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Biomedical subjects

Thomas Henkel

Publications and source records attributed to Thomas Henkel.

13 recordsLinked to original sources
PubMed2005

Chip devices for miniaturized biotechnology.

Chip devices were introduced in chemistry and molecular biology to improve the read-out of information from molecular systems by efficient analytical procedures and to organize automated experiments. Biochips and chip reactor systems are of interest for cellular processes, too, and can be regarded as components in interfaces for the information exchange between living nature and digital electronic systems. In this minireview, different types of chip reactors for biotechnological applications like nanotiterplates, chip thermocyclers and devices for segmented flow operations are discussed. Finally, an outlook is given on the application of chip reactor systems, which are promising tools for automated experiments with highly parallelized screening procedures, for artificial microcompartmentation, cell analogue systems, micro-ecological studies, investigations on modulated morphogenesis, and for a bioanalogue molecular nanotechnology.

Animals↗
PubMed2005

Identification of nicotinamide N-methyltransferase as a novel serum tumor marker for colorectal cancer.

PURPOSE: The goal of this study was to identify and validate novel serum markers of human colorectal cancer as potential candidates for noninvasive detection of early colorectal neoplasm. EXPERIMENTAL DESIGN: Employing two-dimensional gel electrophoresis and mass spectrometry, we analyzed 16 matched colorectal cancer and adjacent normal tissue samples. Proteins found to be elevated in cancer tissue were further validated by generating antibodies which were used for immunoblotting of tissue samples and for the development of highly sensitive immunoassays for assessment of serum samples. RESULTS: In total, 735 different proteins were identified in colon tissue. Strong elevation in colorectal cancer for five proteins was confirmed by immunoblot analysis: transforming growth factor-beta induced protein ig-h3 (betaIG-H3), nicotinamide N-methyltransferase (NNMT), nucleoside diphosphate kinase A (nm23-H1), purine nucleoside phosphorylase (PNPH), and mannose-6-phosphate receptor binding protein 1 (M6P1). Elevated levels of NNMT, which is not predicted to be secreted but is known as a cytoplasmic protein, were found in serum from patients with colorectal cancer. Employing a receiver-operating characteristic curve based on the measurement of 109 patients with colorectal cancer and 317 healthy controls, we obtained an area under the curve of 0.84 for NNMT, which was superior to the established tumor marker carcinoembryogenic antigen with an area under the curve of 0.78. CONCLUSIONS: It is proposed that NNMT serum levels may have significance in the early detection and in the management of patients with colorectal cancer.

Aged↗
PubMed2004

Segmented flow generation by chip reactors for highly parallelized cell cultivation.

Micro system technology offers convenient tools for the production of handling devices for small liquid volumes which can be used in cell cultivation. Here, a modular system for the rapid generation of cell suspension aliquots is presented. The system is used to produce and analyze high numbers of well-separated culture volumes. Selected clones may be retrieved from the system. Therefore, the principle of segmented flow is applied. Portions of aqueous culture medium containing one cell or very small cell ensembles are separated from each other by a nonmiscible liquid like dodecane, tetradecane or mineral oil. In addition, the alkane separates the culture droplets from the innerside of the walls of chip channels and capillaries. This way, compatibility problems between cell wall surfaces and the chemical character of walls are excluded. The separated culture droplets are guided by micro flow transportation in different channel and chamber topologies. The whole system has the character of a serially operating cell processing system. The aliquot generation can be sped up to frequencies of about 30 Hz in each microchannel. That means, that about 10(5) individual cultural volumes can be produced per hour or about 2 million per day. The survival and the growth of microorganisms has been shown for model organisms as well as for organisms from a natural sample (soil).

Cell Culture Techniques↗
PubMed2004

Clinical and physical determinants for toxicity of 125-I seed prostate brachytherapy.

BACKGROUND AND PURPOSE: To assess acute as well as long-term toxicity after permanent prostate seed implantation. To find predictive clinical or dosimetric factors for side effects in order to work out strategies for improvement. PATIENTS AND METHODS: A group of 174 patients with localised prostate cancer was treated with permanent seed implantation between 1999 and 2001, either alone (140 patients) or in combination with external radiotherapy (34 patients). For the majority (114/174, i.e. 66%) a CT was performed four weeks after implantation and analysed in the planning system VariSeed. In the postimplant analysis, dosimetric descriptors (doses, volumes) were determined for the prostate and rectum and compared with the intraoperative values. In addition, a questionnaire was sent to all patients to assess and quantify acute and chronic toxicity (urinary, rectal, sexual) and the impact on subjective acceptance and quality of life (return rate of questionnaires 83%). The derived score changes were correlated with clinical and dosimetric factors. RESULTS: In the mono-brachytherapy group 14% (16/140) required a bladder catheter, of them 8% (9/140) with a manifest urinary obstruction. Long-term rectal toxicity (<5%) and impairment of potency (<30%) are moderate and obviously below other treatment options. Urinary toxicity is dominant with an overall long-term dysuria up to 30% (at a mean observation interval of ten months), and a significant trend to decline with follow-up time. Conversely, the erectile function tends to deteriorate with follow-up time. Nevertheless, quality of life is not significantly reduced and acceptance is high. Our analysis suggests that the main factor for urinary toxicity and impaired erectile function is the dose load to larger portions of the prostate (D(50)>240 Gy), which appears to be attributed to unnecessarily high numbers of seeds (for a fixed activity per seed) and needles. The rectal toxicity is correlated with the high dose regions in the rectum (>/=145 Gy). Urinary toxicity is lower for combined-brachytherapy, while rectal toxicity and impairment of potency are slightly higher. CONCLUSIONS: Toxicity spectrum and quality of life after permanent seed implantation for early prostate cancer are acceptable for nearly all patients (98%). To further improve tolerance we should attempt to achieve a better dose homogeneity, i.e. by reducing D(50). Therefore, special attention should be given to D(50) during the real-time planning process. The necessity of more homogeneous dose distributions might imply a reduction of the activity per seed, e.g. from 0.7 mCi down to 0.6 mCi.

Aged↗
PubMed2003

Generation of larger numbers of separated microbial populations by cultivation in segmented-flow microdevices.

The high speed production of fluid segments for the highly parallelized cultivation of monoclonal cell populations was carried out by the use of microchip segmentor modules. Aqueous fluid segments, embedded in a non-miscible carrier liquid, were produced with frequencies up to 30 s(-1) and showed a high homogeneity in size. This corresponds with the production of about 2.5 million samples per day. The segment volumes can be adapted between about 4 nl and 100 nl. The typical segment size for cultivation experiments is in the range between 40 nl and 80 nl. Nutrient medium can be applied instead of pure water. It is possible to aliquot a cell suspension in such a way that most of the aqueous fluid segments contain only one cell. In model experiments with four microbial species chip-produced aliquots of 60 nl, each containing one or a few cells, were incubated in Teflon capillary tubes. Rapid growth of the microcultures was observed. Cell densities were found to be as high as in conventional shake flask cultures.

Colony Count, Microbial↗
PubMed2003

Inverse automated treatment planning with and without individual optimization in interstitial permanent prostate brachytherapy with high- and low-activity 125I.

PURPOSE: To determine whether dose distribution achieved with treatment plans using high- and low-activity (125)I implants differs. PATIENTS AND METHODS: Based on intraoperative transrectal ultrasound scans of 71 patients, inverse automated treatment plans (IATP) were performed with 15.5-kBq (0.42-mCi) and 25.2-kBq (0.68-mCi) (125)I implants using a commercial 3-D planning system (Variseed). A prescription dose of 145 Gy in 98% of the prostate volume (V100), a maximum dose to the urethra of 250 Gy (D1), and a maximum dose to 10% of the anterior rectal wall of 145 Gy (D10) were required. The plans were manually corrected, if necessary. RESULTS: In the IATP, a better dose coverage of the prostate was found for high-activity seeds (V100 of 98% vs 84%). The prostate dose values increased with the prostate volume. After manual optimization, the differences were only marginal with a prostate V100 of 99% for both activities, a urethra D1 of 247 Gy and 239 Gy, and a rectum D10 of 135 Gy and 124 Gy for high- and low-activity seeds. Low-activity seeds required more sources (66 vs 47) and needles (24 vs 17; all numbers are median values). CONCLUSIONS: Concerning the prostate dose coverage, high-activity seeds are superior in the IATP. After manual adjustment, the dose values for the prostate and the organs at risk are similar. Considering a supposedly decreased toxicity and a shorter implantation time for a lower number of seeds, we recommend high-activity seeds for experienced teams.

Brachytherapy↗
PubMed2003

Emerging therapeutic targets in chronic heart failure: part II.

Chronic heart failure is characterised by functional deficiencies of the myocardium. Structural abnormalities of the left ventricular wall occur in many cases as a consequence of myocardial infarction (MI). The overburdened postMI heart is characterised by an active reorganisation of the remaining myocardium. Increased expression and activity of matrix metalloproteinases lead to altered composition and arrangement of the extracellular matrix, which is accompanied by eccentric hypertrophy of cardiomyocytes. The altered geometry of the heart muscle fosters biomechanical stress, driving the heart into a dead-end situation. Clearly, novel therapeutic concepts must be developed to reverse this process. Part II of the current review will focus on emerging therapeutic targets for small molecule therapeutics in the fields of cardiac remodelling and impaired survival of cardiomyocytes in the diseased heart. Finally, innovative therapeutic concepts for heart gene therapy and replacement options for destroyed post-MI myocardium using embryonic and adult stem cells are described.

Apoptosis↗
PubMed2002

Validation of targets and drug candidates in an engineered three-dimensional cardiac tissue model.

High-throughput target discovery confronts the biopharmaceutical industry with a plethora of target candidates. The validation of these candidates in disease-specific animal models often lacks the required throughput. Here, we discuss perspectives and limitations of a novel engineered three-dimensional cardiac tissue, which enables the influence of gene and drug intervention to be monitored on a cellular and molecular level under physiological conditions in sufficient throughput. The model is an extremely helpful filter to prioritize multiple development candidates before moving a project into large animal models with higher predictivity.

Animals↗
PubMed2002

Emerging therapeutic targets in chronic heart failure: part I.

Chronic heart failure (CHF) is a life threatening disease with an enormous medical requirement. Approximately 15 million people worldwide suffer from CHF. The prevalence will inevitably increase due to the ageing population. Nevertheless, current treatment options based on angiotensin-converting enzyme inhibitors and beta-adrenergic receptor antagonists merely slow progression of the disease. Novel treatment concepts based on new therapeutic targets must have the capability to reverse the severity of this disease. This review, focusing on the emerging targets in the most promising therapeutic areas for the treatment of CHF, will be divided into two parts. In Part I, disease concepts such as altered calcium handling and ion channel activity, pathophysiological hypertrophy and inefficient cardiac metabolism are discussed. Validation status and potential therapeutic value for new targets in each research field is given by summarising the results of in vitro and in vivo studies.

Animals↗
PubMed2002

Traditional Chinese medicine (TCM): are polyphenols and saponins the key ingredients triggering biological activities?

The number of herbal formulae considered to be clinically effective and recorded in the Chinese medical literature is huge. The scientific basis for the remedial effects of these herbal formulae is not yet understood, nor has a clear need been given as to how to make use and combine traditional Chinese medicine (TCM) and Western medicine in an effective way. In this context, it is of interest to ascertain what individual constituents are responsible for the bioactive properties, and thus to extract the common characters of composition of huge formulae to provide a scientific explanation for their modes of action. We consider polyphenols and saponins as the key ingredients in TCM remedies responsible for most of the observed biological effects, reflecting the specific requirements within the TCM philosophy of treatment based on the investigation of its chemical composition.

Drugs, Chinese Herbal↗
PubMed2002

Altersetin, a new antibiotic from cultures of endophytic Alternaria spp. Taxonomy, fermentation, isolation, structure elucidation and biological activities.

A novel antibacterial antibiotic, for which the name altersetin is proposed, was isolated from the culture broth of two endophytic Alternaria species. The relative and absolute configuration were assigned by NOESY or CD data, respectively. Altersetin is chemically related to equisetin and showed potent MIC against several pathogenic gram-positive bacteria, whereas gram-negative bacteria and pathogenic yeast were not or much less susceptible. Moderate in vivo efficiacy was observed for altersetin in a murine sepsis model.

Alternaria↗
PubMedDate not supplied

One step purification of corilagin and ellagic acid from Phyllanthus urinaria using high-speed countercurrent chromatography.

High-speed countercurrent chromatography (HSCCC) has been successfully applied to the preparative separation of corilagin and ellagic acid in one step from the Chinese medicinal plant Phyllanthus urinaria L. by use of direct and successive injections of a crude methanolic extract. Some aspects concerning the practical use of this technique in the described application are considered.

Countercurrent Distribution↗