Search PubMed⌕ Search

Biomedical subjects

M Fischer

Publications and source records attributed to M Fischer.

At least 199 records · Page 11Linked to original sources
PubMed1999

Epidemic serogroup B meningococcal disease in Oregon: the evolving epidemiology of the ET-5 strain.

CONTEXT: In 1993, Oregon's incidence of serogroup B meningococcal disease began to rise because of a highly clonal group of strains designated enzyme type 5 (ET-5), the first such increase observed in the United States. OBJECTIVE: To evaluate the impact that the ET-5 strain has had on the epidemiology of meningococcal disease in Oregon. DESIGN AND SETTING: Epidemiologic analysis of surveillance data on Oregon meningococcal disease cases from 1987 through 1996 and multilocus enzyme electrophoresis typing of serogroup B isolates from June 1993 through April 1995 and from April through June 1996. PATIENTS: A total of 836 persons with invasive meningococcal disease. MAIN OUTCOME MEASURES: Disease frequency and clonality of strains. RESULTS: Serogroup B disease incidence rates more than doubled from the preepidemic period in 1987-1992 (1.0 case per 100000 population) to the recent epidemic period in 1995-1996 (2.2 cases per 100000). The age-specific incidence rate of serogroup B disease among those 15 through 19 years old increased 13-fold between the preepidemic period (0.5 case per 100000) and 1995-1996 (6.4 cases per 100000). However, the proportion of cases with meningococcemia and the case-fatality rate did not change. Of 99 Neisseria meningitidis isolates obtained from 1993-1995, 88 (89%) belonged to the ET-5 complex. Of these, 69 (78%) were a single clone, designated 301. Of 20 serogroup B isolates from 1996, 18 (90%) belonged to the ET-5 complex; 17 (94%) were the 301 clone. CONCLUSION: Serogroup B meningococcal disease incidence continues at high levels in Oregon with increasing predominance of the ET-5 clonal strains.

Adolescent↗
PubMed1999

Ectopic expression of prion protein (PrP) in T lymphocytes or hepatocytes of PrP knockout mice is insufficient to sustain prion replication.

The cellular form of the Prion protein (PrPC) is necessary for prion replication in mice. To determine whether it is also sufficient, we expressed PrP under the control of various cell- or tissue-specific regulatory elements in PrP knockout mice. The interferon regulatory factor-1 promoter/Emu enhancer led to high PrP levels in the spleen and low PrP levels in the brain. Following i.p. scrapie inoculation, high prion titers were found in the spleen but not in the brain at 2 weeks and 6 months, showing that the lymphoreticular system by itself is competent to replicate prions. PrP expression directed by the Lck promoter resulted in high PrP levels on T lymphocytes only but, surprisingly, did not allow prion replication in the thymus, spleen, or brain following i.p. inoculation. A third transgenic line, which expressed PrP in the liver under the control of the albumin promoter/enhancer-albeit at low levels-also failed to replicate prions. These results show that expression of PrP alone is not sufficient to sustain prion replication and suggest that additional components are needed.

Animals↗
PubMed1999

Evidence for kinetic inhomogeneity in the curing of epoxy using the near-infrared multispectral imaging technique.

The kinetics of curing of an epoxy resin by amine was studied using a near-infrared (NIR) multispectral imaging spectrometer. This imaging spectrometer is capable of sensitively and rapidly recording NIR spectral images of a sample because it was constructed with an acousto-optic tunable filter and an InGaAs focal plane array NIR camera. The high sensitivity and fast scanning ability of the spectrometer make it suitable for kinetic determination of fast reactions. Additionally, it has features that conventional NIR spectrometers cannot offer, namely, its ability to provide kinetic information at different positions within a sample. Furthermore, the high spatial resolution and sensitivity of the InGaAs camera make it possible to determine the kinetics from data collected by a single pixel in the camera. The kinetics of curing of epoxy by amine, determined by this multispectral imaging instrument, show that the reaction rates within the sample are very inhomogeneous. Because of this kinetic inhomogeneity, differences in the degrees of cure at different positions within the sample can be as high as 37% when data from only a single pixel were used for calculation. The inhomogeneity was not be observed if an average of a large number of pixels were used.

Epoxy Compounds↗
PubMed1999

Complementation of the fol2 deletion in Saccharomyces cerevisiae by human and Escherichia coli genes encoding GTP cyclohydrolase I.

Saccharomyces cerevisiae is so far the only organism where a knock-out mutant in the gene encoding GTP cyclohydrolase I (FOL2) has been obtained. GTP cyclohydrolase I controls the de novo biosynthetic pathway of tetrahydrobiopterin and folic acid. Since deletion of yeast FOL2 leads to a recessive auxotrophy for folinic acid, we used a yeast fol2Delta mutant for an in vivo functional assay of heterologous GTP cyclohydrolases I. We show that the GTP cyclohydrolase I, encoded either by the E. coli folE gene or by the human cDNA, complements the yeast fol2Delta mutation by restoring folate prototrophy. Furthermore the folE-3x allele of the E. coli gene, carrying three base substitutions, failed to complement the yeast fol2Delta defect. This allele behaved as a negative semidominant to the wild type folE and, when overexpressed, completely abolished complementation of fol2Delta by folE. Thus, the yeast fol2 null mutant is a suitable system to characterize mutations in genes encoding GTP cyclohydrolase I.

Alleles↗
PubMed1999

The designer cytokine hyper-interleukin-6 is a potent activator of STAT3-dependent gene transcription in vivo and in vitro.

Interleukin-6 (IL-6) triggers pivotal pathways in vivo. The designer protein hyper-IL-6 (H-IL-6) fuses the soluble IL-6 receptor (sIL-6R) through an intermediate linker with IL-6. The intracellular pathways that are triggered by H-IL-6 are not defined yet. Therefore, we studied the molecular mechanisms leading to H-IL-6-dependent gene activation. H-IL-6 stimulates haptoglobin mRNA expression in HepG2 cells, which is transcriptionally mediated as assessed by run-off experiments. The increase in haptoglobin gene transcription correlates with higher nuclear translocation of tyrosine-phosphorylated STAT3 and its DNA binding. As H-IL-6 stimulates STAT3-dependent gene transcription, we compared the molecular mechanism between IL-6 and H-IL-6. Transfection experiments were performed with a STAT3-dependent luciferase construct. The same amount of H-IL-6 stimulated luciferase activity faster, stronger, and for a longer period of time. Dose response experiments showed that a 10-fold lower dose of H-IL-6 stimulated STAT3-dependent gene transcription comparable with the higher amount of IL-6. Cotransfection with the gp80 and/or gp130 receptor revealed that the effect of H-IL-6 on STAT3-dependent gene transcription is restricted to the gp80/gp130 receptor ratio. High amounts of gp130 increased and high amounts of gp80 decreased the effect on H-IL-6-dependent gene transcription. To investigate the in vivo effect of H-IL-6 on gene transcription in the liver, H-IL-6 and IL-6 were injected into C3H mice. H-IL-6 was at least 10-fold more effective in stimulating the DNA binding and nuclear translocation of STAT3, which enhances haptoglobin mRNA and protein expression. Thus H-IL-6 stimulates STAT3-dependent gene transcription in liver cells in vitro and in vivo at least 10-fold more effectively than IL-6. Our results provide evidence that H-IL-6 is a promising designer protein for therapeutic intervention during different pathophysiological conditions also in humans.

Animals↗
PubMed1999

Antioxidant status in patients with acute respiratory distress syndrome.

OBJECTIVES: Reactive oxygen species (ROS) have been implicated in the pathophysiology of ARDS. We investigated the pattern of antioxidants in plasma and ROS production by neutrophils in patients with ARDS over 6 days. DESIGN: Observational study. Blood samples were taken when the diagnosis was made (D0) and after 3 (D3) and 6 days (D6) during therapy. SETTING: Intensive care units at a University Hospital. PATIENTS: Eight patients with ARDS were investigated, 17 healthy volunteers served as controls. MEASUREMENTS AND RESULTS: Plasma levels of ascorbate, alpha-tocopherol, retinol, beta-carotene, selenium and lipid peroxidation products (MDA) were determined and the activities of the antioxidative enzymes catalase (CAT), superoxide dismutase (SOD) and glutathione-peroxidase (GSH-PX) in erythrocytes were measured. In addition, ROS production (superoxide anion and hydrogen peroxide) in activated neutrophils was assessed. Plasma levels of alpha-tocopherol, ascorbate, beta-carotene and selenium were reduced from the onset of illness. MDA plasma levels were increased throughout the illness. ROS generation from neutrophils was normal on D0 and decreased to D6 in ARDS patients. CONCLUSION: The antioxidative system is severely compromised in patients with ARDS. Plasma levels of alpha-tocopherol, ascorbate, beta-carotene and selenium are decreased. Elevated MDA levels provide further evidence of massive oxidative stress. The routine replacement of micronutrients according to recommended daily allowances was inadequate to compensate for the increased requirements.

Adult↗
PubMed1999

[Peritoneal mesothelioma--incidence and etiology].

A total of 70 malignant and 4 benign peritoneal mesotheliomas were diagnosed by the German Mesothelioma Registry between 1992 and 1998. Malignant mesotheliomas developed mainly in men (55/70); only one man had a benign peritoneal alteration. Age at first diagnosis of malignant mesotheliomas is about 59 years; the women are on average 4 years younger than the men. Mean survival time ranges about 1 year; in 6 of 38 patients longer survival times of up to 7 years are known. The epitheloid subtype predominates, but no effect on survival time is noticed. The percentage of patients with combined asbestos-associated lung fibrosis is higher than that for pleural mesotheliomas; these patients become ill about 6.5 years earlier. The latency period is 36 years on average. For most patients asbestos exposure is related to their occupation mainly in metal industries, asbestos industries, and in the building trade. There is no evidence for an induction of benign peritoneal alterations by asbestos dust.

Asbestos↗
PubMed1999

Correlation between coronary morphology and molecular markers of fibrinolysis in unstable angina pectoris.

BACKGROUND: In acute coronary syndromes, marked alterations of coagulation and fibrinolysis have been observed, but no data are available concerning a possible relation to coronary stenosis morphology. METHODS: Thirty one patients with unstable angina pectoris were included. Culprit stenosis morphology judged from coronary angiography was graded using the modified ACC/AHA classification. Molecular and functional markers of hemostasis and fibrinolysis were determined from venous plasma samples obtained at admission. RESULTS: Patients with unstable angina pectoris had a moderate procoagulant state, especially a contact phase activation compared with age-matched controls (factor XII 93.9 +/- 5.6 vs 112.8 +/- 5.4%; P < 0.05; high molecular weight kininogen 55.3 +/- 5.4 vs 86.1 +/- 6.5%; P < 0.01). Thrombin-antithrombin (TAT) was not significantly elevated (7.6 +/- 1.9 vs 4.0 +/- 0.5 microg/l). Elevated plasminogen activator mass concentration (16.6 +/- 2.1 vs 5.4 +/- 0.6 ng/ml; P < 0.01) and plasminogen activator inhibitor (PAI) activity (9.9 +/- 3.0 vs 5.6 +/- 3.0 AU/ml; P < 0.05) indicated an alteration of the fibrinolysis. Complexity of coronary stenosis was positively correlated with tissue-type plasminogen activator (TPA) mass concentration (P < 0.01) and PAI activity (P < 0.05). No association was found to markers of a hypercoagulative state. CONCLUSION: These findings indicate a relation between alterations of the fibrinolytic system and coronary morphology, whereas the acute changes of coagulation occur independently of culprit stenosis complexity.

Adult↗
PubMed1999

Resuscitation in Europe: a tale of five European regions.

AIM: To describe cardiac arrest data from five emergency medical services (EMS) systems in Europe with regard to survival from an out-of-hospital cardiac arrest. METHODS: Based on recommendations from various countries in Europe EMS systems were approached with regard to survival from out-of-hospital cardiac arrest. Five EMS systems were asked to report their cardiac arrest data according to the Utstein style. RESULTS: The five selected EMS systems were: Bonn (Germany), Göttingen (Germany), Helsinki (Finland), Reykjavik (Iceland) and Stavanger (Norway). For patients with a bystander witnessed arrest of cardiac aetiology the percentage of patients being discharged alive from hospital in these regions were: 21, 33, 23, 23 and 35. The corresponding percentages for patients fulfilling criteria as above and being found in ventricular fibrillation were: 32, 42, 32, 27 and 55. CONCLUSIONS: Many EMS systems in Europe show extremely good results in terms of survival after an out-of-hospital cardiac arrest. Some of the results should be interpreted with caution since they were based on relatively small sample sizes. Furthermore, the results from one of the regions (Stavanger) was unit based and not community based.

Cardiopulmonary Resuscitation↗
PubMed1999

Are cumulus cells necessary for the spontaneous maturation of germinal vesicle-stage oocytes to metaphase II.

PURPOSE: In this study we investigated the need of the support from cumulus cells for germinal-vesicle (GV) oocytes collected from stimulated ovaries to complete their maturation to metaphase II (MII). METHODS: We compared the maturation rate of GV oocytes after coculture with cumulus cells (study group) with their spontaneous maturation in culture medium alone (control group). RESULTS: Sixty-four and nine-tenths percent of the GV oocytes matured to metaphase II in the coculture group, and of these, 43.5% gave normal 2pn zygotes following intracytoplasmic sperm injection (ICSI), while 73.8% of the GV oocytes spontaneously matured to the MII stage and 30% of these reached the zygote stage after ICSI. CONCLUSIONS: It is probable that a follicular factor is responsible for this arrested maturation in the human and that maturation occurs spontaneously when the oocytes are separated from their follicular fluid environment after collection.

Cell Culture Techniques↗
PubMed1999

The IgG1/G2 subclass shift--a sensitive, tissue non-specific marker for malignancy. Diagnostic performance with squamous cell carcinoma of the head and neck.

A significant decrease in %IgG1 accompanied by an increase in %IgG2 in total serum IgG has been previously reported as a highly sensitive marker for detecting early stages of carcinomas of various localizations. Here we investigated the question as to whether this phenomenon is also observed in sera of patients with squamous cell carcinoma of the head-neck region (SCC-HN), and to evaluate its diagnostic performance in the post-operative monitoring. Using quantitative affinity chromatography, serum concentrations of IgG1, IgG2 and total IgG were determined in 81 patients with different stages of primary and untreated SCC-HN, in 51 SCC-HN patients in post-therapeutical follow up, and in 33 patients with organ matched benign diseases. The data were compared with a total of 174 healthy controls. It was found that (i) 105 SCC-HN patients exhibited a mean value of 56.0 +/- 0.7% IgG1, which likewise differed from healthy controls (63.2 +/- 0.5) and benign diseases (61.5 +/- 1.0) with P < 0.0005, (ii) sensitivities and specificities for discriminating primary malignancies from healthy controls were 70 and 74% respectively, and from benign diseases 65 and 76%, (iii) highest sensitivities and specificities were observed with post-therapeutic cases suffering from tumour recurrence (88% and 75%) or patients with distant metastases (87% and 86%), (iv) apparently tumour-free post-therapeutic patients showed a mean %IgG1 not different from the normal value. The decrease in %IgG1 accompanied by increased %IgG2 is an efficient, sensitive and early marker of SCC-HN, which appears particularly useful for the post-therapeutic monitoring.

Aged↗
PubMed1999

A role for the immunoglobulin-like domain of the human IL-6 receptor. Intracellular protein transport and shedding.

Interleukin (IL)-6, IL-11 and cililary neurotrophic factor (CNTF) belong to the same family of hematopoietic and neurotrophic cytokines. Their receptor complexes contain a cytokine-binding alpha receptor and the common glycoprotein (gp)130 subunit for signal transduction. The extracellular parts of the alpha-receptor subunits consist of a membrane-proximal cytokine-binding domain and an N-terminal immunoglobulin (Ig)-like domain with unknown function. We examined the role of the Ig-like domain of IL-6R by constructing deletion mutants lacking the Ig domain (IL-6RDeltaIg and soluble IL-6RDeltaIg). IL-6RDeltaIg was shed as effectively as wild-type IL-6R from transfected COS-7 cells upon 4beta-phorbol 12-myristate 13-acetate (PMA) treatment, whereas nonstimulated shedding of IL-6RDeltaIg was not observed. The shed sIL-6RDeltaIg from PMA-treated cells, as well as the transmembrane IL-6RDeltaIg, had the same biological activity as wild-type sIL-6R, as measured by the induction of haptoglobin secretion in HepG2-IL-6 cells and IL-6-dependent proliferation of IL-6RDeltaIg transfected BAF/gp130 cells. In COS-7 cells transfected with IL-6RDeltaIg or soluble IL-6RDeltaIg cDNA, transport of the deletion mutants through the secretory pathway appeared to be delayed because a sizeable proportion of the mutants was detected as an endo-beta-N-acetylglucosaminidase-sensitive intermediate, suggesting that transport and processing of the DeltaIg mutants on the secretory pathway were impaired. These experiments suggest that the Ig-like domain of the IL-6R is important for intracellular transport of IL-6R through the secretory pathway. Furthermore, the Ig-like domain is necessary for noninduced shedding of the IL-6R, whereas it has no function in PKC-dependent shedding of the IL-6R.

Animals↗
PubMed1999

Immunologic changes after transfusion of autologous or allogeneic buffy coat-poor versus white cell-reduced blood to patients undergoing arthroplasty. I. Proliferative T-cell responses and the balance of helper and suppressor T cells.

BACKGROUND: Donor white cells (WBCs) contained in red cell (RBC) transfusions are thought to provoke down-regulation of T-cell-mediated immunity. This study investigated this topic in otherwise healthy patients receiving buffy coat-depleted or WBC-filtered RBCs and undergoing standardized perioperative management. STUDY DESIGN AND METHODS: Patients undergoing elective orthopedic surgery (primary hip and knee replacement surgery) were enrolled in a prospective study. Perioperative changes in T-cell proliferation (stimulation with phytohemagglutinin and mixed lymphocyte culture) and T-cell balance (T-lymphocytes, helper T cells, and suppressor T cells) were compared after random assignment to allogeneic buffy coat-depleted (Group 2, n = 8) or WBC-reduced RBC (Group 3, n = 11) transfusion regimens. Recipients of autologous buffy coat-depleted RBC transfusions (n = 15) served as controls (Group 1). RESULTS: Compared to that in autologous transfusion recipients, alloantigen-induced T-cell proliferation was significantly reduced in recipients of allogeneic WBC-reduced RBCs (Day 3, p = 0.0274). After the transfusion of allogeneic buffy coat-depleted RBCs, a weak trend toward decreased T-cell proliferation was observed (p = 0.0933) and the numbers of CD4+ T cells were also significantly lower (Day 7, p = 0.0389). On Day 10, alloantigen-induced T-cell proliferation remained significantly below baseline after transfusion of WBC-reduced RBCs (p = 0.05), the numbers of CD3+ cells decreased in allogeneic RBC recipients (Group 2, p = 0.078; Group 3, p = 0.05), and those of CD8+ cells decreased significantly after the transfusion of allogeneic buffy coat-depleted RBCs (p = 0.0234) concomitant with an increased CD4:CD8 ratio (p = 0.0391). CONCLUSION: Results of the present study confirm the hypothesis of impaired T-cell-mediated immunity after allogeneic transfusion.

Arthroplasty↗
PubMed1999

Action of aprotinin in myocardial ischemia - an investigation using a plasma-free model.

BACKGROUND: The protease inhibitor aprotinin has been reported to have an anti-ischemic effect on left-ventricular myocardium in patients undergoing cardiopulmonary bypass operation. To examine the anti-ischemic properties beside its antifibrinolytic and inhibitory action on the kallikrein-bradykinin system, we investigated this substance in buffer-perfused rat hearts. METHODS: 24 isolated isovolumically contracting rat hearts received a 10-minute infusion of either 10000 units aprotinin or pure saline followed by 30 minutes of no-flow global ischemia and 45 minutes of reperfusion. Hemodynamics, high-energy phosphates, and troponin T as molecular marker of cardiac injury were studied. RESULTS: During 15 minutes of reperfusion steady state function was identical in both groups, with a recovery of the developed left-ventricular pressure to 81.9+/-1.5% after protease inhibition and 83.0+/-2.6% in the controls. Coronary flow, myocardial oxygen consumption, and contractile reserve after maximum Ca++ stimulation were also identical. High-energy phosphates were comparably reduced in both groups (adenine nucleotides: 3.1+/-0.3 micromol/g ww after aprotinin vs. controls 2.7+/-0.4 micromol/g ww and creatine phosphate: 6.5+/-0.9 micromol/g ww vs. controls 4.7+/-1.1 micromol/g ww). However, release of the cardiac specific marker troponin T was lower after ischemia at several measurements (p<0.05). The total release of troponin T was 44+/-10 ng in the aprotinin treated hearts vs. 90+/-17 ng in the postischemic control hearts (p<0.05). CONCLUSIONS: The findings demonstrate that aprotinin in a moderate dose is effective in reducing postischemic troponin release in a non-blood perfused system. Measurement of myocardial high-energy phosphates after aprotinin use was performed for the first time and indicates that not a reduction in severity of direct myocardial ischemic intensity but a beneficial action on processes causing release of troponin is the mode of action of this effect.

Adenosine Triphosphate↗