Biomedical subjects

Christian Schuster

Publications and source records attributed to Christian Schuster.

8 recordsLinked to original sources

PubMed2007

Stereoselective biocatalytic synthesis of (S)-2-hydroxy-2-methylbutyric acid via substrate engineering by using "thio-disguised" precursors and oxynitrilase catalysis.

3-Tetrahydrothiophenone (4) and 4-phenylthiobutan-2-one (7) were used as masked 2-butanone equivalents to give the corresponding cyanohydrins 5 (79 % yield, 91 % ee) and 8 (95 % yield, 96 % ee) in an enzymatic cyanohydrin reaction applying the hydroxynitrile lyase (HNL) from Hevea brasiliensis. After hydrolysis and desulphurisation the desired intermediate (S)-2-hydroxy-2-methylbutyric acid (10) was obtained with 99 % ee. Interestingly, when applying (R)-selective HNL from Prunus amygdalus again the (S)-cyanohydrin 5 was formed (62 % ee). The absolute configuration of 5 was verified by crystal structure determination of the corresponding hydrolysis derived carboxylate. The fact that both enzymes yield the same enantiomer was analysed and interpreted by molecular modelling calculations.

Aldehyde-Lyases↗

PubMed2007

Fast 3D 1H spectroscopic imaging at 3 Tesla using spectroscopic missing-pulse SSFP with 3D spatial preselection.

Three-dimensional (3D) (1)H MR spectroscopic imaging (SI) allows metabolic changes in human tissue to be identified. In clinical practice, fast acquisition techniques are required to achieve an adequate spatial resolution within acceptable total measurement times. In this study a novel fast pulse sequence for 3D (1)H SI based on the condition of steady-state free precession (SSFP), termed "spectroscopic missing-pulse SSFP" (spMP-SSFP), is proposed. It combines 3D spatial preselection with the acquisition of full spin echoes (SEs), and thus makes subsequent phase correction of spectra redundant. The sequence was applied to a phantom and healthy human brains in vivo at 3 Tesla. Metabolic images are acquired with a spatial resolution of 1.8 cm(3) within a total measurement time of about 6 min. With a lower signal-to-noise ratio (SNR) per unit measurement time compared to previous spectroscopic SSFP implementations, 3D spatial preselection can now be realized with spMP-SSFP. Since the method does not require separate techniques for water and lipid suppression, and employs a simple data-processing approach, spMP-SSFP is a robust, fast SI method that requires only minimal user interaction.

Brain↗

PubMed2006

Inhibition of xenograft tumor growth and down-regulation of ErbB receptors by an antibody directed against Lewis Y antigen.

The blood group-related Lewis Y antigen is expressed on the majority of human cancers of epithelial origin with only limited expression on normal tissue. Therefore, the Lewis Y antigen represents an interesting candidate for antibody-based treatment strategies. Previous experiments showed that the humanized Lewis Y-specific monoclonal antibody, IGN311, reduced ErbB-receptor-mediated stimulation of mitogen-activated protein kinase by altering receptor recycling. Here, we tested whether binding of IGN311 to growth factor receptors is relevant also to inhibition of tumor growth in vivo. Prolonged incubation with IGN311 of human tumor cell lines, which express high levels of ErbB1 (A431) or ErbB2 (SK-BR-3), resulted in down-regulation of the receptors and inhibition of cell proliferation. IGN311 inhibited the growth of tumors derived from A431 cells xenografted in nude mice. Treatment with IGN311 was associated with a down-regulation of ErbB1 in the excised tumor tissue. Importantly, these effects of IGN311 were also mimicked by the Fab fragment of IGN311. These data indicate that tumor cell growth inhibition by IGN311 cannot solely be accounted for by invoking cellular and humoral immunological mechanisms. A direct effect on signaling via binding to Lewis Y glycosylated growth factor receptors on tumor cells is also likely to contribute to the therapeutic effect of IGN311 in vivo.

Animals↗

PubMed2006

Simultaneous sustained release of fludarabine monophosphate and Gd-DTPA from an interstitial liposome depot in rats: potential for indirect monitoring of drug release by magnetic resonance imaging.

INTRODUCTION: Cytostatic depot preparations are interstitially administered for local chemotherapy and prevention of tumor recurrence. It would be of interest to monitor in patients as to when, to what extent, and exactly where, the drug is actually released. Liposomes containing a hydrophilic cytostatic and a hydrophilic contrast agent might be expected to release both agents simultaneously. If so, then drug release could be indirectly followed by monitoring contrast enhancement at the injection site. METHODS: Multivesicular liposomes containing the antimetabolite fludarabine monophosphate and the magnetic resonance imaging (MRI) contrast agent Gd-DTPA were subcutaneously injected in rats and both agents were monitored at the injection site for 6 weeks by 19F nuclear magnetic resonance spectroscopy (MRS) in vivo and contrast-enhanced 1H MRI (T1w 3D FLASH), respectively, in a 1.5-T whole-body tomograph. The MRS and MRI data were analyzed simultaneously by pharmacokinetic modeling using NONMEM. RESULTS: During an initial lag time, the amount of drug at the injection site stayed constant while the contrast-enhanced depot volume expanded beyond the volume injected. Drug amount and depot volume then decreased in parallel. Lag time and elimination half-life were 9 and 6 days, respectively, in three animals, and were about 50% shorter in another animal where the depot split into sub-depots. CONCLUSION: The preliminary data in rats suggest that simultaneous release of a hydrophilic cytostatic and a hydrophilic contrast agent from an interstitial depot can be achieved by encapsulation in liposomes. Thus, there seems to be a potential for indirect drug monitoring through imaging.

Algorithms↗

PubMed2005

Macro-video documentation patch tests.

An unequivocal distinction between allergic and irritant patch test reactions is often difficult with patch tests. This study was designed to evaluate the worth of video-macro camera documentation for differentiation between allergic and irritant test reactions and to investigate whether there are characteristic clinical differences in patch test responses between metal salts and fragrances. Patch testing was performed with nickel sulfate, fragrance mix and an irritant, sodium lauryl sulfate 1% aq., on the upper back of 82 patients, with evaluation and computer-aided video documentation after 48 and 72 hr. No reliable clinicomorphological criterion was found for assessing a weak patch test reaction as being definitely allergic. Even characteristic papules and vesicles were not regularly found in allergic reactions. However, unlike fragrance mix, patch test reactions to nickel sulfate were characteristic in that they showed a heterogeneous spread and an association with hair follicle openings, independent of reaction intensity. Evaluation based on additional computer-aided video-macro camera documentation did not add further advantage for the differentiation of allergic and irritant reactions. But well-defined clinicomorphological features and reaction patterns to single test substances or even whole substance categories could be helpful additional criteria for evaluating patch test responses in clinical practice.

Adult↗

PubMed2004

Successful treatment of recalcitrant chronic actinic dermatitis with tacrolimus.

Therapeutically, chronic actinic dermatitis is a problematic condition. Frequently applied sunscreen usually fails to mitigate the clinical symptoms, and steroids--while efficient--exert many undesired side-effects with prolonged usage. We present a case of chronic actinic dermatitis responding well to topically applied tacrolimus (Protopic) in combination with chemical and physical UV protection.

Administration, Topical↗

PubMed2004

TYK2 is a key regulator of the surveillance of B lymphoid tumors.

Aberrant activation of the JAK-STAT pathway has been implicated in tumor formation; for example, constitutive activation of JAK2 kinase or the enforced expression of STAT5 induces leukemia in mice. We show here that the Janus kinase TYK2 serves an opposite function. Mice deficient in TYK2 developed Abelson-induced B lymphoid leukemia/lymphoma as well as TEL-JAK2-induced T lymphoid leukemia with a higher incidence and shortened latency compared with WT controls. The cell-autonomous properties of Abelson murine leukemia virus-transformed (A-MuLV-transformed) TYK2(-/-) cells were unaltered, but the high susceptibility of TYK2(-/-) mice resulted from an impaired tumor surveillance, and accordingly, TYK2(-/-) A-MuLV-induced lymphomas were easily rejected after transplantation into WT hosts. The increased rate of leukemia/lymphoma formation was linked to a decreased in vitro cytotoxic capacity of TYK2(-/-) NK and NKT cells toward tumor-derived cells. RAG2/TYK2 double-knockout mice succumbed to A-MuLV-induced leukemia/lymphoma faster than RAG2(-/-)TYK2(+/-) mice. This defines NK cells as key players in tumor surveillance in Abelson-induced malignancies. Our observations provide compelling evidence that TYK2 is an important regulator of lymphoid tumor surveillance.

Abelson murine leukemia virus↗

PubMed2002

Epidemiology of skin cancer.

The skin is the most common site of malignancy. Due to several mostly unknown factors, the frequency of skin tumors is increasing. Except for malignant melanoma, reliable statistical data on the frequency of skin tumors are scarce. Discussion on the epidemiology of skin tumors may take different aspects and factors into consideration: (1) histogenetic type; (2) race, (3) sex; (4) age, (5) localization; (6) environment. Moreover, precancerous conditions also may play an important role in this context. Epithelial tumors, basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are the most frequent tumors of the skin. Figures show a wide range between 40 and over 700 or 5 and 250 respectively per 100 000 inhabitants per year depending on the country or area of report. Malignant melanoma is more frequently seen in Caucasians living in sunny regions (40) than in northern countries or in dark skinned races (4-12 per 100 000 per year), representing 4% of all skin tumors, but being responsible for 79% of skin cancer deaths. Other types of skin tumors like cutaneous lymphoma, Kaposi sarcoma, lipomas, adnexal tumors etc. are either not reported regularly and reliable epidemiologic data is not available, or are rare cutaneous tumors (taken all together < 1%).

Bowen's Disease↗