The importance of autonomic nervous system function for theories of cognitive brain function.
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Autonomic Nervous System↗
Biomedical subjects
M Peters
Publications and source records attributed to M Peters.
Immunomodulatory effects of breast milk oligosaccharides.
Breast milk oligosaccharides are excreted in urine in amounts that suggest that they may exist in the circulation at levels compatible with a physiological function. Some oligosaccharides have structural similarity to cellular adhesion molecules and may influence adhesion of cells in breast fed infants. In this study, breast milk oligosaccharides were purified and incubated in assays of cell adhesion. They were found to inhibit neutrophil adhesion to stimulated vascular endothelial cells in a dose dependent fashion. In contrast they enhanced platelet-neutrophil complex formation. These results indicate that breast milk oligosaccharides may play a physiological role in modulating cellular adhesion in vivo.
Absorption↗
Canine neosporosis: clinical and pathological findings and first isolation of Neospora caninum in Germany.
Neosporosis was diagnosed in an 11-week-old puppy of the breed Kleiner Münsterländer with progressive hindlimb paresis. Pathohistological and immunohistological examinations revealed a disseminated infection with Neospora caninum. Parasitic stages were demonstrated in the brain, spinal cord, retina, muscles, thymus, heart, liver, kidney, stomach, adrenal gland, and skin. Immunohistochemistry investigations were carried out using polyclonal rabbit antisera developed against N. caninum tachyzoites and the recombinant bradyzoite-specific antigen BAG-5 of Toxoplasma gondii, which is known to cross-react with N. caninum bradyzoites. BAG-5 antibodies recognized tissue cysts within the CNS and some protozoan stages that were not surrounded by a visible cyst wall. All parasite clusters in the retina and some in muscle tissue stained positively with the BAG-5 antiserum. N. caninum was isolated in cell culture and mice inoculated with brain and spinal cord of the puppy. The new isolate is the first reported in Germany and is designated NC-GER1.
Animals↗
Is leukocytosis a predictor of mortality in severe pertussis infection?
Bordetella pertussis causing severe respiratory failure in infants that is unresponsive to treatment is well described. Pulmonary hypertension is a prominent feature of such cases. In this series of 13 critically ill infants with B. pertussis, hyperleukocytosis ( > 100 x 10(9)/l) was an independent predictor of death. We suggest that such extreme leukocytosis may contribute to disease severity via the formation of aggregates in the pulmonary vasculature.
Blood Gas Analysis↗
A shift of attention may be necessary, but it is not sufficient, for the generation of the Simon effect.
The Simon effect is the performance advantage for spatially corresponding, compared to non-corresponding, target-response ensembles when the location of the target is task irrelevant. In four experiments, we tested the predictions of the attention-shift account of the Simon effect. In all experiments, subject made choice responses with respect to the identity of a central target that followed a spatially non-informative peripheral precue. The first experiment showed a Simon effect away from the precue when the precue was a go/no-go signal: responses to spatially non-corresponding precue-response pairs were faster than responses to spatially corresponding precue-response pairs. The results of the second experiment suggested that this "reverse" Simon effect was not due to inhibition. In the third experiment, a secondary working memory task required the encoding, and later recall, of "oddball" precues. Although the Simon effect was absent, larger Simon effects towards the precue (i.e., responses were faster to spatially corresponding, compared to non-corresponding, precue-response ensembles) were correlated with poorer performance on the memory task. In the last experiment, the identity of completely non-informative precues was congruent, incongruent, or unrelated to the identity of the target. With precues that were unrelated to the identity of the target, there was a Simon effect towards the precues. Conversely, the Simon effect occurred away from the precue when the identity of the precue was related to that of the target. The findings suggest that a shift of attention alone is not sufficient to produce the Simon effect. Rather, the shift of attention must originate from an intentionally defined object. The results are discussed within a framework that integrates the attention-shift and referential-coding hypotheses.
Analysis of Variance↗
Astrocytic alterations in interleukin-6/Soluble interleukin-6 receptor alpha double-transgenic mice.
Interleukin-6 (IL-6), a major cytokine with diverse effects on cells mainly of the immune and hematopoietic systems, has been linked to several neurological disorders such as acquired immune deficiency syndrome dementia, multiple sclerosis, and Alzheimer's disease. Central nervous system (CNS)-specific expression of IL-6 caused neurodegeneration, massive gliosis, and vascular proliferation in transgenic mice. However, the effects of systemically circulating IL-6 and its receptor IL-6Ralpha on the CNS are unknown. IL-6Ralpha is the specific component of the IL-6 receptor system and hence an important co-factor of IL-6. IL-6Ralpha is bioactive in a membrane-bound and in a soluble (s) form. We investigated the effects of systemically elevated levels of either human IL-6 or human sIL-6Ralpha or both on the CNS of transgenic mice. Although IL-6 and sIL-6Ralpha single transgenic mice were free of neurological disease, IL-6/sIL-6Ralpha double-transgenic mice showed neurological signs, such as tremor, gait abnormalities, and paresis. However, these mice also frequently showed prominent general weakness probably because of the systemic effects of IL-6/IL-6Ralpha such as liver damage and plasmacytomas. IL-6/sIL-6Ralpha transgenic mice exhibited massive reactive gliosis. Lack of signs of neuronal breakdown versus ample astrogliosis suggested that astrocytes were selectively affected in these mice. There was neither vascular proliferation nor inflammatory infiltration. Ultrastructural analysis revealed blood-brain barrier (BBB) changes manifested by hydropic astrocytic end-feet. However, albumin immunohistochemistry did not reveal major BBB leakage. Our results indicate that increased and constitutive systemic expression of IL-6 together with its soluble receptor sIL-6Ralpha is less harmful to the brain than to other organs. The BBB remains primarily intact. IL-6/IL-6Ralpha, however, might be directly responsible for the selective activation of astrocytes.
Animals↗
Comparison of overall brain volume and midsagittal corpus callosum surface area as obtained from NMR scans and direct anatomical measures: a within-subject study on autopsy brains.
Formalin fixed brains obtained from autopsy were studied by magnetic resonance imaging, using FLASH and MPR sequences. The overall volume and the midsagittal surface area of the corpus callosum (cc) of these brains were also directly measured by water displacement for overall volume determination and morphometry for cc surface area measures, allowing comparisons of these measures in a within-subject design. Thin NMR sections (1 mm thickness for FLASH and 1.25 mm for MPR) yielded overall brain volume estimates that did not differ significantly from direct volume estimations but thicker (5 mm) sections led to a significant overestimation of brain volume for NMR measures relative to direct displacement measures. There was no overall effect of type of NMR measure: FLASH and MPR scans did not yield significantly different values for overall brain volume or callosal surface area. Direct and NMR measures of the corpus callosum surface at midsagittal level did not yield significantly different estimates.
Aged↗
fMRI study of bimanual coordination.
Eleven right-handed subjects performed uni- and bimanual tapping tasks. Hemodynamic responses as measured with functional magnetic resonance imaging (fMRI) in the primary somato-motor cortex (SMC) showed that during bimanual activity the SMC contralateral to the hand taking the faster rate was more strongly activated than the SMC contralateral to hand taking the slower rate. There were no asymmetries, left SMC activation during the right fast/left slow tapping condition was comparable to the right SMC activation during the left fast/right slow condition. A given SMC showed similar activation levels for bimanual and unimanual activity (i.e. left SMC activation for right fast/left slow was similar to left SMC activation for the right fast unimanual condition). In contrast, a given supplementary motor area (SMA) showed significantly more activation for the bimanual than for the unimanual activity. In addition, an asymmetry was observed during bimanual activities: during the right fast/left slow activity, the left SMA showed more activation than the right SMA, but during the left fast/right slow activity, the right SMA was not significantly more activated than the left SMA. For unimanual activities, a clear rate effect (greater activation for faster rate) was seen in the SMC but not in the SMA.
Adult↗
A phase I/II study of recombinant human interleukin-12 in patients with chronic hepatitis B.
BACKGROUND/AIMS: Interleukin-12 (IL-12) may be active against hepatitis B virus (HBV). The objective of the study was to assess the tolerability, activity, pharmacokinetics, and pharmacodynamics of three dose levels (0.03 microg/kg b.w., n=15; 0.25 microg/kg b.w., n=15; 0.50 microg/kg b.w., n=16) of recombinant human (rHu) IL-12 given s.c. once a week for 12 consecutive weeks. METHODS: Forty-six patients with chronic hepatitis B, HBV DNA positivity and aminotransferase elevation were included in a multicenter prospective randomized phase I/II study. RESULTS: Compared with the baseline, HBV DNA levels had decreased significantly at the end of rHuIL-12 treatment and after the 12-week follow-up period (p<0.001). The response to rHuIL-12 treatment was dose-dependent: at the end of the study HBV DNA clearance was greater in patients treated with 0.50 microg/kg b.w. (25%) or with 0.25 microg/kg b.w. (13%) compared with those given 0.03 microg/kg b.w. (7%). Moreover, HBeAg became undetectable at the end of follow-up in five of the patients given the 0.25microg/kg (2/15) or the 0.50 microg/kg (3/16) dose. The drug pharmacology showed that IL-12 had an estimated half-life of 30 h with levels remaining detectable for more than 48 h after rHuIL-12 administration. The serum levels of IL-12, interferon-gamma, IL-10, neopterin and beta2-microglobulin as well as the area under the curve (AUC) were rHuIL-12 dose-related. Side effects were observed more frequently with higher doses, including moderate decreases in lymphocyte and neutrophil counts; three patients withdrew prematurely from treatment. The local reaction observed at the injection site was unrelated to the drug dose. Only one patient showed detectable antibody levels to rHuIL-12 without clinical impact. CONCLUSIONS: Treatment with rHuIL-12 at the doses investigated is safe and tolerable, and appears to be active against HBV in patients with chronic hepatitis B.
Adjuvants, Immunologic↗
Cortical activations in primary and secondary motor areas for complex bimanual movements in professional pianists.
Hemodynamic responses were measured applying functional magnetic resonance imaging in two professional piano players and two carefully matched non-musician control subjects during the performance of self-paced bimanual and unimanual tapping tasks. The bimanual tasks were chosen because they resemble typical movements pianists have to generate during piano exercises. The results showed that the primary and secondary motor areas (M1, SMA, pre-SMA, and CMA) were considerably activated to a much lesser degree in professional pianists than in non-musicians. This difference was strongest for the pre-SMA and CMA, where professional pianists showed very little activation. The results suggest that the long lasting extensive hand skill training of the pianists leads to greater efficiency which is reflected in a smaller number of active neurons needed to perform given finger movements. This in turn enlarges the possible control capacity for a wide range of movements because more movements, or more 'degrees of freedom', are controllable.
Adult↗
Paediatric intensive care transfers: 1.
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Child↗
Intracellular accumulation of factor VIII induced by missense mutations Arg593-->Cys and Asn618-->Ser explains cross-reacting material-reduced haemophilia A.
Patients with cross-reacting material (CRM)-reduced haemophilia A exhibit reduced levels of factor VIII antigen. In this study, we determined the molecular basis of the genetic defect in the factor VIII gene induced by either the Arg593-->Cys or the Asn618-->Ser missense mutation, identified in two CRM-reduced haemophilia A patients. We introduced either the Arg593-->Cys or the Asn618-->Ser mutation into a B-domain-deleted factor VIII cDNA and expressed the modified cDNAs in C127 cells. Reduced levels of factor VIII activity and factor VIII antigen in conditioned medium of transfected cells indicated that the secretion of both factor VIII variants was impaired. The ratio of factor VIII antigen present in cell extract to that in conditioned medium was 1.9 and 2.4 times higher for rFVIII-R593C and rFVIII-N618S, respectively, than for rFVIII. Metabolic labelling and immunoprecipitation of transfected cells revealed that rFVIII-R593C and rFVIII-N618S persisted somewhat longer inside the cell than factor rFVIII. Intracellular accumulation and subsequent degradation of factor VIII-R593C and factor VIII-N618S may explain the reduced levels of both factor VIII activity and antigen in plasma of mild haemophilia A patients with corresponding genetic defects.
Cross Reactions↗
Mutations in the thrombopoietin receptor, Mpl, in children with congenital amegakaryocytic thrombocytopenia.
Congenital amegakaryocytic thrombocytopenia (CAMT) is a rare disorder of undefined aetiology. The disease presents with severe thrombocytopenia and absence of megakaryocytes in the bone marrow. Furthermore, CAMT patients may develop bone marrow aplasia. To obtain more insight into the mechanism underlying CAMT, five children were analysed. All patients had increased plasma thrombopoietin (Tpo) levels, indicating a platelet production defect. Bone marrow-derived CD34+ stem cells from three patients were cultured in an in vitro liquid culture system to study megakaryocytopoiesis. CD34+ cells from two of the three patients failed to differentiate into megakaryocytes. The lack of megakaryocyte formation could imply that a defect in the c-mpl gene, encoding the Tpo receptor, exists. Sequencing of c-mpl revealed mutations in four of five patients. Three patients had point mutations and/or a deletion in the coding regions of c-mpl. All point mutations led to an amino acid substitution or to a premature stop codon. In one patient, a homozygous mutation in the last base of intron 10 was found that resulted in loss of a splice site. This study showed that mutations in c-mpl could be the cause of thrombocytopenia in CAMT in the majority of patients. Furthermore, Tpo has been shown to have an anti-apoptotic effect on stem cells. Therefore, mutations in c-mpl might not only affect megakaryocyte formation but may also impair stem cell survival, which could explain the occurrence of bone marrow failure as final outcome in patients with CAMT.
Amino Acid Substitution↗
Serological investigations of red foxes (Vulpes vulpes L.) for determination of the spread of tick-borne encephalitis in Northrhine-Westphalia.
Serum samples from 786 red foxes shot between January 1995 and August 1996 in the southern half of Northrhine-Westphalia, located in western Germany, were tested for the presence of antibodies against tick-borne encephalitis (TBE) virus using the Immunozym FSME IgG All Species-ELISA (Immuno, Heidelberg, Germany) as a screening test: 759 sera were negative, 23 (2.9%) were borderline, and four (0.5%) were positive. Nine of the 27 ELISA reactive sera were confirmed by the TBE Western-Blot (Immuno, Heidelberg, Germany). Furthermore these 27 sera were tested for neutralizing antibodies by means of a plaque reduction neutralization test (PRNT) against TBE and West Nile viruses. Only one single serum was found to have a neutralization titre (+1:800 PRNT80) against TBE virus. All other 26 sera were negative for neutralizing antibodies against TBE or West Nile virus. Since the titre of the single serum is low, it can be interpreted that if TBE virus is present, its prevalence is extremely low. Northrhine-Westphalia is not classified as a TBE-endemic area. Further calculated serological testing of game and virological investigation of collected ticks in the affected area seem to be meaningful and necessary.
Animals↗
Combined interleukin 6 and soluble interleukin 6 receptor accelerates murine liver regeneration.
BACKGROUND & AIMS: Liver regeneration after loss of hepatic tissue leads to hepatocyte and nonparenchymal cell proliferation and rapid restoration of liver parenchyma. Interleukin (IL)-6 is a key inducer of transcription factors involved in liver regeneration. Whenever IL-6 activates target cells, it binds to a specific IL-6 receptor (IL-6R). The IL-6/IL-6R complex then associates with the signal transducer gp130, leading to activation of intracellular signaling. METHODS: We have recently constructed the designer cytokine Hyper-IL-6 consisting of soluble IL-6R covalently linked to IL-6, which directly stimulates gp130 even in the absence of membrane-bound IL-6R. We compared the influence of IL-6 and Hyper-IL-6 on liver regeneration after partial hepatectomy in mice. RESULTS: The IL-6/soluble IL-6 fusion protein Hyper-IL-6, but not IL-6 alone, led to an earlier onset of hepatocellular proliferation resulting in an acceleration of liver weight restoration. Also, during liver regeneration, soluble IL-6R levels were increased. CONCLUSIONS: These results emphasize a central role for IL-6 and soluble IL-6R in liver regeneration and indicate a possible therapeutic potential for the designer cytokine Hyper-IL-6 in clinical situations associated with liver regeneration such as acute hepatic failure or resection of chronically damaged liver tissue.
Animals↗
Safe motherhood beyond the year 2000: a global perspective.
It would appear that many people are of the opinion that the arrival of the new century will mean the disappearance of maternal mortality. Unfortunately, that is not the case. In this paper the direct and indirect causes of maternal mortality are presented, successful strategies are described and the challenges for society and midwives in the new century are laid down.
Female↗
Carbohydrate-deficient glycoprotein syndrome type 1a: a variant phenotype with borderline cognitive dysfunction, cerebellar hypoplasia, and coagulation disturbances.
An 8-year-old boy is described with borderline cognitive impairment, cerebellar hypoplasia, a stroke-like episode, and venous thrombosis of the left leg after a period of immobilization. The pattern of multiple abnormalities in blood coagulation suggested carbohydrate-deficient glycoprotein syndrome type 1a. Isoelectric focusing of serum transferrin was abnormal. The activity of phosphomannomutase in leukocytes and fibroblasts was decreased. Mutation analysis of the PMM2 gene revealed the R141H/E151G genotype. These results confirm the presence of carbohydrate-deficient glycoprotein syndrome type 1a without severe psychomotor retardation.
Blood Coagulation Disorders↗