensorimotor cortex to finger movements of different rate of the dominant and subdominant hand.

Functional magnetic resonance tomography (fMRI) analysis of unimanual and bimanual sequential movements in righthanders showed the following effects. First, a rate-dependent activation of the somato-motor cortex was confirmed, with faster movement rates producing higher activation both in terms of signal intensity and number of activated voxels. Second, the right hemisphere showed more activation than the left hemisphere during unimanual tasks. Third, during bimanual movements, the left hemisphere showed greater activation than the right hemisphere. Finally, while the left hemisphere showed a marked change in activation patterns from unimanual to bimanual task, the right hemisphere activation patterns were not sensitive to task changes. The hemispheric asymmetries suggest substantial left hemisphere involvement in the coordination of bimanual tasks.

Adult↗
PubMed1998

Monitoring of serum aminoglycoside levels with once-daily dosing.

There is considerable confusion as to how to monitor serum aminoglycoside levels when using once-daily dosing. At least five methods are in use in Australia. We prospectively assessed 100 consecutive once-daily courses of gentamicin or tobramycin, during which 120 pre-dose and 213 sets of immediate post-dose and six hour post-dose levels were taken. By using the six hour post-dose level we were able to compare dosage recommendations made using methods known as ALADDIN, DOSECALC and the Australian Antibiotic Guidelines nomogram (AAGN). There were statistically significant differences in the doses recommended by each method. When comparing each of the three methods, at least 25% of dosage recommendations differed by more than 80 mg per dose. Although we have not been able to determine the clinical significance of these differences, we are concerned that methods used in dosage adjustment of aminoglycosides differ so widely in their recommendations. Presumably the ALADDIN method, which utilises two post-dose levels to determine an area under aminoglycoside concentration-time curve, gives more accurate pharmacokinetic information than methods which rely on a single level. Comparative cost-effectiveness studies of different methods, although in practice difficult to perform, should be undertaken to resolve the optimal management of patients receiving aminoglycosides once-daily.

Adult↗
PubMed1998

Description and validation of a flexible and broadly usable handedness questionnaire.

Empirical evidence is provided which shows that handedness questionnaires should: (a) comprise items that cover skilled and unskilled activities; (b) be sufficiently long to capture a ''mass effect'' of variability in lateral preferences over a range of items; and (c) allow graded answer options for individual items rather than forced left/right choices. When using questionnaires that meet these criteria, it is possible to establish significant correlations between hand preference and performance even within a group of right-handers. In addition, such questionnaires are flexible enough to accommodate a great variety of handedness classification schemes.

Journal Article↗
PubMed1998

Visualising E-selectin in the detection and evaluation of inflammatory bowel disease.

BACKGROUND: Vascular endothelial E-selectin expression is induced by proinflammatory cytokines and contributes to accumulation of leucocytes in tissues. AIMS: To investigate the role of E-selectin in inflammatory bowel disease (IBD). METHODS: E-selectin expression was assessed in patients with ulcerative colitis and Crohn's disease by measuring the concentration of circulating soluble E-selectin (sE-selectin) using ELISA, by immunohistochemistry of colonic biopsy specimens, and by abdominal immunoscintigraphy after injecting radiolabelled F(ab')2 fragment of a monoclonal anti-E-selectin antibody. The value of scintigraphy using anti-E-selectin was judged by a prospective comparative study of autologous leucocyte scanning and E-selectin antibody scanning in 17 patients with IBD. RESULTS: Circulating sE-selectin was elevated in patients with clinically active disease. Tissue expression of E-selectin was enhanced in patients with active inflammation, with weak or absent expression in inactive disease and healthy controls. In-111 labelled anti-E-selectin scintiscans were compared with Tc-99m labelled leucocyte scans performed 24 hours earlier. Twelve patients had areas of active inflammation on leucocyte scan while 11 patients had positive E-selectin scans. The results of the two scans were concordant in 14 patients, with those positive for both (10/17) showing similar disease localisation and extent. CONCLUSIONS: Tissue E-selectin and circulating sE-selectin are increased during active inflammatory bowel disease. Anti-E-selectin imaging with radiolabelled monoclonal antibody identified areas of inflammation in Crohn's disease and ulcerative colitis. The technique should prove useful clinically for identifying the site and extent of disease.

Acute Disease↗
PubMed1998

Memory for locations within regions: spatial biases and visual hemifield differences.

Memory for location of a dot inside a circle was investigated with the circle in the center of a computer screen (Experiment 1) or with the circle presented in either the left or the right visual field (Experiment 2). In both experiments, as in Huttenlocher, Hedges, and Duncan's (1991) study, the task was to relocate the dot by marking the remembered location. When errors in angular and radial estimates were considered separately, it was found that, in both experiments, the angular locations of estimates of the dots' positions regressed toward different locations inside each quadrant of the circle; the radial locations of the estimates of dots' positions tended to regress toward locations near the circumference. These variations in the direction of bias appeared to reflect a general shift of estimates toward the upper left arc of the circle. The second experiment replicated the preceding effects but also revealed that the regressions within quadrants of angular values were stronger after right visual field that after left visual field presentations. We interpret the dissociation between visual fields as evidence that memory for categorical spatial relations (Kosslyn, 1987) is more dependent on left-hemisphere than on right-hemisphere processing.

Female↗