Search PubMed⌕ Search

Biomedical subjects

M Kaufmann

Publications and source records attributed to M Kaufmann.

At least 91 records · Page 5Linked to original sources
PubMed2001

Preeclampsia, a pregnancy-specific disease, is associated with fetal monocyte activation.

The maternal syndrome of preeclampsia is an exclusively pregnancy-related illness involving multiple organs and severe forms may be complicated by HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome. Recently, it has been proposed that both normal pregnancy and preeclampsia are associated with a systemic activation of the nonspecific maternal immune system and that, in particular, monocytes have a central role in the adjustment of maternal immune functions in pregnancy. Here we have investigated the role of the fetal nonadaptive immune system in normal term delivery, uncontrollable preterm labor, and preeclampsia. We demonstrate that spontaneous delivery at term as well as preterm occurrence of preeclampsia or HELLP syndrome are accompanied by an increased intracellular production of IL-6 in fetal monocytes, indicating strong activation of this cell type. In contrast, we show that elective cesarean delivery at term in the absence of labor or preterm delivery due to uncontrollable labor are not accompanied by an increased production of IL-6 in these cells. These results suggest that increased IL-6 synthesis in fetal monocytes may be a process occurring in association with normal spontaneous term delivery and that this process obviously occurs in early pregnancy in case of preeclampsia. Therefore, we propose that the activation of fetal monocytes as effectors of the innate immunity may be involved in mechanisms inducing spontaneous term delivery and that the occurrence of preeclampsia may be based on dysfunctions of probably both the maternal and the fetal innate immune system.

Female↗
PubMed2001

Genomic structure, alternative splicing, and physical mapping of the killer cell lectin-like receptor G1 gene (KLRG1), the mouse homologue of MAFA.

The mouse killer cell lectin-like receptor G1 (KLRG1), the mouse homologue of the mast cell function-associated antigen (MAFA), is an inhibitory C-type lectin expressed on natural killer (NK) cells and activated CD8 T cells. Here we report the complete nucleotide sequence, alternatively spliced variants, and the physical mapping of the KLRG1 gene in the mouse. The gene spans about 13 kb and consists of five exons. Short interspersed repeats of the B1 and B2 family, a LINE-1-like element, and a (CTT)170 triplet repeat were found in intron sequences. In contrast to human KLRG1 and to the murine KLR family members, mouse KLRG1 locates outside the NK complex on Chromosome 6 between the genes encoding CD9 and CD4.

Alternative Splicing↗
PubMed2001

Augmentation of mechanical properties in osteoporotic vertebral bones--a biomechanical investigation of vertebroplasty efficacy with different bone cements.

Recent clinical trials have reported favorable early results for transpedicular vertebral cement reinforcement of osteoporotic vertebral insufficiencies. There is, however, a lack of basic data on the application, safety and biomechanical efficacy of materials such as polymethyl-methacrylate (PMMA) and calciumphospate (CaP) cements. The present study analyzed 33 vertebral pairs from five human cadaver spines. Thirty-nine vertebrae were osteoporotic (bone mineral density < 0.75 g/cm2), 27 showed nearly normal values. The cranial vertebra of each pair was augmented with either PMMA (Palacos E-Flow) or experimental brushite cement (EBC), with the caudal vertebra as a control. PMMA and EBC were easy to inject, and vertebral fillings of 20-50% were achieved. The maximal possible filling was inversely correlated to the bone mineral density (BMD) values. Cement extrusion into the spinal canal was observed in 12% of cases. All specimens were subjected to axial compression tests in a displacement-controlled mode. From load-displacement curves, the stiffness, S, and the maximal force before failure, Fmax, were determined. Compared with the native control vertebrae, a statistically significant increase in vertebral stiffness and Fmax was observed by the augmentation. With PMMA the stiffness increased by 174% (P = 0.018) and Fmax by 195% (P = 0.001); the corresponding augmentation with EBC was 120% (P = 0.03) and 113% (P = 0.002). The lower the initial BMD, the more pronounced was the augmentation effect. Both PMMA and EBC augmentation reliably and significantly raised the stiffness and maximal tolerable force until failure in osteoporotic vertebral bodies. In non-porotic specimens, no significant increase was achieved.

Aged↗
PubMed2001

A directed approach to the selection of bacteria with enhanced catabolic activity.

AIMS: This study was aimed at selecting catabolicly-improved bacteria by in vitro evolution using a specially designed fermentor system. METHODS AND RESULTS: To facilitate this objective, genetic variation was induced by ultraviolet irradiation, and a selective pressure was subsequently exerted by gradual increases in the concentration of organic toxins. During a pilot experiment, a culture was forced to tolerate and catabolize a mixture of phenol and formaldehyde. The population developed a high resistance against formaldehyde and the specific degradation rate increased rapidly. Biochemical analysis of the mutants revealed an increase in the expression of enzymes involved in the pathway oxidizing formaldehyde. CONCLUSIONS: The fermentor system described is, in general, suitable for the selection of bacteria with enhanced catabolic activities. SIGNIFICANCE AND IMPACT OF THE STUDY: The procedure is an alternative to conventional genetic engineering, providing efficient and genetically stable strains suitable for applications in the field of environmental biotechnology.

Bacteria↗
PubMed2001

[Amniotic fluid embolism as an obstetric emergency--description of the syndrome and a case with fatal outcome].

Amnotic fluid embolism is an incompletely understood obstetric emergency presenting with the acute onset of hypoxia, hypotension and severe coagulopathy. Up to 86% of the cases are fatal, maternal death occurs within the first hour of symptom onset in 50% of the patients. This report describes the case of a 29-year-old, HIV-positive patient undergoing elective cesarean section who died despite immediate onset of cardiopulmonary resuscitation. The epidemiology of amniotic fluid embolism, clinical presentation, differential diagnosis, pathology and possible treatment are discussed.

Adult↗
PubMed2001

[Preoperative chemotherapy in primary operable breast cancer with a dose-dense combination of doxorubicin and docetaxel (ADoc) - Experience of the GEPARDO-GABG study group].

OBJECTIVE: The German Adjuvant Breast Cancer Study Group (GABG) conducts trials of preoperative chemotherapy in patients with primary breast cancer using a combination of doxorubicin and docetaxel (ADoc). - PATIENTS AND METHODS: We conducted a parallel-grouped phase IIa-study with 42 patients with a conventionally dosed and a dose-dense ADoc-schedule (4 cycles of Doxorubicin 50 mg/m(2), Docetaxel 75 mg/m(2) i. v. day 1, q day 15 or 22; G-CSF day 3-15 only for the dose-dense schedule) and a randomized phase IIb-study (GEPARDO-Study) with 250 patients with ADoc +/- Tamoxifen. Biological factors were determined immunohistochemically on 197 core biopsies before treatment. A comparison to a sequential AC-Doc regimen including 913 patients has been completed recently. - RESULTS: ADoc can be applicated on schedule in 93 % of all patients. The dose-dense regimen shows a tendency to more toxicity but also to more efficacy. The rate of complete pathological remissions (pCR) was 9.7 %. No difference was found between chemo- and chemoendocrine treatment. Clinically negative lymphnodes and a negative estrogen receptor status is predictive for a higher pCR-rate. To date no differences in toxicity could be found between ADoc and AC-Doc. - CONCLUSIONS: The dose-dense ADoc regimen is well tolerated and highly effective as preoperative therapy of breast cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2001

An efficient algorithm for finding short approximate non-tandem repeats.

We study the problem of approximate non-tandem repeat extraction. Given a long subject string S of length N over a finite alphabet Sigma and a threshold D, we would like to find all short substrings of S of length P that repeat with at most D differences, i.e., insertions, deletions, and mismatches. We give a careful theoretical characterization of the set of seeds (i.e., some maximal exact repeats) required by the algorithm, and prove a sublinear bound on their expected numbers. Using this result, we present a sub-quadratic algorithm for finding all short (i.e., of length O(log N)) approximate repeats. The running time of our algorithm is O(DN(3pow(epsilon)-1)log N), where epsilon = D/P and pow(epsilon) is an increasing, concave function that is 0 when epsilon = 0 and about 0.9 for DNA and protein sequences.

Algorithms↗
PubMed2001

Favourable effect of an acidified milk (LC-1) on Helicobacter pylori gastritis in man.

OBJECTIVE: The supernatant of Lactobacillus johnsonii La1 culture was shown to be bactericidal and to have a partial, acid-independent suppressive effect on Helicobacter pylori in humans. The aim of the present study was to investigate the effect of L. johnsonii La1-acidified milk (LC-1) on H. pylori infection. DESIGN AND METHODS: Fifty-three volunteers infected with H. pylori as determined by positive 13C-urea breath test and positive serology were randomized to receive either LC-1 or a placebo 180 ml twice a day for 3 weeks. All subjects also received clarithromycin 500 mg bid during the last two weeks of acidified milk therapy. Oesophagogastroduodenoscopy and biopsies were performed at inclusion and repeated 4-8 weeks after the end of the treatment. H. pylori infection was confirmed by urease test and histology. H. pylori density and inflammation were scored using a modified Sydney classification. RESULTS: LC-1 ingestion induced a decrease in H. pylori density in the antrum (P= 0.02) and the corpus (P= 0.04). LC-1 also reduced inflammation and gastritis activity in the antrum (P= 0.02 and P= 0.01, respectively) and of activity in the corpus (P= 0.02). Clarithromycin eradicated H. pylori in 26% of the subjects; LC-1 did not improve the antibiotic effect. CONCLUSION: These results suggest that H. pylori infection and gastritis can be down-regulated by LC-1.

Animals↗
PubMed2001

Introduction.

Explore the source record for details and available documents.

Journal Article↗
PubMed2001

Natural history of twin-twin transfusion syndrome.

OBJECTIVE: To determine the natural history of pregnancies with twin-twin transfusion syndrome (TTTS). STUDY DESIGN: All cases of TTTS at our institution since 1991 and in a MED-LINE search since 1966 were retrospectively reviewed. The prenatal diagnosis of TTTS required the presence of monochorionic/diamniotic placentation (absence of twin-peak sign, thin membrane, single placenta, same sex) and of polyhydramnios (largest pocket > 8 cm) in one sac and oligohydramnios (largest pocket < 2 cm or stuck twin) in the other. Only cases diagnosed at < or = 28 weeks were included. Upon diagnosis, all patients were counseled as to the availability, risks and benefits of serial amniocentesis, laser therapy, septostomy, umbilical cord ligation, and other medical and surgical interventions. RESULTS: Of 29 pregnancies identified at our institution with the above strict criteria for TTTS, 5 (17%) declined in utero therapy and were managed expectantly. The mean gestational age at presentation was 19.2 weeks (range, 16-28) and at delivery, 33.8 weeks (range, 22-41). Four (40%) of the twins survived past the neonatal period, and of the three with follow-up, all are free of neurologic sequelae despite the death in utero of their cotwin. From the literature, 136 fetuses with TTTS as defined above and managed expectantly were identified; 37 (27%) survived; 75% (9/12) of survivors with follow-up are neurologically normal. The most recent four studies have reported survival of untreated cases of 50% (17/34) when diagnosed at < or = 26 weeks and of 63% (20/32) when diagnosed at < or = 28 weeks. CONCLUSION: The perinatal survival of TTTS pregnancies managed without in utero procedures is approximately 30% overall and 63% in the four most recent series when diagnosed at < or = 28 weeks. The success of in utero therapeutic intervention should be assessed by randomized studies or at least compared to that in similar cases managed without such intervention.

Amniocentesis↗
PubMed2000

Adhesion induced expression of the serine/threonine kinase Fnk in human macrophages.

Members of the polo subfamily of protein kinases play crucial roles in cell proliferation. To study the function of this family in more detail, we isolated the cDNA of human Fnk (FGF-inducible kinase) which codes for a serine/threonine kinase of 646 aa. Despite the homology to the proliferation-associated polo-like kinase (Plk), tissue distribution of Fnk transcripts and expression kinetics differed clearly. In contrast to Plk no correlation between cell proliferation and Fnk gene expression was found. Instead high levels of Fnk mRNA were detectable in blood cells undergoing adhesion. The transition of monocytes from peripheral blood to matrix bound macrophages was accompanied by increasing levels of Fnk with time in culture. Neither treatment of monocytes with inducers of differentiation nor withdrawal of serum did influence Fnk mRNA levels significantly, suggesting that cell attachment triggers the onset of Fnk gene transcription. The idea that Fnk is part of the signalling network controlling cellular adhesion was supported by the analysis of the cytoplasmic distribution of the Fnk protein and the influence of its overexpression on the cellular architecture. Fnk as fusion protein with GFP localized at the cellular membrane in COS cells. Dysregulated Fnk gene expression disrupted the cellular f-actin network and induced a spherical morphology. Furthermore, Fnk binds to the Ca2+/integrin-binding protein Cib in two-hybrid-analyses and co-immunoprecipitation in assays. Moreover, both proteins were shown to co-localize in mammalian cells. The homology of Cib with calmodulin and with calcineurin B suggests that Cib might be a regulatory subunit of polo-like kinases.

Actins↗
PubMed2000

Identification and functional characterization of the human and murine fibroblast growth factor receptor 4 promoters.

Fibroblast growth factor receptors (FGFRs) play crucial roles in signal transduction of adult tissues and during embryonic development. To study the transcriptional control, we isolated and characterized the promoter of human FGFR4. Two transcription initiation sites were identified. The deletion analysis in different cell types defined a core promoter reaching from -9 to -198, lacking TATA and CCAAT boxes but displaying high GC content (77%) in a stretch of 300 bp upstream of the major mRNA start. This region harbors multiple binding motifs for transcription factors. Moreover, the region between -1085 and -1140 contains a potential repressor element, which downregulates transcriptional activity. To identify conserved regulatory elements, we isolated and analyzed also the murine FGFR4 promoter. Only one transcription start was identified using RNase protection assays. Sequence alignment of human and mouse shows a striking similarity in the core promoter region of both genes, encompassing conserved transcription factor binding sites and a splice acceptor site. Furthermore, the region containing the putative repressor element is also conserved suggesting a functional role for gene expression.

Animals↗
PubMed2000

Relation of cell proliferation to expression of peripheral benzodiazepine receptors in human breast cancer cell lines.

Peripheral benzodiazepine receptor (PBR) agonist [(3)H]Ro5-4864 has been shown to bind with high affinity to the human breast cancer cell line BT-20. Therefore, we investigated different human breast cancer cell lines with regard to binding to [(3)H]Ro5-4864 and staining with the PBR-specific monoclonal antibody 8D7. Results were correlated with cell proliferation characteristics. In flow cytometric analysis, the estrogen receptor (ER)-negative breast cancer cell lines BT-20, MDA-MB-435-S, and SK-BR-3 showed significantly higher PBR expression (relative fluorescence intensity) than the ER-positive cells T47-D, MCF-7 and BT-474 (P<0.05). Accordingly, BT-20 and MDA-MB-435-S had the highest capacity for binding [(3)H]-Ro5-4864, while the ER-positive cells exhibited only low binding of the benzodiazepine. PBR expression correlated inversely with cell doubling time (r = 0.78) and positively with Ki-67 expression (r = 0.77). The amount of mitochondria was significantly higher in cells with high PBR expression. As PBR could be demonstrated only after permeabilization of cells, PBR is suggested to be localized within the cytoplasm. Moreover, colocalization of PBR and mitochondria was shown by confocal microscopy analysis. The highest amounts of both PBR and mitochondria were found in cell lines with high mitotic activity. Therefore, it is concluded that the level of PBR is dependent on the number of mitochondria. PBR and its putative endogenous ligand diazepam-binding inhibitor are possibly involved in the regulation of cell proliferation of human breast cancer cell lines.

Benzodiazepines↗
PubMed2000

The glucose transporter of the Escherichia coli phosphotransferase system: linker insertion mutants and split variants.

The IICB(Glc) subunit of the glucose transporter acts by a mechanism which couples vectorial translocation with phosphorylation of the substrate. It contains 8 transmembrane segments connected by 4 periplasmic, 2 short, 1 long (80 residues), cytoplasmic loops and an independently folding cytoplasmic domain at the C-terminus. Random DNase I cleavage, EcoRI linker insertion, and screening for transport-active mutants afforded 12 variants with between 46% and 116% of wild-type sugar phosphorylation activity. They carried inserts of up to 29 residues and short deletions in periplasmic loops 1, 2, and 3, in the long cytoplasmic loop 3, and in the linker region between the membrane spanning IIC(Glc) and the cytoplasmic IIB(Glc) domains. Disruption of the gene at the sites of linker insertion decreased the expression level and diminished phosphotransferase activity to between 7% and 32%. IICB(Glc) with a discontinuity in the cytoplasmic loop was purified to homogeneity as a stable complex. It was active only if encoded by a dicistronic operon but not if encoded by two genes on two different replicons, suggesting that spatial proximity of the nascent polypeptide chains is important for folding and membrane assembly.

Amino Acid Sequence↗
PubMed2000

Simultaneous attainment of high electron and ion temperatures in discharges with internal transport barriers in ASDEX upgrade

Internal transport barriers have been demonstrated to exist also under conditions with T(e) approximately T(i) approximately 10 keV and predominant electron heating of the tokamak core region. Central electron cyclotron heating was added to neutral beam injection-heated ASDEX Upgrade discharges with a preexisting internal transport barrier, established through programmed current ramping leading to shear reversal. Compared to a reference internal transport barrier discharge without electron cyclotron resonance heating, the electron heat conductivity in the barrier region was found not to increase, in spite of a fivefold increase in electron heat flux, and also angular momentum and ion energy transport did not deteriorate.

Journal Article↗
PubMed2000

Serum intercellular adhesion molecule-1 levels and histologic chorioamnionitis.

OBJECTIVE: To compare the diagnostic value of intercellular adhesion molecule (ICAM)-1 with that of C-reactive protein (CRP) and white blood cell (WBC) count for detecting histologic chorioamnionitis in serum of women with preterm labor. METHODS: Maternal blood was collected from 97 consecutive women admitted with preterm delivery before 37 weeks' gestation, and 50 women after normal term delivery (38-41 weeks' gestation). Intercellular adhesion molecule-1, CRP, and WBC count were measured before delivery. RESULTS: Histologic chorioamnionitis was diagnosed in 48 of 97 women (48%) who delivered preterm and in none who delivered at term. Maternal serum levels of ICAM-1 (median 169 ng/mL, range 94-510 ng/mL, P <.001), CRP (median 2.8 ng/mL, range 0.5-13.2 mg/dL, P <.001) and WBC count (12.6 x 10(3)/microL, range 6.4-30.6 x 10(3)/microL, P <.02) were statistically significantly higher in women with histologic chorioamnionitis than those without it (ICAM-1 median 70 ng/mL, range 23-107 ng/mL; CRP median 0.7 mg/dL, range 0.5-6.7 mg/dL; WBC count median 10.9 x 10(3)/microL, range 4.3-22.2 x 10(3)/microL). The sensitivity and specificity of maternal serum ICAM-1 (cutoff 106 ng/mL), CRP (cutoff 1.1 mg/dL), and WBC count (cutoff 11.8 x 10(3)/microL) for diagnosing histologic chorioamnionitis were 98.0% and 93.8%, 75.5% and 71.4%, and 63.3% and 61.2%, respectively. CONCLUSION: In women with preterm labor, ICAM-1 is a more reliable indicator of histologic chorioamnionitis than CRP or WBC count.

Adult↗