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Biomedical subjects

A Wagner

Publications and source records attributed to A Wagner.

At least 181 records · Page 10Linked to original sources
PubMed2000

Induction of cellular genes is mediated by the Bel1 transactivator in foamy virus-infected human cells.

To gain insight into human foamy virus (HFV; also called spumaretrovirus)-induced alterations of cellular genes, the expression profiles of defined genes in HFV-infected primary human cells were analyzed by cDNA array assays. Several distinct cellular genes activated by HFV infection were identified; the identities of the cellular genes were confirmed by RNA blot analyses. Compared with mock-infected controls, the concentrations of cellular Kip2, Egr-1, COUP-TF1, insulin-like growth factor II (IGF-II), and EphB3 mRNAs were significantly increased in HFV-infected cells and showed a gene-specific and time-dependent induction. Immunoblot analyses with antibodies against some of the cellular gene products revealed increased levels of the corresponding proteins. To investigate mechanisms of HFV-induced alterations in cellular gene expression, the capacity of known HFV genes to increase expression of defined cellular genes was analyzed by transient expression experiments. Plasmids that encode the HFV Bel1 transcriptional transactivator were necessary and sufficient to strongly increase expression of p57Kip2, IGF-II, and EphB3 genes in 293T cells. Potential mechanisms and consequences of activation of cellular genes during HFV infection and Bel1 transactivation of the Kip2 gene are discussed.

Blotting, Northern↗
PubMed2000

The intact retroviral Env glycoprotein of human foamy virus is a trimer.

Electron microscopy of negatively stained human foamy virus particles provides direct evidence for the trimeric nature of intact Env surface glycoproteins. Three-dimensional image reconstruction reveals that the Env trimer is a tapering spike 14 nm in length. The spikes were often arranged in hexagonal rings which shared adjacent Env trimers.

Gene Products, env↗
PubMed2000

Interferon-alpha-associated development of bullous lesions in mycosis fungoides.

We report a 67-year-old woman with mycosis fungoides (MF) who was receiving subcutaneous injections of recombinant interferon alpha-2b (IFN-alpha). After 2 months of IFN-alpha treatment, bullous lesions appeared on her trunk and extremities. A skin biopsy specimen from the trunk revealed histopathologic features of bullous MF. Bullous lesions with specific infiltrates of MF are very rare; to the best of our knowledge, this is the first case showing specific bullous lesions of MF developed under IFN-alpha treatment.

Aged↗
PubMed2000

Pulsatile expansion therapy for orbital enlargement.

Experimental and clinical investigations have documented the modulatory role of the globe in the development of the orbit. In cases of absence or early loss of the globe, severe hypoplasia of the orbit and midface has been reported by several authors. Statical conformers and orbital osteotomies have been used to correct the resulting facial asymmetry. When replacing such conformers by increasingly larger ones, orbital structures are negatively influenced by the repeated trauma of surgical interventions. Simulating the modulatory role of the globe on orbital growth was the objective when developing a pulsatile device for orbital enlargement in cases of anophthalmia and microrbitism. The design, application and preliminary experience with a dynamic, pulsatile expanding system are presented.

Anophthalmos↗
PubMed2000

Quantitative analysis of tumor initiation in rat liver: role of cell replication and cell death (apoptosis).

The formation and development of initiated cells has been studied at the beginning of hepatocarcinogenesis. Rats received the genotoxic carcinogen N-nitrosomorpholine (NNM); placental glutathione S-transferase was used as a marker of initiated cells (G+ cells). Single G+ cells appeared within 24 h after NNM; their frequency increased steeply for approximately 2 weeks, then decreased and finally remained constant. G+ foci consisting of >/=2 G+ cells appeared successively after the single cells. Histological determination of DNA replication and apoptosis revealed that: the formation of single G+ cells may not depend on DNA replication of precursor cells; single G+ cells showed considerably lower DNA replication than G- normal hepatocytes; from the 2-cell stage onwards G+ foci displayed enhanced DNA replication and apoptosis. Data from histological sections were transformed into the third dimension by a new stereological method which considers the non-spherical shape of many G+ lesions. Rates of division and death of G+ cells and of formation and growth of G+ foci were estimated by a stochastic model: initially G+ clones appeared at a rate of 12 000 per day and liver until a maximal number of 176 000 (phase I) was reached; thereafter they declined to 134 000 (phase II); they then remained constant (phase III). Estimated division rates of G+ cells decreased from phase I to phase III, while the death rate increased in phase II, when every third G+ clone disappeared. As a result, at day 50 after NNM only 0.3% of G+ single cells had formed a clone containing >/=5 cells. In conclusion, experimental and computed parameters provide direct evidence that hepatocarcinogenesis evolves clonally and that initiated hepatocytes have a selective proliferation advantage, associated with an enhanced potential to undergo apoptosis. Thereby, depending on the conditions, initiated clones expand or become extinct. Extinction may lead to reversion of the biological effects of initiation.

Animals↗
PubMed2000

Sugar uptake and carbon catabolite repression in Bacillus megaterium strains with inactivated ptsHI.

We have determined the role played by the phosphoenolpyruvate:sugar phosphotransferase system (PTS) in carbon catabolite repression (CCR) of xylose utilization in Bacillus megaterium. For that purpose we have cloned, sequenced and inactivated the genes ptsH and ptsl of B. megaterium, encoding HPr and EI of the PTS, respectively. While glucose uptake of a ptsHI mutant is not affected at 12.5 mM of glucose, CCR of the xyl operon is reduced in this mutant from 16-fold to 3-fold. This may be attributed to the loss of the corepressor of CcpA, HPr(Ser-P), or could result from the slower growth rate of the mutant. In contrast, CCR exerted by fructose or mannitol is completely abolished. We conclude that glucose triggers additional mechanisms of CCR than fructose or mannitol. The remaining 3-fold glucose repression is relieved in a strain in which ptsHI and glk, encoding glucokinase, are inactivated. This result indicates that glucose metabolism is necessary for CCR. The ability of the ptsHI mutant to take up glucose suggests the existence of a second, non-PTS glucose uptake system. The Km and vmax values of this transporter ranged between 2 and 5 mM and 154 to 219 nmol/[(mg protein)*min], respectively.

Bacillus megaterium↗
PubMed2000

[Financial development of the Munich General Hospital 1830-1894].

The Munich General Hospital is typical for the modern hospital developing in the late 18th century. Before the introduction of the compulsory Imperial Health Insurance in 1884 in many southern states of Germany municipals installed some kind of insurance system to take care for their poor. These insurance systems were intended to provide hospital care for the lower classes and give the hospital a new source of income. The Munich General Hospital has been founded in 1813 and a voluntary insurance scheme was installed. This paper examines the financial development of the Munich General Hospital in the long run through studying its expenditures and sources of income from 1830/31 until 1894. Especially the effects of the various kinds of insurance schemes from the first voluntary insurance system (1813) until the compulsory Imperial Health Insurance (1884) on the hospital's financial capacity have been analysed. Until the 1830s the hospital struggled with serious financial problems because the founding fund was too small for the high number of non-paying patients. This situation was aggravated through the failure of the first insurance system which was subsequently reformed in 1832. With the new mandatory insurance scheme and the revenues of the founding fund the hospital reached in the following decades a high level of independence from traditional financing sources such as donations and public subsidies. The compulsory Imperial Health Insurance reinforced this trend. In consequence the hospital did not need any municipal subsidies to finance its regular expenditures.

Economics, Hospital↗
PubMed1999

Viral RNA and evolved mutational robustness.

Many properties of organisms show great robustness against mutations. Whether this robustness is an evolved property or intrinsic to genetic systems is by and large unknown. An evolutionary origin of robustness would require a rethinking of key concepts in the field of molecular evolution, such as gene-specific neutral mutation rates, or the context-independence of deleterious mutations. We provide evidence that mutational robustness of the genome of RNA viruses to mutational changes in secondary structure has evolved. J. Exp. Zool. ( Mol. Dev. Evol.) 285:119-127, 1999.

Animals↗
PubMed1999

Cerebral and meningeal multiple myeloma after autologous stem cell transplantation. A case report and review of the literature.

Meningeal involvement of multiple myeloma is a very rare complication. Defining meningeal myelomatosis (MeM) as the presence of plasma cells in the cerebrospinal fluid in a patient with multiple myeloma, we have found 53 previously reported cases in the literature, where the diagnosis MeM has been made while the patient was alive. Using Kaplan Meier statistics we have found the median survival, from the time of diagnosis of MeM, to be 1.5 months. We report a case with MeM and possible cerebral myeloma shortly after autologous stem cell transplantation, and compare it with earlier published cases.

Adult↗
PubMed1999

Pharmacokinetics of anticancer drugs in vitro.

It is generally assumed that drug concentration does not change significantly under cell culture conditions. Nevertheless, most of the therapeutic trials in acute leukemia that were based on in vitro drug sensitivity assays of patient samples have been disappointing. In order to show possible pitfalls of unphysiological alterations in vitro we investigated concentration versus time curves, metabolism and effects on the culture media for some antineoplastic drugs. Oxazaphosphorines and cytarabine were incubated in RPMI and in established cell lines and measured by HPLC. HPLC also served to measure enzyme activity and levels of related amino acids at various concentrations of asparaginase, ammonia release was photometrically determined. Etoposide was monitored by HPLC relative to different contents of FCS in RPMI. All oxazaphosphorines showed a rapid decrease of in vitro activity down to about 10% within 4-6 h, and 2% within 72 h. The level of cytarabine, when incubated in RPMI, was stable over 24h, and no change was seen with K562, while a rapid decrease to below 50% occurred within 6h in the presence of HL 60 and BLIN. 2 U/L of asparaginase led to asparagine depletion of the medium within 4h, while 200 U/L were associated with a preferential increase of glutamic acid and ammonia. Further, there was evidence of instability by rapid adsorption to plastic surfaces (paclitaxel) or isomerisation (etoposide) in RPMI with low FCS content. The instability of drugs in vitro is attributed to a variety of different factors: i.e. physico-chemical instability results in inactivation of oxazaphosphorines, cytarabine disappears by cellular metabolism without saturation depending on the cell-line. Epiphenomena like adsorption and isomerisation in vitro are unphysiological. Results of drug sensitivity assays should be interpreted with great caution.

Amino Acids↗
PubMed1999

Small-cell carcinoma of the ovary of the hypercalcemic type in an 8-year-old girl.

Tumors of the ovary in girls represent about 80% of pediatric genital tumors; approximately 30% of these tumors are malignant. The risk of malignancy increases with decreasing age. The most frequent finding is a teratoma; other tumors are rare. Small-cell carcinoma (SCCO) of the ovary is extremely rare, occurring mostly in young women. We present an 8-year-old girl with a SCCO of the hypercalcemic type. The findings and treatment are discussed with emphasis on the poor prognosis in these patients, even in stage 1 disease. The current literature is reviewed.

Abdominal Pain↗