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M Frank

Publications and source records attributed to M Frank.

At least 19 recordsLinked to original sources

GlycoMapsDB: a database of the accessible conformational space of glycosidic linkages.

Conformational energy maps of the glycosidic linkages are a valuable resource to gain information about preferred conformations and flexibility of carbohydrates. Here we present GlycoMapsDB, a new database containing more than 2500 calculated conformational maps for a variety of di- to pentasaccharide fragments contained in N- and O-glycans. Oligosaccharides representing branchpoints of N-glycans are included in the set of fragments, thus the influence of neighbouring residues is reflected in the conformational maps. During refinement of new crystal structures, maps contained in GlycoMapsDB can serve as a valuable resource to check whether the torsion values of a glycosidic linkage are located in an 'allowed' region similar to the Ramachandran plot analysis for proteins. This might help to improve the structural quality of the glycan data contained in the Protein Data Bank (PDB). A link between GlycoMapsDB and the PDB has been established so that the glycosidic torsions of all glycans contained in the PDB can be retrieved and compared to calculated data. The service is available at www.glycosciences.de/modeling/glycomapsdb/.

Carbohydrate Conformation↗

[Endovascular repair of a tuberculous aortic false aneurysm].

INTRODUCTION: Aortic aneurysms are a well known but rare complication of tuberculosis. Their major complication is aneurysmal rupture, unforeseeable and lethal. EXEGESIS: Chest pain and hemoptoic expectoration revealed a false aneurysm of the aortic isthmus in a 48-year-old man. Endovascular repair with a stent graft was urgently undertaken. Tuberculosis was diagnosed 6 weeks thereafter by the growth of gastric juice cultures and medically treated. Most tuberculous aortic aneurysms are false aneurysms, caused by an adjacent tuberculous focus eroding the aortic wall. They present with pain, bleeding or as para-aortic masses. CONCLUSION: Tuberculous false aneurysms of the aorta necessitate an early intervention before they rupture. Surgical treatment remains the preferred option but endovascular repair with a stent graft is a therapeutic alternative, to be considered in high-risk surgical patients.

Aneurysm, False↗

Fast determination of the relative elemental and organic carbon content of aerosol samples by on-line single-particle aerosol time-of-flight mass spectrometry.

Different particulate matter (PM) samples were investigated by on-line single-particle aerosol time-of-flight mass spectrometry (ATOFMS). The samples consist of soot particulates made by a diffusion flame soot generator (combustion aerosol standard, CAST), industrially produced soot material (printex), soot from a diesel passenger car as well as ambient particulates (urban dust (NIST) and road tunnel dust). Five different CAST soot particle samples were generated with different elemental carbon (EC) and organic carbon (OC) content. The samples were reaerosolized and on-line analyzed by ATOFMS, as well as precipitated on quartz filters for conventional EC/OC analysis. For each sample ca. 1000 ATOFMS single-particle mass spectra were recorded and averaged. A typical averaged soot ATOFMS mass spectrum shows characteristic carbon cluster peak progressions (Cn+) as well as hydrogen-poor carbon cluster peaks (CnH(1-3)+). These peaks are originated predominately from the elemental carbon (EC) content of the particles. Often additional peaks, which are not due to carbon clusters, are observed, which either are originated from organic compounds (OC-organic carbon), or from the non-carbonaceous inorganic content of the particles. By classification of the mass spectral peaks as elemental carbon (i.e., the carbon cluster progression peaks) or as peaks originated from organic compounds (i.e., molecular and fragment ions), the relative abundance of elemental (EC) and organic carbon (OC) can be determined. The dimensionless TC/EC values, i.e., the ratio of total carbon content (TC, TC = OC + EC) to elemental carbon (EC), were derived from the ATOFMS single-particle aerosol mass spectrometry data. The EC/TC values measured by ATOFMS were compared with the TC/EC values determined by the thermal standard techniques (thermooptical and thermocoulometric method). A good agreement between the EC/TC values obtained by on-line ATOFMS and the offline standard method was found.

Aerosols↗

[B-cell lymphoma of the testes].

The occurrence of primary non-Hodgkin's lymphomas of the testes is described in just a few studies in the urological literature. The clinical symptomatology and especially the treatment concept for this relatively rare tumor entity are hardly discussed. Imaging diagnostics, e.g., with CT or MRI, play a decisive role in determining the diagnosis and whether a primary testicular disease is involved or a generalized systemic disease. In cases of primary B-cell lymphomas of the testes, a high inguinal orchiectomy should be performed for diagnostic and therapeutic purposes. The standard chemotherapy for aggressive non-Hodgkin's lymphomas is the CHOP regimen consisting of cyclophosphamide, doxorubicin, vincristine, and prednisone. This article presents two adults aged 67 and 75 years with histologically proven B-cell lymphoma of the testes and discusses the characteristics of this relatively rare clinical picture as well as treatment and prognosis.

Aged↗

[Oral controlled-release oxycodone for the treatment of chronic pain. Data from 4196 patients].

Oral controlled-release oxycodone has been available for the treatment of chronic pain in Germany since 1998. Controlled trials have shown good clinical efficacy and tolerability. This survey reports results from six open prospective multicenter trials. In these trials 4196 patients suffering from cancer pain and non-cancer-related pain with inadequate pain relief were treated with oral controlled-release oxycodone for 3-4 weeks. Only a few participating physicians were pain specialists. A total of 356 patients suffering from pain of the musculoskeletal system and receiving oxycodone therapy were monitored for 6 months. Exclusion from the studies was due mainly to inadequate analgesia, side effects, and noncompliance. The efficacy of oxycodone was rated to be better than moderate by most of the patients, quality of life parameters increased significantly, and patient satisfaction was high. The treatment with oral controlled-release oxycodone was a safe and effective option even when used by nonspecialized physicians.

Administration, Oral↗

A therapeutic platelet transfusion strategy is safe and feasible in patients after autologous peripheral blood stem cell transplantation.

Prophylactic platelet transfusions are considered as standard in most hematology centers, but there is a long-standing controversy as to whether standard prophylactic platelet transfusions are necessary or whether this strategy could be replaced by a therapeutic transfusion strategy. In 106 consecutive cases of patients receiving 140 autologous peripheral blood stem cell transplantations, we used a therapeutic platelet transfusion protocol when patients were in a clinically stable condition. Platelet transfusions were only used when relevant bleeding occurred (more than petechial). Median duration of thrombocytopenia <20 x 10(9)/l and <10 x 10(9)/l was 6 and 3 days, which resulted in a total of 989 and 508 days, respectively. In only 26 out of 140 transplants (19%), we observed clinically relevant bleeding of minor or moderate severity. No severe or life-threatening bleeding was registered. The median and mean number of single donor platelet transfusions was one per transplant (range 0-18). One-third of all transplants, and 47% after high-dose melphalan could be performed without any platelet transfusion. Compared with a historical control group, we could reduce the number of platelet transfusions by one half. This therapeutic platelet transfusion strategy can be performed safely resulting in a considerable reduction in prophylactic platelet transfusions.

Adolescent↗

Differential modulation of gene expression in the NMDA postsynaptic density of schizophrenic and control smokers.

Nicotine is known to induce the release of multiple neurotransmitters, including glutamate and dopamine, through activation of nicotinic receptors. Gene expression in the N-methyl-d-aspartate postsynaptic density (NMDA-PSD), as well as other functional groups, was compared in postmortem hippocampus of schizophrenic and nonmentally ill smokers and nonsmokers utilizing a microarray and quantitative RT-PCR approach. The expression of 277 genes was significantly changed between all smokers and nonsmokers. Specific gene groups, most notably genes expressed in the NMDA-PSD, were prevalent among these transcripts. Analysis of the interaction between smoking and schizophrenia identified several genes in the NMDA-PSD that were differentially affected by smoking in patients. The present findings suggest that smoking may differentially modulate glutamatergic function in schizophrenic patients and control subjects. The biological mechanisms underlying chronic tobacco use are likely to differ substantially between these two groups.

Aged↗

[Controlled-release oxycodone--a therapeutic option for severe neuropathic pain. Two multicenter observational studies].

Two postmarketing studies (PMS) involving 603 patients with neuropathic pain treated with controlled-release oxycodone were performed. Pain intensity and impairment of performance were evaluated using a numeric rating scale (NRS) ranging from 0 to 10 (0 = no pain/impairment, 10 = most severe pain/impairment) measured at the start of the study, and at one week and some three weeks into the study. Mean pain intensity decreased from more than 6 at the start of the PMS to about 4 after one week, and under 3 after three weeks, of treatment. The mean dose of oxycodone after three weeks was slightly more than 40 mg per day. Impairment, quality of life and performance (daily activities, mood, sleep quality and joie de vivre) improved substantially.

Adult↗

[The elderly patient with urge incontinence or urge-stress incontinence - efficacy and cardiac safety of propiverine].

PURPOSE: The efficacy of propiverine in elderly patients suffering from urge incontinence or urge-stress incontinence was intended to be investigated. Especially in elderly patients a cardiac influence of propiverine is possible due to its dual mode of action. That is why besides the efficacy especially the cardiac safety was intended to be investigated. MATERIAL AND METHODS: Ninety-eight patients (21 male, 77 female; 67.7 +/- 6.3 years of age) suffering from urgency, urge incontinence or mixed urge-stress incontinence were included in the double-blind, multicentre, placebo-controlled, randomized study. After a two-week placebo run-in period, the patients received propiverine (15 mg t. i. d.) or placebo (t. i. d.) for four weeks. Before (U 1, U 2) and during the treatment period (U 3, U 4), standard ECG's and 24 h long-term ECG's were recorded. RESULTS: Propiverine caused a significant reduction in the micturition frequency (U 2 : 8.7 +/- 4.2, U 4 : 6.5 +/- 3.2 ml; p < 0.01) reflected in a significant increase in the average micturition volume (U 2 : 163.5 +/- 65.9, U 4 : 216.3 +/- 101.5 ml; p < 0.01) and a significant reduction in the episodes of incontinence (- 54 %; p < or = 0.05). These findings were confirmed by the overall assessment after four weeks in which approximately 90 % of patients under propiverine were either free from urge incontinence and urge symptoms or improved. The efficacy parameters demonstrated a better efficacy for urge incontinence than for mixed urge-stress incontinence. Resting and ambulatory electrocardiograms evidenced no significant changes. Neither QTc interval nor other cardiac parameters were relevantly altered. The frequency of cardiac events (Lown classes IV a/b) was fortuitous, revealing no difference between placebo and propiverine. The incidence of adverse events was very low (2 % dryness of the mouth under propiverine) and confirmed by the findings from the quality of life questionnaires. CONCLUSIONS: A favourable benefit-risk ratio in the treatment of elderly patients suffering from urgency, urge incontinence or combined urge-stress incontinence is therefore proven for propiverine. Cardiac arrhythmia were not induced.

Age Factors↗

[AFP-producing adenocarcinoma of the stomach. A rare tumor with poor prognosis].

A 27-year-old, previously healthy man with abdominal discomfort was diagnosed with a small gastric tumor of the cardia by means of gastroscopy. Further staging revealed diffuse hepatic metastases and enlarged mediastinal lymph nodes. Serum alpha-fetoprotein (AFP) was grossly increased (7179 micro g/l). Biopsies taken from the gastric tumor and one of the hepatic metastases revealed a poorly differentiated adenocarcinoma (grade 3) with papillary and small solid areas and frequent clear cells. Cytoplasmic hyaline droplets were positive with PAS staining (diastase-resistant). Immunohistochemistry revealed focal tumor cells strongly positive for AFP and there was luminal expression of CEA. The diagnosis of an AFP-producing adenocarcinoma of the stomach was made. In spite of intensive combination chemotherapy the patient succumbed to his disease 3 months after diagnosis. The rare AFP-producing adenocarcinoma of the stomach is characterised by a distinct morphology and immunohistochemistry. A hepatoid differentiation may occur but is not obligatory as this case shows. In differential diagnosis, a metastasising germ cell tumor should be excluded. The prognosis for an AFP-positive adenocarcinoma is poor.

Adult↗

Rafts in adult peripheral nerve myelin contain major structural myelin proteins and myelin and lymphocyte protein (MAL) and CD59 as specific markers.

The myelin and lymphocyte protein (MAL) proteolipid is localized in central and peripheral compact myelin membranes, as well as in apical membranes of particular polarized cells. In this study, we addressed the question whether MAL and other peripheral myelin proteins are sorted and targeted to myelin membranes using mechanisms similar to those observed in polarized epithelial cells. To investigate the presence of raft-mediated sorting pathways in Schwann cells, we have isolated and analysed their composition in myelin membranes. Here, we show that rafts are present in adult human and rat peripheral compact myelin membranes and contain MAL, the GPI-anchored protein CD59, and substantial amounts of the PMP22 and P0. Colocalization studies show that CD59, and MAL have an almost identical expression pattern within compact myelin. Moreover, immuno-electron microscopy revealed that MAL, besides its localization in compact myelin, is also localized to Schmidt-Lanterman incisures. Taken together, our results demonstrate the presence of detergent-insoluble glycolipid-enriched complexes (DIGs) in different compartments of myelin membranes and indicate an important role for DIG-mediated transport mechanisms in the maintenance of the adult myelin sheath.

Aged↗

The presynaptic particle web: ultrastructure, composition, dissolution, and reconstitution.

We report the purification of a presynaptic "particle web" consisting of approximately 50 nm pyramidally shaped particles interconnected by approximately 100 nm spaced fibrils. This is the "presynaptic grid" described in early EM studies. It is completely soluble above pH 8, but reconstitutes after dialysis against pH 6. Interestingly, reconstituted particles orient and bind PSDs asymmetrically. Mass spectrometry of purified web components reveals major proteins involved in the exocytosis of synaptic vesicles and in membrane retrieval. Our data support the idea that the CNS synaptic junction is organized by transmembrane adhesion molecules interlinked in the synaptic cleft, connected via their intracytoplasmic domains to the presynaptic web on one side and to the postsynaptic density on the other. The CNS synaptic junction may therefore be conceptualized as a complicated macromolecular scaffold that isostatically bridges two closely aligned plasma membranes.

Animals↗

Requirement for transforming growth factor beta1 in controlling T cell apoptosis.

Transforming growth factor (TGF)-beta1, a potent immunoregulatory molecule, was found to control the life and death decisions of T lymphocytes. Both thymic and peripheral T cell apoptosis was increased in mice lacking TGF-beta1 (TGF-beta1(-/-)) compared with wild-type littermates. Engagement of the T cell receptor enhanced this aberrant T cell apoptosis, as did signaling through either the death receptor Fas or the tumor necrosis factor alpha receptor in peripheral T cells. Strikingly, TGF-beta was localized within the mitochondria of normal T cells, and the absence of TGF-beta1 resulted in disruption of mitochondrial membrane potential (Deltapsi(m)), which marks the point of no return in a cell condemned to die. This TGF-beta-dependent regulation of viability appears dissociable from the TGF-beta1 membrane receptor-Smad3 signaling pathway, but associated with a mitochondrial antiapoptotic protein Bcl-XL. Thus, TGF-beta1 may protect T cells at multiple sites in the death pathway, particularly by maintaining the essential integrity of mitochondria. These findings may have broad implications not only for T cell selection and death in immune responses and in the generation of tolerance, but also for defining the mechanisms of programmed cell death in general.

Animals↗

"Electronic nose" detects major histocompatibility complex-dependent prerenal and postrenal odor components.

Mice prefer to mate with individuals expressing different MHC genes from their own. Volatile components presenting MHC-dependent odor types are present in urine and can be detected by mice, as shown by extensive behavioral studies. Similar odor types are suspected to influence human behavior as well. Although a recent report indicates that MHC expression influences the ratio of volatile compounds such as phenylacetic acid, so far no other means than studying the behavior of mice or rats has been available to assess odor types. Here, we report the ability of a gas sensor array (referred to as "electronic nose") to detect MHC-dependent odor types. The electronic nose consists of an array of chemophysical detectors, in our case quartz crystal microbalances and semiconducting metal-oxide sensors that change frequency or conductivity upon binding of very small numbers of individual molecules present in the gas phase of odorous fluids. The pattern of changes is characteristic for a particular smell. Our electronic nose distinguishes the urine odor types of MHC congenic mouse strains, MHC class I mutant mice, and HLA-A2 transgenic mice. In addition, MHC-dependent odor types can be detected in serum. The device also clearly differentiates between individual odor types of human sera from HLA homozygous individuals; however, HLA expression seems to have only a secondary influence. Thus, odor-type research can now be carried out with an objective and fast through-put system independent of behavioral studies.

Animals↗