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Biomedical subjects

U Maier

Publications and source records attributed to U Maier.

At least 19 recordsLinked to original sources
PubMed2001

Optical method for the determination of the oxygen-transfer capacity of small bioreactors based on sulfite oxidation.

The growth of microorganisms may be limited by operating conditions which provide an inadequate supply of oxygen. To determine the oxygen-transfer capacities of small-scale bioreactors such as shaking flasks, test tubes, and microtiter plates, a noninvasive easy-to-use optical method based on sulfite oxidation has been developed. The model system of sodium sulfite was first optimized in shaking-flask experiments for this special application. The reaction conditions (pH, buffer, and catalyst concentration) were adjusted to obtain a constant oxygen transfer rate for the whole period of the sulfite oxidation reaction. The sharp decrease of the pH at the end of the oxidation, which is typical for this reaction, is visualized by adding a pH dye and used to measure the length of the reaction period. The oxygen-transfer capacity can then be calculated by the oxygen consumed during the complete stoichiometric transformation of sodium sulfite and the visually determined reaction time. The suitability of this optical measuring method for the determination of oxygen-transfer capacities in small-scale bioreactors was confirmed with an independent physical method applying an oxygen electrode. The correlation factor for the maximum oxygen-transfer capacity between the chemical model system and a culture of Pseudomonas putida CA-3 was determined in shaking flasks. The newly developed optical measuring method was finally used for the determination of oxygen-transfer capacities of different types of transparent small-scale bioreactors.

Bioreactors↗
PubMed2001

Twelve-year experience with two courses of adjuvant single-agent carboplatin therapy for clinical stage I seminoma.

PURPOSE: During the past 30 years, radiation therapy with 28 to 30 Gy for para-aortic and ipsilateral iliac node areas was the standard adjuvant treatment for clinical stage I seminoma after orchiectomy. However, late effects of radiotherapy prompted a search for alternative adjuvant treatment approaches, including surveillance and application of carboplatin. In this retrospective analysis, we evaluated the efficacy and toxicity of two adjuvant single-agent carboplatin courses in 107 patients who were diagnosed with clinical stage I seminoma at our study centers between 1988 and 1999. PATIENTS AND METHODS: All 107 patients (median age, 39 years; range, 24 to 63 years) received two postoperative adjuvant cycles of carboplatin (400 mg/m(2)). The pathologic tumor stage was pT1 in 84 patients, pT2 in 18 patients, and pT3 in five patients. Whole blood count and serum chemistry were evaluated weekly during treatment to assess hematologic and nonhematologic toxicity. RESULTS: Six patients died from tumor-unrelated causes. The remaining 101 patients are currently alive and free of disease after a median follow-up of 74 months (range, 5 to 145 months). A detailed analysis of hematologic toxicity showed only World Health Organization (WHO) grade 1 leukocytopenia in 10.7% of all cycles and WHO grade 2 leukocytopenia in 2.1% of all cycles. CONCLUSION: Regarding the absence of tumor recurrences in our retrospective analysis and the favorable toxicity profile with no episodes of long-term toxicity, we suggest that two adjuvant courses of single-agent carboplatin for clinical stage I seminoma patients might be equivalent to radiotherapy.

Adult↗
PubMed2001

Molecular chaperones encoded by a reduced nucleus: the cryptomonad nucleomorph.

Molecular chaperones mediate the correct folding of nascent or denatured proteins and are found in both the organelles and cytoplasm of eukaryotic cells. Cryptomonad algae are unusual in possessing an extra cytoplasmic compartment (the periplastid space), the result of having engulfed and retained a photosynthetic eukaryote. Within the periplastid space is a diminutive nucleus (the nucleomorph) that encodes mostly genes for its own expression as well as a few needed by the plastid. Two plastid-encoded chaperones (GroEL and DnaK) and a nucleomorph-encoded chaperone (Cpn60) have been reported from the cryptomonad, Guillardia theta. Here we analyse G. theta nucleomorph genes for members of the cytosolic HSP70 and HSP90 families of molecular chaperones, a heat shock transcription factor (HSF), and all eight subunits of the group II chaperonin, CCT. These are presumably all active in the periplastid space, assisting in the maturation of polypeptides required by the cell; we propose a central role for them also in the structure and assembly of a putative relict mitotic apparatus. Curiously, none of the genes for co-chaperones of HSP70, HSP90, or CCT have been detected in the nucleomorph genome; they are either not needed or are encoded in the host nuclear genome and targeted back into the periplastid space. Endoplasmic reticulum (ER) homologs of HSP70 and HSP90 are also not present. Striking differences in the degree of conservation of the various nucleomorph-encoded molecular chaperones were observed. While the G. theta HSP70 and HSP90 homologs are well conserved, each of the eight CCT subunits (alpha, beta, gamma, delta, epsilon, eta, theta, and zeta) is remarkably divergent. Such differences are likely evidence for reduced/different functional constraints on the various molecular chaperones functioning in the periplastid space.

Amino Acid Motifs↗
PubMed2001

Leiomyoma of the vesicovaginal septum.

A 69-year-old woman presented with a solid homogenous mass in the area of the posterior wall of the urinary bladder. A transvaginal approach was used to remove the mass located in the vesicovaginal septum. Histology revealed a benign smooth spindle cell tumor and immunohistochemistry confirmed leiomyoma.

Actins↗
PubMed2001

Characterisation of the gas-liquid mass transfer in shaking bioreactors.

The maximum gas-liquid mass transfer capacity of 250ml shaking flasks on orbital shaking machines has been experimentally investigated using the sulphite oxidation method under variation of the shaking frequency, shaking diameter, filling volume and viscosity of the medium. The distribution of the liquid within the flask has been modelled by the intersection between the rotational hyperboloid of the liquid and the inner wall of the shaking flask. This model allows for the calculation of the specific exchange area (a), the mass transfer coefficient (k(L)) and the maximum oxygen transfer capacity (OTR(max)) for given operating conditions and requires no fitting parameters. The model agrees well with the experimental results. It was furthermore shown that the liquid film on the flask wall contributes significantly to the specific mass transfer area (a) and to the oxygen transfer rate (OTR).

Journal Article↗
PubMed2001

Local intratumoral tumor necrosis factor-alpha and systemic IFN-alpha 2b in patients with locally advanced prostate cancer.

To examine tolerability and activity of local, intratumoral tumor necrosis factor-alpha (TNF-alpha) and systemic interferon-alpha2b (IFN-alpha2b) in locally advanced, hormone-resistant prostate cancer (LA-HRPC), 10 patients with LA-HRPC (T4N x M0, n = 3, T4N x M1, n = 5; T4N1M1, n = 2) were treated with recombinant TNF-alpha injected locally into prostate tumor tissue at 4-week intervals (maximum of four cycles) combined with intermittent subcutaneous (s.c.) administration of 5 x 10(6) IU IFN-alpha2b. Twenty-nine TNF-alpha cycles were administered. Despite significant TNF-alpha leakage into the systemic circulation 2 h after intraprostatic application (from a mean of 9 to a mean of 416 pg/ml; p = 0.0034), TNF-alpha (and IFN-alpha2b) was well tolerated (WHO grade 1-2 toxicity), possibly because of its rapid neutralization by increasing soluble 55-kDa and 75-kDa TNF receptor levels in the serum (mean increase 268% and 91%, respectively) at the same time. TNF-alpha induced prostate tumor cell necrosis in all patients, leading to a significant reduction of prostate volume in 9 of 10 cases (mean 38%; p = 0.0025). The significant short-term increase of prostate-specific antigen (PSA) (mean 65%; p < 0.001), tissue polypeptide-specific antigen (TPS) (mean 85%; p = 0.001), and possibly interleukin-8 (IL-8) (mean 2687%; p < 0.009) serum levels within 4 h after TNF-alpha confirmed the cytotoxic effect in vivo. In the long term, serum PSA levels dropped by 18%-87%, reaching the nadir value 7 weeks after baseline. Objective responses of metastases were not seen. Intraprostatic administration of TNF-alpha is feasible at a tolerable toxicity in patients with LA-HRPC and, thus, may be a new treatment option for these patients.

Aged↗
PubMed2001

[Hormone profile in the aging man].

During male ageing serum levels of testosterone, free testosterone, DHEA, growth hormone and maltonin decrease in contrary to the increase of FSH, LH, SHBG. Estradiol, Prolaktin and dihydrotestosterone show no significant changes. The terminus "andropause" is not correct, because there is no sudden decrease in sexual hormones, which is seen in the female (menopause). We should characterize the hormonE changes as "partial endocrine variations of the ageing male" or "partial androgen deficiency of the ageing male". Wether hormone replacement therapy leads to delay of ageing or increase of well being in ageing males can only be demonstrated in long term studies over ten years. Otherwise an evidence is required to demonstrate that long time hormone replacement therapy will not lead to tumour induction or increase of tumour growing.

Adolescent↗
PubMed2000

Power consumption in shaking flasks on rotary shaking machines: I. Power consumption measurement in unbaffled flasks at low liquid viscosity.

In this first article of a series a new method is introduced that enables the accurate determination of the power consumption in a shaking flask. The method is based on torque measurements in the drive and appropriate compensation of the friction losses. The results for unbaffled shaking flasks at low viscosities are presented after varying shaking frequency, flask size, filling volume, shaking diameter, and surface quality (hydrophilic and hydrophobic) of the inner flask walls. The order of magnitude of the values of power consumption in shaking flasks is equal to, or even higher than, the values typical for agitated tank bioreactors. A physically based model equation for shaking flasks is derived that introduces a modified power number and a resulting constant as the only fitting parameter. With this equation, the measured results are correlated with sufficient accuracy. For the first time, comprehensive data for the power consumption in unbaffled shaking flasks at low viscosity is available, giving a detailed picture of the influences of the different variables.

Biotechnology↗
PubMed2000

Power consumption in shaking flasks on rotary shaking machines: II. Nondimensional description of specific power consumption and flow regimes in unbaffled flasks at elevated liquid viscosity.

This article is the second part of a series presenting and modeling the hydrodynamics and specific power consumption in shaking flasks on rotary (orbital) shaking machines. In part I, a new method was introduced that enables the accurate determination of the specific power consumption in shaking flasks. The method was first applied to investigate unbaffled flasks with a nominal volume of < or =1 L at low viscosity. In part II, the results for the specific power consumption of unbaffled shaking flasks at elevated viscosities are investigated after varying shaking frequency, flask size, filling volume, and shaking diameter. The theory introduced in part I is extended to liquids of elevated viscosities using nondimensional equations. With these results, the specific power consumption in unbaffled shaking flasks can now be fully described. For the first time, the phenomenon of the liquid being "out of phase" is observed and described. This occurs at certain operating conditions and is characterized by an increasing amount of liquid not following the movement of the shaking table, thus reducing the specific power consumption. This, of course, has much relevance for practical work with microbial cultures. The phenomenon of being "out-of-phase" is described in the form of a newly defined nondimensional phase number (Ph) in analogy to a partially filled, rotating horizontal drum. The Ph can be used to determine reasonable operating conditions for shaking flask experiments when using viscous media, avoiding unfavorable "out-of-phase" operation.

Biotechnology↗
PubMed2000

Gbeta 5gamma 2 is a highly selective activator of phospholipid-dependent enzymes.

In this study, Gbeta specificity in the regulation of Gbetagamma-sensitive phosphoinositide 3-kinases (PI3Ks) and phospholipase Cbeta (PLCbeta) isozymes was examined. Recombinant mammalian Gbeta(1-3)gamma(2) complexes purified from Sf9 membranes stimulated PI3Kgamma lipid kinase activity with similar potency (10-30 nm) and efficacy, whereas transducin Gbetagamma was less potent. Functionally active Gbeta(5)gamma(2) dimers were purified from Sf9 cell membranes following coexpression of Gbeta(5) and Ggamma(2-His). This preparation as well as Gbeta(1)gamma(2-His) supported pertussis toxin-mediated ADP-ribosylation of Galpha(i1). Gbeta(1)gamma(2-His) stimulated PI3Kgamma lipid and protein kinase activities at nanomolar concentrations, whereas Gbeta(5)gamma(2-His) had no effect. Accordingly, Gbeta(1)gamma(2-His), but not Gbeta(5)gamma(2-His), significantly stimulated the lipid kinase activity of PI3Kbeta in the presence or absence of tyrosine-phosphorylated peptides derived from the p85-binding domain of the platelet derived-growth factor receptor. Conversely, both preparations were able to stimulate PLCbeta(2) and PLCbeta(1). However, Gbeta(1)gamma(2-His), but not Gbeta(5)gamma(2-His), activated PLCbeta(3). Experimental evidence suggests that the mechanism of Gbeta(5)-dependent effector selectivity may differ between PI3K and PLCbeta. In conclusion, these data indicate that Gbeta subunits are able to discriminate among effectors independently of Galpha due to selective protein-protein interaction.

Enzyme Activation↗
PubMed2000

Two-step disordering of perpendicularly magnetized ultrathin films.

We have imaged the stripe domain structure of perpendicularly magnetized fcc ultrathin Fe films grown on Cu(100). The stripe phase has a strong local orientational order and sustains the two kinds of fluctuations predicted by Abanov et al. [Phys. Rev. B 51, 1023 (1995)]: meandering and dislocations. Before reaching the Curie temperature, the stripes transform into a new and so far unobserved domain structure, characterized by domains with predominantly square corners. We argue that this phase is the tetragonal liquid phase proposed by Abanov et al. to separate the stripe phase from the paramagnetic phase. This two-step disordering is reminiscent of a two-dimensional melting process.

Journal Article↗
PubMed2000

Comparative study of two different TRUS-guided sextant biopsy techniques in detecting prostate cancer in one biopsy session.

OBJECTIVE: The aim of this study was to compare a transrectal ultrasound (TRUS)-guided sextant biopsy technique, which puts more emphasis on the apical region of the prostate where most prostate carcinomas (PCs) develop, with the standard sextant biopsy technique. METHODS: A total of 280 patients with suspected PC were included in this analysis. Twelve biopsy cores were obtained from all patients. Six biopsy cores were taken within a lateral parasagittal plane from each lobe at the apex, middle and basis, with an angle of approximately 45 degrees (technique A), and 6 further biopsy cores were taken from the left to the right lateral margin always penetrating the prostate in the apex with the same angle (socalled fan-shaped technique, technique B). Technique A predominantly samples in the sagittal and technique B samples more in the transversal plane with emphasis on the apical region where most PCs develop. The sensitivity in detecting PCs for both techniques was calculated and correlated to the serum prostate-specific antigen (PSA) levels. RESULTS: A total of 72 PCs (25.7%) were diagnosed. We subsequently performed subgroup analysis depending on the serum PSA levels: in patients with a PSA of </=10 ng/ml (n = 27) technique A has a PC sensitivity of 88.8% (p = 0.037) and technique B 96.2% (p = 0.326) as compared to our reference standard of 100% by sampling 12 biopsy cores in the same prostate. The number of positive biopsy cores using technique B was superior in 12 cases as compared to 3 cases with technique A (p = 0.04). In 12 patients the number of positive biopsy cores was identically. In patients with a PSA of >10 ng/ml (n = 45) technique A has a PC sensitivity of 93.3% (p = 0.083) and technique B 88.8% (p = 0.023) as compared to our reference standard. The number of positive core biopsies using technique A was superior in 14 cases as compared to 12 with technique B (p = 0.154). In 19 patients the number of positive biopsies was identical. CONCLUSION: Our data suggest that in patients with PSA of </=10 ng/ml technique B bring significant benefit with regard to the number of positive core biopsies, as well as an enhanced PC detection rate which is near the 12-core biopsy. Due to the fact that technique B samples more in the apical region where most cancers develop, it should be performed in suspected early stage cancers of the prostate (PSA</=10 ng/ml).

Adolescent↗
PubMed1999

Roles of non-catalytic subunits in gbetagamma-induced activation of class I phosphoinositide 3-kinase isoforms beta and gamma.

By using purified preparations we show that nanomolar concentrations of Gbetagamma significantly stimulated lipid kinase activity of phosphatidylinositol 3-kinase (PI3K) beta and PI3Kgamma in the presence as well as in the absence of non-catalytic subunits such as p85alpha or p101. Concomitantly, Gbetagamma stimulated autophosphorylation of the catalytic subunit of PI3Kgamma (EC(50), 30 nM; stoichiometry >/=0.6 mol of P(i)/mol of p110gamma), which also occurred in the absence of p101. Surprisingly, we found that p101 affected the lipid substrate preference of PI3Kgamma in its Gbetagamma-stimulated state. With phosphatidylinositol as substrate, p110gamma but not p101/p110gamma was significantly stimulated by Gbetagamma to form PI-3-phosphate (EC(50), 20 nM). The opposite situation was found when PI-4,5-bisphosphate served as substrate. Gbetagamma efficiently and potently (EC(50), 5 nM) activated the p101/p110gamma heterodimer but negligibly stimulated the p110gamma monomer to form PI-3,4,5-trisphosphate. However, this weak stimulatory effect on p110gamma was overcome by excess concentrations of Gbetagamma (EC(50), 100 nM). This finding is in accordance with the in vivo situation, where activated PI3K catalyzes the formation of PI-3,4,5-trisphosphate but not PI-3-phosphate. We conclude that p101 is responsible for PI-4, 5-bisphosphate substrate selectivity of PI3Kgamma by sensitizing p110gamma toward Gbetagamma in the presence of PI-4,5-P(2).

Androstadienes↗
PubMed1999

Differential distribution of G-protein beta-subunits in brain: an immunocytochemical analysis.

Heterotrimeric G proteins play central roles in signal transduction of neurons and other cells. The variety of their alpha-, beta-, and gamma-subunits allows numerous combinations thereby confering specificity to receptor-G-protein-effector interactions. Using antisera against individual G-protein beta-subunits we here present a regional and subcellular distribution of Gbeta1, Gbeta2, and Gbeta5 in rat brain. Immunocytochemical specificity of the subtype-specific antisera is revealed in Sf9 cells infected with various G-protein beta-subunits. Since Gbeta-subunits together with a G-protein gamma-subunit affect signal cascades we include a distribution of the neuron-specific Ggamma2- and Ggamma3-subunits in selected brain areas. Gbeta1, Gbeta2, and Gbeta5 are preferentially distributed in the neuropil of hippocampus, cerebellum and spinal cord. Gbeta2 is highly concentrated in the mossy fibres of dentate gyrus neurons ending in the stratum lucidum of hippocampal CA3-area. High amounts of Gbeta2 also occur in interneurons innervating spinal cord alpha-motoneurons. Gbeta5 is differentially distributed in all brain areas studied. It is found in the pyramidal cells of hippocampal CA1-CA3 as well as in the granule cell layer of dentate gyrus and in some interneurons. In the spinal cord Gbeta5 in contrast to Gbeta2 concentrates around alpha-motoneurons. In cultivated mouse hippocampal and hypothalamic neurons Gbeta2 and Gbeta5 are found in different subcellular compartments. Whereas Gbeta5 is restricted to the perikarya, Gbeta2 is also found in processes and synaptic contacts where it partially colocalizes with the synaptic vesicle protein synaptobrevin. An antiserum recognizing Ggamma2 and Ggamma3 reveals that these subunits are less expressed in hippocampus and cerebellum. Presumably this antiserum specifically recognizes Ggamma2 and Ggamma3 in combinations with certain G alphas and/or Gbetas. The widespread but regionally and cellularly rather different distribution of Gbeta- and Ggamma2/3-subunits suggests that region-specific combinations of G-protein subunits mediate signal transduction in the central nervous system. The different subcellular distribution of Gbeta-subunits in cultivated neurons reflects that observed in tissue where Gbeta5 and Gbeta2 associate preferentially with the perikarya and the neuropil, respectively, and suggests an additional association of Gbeta2 with secretory vesicles.

Amino Acid Sequence↗
PubMed1999

Gbetagamma dimers stimulate vascular L-type Ca2+ channels via phosphoinositide 3-kinase.

We have previously reported that, in venous myocytes, Gbetagamma scavengers inhibit angiotensin AT1A receptor-induced stimulation of L-type Ca2+ channels (1). Here, we demonstrate that intracellular infusion of purified Gbetagamma complexes stimulates the L-type Ca2+ channel current in a concentration-dependent manner. Additional intracellular dialysis of GDP-bound inactive Galphao or of a peptide corresponding to the Gbetagamma binding region of the beta-adrenergic receptor kinase completely inhibited the Gbetagamma-induced stimulation of Ca2+ channel currents. The gating properties of the channel were not affected by intracellular application of Gbetagamma, suggesting that Gbetagamma increased the whole-cell calcium conductance. In addition, both the angiotensin AT1A receptor- and the Gbetagamma-induced stimulation of L-type Ca2+ channels were blocked by pretreatment of the cells with wortmannin, at nanomolar concentrations. Correspondingly, intracellular infusion of an enzymatically active purified recombinant Gbetagamma-sensitive phosphoinositide 3-kinase, PI3Kgamma, mimicked Gbetagamma-induced stimulation of Ca2+ channels. Both Gbetagamma- and PI3Kgamma-induced stimulations of Ca2+ channel currents were reduced by protein kinase C inhibitors suggesting that the Gbetagamma/PI3Kgamma-activated transduction pathway involves a protein kinase C. These results indicate for the first time that Gbetagamma dimers stimulate the vascular L-type Ca2+ channels through a Gbetagamma-sensitive PI3K.

Animals↗
PubMed1998

Two-dimensional magnetic particles

Single two-dimensional (2D) atomically thick magnetic particles of cobalt and iron with variable size and shape were fabricated by combining a mask technique with standard molecular beam epitaxy. Reduction of the lateral size of in-plane magnetized 2D cobalt films down to about 100 nanometers did not essentially modify their magnetic properties; although the separation of boundaries decreased greatly, neither domain penetrated the particle, nor was any sizable shape anisotropy observed. The mutual interaction of 2D cobalt particles was negligible, and the magnetic state of a single particle could be switched without modifying the state of the neighbors. Perpendicularly magnetized iron particles did not exhibit such responses. These results suggest that only a few atoms forming a 2D in-plane magnetized dot may provide a stable elementary bit for nanorecording.

Journal Article↗