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Biomedical subjects

C Förster

Publications and source records attributed to C Förster.

At least 19 recordsLinked to original sources
PubMed2004

[Microcystic adnexal carcinoma (malignant syringoma) of the nose: case report and review of the literature].

A case of Malignant Syringoma (syn. = Microcystic Adnexal Carcinoma, Sclerosing Swat Duct Carcinoma) of the nose in a 44 year old female patient is reported. The tumor had been misdiagnosed as a Rhinophyma some 20 years before and had thus been treated under cosmetic aspects. Besides the appearance, the patient did not suffer any complaints and was referred to the ENT-department of the Klinikum Hannover for cosmetic reasons. Histopathological examination after removal revealed a malignant syringoma, which, due to its extensive size and subepithelial growth pattern, made a complete ablation of the entire nose and the adjacent soft tissue of the face necessary. Pathohistologically cellular atypia, invasive growth pattern, perineural and perivascular infiltration was characteristic. Quantitative DNA anaylsis revealed a tumor with a diploid stem line and only few aneuploid cells. Malignant syringoma is a rare differential diagnosis of face skin tumors. The present case is discussed based on a review of the literature.

Adolescent↗
PubMed2001

Carrier-mediated transport of riboflavin in Ashbya gossypii.

The filamentous hemiascomycete Ashbya gossypii is used for industrial riboflavin production. We examined riboflavin uptake and excretion at the plasma membrane using riboflavin auxotrophic and overproducing mutants. The riboflavin uptake system had low activity [Vmax = 20 +/- 4 nmol min(-1) g(-1) mycelial dry weight (dw)] and high affinity (KM = 40 +/- 12 microM). Inhibitor studies with the analogs FMN and FAD revealed high specificity of the uptake system. Excretion of riboflavin was not the consequence of non-specific permeability of the plasma membrane. Excretion rates in the mid-production phase were determined to be 2.5 nmol min(-1) g(-1) dw for wild-type cells and 66.7 nmol min(-1) g(-1) dw for an overproducing mutant, respectively. Inhibition of the reverse reaction, riboflavin uptake, led to an increase in apparent riboflavin efflux in the early production phase, indicating the presence of a separate excretion carrier. Riboflavin accumulation in A. gossypii vacuoles leading to product retention was found to be a secondary transport process. To address the question of whether a flux from the vacuoles back into the cytoplasm is present, we characterized efflux in hyphae in which the plasma membrane was permeabilized with digitonin. Efflux kinetics across the vacuolar membrane were unaffected by the lack of vacuolar H+ATPase activity and ATP, suggesting a passive mechanism. Based on the characterization of riboflavin transport processes in this study, the design of new production strains with improved riboflavin excretion may be possible.

Ascomycota↗
PubMed2001

[Clinical use of the birth simulation program "Anapelvis 2.0" for prediction of feto-maternal disproportion].

INTRODUCTION: The birth simulation program Anapelvis 2.0 was developed to predict feto-maternal disproportion in order to avoid the unfavourable accompanying phenomena of a secondary caesarean section. - PATIENTS AND METHODS: The system was used in 71 patients of the Women's Hospital of the University of Mannheim during the period 01. 01. 1999 to 28. 02. 2001. These women were prone to feto-maternal disproportion according to their obstetrical history or to clinical findings. They were informed about the possibility of a computed birth simulation which was carried out in accordance with a standardized scheme. - RESULTS: 87.3 % of all patients followed the suggestion of the birth simulation in their decision concerning birth planning. In 76.1 % of the evaluated cases the delivery process was correctly predicted. - DISCUSSION: Even though the computed birth simulation has not yet been finally evaluated, it represents a source of important information for birth planning which numerous patients appreciate. It is essential for the acceptance and validity of the procedure to inform the patient comprehensively and to generate exact pelvimetric and fetometric data.

Cesarean Section↗
PubMed2000

De novo formation of an aneurysm in a case of unusual intracranial fibromuscular dysplasia.

Intracranial fibromuscular dysplasia (FMD) is a vascular disease of unknown origin occurring predominantly in young women. The internal carotid artery is most often involved, but other cerebral arteries may also be affected. We report the case of a young woman presenting with an unusual angiographic appearance of intracranial FMD of the internal carotid artery (ICA) that could not be categorized into any type of the Osborn-Anderson classification. During follow up the patient presented with an intracerebral and subarachnoid hemorrhage. Repeated angiography revealed multiple aneurysms in the pathologic segment of the vessel. The patient underwent surgical treatment with clipping of the aneurysms, wrapping of the pathologic segment of the ICA and biopsy of the superficial temporal artery. Histopathological sections revealed FMD of the intimal type. alpha(1)-antitrypsin blood levels were normal. Cases of intracranial FMD previously reported in the literature are reviewed and various aspects of this rare disease are discussed.

Adult↗
PubMed1999

Physiological consequence of disruption of the VMA1 gene in the riboflavin overproducer Ashbya gossypii.

The vacuolar ATPase subunit A structural gene VMA1 of the biotechnologically important riboflavin overproducer Ashbya gossypii was cloned and disrupted to prevent riboflavin retention in the vacuolar compartment and to redirect the riboflavin flux into the medium. Cloning was achieved by polymerase chain reaction using oligonucleotide primers derived form conserved sequences of the Vma1 proteins from yeast and filamentous fungi. The deduced polypeptide comprises 617 amino acids with a calculated molecular mass of 67.8 kDa. The deduced amino acid sequence is highly similar to that of the catalytic subunits of Saccharomyces cerevisiae (67 kDa), Candida tropicalis (67 kDa), and Neurospora crassa (67 kDa) with 89, 87, and 60% identity, respectively, and shows about 25% identity to the beta-subunit of the FoF1-ATPase of S. cerevisiae and Schizosaccharomyces pombe. In contrast to S. cerevisiae, however, where disruption of the VMA1 gene was conditionally lethal, and to N. crassa, where viable disruptants could not be isolated, disruption of the VMA1 gene in A. gossypii did not cause a lethal phenotype. Disruption of the AgVMA1 gene led to complete excretion of riboflavin into the medium instead of retention in the vacuolar compartment, as observed in the wild type.

Amino Acid Sequence↗
PubMed1999

Crystallization and X-ray diffraction data of a tRNASec acceptor-stem helix.

tRNASec is a UGA suppressor tRNA which co-translationally inserts selenocysteine into proteins. Its eight-base-pair tRNASec acceptor stem, which contains key recognition elements, was synthesized using solid-phase phosphoramidite RNA chemistry. High-resolution X-ray diffraction data were collected using synchrotron radiation under cryogenic cooling conditions. The crystals diffract to a maximal resolution of 1.8 A. X-ray diffraction data were processed to 2.4 A. tRNASec microhelix crystallizes in space group R32, with cell constants a = 47.02, b = 47.02, c = 373.03 A, alpha = beta = 90, gamma = 120 degrees. The crystals contain three RNA molecules per asymmetric unit.

Crystallization↗
PubMed1999

Preliminary characterization by X-ray diffraction and Raman spectroscopy of a crystalline complex of Bacillus stearothermophilus initiation factor 2 C-domain and fMet-tRNAfMet.

Bacillus stearothermophilus translation initiation factor 2 (IF2) specifically binds initiator fMet-tRNAfMet and positions it into the ribosomal peptidyl site in the course of the initiation of protein biosynthesis. The isolated C-terminal domain of IF2 is capable of binding fMet-tRNAfMet, as shown by RNase A and hydrolysis protection experiments. In the presence of fMet-tRNAfMet, the IF2 C-domain yielded orthorhombic crystals of space group I222 (I212121) diffracting to 3.4 A resolution. The existence of equimolar amounts of tRNA and protein in the crystals was proven by Raman spectroscopy. The observed unit cell suggests the presence of two IF2 C- domain-fMet-tRNAfMet complexes per asymmetric unit of the crystal.

Crystallography, X-Ray↗
PubMed1998

Organelle purification and selective permeabilisation of the plasma membrane: two different approaches to study vacuoles of the filamentous fungus Ashbya gossypii.

Two different approaches to prepare and characterise vacuoles from the filamentous fungus Ashbya gossypii are described, i.e. the isolation of vacuoles from hyphal cells and the controlled permeabilisation of the plasma membrane. By mechanical lysis of protoplasts and separation of the organelles on a stepped density gradient, we obtained a vacuolar fraction virtually free of contamination by other organelles, unlysed protoplasts and cell debris. The integrity of the isolated organelles was characterised by vital-staining, the presence of alpha-mannosidase, and retained accumulation of basic amino acids. In a second approach, the cell membrane of the fungus was selectively permeabilised by use of the saponin digitonin leaving the vacuoles in their physiological surrounding, i.e. protected by the rigid cell wall. The permeabilisation was monitored by the latency of predominantly cytosolic amino acids and the ATP status of the cells. Functional intactness of the vacuoles within the permeabilised hyphae was demonstrated by maintenance of the pH gradient across the vacuolar membrane as detected by accumulation of the fluorescent dye, Acridine orange. These two methods are well-suited tools for the in situ assay of intracellular compartmentation of metabolites, for vacuolar transmembrane fluxes in Ashbya gossypii, as well as for the direct access to vacuolar membranes and enzymes of this fungus.

Acridine Orange↗
PubMed1998

Effects of fluoroquinolones and magnesium deficiency in murine limb bud cultures.

Quinolone-induced arthropathy is probably caused by a lack of functionally available magnesium in immature joint cartilage. We used an in vitro assay to study the effects of fluoroquinolones on cartilage formation in mouse limb buds from 12-day-old mouse embryos in regular and in magnesium-deficient medium. Omission of magnesium from the medium had no adverse effect on the outcome of the culture: limb buds grew and differentiated well in regular and in magnesium-deficient Bigger's medium. Lack of calcium, however, severely impaired the development of the explants; this result was even more enhanced when both minerals (magnesium and calcium) were omitted. Electron microscopy revealed cell necrosis and deposition of electron-dense material in the vicinity of chondrocytes from limb buds after 6 days in a magnesium-free medium. A series of seven fluoroquinolones was tested at 30, 60, and 100 mg/l medium. At a concentration of 30 mg/l sparfloxacin only had a slight effect on limb development. At concentrations of 60 and 100 mg/l sparfloxacin, temafloxacin and ciprofloxacin impaired limb development in vitro concentration-dependently. The effects were enhanced in a magnesium-deficient medium (concentration of magnesium <10 micromol/l). Fleroxacin, lomefloxacin and ofloxacin impaired limb development only slightly; no significant differences were recognizable between the outcome in regular and in magnesium-deficient medium. Pefloxacin did not show any effect on limb development in both media. Using electron microscopy, very similar alterations as described above for the limbs cultured in magnesium-deficient medium were observed with ofloxacin at a concentration of 30 mg/l, which had no effect on the growth of the explants when evaluated macroscopically. The affinity of six fluoroquinolones to magnesium was determined by the use of a fluorescence assay. The affinity to magnesium correlated with the activity of the drugs in the limb bud assay. We conclude that fluoroquinolones have no effect on murine limb development in vitro at concentrations that are achieved under therapeutic conditions (peak concentrations approx. 1-5 mg/l in plasma). Effects at higher concentrations (60 and 100 mg/l) are slightly enhanced (factor 2) if the magnesium concentration in the medium is low. Macroscopically, limbs develop regularly in a magnesium-free medium, but ultrastructurally typical alterations are exhibited (e.g. cell necrosis and pericellular deposition of electron-dense material).

Animals↗
PubMed1998

Chondrotoxicity and toxicokinetics of sparfloxacin in juvenile rats.

Sparfloxacin is a fluoroquinolone with improved antibacterial activity against gram-positive pathogens. Like other quinolones, use of this drug is contraindicated in children and adolescents because of its potential chondrotoxicity in juveniles. We performed histological and immunohistochemical studies on the knee joint cartilage in 5-week-old rats after treatment with 600 or 1,800 mg of sparfloxacin/kg of body weight. Treatment with single or multiple oral doses of 600 mg of sparfloxacin/kg was not sufficient to induce joint cartilage lesions. However, five of eight rats treated with a single oral dose of 1,800 mg of sparfloxacin/kg of body weight showed typical cartilage lesions in the femoral part of the knee joint. The concentrations of the drug in plasma measured 0.25, 0.75, 1.5, 3, 6, 12, and 24 h after the administration of an oral dose of 600 mg of sparfloxacin/kg were 6.3 +/- 1.8, 9.2 +/- 1.7, 9.6 +/- 2.7, 13.0 +/- 1.8, 12.3 +/- 1.6, 3.4 +/- 0.4, and 0.30 +/- 0.20 mg/liter, respectively (mean +/- standard deviation [SD]; n = 5 to 6 per group). The concentrations in plasma measured 0.75, 1.5, 3, 6, 24, and 48 h after the administration of an oral dose of 1,800 mg of sparfloxacin/kg were 10.9 +/- 1.5, 15.9 +/- 1.6, 19.1 +/- 1.7, 14.9 +/- 3.1, 4.1 +/- 0.6, and 0.46 +/- 0.37 mg/liter, respectively (mean +/- SD; n = 3 to 4 per group). The concentrations of sparfloxacin in joint cartilage were significantly higher at all time points studied (114.8 +/- 80, 99.4 +/- 31.5, 84.9 +/- 16.8, 44.4 +/- 13.9, and 14.2 +/- 4.8 mg of sparfloxacin/kg at 1.5, 3, 6, 24, and 48 h after the administration of 1,800 mg/kg, respectively). The range of concentrations in bone were similar to the range of concentrations in cartilage (peak, 115 +/- 12 mg/kg after 3 h). Our data indicate that chondrotoxic doses of sparfloxacin in juvenile rats are approximately 300 times higher than the doses of sparfloxacin used therapeutically (1,800 versus approximately 6 mg/kg of body weight), but due to species differences in kinetics, concentrations in plasma differ by a factor of only approximately 15. More data on quinolone concentrations in cartilage from animals and humans could provide a better basis for a reasonable risk assessment.

Animals↗
PubMed1997

In vitro evidence for a Donnan distribution of Mg2+ and Ca2+ by chondroitin sulphate in cartilage.

Fluoroquinolones are known for their ability to form chelate complexes with magnesium. Cartilage lesions observed in juvenile animals after quinolone treatment very probably are a consequence of the lack of functionally available magnesium. In cartilage, which contains high amounts of negatively charged proteoglycans, a Donnan distribution can be expected leading to an inhomogeneous distribution of ions (such as magnesium), which may support the toxic effects of magnesium deficiency or quinolone treatment of cartilage. We performed in vitro experiments using dialysis tubes to simulate the unequal distribution of proteoglycans in cartilage and measured the distribution of magnesium, calcium and ofloxacin. We found that the concentration of free magnesium is significantly reduced with the chondroitin sulphate-free solution due to a Donnan effect. For example, using a 3% chondroitin sulphate solution (outside the tubing) dialysed against a chondroitin sulphate-free solution (inside the tubing) the magnesium concentration decreased by 24% from 0.55 +/- 0.02 to 0.42 +/- 0.04 mmol/l inside the tubing during 48 h observation (P < 0.01). Under physiological conditions this unequal distribution of magnesium probably will be much more pronounced because chondroitin sulphate concentrations in cartilage are higher; nevertheless, magnesium concentration is sufficient for regular function of the tissue. During the sensitive phase of quinolone toxicity, magnesium in juvenile cartilage is lower than at other time points during postnatal development. Moreover, additional complexation by quinolones may further reduce the concentration of functionally available magnesium below the critical level.

Animals↗
PubMed1997

Quinolone-induced arthropathy: exposure of magnesium-deficient aged rats or immature rats, mineral concentrations in target tissues and pharmacokinetics.

Quinolone treatment or magnesium deficiency induce identical cartilage lesions in juvenile rats and show additive arthropathogenic effects. It has been shown previously that neither condition is arthropathogenic in 8-week-old rats. Joint cartilage from aged individuals is rather prone to pathological alterations but information on prolonged quinolone treatment and/or dietarily induced magnesium deficiency in aged animals is not available. We treated magnesium-deficient (n = 9) aged Wistar rats (age 15 months) and age-matched controls with daily doses of 600 mg ofloxacin/kg body wt. by gastric intubation for 28 days. Further groups of magnesium-deficient and control rats (n = 9 and n = 10, respectively) received the vehicle only. Peak plasma concentrations of ofloxacin in adult rats were 20.5 +/- 5.6 mg/l (mean +/- SD) following treatment with a single dose of 600 mg/kg body wt. At the end of the experiment the degree of magnesium deficiency was most pronounced in plasma (Mg2+-def., 0.33 +/- 0.12 mmol/l; control, 0.97 +/- 0.08 mmol/l) and less pronounced in sternal cartilage (Mg2+-def., 10.8 +/- 3.6 mmol/kg dry wt; control, 13.3 +/- 2.8 mmol/kg dry wt), whereas the magnesium concentration in femoral bone remained unchanged (Mg2+-def., 201 +/- 13 mmol/kg dry wt; control, 204 +/- 11 mmol/kg dry wt). Histological investigation of the knee joints revealed no cartilage lesions following ofloxacin treatment, magnesium deficiency or a combination of both conditions. By contrast, cartilage lesions such as scars and erosions of the joint surface, chondrocyte clusters within acellular areas of the cartilage matrix and persisting clefts were detectable in knee joints from 7 of 10 adult rats (age 9 months) which had been treated with 4 x 600 mg fleroxacin/kg body wt. at 5 weeks of age. Mean plasma concentration of fleroxacin in juvenile rats was approx. 50 mg/l between 1.5 and 6 h after dosing and the drug was still detectable in plasma 48 h after dosing (0.4 +/- 0.1 mg/l). Our data indicate that joint cartilage in aged rats is not altered by a 4-week quinolone treatment, even during magnesium deficiency. Cartilage lesions in adult rats were only detectable if the animals had been treated during the sensitive phase at 5 weeks postnatally.

Age Factors↗
PubMed1997

Effects of magnesium deficiency on magnesium and calcium content in bone and cartilage in developing rats in correlation to chondrotoxicity.

Quinolone-induced arthropathy has been described in juvenile rats between 3 and 6 weeks of age, but not in adult rats. The mechanism of this chondrotoxic effect is probably related to the Mg2+-chelating properties of the drugs, since identical cartilage lesions were observed in magnesium-deficient juvenile rats without quinolone treatment. However, the reasons for the phase-specificity of the effect are unknown. In the present study, we fed a magnesium-deficient diet to Wistar rats at different postnatal developmental stages. Cartilage lesions were only observed in magnesium-deficient rats between 3 and 5 weeks of age, but not in rats receiving the magnesium-deficient diet during weeks 5 to 8, weeks 8 to 11, or months 15 to 16. The formation of cartilage lesions was not related to the magnesium concentration in plasma, since magnesium concentrations in plasma were similarly reduced in rats with and without cartilage lesions. However, chondrotoxicity correlated with magnesium content in articular cartilage. In articular cartilage (articular and epiphyseal cartilage in immature rats) and bone, magnesium content was more reduced in rats receiving the magnesium-deficient diet between 3 and 5 weeks of age as compared with rats receiving the magnesium-deficient diet during weeks 8 to 11 postnatally. It was not possible to reduce the magnesium content in bone tissue of 15-month-old Wistar rats, which suggests a lower magnesium turnover in aged rats. Magnesium content in epiphyseal cartilage of 2-week-old rats (total femoral head) was 41.9 +/- 16.9 mmol/kg dry weight. The magnesium content in joint hyaline cartilage was significantly lower in 4-week-old rats (19.5 +/- 3.6 mmol/kg dry weight) and increased subsequently again to 48.5 +/- 9.2 mmol/kg dry weight (mean +/- SD; n = 8 to 16). Increase of the magnesium content in femoral bone between weeks 4 and 6 postnatally was less pronounced (139 +/- 10 and 175 +/- 15 mmol/kg dry weight, respectively). Taken together, these data show that in 4-week-old rats, magnesium concentration in joint hyaline cartilage is significantly lower than at other times during postnatal development. Only at this developmental stage can cartilage lesions be induced by feeding rats a magnesium-deficient diet. This period correlates well with the sensitive phase of immature rats toward the chondrotoxic action of quinolones.

Aging↗
PubMed1997

Small cell carcinoma of the ovary, hypercalcemic type. A case report with immunohistochemical, ultrastructural and cytophotometric analysis and review of the literature.

Small cell carcinomas of the ovary, hypercalcemic type, are unilateral tumors occurring almost exclusively in young women. 60% of the cases are associated with hypercalcemia. Microscopic examination shows diffuse clusters of small cells and follicle-like spaces. Immunohistochemically, the tumor cells are positive for epithelial and mesenchymal markers, and ultrastructurally they contain an abundance of dilated rough endoplasmatic reticulum and numerous free ribosomes. By DNA-single cell photometry, the neoplastic cells show a diploid DNA-content.

Adult↗
PubMed1996

Integrins on joint cartilage chondrocytes and alterations by ofloxacin or magnesium deficiency in immature rats.

Recently, we showed that magnesium deficiency induces lesions in knee joint cartilage from 5-week-old rats that are very similar to ofloxacin-induced cartilage defects. We concluded that quinolone-induced arthropathy is probably due to chelation of magnesium and thus a deficit in functionally available magnesium in joint cartilage (Stahlmann et al. 1995). As magnesium deficiency in joint cartilage could impair chondrocyte-matrix interaction which is mediated by cation-dependent integrin receptors of the beta 1-subfamily, we investigated integrin expression in joint cartilage from untreated, ofloxacin-treated and magnesium-deficient Wistar rats. With immunohistochemical methods using monoclonal and polyclonal antibodies, we showed that the integrin pattern in joint cartilage from rats corresponded largely to integrin expression described for human cartilage tissue: beta 1, alpha 1, alpha 3 and alpha v subunits and the alpha 5 beta 1 and alpha v beta 3 heterodimers were consistently expressed. Joint cartilage lesions were detected in ofloxacin-treated and magnesium-deficient rats. Lesions were more pronounced in the quinolone-treated group. Expression of several integrins was reduced in the vicinity of lesions after oral treatment with 2 x 600 mg ofloxacin/kg for 1 day. Gross-structural lesions (e.g., cleft formation, unmasked collagen fibres) in magnesium-deficient rats were very similar but changes in integrin expression were less pronounced. On the other hand, changes in cartilage matrix composition showed similar alterations in ofloxacin-treated and magnesium-deficient rats: fibronectin deposition in the cartilage matrix increased in both groups while glycosaminoglycan content decreased. In summary, similar defects occur in ofloxacin-treated and magnesium-deficient rats and with immunohistochemical methods subtle differences are demonstrable.

Animals↗
PubMed1996

Quinolone-induced cartilage lesions are not reversible in rats.

The reversibility of quinolone-induced cartilage lesions has not been studied in detail. We treated five groups of five to seven juvenile Wistar rats (male and female; age: 5 weeks) with 2 x 600 mg ofloxacin/kg by gastric intubation on 1 day only (9:00 a.m. and 5:00 p.m.) and studied the knee joints histologically 3 days, 1, 3, 8 and 17 weeks later. In addition, joint cartilage specimens from vehicle-treated control rats (n = 21) at corresponding age were examined. Cartilage lesions such as matrix swelling, loss of proteoglycans and horizontal clefts were found in nearly all knee joints (26 of 27 joints; incidence: 96%) of the ofloxacin-treated rats. Within the observation period of 4 months the size of these lesions in knee joint cartilage did not decrease significantly. The diameter of the lesions at the time points of evaluation was 1146 +/- 535, 1713 +/- 309, 1250 +/- 585, 1406 +/- 356, and 1542 +/- 467 microns, respectively (mean values +/- sd). Chondrocyte clusters producing glycosaminoglycans were observed 3 weeks after dosing and at later time points. They are considered to reflect the onset of repair but chondrocyte organization did not normalize during the study period, thus indicating the irreversibility of the effect under the experimental conditions. In principle, long-term joint cartilage damage has to be taken into account when the use of quinolones in children is considered. More detailed pharmacokinetic data are necessary for a reasonable risk assessment approach.

Animals↗
PubMed1995

[Oncocytoma of the nose. A case report and review of the literature].

Oncocytomas are rare epithelial tumors of the major and minor salivary glands. Reported is an oncocytoma of the lateral wall of the left nasal cavity in a 60-year-old man. Because of its locally invasive character, with rupture into the left nasal cavity and partial dedifferentiation with loss of typically oncocytic features, we classified the tumor as oncocytoma of low malignant potential.

Adenoma, Oxyphilic↗