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1.
Forensic Sci Int Genet ; 71: 103053, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38728819

ABSTRACT

The Forensic Databases Advisory Board (FDAB), an independent board that assists the International Society for Forensic Genetics (ISFG), has presented a First Report on ethical aspects of the following Forensic Genetic Frequency Databases (FGFD): EMPOP, STRidER and YHRD. The FDAB designed an ethical framework to evaluate the content of these FGFD, and the factors to be considered for retention and acceptance of submissions. The FDAB framework proposes to categorize submissions according to the risk of having contravened the universal ethical principles outlined by international organizations, and the guidelines adopted by the ISFG. The report has been open to discussion by the scientific community since 2023. Herein we present the conception and development of the First Report along with a summary of its content, with consideration of the feedback received.


Subject(s)
Forensic Genetics , Humans , Forensic Genetics/ethics , Gene Frequency , Databases, Genetic , Databases, Nucleic Acid/ethics , DNA Fingerprinting/ethics
2.
Rev Neurol (Paris) ; 179(3): 218-222, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36473747

ABSTRACT

Facial nerve paralysis or Bell's palsy have been suggested as possible consequences of SARS-CoV-2 infections, as well as possible side effects of COVID-19 vaccinations. Google Trends data have been used to evaluate worldwide levels of public awareness for these topics for pre- and post-pandemic years. The results demonstrate a relatively low public interest in facial nerve paralysis in comparison to other more common COVID-19 related topics. Some peaks of interest in Bell's palsy can most likely be explained as triggered by the media. Therefore, Google Trends has shown public's relatively low awareness of this rare neurological phenomenon during the pandemic.


Subject(s)
Bell Palsy , COVID-19 , Facial Paralysis , Humans , COVID-19 Vaccines , Facial Nerve , Search Engine , SARS-CoV-2
3.
Hautarzt ; 71(2): 101-108, 2020 Feb.
Article in German | MEDLINE | ID: mdl-31965207

ABSTRACT

BACKGROUND: Since the establishment of dermoscopy as a routine examination procedure in dermatology, the spectrum of noninvasive, optical devices has further expanded. In difficult-to-diagnose clinical cases, these systems may support dermatologists to arrive at a correct diagnosis without the need for a surgical biopsy. OBJECTIVE: To give an overview about technical background, indications and diagnostic performance regarding four new optical procedures: reflectance confocal microscopy, in vivo multiphoton tomography, dermatofluoroscopy, and systems based on image analysis by artificial intelligence (AI). MATERIALS AND METHODS: This article is based on a selective review of the literature, as well as the authors' personal experience from clinical studies relevant for market approval of the devices. RESULTS: In contrast to standard histopathological slides with vertical cross sections, reflectance confocal microscopy and in vivo multiphoton tomography allow for "optical biopsies" with horizontal cross sections. Dermatofluoroscopy and AI-based image analyzers provide a numerical score, which helps to correctly classify a skin lesion. The presented new optical procedures may be applied for the diagnosis of skin cancer as well as inflammatory skin diseases. CONCLUSION: The presented optical procedures provide valuable additional information that supports dermatologists in making the correct diagnosis. However, a surgical biopsy followed by dermatohistopathological examination remains the diagnostic gold standard in dermatology.


Subject(s)
Dermatology , Skin Diseases , Skin Neoplasms , Dermoscopy , Humans , Microscopy, Confocal , Skin , Skin Diseases/diagnosis , Skin Neoplasms/diagnosis
4.
Skin Res Technol ; 25(1): 68-78, 2019 Jan.
Article in English | MEDLINE | ID: mdl-29923636

ABSTRACT

BACKGROUND: Diagnostics of healing, infection, and inflammation in chronic wounds in comparison with physiological wound healing in acute wounds may help for therapy decisions toward individualized therapy management. With emerging new optical techniques the coupling of optical diagnostic devices with tissue provides a great challenge. Traditional coupling with cover slips is used since the early days of microscopy. In modern health care, hygienic covering of surfaces is necessary to avoid infections and cross-contaminations. METHODS: Measurements in chronic wounds were performed at three different areas including the center of the wound, the border of the wound and healthy skin as comparison area. For each measurement area, three vertical stacks were taken by MPT. Additionally, three different optical measuring procedures (MPT, OCT, CLSM) were used for the examination of BNC foil. Examinations of BNC foil were carried out at two different areas of healthy skin compared to a standard setup as control. RESULTS: The MPT evaluation revealed a distinct difference in the second harmonic generation-to-autofluorescence aging index of dermis (SAAID) behavior between the vertical stacks taken at central wound areas and wound margins as well as unaffected skin. Through BNC foil covers, MPT CLSM and OCT images were captured with good quantitative and qualitative results. CONCLUSIONS: Phases in chronic wounds could be matched with physiologically healing in acute wounds according to SAAID and MPT imaging. BNC provided an alternative covering for MPT, OCT, and CLSM with clear morphological images.


Subject(s)
Bacteria/metabolism , Cellulose/pharmacology , Skin/injuries , Wound Healing/drug effects , Bandages , Humans , Microscopy, Fluorescence, Multiphoton , Nanostructures/chemistry , Skin/drug effects , Tomography, Optical Coherence/methods
5.
Skin Res Technol ; 24(3): 445-449, 2018 Aug.
Article in English | MEDLINE | ID: mdl-29405439

ABSTRACT

BACKGROUND: Mucous membranes may be affected by various diseases and the diagnostic accessibility is limited. Multiphoton laser tomography (MPT) is a useful tool for in vivo evaluation of superficial skin structures and might also be useful for the imaging of mucosa. OBJECTIVES: In order to investigate the suitability of MPT for the evaluation of mucous membranes, tissue samples of different donors and anatomical localizations have been imaged. METHODS: Human mucosa samples from the urinary bladder, palatine tonsil and ocular conjunctiva were investigated by MPT and subsequently compared with conventional histology. RESULTS: Horizontal images of the epithelium and the underlying connective tissue were obtained using the autofluorescence and second harmonics generation signals by MPT. The stratification of multilayered epithelium was consistently reproduced. Also inflammatory changes like lymphocytic infiltrates and widened intercellular spaces were imaged in some cases. CONCLUSION: Mucous tissue samples were obtained and MPT imaging was successfully performed. In the direct comparison with histology of the same tissue samples, the characteristic morphology of the epithelia was found. Further studies are necessary in order to compare images of healthy and diseased mucosal epithelium and the use of MPT for its evaluation in vivo.


Subject(s)
Conjunctiva/anatomy & histology , Mucous Membrane/anatomy & histology , Palatine Tonsil/anatomy & histology , Urinary Bladder/anatomy & histology , Humans , Lasers , Mucous Membrane/pathology , Palatine Tonsil/pathology , Tomography
6.
Skin Res Technol ; 23(4): 452-458, 2017 Nov.
Article in English | MEDLINE | ID: mdl-28271554

ABSTRACT

BACKGROUND: The multiphoton tomography (MPT) has evolved into a useful tool for the non-invasive investigation of morphological and biophysical characteristics of human skin in vivo. Until now, changes of the skin have been evaluated mainly by using clinical and histological techniques. In this study, the progress of wound healing was investigated by MPT over 3 weeks with a final examination after 24 months. Especially, the collagen degradation, reepithelization and tissue formation were examined. As specific parameter for wound healing and its course the second-harmonic generation-to-autofluorescence aging index of dermis (SAAID) was used. METHODS: About 10 volunteers aged between 25 and 58 years were examined. Acute wounds were scanned with three Z-stacks taken per visit. The stacks were taken up to a depth of 225 µm at increments of 5 µm and a scan time for 3 seconds per scan. Subsequently, the SAAID was evaluated as an indicator for wound healing. Furthermore, single scans were taken for morphological investigations. RESULTS: The evaluation revealed a distinct difference in the SAAID behavior between the Z-stacks taken at each visit. Furthermore, the degradation of collagen and cells and their reappearance could be shown in the course of the visits. CONCLUSIONS: Clear differences in the curve behavior of the SAAID at every visit were shown in this study. The SAAID curves and morphological images could be correlated with findings of the clinical examination of different wound healing phases. Therefore, SAAID curves and morphological MPT imaging could provide a non-invasive tool for the determination of wound healing phases in patients in vivo.


Subject(s)
Wound Healing/physiology , Adult , Collagen/physiology , Curettage , Epidermis/diagnostic imaging , Humans , Microscopy, Fluorescence, Multiphoton/methods , Middle Aged , Postoperative Care , Tomography/methods
7.
Hautarzt ; 67(2): 117-24, 2016 Feb.
Article in German | MEDLINE | ID: mdl-26746403

ABSTRACT

Aging affects human skin and is becoming increasingly important with regard to medical, social and aesthetic issues. Detection of intrinsic and extrinsic components of skin aging requires reliable measurement methods. Modern techniques, e.g., based on direct imaging, spectroscopy or skin physiological measurements, provide a broad spectrum of parameters for different applications.


Subject(s)
Dermoscopy/methods , Materials Testing/methods , Skin Aging/pathology , Skin Aging/physiology , Skin/pathology , Tomography, Optical Coherence/methods , Biomarkers/metabolism , Humans , Mass Spectrometry/methods , Microscopy, Confocal/methods , Microscopy, Fluorescence, Multiphoton/methods , Water Loss, Insensible/physiology
8.
Skin Res Technol ; 22(3): 356-62, 2016 Aug.
Article in English | MEDLINE | ID: mdl-26456590

ABSTRACT

BACKGROUND: The in vivo multiphoton tomography has evolved into a useful tool for the non-invasive investigation of morphological and biophysical characteristics of human skin. Until now, changes of skin have been evaluated mainly by clinical and histological techniques. The current study addresses the effects of a changed acquisition time for single scans in a Z-stack on the directly related qualitative and quantitative interpretability of the data. METHODS: A test area of the skin was used for scanning 12 Z-stacks of 10 volunteers aged between 25 and 34 years. The stacks were taken up to a depth of 220 µm at increments of 10 µm at four different times, 1, 3, 7, 13 s, per scan. Subsequently, the second harmonic generation (SHG)-to-autofluorescence aging index of dermis (SAAID) was evaluated at three different measuring depths, i.e. at the maximum of SHG as well as at depths of 60 and 150 µm. RESULTS: The evaluation did not reveal any significant differences in the SAAID behavior between the Z-stacks of each test area scanned at different acquisition times. However, the acquisition time of 1 s/frame increases the measurement stability without influencing the SAAID behavior. The resolution of subcellular structures decreases significantly at scan times ≤3 s, whereas the acquisition time from 7 to 13 s warrants a high image quality. CONCLUSION: The study has shown that there are no significant differences between the scan speeds per scan in a Z-stack and the resulting SAAID. Acquisition times of 7 s are suitable for the morphological evaluation whereas a further extension to 13 s does not result in any benefits. A scan time per image of 1 s is sufficient for the quantitative evaluation of SAAID thus substantially reducing the possible influence of movement artifacts.


Subject(s)
Algorithms , Image Enhancement/methods , Intravital Microscopy/methods , Microscopy, Fluorescence, Multiphoton/methods , Skin/cytology , Tomography, Optical/methods , Adult , Female , Humans , Male , Reproducibility of Results , Sensitivity and Specificity
9.
Hautarzt ; 66(7): 511-21, 2015 Jul.
Article in German | MEDLINE | ID: mdl-25943693

ABSTRACT

In recent years, multiphoton tomography (MPT) and multiphoton microscopy have gained increasing importance as noninvasive examination techniques in dermatology. MPT imaging is based on the specific stimulation of biogenic fluorophores. The induction of second harmonic generation is also used for imaging of particular molecules. Additional fluorescence staining or fluorescence markers are not necessary-an important advantage for the in vivo examination of human skin. Multiphoton techniques are not only appropriate for clinical diagnostics but also for biomedical research. MPT provides an optical biopsy depth up to 200 µm with subcellular resolution depicting cellular and extracellular structures. In combination with fluorescence lifetime imaging, additional information about the microenvironment, the energetic state and the cellular metabolism can be obtained. This review presents recent developments of MPT for the in vivo evaluation of physiological and pathological changes of skin and diagnostics of dermal diseases.


Subject(s)
Microscopy, Fluorescence, Multiphoton/methods , Molecular Imaging/methods , Skin Diseases/metabolism , Skin Diseases/pathology , Skin/metabolism , Skin/pathology , Biomarkers/metabolism , Dermoscopy/methods , Humans , Image Enhancement/methods , Image Interpretation, Computer-Assisted/methods
10.
J Neurol Surg A Cent Eur Neurosurg ; 73(1): 29-37, 2012 Jan.
Article in English | MEDLINE | ID: mdl-21975606

ABSTRACT

BACKGROUND: Recent studies examined the role of psychiatric comorbidity in the process of rehabilitation in patients undergoing herniated disc surgery. These patients suffer from physical and psychosocial complaints or symptoms, which impact their everyday life negatively and the success of rehabilitation potentially. The objectives of this study are (1) to examine the quality of life (QoL) in disc surgery patients and to compare the findings with reference data from the general German population, and (2) to investigate the impact of psychiatric comorbidity on QoL of patients undergoing herniated disc surgery. METHODS: This study consists of 305 patients aged between 18 and 55 years who took part in face-to-face interviews during their hospital stay. Psychiatric comorbidity was assessed with the Composite International Diagnostic Interview (CIDI-DIA-X). By means of the 36-Item Short-Form Health Survey (SF-36), QoL was assessed in patients undergoing herniated disc surgery with and without psychiatric comorbidity. These findings were compared with the QoL of a representative sample of the general German population. RESULTS: Compared with the general population, QoL in patients with herniated disc surgery was lower in all domains of the SF-36. Psychiatric comorbidity impacts the QoL in patients with herniated disc surgery in all SF-36 domains except "physical function". The patients with psychiatric comorbidity showed significantly lower levels of QoL in the domains "bodily pain", "vitality", "social function", "role emotional", and "mental health". CONCLUSIONS: Psychiatric comorbidity has a substantial adverse effect on QoL in patients undergoing disc surgery. Therefore, it will be necessary to diagnose psychiatric comorbidities at an early stage and to include psychosocial interventions in the treatment of herniated disc patients aimed at improving deficits in psychosocial functioning and QoL.


Subject(s)
Intervertebral Disc Displacement/surgery , Mental Disorders/complications , Orthopedic Procedures/psychology , Quality of Life/psychology , Adolescent , Adult , Female , Humans , Intervertebral Disc Displacement/complications , Intervertebral Disc Displacement/psychology , Male , Mental Disorders/psychology , Middle Aged , Orthopedic Procedures/rehabilitation , Surveys and Questionnaires , Treatment Outcome , Young Adult
11.
Cent Eur Neurosurg ; 71(1): 26-34, 2010 Feb.
Article in English | MEDLINE | ID: mdl-20094980

ABSTRACT

BACKGROUND: An association between depression and anxiety and musculoskeletal disorders has been consistently reported in the past years. This article provides a systematic overview of the literature on the prevalence rates of depression and anxiety in patients undergoing surgery for a herniated disc. METHODS: A systematic literature search was conducted in the following electronic databases: PubMed, PsycINFO, Web of Science, Cochrane Library and PSYNDEXplus. The identified articles were evaluated for prevalence rates of depression and anxiety, methodological issues, change of depression and anxiety over time, and major findings on the impact of depression and anxiety on patients undergoing disc surgery. RESULTS: Fourteen studies were identified. Prevalence rates for depression and anxiety in patients undergoing disc surgery varied between 21.5% and 49.3% before and between 4.1% and 79.6% after disc surgery. The study designs, the use of assessment instruments and cut-off values varied greatly. Depression and anxiety decreased within the population of disc surgery patients over time. Depression and anxiety were found to have a great impact on the postoperative outcome of surgery, return to work, analgesia abuse, pain experience, and abnormal illness behaviour. CONCLUSIONS: Little research has been done to investigate depression and anxiety in patients undergoing surgery for a herniated disc. Evidently disc surgery patients are at higher risk of suffering from depression and anxiety than the general population. The review outlines the importance for clinicians to be more sensitive to psychological concerns in patients undergoing disc surgery. Psychological assessment and assistance from mental health professionals should be considered during the hospital stay and rehabilitation period, depending on local feasibility. Further investigations are necessary to examine whether the implementation of a multidisciplinary in-patient treatment program will improve postoperative outcome in patients undergoing intervertebral disc surgery.


Subject(s)
Anxiety/psychology , Depression/psychology , Intervertebral Disc Displacement/psychology , Intervertebral Disc Displacement/surgery , Orthopedic Procedures/psychology , Perioperative Care/psychology , Anxiety/epidemiology , Anxiety/etiology , Databases, Factual , Depression/epidemiology , Depression/etiology , Follow-Up Studies , Humans , Postoperative Complications/psychology , Psychiatric Status Rating Scales , Psychometrics
12.
Z Orthop Unfall ; 147(6): 727-33, 2009.
Article in German | MEDLINE | ID: mdl-20183751

ABSTRACT

AIM: Determination of the femoral head position after closed or open reduction and application of a spica cast is possible by X-ray, MRI, CT or transinguinal ultrasound. In this study we compared the efficacy of transinguinal ultrasound and radiography. Further options with transinguinal ultrasound such as the determination of soft tissue and intraoperative possibilities are also described. MATERIAL AND METHODS: In a first cohort of 25 patients with 33 affected hips ultrasound and radiography were compared. In a second cohort of 8 patients with 11 affected hips ultrasound and arthrography were compared. RESULTS: 32 radiographs proved to be not useful for the precise determination of the femoral head position. In all ultrasound images the criteria described by van Douveren et al. could be identified. All ultrasound images in the study were useful and gave reliable information with regard to the femoral head position. CONCLUSION: Consequently, standard radiographic documentation is no longer used as a standard in our clinic. MRI and CT are reserved for special cases. We recommend transinguinal ultrasound as a standard diagnostic method for determination of the femoral head position in hip spica casts. With a portable ultasound system, determination of the hip position using transinguinal ultrasound is immediately possible in the operating theatre.


Subject(s)
Casts, Surgical , Femur Head/diagnostic imaging , Hip Dislocation, Congenital/diagnostic imaging , Hip Dislocation, Congenital/surgery , Inguinal Canal/diagnostic imaging , Splints , Arthrography , Decision Support Techniques , Female , Humans , Infant , Magnetic Resonance Imaging , Male , Postoperative Complications/diagnostic imaging , Sensitivity and Specificity , Tomography, X-Ray Computed , Ultrasonography
13.
Hamostaseologie ; 27(2): 105-10, 2007 May.
Article in German | MEDLINE | ID: mdl-17479173

ABSTRACT

The central enzyme of blood coagulation, the serine proteinase thrombin, is capable to modify the growth of tumour cells by interaction with protease activated receptors 1 and 4 of the tumour cells. Thrombin is permanently available in tumour micro environment; meizothrombin is generated from prothrombin at a tumour specific activation complex and can influence tumour cell growth via PAR-1 and 7-transdomain protein receptor signalling pathway, too. PEG-coupled direct thrombin inhibitors that possess special pharmacokinetic characteristics and that have been designed for long lasting efficacy in extracellular space, control serine proteinase activity in tumour micro environment and therefore they own a high potential anti-tumour efficacy. In xenographic tumour models this new substance class has shown a significant carcinostatic effect.


Subject(s)
Cell Division/drug effects , Neoplasms/pathology , Receptors, Thrombin/physiology , Thrombin/adverse effects , Amino Acid Sequence , Hirudins/pharmacology , Humans , Models, Molecular , Molecular Sequence Data , Protein Conformation , Receptor, PAR-1/physiology , Receptors, Thrombin/chemistry , Signal Transduction
14.
Transplant Proc ; 36(4): 1139-42, 2004 May.
Article in English | MEDLINE | ID: mdl-15194397

ABSTRACT

Although cryopreservation of pancreatic islets would add flexibility to transplantation, the recoveries are only 60% to 90% and function is decreased. Islets are multicellular structures approximately 50 to 250 microm in diameter organized into a network of cells and vascular channels. Due to this complexity, islets are more susceptible to damage during cryopreservation than an individual cell. This study investigated porcine small intestinal submucosa (SIS) as a matrix to support islets recovery and function post-thaw. Groups of frozen/thawed human islets (150 IE/condition; n = 4 preparations) were cultured for 5 weeks in plates containing noncoated Biopore membrane inserts alone or inserts covered with SIS. Islets were placed directly on the insert post-thaw (SIS(1)), or cultured overnight in standard plates, washed, and then transferred to the SIS (SIS(2)). Function was assessed by determining glucose-stimulated release of insulin, which was measured by radioimmunoassay. Analysis of basal insulin secretion showed time and treatment to be significantly different (P =.0043 and P =.0123, respectively) but without an interaction (P >.05). The two SIS treatments were not significantly different (P >.05); however, both SIS(1) and SIS(2) were significantly different from controls (P =.0108 and P =.0420, respectively). Similar results were obtained for stimulation indices; time and treatment were significantly different (P =.0161 and P =.0264, respectively) but not an interaction (P >.05). The two SIS treatments were not significantly different (P =.05); however, both SIS(1) and SIS(2) differed from controls (P =.0248 and P =.0407, respectively). The results indicate that SIS enables frozen-thawed islets to exhibit superior post-thaw function compared with a non-SIS-supported condition.


Subject(s)
Cryopreservation/methods , Islets of Langerhans/cytology , Animals , Cell Culture Techniques/methods , Cell Separation/methods , Cells, Cultured , Glucose/pharmacology , Humans , Insulin/metabolism , Insulin Secretion , Intestinal Mucosa/cytology , Islets of Langerhans/metabolism , Swine
15.
Transplant Proc ; 36(4): 1175-7, 2004 May.
Article in English | MEDLINE | ID: mdl-15194407

ABSTRACT

Transplantation of human pancreatic islets has been demonstrated to be a viable alternative to exogenous insulin therapy for diabetes mellitus. However, optimum results require transplantation of islets from two to three pancreas donors after a minimum number of days in culture. This implies that a substantial part of the transplanted islet mass may be nonfunctional. This study investigates the ability of an optimized technique to retain islet function using porcine-derived small intestinal submucosa (SIS) during in vitro culture. Groups of purified human islets were cultured for 3 weeks in modified standard islet culture conditions of CMRL = 1066 tissue culture medium supplemented with 25 mmol/L HEPES, penicillin/streptomycin, and a commercial insulin-transferin-selenium (ITS) supplement. Islets (50 to 200 IE/condition; n = 5 preparations) were cultured in plates containing noncoated Biopore membrane inserts alone, or on inserts that had been covered with SIS. Function was assessed by static incubation with low (4 mmol/L), or high (20 mmol/L) glucose at the end of each week. Glucose-stimulated release of human insulin was measured by radioimmunoassay (Linco, St. Charles, Missouri). Remaining islets were stained and evaluated visually. Neither culture condition resulted in significantly different basal secretion until week 3 (P =.05). However, by the end of week 2 and for the duration of the experiment thereafter, SIS-treated islets exhibited a higher SI (P <.05). At the end of the experiment, islets cultured on the SIS exhibited excellent morphology, with greater than 90% staining positive with Dithizone. Islets cultured on the inserts alone lost their initial morphology, becoming "loose" in appearance. The results of this study indicate that SIS enables enhanced function of islets in vitro as compared to non-SIS supported culture conditions.


Subject(s)
Insulin/metabolism , Intestinal Mucosa/cytology , Islets of Langerhans/metabolism , Cell Culture Techniques/methods , Glucose/pharmacology , Humans , Insulin Secretion , Islets of Langerhans/cytology , Islets of Langerhans/drug effects , Kinetics , Time Factors
16.
Burns ; 30(2): 148-50, 2004 Mar.
Article in English | MEDLINE | ID: mdl-15019122

ABSTRACT

PURPOSE: Children with attention-deficit/hyperactivity disorder (ADHD) are at increased risk for traumatic injury than non-ADHD-children. Burn injuries in ADHD-children have not been studied. This study was conducted to determine differences in burn injuries between these groups. METHODS: The charts of all children ages 5-18, admitted over a 7-year period to a single regional pediatric burn center, were reviewed. ADHD-children were compared to non-ADHD-children regarding age and gender, type and extent of burn, and burn injury outcome. FINDINGS: There were 278 children included, 35 (13%) having ADHD. ADHD-children were more likely male but did not differ in age compared to non-ADHD-children. ADHD-children were more likely to experience a thermal rather than flame burn (83% versus 58% thermal, P < 0.01) and had more extensive burn injury (10% versus 5% median TBSA, P = 0.03). The ADHD group had a longer length of stay (11 versus 7 days, P = 0.05) and was less likely to be discharged to home (86% versus 93%, P = 0.17). CONCLUSIONS: ADHD-children do differ from non-ADHD-children in their pattern and extent of burn injury. The impulsivity and vigilance deficits that characterize ADHD may place these children at higher risk for specific types of burn injuries.


Subject(s)
Attention Deficit Disorder with Hyperactivity/complications , Burns/psychology , Adolescent , Burns/prevention & control , Child , Child, Preschool , Female , Humans , Length of Stay , Male , Risk Factors , Sex Factors
17.
Cancer Lett ; 180(2): 183-90, 2002 Jun 28.
Article in English | MEDLINE | ID: mdl-12175550

ABSTRACT

In this study, we demonstrated that thrombin activates protein kinase C (PKC), mitogen activated protein kinases (MAP kinases), transcription factor nuclear factor-kappa B (NF-kappa B), and cAMP-dependent protein kinase (PKA) in the human renal carcinoma cell line A-498. In addition, it enhanced the migratory capacity, but had no effect on the proliferation of A-498 cells. The effect of thrombin on migration could be blocked by the PKA inhibitor H-89 but was not influenced by inhibition of PKC, MAP kinases or NF-kappa B. We concluded, that thrombin acts as a regulator on human A-498 renal carcinoma cell migration including PKA.


Subject(s)
Cyclic AMP-Dependent Protein Kinases/physiology , Kidney Neoplasms/pathology , Thrombin/pharmacology , Cell Division/drug effects , Cell Movement/drug effects , Cell Nucleus/metabolism , Chemotaxis/drug effects , Enzyme Activation , Humans , Mitogen-Activated Protein Kinases/metabolism , NF-kappa B/metabolism , Protein Kinase C/physiology , Transcription Factor RelA , Tumor Cells, Cultured
18.
Cytokine ; 15(2): 75-9, 2001 Jul 21.
Article in English | MEDLINE | ID: mdl-11500082

ABSTRACT

Thrombopoietin (TPO) plays a crucial role in megakaryocyte development. TPO signalling, which is mediated by its receptor Mpl, includes Janus kinase, (JAK) signal transducer and activator of transcription (STAT) and Shc/Ras/mitogen-activated protein kinase (MAPK) pathways. The precise nature of these signalling routes has not been clarified in detail up until now. We investigated the effect of TPO on activation of cAMP-dependent protein kinase (PKA) and its involvement in MAPK signalling in human megakaryoblastic leukaemia CMK cells. For estimation of PKA activity, phosphorylation of a PKA-specific peptide substrate was assayed in CMK cell lysates. Since activation of PKA is associated with translocation of its catalytic subunit alpha (C-PKA) into the cell nucleus, Western blot analysis of nuclear fractions with an anti-C-PKA antibody was additionally performed. The activation of TPO-induced MAPK activation and the effect of the PKA inhibitor H-89 was measured using immunoblotting with a monoclonal anti-pERK antibody. TPO enhanced cAMP and induced activation of PKA in CMK cells. In addition, H-89 partly blocked TPO-induced MAPK activation in CMK cells. Our results indicate a novel TPO-triggered signalling event, activation of the cAMP/PKA pathway in human megakaryoblastic CMK cells. This signal transduction route seems to be involved in TPO-induced MAPK signaling.


Subject(s)
Cyclic AMP-Dependent Protein Kinases/metabolism , Cyclic AMP/metabolism , Leukemia, Megakaryoblastic, Acute/metabolism , Mitogen-Activated Protein Kinases/metabolism , Signal Transduction/physiology , Sulfonamides , Thrombopoietin/metabolism , Cell Nucleus/metabolism , Cyclic AMP/agonists , Cyclic AMP-Dependent Protein Kinases/drug effects , Enzyme Activation , Humans , Isoquinolines/antagonists & inhibitors , Isoquinolines/metabolism , Mitogen-Activated Protein Kinases/drug effects , Protein Transport/drug effects , Protein Transport/physiology , Thrombopoietin/pharmacology , Tumor Cells, Cultured/metabolism
19.
Biochem Biophys Res Commun ; 282(4): 952-7, 2001 Apr 13.
Article in English | MEDLINE | ID: mdl-11352644

ABSTRACT

Cellular effects of thrombin are mediated by members of a new subfamily of G protein-coupled receptors designated proteinase-activated receptors (PARs) with the prototype PAR-1. Investigation of PAR-1-induced signaling has been shown to be very important in clarifying thrombin's role in cell metabolism, differentiation, and growth. We evaluated connection of PAR-1 with the cAMP/PKA pathway in SNB-19 glioblastoma cells. Alpha-thrombin and the synthetic PAR-1 agonist SFLLRN stimulated PKA as shown by increased PKA activity and translocation of the catalytic PKA alpha subunits (PKA(cat)alpha) into the nucleus. However, no effect on cAMP could be observed. PKA(cat)alpha was found to be associated with nuclear factor-kappa B (NF-kappaB) p65 and its inhibitor protein IkappaB in SNB-19 cells. After PAR-1 stimulation, this association was markedly diminished. We conclude that PAR-1 mediates PKA activation without altering cAMP levels but includes NF-kappaB-associated PKA(cat)alpha in SNB-19 glioblastoma cells. This is the first evidence for a cAMP-independent PKA signaling by a G protein-coupled receptor.


Subject(s)
Cyclic AMP-Dependent Protein Kinases/metabolism , Receptors, Thrombin/metabolism , Signal Transduction , Active Transport, Cell Nucleus , Cell Nucleus/metabolism , Cyclic AMP/metabolism , Enzyme Activation , Glioblastoma , Humans , I-kappa B Proteins/metabolism , Kinetics , NF-kappa B/metabolism , Peptide Fragments/pharmacology , Receptor, PAR-1 , Thrombin/pharmacology , Tumor Cells, Cultured
20.
Cell Tissue Bank ; 2(4): 217-24, 2001.
Article in English | MEDLINE | ID: mdl-15256904

ABSTRACT

In vitro proliferation of isolated pancreatic islets has become an area of great interest given the scarcity of clinical islet donors and the islet mass requirements for clinical islet transplantation. Small intestinal submucosa (SIS), a naturally occurring extracellular matrix, has been investigated to promote wound healing, tissue remodeling and cell growth. This study evaluated recovery and function of isolated canine pancreatic islets following in vitro tissue culture. Pancreatic islets were isolated from mongrel dogs using standard surgical procurement followed by intraductal collagenase distension, mechanical dissociation and EuroFicoll purification. Groups of purified islets were cultured in a humidified atmosphere of 95% air and 5% CO(2) for 48 hours in standard islet culture conditions of CMRL 1066 tissue culture media (Gibco) which had been supplemented with 25microM HEPES, penicillin/streptomycin and either 10% heat inactivated fetal calf serum (FCS, Gibco) or solubilized SIS solution (Cook Biotech, Inc., West Lafayette, IN). The mean recovery of islets following the culture period was determined by sizing duplicate counts of a known volume and viability was assessed by static incubation with low glucose (2.8 mM), high glucose (20 mM) and high glucose solution supplemented with 50 microm IBMX solution. Remaining islets were embedded histologically. From a consecutive series of six culture experiments, a significantly higher (p < 0.05) recovery of islets co-cultured with SIS was observed when compared to controls. Mean islet recovery was 84.5 +/- 2.9% (mean +/- SEM) from the SIS cultured group compared with 64.7 +/- 4.5% from the control group cultured in FCS (p < 0.05, n=6). Islets from the SIS treated group exhibited a significantly higher (p <, 0.05) insulin response to the high glucose stimulus than islets cultured in the standard FCS cultured solution. The calculated stimulation index was 12.3 +/- 3.4 for the SIS-treated group compared with 5.6 +/- 1.8 for the standard cultured group (p < 0.05). The overall mean numbers of islets recovered following in vitro culture was also higher in the SIS-treated group. The proportion of islets with a mean diameter >150 microm increased from 24% to 31% in the SIS-treated group, whereas the same proportion decreased to 18% from 22% in the control (FCS-treated) group. Histological evaluation of fixed tissue samples collected following the culture period identified insulin and glucagon-secreting cells in the SIS and FCS treated groups, however a higher frequency of insulin positive cells were detected consistently in the SIS treated group. A proliferation marker (PCNA) identified positive cells within both groups as well. This study suggests that co-culture of freshly isolated canine islets in medium supplemented with solubilized SIS can improve the post-culture recovery and in vitro islet function. Future investigations will focus on the cellular interactions of SIS, both in vitro and in vivo.

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