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Biomedical subjects

M Schmidt

Publications and source records attributed to M Schmidt.

At least 19 recordsLinked to original sources
PubMed2007

Role of the progesterone receptor for paclitaxel resistance in primary breast cancer.

Paclitaxel plays an important role in the treatment of primary breast cancer. However, a substantial proportion of patients treated with paclitaxel does not appear to derive any benefit from this therapy. We performed a prospective study using tumour cells isolated from 50 primary breast carcinomas. Sensitivity of primary tumour cells to paclitaxel was determined in a clinically relevant range of concentrations (0.85-27.2 microg ml(-1) paclitaxel) using an ATP assay. Chemosensitivity data were used to study a possible association with immunohistochemically determined oestrogen and progesterone receptor (ER and PR) status, as well as histopathological parameters. Progesterone receptor (PR) mRNA expression was also determined by quantitative RT-PCR. We observed a clear association of the PR status with chemosensitivity to paclitaxel. Higher levels of immunohistochemically detected PR expression correlated with decreased chemosensitivity (P=0.008). Similarly, high levels of PR mRNA expression were associated with decreased paclitaxel chemosensitivity (P=0.007). Cells from carcinomas with T-stages 3 and 4 were less sensitive compared to stages 1 and 2 (P=0.013). Multiple regression analysis identified PR receptor status and T-stage as independent predictors of paclitaxel chemosensitivity, whereas the ER, N-stage, grading and age were not influential. In conclusion, in vitro sensitivity to paclitaxel was higher for PR-negative compared with PR-positive breast carcinoma cells. Thus, PR status should be considered as a possible factor of influence when designing new trials and chemotherapy protocols.

Antineoplastic Agents, Phytogenic↗
PubMed2007

Comparison of three bacterial detection methods under routine conditions.

BACKGROUND AND OBJECTIVES: Since 2004, bacterial screening of platelets has been required in the USA and is also done on a voluntary basis in many European countries. The German Red Cross blood donor services conducted a prospective multicentre study in order to investigate the prevalence of bacterially contaminated pool platelet concentrates and apheresis platelet concentrates. This substudy compares three different bacterial detection systems. STUDY DESIGN AND METHODS: Platelet concentrates were tested in parallel with BacT/ALERT, Scansystem and Pall eBDS (n = 6307) in pool platelets. Apheresis platelets were tested in parallel with BacT/ALERT and Pall eBDS (n = 4730). All initially positive results were evaluated by a standardized procedure including evaluation by a microbiology reference laboratory. RESULTS: One in 6307 pool platelets were confirmed positive by BacT/ALERT, whereas Pall eBDS and Scansystem failed to detect these samples. Only three samples were initially reactive with Pall eBDS without proof of any bacteria strains. The rate of false-positive results was substantially higher for BacT/ALERT (0.25%, 28 in 11,037 tested samples) than for eBDS (0.03%, 3 in 11 037 tested samples) or Scansystem (0.0%, 0 in 6307 tested samples). Three of 4730 apheresis platelets were confirmed positive by BacT/ALERT. These were negative with Pall eBDS. CONCLUSION: Sensitivity was best for BacT/ALERT, whereas specificity was enhanced for Pall eBDS and Scansystem. Scansystem required specially trained staff, whereas BacT/ALERT and Pall eBDS were easy, quick, user-friendly and objective methods.

Bacteria↗
PubMed2006

Contribution of anthropogenic and natural sources to atmospheric methane variability.

Methane is an important greenhouse gas, and its atmospheric concentration has nearly tripled since pre-industrial times. The growth rate of atmospheric methane is determined by the balance between surface emissions and photochemical destruction by the hydroxyl radical, the major atmospheric oxidant. Remarkably, this growth rate has decreased markedly since the early 1990s, and the level of methane has remained relatively constant since 1999, leading to a downward revision of its projected influence on global temperatures. Large fluctuations in the growth rate of atmospheric methane are also observed from one year to the next, but their causes remain uncertain. Here we quantify the processes that controlled variations in methane emissions between 1984 and 2003 using an inversion model of atmospheric transport and chemistry. Our results indicate that wetland emissions dominated the inter-annual variability of methane sources, whereas fire emissions played a smaller role, except during the 1997-1998 El Niño event. These top-down estimates of changes in wetland and fire emissions are in good agreement with independent estimates based on remote sensing information and biogeochemical models. On longer timescales, our results show that the decrease in atmospheric methane growth during the 1990s was caused by a decline in anthropogenic emissions. Since 1999, however, they indicate that anthropogenic emissions of methane have risen again. The effect of this increase on the growth rate of atmospheric methane has been masked by a coincident decrease in wetland emissions, but atmospheric methane levels may increase in the near future if wetland emissions return to their mean 1990s levels.

Atmosphere↗
PubMed2006

Isotropic-nematic interface and wetting in suspensions of colloidal platelets.

We study interfacial phenomena in a colloidal dispersion of sterically stabilized gibbsite platelets, exhibiting coexisting isotropic and nematic phases separated by a sharp horizontal interface. The nematic phase wets a vertical glass wall and polarized light micrographs reveal homeotropic surface anchoring both at the free isotropic-nematic interface and at the wall. On the basis of complete wetting of the wall by the nematic phase, as found in our density functional calculations and computer simulations, we analyze the balance between Frank elasticity and surface anchoring near the contact line. Because of weak surface anchoring, the director field in the capillary rise region is uniform. From the measured rise (6 microm) of the meniscus at the wall we determine the isotropic-nematic surface tension to be 3 nN/m, in quantitative agreement with our theoretical and simulation results.

Journal Article↗
PubMed2006

Safety of ethanolic kava extract: Results of a study of chronic toxicity in rats.

BACKGROUND: Recently, potential liver toxicity was discussed with the intake of kava extract preparations (Piper methysticum) as anxiolytic drugs. The aim of this study was to test chronic toxicity in rats by oral application of an ethanolic kava full extract. METHODS: Wistar rats of both sexes were fed 7.3 or 73 mg/kg body weight of ethanolic kava extract for 3 and 6 months. The animals were examined for changes in body weight, hematological and liver parameters, and macroscopical and microscopical histological changes in the major organs. RESULTS: No signs of toxicity could be found. CONCLUSIONS: The results are in accordance with the medical experience regarding the use of kava preparations and the long tradition of kava drinking in the South Pacific island states. Specifically, the results do not back the suspicion of potential liver toxicity.

Animals↗
PubMed2006

The impact of genomic alterations on the transcriptome: a prostate cancer cell line case study.

Genetic instability may lead to the loss/gain of transcriptional control. Here we investigated the effect of genomic instability, that is loss/gain of chromosomal regions on the global transcriptome of prostate cancer cell line DU145. The genomic loss/gain map obtained through BAC array-based CGH was superimposed on the dynamic transcriptome of DU145 cells treated with serum for 0 h (serum starved), 2 h and 12 h. The genomic analysis suggested that in DU145 cells: (1) chromosomal gains are prominent than losses and (2) copy number changes are associated with chromosome-specific and dynamic gene expression regulatory mechanisms. A significant proportion of the genes in the stable regions of the chromosome were up-regulated whereas a higher proportion of genes were down-regulated at 2 and 12 h in the deleted regions of the chromosomes following serum treatment. No change in expression was observed for the genes in the gained regions over a period of time. This analysis led us to propose that loss of heterozygosity leads to an overall transcriptional down-regulation that may further lead to a decrease in the expression of putative tumor suppressors. The genomic profile of DU145 is similar to pathological specimens of prostate cancer, hence the genomic/transcriptomic signature of DU145 can be used to understand the pathology of prostate cancer. It is expected that this analysis will allow a better understanding of transcriptional regulatory mechanisms in the context of genomic loss and gain and may lead to the discovery of novel oncogenes and tumor suppressors and the underlying regulatory pathways.

Cell Line, Tumor↗
PubMed2006

FGFR4 Arg388 allele correlates with tumour thickness and FGFR4 protein expression with survival of melanoma patients.

A single nucleotide polymorphism in the gene for FGFR4 (-Arg388) has been associated with progression in various types of human cancer. Although fibroblast growth factors (FGFs) belong to the most important growth factors in melanoma, expression of FGF receptor subtype 4 has not been investigated yet. In this study, the protein expression of this receptor was analysed in 137 melanoma tissues of different progression stages by immunohistochemistry. FGFR4 protein was expressed in 45% of the specimens and correlated with pTNM tumour stages (UICC, P = 0.023 and AJCC, P = 0.046), presence of microulceration (P = 0.009), tumour vascularity (P = 0.001), metastases (P = 0.025), number of primary tumours (P = 0.022), overall survival (P = 0.047) and disease-free survival (P = 0.024). Furthermore, FGFR4 Arg388 polymorphism was analysed in 185 melanoma patients by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The Arg388 allele was detected in 45% of the melanoma patients and was significantly associated with tumour thickness (by Clark's level of invasion (P = 0.004) and by Breslow in mm (P = 0.02)) and the tumour subtype nodular melanoma (P = 0.002). However, there was no correlation of the FGFR4 Arg388 allele with overall and disease-free survival. In conclusion, the Arg388 genotype and the protein expression of FGFR4 may be potential markers for progression of melanoma.

Adult↗
PubMed2006

[Prevention of thromboembolism in patients with atrial fibrillation].

Provided that account is taken of the criteria discussed in the present article, there is no doubt about the therapeutic benefits of effective anticoagulation in patients with chronic atrial fibrillation. Indeed, it is to be expected that the previously valid therapeutic guidelines are more likely to be expanded to reduce feared thromboembolic complications to a minimum, as is exemplified by the recommendation that the application of anticoagulation treatment with vitamin K antagonists should be continued over the longer term, that is, after the restoration of sinus rhythm. Furthermore, there is hope that effective drugs with a calculable (level of) safety and simplicity of administration may soon become available.

Administration, Oral↗
PubMed2006

The implications of 18F-FDG PET for the diagnosis of endoprosthetic loosening and infection in hip and knee arthroplasty: results from a prospective, blinded study.

BACKGROUND: The most frequent complications of joint arthroplasty are septic or aseptic loosening of endoprostheses. Preoperative differentiation is essential, since very different treatment methods result from the diagnoses. The aim of the current study was to evaluate the clinical value of 18F-Fluoro-deoxyglucose positron emission tomography (18F-FDG PET) as a diagnostic modality for inflammation and loosening in hip and knee joint prostheses. METHODS: 18F-FDG-PET examinations and multiphase bone scan were performed on hip and knee endoprostheses in 27 patients prior to revision surgical procedures planned for prosthetic loosening. Intact prostheses were found at the opposite site in some patients so that additional 9 joints could be examined with the field of view of 18F-FDG PET. Verification and valuation of the PET and scintigraphic image findings were conducted by comparing them with information combined from intraoperative findings, histopathology, and microbiological investigations. RESULTS: Evidence of loosening was correctly determined in 76.4% of cases using 18F-FDG-PET, and in 75% of cases using bone scan. The detection of periprosthetic inflammation using 18F-FDG-PET had a sensitivity of 100% for septic cases and of 45.5% in cases of increased abrasion and aseptic foreign-body reactions. However, reliable differentiation between abrasion-induced and bacterial-caused inflammation was not possible using 18F-FDG-PET. CONCLUSION: 18F-Fluoro-deoxyglucose positron emission tomography (18F-FDG-PET) allows reliable prediction of peri-prosthetic septical inflammatory tissue reactions. Because of the high sensitivity of this method, a negative PET result in the setting of a diagnostically unclear situation eliminates the need for revision surgery. In contrast, a positive PET result gives no clear differentiation regarding the cause of inflammation.

Aged↗
PubMed2006

Fragile sites are preferential targets for integrations of MLV vectors in gene therapy.

Following gene therapy of SCID-X1 using murine leukemia virus (MLV) derived vector, two patients developed leukemia owing to an activating vector integration near the LMO2 gene. We found that these integrations reside within FRA11E, a common fragile site known to correlate with chromosomal breakpoints in tumors. Further analysis showed that fragile sites attract a nonrandom number of MLV integrations, shedding light on its integration mechanism and risk-to-benefit ratio in gene therapy.

Cells, Cultured↗
PubMed2006

Free functional muscle transplantation for facial reanimation: experimental comparison between the one- and two-stage approach.

To investigate functional results of either one- or two-staged free muscle transplantation the scutuloauricularis model in the New Zealand white rabbit was used. Thirty rabbits were allocated to two groups with 15 animals each. In Group 1 (one-stage approach) peroneus brevis (PB) was harvested as a free muscle graft with a 7cm long motor branch. The graft was positioned instead of right scutuloauricularis (SCUT) and its vascular supply microsurgically re-established. The motor branch was transferred to the contralateral side and its proximal end coapted to the cut facial motor branch to left SCUT. Before nerve coaptation biopsies were harvested from the cut motor branch for morphological analysis. In Group 2 (two-stage approach) a 7cm long saphenous nerve graft was taken and coapted to the cut motor branch of SCUT and crossed over to the contralateral side. Nerve specimens from the cut motor branch were taken. Eight months later the free transplantation of PB was performed and its motor branch coapted to the distal end of the cross-over nerve graft. After a total time period of 13 months the final experiments were carried out in each group. Maximal tetanic tensions in reinnervated PB were measured and biopsies of muscle grafts together with nerve biopsies from the distal part of the motor branch were harvested for morphological analysis. Muscle grafts of Group 1 revealed tetanic tension values of 12.5N (SD 3.1) in comparison to 10.6N (SD 3.5) obtained in Group 2. This difference was not statistically significant (p=0.303). In Group 1, the amount of regenerated nerve fibers counted at the distal motor branch site (mean: 2798, SD 1242) was significantly higher (p=0.008) than in Group 2 (mean: 1138, SD 1004). Muscle graft morphology revealed significantly less Type I fibers (p=0.016) and more Type IIb/d fibers (p=0.011) in Group 1 compared to Group 2. However, the overall amount of perimysial connective tissue showed no significant difference in both groups (p=0.478). Free muscle transplantation in a one-stage approach offers similar functional results in comparison to the two-stage approach. Although muscle grafts of the one-stage transplantation underwent a longer period of denervation similar contents of perimysial connective tissue could be observed.

Animals↗
PubMed2006

Soft core fluid in a quenched matrix of soft core particles: a mobile mixture in a model gel.

We present a density-functional study of a binary phase-separating mixture of soft core particles immersed in a random matrix of quenched soft core particles of larger size. This is a model for a binary polymer mixture immersed in a cross-linked rigid polymer network. Using the replica "trick" for quenched-annealed mixtures we derive an explicit density functional theory that treats the quenched species on the level of its one-body density distribution. The relation to a set of effective external potentials acting on the annealed components is discussed. We relate matrix-induced condensation in bulk to the behavior of the mixture around a single large particle. The interfacial properties of the binary mixture at a surface of the quenched matrix display a rich interplay between capillary condensation inside the bulk matrix and wetting phenomena at the matrix surface.

Journal Article↗
PubMed2006

[Bronchial asthma. Update 2006].

Bronchial asthma, with a prevalence in Germany of 5% among adults and 10% among children, remains a frequent disease. Newer cell biological data show a separate regulation of the allergy (interleukin 4, IL-4, pathway) and of the eosinophilic inflammation in asthma (IL-5 pathway). Both conditions require a therapeutic approach. To prevent irreversible bronchial remodeling, early diagnosis and targeted therapy are decisive. Bronchial asthma is regarded as evident when the paroxysmal character of the disease is confirmed and an-at least intermittent-obstructive ventilation disorder is apparent which responds well to short-acting beta2-adrenergic agents. Current asthma treatment has been assured in many studies (evidence level A) and is based on therapy in stages which classifies therapeutic measures depending on four grades of severity. Accordingly, most patients are largely without complaints, and nocturnal attacks are now rare. New medications are intended to overcome any remaining therapeutic weak points. Antileukotrienes and anti-IgE antibodies can contribute to reducing the necessary corticosteroids. Pharmaceutical agents that intervene in the IL-4 or IL-5 regulation or prevent remodeling are being developed.

Asthma↗
PubMed2006

[Schizophrenia and depression].

BACKGROUND: Comparison of symptom-related and social role development between patients with schizophrenia, major depression and healthy controls provided insights into the untreated early course of the two disorders. SAMPLES AND METHODS: Symptoms, functional impairment and social disability were assessed and compared using the IRAOS and several other cross-sectional instruments in three samples. RESULTS: At the early illness stages there was considerable overlap in the symptom patterns and impairments presented by persons with schizophrenia and severe depression. The two disorders did not diverge until later in the early illness course with the onset of psychotic symptoms. Depressive symptoms showed a maximum in the first psychotic episode and relapse episodes and decreased with the remitting episode. Due to differences in cognitive appraisal depressed patients reported more functional impairment and social disability than patients with schizophrenia did. CONCLUSION: The early course of symptoms and social impairment in schizophrenia and depression seems to offer an opportunity to distinguish these disorders from variants of normal development fairly early. However, early diagnostic distinction and prediction of psychosis versus depression risk at the pre-psychotic prodromal stage do not seem promising due to the broad overlap in symptoms and impairment.

Adult↗
PubMed2006

Chemical and biochemical generation of carbohydrates from lignocellulose-feedstock (Lupinus nootkatensis)--quantification of glucose.

Different chemical and enzymatic methods were applied for the hydrolysis of main stems from Lupinus nootkatensis (harvest November 2002). The whole process (all steps) is based on the lignocellulose-feedstock biorefinery regime. The acid hydrolysis of L. was performed with concentrated hydrochloric acid; advantages in this process are exothermic hydrolysis and the possibility of acid recovery. Enzymatic hydrolysis achieved high yields of fermentable carbohydrates (regarding to input cellulose) with high selectivity. However, this way requires the generation of cellulose from L. by chemical pulping. Monosaccharide derivatives thus obtained were identified by their GC retention times and the corresponding MS fragmentation. Hexamethyldisilazane was used as derivatization reagent to prepare the trimethylsilyl derivatives of the carbohydrates and of the degradations products of cellulose from the different fractions. The glucose content was quantified by GC peak integration with respect to an internal standard.

Biomass↗
PubMed2006

Enhanced transduction of mouse salivary glands with AAV5-based vectors.

We previously demonstrated that recombinant adeno-associated virus vectors based on serotype 2 (rAAV2) can direct transgene expression in salivary gland cells in vitro and in vivo. However, it is not known how other rAAV serotypes perform when infused into salivary glands. The capsids of serotypes 4 and 5 are distinct from rAAV2 and from each other, suggesting that they may direct binding and entry into different cell types. In the present study, we investigated the tropisms, transduction efficiencies, and antibody response to AAV vectors based on AAV serotypes 2, 4, and 5. Administration of rAAV2beta-galactosidase (betagal), rAAV4betagal, or rAAV5betagal to murine submandibular salivary glands by retrograde ductal instillation resulted in efficient transduction of salivary epithelial cells, with AAV4 and AAV5 producing 2.3 and 7.3 times more betagal activity compared with AAV2. Improved transduction with AAV5 was confirmed by QPCR of DNA extracted from glands and immunohistochemical staining for transgene expression. Like AAV2, AAV5 primarily transduced striated and intercalated ductal cells. AAV4 transduction was evident in striated, intercalated, and excretory ductal cells, as well as in convoluted granular tubules. In keeping with the encapsulated nature of the salivary gland, the majority of persistent viral genomes were found in the gland and not in other tissues. Neutralizing antibodies (NABs) found in the serum of virus-infused animals were serotype specific and there was no crossreactivity between serotypes. No NABs were detected in saliva but sialic acid conjugates present in saliva could neutralize AAV4 at low dilutions. Together our data suggest that because of differences in receptor binding and transduction pathways, other serotypes may have improved utility as gene transfer vectors in the salivary gland and these differences could be exploited in gene therapy applications.

Animals↗
PubMed2006

[Second reading of breast imaging at the hospital department of radiology: reasonable or waste of money?].

PURPOSE: To assess the effect of a second diagnostic reading of breast imaging at a university department of radiology. MATERIAL AND METHODS: The diagnostic reports of first readers from different private radiology practices and the reports of second readers from the university department of radiology were compared with the histological results (n = 214) and outcome of follow-ups for 4 years (n = 74) in 236 patients (mean age 55 years). BI-RADS categories were used for this purpose. The initial examinations had been performed because of symptoms (n = 117), early detection outside an organized screening program (n = 102), evaluations following breast cancer therapy (n = 13) and unknown primary tumors (n = 4). In addition, the number of complementary examinations and the influence of a second reading on patient management were evaluated. RESULTS: A total of 140 lesions were malignant and 148 were benign. Of the 288 lesions, 49 % were classified identically in the second reading; 36 % (79/217) of the lesions initially classified as BI-RADS 4 and 5 were downgraded to benign; and 41 % (29/71) of the lesions classified as BI-RADS 1 to 3 were upgraded as suspected of being malignant. The kappa value between the first and second readers was 0.34 with respect to each BI-RADS category separately and 0.18 with respect to categories 1 to 3 (benign) versus 4 and 5 (malignant). A second reading increased the sensitivity from 81 % (114/140) to 96 % (135/140) and the specificity from 30 % (45/148) to 78 % (116/148). Second readers detected 23 additional malignant lesions, changed two lesions correctly classified as malignant to benign categories and caused 6 additional false-positive findings. In all, 38 surgical biopsies could be prevented, one biopsy was erroneously delayed and three unnecessary excisional biopsies were initiated. In the study group, 49 MRI examinations revealed 5 additional malignant lesions and positively influenced surgical planning in 28 patients. In addition to these MRI examinations, 221 patients were examined using ultrasonography, 62 patients using complementary mammography, and 7 using galactography. CONCLUSION: The benefit of a second reading outweighs the expenditure.

Biopsy↗