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Biomedical subjects

O Sezer

Publications and source records attributed to O Sezer.

66 records · Page 4Linked to original sources

Quality monitoring, standardized documentation and management with a computerized system in oncology.

Within the last years the prerequisite was prepared to develop a computerized tumor--patient documentation system including quality monitoring and oncological therapy recommendations for every day use. In medicine today, there is an increasing need for quality oriented low cost and transparent management--what is especially true in the field of oncology. The German Federal Authority of Health demands the documentation of all tumor disorders for the establishment of an cancer registry. For these reasons our study group established the program "OncoDoc" in cooperation with the laboratory for Artificial Intelligence of the University Bremen.

Artificial Intelligence↗

[Gastrointestinal lymphomas: results of multimodal therapy in 57 patients of one center].

From 1982-1995, 57 patients with primary gastrointestinal lymphoma were treated with a multimodality therapy. Of these patients, 36 were primary operated, 43 were given an isolated or postoperative chemotherapy and 17 were treated with radiation. Primary operated patients have a significantly better chance of relapse-free survival than those only treated conservatively.

Antineoplastic Combined Chemotherapy Protocols↗

A pyruvate-stimulated adenylate cyclase has a sequence related to the fes/fps oncogenes and to eukaryotic cyclases.

The pyruvate-stimulated adenylate cyclase from Brevibacterium liquefaciens produces up to 450 microM cyclic AMP in the culture medium when the bacterium is grown on glucose and alanine. In this paper we report the cloning, expression and sequencing of the gene for this enzyme. Residues were identified, within the C-terminal domain, which are conserved in adenylate and guanylate cyclase sequences from eukaryotes and in the adenylate cyclase of the prokaryote Rhizobium meliloti. We have also identified a sequence of 30 residues near the N-terminus of the protein which is homologous to part of the regulatory domain of the cellular homologues of the oncogenes fes and fps; this sequence is also present in the avian Fujinami sarcoma virus fps gene.

Adenylyl Cyclases↗

Cloning and expression of mouse-brain calmodulin as an activator of Bordetella pertussis adenylate cyclase in Escherichia coli.

Cloning of higher eukaryotic genes has seldom been performed by complementation of a defective prokaryotic function. This is especially true in the case of functions that are normally absent from the prokaryotic host. We demonstrate here that it is possible to identify by complementation the cDNA from mouse brain, which encodes calmodulin (CaM) synthesis, in spite of the fact that the recipient strain, Escherichia coli, does not normally harbour a CaM function. A three-component cloning procedure in which a gene product requiring CaM for activity, adenylate cyclase from the pathogen Bordetella pertussis, was used to screen a cDNA library for cAMP synthesis in E. coli. The nucleotide sequence of the corresponding cDNA is also reported.

Adenylyl Cyclases↗

Structural homology between virulence-associated bacterial adenylate cyclases.

The primary structure of the calmodulin-sensitive adenylate cyclase toxin from Bacillus anthracis has been determined from the corresponding nucleotide sequence and compared to that of the homologous toxin secreted by Bordetella pertussis. The cya gene of Bacillus anthracis encodes an 800 amino acid (aa) protein beginning with an N-terminal signal peptide. The central part of the B. anthracis adenylate cyclase includes a region of striking homology with the N-terminal part of the B. pertussis enzyme. In this region a particularly well conserved 24-aa peptide and two other less homologous peptides have been identified. These data corroborate the immunological relatedness of the two enzymes and suggest that the two prokaryotic calmodulin-sensitive adenylate cyclases originate from a common ancestor.

Adenylyl Cyclases↗

The calmodulin-sensitive adenylate cyclase of Bordetella pertussis: cloning and expression in Escherichia coli.

The adenylate cyclase toxin of the prokaryote Bordetella pertussis is stimulated by the eukaryotic regulatory protein, calmodulin. A general strategy, using the adenylate-cyclase-calmodulin interaction as a tool, has permitted cloning and expression of the toxin in Escherichia coli in the absence of any B. pertussis trans-activating factor. We show that the protein is synthesized in a large precursor form composed of 1706 amino acids. The calmodulin-stimulated catalytic activity resides in the amino-terminal 450 amino acids of the adenylate cyclase. The enzyme expressed in E. coli is recognized in Western blots by antibodies directed against purified B. pertussis adenylate cyclase, and its activity is inhibited by these antibodies.

Adenylate Cyclase Toxin↗

Development of ischemia-induced damage in defined mitochondrial subpopulations.

Two mitochondrial subpopulations were isolated from guinea-pig heart by density gradient centrifugation. Under control conditions, both contain functionally intact mitochondria in which ischemic damage develops similarly. However, in one subpopulation adenine nucleotide content, adenine nucleotide translocase activity, oxidative phosphorylation and Ca2+ uptake are a quarter lower than in the other one when related to mitochondrial protein mass. Cytochrome contents and uncoupled electron flux are the same. Changes develop most evidently at the very beginning of ischemia for NAD-linked respiration. When ischemia progresses, cytochromes and the translocator protein are gradually lost or inactivated. Thereupon only partial recovery of mitochondrial function can be obtained after 20 min of reperfusion.

Adenine Nucleotides↗

Fatty acid-membrane interactions in isolated cardiac mitochondria and erythrocytes.

The effects of long-chain fatty acids on mitochondrial functions and red cell stability were studied. In albumin-containing incubation media, fatty acid distribution between the albumin-bound and the unbound fraction was estimated by calculation. When fatty acids are compared to one another on the basis of identical unbound concentrations, their effectiveness differs by orders of magnitude. Fatty acids stimulate mitochondrial basic oxygen consumption, thus lowering the respiratory control index, without changing the ATP/O ratio at lower concentrations. Lower concentrations increase Ca2+ uptake velocity, but decrease maximal Ca2+ storage capacity. The order of effectiveness of different fatty acids is the same for both oxidative phosphorylation and Ca2+ uptake. The influence of fatty acids on red cell stability in hypotonic media is similar to these effects both in concentration range and in order of effectiveness. The influence of fatty acids on red cell stability and their critical micellar concentrations were investigated because these are general characteristics of 'detergent-like' compounds. Critical micellar concentrations of the fatty acids in physiological salt buffers are, in general, at least 10-fold higher than the concentrations exhibiting membrane effects in vitro. Based on these findings it is suggested that, of the various concentrations reported in literature for myocardial non-esterified fatty acids, only the lowest values are physiologically possible.

Animals↗

Acyl-carnitine effects on isolated cardiac mitochondria and erythrocytes.

The effects of various long-chain acyl-carnitines (AC) on mitochondrial functions and red cell membrane stability were studied. Lower concentrations slightly stimulate respiration-dependent functions such as phosphorylation rate and Ca++ uptake velocity, whereas higher concentrations inhibit these functions with concomitant depression of the ATP/O ratio. The order of effectiveness among the AC is very similar for different mitochondrial functions. The differences among AC in their actions on red cell stability in hypotonic media and their differences in influence on mitochondrial functions exhibit less resemblance. The relative order of erythrolytic concentrations of AC follows the order of their critical micellar concentrations. Model calculations indicate that the concentrations of AC found in ischemic hearts are below those which exhibit inhibitory effects in vitro. Ultrastructural changes in mitochondria incubated with AC are different from those found in ischemic tissue. From this, it seems questionable whether the elevated AC levels in ischemic hearts are indeed as important for the development of membrane damage as is often supposed.

Adenosine Triphosphate↗

Disseminated mucormycosis caused by Absidia corymbifera leading to cerebral vasculitis.

An 18-year-old woman was admitted to hospital because of subcutaneous hematoma and fever of unknown origin. Acute myeloid leukemia was diagnosed and empirical antimicrobial treatment and induction chemotherapy were started. After initial defervescence, fever relapsed 2 days after the onset of neutropenia. The CT scan of the lung was consistent with an invasive fungal infection. Treatment with amphotericin B was started and antimicrobial treatment was continued with liposomal amphotericin B because of an increase in creatinine later. The fever persisted and the patient suddenly developed progressive neurological symptoms. CT scan of the head suggested cerebral infarction and angiography of the extra- and intracranial arteries showed signs of vasculitis. Six days after the onset of neurological symptoms cerebral death was diagnosed. Autopsy revealed non-septate, irregularly branched hyphae in various histologic sections including brain. Absidia corymbifera could be isolated from lung tissue confirming the diagnosis of disseminated mucormycosis. In this case, angiographic findings suggested severe cerebral vasculitis which was in fact caused by thromboembolic dissemination of fungal hyphae. This case underlines the fact that cerebral symptoms in febrile neutropenic patients are highly indicative for fungal infections of the brain.

Absidia↗

Adjuvant high-dose chemotherapy with epirubicin and ifosfamide in nodal positive breast cancer.

INTRODUCTION: Morbidity and mortality, disease-free- and overall survival were analysed in an adjuvant high-dose chemotherapy (HDCT) study with ifosfamide and epirubicin for high-risk (> or = 10 positive lymph nodes) breast cancer. PATIENTS AND METHODS: A total of 21 patients (pts) were treated with 4 cycles of ViEC (vindesine, epirubicin, cyclophosphamide) as standard chemotherapy. After the second cycle, CD34+ stem cells were mobilised with G-CSF. HDCT consisted of epirubicin 100 mg/m2 on days (-5)-(-4) before stem-cell rescue and ifosfamide 5000 mg/m2 on days (-5)-(-2). RESULTS: No therapy-related deaths occurred. Mucositis WHO grade III/IV in 52% and neutropenic fever in 81% were the most relevant toxicities. Nausea and vomiting WHO grades III/IV were found in 62.2%. The median duration of leucopenia grade IV was 7 days (range: 4-11) with a median time to platelet recovery > 50,000/microliter of 6 days (range: 4-11). After a median follow-up time of 21 months (range: 12-49 months), six of 21 pts (28.6%) relapsed. Two patients died 12 and 18 months after initial diagnosis. CONCLUSIONS: Adjuvant HDCT with epirubicin and ifosfamide is safe and shows good tolerability for high-risk breast cancer.

Adult↗