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Biomedical subjects

M Peters

Publications and source records attributed to M Peters.

At least 19 recordsLinked to original sources
PubMed2007

Calcium/calmodulin kinase kinase beta has a male-specific role in memory formation.

The calcium/calmodulin (CaM) kinase cascade regulates gene transcription, which is required for long-term memory formation. Previous studies with Camkk2 null mutant mice have shown that in males calcium/calmodulin kinase kinase beta (CaMKKbeta) is required for spatial memory formation and for activation of the transcription factor cyclic AMP-responsive element binding protein (CREB) in the hippocampus by spatial training. Here we show that CaMKKbeta is not required for spatial memory formation in female mice as female Camkk2 null mutants were not impaired in spatial memory formation and they had the same level of hippocampal CREB phosphorylation after spatial training as female wild-type mice. Furthermore, we show that male but not female Camkk2 null mutants were impaired in long-term potentiation (LTP) at hippocampal CA1 synapses. Finally, a transcriptional analysis of male Camkk2 null mutants led to the identification of a gene, glycosyl phosphatidyl-inositol anchor attachment protein 1 (GAA1), whose hippocampal mRNA expression was up-regulated by spatial and contextual training in male but not in female wild-type mice. Taken together, we conclude that CaMKKbeta has a male-specific function in hippocampal memory formation and we have identified male-restricted transcription occurring during hippocampal memory formation.

Animals↗
PubMed2006

Safety and feasibility of exhaled breath condensate collection in ventilated infants and children.

The aim of this study was to develop a technique for the collection of exhaled breath condensate (EBC) from ventilated children and assess its safety and feasibility. Collection of EBC is used to investigate markers of oxidative stress in the lower airway. No studies have assessed its safety in ventilated children. An in vitro model was developed by connecting a ventilator to an artificial lung; 14 clinical and ventilatory parameters were measured during EBC collection from ventilated children. Levels of 8-isoprostane were measured following collection with and without humidification of the inhaled gas. Amount of water vapour collected was linearly related to time and to minute ventilation in the in vitro model. EBC collections (n = 68) were made from ventilated children. In the nonhumidified group, the mean (range) positive end-expiratory pressure increased by 4.1% (2.8-5.5%) and the peak inspiratory flow decreased by 6.1% (11.0-1.3%) during collection. Detectable levels of 8-isoprostane were only found in 10 out of 18 nonhumidified EBC samples (median (range) 4.7 pg x mL(-1) (0-5.8)). Collection of exhaled breath condensate from ventilated infants and children is feasible and safe. Discontinuation of humidification is likely to be important in standardising the measurement of inflammatory parameters in exhaled breath condensate collected from ventilated children.

Air↗
PubMed2006

Evaluation of chemotherapy with magnetic resonance imaging in patients with regionally metastatic or unresectable bladder cancer.

OBJECTIVES: To determine whether the failure of chemotherapy in patients with regionally metastatic or unresectable transitional cell carcinoma (TCC) of the bladder can be predicted early in the course of chemotherapy with magnetic resonance (MR) imaging. METHODS: In this prospective study, 36 patients with regionally metastatic or unresectable TCC of the urinary bladder underwent MR imaging before and after two, four, and six cycles of chemotherapy with Methotrexate, Vinblastine, Adriamycin (doxorubicin) and Cisplatin (MVAC). The response after two cycles of MVAC was evaluated by using conventional tumour size parameters with unenhanced MR imaging and with changes in the time to the start of tumour or lymph node enhanced at fast dynamic contrast-enhanced MR imaging. The results obtained with these techniques were compared with the findings at histopathology in cystectomy or transurethral resection specimens that were obtained after chemotherapy. Duration of survival was defined as the time from the start of chemotherapy until disease-specific death. Kaplan-Meier curves were drawn to determine the difference in prognosis between responders and nonresponders. RESULTS: After two cycles of chemotherapy, the accuracy, sensitivity, and specificity in distinguishing responders from nonresponders with conventional MR imaging were 69%, 81%, and 50%, respectively. With the fast dynamic contrast-enhanced technique, accuracy, sensitivity, and specificity were 92%, 91%, and 93% respectively. The median bladder cancer specific survival was 28 months for all patients studied. Responders to chemotherapy at fast dynamic contrast-enhanced MR had better median disease-specific survival than nonresponders (42 months vs. 12 months [p<0.0001]). CONCLUSION: We can predict whether a patient will respond to chemotherapy after two cycles of chemotherapy with fast dynamic contrast-enhanced MR imaging.

Adult↗
PubMed2006

Enhanced memory performance on an internal-internal source monitoring test following acute psychosocial stress.

Research on the effect of acute stress and high levels of glucocorticoids on memory has largely focused on memory tasks involving the medial temporal lobe (e.g., declarative memory). Less is known, however, about the effects of stress and glucocorticoids on more strategic memory processes regulated by the prefrontal cortex (e.g., source monitoring). In the current study, the authors investigated whether exposure to acute psychosocial stress would result in altered source monitoring performance relative to the performance of a nonstressed control group. To this end, the authors assigned nonsmoking, healthy, young men to either a stress (n = 22) or a control (n = 18) condition, after which the men were given an internal source monitoring test. Results show that relative to control participants, stressed participants made fewer source monitoring errors. This study suggests that stress may have differential effects on memory, depending on whether the memory test is regulated by the prefrontal cortex or the medial temporal lobe.

Adult↗
PubMed2006

American foulbrood of the honey bee: occurrence and distribution of different genotypes of Paenibacillus larvae in the administrative district of Arnsberg (North Rhine-Westphalia).

Between March 2003 and October 2004, Paenibacillus larvae, the aetiological agent of American foulbrood disease of the honey bee, was isolated from broodcombs and honey samples of 54 apiaries in the administrative district of Arnsberg (North Rhine-Westphalia, Germany). Genotyping of 176 P. larvae isolates with repetitive element polymerase chain reaction fingerprinting (rep-PCR) using BOX A1R and MBO REP1 primers revealed five different genotypes (AB, Ab, ab, ass, Acapital BE, Cyrillic). In samples of three apiaries, more than one genotype was detected. A combination of two genotypes was isolated from honey samples of the same hive two times (ab/ass and Ab/ab). The five genotypes were not randomly distributed in the district, but revealed a certain geographical clustering. Possible factors with impact on the genotype diversity and the distribution pattern are discussed.

Animals↗
PubMed2006

Mortality and causes of death in patients with hemophilia, 1992-2001: a prospective cohort study.

BACKGROUND: Clotting factor products have been safe for HIV since 1985, and for hepatitis C since 1992. Few studies have reported on mortality in the total population of hemophilia patients after the period of risk of viral infection transmission. OBJECTIVES: We studied the mortality, causes of death, and life expectancy of hemophilia patients between 1992 and 2001. We compared these findings with those of previous cohorts, together spanning the periods before, during, and after the use of potentially contaminated clotting products. PATIENTS AND METHODS: We performed a prospective cohort study among 967 patients with hemophilia A and B. Death rates, overall and cause-specific, were compared with national mortality figures for males adjusted for age and calendar period as standardized mortality ratio (SMRs). RESULTS: Between 1992 and 2001, 94 (9.7%) patients had died and two patients were lost to follow-up (0.2%). Mortality was 2.3-times higher in hemophilia patients than in the general male population (SMR 2.3 95% confidence interval 1.9-2.8). In patients with severe hemophilia, life expectancy decreased from 63 (1972-1985) to 59 years (1992-2001). Exclusion of virus-related deaths resulted in a life expectancy at birth of 72 years. CONCLUSIONS: AIDS was the main cause of death (26%) and 22% of deaths were because of hepatitis C. In patients not affected by viral infections, there still appeared to be a trend toward a moderately increased mortality compared with the Dutch male population. Thus, mortality of patients with hemophilia is still increased; this is largely because of the consequences of viral infections.

Adolescent↗
PubMed2005

Inhalation of stable dust extract prevents allergen induced airway inflammation and hyperresponsiveness.

BACKGROUND: Recent epidemiological studies have shown that growing up on a traditional farm provides protection from the development of allergic disorders such as hay fever and allergic asthma. We present experimental evidence that substances providing protection from the development of allergic diseases can be extracted from dust collected in stables of animal farms. METHODS: Stable dust was collected from 30 randomly selected farms located in rural regions of the Alps (Austria, Germany and Switzerland). The dust was homogenised with glass beads and extracted with physiological sodium chloride solution. This extract was used to modulate immune response in a well established mouse model of allergic asthma. RESULTS: Treatment of mice by inhalation of stable dust extract during sensitisation to ovalbumin inhibited the development of airway hyperresponsiveness and airway eosinophilia upon challenge, as well as the production of interleukin 5 by splenocytes and of antigen specific IgG(1) and IgE. Dust extract also suppressed the generation of human dendritic cells in vitro. The biological activity of the dust extract was not exclusively mediated by lipopolysaccharide. CONCLUSIONS: Stable dust from animal farms contains strong immune modulating substances. These substances can interfere with the development of both cellular and humoral immunity against allergens, thus suppressing allergen sensitisation, airway inflammation, and airway hyperresponsiveness in a murine model of allergic asthma.

Allergens↗
PubMed2005

[Haemolytic anaemia and a clotting disorder as first signs of cystic fibrosis in two infants].

2 infants, a boy aged 8 weeks and a girl aged 5 months, presented with symptoms of fat-soluble vitamin deficiencies. The first infant had frequently voluminous bowel movements, anaemia and was not thriving; he had anaemia due to vitamin-E deficiency. The second infant had multiple haematomas on the trunk and legs due to a vitamin-K deficiency-related clotting disorder. The sweat test was positive in both cases, confirming the diagnosis of cystic fibrosis. The infants were treated with supplementary pancreatic enzymes and fat-soluble vitamins A, D, E and K. Cystic fibrosis rarely presents with symptoms of fat-soluble vitamin deficiency. However, in cases of unexplained haemolytic anaemia or haemorrhagic disorder due to vitamin E or K deficiencies, respectively, cystic fibrosis should be considered as a possible cause.

Anemia, Hemolytic↗
PubMed2005

[Pathophysiology and treatment of sickle-cell disease].

Sickle-cell disease is a hereditary haemoglobinopathy caused by a mutation in the beta-globin gene. The disease is characterised by recurrent vaso-occlusive crises resulting in severe organ damage and a sharply reduced life expectancy. The formation of haemoglobin-S polymers in hypoxic conditions plays a pivotal role in sickle-cell disease and produces the characteristic phenotype of sickle-shaped erythrocytes that promote vasoocclusion. Endothelial cell activation, enhanced erythrocyte and leukocyte adhesion, vasoconstriction and coagulation activation play an important role in vaso-occlusive crises. Treatment of pain and hydration remain the main interventions in the management ofvaso-occlusive crises. Hydroxyurea has been shown to prevent vaso-occlusive crises by increasing the amount of foetal haemoglobin. Allogeneic stem-cell transplantation is the only curative therapy. However, transplantation-related mortality, graft-versus-host disease and the limited availability of HLA-identical donors restrict this therapeutic option.

Anemia, Sickle Cell↗
PubMed2005

[The treatment of chronic hepatitis C virus infection in children].

A 9-year-old boy, a 15-year-old boy, and a 6-year-old girl were infected with chronic hepatitis C virus (HCV). They had no physical complaints and a virus genotype that was favourable to treatment with peginterferon-alpha and ribavirin. The younger boy and the girl had liver fibrosis and were treated for 6 months; the virus was eradicated from the boy's plasma and the fibrosis diminished, while the girl's plasma virus was again present shortly after the end of treatment. In the older boy with no fibrosis, treatment was temporarily suspended due to behaviour problems. HCV infection is a frequent cause of chronic hepatitis in children. A better understanding of its natural history, improvements in the efficacy of treatment, and more favourable outcomes seen in children compared with adults have gradually changed the consideration to treat children with chronic HCV infection over the last 10 years. The decision whether or not to treat depends primarily on the degree of liver damage, virus genotype, and the psychological condition and motivation of the patient. Screening patients at risk for chronic HCV infection and careful follow-up for liver damage in those with HCV infection have become even more important given the new insights regarding treatment.

Adolescent↗
PubMed2005

Cellular and complement-dependent cytotoxicity of Ep-CAM-specific monoclonal antibody MT201 against breast cancer cell lines.

MT201 is a fully human monoclonal IgG1 antibody with moderate affinity for epithelial cell adhesion molecule (Ep-CAM) being clinically developed for the treatment of carcinomas. Like many other clinically validated IgG1 monoclonal antibodies, MT201 primarily acts by antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). Here, we analysed ADCC and CDC induced by MT201 and, as reference, trastuzumab against a panel of nine human breast cancer cell lines expressing distinct surface levels of Ep-CAM and human epithelial growth factor receptor type 2 antigen. Maximal cell lysis by ADCC by MT201 and trastuzumab in the presence of peripheral mononuclear cells did not significantly differ when averaged over the nine cell lines, but showed marked differences with respect to individual cell lines. The extent of cell lysis at intermediate surface target density was highly variable, suggesting a dominant influence of other susceptibility factors. Only one breast cancer cell line was eliminated via CDC, but only by MT201. Resistance to CDC appeared to correlate with high expression levels of complement resistance factors. Our present data as well as recent data on the prevalence and prognostic relevance of Ep-CAM expression in metastatic breast cancer suggest that Ep-CAM-specific monoclonal IgG1 antibodies may have a significant therapeutic potential in the treatment of breast cancer.

Animals↗
PubMed2005

Imported leishmaniasis in Germany 2001-2004: data of the SIMPID surveillance network.

Leishmaniasis is a rare, non-notifiable disease in Germany. Epidemiological and clinical data, therefore, are scarce. Most infections seen in Germany are contracted outside the country. The German surveillance network for imported infectious diseases (Surveillance Importierter Infektionen in Deutschland, or SIPMID) recorded 42 cases of imported leishmaniasis (16 visceral, 23 cutaneous, and 3 mucocutaneous) from January 2001 to June 2004. Although most infections were acquired in European Mediterranean countries, the risk of infection was highest for travelers to Latin America. HIV coinfection was observed significantly more often in patients with visceral leishmaniasis than in patients with cutaneous/mucocutaneous leishmaniasis (31 vs. 4%, p=0.02). The median time to a definitive diagnosis was 85 days in cases of visceral leishmaniasis and 61 days in cases of cutaneous/mucocutaneous leishmaniasis, reflecting the unfamiliarity of German physicians with leishmanial infections. Visceral leishmaniasis was treated most frequently with amphotericin B, whereas cutaneous/mucocutaneous leishmaniasis was treated with a variety of local and systemic therapies. The findings presented here should serve to increase awareness as well as improve clinical management of leishmaniasis in Germany.

Adolescent↗
PubMed2005

Congenital deficiency of factor XIII caused by two missense mutations in a Dutch family.

We present the clinical, biochemical and genomic findings of a family with congenital factor XIII (FXIII) deficiency. Congenital FXIII deficiency is a very rare autosomal recessive bleeding disorder, characterized by umbilical cord bleeding at birth and spontaneous intracranial haemorrhage. Routine clotting tests are normal, which may delay the diagnosis, leading to an increased chance of severe sequelae. The propositus and her brother, known with haemorrhagic diathesis, were found to be compound heterozygous with a known missense mutation (1050 G --> T transversion in exon 7, Val316Phe substitution) and a novel mutation 889 G --> A in exon 6, which predicts a Gly262Glu substitution. As these mutations were known in the family, DNA obtained from cord blood of the youngest sister was analysed for mutations in exons 6 and 7 only. We postulate that the diagnosis was facilitated by determining the two different mutations in the genotype of this family. The analysis showed that she was heterozygous for the exon 7 mutation. Hence, she was not at risk of experiencing haemorrhagic diathesis. This diagnosis avoided the administration of FXIII concentrate to the newborn.

Adult↗
PubMed2004

Does handedness influence the strength of phantom limb illusions in the virtual reality box?

Subjects had to judge the size of a tactile stimulus held in the unseen hand, while a visible phantom hand representing that unseen hand held a tactile stimulus of same or different size. No asymmetries in interference effects were found that could be related to hand or handedness. The method lends itself to quantification of virtual reality box illusions and can be used to evaluate the role of experience and sources of variability in the strength of the illusion across subjects.

Computer Simulation↗
PubMed2004

Hyperglycemia is associated with increased morbidity and mortality rates in neonates with necrotizing enterocolitis.

BACKGROUND PURPOSE: An association between hyperglycaemia and poor outcome has been reported in critically ill adults and children. The authors investigated the incidence of hyperglycemia in infants with necrotizing enterocolitis (NEC) and the relationship between glucose levels and outcome in these infants. METHODS: All glucose measurements (n = 6508) in 95 neonates with confirmed NEC admitted to the surgical intensive care unit (ICU) were reviewed. Maximum glucose concentration during admission (Gmax) was determined for each infant and correlated with outcome. Eleven infants in whom treatment was withdrawn within 24 hours owing to unsalvageable panintestinal NEC were excluded from the analysis. RESULTS: Glucose levels ranged from 0.5 to 35.0 mmol/L and 69% of infants became hyperglycemic (>8 mmol/L) during their admission. Thirty-two infants died. Mortality rate tended to be higher in infants with Gmax greater than 11.9 mmol/L compared with those with Gmax less than 11.9 mmol/L, and late (>10 days admission) mortality rate was significantly higher in these infants (29% v, 2%; P =.0009). Median length of stay was 9.3 days. Linear regression analysis indicated that Gmax was significantly related to length of stay (P <.0001). CONCLUSIONS: Hyperglycemia is common in infants with NEC admitted to the ICU and is associated with an increase in late mortality and longer intensive care stay. Aggressive glycemic control may improve outcome in this group of infants.

Birth Weight↗
PubMed2004

S100B potently activates p65/c-Rel transcriptional complexes in hippocampal neurons: Clinical implications for the role of S100B in excitotoxic brain injury.

Increased serum levels of S100B are positively correlated with multiple forms of CNS damage, such as stroke, CNS trauma and neurodegenerative diseases, but also in psychiatric disorders. However, it is currently not known whether increased serum levels of S100B reflect a neuroregenerative or neurodegenerative response. Since glutamate receptor overactivation (excitotoxicity) may contribute to neuronal pathology in psychiatric disorders, we investigated the effect of S100B on N-methyl-d-aspartate (NMDA)-induced neuronal cell death. Here we demonstrate that very low concentrations of S100B significantly protect primary rat hippocampal neurons against NMDA toxicity by activation of transcription factors of the Rel/nuclear factor kappaB (NF-kappaB) family. Further experiments suggest that i) S100B activated expression of the receptor of advanced glycation products (RAGE) gene in neurons and ii) S100B induced a unique composition of the active NF-kappaB complex consisting of the p65 and c-Rel subunits suggesting a novel mechanism for NF-kappaB activation involved in S100B-mediated neuroprotection. Our data suggest that S100B secreted during the glial response to brain injury potently activates p65/c-Rel in a RAGE-dependent manner and may exert neuroprotective and neuroregenerative effects in psychiatric disorders.

Animals↗