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M Frosch

Publications and source records attributed to M Frosch.

At least 19 recordsLinked to original sources
PubMed2006

Clinical and biochemical correlates of insoluble alpha-synuclein in dementia with Lewy bodies.

Alpha-synuclein is a major constituent of Lewy bodies, the fibrillar aggregates that form within neurons in Parkinson's disease and dementia with Lewy bodies (DLB). Recent biochemical data show that alpha-synuclein accumulates in Parkinson's disease in a detergent insoluble form. We now examine the relationship between detergent insoluble alpha-synuclein and the presence of Lewy bodies, clinical measures of dementia and biochemical parameters in a series of individuals with DLB. We found that Triton X-100 insoluble alpha-synuclein enriched nearly twofold in the temporal cortex of patients with DLB compared to age-matched controls. By contrast the total amount of alpha-synuclein protein was unchanged. Surprisingly, the degree of Triton X-100 insoluble alpha-synuclein did not correlate with either the duration of illness or the number of Lewy bodies counted using stereological methods from an adjacent block of tissue. However, the Triton X-100 soluble fraction of alpha-synuclein did correlate strongly with the expression of several heat shock proteins (HSPs) in DLB but not control cases, suggesting a coordinated HSP response in DLB neocortex.

Aged↗
PubMed2006

First case of febrile bacteremia due to a wild type and small-colony variant of Escherichia coli.

Reported here is a case of a febrile illness caused by a wild type and small-colony variant of Escherichia coli in an anorectic patient. A review of the literature revealed that the formation of small-colony variants in E. coli has been recognized since 1931. In recent years, an association has been established between those variants and chronic recurrent infections. This report describes for the first time the isolation of an E. coli small-colony variant from a blood culture of a patient who had suffered from chronic urinary tract infections in the past.

Adult↗
PubMed2004

Methotrexate treatment in juvenile idiopathic arthritis: when is the right time to stop?

OBJECTIVES: To investigate whether prolonged methotrexate (MTX) treatment after induction of remission influences the subsequent duration of remission in patients with juvenile idiopathic arthritis (JIA), and to analyse the usefulness of myeloid related proteins 8 and 14 (MRP8/MRP14) as predictive markers for the stability of remission at the time when MTX is withdrawn. METHODS: Twenty five patients with oligoarticular and polyarticular JIA who received MTX to induce remission were followed up. MTX treatment was stopped after a mean of 3.8 months (group 1) or 12.6 months (group 2) after remission was documented. Differences in the number of relapses between these groups were looked for. Additionally, MRP8/MRP14 were analysed by ELISA in 22 patients. RESULTS: No difference was found in the number of relapses between patients with prolonged or early discontinued MTX treatment. Patients who were in stable remission had significantly lower MRP levels when MTX was discontinued than patients with relapses. With a cut off point for MRP8/MRP14 at 250 ng/ml, sensitivity and specificity were 100% and 70%, respectively. CONCLUSION: Longer duration of MTX treatment after induction of remission does not generally improve the status of remission in patients with JIA. Residual synovial inflammation seems to influence the rate of relapses after discontinuation of MTX treatment. MRP8/MRP14 indicate residual activity even in the absence of other laboratory or clinical signs of continuing inflammation. Normal serum concentrations of MRP8/MRP14 in clinical inactive arthritis may help to identify patients in whom MTX can be safely withdrawn after remission is achieved.

Adult↗
PubMed2003

Postmortem isolation of Pseudotaeniolina globosa from a patient with aortic aneurysm.

We describe the isolation of the melanized meristematic fungus Pseudotaeniolina globosa from the aortic wall of a patient who died while undergoing surgery for aortic aneurysm and aortic valve regurgitation as a result of dilated cardiomyopathy. Meristematic fungi related to P. globosa have until now been considered as environmental saprobes found predominantly in ecological niches with low water activity. The isolate was identified by phenotypic analyses and by sequencing of the rDNA internal-transcribed spacer domain. The clinical significance of this isolation remains unclear but isolation of meristematic fungi from clinical specimen should be thoroughly evaluated in terms of their significance in future.

Aorta↗
PubMed2003

Combined surgical and antifungal treatment of a subcutaneous infection due to Paecilomyces lilacinus.

Paecilomyces lilacinus was the causal agent of a case of subcutaneous infection in a patient with liver cirrhosis. Surgical treatment in combination with systemic amphotericin B therapy led to complete recovery. Retrospectively performed microdilution testing revealed dose dependent in vitro susceptibility of the isolate to voriconazole (MIC = 2 g/ml) and terbinafine (MIC = 1 microg/ml).

Abscess↗
PubMed2003

Myeloid related protein 8 and 14 secretion reflects phagocyte activation and correlates with disease activity in juvenile idiopathic arthritis treated with autologous stem cell transplantation.

OBJECTIVES: To determine whether myeloid related proteins (MRP8/MRP14), a complex of two S100 proteins related to neutrophil and monocyte activation, might be used as a marker for disease activity, and as an early indicator of relapse in juvenile idiopathic arthritis. PATIENTS AND METHODS: A group of 12 patients who underwent an autologous haematopoietic stem cell transplantation (ASCT) for refractory juvenile idiopathic arthritis (JIA) were studied. MRP8/MRP14 serum concentrations were determined by a sandwich enzyme linked immunosorbent assay (ELISA) as described. Improvement from baseline was described by a definition of improvement employing a core set of criteria as detailed previously by Giannini. RESULTS: After ASCT, MRP8/MRP14 serum concentrations in JIA showed a positive correlation with the Child Health Assessment Questionnaire (CHAQ; r=0.80) and erythrocyte sedimentation rate (r=0.45), but not with the total leucocyte count (r=0.26). Mean MRP8/MRP14 serum concentrations dropped markedly in the first three months after ASCT (p=0.0039) and clinical parameters of disease activity such as CHAQ markedly improved (p=0.0039). During a transient relapse there was an increase in MRP8/MRP14. CONCLUSIONS: MRP8/MRP14 serum concentration can be used as a marker for disease activity in patients who receive an ASCT for refractory JIA. This indicates a role of macrophage activation in the pathogenesis of JIA. The occurrence of MAS in three patients in this study was not preceded by significant changes in MRP8/MRP14 concentration.

Adolescent↗
PubMed2003

Arthrosonography of hip and knee joints in the follow up of juvenile rheumatoid arthritis.

OBJECTIVE: To evaluate sensitivity of arthrosonography of hip and knee joints for monitoring disease activity in juvenile rheumatoid arthritis (JRA). METHODS: Twenty eight patients with JRA with active disease at entry in 15 hips and 38 knee joints were followed up three times in intervals of 4-6 weeks. Sonographic, clinical, and laboratory findings were documented at the same time in clinically active and inactive disease. As controls of the sonographic variables 10 children without a history of arthritis were examined by ultrasound. RESULTS: In active arthritis of the hip joint 19/31 (61%) examinations showed a pathological widening of the synovial joint space. There was no significant correlation between sonographic and clinical measures of disease activity in coxitis. Marked effusion within the suprapatellar pouch was seen in 87% and thickening of the synovial membrane in 92% of cases of active gonarthritis in patients with JRA. There was a significant difference in the number of patients with joint effusion and in the mean joint effusion between patients with clinically active gonarthritis at entry and inactive arthritis at follow up (p<0.001). In contrast, synovial thickening persisted in about 80% after induction of clinical remission. CONCLUSION: The data confirm the high sensitivity of arthrosonography in imaging changes in hip and knee joints of patients with JRA. Sonographic effusion of the knee provided the highest correlation with measures of clinical disease activity. Further prospective studies should evaluate whether persistent thickening of the synovial membrane detected by ultrasound in clinically inactive arthritis indicates residual inflammatory activity and an increased risk of relapse.

Arthritis, Juvenile↗
PubMed2002

[Pulmonary aspergillosis as initial manifestation of septic granulomatosis (chronic granulomatous disease, CGD) in a premature monozygotic female twin and FDG-PET diagnosis of spread of the disease].

PURPOSE: To present the unusual case of chronic granulomatous disease (CGD) manifestating as pulmonal aspergillosis in female enzygotic twins during the neonatal period. To demonstrate and to discuss the complex diagnosis and the diagnostic value of FDG-PET in monitoring the spread and activity of the disease. PATIENTS: Plain chest x-ray and CT of the lung showed multiple, mostly round lesions in one of the former preterm twins at the age of 8 weeks. The girl with known ASD II was then suffering from dyspnoea and recurrent pulmonary infections. Because of the imaging findings invasive pulmonary aspergillosis due to an underlying immunodeficiency was suspected. RESULTS: Aspergillosis was confirmed histologically and microbiologically by specimens taken from an open lung biopsy. Because of coexisting granulocytic dysfunction the diagnosis of CGD was made. This diagnosis was equally confirmed by noninvasive methods in the asymptomatic sister. FDG-PET did not show any evidence of extra-pulmonary spread of disease. CONCLUSION: CGD can present as isolated pulmonal aspergillosis even in the neonatal period when an immunodeficiency is discussed. In enzygotic twins screening of the asymptomatic twin is mandatory. FDG-PET is a useful tool in screening for spread of the disease and in evaluating disease activity.

Age Factors↗
PubMed2001

Acute and long-term effects of booster immunisation on frequencies of antigen-specific memory B-lymphocytes.

In search for a parameter that is predictive of long-term immunity, we analysed the influence of booster immunisations on frequencies of circulating memory B-lymphocytes. Specific IgG-secreting B-cells were determined by ELISPOTassay in 13 healthy adults, using diphtheria and tetanus toxoid as model antigens. Our results show that memory B-cells accumulate with every immunisation dose and remain elevated over several years. In addition, secondary B-cell responses were studied during the first 90 days after diphtheria re-immunisation. A significant indirect correlation was found between the number of previous boosters and the magnitude of specific B-cell expansion. In contrast, effects of booster immunisations did not correlate likewise with antigen-specific serology. Hence, this study illustrates that frequencies of antigen-specific B-lymphocytes can be used as an indirect measure for immunological memory. This parameter could be helpful to find scientifically based immunisation strategies for currently available and novel vaccines.

Adult↗
PubMed2001

Mannose-binding lectin regulates the inflammatory response of human professional phagocytes to Neisseria meningitidis serogroup B.

The influence of the innate immune protein mannose-binding lectin (MBL) on the response of human phagocytes to Neisseria meningitidis was investigated. MBL increased the association of killed meningococci with neutrophils, monocytes, and macrophages by increasing the proportion of cells that recognized bacteria. MBL down-regulated the normal change in expression of the leukocyte adhesion molecules CD11b and CD62L. In an ex vivo model, the addition of MBL to the blood of MBL-deficient donors influenced the production of monocyte-derived inflammatory cytokines. The addition of high concentrations of MBL (>6 microg/mL) profoundly decreased the production of interleukin (IL)-6, IL-1beta, and tumor necrosis factor-alpha by monocytes in response to meningococci, whereas lower concentrations enhanced the production of IL-6 and IL-1beta. These results suggest that MBL not only is involved in complement activation but also is a potent regulator of inflammatory pathways and, as such, may affect the severity of meningococcal disease.

CD11 Antigens↗
PubMed2001

Complex O-acetylation in Legionella pneumophila serogroup 1 lipopolysaccharide. Evidence for two genes involved in 8-O-acetylation of legionaminic acid.

A putative gene encoding an O-acetyl transferase, lag-1, is involved in biosynthesis of the O-polysaccharide (polylegionaminic acid) in some Legionella pneumophila serogroup 1 strains. To study the effect of the presence and absence of the gene on the O-polysaccharide O-acetylation, lag-1 from strain Philadelphia 1 was expressed in trans in the naturally lag-1-negative OLDA strain RC1, and immunoblot analysis revealed that the lag-1-encoded O-acetyl transferase is active. O-Polysaccharides of different size were prepared from the lipopolysaccharides of wild-type and transformant strains by mild acid degradation followed by gel-permeation chromatography. Using NMR spectroscopy and MALDI-TOF mass spectrometry, it was found that O-acetylation of the first three legionaminic acid residues next to the core occurs in the short-chain O-polysaccharide (<10 sugars) from both strains. Hence, there is another O-acetyl transferase encoded by a gene different from lag-1. In the longer-chain O-polysaccharide, a legionaminic acid residue proximal to the core is N-methylated and could be further 8-O-acetylated in the lag-1-dependent manner. Only strains expressing a functional lag-1 gene were recognized in Western blot analysis by monoclonal antibody 3/1 requiring 8-O-acetylated polylegionaminic acid for binding. The highly O-acetylated outer core region of the lipopolysaccharide is involved in the epitope of another serogroup 1-specific monoclonal antibody termed LPS-1. The O-acetylation pattern of the L. pneumophila serogroup 1 core oligosaccharide was revised using MALDI-TOF mass spectrometry. lag-1-independent O-acetylation of the core and short-chain O-polysaccharide was found to be a common feature of L. pneumophila serogroup 1 strains. The biological importance of conserved lag-1-independent and variable lag-1-dependent O-acetylation is discussed.

Acetylation↗
PubMed2001

Autologous peripheral blood stem cell transplantation and anti-B-cell directed immunotherapy for refractory auto-immune haemolytic anaemia.

UNLABELLED: We report the clinical course of a 6.5-year-old boy with refractory auto-immune haemolytic anaemia. Due to failure of conventional immunosuppressive therapy, an autologous peripheral blood stem cell transplantation was performed. The conditioning regimen consisted of cyclophosphamide and anti-thymocyte globulin. The patient was reinfused with 2.6 x 10(6) CD34 positive selected, B- and T-cell-depleted peripheral blood stem cells per kg body weight. He showed a partial response with a reduced demand for red blood cell transfusions. However, due to persistence of the haemolytic process he was started on rituximab therapy on day +40 post-transplant. Following two doses of rituximab, the patient improved rapidly and developed a sustained complete response. After 10 months, haemolysis recurred and responded again to rituximab therapy without the necessity for red blood cell transfusions. 15 months after initial antibody treatment, however, the patient developed a second relapse which was now refractory to rituximab therapy although CD20+ B-lymphocytes were cleared from the peripheral blood. CONCLUSION: Our case report suggests that rituximab and autologous peripheral blood stem cell transplantation are important though not curative elements in the treatment of patients with severe auto-immune haemolytic anaemia who are refractory to conventional immunosuppressive therapy.

Anemia, Hemolytic, Autoimmune↗