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Biomedical subjects

C Weber

Publications and source records attributed to C Weber.

At least 37 records · Page 2Linked to original sources
PubMed2004

[Low-dose spiral CT of the lung in the follow-up of non-malignant lung disease].

PURPOSE: To assess image quality of chest CT with an 80 to 90 percent dose reduction in follow-up studies of patients with lung disease, dose and image quality of a low-dose protocol was investigated. MATERIALS AND METHODS: A follow-up low-dose CT (ND-CT, 120 kV, 10 mAs/slice, 3 mm slice thickness) was performed on 35 patients with non-malignant lung disease and compared with the initial standard dose CT (= SD-CT, 100 mAs/slice, 3 or 5 mm slice thickness). The dose was measured by thermo-luminescence in an Alderson phantom. Image quality was assessed by four independent radiologists in six perihilar, central and peripheral lung regions using a 4-point-scale ("very good", "good", "moderate", and "poor"). RESULTS: Effective dose was 0.5 mSv for ND-CT and 4.0 - 5.0 mSv for SD-CT. The ratings "very good"/"good" were given in the perihilar regions in ND-CT 97.5 % versus SD-CT 99.3 % (n. s.), in the central regions in ND-CT 96.4 % versus SD-CT 94.6 % (n. s.), and in the peripheral regions in ND-CT 70.0 % versus SD-CT 88.2 % (p < 0.01). CONCLUSION: Follow-up CT of pulmonary structures in patients with chronic lung disease can be performed with substantial dose reduction. A decrease of image quality may result in peripheral lung regions.

Adolescent↗
PubMed2004

[Diagnostic imaging in polytrauma: comparison of radiation exposure from whole-body MSCT and conventional radiography with organ-specific CT].

PURPOSE: To compare the radiation dose of whole-body multislice CT (MSCT) and conventional radiography with organ-specific CT in polytrauma. MATERIALS AND METHODS: The whole-body MSCT encompassing brain, neck and midface, chest, abdomen and pelvis was performed on a Somatom Volume Zoom (Siemens). Conventional radiography consisted of chest and cervical, thoracic and lumbar spine in two views as well as pelvis (Polymat, Siemens). Three combinations of organ specific CT were chosen: CT examination of (1) head and cervical spine, (2) head, cervical spine and chest, (3) head, cervical spine and abdomen. The effective doses of whole-body MSCT and conventional radiography with organ-specific CT were calculated. RESULTS: Effective doses were 20 mSv for whole-body MSCT, 2 mSv for conventional x-ray, and 5 mSv for combination (1), 8 mSv for combination (2) and (3) 16 mSv for combination (3) of the organ-specific CT. The ratio of radiation dose between whole-body MSCT and radiography was 10 : 1. This ratio was reduced to 3 : 1, 2 : 1 and 1 : 1 when a combination of radiography and CT was performed. CONCLUSIONS: Whole-body MSCT in polytrauma compared to conventional radiography with organ-specific CT induces a threefold increased dose in unfavorable situations and no increased dose in favorable situations. Nevertheless, routine use of whole-body MSCT should be critically evaluated and should be adapted to the clinical benefit.

Humans↗
PubMed2004

[Image quality of thin- and thick-slice MSCT reconstructions in low-contrast objects (liver lesions) with equal doses].

PURPOSE: To evaluate the image quality of thin-section MSCT examinations of low-contrast objects such as liver lesions, and to find out whether a thin slice technique requires an increase in radiation dose. MATERIALS AND METHODS: MSCT examinations of the liver were performed in the portal venous phase on a Volume Zoom Scanner (Siemens, Erlangen) with a collimation of 4 x 2.5 mm, 120 kV, 125 mAs and table speed of 12.5 mm. Forty small hypodense liver lesions with a mean size of 3 mm (1 to 8 mm) were reconstructed using a slice thickness of 3, 5, 7, and 10 mm. All lesions were evaluated for each slice thickness by 3 independent radiologists using a 5-point scale (excellent to poor) for the following 7 criteria: contrast, demarcation and contour of the lesion, image noise and quality, demarcation of liver veins and liver contour. The mean values of the reviewers' scores were calculated. The correlation of the three observers in the evaluation of the criteria was determined using the Kendall's Tau coefficient. RESULTS: The 3-mm thin sections were excellent in the evaluation of lesion detection, lesion contrast and lesion contour with a mean score of 1.4 compared to 4.1 for 10-mm sections. Concerning the criteria image quality and liver contour, thin sections achieved the best results in our series. Image noise was pronounced in thin sections but did not affect negatively the image analysis. Interrater agreement was 0.53 for the criterium image noise. CONCLUSION: Thin sections in MSCT examinations of low contrast objects such as liver lesions do not require an increase in radiation dose because the increase in image noise is compensated by improved lesion contrast.

Contrast Media↗
PubMed2004

Evaluation of balanced steady-state free precession (TrueFISP) and K-space segmented gradient echo sequences for 3D coronary MR angiography with navigator gating at 3 Tesla.

PURPOSE: To test the feasibility of k-space segmented gradient-echo pulse sequences for free-breathing coronary magnetic resonance angiography (cMRA) on a clinical 3T system. MATERIALS AND METHODS: T2-prepared, fat-suppressed turbo field echo (TFE, turboFLASH, SFPGR) as well as balanced TFE (b-TFE, trueFISP, FIESTA, segmented SSFP) sequences with navigator gating for prospective motion correction were applied on a 3T system equipped with a six-element phased-array cardiac coil. In 15 healthy volunteers, the right coronary artery (RCA) was examined with TFE and b-TFE sequences. Due to examination time limitations, the left coronary artery (LM/LAD) was examined exclusively with the TFE sequence in ten volunteers. Image quality was graded on a five point scale (0 = not visualized to 4 = excellent). The length, diameter and sharpness of the vessels and the contrast-to-noise ratios (CNR) were measured. RESULTS: 98 % of all major segments (proximal/middle/distal) of the RCA could be seen with the TFE sequence and 82 % with the b-TFE sequence. The image quality for the three segments was graded higher for the TFE sequence (2.7/2.7/1.5) than for the b-TFE sequence (1.9/1.6/0.9) with P: (< or = 0.001/< or = 0.004/< or = 0.056). The kappa of the interobserver variability was 0.75 for the TFE sequence and 0.8 for the b-TFE sequence. The measured vessel lengths were longer for the TFE sequence (95 +/- 22 mm) than for the b-TFE sequence (80 +/- 40 mm; P < or = 0.115). No significant changes (P < or = 0.074, P < or = 0.145) in diameter and vessel sharpness of the RCAs were observed between the TFE (2.4 +/- 0.3 mm, 60 % +/- 5) and b-TFE sequences (2.4 +/- 0.3 mm, 62 % +/- 6). The CNR was higher for the TFE sequence (10.1 +/- 3.4) than for the b-TFE sequence (6.6 +/- 2.1; P < or = 0.014). All ten main and proximal segments of the LM/LAD, which were examined exclusively with the TFE sequence, were visible with grade 2.5 and 2.1. The middle segment was visible in seven cases with grade 1.3. In three cases, the distal segment was visible with grade 0.5. The vessel length was 78 +/- 27 mm and the CNR 11.9 +/- 2.4. CONCLUSION: The conventional TFE technique has demonstrated good feasibility for cMRA at 3T. In its operational availability at 3T, the b-TFE sequence is inferior to the TFE sequence.

Adult↗
PubMed2004

[Multislice CT of the pelvis: dose reduction with regard to image quality].

PURPOSE: To optimize the examination protocols of multislice CT (MSCT) of the pelvis for dose reduction with regard to image quality. MATERIALS AND METHODS: MSCT of the pelvis was performed on 5 cadaver specimens with stepwise reduction of the tube current at 140 kV (250, 200, 150, 100, 75, 50, 35, 25 mAs) and 120 kV (50, 27 mAs). The remaining scan parameters like collimation (4 x 1 mm) and table speed of 4 mm per rotation remained unchanged. Axial sections and coronal reconstructions were used to evaluate cortex, trabecular structures, subjective image quality, image noise and detail detectability (pelvis and SI joint), with evaluation performed independently by four blinded experienced radiologists on a 5-point scale. Kappa coefficient, accuracy of the observers to sort the films with regard to dose reduction and mean scores of image evaluation were determined for statistical analysis. RESULTS: The deterioration of the image quality was most pronounced for all criteria between 75 mAs and 50 mAs at 140 kV. Good results with adequate image quality were obtained for detail detectability at 50 mAs and 140 kV (effective dose [E]: 3.3 mSv) and for the remaining four criteria at 75 mAs (E: 4.9 mSv). There was a moderate agreement between the four observers (kappa coefficient: 0.27). All observers were excellent in arranging the images according to the increasing dose reduction. CONCLUSIONS: Image quality of MSCT of the pelvis appears to be acceptable at 75 mAs and 140 kV with the dose reduced to 46% of the average value of the nation-wide survey of the German Roentgen Society in 1999 for this type of examination.

Acetabulum↗
PubMed2004

[Clinical relevance of computed tomography under emergency conditions--diagnostic accuracy, therapeutic consequences].

PURPOSE: To evaluate the diagnostic accuracy and therapeutic consequences of computed tomography performed on an emergency basis in a primary care hospital. MATERIAL AND METHODS: In 418 patients, 463 computed tomographies (thorax, abdomen, pelvis, spine, aorta, neck and extremities) were performed with-in 12 months, providing 999 diagnoses. The computed tomography diagnoses were retrospectively evaluated and correlated to surgery and discharge diagnoses. Therapeutical consequences were analyzed and allocated to a time period < 36 h (urgent) and > or = 36 - 72 h (elective). Average age was 49 (1 - 94) years (41% female and 59% male). Discharge diagnosis was defined as gold standard, provided that it was supported by clinical, blood chemical, diagnostic and possible surgical data. RESULTS: In 176 of 999 diagnoses (18%), the diagnoses were classified as "non-correlatable". Of the 823 correlated diagnoses, 431 were true positive, 14 false positive, 66 false negative and 312 true negative. Sensitivity, specificity and diagnostic accuracy of computed tomography was 87, 96 and 90%. Computed tomography had therapeutic consequences (surgery, drainage, puncture, reposition, thrombolytic therapy, chemotherapy, bronchoscopy, endoscopy, percutaneous transluminal angioplasty, coiling etc.) in 57% and no direct therapeutic interventions in 43%. Computed tomography excluded the suspected diagnosis in 36% and resulted in a conservative therapeutic regiment in 7%. Surgery was performed on 134 of the 418 patients (32%) who underwent computed tomography, with the surgery urgent in 71 (17%) and elective in 63 (15%) of the 418 patients. CONCLUSION: The high diagnostic accuracy and consecutive therapeutic consequences of computed tomography in establishing a precise, timely and reproducible diagnosis confirm its important role as primary diagnostic method on an emergency basis.

Adolescent↗
PubMed2004

Electrophysiological evidence for delayed mismatch response in infants at-risk for specific language impairment.

The present study investigated whether delayed auditory processing typically found in children with specific language impairment (SLI) can already be observed in the event-related potentials of 2-month-old infants. Infants with and without a family history of SLI were tested in a passive auditory oddball paradigm with CV-syllables differing in vowel duration. For the long syllable, a positive mismatch response occurred in the difference wave between deviant and standard. Its amplitude was higher in infants during quiet sleep than in awake infants, although its peak latency remained unaffected by alertness. Awake infants showed an adultlike mismatch negativity preceding the positivity. Risk for SLI was reflected in the latency of the positive mismatch response, which was delayed in infants with risk compared to infants without risk. This latency difference suggests that 2-month-old infants at risk for SLI are already affected in processing an auditory stimulus change of duration.

Acoustic Stimulation↗
PubMed2004

A multicentre randomised controlled trial of an intervention to improve the accuracy of linear growth measurement.

AIMS: To evaluate linear growth assessment and the effect of an intervention on measurement accuracy in primary care practices (PCP) within eight US geographical areas. METHODS: In this multicentre randomised controlled intervention study, paediatric endocrine nurses as site coordinators (SC) visited 55 randomly assigned PCP to evaluate growth assessment of staff performing linear measurements. SC observed 127 measurers assessing a total of 878 children: 307 (baseline), 282 (3 months), and 289 (6 months). Accuracy was determined by SC re-measuring each child with correct technique and equipment. State of the art equipment and a standardised growth training session were provided to the intervention group (IG) following the baseline visit. SC repeated data collection at all PCP at 3 and 6 months. RESULTS: There were no baseline differences between IG and CG equipment, technique, or accuracy; only 30% of measurements were accurate (< or =0.5 cm from SC). Post-intervention, significantly more IG measurements were accurate: IG = 55%, CG = 37% at 3 months; IG = 70%, CG = 34% at 6 months. Odds ratio of accuracy for IG versus CG was 2.1 at 3 months and 4.5 at 6 months. At 6 months, mean difference from the SC measurements was 0.5 cm in IG and 1.1 cm in CG. CONCLUSIONS: In PCP, children are measured inaccurately. Our intervention significantly improved measurement accuracy. Improved accuracy could yield more rapid detection and diagnosis of paediatric growth disorders.

Adolescent↗
PubMed2003

Phonon-assisted damping of Rabi oscillations in semiconductor quantum dots.

Electron-phonon interaction is a major source of optical dephasing in semiconductor quantum dots. Within a density matrix theory the electron-phonon interaction is considered up to the second order of a correlation expansion, allowing the calculation of the quantum kinetic dephasing dynamics of optically induced nonlinearities in GaAs quantum dots for arbitrary pulse strengths and shapes. We find Rabi oscillations renormalized and a damping that depends on the input pulse strength, a behavior not known from exponential dephasing mechanisms.

Journal Article↗
PubMed2003

The interleukin-6 promoter polymorphism is associated with elevated leukocyte, lymphocyte, and monocyte counts and reduced physical fitness in young healthy smokers.

Smoking and interleukin-6 are important factors in driving inflammation. This study assessed the relationship between smoking, interleukin-6 genotype, physical fitness, and peripheral blood count in healthy young men. For this interleukin-6 promoter polymorphism -174 genotype-phenotype association study 1,929 healthy German male aviators recruited at the central German Air Force Institute of Aviation Medicine were stratified by smoking habits. Cardiovascular fitness was expressed as maximal physical working capacity (PWCmax) in watts per kilogram body weight as assessed by maximal exercise testing by cycle ergometry up to physical exhaustion. Smokers had higher leukocyte and lymphocyte counts than nonsmokers and lower PWCmax. In the overall study population the C allele of the interleukin-6 polymorphism was weakly associated with elevated leukocytes and lymphocytes; in nonsmokers the interleukin-6 polymorphism was not associated with altered phenotypes, but in smokers the interleukin-6 C allele was associated with higher leukocytes, lymphocytes, and monocytes and with lower PWCmax. Smoking is thus associated with elevated leukocytes and lymphocytes and with reduced physical fitness. Gene carriers with the interleukin-6 C allele may suffer particularly from cigarette smoking.

Adult↗
PubMed2003

Risk-adapted postremission therapy in acute myeloid leukemia: results of the German multicenter AML HD93 treatment trial.

The objective of the AML HD93 treatment trial was to evaluate the outcome in young adults with acute myeloid leukemia (AML) after postremission therapy was stratified according to cytogenetically defined risk. The rationales for the study design were based (i) on previous favorable results with high-dose cytarabine in AML with t(8;21), inv/t(16q22) and in AML with normal karyotype, and ii) on encouraging results obtained in several phase II trials using autologous stem cell transplantation (SCT). Between July 1993 and January 1998, 223 eligible patients, 16-60 years of age with newly diagnosed AML other than French-American-British type M3/M3v, were entered into the trial. Risk groups were defined as follows: low risk: t(8;21) or inv/t(16q22); intermediate risk: normal karyotype; high risk: all other chromosomal abnormalities. Following intensive double induction therapy with idarubicin, cytarabine and etoposide, all patients in complete remission (CR) received a first consolidation therapy with high-dose cytarabine and mitoxantrone (HAM). A second consolidation therapy was stratified according to the risk group: low risk: HAM; intermediate risk: related allogeneic SCT or sequential HAM; high risk: related allogeneic or autologous SCT. Double induction therapy resulted in a high CR rate of 74.5%, and 90% of the responding patients were eligible for consolidation therapy. Survival for all 223 trial entrants was 40%, and for the 166 patients who entered CR, disease-free (DFS) and overall survival were 40 and 51% after 5 years, respectively. Within the low-, intermediate- and high-risk groups, DFS and survival after 5 years were 62.5 and 87, 40 and 49 and 17 and 26% respectively, without advantage for allogeneic transplantation in the intermediate- and high-risk groups. Postremission therapy-related mortality was 0, 7 and 14%, respectively. This study demonstrates the feasibility of cytogenetically defined risk-adapted consolidation therapy. The overall trial results are at least equivalent to those of published trials supporting the risk-adapted treatment strategy.

Acute Disease↗
PubMed2003

[MRCP in primary sclerosing cholangitis].

PURPOSE: Evaluation of MR-cholangiopancreaticography (MRCP) for the diagnosis of primary sclerosing cholangitis (PSC) in correlation with endoscopic retrograde cholangiopancreaticography (ERCP) and in comparison to the diagnostic accuracy of various T2-weighted sequences. METHODS AND MATERIALS: Fifty-five patients (34 males, 21 females; mean age 40 years, range 16 to 65 years) with suspected PSC were examined in a 1.5 T MR unit (Magnetom Vision, Siemens, Erlangen), using breath-hold transverse and coronal HASTE, paracoronal RARE and thin-sliced HASTE (TS-HASTE) sequences. Applying a five-point-scale, two blinded investigators assessed the image quality for ROC analysis. Morphologic criteria of PSC were documented and correlated with ERCP, which served as the gold standard, and sensitivity, specificity and diagnostic accuracy were calculated. RESULTS: PSC was confirmed in 40 of 55 patients (ERCP 55 of 55, liver biopsy 37 of 55), with concomitant chronic ulcerative colitis in 27 and Crohn's disease in 6 of the 40 patients. Qualitative analysis of the image quality showed no significant difference between RARE, HASTE and thin-sliced HASTE sequences (3.4/3.5/3.2). The RARE sequence had the highest sensitivity (97 %), specificity (64 %) and accuracy (84 %) for the detection of PSC. The difference between HASTE and thin-sliced HASTE was statistically significant (p < 0.01). Of the 40 patients with confirmed PSC, 29 were followed by MRI and 3 underwent a liver transplantation within the follow-up period. A Klatskin tumor, which was misdiagnosed by MRCP, was diagnosed by brush biopsy in 1 of the 40 patients. Interobserver variability was adequate to good (kappa 0.4 to 0.7), depending on the chosen sequence. CONCLUSION: MRCP seems to be a reliable non-invasive imaging method to diagnose and follow PSC. The RARE sequence showed the highest diagnostic accuracy of the T2-weighted sequences.

Adolescent↗
PubMed2003

[Clinical relevance of cranial CT under emergency conditions--basic neuroradiologic investigations].

PURPOSE: To determine the diagnostic accuracy of cranial CT under emergency conditions. MATERIAL AND METHODS: Four hundred cranial CT examinations (cerebrum, petrosal bone, fascial bone, sinuses, orbita) were evaluated retrospectively and correlated with the initial neurologic examination, the discharge and surgical diagnoses, and the results of other imaging modalities (conventional X-Ray, MRI, angiography). The average age was 49 (2 to 89) years, with 42 % male and 58 % female patients. The discharge diagnosis was defined as the gold standard, assuming that clinical examinations and laboratory and imaging studies were maximized to establish the diagnosis, together with any possible surgery. RESULTS: Overall sensitivity, specificity and diagnostic accuracy was 85 %, 70 % and 82 % for cranial CT, 66 %, 45 % and 61 % for the initial neurologic examination, 79 % and 29 % for acute cerebral infarction, and 65% and 13% for intracranial bleeding. Correlation of the CT diagnoses to the discharge and surgical diagnoses was high (82 % and 80 %, respectively; p < 0.01), to the diagnosis of conventional x-ray moderate and to the diagnoses of angiography and MRI unsatisfactory (74 % and 68 % and 60 %, respectively; p > 0.05). Craniotomy was performed in 47 of 400 (12%) patients after cranial CT, within 12 hours in 29, in 12 to 24 hours in 8, and after 24 hours in 10 patients. The risk for intracranial bleeding in patients with a skull fracture was increased by a factor of 3.3. CONCLUSION: The high diagnostic accuracy of cranial CT in establishing a precise, timely and reproducible diagnosis confirms the important role of CT as primary diagnostic method under emergency conditions.

Adolescent↗
PubMed2003

[Respiratory diseases in European farmers-II. Part of the European farmers' project].

BACKGROUND: The aim of the European Farmers' Project was to estimate the prevalence of respiratory diseases in farmers across Europe. Furthermore, risk factors for respiratory symptoms in different parts of agricultural production should be assessed. METHODS: In the first part of the study, 7496 farmers from four European countries answered a written questionaire. Of these, 229 were visited at their farms in the second part of the survey. On site, spirometry, allergy tests, as well exposure measurements were performed. RESULTS: Farmers with animal production had a significantly lower prevalence of allergic diseases than the general population. In contrast, the prevalence of chronic phlegm was higher in animal farmers. Organic dust toxic syndrome (ODTS) was a major predictor of chronic bronchitis. It was indicated that allergens found in the working environment could be transfered to the living environment of the farmer. Poor ventilation as well as high temperatures inside the animal buildings were shown to have a negative impact on respiratory symptoms and lung function parameters. CONCLUSION: Animal farmers are at high risk of chronic bronchitis. Intervention studies on the efficacy of different types of ventilation are now warranted. Furthermore, prospective studies on the associaton between ODTS and COPD should be done.

Adult↗
PubMed2002

Vitamin E analogs: a new class of multiple action agents with anti-neoplastic and anti-atherogenic activity.

The incidence of cancer and atherosclerosis, two most common causes of death in developed countries, has been stagnating or, even, increasing. Drugs effective against such conditions are needed and, in this regard, the potential anti-atherosclerotic activity of vitamin E analogs has been studied extensively. Surprisingly, recent results indicate that these agents may also exert anti-neoplastic effects. Here we review the evidence that particular analogs of vitamin E may act as both antiatherogenic and anti-cancer agents, and discuss the possible molecular bases for these actions.

Animals↗
PubMed2002

[The role of MRI for the evaluation of atrial septal defects before and after percutaneous occlusion with the amplatzer septal occluder(R)].

PURPOSE: Evaluation of morphologic and functional MRI of atrial septal defects (ASD) before and after percutaneous occlusion with the Amplatzer Septal Occluder (AOC). Comparison of MRI with transesophageal echocardiography (TEE), balloon measurement (IVBM) and cardiac catheterization with shunt quantification (CCSQ). MATERIALS AND METHODS: Twenty patients with ASD were examined before and three months after AOC implantation. ECG-triggered, breath-hold T1-weighted Turbo Spin Echo Segmented FLASH 2D and dynamic turbo-FLASH-GRE sequences after application of 0.2 mmol gadolinium DTPA per kg body weight were obtained in a 1.5 T MRI system. Defect size, and distance to coronal sinus (CS) and right upper pulmonary vein (RUPV) were determined for pre-interventional planning, and the AOC size was measured quantitatively for post-interventional follow-up. The shunts were evaluated qualitatively (occurrence of jets), semiquantitatively (jet length, turbulence square product) and quantitatively (flow measurement in the thoracic aorta and in the left and right pulmonary arteries). RESULTS: The average size of the ASD measured by MRI was 17.6 mm (11 - 24.8 mm) in the axial view, 15.9 mm (10.8 - 28.9 mm) in the sagittal view and 16.4 mm (12.1 - 24.8 mm) in the short axis view. In comparison, the average defect size was 15 mm (8 - 24 mm) by TEE and 20 mm (13 - 27 mm) by IVBM. The average distance to the RUPV was 17 mm (9.6 - 21.9 mm) and to the CS 11.2 mm (5 - 17 mm). The AOC was visualized with only minimal artifacts. Qualitative analysis of the MRI findings revealed an occurrence of jets in 17/20 patients. Semiquantitative analysis documented a high correlation for jet length and square product of the turbulence to defect size r = 0.81 resp. r = 0.82. Mean QP/QS-ratio measured by MR-volumetry was 1.6 +/- 0.29 and by MR-flow 1.6 +/- 0.26. The corresponding measurements were 1.7 +/- 0.3 for TEE and 1.5 +/- 0.5 for CCSQ. In comparison to TEE, the correlation coefficient was r = 0.96 for MR-volumetry and r = 0.85 for MR-flow measurement. CONCLUSION: MRI is found to be a valuable diagnostic method for pre-interventional planning and post-interventional follow-up of atrial septal defects occluded by the Amplatzer septal occluder.

Adult↗
PubMed2001

Cytohesin-1 is a dynamic regulator of distinct LFA-1 functions in leukocyte arrest and transmigration triggered by chemokines.

Cytohesin-1 is a regulatory interaction partner of the beta2 integrin alphaLbeta2 (LFA-1) and a guanine exchange factor (GEF) for ADP ribosylation factor (ARF)-GTPases. However, a functional role of cytohesin-1 in leukocyte adhesion to activated endothelium and subsequent transmigration in response to chemokines has not been defined. Overexpression of cytohesin-1 increased LFA-1-dependent arrest of leukocytic cells triggered by chemokines on cytokine-activated endothelium in flow while reducing the fraction of rolling cells. Conversely, a dominant-negative PH domain construct of cytohesin-1 but not a mutant deficient in GEF activity impaired arrest, indicating an involvement of the PH domain while GEF function is not required. Expression of these constructs and a beta2 mutant interrupting the interaction with cytohesin-1 indicated that shape change in flow and transendothelial chemotaxis involve both LFA-1 avidity regulation and GEF activity of cytohesin-1. As a potential downstream target, ARF6 but not ARF1 was identified to participate in chemotaxis. Our data suggest that cytohesin-1 and ARF6 are involved in the dynamic regulation of complex signaling pathways and cytoskeletal remodeling processes governing LFA-1 functions in leukocyte recruitment. Differential effects of cytohesin-1 and ARF6 mutants in our systems reveal that cytohesin-1 with its GEF activity controls both conversion of rolling into firm arrest and transmigration triggered by chemokines, whereas a cyclical activity of ARF6 plays a more important role in diapedesis.

Cell Adhesion Molecules↗