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Biomedical subjects

E Bauer

Publications and source records attributed to E Bauer.

At least 55 records · Page 3Linked to original sources
PubMed1999

Molecular effects of topoisomerase II inhibitors in AML cell lines: correlation of apoptosis with topoisomerase II activity but not with DNA damage.

We examined the cellular effects of topo II inhibitors in two human myeloid cell lines, HL-60 and KG-1 cells, with the purpose of finding molecular markers for the sensitivity of leukemia cells to topo II inhibitors. These cell lines are widely used, well characterized and they differ in their sensitivities to topo II inhibitors. Despite the fact that HL-60 cells are p53-negative, they are much more sensitive than KG-1 cells. Three different topo II inhibitors with distinct molecular ways of action have been used. Daunorubicin and aclarubicin are DNA intercalators that secondarily interact with topo II; etoposide, on the other hand, directly binds to the enzyme. In contrast to daunorubicin, which induces protein-associated DNA double-strand breaks due to the blockage of topo II action, aclarubicin inhibits the access of DNA by topo II. No correlation could be established between the drug-induced DNA damage and apoptosis. In fact, the amount and pattern of DNA damage examined with the 'comet assay' was characteristic for each drug in both cell lines. The DNA binding of daunorubicin was slightly higher in HL-60 cells, but there was no notable variance between the cell lines for aclarubicin. The most striking difference could be found for the nuclear topo II activity, which was about half in KG-1 cells and, additionally, less than 1% of the nuclear topo II activity was bound to the DNA in KG-1 cells when compared to HL-60 cells. This fraction of topo II interacts with the inhibitors; subsequently these findings might well explain the variance in the cellular sensitivity. Additional factors are alterations of the apoptotic pathways, eg loss of p53 in HL-60 cells. Although we found no differences in the quantity of DNA damage between the cell lines after drug treatment, the quality of DNA damage appeared to be distinct for each topo II inhibitor. The morphological appearance of the comet tails after treatment was characteristic for each drug. Further studies are necessary to decide whether these in vitro data are compatible with the clinical situation.

Aclarubicin↗
PubMed1999

Implementing the right to community integration for children with disabilities in Russia: a human rights framework for international action.

Human rights organizations have documented a widespread pattern of abuse in Russia's orphanages and institutions for children with disabilities. Community integration is critical to attack the underlying causes of discrimination and abuse of children in institutions. While there is an immediate need to protect children in institutions, investment in improving orphanages may inadvertently strengthen an outmoded system of segregated services, delaying long-term reform. This article describes a response to abuses in institutions based on the internationally recognized right to community integration for all children, including children with mental and physical disabilities. While tailored to Russia, the framework for action described here applies to many countries in which children and adults with disabilities are similarly segregated from society in closed institutions.

Child↗
PubMed1998

Comet assay detects cold repair of UV-A damages in a human B-lymphoblast cell line.

During DNA repair studies, cells are occasionally kept on ice in order to suppress DNA repair. In the present studies cultivated human NC37 B-lymphoblasts were damaged by UV-A irradiation (365 nm) and DNA single strand breaks were detected at the single cell level with the alkaline comet assay in the temperature range from 4 degrees C to 44 degrees C. Single cell studies, in contrast to bulk experiments, allow to identify apoptotic or necrotic cells, which can be omitted for data analysis. Unexpectedly, similarly efficient single phase repair kinetics was found at all temperatures below 37 degrees C, i.e., particularly also in the cold. For recovery times below 20 min a linear decrease of DNA damage was detected. After 20 min, no additional repair was observed, i.e., complete repair of single strand breaks was not achieved. At 44 degrees C DNA damage increased with time, probably due to heat damage and cell death. Nucleotide excision repair inhibitors such as aphidicolin, 1-beta-D-arabinofuranosyl cytosine (araC) and hydroxyurea, but not the base excision repair inhibitor methoxyamine caused a strong increase in DNA strand breaks. The use of repair inhibitors confirmed DNA repair at 4 degrees C. In conclusion, partial repair of UV-A damage is similar at 37 degrees C and 4 degrees C and is probably governed by nucleotide excision repair. Keeping samples on ice may not result in a total suppression of DNA repair.

B-Lymphocytes↗
PubMed1998

The distribution of the tail moments in single cell gel electrophoresis (comet assay) obeys a chi-square (chi2) not a gaussian distribution.

The parameter tail moment in single cell gel electrophoresis (comet assay) is calculated as the product of the two values: the percentage of DNA in the comet tail and the tail length in microm. Experiments were performed with cultured mammalian cells: B-Lymphoblasts, epithelial cells of a kidney tissue and a plate-epithelial cell line of a human carcinoma. They were irradiated in suspension with UV A at lambda = 343 nm, generated by an excimer laser-pumped dye laser. DNA migration was assessed and analysed. It is demonstrated that the distribution of the tail moments can be fitted by a chi2 (chi-square) distribution, whereas the factors of the product tail moment tend to be normally distributed. From this result, consequences for the statistical evaluation of the results can arise, especially for the computation of the confidence limits and for the valuation of the parameter tail moment from other comet assay experiments.

Cells, Cultured↗
PubMed1998

Arthritis-related B cell epitopes in collagen II are conformation-dependent and sterically privileged in accessible sites of cartilage collagen fibrils.

In collagen-induced arthritis, a murine autoimmune model for rheumatoid arthritis, immunization with native but not heat-denatured cartilage-specific collagen type II (CII) induces a B cell response that largely contributes to arthritogenicity. Previously, we have shown that monoclonal antibodies established from arthritis prone DBA/1 mice require the triple-helical conformation of their epitopes for antigen recognition. Here, we present a novel approach to characterize arthritis-related conformational epitopes by preparing a panel of 130 chimeric collagen X/CII molecules. The insertion of a series of CII cassettes into the triple-helical recombinant collagen X allowed for the first time the identification of five triple-helical immunodominant domains of 5-11 amino acid length, to which 75% of 36 monoclonal antibodies bound. A consensus motif, "R G hydrophobic," was found in all immunodominant epitopes. The antibodies were encoded by a certain combination of V-genes in germline configuration, indicating a role of the consensus motif in V-gene selection. The immunodominant domains are spread over the entire monomeric CII molecule with no apparent order; however, a highly organized arrangement became apparent when the CII molecules were displayed in the quarter-staggered assembly within a fibril. This discrete epitope organization most likely reflects structural constraints that restrict the exposure of CII epitopes on the surface of heterotypically assembled cartilage fibrils. Thus, our data suggest a preimmune B cell selection process that is biased by the accessibility of CII determinants in the intact cartilage tissue.

Animals↗
PubMed1998

Expression of the fixR-nifA operon in Bradyrhizobium japonicum depends on a new response regulator, RegR.

Many nitrogen fixation-associated genes in the soybean symbiont Bradyrhizobium japonicum are regulated by the transcriptional activator NifA, whose activity is inhibited by aerobiosis. NifA is encoded in the fixR-nifA operon, which is expressed at a low level under aerobic conditions and induced approximately fivefold under low-oxygen tension. This induction depends on a -24/-12-type promoter (fixRp1) that is recognized by the sigma54 RNA polymerase and activated by NifA. Low-level aerobic expression and part of the anaerobic expression originates from a second promoter (fixRp2) that overlaps with fixRp1 and depends on an upstream DNA region (UAS) located around position -68 (H. Barrios, H. M. Fischer, H. Hennecke, and E. Morett, J. Bacteriol. 177:1760-1765, 1995). A protein binding to the UAS was previously postulated to act as an activator. This protein has now been purified, and the corresponding gene (regR) has been cloned. On the basis of the predicted amino acid sequence, RegR belongs to the family of response regulators of two-component regulatory systems. We identified upstream of the regR gene an additional gene (regS) encoding a putative sensor kinase. A regR mutant was constructed in which neither a specific UAS-binding activity nor fixRp2-dependent transcript formation and fixR'-'lacZ expression was detected in aerobically grown cells. Anaerobic fixR'-'lacZ expression was also decreased in regR mutants to about 10% of the level observed in the wild type. Similarly, regR mutants showed only about 2% residual nitrogen fixation activity, but unlike nodules induced by nifA mutants, the morphology of those nodules was normal, displaying no signs of necrosis. While regR mutants grew only slightly slower in free-living, aerobic conditions, they displayed a strong growth defect under anaerobic conditions. The phenotypic properties of regS mutants differed only marginally, if at all, from those of the wild type, suggesting the existence of a compensating sensor activity in these strains. The newly identified RegR protein may be regarded as a master regulator in the NifA-dependent network controlling nif and fix gene expression in B. japonicum.

Aerobiosis↗
PubMed1998

Resistance reflex that maintains upright head posture in the flesh fly neobellieria bullata (Sarcophagidae)

In flesh flies Neobellieria bullata, we investigated a resistance reflex that maintains upright head posture around the roll axis relative to the thorax. The gain of the reflex depends upon the fly's behavioral state: moving flies immediately correct 90 % of the amplitude of experimentally imposed roll perturbations, returning the head almost to the fully upright position; motionless flies allow perturbations to persist for minutes before correcting only 70 % of perturbation amplitude. To investigate the role of various neural pathways, we examined the control of head posture after sectioning relevant propriosensory or motor nerves. Excision of the prosternal chordotonal organ causes no decrements in the control of head posture. Unilateral deafferentation of a cervical propriosensory organ, the prosternal organ, induces roll towards the cut side. Unilateral section of the frontal nerve, a mixed motor nerve that supplies the neck depressors and levators, leads to unilateral deficits in correcting perturbations towards the contralateral side. After bilateral propriosensory or frontal motor nerve section, approximately 40 % of perturbation amplitude is still corrected. To determine the contributions of the passive elastic properties of the neck skeleto-muscular system, flies were tested under reversible nitrogen anesthesia. They immediately corrected 40 % of perturbation amplitude. Taken together, the results demonstrate that passive elasticity plus active prosternal nerve afference to contralateral depressors innervated by the frontal nerve in combination constitute a sufficient and necessary reflex loop to control head roll posture.

Journal Article↗
PubMed1998

[Not Available].

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Academies and Institutes↗
PubMed1998

[Value of computerized tomography in diagnosis of Boerhaave syndrome].

The mortality rate of spontaneous oesophageal rupture can be reduced by rapid diagnostic evaluation and early therapeutic intervention above all. We report on the prompt diagnosis of Boerhaave syndrome by thoracoabdominal CT scan and oesophagoscopy in a 75 year old female patient with false negative oesophagogram. The oesophageal rupture was transabdominally approached and closed by suture and a gastric fundus patch 6 hours after admission to the hospital. Pleural space lavage and drainage was done thru a left thoracotomy. The patient developed bronchopneumonia and sepsis and was discharged from the hospital 8 weeks post admission.

Aged↗
PubMed1998

Factors important in the purchase of partnership long-term care insurance.

OBJECTIVE: To understand the factors important in the purchase of long-term care insurance through the Robert Wood Johnson Foundation Partnership for Long-Term Care. DATA SOURCES: Information on the Partnership programs, telephone surveys, data on Partnership purchasers, and random sample frames. STUDY DESIGN: Logistic regression analysis is used to examine characteristics associated with the purchase of a Partnership insurance policy. Independent variables are health status, demographic and financial characteristics, knowledge, and attitudes. DATA COLLECTION: A telephone survey of Partnership purchasers and a random sample of the population in each Partnership state were conducted. Survey questions included health status, opinions about long-term care and long-term care insurance, financial planning, demographic characteristics, and income and assets. PRINCIPAL FINDINGS: Important in the purchase of a Partnership policy were variables associated with education and knowledge about long-term care. Other important factors include attitudes and health status. Partnership purchase is associated with higher income and asset levels up to a point, with the effect plateauing and decreasing at the highest income and asset levels. CONCLUSIONS: Improved education and knowledge are important in increasing long-term care insurance purchase. Attitudes about having a caregiver, and about the government's role in paying for long-term care as well as the potential purchaser's willingness to consider nursing home care affect policy purchase. Also associated with Partnership policy purchase are better health and middle income and asset levels.

Aged↗
PubMed1998

Imaging of adenoviral-directed herpes simplex virus type 1 thymidine kinase reporter gene expression in mice with radiolabeled ganciclovir.

UNLABELLED: We are developing procedures to repeatedly and noninvasively image the expression of transplanted reporter genes in living animals and in patients, using PET. We have investigated the use of the Herpes Simplex Virus type 1 thymidine kinase gene (HSV1-tk) as a reporter gene and [8-14C]-ganciclovir as a reporter probe. HSV1-tk, when expressed, leads to phosphorylation of [8-14C]-ganciclovir. As a result, specific accumulation of phosphorylated [8-14C]-ganciclovir should occur almost exclusively in tissues expressing the HSV1-tk gene. METHODS: An adenoviral vector was constructed carrying the HSV1-tk gene along with a control vector. C6 rat glioma cells were infected with either viral vector and uptake of [8-3H]-ganciclovir was determined. In addition, 12 mice were injected with varying levels of either viral vector. Adenovirus administration in mice leads primarily to liver infection. Forty-eight hours later the mice were injected with [8-14C]-ganciclovir, and 1 hr later the mice were sacrificed and biodistribution studies performed. Digital whole-body autoradiography also was performed on separate animals. HSV1-tk expression was assayed, using both normalized HSV1-tk mRNA levels and relative HSV1-TK enzyme levels, in both the cell culture and murine studies. RESULTS: Cell culture, murine tissue biodistribution and murine in vivo digital whole-body autoradiography all demonstrate the feasibility of HSV1-tk as a reporter gene and [8-14C]-ganciclovir as an imaging reporter probe. A good correlation (r2 = 0.86) between the [8-14C]-ganciclovir percent injected dose per gram tissue from HSV1-tk positive tissues and HSV1-TK enzyme levels in vivo was found. An initial study in mice with [8-18F]-fluoroganciclovir and microPET imaging supports further investigation of [8-18F]-fluoroganciclovir as a PET reporter probe for imaging HSV1-tk gene expression. CONCLUSION: These results demonstrate the feasibility of using [8-14C]-ganciclovir as a reporter probe for the HSV1-tk reporter gene, using an in vivo adenoviral mediated gene delivery system in a murine model. The results form the foundation for further investigation of [8-18F]-fluoroganciclovir for noninvasive and repeated imaging of gene expression with PET.

Adenoviridae↗
PubMed1997

Cyclosporine as maintenance therapy in patients with severe psoriasis.

BACKGROUND: Low-dose cyclosporine therapy for severe plaque psoriasis is effective. Most side effects can be controlled by patient monitoring, with appropriate dose adjustment or pharmacologic intervention, or both, if indicated. Prevention or reversibility of laboratory and chemical abnormalities may be achieved by discontinuation of therapy after the induction of clearing. However, relapse occurs rapidly on discontinuation. Maintenance therapy with cyclosporine after induction has not been fully evaluated. OBJECTIVE: Our purpose was to compare a regimen of 3.0 mg/kg per day of oral cyclosporine with placebo in maintaining remission or improvement in patients with psoriasis. METHODS: After a 16-week unblinded induction phase in which 181 patients received cyclosporine, 5.0 mg/kg per day (an increase up to 6.0 mg/kg per day and a decrease to 3.0 mg/kg per day were allowed, if required, to achieve efficacy or tolerability, respectively), those patients showing a 70% decrease or more in involved body surface area (BSA) entered the 24-week maintenance phase and were randomly assigned to either placebo, cyclosporine, 1.5 mg/kg per day, or cyclosporine, 3.0 mg/kg per day. Patients were considered to have had a relapse when BSA returned to 50% or more of the prestudy baseline value. Clinical efficacy, adverse effects, and laboratory values were monitored regularly throughout both study phases. RESULTS: During induction, cyclosporine at approximately 5.0 mg/kg per day produced a reduction in BSA of 70% or more in 86% of the patients. During maintenance, the median time to relapse was 6 weeks in both the placebo and cyclosporine 1.5 mg/kg per day groups, but was longer than the 24-week maintenance period in the 3.0 mg/kg per day group (p < 0.001 vs placebo). By the end of the maintenance period, 42% of the patients in the 3.0 mg/kg per day cyclosporine group had a relapse compared with 84% in the placebo group. Changes in laboratory values associated with the higher induction dosage generally exhibited partial or complete return toward mean prestudy baseline values during the maintenance phase, with the greatest degree of normalization in the placebo group. CONCLUSION: Cyclosporine, 3.0 mg/kg per day, adequately and safely maintained 58% of patients with psoriasis for a 6-month period after clearing of their psoriasis with doses of approximately 5.0 mg/kg per day.

Administration, Oral↗