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Biomedical subjects

G Sommer

Publications and source records attributed to G Sommer.

At least 19 recordsLinked to original sources
PubMed2005

In situ tensile testing of human aortas by time-resolved small-angle X-ray scattering.

The collagen diffraction patterns of human aortas under uniaxial tensile test conditions have been investigated by synchrotron small-angle X-ray scattering. Using a recently designed tensile testing device the orientation and d-spacing of the collagen fibers in the adventitial layer have been measured in situ with the macroscopic force and sample stretching under physiological conditions. The results show a direct relation between the orientation and extension of the collagen fibers on the nanoscopic level and the macroscopic stress and strain. This is attributed first to a straightening, second to a reorientation of the collagen fibers, and third to an uptake of the increasing loads by the collagen fibers.

Aorta↗
PubMed2004

Catheter-based ultrasound applicators for selective thermal ablation: progress towards MRI-guided applications in prostate.

High-temperature thermal therapy is emerging as a feasible treatment option for prostate cancer and benign prostatic hyperplasia. Previous investigations have demonstrated distinct advantages of catheter-based ultrasound technology over other heating modalities for thermal ablation therapies, with significant potential for better spatial control and faster heating times. The purpose of this study was to develop ultrasound devices and techniques specifically for treating prostate cancer in conjunction with magnetic resonance thermal imaging (MRTI) to monitor and control treatment progression. Directional transurethral applicators have been designed with arrays of sectored tubular (90 degrees active acoustic sector) or with narrow planar transducer segments and integrated with a flexible delivery catheter with a cooling balloon. This applicator can be rotated within the prostatic urethra to target specific regions during treatment. MRI compatible catheter-cooled interstitial ultrasound applicators with 180 degrees active acoustic sectors were developed specifically to treat the prostate. These applicators may be implanted through the perineum into the posterior portion of the prostate, with their heating energy directed away from the rectum. Both heating strategies were evaluated via biothermal simulations and in vivo experiments within canine prostate (n = 3). During the in vivo studies, MRTI was used to monitor treatment temperatures, cytotoxic thermal doses (t43 > 240 min) and corresponding maximum temperature thresholds (Tmax > 52 degrees C) within three imaging planes simultaneously. Urethral and endorectal cooling was employed with both treatment strategies to provide further protection of the urethral mucosa and rectum from thermal damage. Results using the transurethral applicators demonstrated that narrow zones of coagulation (approximately 30 degrees sector for planar, approximately 90 degrees for tubular), extending up to 20 mm from the urethra to the periphery of the prostate gland, could be produced within 10-15 min. Further, rotation of the applicator during treatment could be used to destroy larger regions in the prostate. Experiments using multiple interstitial directional applicators (approximately 180 degrees active sectors), implanted within the posterior margin of the prostate with the energy directed away from the rectum, produced contiguous zones of thermal coagulation which extended from the posterior prostate toward the anterior-lateral periphery of the gland. Both transurethral and interstitial treatment strategies demonstrated significant potential for thermal ablation of localized prostate cancer, particularly when MRTI is used to guide and assess treatment.

Animals↗
PubMed2002

Wavelet networks for face processing.

Wavelet networks (WNs) were introduced in 1992 as a combination of artificial neural radial basis function (RBF) networks and wavelet decomposition. Since then, however, WNs have received only a little attention. We believe that the potential of WNs has been generally underestimated. WNs have the advantage that the wavelet coefficients are directly related to the image data through the wavelet transform. In addition, the parameters of the wavelets in the WNs are subject to optimization, which results in a direct relation between the represented function and the optimized wavelets, leading to considerable data reduction (thus making subsequent algorithms much more efficient) as well as to wavelets that can be used as an optimized filter bank. In our study we analyze some WN properties and highlight their advantages for object representation purposes. We then present a series of results of experiments in which we used WNs for face tracking. We exploit the efficiency that is due to data reduction for face recognition and face-pose estimation by applying the optimized-filter-bank principle of the WNs.

Journal Article↗
PubMed2001

Biglycan is overexpressed in pancreatic cancer and induces G1-arrest in pancreatic cancer cell lines.

BACKGROUND & AIMS: Biglycan (PG-I), a component of the extracellular matrix (ECM), is overexpressed in pancreatic cancer. To determine possible matrix-tumor interactions, we investigated the effects of PG-I on pancreatic cancer. METHODS: PG-I expression in cell lines and tissue samples was examined by Northern blot and immunofluorescence. The effect of PG-I on proliferation was determined by measuring activity of Ras, ERK, Rb, [(3)H]-thymidine incorporation, and cell cycle analysis. Expression of cyclin A, B1, D1, E1, G1, PCNA, p21, and p27 was analyzed by Northern and Western blots. RESULTS: PG-I was overexpressed in the ECM of pancreatic cancer samples compared with normal pancreas or chronic pancreatitis tissues. Addition of transforming growth factor (TGF)-beta induced PG-I expression in HFL and HFFF2 fibroblasts as well as in the pancreatic cancer cell line PANC-1. PG-I inhibited growth of both TGF-beta-responsive and TGF-beta-unresponsive pancreatic cancer cells by inducing G1-arrest, which is accompanied by an increase of p27 and reduction of cyclin A and proliferating cell nuclear antigen. Furthermore, endogenous Ras and ERK activation was partly reduced by PG-I in vitro. CONCLUSIONS: The ECM protein PG-I inhibits growth by arresting pancreatic cancer cells in G1 and may be part of a host defense mechanism aimed at slowing down pancreatic tumor progression.

Adult↗
PubMed2001

Repopulation of mouse liver with human hepatocytes and in vivo infection with hepatitis B virus.

Mice containing livers repopulated with human hepatocytes would provide excellent in vivo models for studies on human liver diseases and hepatotropic viruses, for which no permissive cell lines exist. Here, we report partial repopulation of the liver of immunodeficient urokinase-type plasminogen activator (uPA)/recombinant activation gene-2 (RAG-2) mice with normal human hepatocytes isolated from the adult liver. In the transplanted mice, the production of human albumin was demonstrated, indicating that human hepatocytes remained functional in the mouse liver for at least 2 months after transplantation. Inoculation of transplanted mice with human hepatitis B virus (HBV) led to the establishment of productive HBV infection. According to human-specific genomic DNA analysis and immunostaining of cryostat liver sections, human hepatocytes were estimated to constitute up to 15% of the uPA/RAG-2 mouse liver. This is proof that normal human hepatocytes can integrate into the mouse hepatic parenchyma, undergo multiple cell divisions, and remain permissive for a human hepatotropic virus in a xenogenic liver. This system will provide new opportunities for studies on etiology and therapy of viral and nonviral human liver diseases, as well as on hepatocyte biology and hepatocellular transplantation.

Adult↗
PubMed2000

Genotype-specific synthesis and secretion of spliced hepatitis B virus genomes in hepatoma cells.

Hepatitis B virus-infected patients frequently have viral particles with DNA derived from differently spliced RNA. Which factors influence the synthesis of these splice variants is unclear. We analysed the type of splice variants produced from different genotypes and determined whether they are secreted as efficiently as wild-type virus. We demonstrate production of a single splice variant from genotypes D, C, and E as dominant species in two hepatoma cell lines. The type of minor splice variants synthesised varied between genotypes but was identical in both hepatoma cell lines. A novel splice variant with a deletion in the core gene was identified for genotype D. Viral DNA from intracellular compared with extracellular viral particles was spliced approximately five times more often than wild-type-sized genomes. A variable amount of the major splice variant was also identified in sera from patients infected with genotypes A, D, and C. These data indicate genotype A-, C-, D-, and E- as well as hepatoma cell line-independent synthesis of a dominant single splice variant and argue for a biological function of the corresponding splice sites. This study clearly demonstrates the intracellular accumulation of viral particles containing spliced genomes and offers a tool for the investigation of underlying mechanisms.

Alternative Splicing↗
PubMed2000

Combined radiochemotherapy with docetaxel in patients with unresectable locally advanced head and neck tumors.

BACKGROUND: As the treatment with docetaxel in metastatic head and neck cancer resulted in an encouraging response rate, the following phase-I study examined the effects of a combined radiochemotherapy with weekly docetaxel in patients with inoperable advanced head and neck tumors. PATIENTS AND METHODS: Six patients with Stage IV head and neck cancer were included into the study. Within the treatment regimen the primary tumor and the involved lymph nodes were irradiated up to a total dose of 70 Gy, the non involved cervical and supraclavicular lymph nodes received 50 Gy in conventional fractionation. Simultaneously docetaxel was given 1 hour before radiotherapy. The initial dose was 15 mg/m2. RESULTS: A dose escalation was impossible because of several dose limiting toxicities (NCI-CTC) already in the first dose level. Two patients showed skin reactions Grade 4, 2 patients pulmonary complications Grade 4, 2 patient neurologic side effects Grade 3 and 1 a thrombocytopenia Grade 3. The response rate resulted in 3 complete and 1 partial remission, 1 death, 1 patient was not evaluable. CONCLUSION: Unexpectedly already in the first dose level several dose limiting toxicities were evaluated. For that reason the treatment scheme is not feasible.

Adult↗
PubMed2000

Inverse covariation of spectral density and correlation dimension in cyclic EEG dynamics of the human brain.

The responsiveness or excitability of the central nervous system (CNS) to external or internal stimuli is systematically altered corresponding to transient changes of the EEG background activity, mainly in the alpha range. We hypothesise that a transient alpha power increase is due to an underlying increase in synchronisation or coupling strength between various neuronal elements or cortical networks. Consequently, the 'network' of the CNS may be more ordered and, hence, less complex in the case of high spectral density, and vice versa. The goals of the present paper are (1) to prove the inverse covariation between spectral density and correlation dimension for a set of human EEG data, (2) to falsify the null hypothesis that the observed relationship is a random one, and (3) to propose a neuronal approach which may explain the observed correlations. A sliding computation of the spectral density and correlation dimension [Grassberger P, Procaccia I (1983) Physica D 9:189-208] of mid-occipital EEG recordings derived from eight awake subjects with eyes closed was performed. The similarity between the two time courses was quantified by similarity measures and descriptive correlation coefficients. The temporal pattern of dimensional complexity showed an inverse relationship with simultaneously computed spectral power changes most pronounced in the alpha range. The group means of similarity measures and correlation coefficients were compared with the corresponding means of a sample set established by 20 Gaussian random signals. Statistically significant differences were obtained at the 0.1% level, rejecting the null hypothesis that the observed relationship is a random one. The results support the idea that the dynamics of the EEG signals investigated reflect a chaotic deterministic process with state transitions from 'high-dimensional' to 'low-dimensional' non-linear dynamics, and vice versa. Adequate neuronal models and approaches to interpret the disclosed transients and the inverse covariation between spectral density and dimensional complexity are proposed, giving additional insight into the integrative functioning of the CNS with respect to the strategy of information processing.

Brain↗
PubMed2000

Changes in the physiological and agricultural characteristics of peat-based Bradyrhizobium japonicum inoculants after long-term storage.

Commercial soybean inoculants processed with sterilised peat and stored at 20 degrees C for 1-8 years were used as experimental materials to assess the changes in the physiological activity of Bradyrhizobium japonicum after storage. Viable counts decreased and physiological characteristics of the bacterium changed during storage, with an increase in the time taken for colony appearance on a medium without yeast extract, an increase in the lag time for nodule appearance on soybean grown in glass tubes and a decrease in survival on seeds. All the inoculants produced a significant increase in grain yield in a field experiment. The percentage of efficient cells in the field (relative to the plate counts) decreased as the length of storage increased. These results suggest that the physiological activity of B. japonicum cells changes after storage. Practical implications for inoculant quality control are discussed.

Bradyrhizobium↗
PubMed1999

Use of representational difference analysis to study the effect of TGFB on the expression profile of a pancreatic cancer cell line.

It has been shown that TGFBs, their receptors, or downstream targets show genetic alterations in pancreatic cancer. This study was designed to identify transcriptional alterations induced by prolonged treatment of pancreatic cancer cell lines with TGFB. The TGFB-responsive PANC-1 cell line was treated with 10-ng/ml TGFB1 for 24 hr. cDNA representational difference analysis was used to generate subtracted hybridization probes enriched for TGFB regulated genes. These probes were hybridized on gridded arrays of cDNA clones containing genes differentially expressed in pancreatic cancer. Twenty-seven distinct cDNA clones were shown to be TGFB target genes. Eleven genes were upregulated by TGFB and were associated with extracellular matrix composition and formation, including genes usually transcribed by cells of mesenchymal origin only. Transcript levels of 16 genes were downregulated by TGFB and could mainly be classified into markers of epithelial differentiation and genes involved in the transcriptional and translational machinery. In conclusion, a 24-hr treatment of PANC-1 cells with TGFB induced a loss of epithelial and a gain of mesenchymal markers. As in other tumors, this epithelial-mesenchymal transdifferentiation may be of general importance during pancreatic carcinogenesis, and may participate, e.g., in the development of the desmoplastic reaction or the acquisition of an invasive phenotype of pancreatic tumor cells. This study demonstrates the usefulness of cDNA RDA and gridded clone libraries to study the effect of signaling cascades on the expression profile of tumor cells. Similar approaches may be helpful in the context of the genome project for the characterization of novel genes. Genes Chromosomes Cancer 26:70-79, 1999.

Cell Division↗
PubMed1999

[Critical life events during the course of 2 years of 'major depression.' A prospective study with inpatients].

A number of studies has shown a significant relationship between life events/life conditions and depression. However, there is only a small number of studies investigating the effect of life events/life conditions in patients with severe depression from the endogenous subtype. The results are inconsistent. The present study examines the significance of the patients' life events/life conditions for the two year outcome of the illness in a prospective study with assessments every three months. Patients are compared to healthy controls with regard to the period three months prior to the admission to the hospital at the index episode. The results confirm the importance of life events and life conditions for the long term outcome of depressed patients with endogenous subtype respectively severe major depression in-patients. Relapsers show considerably more undesirable life conditions than non-relapsers three to six months prior to their relapse. Depressed patients indicate significantly more undesirable life events and life conditions and fewer desirable life conditions in comparison to the control group for the time span three months prior to their hospitalization. Clinical implications are discussed.

Adult↗
PubMed1999

Liver tumors: utility of characterization at dual-frequency US.

PURPOSE: To evaluate the potential utility of a technique for analysis of ultrasonographic (US) images obtained at two center frequencies in a phantom model and in a clinical study of liver tumors. MATERIALS AND METHODS: A US phantom was built that contained target regions with polystyrene scatterers both smaller and larger than scatterers in the background material. High- and low-frequency US images of target regions were obtained, and changes in the contrast-to-noise ratio (CNR) of the targets relative to the background were determined. In a clinical evaluation, 12 hemangiomas, 13 liver metastases, one adenoma, and two hepatomas were evaluated in a similar manner, and the results were correlated with the histologic findings in resected lesions. RESULTS: For targets containing scatterers smaller than those in the background, there was an increase in CNR of higher frequency images. The converse was true for target regions having scatterers larger than those in the background. Liver metastases generally showed an increase in CNR of higher frequency images, whereas hemangiomas generally showed somewhat decreased CNR of higher frequency images, differing significantly from metastases (P < .01-.001). CONCLUSION: Changes in CNRs of relatively high- and low-frequency US images may give useful information on the frequency dependence of backscattering, which is descriptive of the histologic findings in lesions and which is not evident with conventional US images.

Adult↗
PubMed1999

Handling 22NaCl by the blood-brain barrier and kidney: its relevance to salt-induced hypertension in dahl rats.

We previously reported that inappropriate renal vasoconstriction in Dahl salt-sensitive (DS) rats fed high NaCl diets may cause sodium retention. The present study examined the distribution and elimination of 22Na in DS and Dahl salt-resistant (DR) rats, and we determined whether an abnormality in renal function might also cause sodium retention in DS rats. Following an intravenous bolus of 4 microCi 22NaCl in prehypertensive DS and DR rats with similar blood pressures on low (0.23%) or high (8% for 4 days) NaCl diets, urinary clearance of 22Na in 1 hour was about 4 times less in DS than DR rats, and renal retention of 22Na was up to 8 times greater in DS than DR rats (P<0.01), suggesting that a renal functional defect may contribute to salt retention in DS rats; however, its uptake in tail artery, heart, lungs, liver, and spleen was similar in DS and DR rats. Uptake in brain was up to 5 times greater in DS than DR rats (P<0.01). Cerebrospinal fluid 22Na radioactivity (in counts per minute) revealed that the blood-brain barrier is 5 to 8 times more permeable to sodium in DS than DR rats (P<0.01). Cerebrospinal fluid volume and brain water content increased significantly (P<0.01) in DS but not DR rats on an 8% NaCl diet. Intracerebroventricular bolus injection of 0.06 mL of 4.5 mol/L NaCl acutely and transiently induced the same degree of hypertension in DR and DS rats, whereas similar volume injections of isotonic saline, 4.5 mol/L Na-acetate, or 4.5 mol/L NaBr did not produce hypertension in either strain. We conclude that functional abnormalities in DS rat kidneys may cause retention of NaCl and that an increased blood-brain barrier permeability to NaCl may enhance its access to sites in the brain that are then activated and induce hypertension.

Animals↗
PubMed1998

Feasibility study of lactate imaging of head and neck tumors.

A proton spectroscopic imaging sequence was used to investigate the feasibility of lactate imaging in head and neck tumors. The sequence employs a two-shot lactate editing method with inversion recovery for additional lipid suppression, and a restricted field of view to suppress motion artifacts. Variations in acquisition parameters and two different receive coils were investigated on twelve patients. Elevated lactate was detected in three patients, no lactate was observed in seven patients, and two studies were inconclusive because of severe motion or inhomogeneity artifacts. Best results were obtained with an anterior/posterior neck coil at a 288 ms echo time (TE).

Adult↗
PubMed1998

Amplification of full-length hepatitis B virus genomes from samples from patients with low levels of viremia: frequency and functional consequences of PCR-introduced mutations.

To facilitate the investigation of hepatitis B virus (HBV) sequence variation, we recently established a method for functional analysis of PCR-amplified full-length HBV genomes. This study aimed at estimating the number of mutations introduced during amplification of genomes from samples from patients with low levels of viremia and their influence on replication and antigen expression. Wild-type HBV DNA template molecules in concentrations like those present in samples from patients with very low levels of viremia were amplified, sequenced (30 kb total), and functionally tested. We found that Taq polymerase and a Taq-Pwo polymerase mixture introduced an average of 5.7 and 3.1 mutations per genome, respectively, corresponding to polymerase error rates of 12.1 x 10(-5) and 6.0 x 1(0-5). One of 8 genomes (12%) amplified with Taq polymerase, but 7 of 17 genomes amplified with Taq-Pwo polymerases (41%), remained replication competent. All replication-competent genomes expressed HBs and HBe antigens and had an average of only 0.9 mutations per genome. In contrast, replication-defective genomes had an average of 5.4 mutations, which frequently also disturbed viral antigen expression. From these data we conclude that many of the replication-competent HBV genomes from a clinical specimen will retain their replication and antigen expression phenotypes even after extensive amplification with Taq-Pwo polymerases. Because replication competence is highly sensitive to random mutations, it is the best marker for the identification of HBV genomes with few or no PCR-introduced mutations.

Cloning, Molecular↗
PubMed1998

Renal blood flow: measurement in vivo with rapid spiral MR imaging.

PURPOSE: To assess the ability of three cine phase-contrast magnetic resonance (MR) imaging techniques to measure normal human renal blood flow (RBF) in vivo. MATERIALS AND METHODS: Eighteen healthy volunteers were studied with three cine phase-contrast MR imaging techniques: breath-hold, segmented k-space, two-dimensional, Fourier transform technique (ie, time-resolved imaging with automatic data segmentation, or TRIADS); a breath-hold rapid spiral acquisition; and a non-breath-hold rapid spiral acquisition that allowed resolution of both cardiac and respiratory cycles. In each case, total arterial RBF and blood flow per unit of renal volume were calculated. For each subject, RBF was measured with a standard technique of p-aminohippuric acid (PAH)-clearance hematocrit on the same day as the MR imaging examination was performed. RESULTS: The range of agreement (2 standard deviations, or 95% confidence interval) between RBF measurements obtained with the PAH-clearance hematocrit technique and the various cine phase-contrast techniques varied from +/- 17.6% to +/- 26.5%. The best agreement was obtained with non-breath-hold rapid spiral data, by using data from the end-expiratory phase of respiration. CONCLUSION: Findings with cine phase-contrast MR imaging employing rapid spiral acquisition are in good agreement with measurements made with PAH-clearance hematocrit and give the promise of clinical measurements of RBF.

Adult↗