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Biomedical subjects

A Stahl

Publications and source records attributed to A Stahl.

At least 19 recordsLinked to original sources
PubMed2004

Comparison of different SUV-based methods for monitoring cytotoxic therapy with FDG PET.

PURPOSE: Fluorine-18 fluorodeoxyglucose positron emission tomography (FDG PET) is a promising tool for monitoring cytotoxic therapy in tumours. Due to the limited data available, a standard imaging protocol for the prediction of tumour response has not yet been approved. The aim of this study was to compare commonly applied imaging protocols and calculations of the standardised uptake value (SUV) for the early prediction of histopathological response to chemotherapy. METHODS: Serial FDG PET scans of 43 patients with gastric carcinomas were retrospectively analysed. All patients received two consecutive scans (one bed position at 40 min p.i. and four bed positions at 90 min p.i.) at baseline and during the first cycle of cisplatinum-based chemotherapy. Reconstruction of the images was performed by filtered back-projection (FBP) and using an iterative algorithm (OSEM). SUVs were calculated with and without correction for the blood glucose level using normalisation by body weight, body surface area and lean body mass. Relative percentage changes between SUVs at baseline and follow-up were calculated and analysed for their potential to predict histopathological response to chemotherapy (ROC analysis). Response was defined as less than 10% viable tumour cells in the tumour specimen obtained by surgery 3-4 weeks after the completion of chemotherapy. RESULTS: Eight of 43 patients were histopathological responders to chemotherapy. The percentage changes in SUV(body weight) for responders and non-responders were -52.2 (+/-13.2) and -25.2 (+/-15.2), -54.7 (+/-18.2) and -24.5 (+/-16.1), -53.9 (+/-24.2) and -22.7 (+/-21.3), and -56.7 (+/-21.6) and -26.1 (+/-18.9) for serial scans at 40-min FBP, 40-min OSEM, 90-min FBP and 90-min OSEM, respectively (responders versus non-responders: p<0.01 in each case). According to ROC analysis, neither the scan protocol nor correction for blood glucose significantly influenced the accuracy (approx. 80%) or the cut-off value (approx. -40% change in tumour SUV) for the prediction of response. Normalisation of SUVs by body surface area or lean body mass instead of body weight yielded essentially identical results. CONCLUSION: In gastric carcinomas the prediction of response to chemotherapy on the basis of relative tumour SUV changes is not essentially influenced by any of the methodological variations investigated (time delay after FDG administration, acquisition protocol, reconstruction algorithm, normalisation of SUV). This demonstrates the robustness of FDG PET for therapeutic monitoring and facilitates the comparability of studies obtained at different institutions and with different protocols. However, whichever method is used for therapy monitoring with FDG PET, a highly standardised protocol must be observed to take the dynamics of tumour FDG uptake into account.

Algorithms↗
PubMed2004

Colorectal cancer patients before resection of hepatic metastases. Impact of (18)F-FDG PET on detecting extrahepatic disease.

AIM: Evaluation of the role of FDG-PET in comparison to conventional staging methods for detecting extrahepatic tumour deposits prior to resection of liver metastases. PATIENTS, METHODS: In our prospective study, 58 patients (24 women, 34 men; age 33-81 years) with liver metastases of colorectal carcinoma underwent FDG-PET. Images were acquired in 3D-mode including transmission scans and reconstructed iteratively. For conventional staging all patients underwent abdominal ultrasound, helical computed tomography (CT) of the thorax and abdomen, and colonoscopy/rectoscopy. A preliminary therapeutic decision was established without knowledge of the FDG-PET findings. Thereafter, it was revised or confirmed according to the results of FDG-PET. RESULTS: In 3/58 patients extrahepatic tumour deposits were concordantly identified with both conventional staging methods and FDG-PET. However, in one case, both conventional methods and FDG-PET were false positive regarding pulmonary metastases. In 12/58 patients, nothing but FDG-PET detected extrahepatic tumour masses, which were later confirmed either by histology or follow-up. CONCLUSION: Our study suggests that in 21% of patients exclusively FDG-PET is an appropriate diagnostic tool to reveal extrahepatic metastases or local recurrence of colorectal carcinoma. Our results demonstrate that FDG-PET provides relevant additional information for accurate therapeutic planning as compared to the conventional combination of staging methods. Therefore, FDG-PET has to exert a decisive influence on the decision for resection of hepatic metastases.

Adult↗
PubMed2003

Satisfaction with rollators among community-living users: a follow-up study.

PURPOSE: Rollators are used in order to make mobility possible for people with restricted walking ability. The use of rollators is increasing, but little is known about outcomes. The aim of this study was to investigate users' satisfaction with rollators. METHOD: A follow-up study was carried out in seven Danish municipalities. One month after they got their device, 89 users of rollators were interviewed by means of the QUEST 1.0. Three months after the first interview a second interview took place and data from the 64 users available for follow-up were analysed. RESULTS: The users were satisfied with their rollators, and the frequency of use was high. However, many of the users were frail, and some of them were not fully satisfied in all respects. Women especially, users living alone and first time users were likely to be dissatisfied. The main problem identified was handling the rollator, and for several users the physical environment caused accessibility problems. CONCLUSIONS: Rollators are valuable for the users and a relevant societal intervention. However, a better match between person and technology, enhanced user training and follow-up can improve the outcome of the intervention. Furthermore, better rollator design is called for, and buses and the outdoor environment need to be made more accessible.

Adult↗
PubMed2002

Excretion of FDG into saliva and its significance for PET imaging.

AIM: Assessment of the salivary excretion of FDG and its significance during PET imaging. METHODS: Salivary samples from 16 patients were obtained during the first three hours after FDG injection and their activity concentrations were measured. Furthermore, regional FDG accumulations in whole body PET scans (60 min p.i., ROI technique) were determined in the following locations: vestibulum oris, floor of the mouth, hypopharynx, parotid gland, submandibular gland. This ROI analysis was repeated after drinking water (0.2 l) and a second scan (120 min p.i.). RESULTS: The salivary FDG concentrations (SUV) at the first, second and third hour p.i. were 0.2 +/- 0.1, 0.4 +/- 0.2, and 0.3 +/- 0.2, respectively. The FDG uptake in the investigated cranial and cervical sites ranged from SUV 1.2 +/- 0.5 in the major salivary glands to 2.1 +/- 0.5 in the floor of the mouth. These values remained unchanged after drinking of water. CONCLUSION: The salivary FDG concentration is higher than expected from the low physiologic content of glucose. This may--similarly to renal excretion--reflect a different behavior of FDG and glucose during reabsorption processes. Nevertheless, the salivary concentration of FDG is so low that no relevant influence on PET imaging is to be expected. Accordingly, the drinking of water prior to the scan is of no benefit for FDG PET imaging of the head and the neck.

Fluorodeoxyglucose F18↗
PubMed2001

Fatty acid transport proteins: a current view of a growing family.

Long-chain fatty acids (LCFAs) are a major caloric component of our diet and are key metabolites for energy generation and storage. Physiological uptake of LCFAs across cell membranes is a saturable and competable process occurring at low concentrations, indicative of protein-mediated transport. Fatty acid transport proteins are a family of transmembrane proteins that enhance LCFA uptake and are produced in all fatty acid-utilizing tissues. Here, we review our current understanding of the function, expression patterns and regulation and subcellular localization of this interesting family of proteins.

Animals↗
PubMed2001

Butyrate and propionate downregulate ERK phosphorylation in HT-29 colon carcinoma cells prior to differentiation.

We have characterized the effects of different short-chain fatty acids (SCFAs) on cell growth and differentiation as well as the phosphorylation state of ERK1 and 2 in the human colon adenocarcinoma cell line HT-29. Of the five SCFAs tested, only butyrate and propionate impaired cellular proliferation. Moreover, butyrate and propionate specifically resulted in a decrease in ERK1 and 2 phosphorylation at 3 and 6 hours post-treatment, suggesting a correlation between the ability of these SCFAs to inhibit cellular proliferation and decrease ERK phosphorylation. Notably, the decrease in ERK phosphorylation was observed prior to the induction of the differentiation markers alkaline phosphatase (AP) and carcinoembryonic antigen (CEA) by butyrate and propionate from days 6 to 18 post-treatment. In the case of butyrate- and propionate-induced differentiation, ERK phosphorylation is a marker and may play a role in the proliferation and/or differentiation states of this cell line.

Alkaline Phosphatase↗
PubMed2000

First direct measurement of the parity-violating coupling of the Z0 to the s quark

We present the first direct measurement of A(s), the parity-violating coupling of the Z0 boson to the strange quark, using approximately 550 000 e(+)e(-)-->Z0-->hadrons events recorded by the SLC Large Detector with a polarized e(-) beam. We tagged Z0-->s&smacr; events by the absence of B or D hadrons and the presence in each hemisphere of a high momentum K+/- or K(0)(s). Fitting the polar angle distributions of the strangeness-signed thrust axis gave A(s) = 0.895+/-0.066(stat)+/-0.062(syst). The analyzing power and uu+d&dmacr; background were constrained using the data, greatly reducing any model dependence.

Journal Article↗
PubMed2000

Precise measurement of the b-quark fragmentation function in Z0 boson decays

We have developed a new technique for inclusive reconstruction of the energy of B hadrons. The excellent efficiency and resolution of this technique allow us to make the most precise determination of the b-quark fragmentation function, using e(+)e(-)-->Z0 decays recorded in the SLAC Large Detector experiment. We compared our measurement with the predictions of a number of fragmentation models. We excluded several of these models and measured the average scaled energy of weakly decaying B hadrons to be = 0.714+/-0. 005(stat)+/-0.007(syst)+/-0.002 (model dependence).

Journal Article↗
PubMed2000

Effect of N-butylscopolamine on intestinal uptake of fluorine-18-fluorodeoxyglucose in PET imaging of the abdomen.

AIM: Circumscribed or diffuse intestinal uptake of F-18-fluorodeoxyglucose (FDG) is a frequent finding in PET imaging of the abdomen often interfering with correct scan interpretation. The aim of the present study was to determine whether the antiperistaltic agent N-butylscopolamine reduces intestinal FDG-uptake. METHODS: Whole body scans from 40 patients with malignant lymphoma and no evidence for intraabdominal tumor involvement were analyzed (6 bed positions; scan start 60 min post injection of approximately 350 MBq FDG; emission time 9 min per position; no attenuation correction). Twenty patients received 20 mg N-butylscopolamine in combination with an intravenous injection of FDG (test group) and 20 patients received only FDG (control group). For analysis, the intensity of bowel loops and diffuse abdominal background were compared to normal liver on a 4 point scale (0 = lowest intensity, 3 = highest) by two experienced nuclear medicine physicians. Furthermore, focal intestinal uptake was evaluated quantitatively by a ROI technique and bowel to liver ratios (b/l) were calculated. RESULTS: Bowel loops had lower intensity and occupied less abdominal regions in the test group than in the control group (visual score 1 vs. 1.5, p = 0.01; abdominal regions 1 of 5 vs. 2.5 of 5, p = 0.04). The visual score for diffuse abdominal background was 0.5 in the test group and 1 in the control group (p = 0.04). Bowel uptake interfered with scan interpretation in 1 of 20 patients in the test group and 6 of 20 patients in the control group (p = 0.01). The b/l ratios were 1.5 +/- 0.7 in the test group and 2.3 +/- 1.4 in the control group (p = 0.08). CONCLUSION: Administration of N-butylscopolamine reduces intestinal uptake of FDG and may facilitate accurate interpretation of abdominal FDG-PET studies.

Abdomen↗
PubMed1999

Identification of the major intestinal fatty acid transport protein.

While intestinal transport systems for metabolites such as carbohydrates have been well characterized, the molecular mechanisms of fatty acid (FA) transport across the apical plasmalemma of enterocytes have remained largely unclear. Here, we show that FATP4, a member of a large family of FA transport proteins (FATPs), is expressed at high levels on the apical side of mature enterocytes in the small intestine. Further, overexpression of FATP4 in 293 cells facilitates uptake of long chain FAs with the same specificity as enterocytes, while reduction of FATP4 expression in primary enterocytes by antisense oligonucleotides inhibits FA uptake by 50%. This suggests that FATP4 is the principal fatty acid transporter in enterocytes and may constitute a novel target for antiobesity therapy.

Binding, Competitive↗
PubMed1998

A family of fatty acid transporters conserved from mycobacterium to man.

Long chain fatty acids (LCFAs) are an important source of energy for most organisms. They also function as blood hormones, regulating key metabolic functions such as hepatic glucose production. Although LCFAs can diffuse through the hydrophobic core of the plasma membrane into cells, this nonspecific transport cannot account for the high affinity and specific transport of LCFAs exhibited by cells such as cardiac muscle, hepatocytes, and adipocytes. Transport of LCFAs across the plasma membrane is facilitated by fatty acid transport protein (FATP), a plasma membrane protein that increases LCFA uptake when expressed in cultured mammalian cells [Schaffer, J. E. & Lodish, H. F. (1994) Cell 79, 427-436]. Here, we report the identification of four novel murine FATPs, one of which is expressed exclusively in liver and another only in liver and kidney. Both genes increase fatty acid uptake when expressed in mammalian cells. All five murine FATPs have homologues in humans in addition to a sixth FATP gene. FATPs are found in such diverse organisms as Fugu rubripes, Caenorhabditis elegans, Drosophila melanogaster, Saccharomyces cerevisiae, and Mycobacterium tuberculosis. The function of the FATP gene family is conserved throughout evolution as the C. elegans and mycobacterial FATPs facilitate LCFA uptake when overexpressed in COS cells or Escherichia coli, respectively. The identification of this evolutionary conserved fatty acid transporter family will allow us to gain a better understanding of the mechanisms whereby LCFAs traverse the lipid bilayer as well as yield insight into the control of energy homeostasis and its dysregulation in diseases such as diabetes and obesity.

Amino Acid Sequence↗
PubMed1997

Melanoma cell migration on vitronectin: regulation by components of the plasminogen activation system.

Tumor cell migration and invasion require complex interactions between tumor cells and the surrounding extracellular matrix. These interactions are modified by cell adhesion receptors, as well as by proteolytic enzymes and their receptors. Here, we study the influence of the protease urokinasetype plasminogen activator (uPA) and its receptor (uPAR) on melanoma cell adhesion to, and migration on, the extracellular matrix protein vitronectin (VN). Cell adhesion to VN, but not to type I collagen, is significantly enhanced in the presence of either uPA or its amino-terminal fragment (ATF). Soluble uPAR can inhibit this effect, indicating that uPA/uPAR on melanoma cells can function as a VN receptor. In the absence of bivalent cations, uPA/uPAR can promote cell attachment on VN, but not cell spreading, suggesting that the glycosylphosphatidylinositol (GPI)-anchored uPAR alone is unable to organize the cytoskeleton. Chemotactic melanoma cell migration on a uniform VN matrix is inhibited by uPA and ATF, implying that cell motility decreases when uPA/uPAR acts as a VN receptor. In contrast, plasminogen activator inhibitor I (PAI-I) can stimulate melanoma cell migration on VN, presumably by inhibiting uPA/uPAR-mediated cell adhesion to VN and thereby releasing the inhibition of cell migration induced by uPA. Together, our data implicate components of the plasminogen activation system in the direct regulation of cell adhesion and migration, thereby modulating the behavior of malignant tumor cells.

Cell Movement↗
PubMed1996

Localization of ribosomal genes in human spermatogonia by fluorescent in situ hybridization and confocal microscopy.

The distribution of ribosomal RNA genes in nucleoli is still a matter of controversy. We have investigated the nucleolus of human type A spermatogonia, which displays a single, large fibrillar center. Silver-staining was used to localize the fibrillar center by light microscopy. Fluorescent in situ hybridization was performed on the same cell, using a 5.8-kb probe specific for a transcribed region of the ribosomal genes. The fluorescent area exactly corresponded to the silver-stained area. The three-dimensional distribution of rDNA was studied in horizontal and orthogonal sections using a confocal laser scanning microscope. The presence of the fluorescent signal throughout the whole silver-stained structure demonstrated that the fibrillar center, and at least a part of the dense fibrillar component, contained most of the rDNA.

Cell Nucleolus↗
PubMed1996

The distribution of Ag-NORs proteins and ribosomal RNA genes in human spermatogonia: an original procedure associating silver-staining, fish and confocal microscopy.

It is generally accepted that Ag-NORs proteins are associated with nucleolar components engaged in rRNA synthesis. Since conflicting results have been reported concerning the intranucleolar sites of active ribosomal genes, the relationships between the silver-stained areas and the distribution of rDNA were analyzed in human spermatogonia using confocal microscopy of fluorescent in situ hybridized preparations previously stained with silver. The fluorescent signal strictly corresponded to the silver-stained area, identified at the ultrastructural level as the fibrillar center and the surrounding dense fibrillar component. A quantitative evaluation of nucleolar activity solely based on silver-staining may be misleading, taking into account that only Ag-positive proteins located in the dense fibrillar component can be associated with transcriptional activity, while those stored in the fibrillar center are associated with non-transcribed rRNA genes.

DNA, Ribosomal↗