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Biomedical subjects

D Schneider

Publications and source records attributed to D Schneider.

At least 91 records · Page 5Linked to original sources
PubMed2000

Long-term experimental evolution in Escherichia coli. IX. Characterization of insertion sequence-mediated mutations and rearrangements.

As part of a long-term evolution experiment, two populations of Escherichia coli B adapted to a glucose minimal medium for 10,000 generations. In both populations, multiple IS-associated mutations arose that then went to fixation. We identify the affected genetic loci and characterize the molecular events that produced nine of these mutations. All nine were IS-mediated events, including simple insertions as well as recombination between homologous elements that generated inversions and deletions. Sequencing DNA adjacent to the insertions indicates that the affected genes are involved in central metabolism (knockouts of pykF and nadR), cell wall synthesis (adjacent to the promoter of pbpA-rodA), and ill-defined functions (knockouts of hokB-sokB and yfcU). These genes are candidates for manipulation and competition experiments to determine whether the mutations were beneficial or merely hitchhiked to fixation.

Biological Evolution↗
PubMed2000

Mechanical ventilation in patients with hemispheric ischemic stroke.

OBJECTIVE: Whether stroke patients should be ventilated mechanically is still a contentious issue, because their outcome is very poor. We wanted to investigate how often mechanical ventilation is indicated in patients with hemispheric ischemic stroke as well as the outcome of these patients and the factors by which outcome is influenced. DESIGN: Prospective case series. SETTING: University hospital, neurocritical care unit. SUBJECTS: Subjects were 218 patients who met the following inclusion criteria: age 18-85 yrs, acute hemispheric ischemic infarction, clinical examination, and computed tomography within 6 hrs after the onset of symptoms. INTERVENTIONS: Mechanical ventilation was instituted with one or more of the following conditions: deterioration of consciousness with the inability to protect the airway; PaO2 of <60; P(CO2) of >60 mm Hg; breath rate of >40 breaths/min; and left heart insufficiency with definitive or impending pulmonary edema. MEASUREMENTS AND MAIN RESULTS: Mechanical ventilation was indicated for 52 (24%) of the 218 patients: in 47 (90%) patients because of deterioration of consciousness, and in five (10%) patients because of heart insufficiency and/or pneumonia. In a logistic regression model, the history of hypertension and a size of infarction exceeding two thirds of the middle cerebral artery territory were independent variables for the application of mechanical ventilation. After 3 months, 42 (81%) of these 52 patients had died. The most common cause of death was fatal midbrain herniation caused by complete middle cerebral artery infarction. Patients who survived had a good-to-fair outcome. CONCLUSIONS: New therapeutic strategies (e.g., hemicraniectomy) must be developed to reduce mortality and improve the outcome for this subgroup of ischemic stroke patients. Mechanical ventilation is and will remain a crucial element within such new concepts.

Adolescent↗
PubMed2000

Placental levels of human decidua- associated protein 200 in normal pregnancy and missed abortion.

Levels of human decidua-associated protein (hDP)200 were measured in homogenized placental tissue samples obtained from 26 induced and 24 missed abortions at 8-23 weeks of pregnancy. No significant difference in the level of placental hDP200 was observed comparing normal pregnancies and missed abortions. Moreover, no significant change in the level of placental hDP200 was demonstrated throughout normal pregnancies and those ending with missed abortions. Our results show that the level of hDP200 in placental tissue, measured by double-site ELISA, is probably incompatible with the normal continuation of pregnancy.

Abortion, Missed↗
PubMed2000

Placental apoptosis in normal and abnormal pregnancies.

The aim of this study was to demonstrate apoptosis in the human placenta in normal and abnormal pregnancies. The percentage of apoptotic cells in placental samples was quantified by analyzing the cell cycle of nuclei stained with propidium iodide using a flow cytometer. No significant difference in the percentage of apoptotic cells was observed comparing the group of normal pregnancies (first and second trimesters) with those of missed abortions. There was also no difference in the incidence of apoptosis comparing placental samples obtained from chromosomally normal and abnormal pregnancies. Yet, there was a significant increase in the incidence of apoptosis in placental samples obtained from second and third trimesters as compared with those obtained from the first trimester (p<0.04 and p<0.01, respectively). There was also a significant increase in the incidence of placental apoptosis in the third as compared with the second trimester (p<0.03).

Abortion, Missed↗
PubMed2000

Reperfusion and metabolic recovery of brain tissue and clinical outcome after ischemic stroke and thrombolytic therapy.

BACKGROUND AND PURPOSE: It is unclear from recent clinical trials whether thrombolytic agents are capable of facilitating reperfusion and metabolic recovery over time or whether a beneficial effect is counteracted by an increase in the risk of brain hemorrhage. We studied the effect of thrombolytic treatment on metabolic recovery after reperfusion and clinical outcome. METHODS: Patients were prospectively studied with (99m)Tc-ethyl cysteinate dimer single photon emission computed tomography ((99m)Tc-ECD-SPECT) before treatment with recombinant tissue plasminogen activator (rTPA; 0.9 mg/kg IV; n=26) or placebo (n=26) 6 to 8 hours after treatment and at 7+/-1 days. Activity deficits were graded, compared between the treatment groups, and correlated with clinical outcome and the incidence of brain hemorrhage. Metabolic recovery of ischemic brain tissue was defined as a 25% decrease on the SPECT graded scale. RESULTS: Patients with metabolic recovery (n=28) had a better chance of being functionally unimpaired 3 months after stroke than patients without recovery (n=24) (OR 4.5, 95% CI 1.09 to 18.89) and had smaller infarcts on follow-up CT (36+/-38 versus 167+/-162 mL), regardless of whether metabolic recovery was observed within 6 to 8 hours of treatment or at 7 days. None of the 28 patients with metabolic recovery had a fatal parenchymal hemorrhage versus 5 of 24 patients without recovery (P=0.016). Treatment did not affect the incidence of brain tissue metabolic recovery. CONCLUSIONS: Brain tissue metabolic recovery after ischemic stroke was associated with a beneficial effect on clinical outcome and was not facilitated by treatment with 0.9 mg of intravenous rTPA.

Aged↗
PubMed2000

Dismal rehabilitation in predominantly type II diabetics on dialysis in Inner-City Brooklyn.

AIM: In order to define their demographics and medical conditions, 218 diabetic patients undergoing hemodialysis in Brooklyn were interviewed and their charts reviewed. METHODS: Patient rehabilitation was assessed with the Karnofsky score, and the urea reduction rate as well as serum albumin and hematocrit levels evaluated adequacy of hemodialysis. RESULTS: The majority of patients (167) were African-American, 25 were Whites, 19 patients were Hispanic and 6 were Asian. One patient was a Native American. The mean age was 60.5 years (range 16-88), and the majority, 52%, were women. Rehabilitation was poor, the mean Karnofsky score being 65.1+/-20.8, and only 6% of patients were working. By linear regression, there was no difference in the Karnofsky score according to gender, age, race, type of diabetes, education, family income or hematocrit level. Only the patients' self-perception of their psyche function, or how well they thought they were doing, was significant. CONCLUSION: Further work is needed to examine the reasons for the poor rehabilitation of diabetics on dialysis in Brooklyn.

Diabetes Mellitus, Type 1↗
PubMed2000

The existence of insoluble-rheumatoid factor based immune complexes in menstrual fluid.

The aim of this study was to examine the existence of insoluble immune complexes, composed of monoclonal rheumatoid factor (human decidua-associated protein-hDP 200) in the precipitate of menstrual fluid. The identification of precipitable immune aggregates was based on immunofluorescent staining and ELISA. Both assays demonstrated the existence of rheumatoid factor, as well as immunoglobulins IgG, IgM, IgA and IgE. The quantification of immunoglobulins by ELISA demonstrated the predominance of IgG and rheumatoid factor. Furthermore, ELISA was performed to demonstrate the rheumatoid factor activity in the precipitate obtained from menstrual fluid. Thus, the rheumatoid factor, identified by monoclonal antibody DEC 21, was demonstrated to form precipitable immune complexes, which might provide a physiological mechanism to remove the unnecessary antibodies formed due to fetal allograft or intra-uterine infection.

Antigen-Antibody Complex↗
PubMed2000

Overexpression and reconstitution of a Rieske iron-sulfur protein from the cyanobacterium Synechocystis PCC 6803.

Chloroplast cyt b6f complexes as well as mitochondrial and bacterial cyt bc1 complexes contain a high potential Rieske iron-sulfur protein which is essential for their function. To characterise the isolated Rieske protein from the mesophilic cyanobacterium Synechocystis PCC6803 we cloned the encoding gene into an expression vector and overexpressed the protein in E. coli. In cells overexpressing the protein no typical Rieske type EPR signal was detected neither in membranes nor in inclusion bodies where the majority of the protein was deposited. The inclusion bodies were isolated from the E. coli cells and denaturated with 8 M urea. With a single anion exchange chromatographic step a pure protein could be obtained which was used for further experiments. The NifS like protein IscS was recently reported to mediate the incorporation of iron-sulfur clusters into ferredoxin in vitro. We used the recombinant IscS protein for the incorporation of the cluster into the folded Rieske apoprotein. Spectroscopic characterisation of the resultant protein by CD and EPR spectroscopy showed the presence of a typical Rieske iron-sulfur centre.

Base Sequence↗
PubMed2000

Competitive-kinesthetic interaction therapy.

The competitive-kinesthetic interaction therapy is based on several clinical observations of patients who are treated with the Brügger therapy in the "Murnau approach" and who are suffering from different pain syndromes in their movement system. These patients reported definite lessening of their tinnitus, including (in some cases) a complete cessation of their subjective ear noise, as a result of our therapy on the movement system. Our goal is to modulate and automate the civilizatory unforable engraved individual global movement patterns. This success, which accompanied the therapeutic removal of movement imbalance and related posture and motion disorders, suggests the possibility of influencing the balance-surveying organs of the complex equilibrium system, summarizing the information from the equilibrium tetrad within a central space-oriented data processing system, via the muscles of the entire locomotor system. A very important point is that the subjective improvements can be objectified in brain electrical activity mapping of vestibular evoked potentials. Two-hundred patients were treated with this therapy and were examined between April 1998 and April 1999.

Adolescent↗
PubMed2000

Gingko biloba (Rökan) therapy in tinnitus patients and measurable interactions between tinnitus and vestibular disturbances.

Tinnitus is one of the most important symptoms in neurootology after vertigo, nausea, and hearing loss. In most cases, the origin of the tinnitus remains inexplicable. Well-known, however, is that tinnitus may arise in any part of the hearing pathway (i.e., both within the cochlea receptor and in the temporal lobe and projections). Tinnitus also is associated frequently with vertigo, nausea and hearing loss. An age predominance exists, with tinnitus more common among those older than 40 years. From this starting point, a great demand exists today for new ideas and developments in the diagnosis and treatment of tinnitus.

Audiometry↗
PubMed2000

Audiovestibular findings prior to and after acoustic neuroma surgery.

We performed a retrospective study of 131 patients who underwent microsurgical removal of statoacoustic neuroma at the University of Wuerzburg. Our goal was to evaluate objective audiovestibular findings prior to and after surgery. Our analysis focused on the evaluation of quantitative parameters in speech and pure-tone audiometry and on the reactivity of the vestibular system.

Adolescent↗
PubMed1999

[Expression of selenoproteins in monocytes and macrophages--implications for the immune system].

Monocytes differentiate from myeloid precursors towards the macrophage state of differentiation under the influence of 1,25-dihydroxy vitamins D3 (1,25 [OH]2 vitamin D3) and other factors and this is further propagated by colony stimulating factors (MCSF and GMCSF). Macrophage activation and phagocytosis of foreign particles are regularly accompanied by a so called "respiratory burst", an increase in the production of reactive oxygen species (ROS), exerted by the enzyme complex NADPH oxidase. A number of antioxidant enzymes is expressed at the same time to protect the cells from the cytotoxic effects of ROS directed against engulfed microorganisms. The selenium-dependent glutathione peroxidases and thioredoxin reductases are important examples. The cytosolic GPx isoenzyme (cGPx) and thioredoxin reductase alpha (TrxR alpha) are upregulated during the process of differentiation and under the influence of 1.25 (OH)2 vitamin D3. GPx isoenzymes neutralize H2O2. TrxR reduce sulfhydryl-groups like in cysteins either directly or via their cofactor thioredoxin and thus are involved in protein folding and critical protein-protein and protein-DNA interactions, e.g. modulation of dimerization and/or DNA-binding and ligand binding of transcription factors (glucocorticoid receptor and other steroid receptors, NF kappa B). In addition, the antibiotic peptide NK-lysin was shown to be a substrate for TrxR alpha, suggesting that TrxR protects the cell itself from the cytotoxic effects of NK-lysin. Selenium is incorporated into selenocysteine (Secys) in a regulated fashion in the presence of a hairpin structure (Secis element) in the 3'UTR of selenoprotein genes. Secis elements direct the insertion of Secys at UGA codons, which function as opal stop codons in the absence of a suitable Secis element and in selenium deficiency. The above mentioned processes might therefore be altered in relative selenium deficiency or vice versa be upregulated through selenium supplementation. We have shown that TrxR alpha is a 1.25 (OH)2 vitamin D3-responsive early gene in monocytic cells and that TrxR activity as well as GPx activity in these cells can be upregulated by the addition of selenium in vitro and ex vivo. Recent work demonstrates that thioredoxin rapidly enters the cell nucleus upon treatment of cells with H2O2, but little is known about the compartimentalization of the respiratory burst and the intracellular localization of antioxidant enzymes during that process. Macrophage function is insufficient if the generation of a respiratory burst is altered like in hereditary chronic granulomatous disease on one hand, but on the other hand is as well disturbed, if there is a lack in antioxidant enzyme activity. Thioredoxin has been identified as a lymphocyte growth factor and might therefore be involved in the crosstalk between macrophages and lymphocytes. The relevance of the above mentioned and other yet undefined monocytic selenoproteins remains to be elucidated in detail as well as the relevance of selenium supplementation in nutrition in general and in situations of critical infectious disease and autoimmunity.

Animals↗
PubMed1999

Unique lipoproteins secreted by primary astrocytes from wild type, apoE (-/-), and human apoE transgenic mice.

Composition of central nervous system lipoproteins affects the metabolism of lipoprotein constituents within the brain. The epsilon4 allele of apolipoprotein E (apoE) is a risk factor for Alzheimer's disease via an unknown mechanism(s). As glia are the primary central nervous system cell type that synthesize apoE, we characterized lipoproteins secreted by astrocytes from wild type (WT), apoE (-/-), and apoE transgenic mice expressing human apoE3 or apoE4 in a mouse apoE (-/-) background. Nondenaturing size exclusion chromatography demonstrates that WT, apoE3, and apoE4 astrocytes secrete particles the size of plasma high density lipoprotein (HDL) composed of phospholipid, free cholesterol, and protein, primarily apoE and apoJ. However, the lipid:apoE ratio of particles containing human apoE is significantly lower than WT. ApoE localizes across HDL-like particle sizes. ApoJ localizes to the smallest HDL-like particles. ApoE (-/-) astrocytes secrete little phospholipid or free cholesterol despite comparable apoJ expression, suggesting that apoE is required for normal secretion of astrocyte lipoproteins. Further, particles were not detected in apoE (-/-) samples by electron microscopy. Nondenaturing immunoprecipitation experiments indicate that apoE and apoJ reside predominantly on distinct particles. These studies suggest that apoE expression influences the unique structure of astrocyte lipoproteins, a process further modified by apoE species.

Animals↗
PubMed1999

Genomic evolution during a 10,000-generation experiment with bacteria.

Molecular methods are used widely to measure genetic diversity within populations and determine relationships among species. However, it is difficult to observe genomic evolution in action because these dynamics are too slow in most organisms. To overcome this limitation, we sampled genomes from populations of Escherichia coli evolving in the laboratory for 10,000 generations. We analyzed the genomes for restriction fragment length polymorphisms (RFLP) using seven insertion sequences (IS) as probes; most polymorphisms detected by this approach reflect rearrangements (including transpositions) rather than point mutations. The evolving genomes became increasingly different from their ancestor over time. Moreover, tremendous diversity accumulated within each population, such that almost every individual had a different genetic fingerprint after 10,000 generations. As has been often suggested, but not previously shown by experiment, the rates of phenotypic and genomic change were discordant, both across replicate populations and over time within a population. Certain pivotal mutations were shared by all descendants in a population, and these are candidates for beneficial mutations, which are rare and difficult to find. More generally, these data show that the genome is highly dynamic even over a time scale that is, from an evolutionary perspective, very brief.

Biological Evolution↗
PubMed1999

Mortality after all major types of osteoporotic fracture in men and women: an observational study.

BACKGROUND: Mortality increases after hip fractures in women and more so in men. Little is known, however, about mortality after other fractures. We investigated the mortality associated with all fracture types in elderly women and men. METHODS: We did a 5-year prospective cohort study in the semi-urban city of Dubbo, Australia, of all residents aged 60 years and older (2413 women and 1898 men). Low-trauma osteoporotic fractures that occurred between 1989 and 1994, confirmed by radiography and personal interview, were classified as proximal femur, vertebral, and groupings of other major and minor fractures. We calculated standardised mortality rates from death certificates for people with fractures compared with the Dubbo population. FINDINGS: 356 women and 137 men had low-trauma fractures. In women and men, mortality was increased in the first year after all major fractures. In women, age-standardised mortality ratios were 2.18 (95% CI 2.03-2.32) for proximal femur, 1.66 (1.51-1.80) for vertebral, 1.92 (1.70-2.14) for other major, and 0.75 (0.66-0.84) for minor fractures. In men, these ratios were 3.17 (2.90-3.44) for proximal femur, 2.38 (2.17-2.59) for vertebral, 2.22 (1.91-2.52) for other major, and 1.45 (1.25-1.65) for minor fractures. There were excess deaths (excluding minor fractures in women) in all age-groups. INTERPRETATION: All major fractures were associated with increased mortality, especially in men. The loss of potential years of life in the younger age-group shows that preventative strategies for fracture should not focus on older patients at the expense of younger women and of men.

Age Distribution↗
PubMed1999

[Endovascular treatment of the abdominal aortic aneurysm: assessment, implantation technique, after-care and results].

BACKGROUND: Endovascular treatment of abdominal aortic aneurysm (AAA) is a new minimally invasive alternative to surgical repair. Patient selection, perioperative management, the procedure itself and postoperative follow-up are new aspects. PATIENTS: From June 1997 to June 1998, 37/70 patients (53%) with AAA were treated by the endovascular method. There were 35 males and two females, mean age 74 +/- 7 years, with a mean ASA class of 3.5 +/- 0.5. Graft repair was performed in 33 patients, due to inappropriate aortic anatomy for the endovascular technique in 24 and leaking aneurysm in 9. METHODS: Feasibility is based upon computed tomography and angiography. The procedure was performed in the operating room, under general, regional and local anaesthesia in 14, 3 and 20 patients, respectively. 36 bifurcated and one tube endoprosthesis were implanted. An open access on one femoral or iliac artery and, in case of bifurcated prosthesis, usually a percutaneous access (10 Fr) on the other side were performed. Positioning and delivery were monitored under fluoroscopy. RESULTS: All the AAA could be sealed by the endovascular technique. In one patient, an iliac limb was removed surgically because of proximal misplacement, but the procedure was completed by the endovascular technique. Mean operation time was 140 +/- 67 minutes. ICU stay was 1.4 +/- 1.6 days and patients were discharged after 6.5 +/- 3.5 days. Postoperative radiological follow-up showed totally sealed aneurysms in 34/37 patients (91%). In 3 patients a residual perfusion originating from a lumbar artery was observed. In 7/14 patients with AAA diameter > 6 cm and without residual leakage on the control CT scan, aneurysm pulsation remained after endovascular treatment. There was no early or late death after endovascular repair. During the follow-up period of 4 +/- 3 months patients are doing well. One patient needed balloon dilatation of an iliac limb. CONCLUSIONS: Endovascular treatment of AAA is a minimally invasive technique with short recovery time. This technique seems to be particularly advantageous in elderly or severely ill patients. Long-term controls are mandatory to identify potential complications, particularly when residual perfusion or aneurysm pulsation persists.

Aged↗