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1.
ChemPhotoChem ; 2: 994-1001, 2018 Nov.
Article in English | MEDLINE | ID: mdl-32895634

ABSTRACT

Adsorption of organic molecules at ZnO nanoparticle surfaces enables the transfer of energy or charge across resulting organic-inorganic interfaces and, consequently, determines the optoelectronic performance of ZnO based hybrids. We investigated on aqueous colloidal ZnO dispersions adsorption-induced changes with photoluminescence (PL) and electron paramagnetic resonance (EPR) spectroscopy. Citrate and acetate ion adsorption increases or decreases radiative exciton annihilation at hν = 3.3 eV and at room temperature, respectively. Searching for a correspondence between PL emission and the yield of trapped charge carriers originating from exciton separation - using photon energies of hν = 4.6 eV and fluxes of = 1014 cm-2 s-1 for excitation - we found that there is a negligible fraction of paramagnetic products that originate from exciton separation. Upon polychromatic excitation with significantly higher photon fluxes (N ph = 1016 cm-2·s-1), ZnO specific shallow defects trap unpaired electrons in citrate and acetate functionalized samples. The adsorption dependent PL intensity changes and the excitation parameter dependent yield of separated charges (EPR) in colloidal ZnO nanoparticles underline that the distribution over the different exciton annihilation channels sensitively depends on interface composition and the intensity of the photoexcitation light.

2.
Eur J Trauma Emerg Surg ; 44(2): 235-243, 2018 Apr.
Article in English | MEDLINE | ID: mdl-28280873

ABSTRACT

INTRODUCTION: The incidence of radial nerve injury after humeral shaft fractures is on average 11.8% (Shao et al., J Bone Jt Surg Br 87(12):1647-1652, 2005) representing the most common peripheral nerve injury associated with long bone fractures (Korompilias et al., Injury, 2013). The purpose of this study was to analyze our current policy and long-term outcome, regarding surgically treated humeral shaft fractures in combination with radial nerve palsy. MATERIALS AND METHODS: We retrospectively analyzed the data of patients with surgically treated humeral shaft fractures from 01/01/2003 to 28/02/2013. The analysis included fracture type, soft tissue injury regarding closed and open fractures, type of fixation, management, and outcome of radial nerve palsy. RESULTS: A total of 151 humeral shaft fractures were fixed in our hospital. In 20 (13%) cases, primary radial palsy was observed. Primary nerve exploration was performed in nine cases. Out of the 13 patients with follow-up, 10 showed a complete, 2 a partial, and 1 a minimal nerve recovery. Two of them underwent a revision procedure. Secondary radial nerve palsy occurred in 9 (6%) patients postoperatively. In five patients, the radial nerve was not exposed during the initial surgery and, therefore, underwent revision with nerve exploration. In all 5, a potential cause for the palsy was found and corrected as far as possible with full recovery in 3 and minimal recovery in one patient. In four patients with exposure of the nerve during the initial surgery, no revision was performed. All of these 4 showed a full recovery. CONCLUSION: Our study showed an overall rate of 19% radial nerve palsy in surgically treated humeral shaft fractures. Most of the primary palsies (13%) recovered spontaneously, and therefore, nerve exploration was only exceptionally needed. The incidence of secondary palsy after surgery (6%) was high and mainly seen after plate fixation. In these cases, we recommend early nerve exploration, to detect and treat potential curable neural lesions.


Subject(s)
Humeral Fractures/surgery , Humerus/innervation , Radial Neuropathy/surgery , Adult , Female , Fracture Fixation, Internal , Humans , Humeral Fractures/complications , Male , Middle Aged , Radial Nerve , Radial Neuropathy/complications , Recovery of Function , Treatment Outcome
6.
Biosens Bioelectron ; 67: 490-6, 2015 May 15.
Article in English | MEDLINE | ID: mdl-25241122

ABSTRACT

Dementia is one of the big medical challenges of our time with Alzheimer's, Huntington's and Parkinson's disease among its most common forms. In year 2000, 4.5 million people were diagnosed with Alzheimer's disease in the United States. In the case of Alzheimer's disease one of many contributing factors is a metabolic imbalance that leads to elevated oxidative stress levels. Consequences of this imbalance can be symptoms like apraxia, agnosia or sundowning. The use of field-effect transistors is a novel approach to study the effects of external stimuli on cells in vitro to provide researchers with a new tool for high resolution and high throughput studies to better understand cellular interaction and the effects of pharmacological compounds. In our study we use ion-sensitive field-effect transistors (FETs) to analyze the apoptosis inducing effects of hydrogen peroxide treatment on primary cells obtained from the subventricular zone of postnatal BALB/c mice. Upon apoptosis, the cell-substrate adhesion of the neurons is gradually weakened until complete detachment. In former studies we used our FET devices to conduct Electrical Cell-substrate Impedance Sensing (ECIS) experiments on the single cell level using morphologically different cell lines. Here we demonstrate that our novel approach of ECIS using FET devices can be expanded to primary neuronal tissue with high prospects for further studies in the field of pharmacological research.


Subject(s)
Apoptosis/drug effects , Biosensing Techniques , Lateral Ventricles/drug effects , Oxidative Stress/drug effects , Animals , Cell Adhesion/drug effects , Dielectric Spectroscopy , Hydrogen Peroxide/administration & dosage , Lateral Ventricles/cytology , Mice , Nerve Degeneration/drug therapy , Nerve Degeneration/pathology , Primary Cell Culture
7.
Opt Express ; 21(14): 16319-30, 2013 Jul 15.
Article in English | MEDLINE | ID: mdl-23938484

ABSTRACT

Bragg scattering effects in bottom-emitting organic light-emitting diodes (OLEDs) grown on corrugated aluminum-doped zinc oxide electrodes are analyzed. Periodic corrugation is introduced by structuring the oxide electrode via UV laser ablation, a process that enables flexible adjustment of the period and height of corrugation. We demonstrate that fabrication of stable and electrically efficient OLEDs on these rough substrates is feasible. Sharp spectral features are superimposed onto the broad emission spectra of the OLEDs, providing clear evidence for Bragg scattering of light from guided modes into the air cone. Theoretical analysis based on an emissive dipole model and conservation of momentum considerations allows a quantitative description of scattering and the associated dispersion relations.


Subject(s)
Lighting/instrumentation , Models, Theoretical , Organic Chemicals/chemistry , Refractometry/instrumentation , Semiconductors , Computer Simulation , Equipment Design , Equipment Failure Analysis , Light , Scattering, Radiation , Surface Properties
8.
Ann Anat ; 195(1): 57-67, 2013 Jan.
Article in English | MEDLINE | ID: mdl-22683001

ABSTRACT

Ultrasound is widely used in clinical practice, mostly in diagnostic studies, but increasingly in therapeutic applications as well. This may be the case in acceleration of wound healing or treatment of cancer. Still, little is known about the direct effect of frequency or energy density of the ultrasound upon the cells themselves. We therefore investigated the impact of three different protocols using high, medium and low energy densities at three different frequencies on normal endothelial and epithelial as well as carcinoma cell lines (neuroblastoma and adenocarcinoma cell lines). Proliferation of endothelial and epithelial cell lines was significantly increased depending on the frequency and energy density applied. No influence on actin cytoskeleton formation was seen in these cells after treatment, while a significant decrease in the density of microvilli and the length of filopodia in the epithelial cell line could be noted. The proliferation rate of the carcinoma cell lines was reduced and cells destroyed. Apoptosis was induced in the adenocarcinoma cells after ultrasound exposure. Additionally, the expression of neurofilament was increased in neuroblastoma cells as evidence of beginning differentiation. So, different settings of frequency and energy density in an ultrasonic treatment protocol lead to different impacts on proliferation, morphology and differentiation and might be used to stimulate or inhibit the growth of individual cell types.


Subject(s)
Cells/radiation effects , Ultrasonics , Animals , Apoptosis/radiation effects , Cell Differentiation/radiation effects , Cell Line , Cell Line, Tumor , Cell Proliferation/radiation effects , Dogs , Dose-Response Relationship, Radiation , Electrophoresis, Gel, Two-Dimensional , Fluorescent Antibody Technique , Humans , Liposomes , Mice , Microscopy, Electron, Scanning , Proteome , Ultrasonics/instrumentation
9.
Am J Transplant ; 11(4): 698-707, 2011 Apr.
Article in English | MEDLINE | ID: mdl-21062418

ABSTRACT

Previous studies suggest that the majority of renal allografts are affected by progressive, severe chronic histologic injury, yet studies using current protocols are lacking. The goal of this study was to examine the prevalence and progression of histologic changes using protocol allograft biopsies at 1 and 5 years after solitary kidney transplantation in patients transplanted between 1998 and 2004. Chronic histologic changes generally were mild at both 1 and 5 years and were similar in deceased and living donor kidneys. The overall prevalence of moderate or severe fibrosis was 13% (60/447) at 1 year and 17% (60/343) at 5 years. In a subgroup of 296 patients who underwent both 1- and 5-year biopsies, mild fibrosis present at 1 year progressed to more severe forms at 5 years in 23% of allografts. The prevalence of moderate or severe arteriolar hyalinosis was similar in tacrolimus and calcineurin inhibitor-free immunosuppression. These results in the recent era of transplantation demonstrate fewer, less severe and less progressive chronic histologic changes in the first 5 years after transplantation than previously reported.


Subject(s)
Fibrosis/pathology , Graft Rejection/pathology , Kidney Diseases/pathology , Kidney Transplantation , Adolescent , Adult , Aged , Aged, 80 and over , Biopsy , Disease Progression , Female , Humans , Male , Middle Aged , Time Factors , Tissue Donors , Transplantation, Homologous , Young Adult
10.
Resuscitation ; 81(8): 943-9, 2010 Aug.
Article in English | MEDLINE | ID: mdl-20627524

ABSTRACT

AIM: Mild therapeutic hypothermia improves survival and neurologic recovery in primary comatose survivors of cardiac arrest. Cooling effectivity, safety and feasibility of nasopharyngeal cooling with the RhinoChill device (BeneChill Inc., San Diego, USA) were determined for induction of therapeutic hypothermia. METHODS: Eleven emergency departments and intensive care units participated in this multi-centre, single-arm descriptive study. Eighty-four patients after successful resuscitation from cardiac arrest were cooled with nasopharyngeal delivery of an evaporative coolant for 1h. Subsequently, temperature was controlled with systemic cooling at 33 degrees C. Cooling rates, adverse events and neurologic outcome at hospital discharge using cerebral performance categories (CPC; CPC 1=normal to CPC 5=dead) were documented. Temperatures are presented as median and the range from the first to the third quartile. RESULTS: Nasopharyngeal cooling for 1h reduced tympanic temperature by median 2.3 (1.6; 3.0) degrees C, core temperature by 1.1 (0.7; 1.5) degrees C. Nasal discoloration occurred during the procedure in 10 (12%) patients, resolved in 9, and was persistent in 1 (1%). Epistaxis was observed in 2 (2%) patients. Periorbital gas emphysema occurred in 1 (1%) patient and resolved spontaneously. Thirty-four of 84 patients (40%) patients survived, 26/34 with favorable neurological outcome (CPC of 1-2) at discharge. CONCLUSIONS: Nasopharyngeal evaporative cooling used for 1h in primary cardiac arrest survivors is feasible and safe at flow rates of 40-50L/min in a hospital setting.


Subject(s)
Cardiopulmonary Resuscitation/methods , Emergency Service, Hospital , Heart Arrest/therapy , Hypothermia, Induced/instrumentation , Nasopharynx , Administration, Intranasal , Aged , Body Temperature/physiology , Cold Temperature , Equipment Design , Feasibility Studies , Female , Follow-Up Studies , Heart Arrest/physiopathology , Humans , Male , Middle Aged , Prospective Studies , Treatment Outcome
11.
Am J Transplant ; 10(3): 558-62, 2010 Mar.
Article in English | MEDLINE | ID: mdl-20055804

ABSTRACT

Nephrogenic systemic fibrosis (NSF) is a debilitating disease in patients with severely diminished kidney function. Currently, no standard treatment exists but improvement has been reported after restoration of kidney function. We retrospectively studied 17 NSF patients with and without successful kidney transplantation (KTx) to evaluate the effects of KTx on NSF. Nine of the 11 KTx developed NSF pretransplant whereas two developed NSF immediately after KTx with delayed graft function. Two of the six dialysis patients had previous failed kidney transplants. Age and sex were well matched. All but one patient was dialysis dependent at the time of NSF. Median follow-up was 35 months for KTx patients and 9 months for dialysis patients. Kidney transplants achieved adequate renal function with median serum creatinine of 1.4 (0.9-2.8) mg/dL and a glomerular filtration rate of 42 (19-60) mL/min/1.73 m(2). NSF improved in 54.6% of the transplanted patients and 50% of the nontransplanted patients (p = 0.86). Two KTx patients had complete resolution of their symptoms whereas four had partial improvement. Improvement in the dialysis patients was all partial. Successful KTx did not insure improvement in NSF and in fact appeared to have no significant benefit over dialysis.


Subject(s)
Kidney Transplantation/methods , Nephrogenic Fibrosing Dermopathy/therapy , Adult , Aged , Creatinine/blood , Disease Progression , Female , Follow-Up Studies , Glomerular Filtration Rate , Graft Survival , Humans , Kidney Transplantation/adverse effects , Male , Middle Aged , Retrospective Studies , Treatment Outcome
12.
Dtsch Med Wochenschr ; 134(18): 935-7, 2009 Apr.
Article in German | MEDLINE | ID: mdl-19384813

ABSTRACT

HISTORY AND ADMISSION FINDINGS: A 24-year-old man with known abuse of gamma-butyrolactone (GBL) was found with stupor and myoclonies on all extremities. He had been known to have ingested 2 ml of pure GBL every half an hour. Decubiti were detected on the knuckle of the right foot, on both elbows and at the rump. INVESTIGATIONS: Laboratory findings revealed signs of severe rhabdomyolysis and renal failure as well as elevated markers of inflammation. Other routine laboratory parameters were normal. A toxicological screening revealed no signs of an acute intoxication. DIAGNOSIS, TREATMENT AND COURSE: A GBL withdrawal syndrome was diagnosed. The treatment of agitation and myoclonies required repeated applications of benzodiazepines. Because of the resulting respiratory depression the patient had to be intubated. To cope with myoclonies and other symptoms of substance withdrawal we had to administer midazolame and clonidine continuously until day four. Because of acute renal failure resulting from rhabdomyolysis hemodialysis was necessary three times. After 19 days the patient was transferred to a psychiatric clinic. CONCLUSIONS: Primary care physicians treating patients with a coma of unknown cause always have to think of the possibility of GBL withdrawal. The treatment will be symptomatic.


Subject(s)
4-Butyrolactone/adverse effects , Acute Kidney Injury/chemically induced , Rhabdomyolysis/chemically induced , Solvents/adverse effects , Substance Withdrawal Syndrome , Acute Kidney Injury/therapy , Adrenergic alpha-Agonists/administration & dosage , Benzodiazepines/administration & dosage , Clonidine/administration & dosage , GABA Modulators/administration & dosage , Humans , Intubation, Intratracheal , Male , Midazolam/administration & dosage , Myoclonus/chemically induced , Myoclonus/drug therapy , Renal Dialysis , Respiration, Artificial , Respiratory Insufficiency/therapy , Rhabdomyolysis/drug therapy , Substance Withdrawal Syndrome/therapy , Young Adult
13.
Anaesthesist ; 57(12): 1155-60, 2008 Dec.
Article in German | MEDLINE | ID: mdl-18958431

ABSTRACT

INTRODUCTION: Time course, time necessary to achieve the target temperature and stable maintenance, as well as a controlled rewarming period are important factors influencing the outcome of patients after successful cardiopulmonary resuscitation. METHODS: After successful cardiopulmonary resuscitation a total of 49 patients were cooled via an endovascular or external cooling device to a target temperature of 33 degrees C. Relevant cooling parameters, such as time between admission and initiation of cooling, achievement of target temperature and stable maintenance of cooling therapy, were compared between both groups. RESULTS: In the endovascular cooling group the target temperature was reached significantly faster (154 +/- 97 min vs. 268 +/- 95 min, p = 0.0002) and showed stable and controlled maintenance of cooling therapy (deviation from target temperature: 0.189 +/- 0.23 degrees C vs 0.596 +/- 0.61 degrees C, p = 0.00006). The rewarming phase was better controlled and length of ICU stay was shorter in the group with endovascular cooling (8.8 +/- 3 vs. 12.9 +/- 6 days). CONCLUSION: Endovascular cooling offers the possibility to reach the target temperature significantly faster and a stable maintenance of therapeutic hypothermia. It is capable of a more controlled rewarming period and shortens the length of ICU stay.


Subject(s)
Heart Arrest/therapy , Hypothermia, Induced , Aged , Blood Vessels/physiology , Body Temperature , Cardiopulmonary Resuscitation , Critical Care , Female , Humans , Hypothermia, Induced/instrumentation , Male , Middle Aged , Rewarming
14.
Auton Autacoid Pharmacol ; 26(4): 335-44, 2006 Oct.
Article in English | MEDLINE | ID: mdl-16968472

ABSTRACT

The aim of this study was to characterize the effects of 4-methylthioamphetamine (4-MTA) on contractility and noradrenaline (NA) transport and release in the isolated rat aorta. Descending thoracic aortic rings were isolated from male Wistar rats (220-240 g) and the effect of 4-MTA on contractility was measured by isometric force displacement. 4-MTA (0.1 microm-1 mm) induced a concentration-dependent contraction of aortic rings, with a pD(2) of 4.40 +/- 0.38, and an E(max) of 0.80 +/- 0.05 g tension. The alpha(1)-adrenoceptor antagonist, prazosin (1 microm) and alpha(2) antagonist, yohimbine (1 microm) inhibited maximal contraction to 100 microm 4-MTA by 45.0 +/- 6.7% and 53.5 +/- 7.1% of control values respectively, whereas the 5-hydroxytryptamine (5-HT) antagonist, ketanserin (100 nm) had no effect on the 4-MTA-mediated contraction. The specific NA transport inhibitor, nisoxetine (1 microm) abolished contraction of the aorta by 4-MTA. 4 Nisoxetine-sensitive [(3)H]-NA transport in aortic rings was measured over a concentration range of 0-5 microm [(3)H]-NA, and had a maximal rate of transport (V(max)) of 0.77 +/- 0.07 pmol [(3)H]-NA min(-1) mg(-1) protein and a Michaelis affinity constant (K(M)) of 2.3 +/- 0.5 microm. 4-MTA inhibited nisoxetine-sensitive [(3)H]-NA transport with a pIC(50) of 6.16 +/- 0.18 and the pIC(50) for inhibition of nisoxetine-sensitive [(3)H]-NA transport by 3,4-methylenedioxymethamphetamine (MDMA) was 6.83 +/- 0.13. 4-MTA (1-100 microm) significantly stimulated release of pre-loaded [(3)H]-NA from aortic rings and 4-MTA-induced [(3)H]-NA release was inhibited by 1 microm nisoxetine. These data suggest that 4-MTA causes contraction of the rat aorta in vitro by a mechanism that is consistent with an ability to cause release of NA at the level of the NA transporter. It is concluded that 4-MTA has the potential to increase the extracellular concentration of NA peripherally as well as centrally, and that this may cause adverse cardiovascular effects in its users.


Subject(s)
Amphetamines/pharmacology , Aorta, Thoracic/drug effects , Norepinephrine/metabolism , Vasoconstriction/drug effects , Adrenergic Uptake Inhibitors/pharmacology , Animals , Aorta, Thoracic/metabolism , Aorta, Thoracic/physiology , Biological Transport/drug effects , Brain/cytology , Brain/drug effects , Brain/metabolism , Dose-Response Relationship, Drug , Fluoxetine/analogs & derivatives , Fluoxetine/pharmacology , In Vitro Techniques , Male , N-Methyl-3,4-methylenedioxyamphetamine/pharmacology , Norepinephrine/antagonists & inhibitors , Rats , Rats, Wistar , Synaptosomes/drug effects , Synaptosomes/metabolism , Tritium
15.
Am J Transplant ; 6(5 Pt 1): 1025-32, 2006 May.
Article in English | MEDLINE | ID: mdl-16611340

ABSTRACT

Polyomavirus-associated nephropathy (PVAN) is managed by reduced immunosuppression with or without antiviral therapy. Data from 55 patients with biopsy-proven PVAN were analyzed for adverse outcomes and influence of baseline variables and interventions. During 20+/-11 months follow-up, the frequencies of graft loss, major and any functional decline were 15%, 24% and 38%, respectively. Repeat biopsies were performed in 45 patients with persistent PVAN in 47%. Low-dose cidofovir, IVIG and cyclosporine conversion were used in 55%, 20% and 55% of patients. No single intervention was associated with improved outcome. Of the variables examined, only degree of interstitial fibrosis at diagnosis was associated with kidney function decline. In contrast, donor source, interstitial fibrosis, proportion of BKV positive tubules and plasma viral load at diagnosis were all associated with failure of histological viral clearance. This retrospective, nonrandomized analysis suggests that: (i) Graft loss within 2 years of PVAN diagnosis is now uncommon, but ongoing functional decline and persistent infection occur frequently. (ii) Low-dose cidofovir, IVIG and conversion to cyclosporine do not abrogate adverse outcomes following diagnosis. (iii) Fibrosis at the time of diagnosis predicts subsequent functional decline. Further elucidation of the natural history of PVAN and its response to individual interventions will require prospective clinical trials.


Subject(s)
Kidney Diseases/pathology , Kidney Diseases/virology , Kidney Transplantation/physiology , Polyomavirus Infections/complications , Adult , Antiviral Agents/therapeutic use , Biopsy , Cidofovir , Cyclosporine/therapeutic use , Cytosine/analogs & derivatives , Cytosine/therapeutic use , Female , Follow-Up Studies , Humans , Immunosuppression Therapy/methods , Kidney Diseases/drug therapy , Kidney Diseases/etiology , Kidney Diseases/surgery , Kidney Transplantation/pathology , Male , Middle Aged , Organophosphonates/therapeutic use , Polyomavirus Infections/drug therapy , Postoperative Complications/pathology , Treatment Outcome
16.
Am J Transplant ; 6(3): 514-22, 2006 Mar.
Article in English | MEDLINE | ID: mdl-16468960

ABSTRACT

Calcineurin inhibitors have decreased acute rejection and improved early renal allograft survival, but their use has been implicated in the development of chronic nephrotoxicity. We performed a prospective, randomized trial in kidney transplantation comparing sirolimus-MMF-prednisone to tacrolimus-MMF-prednisone. Eighty-one patients in the sirolimus group and 84 patients in the tacrolimus group were enrolled (mean follow-up = 33 months; range 13-47 months). At 1 year, patient survival was similar in the groups (98% with sirolimus, 96% with tacrolimus; p = 0.42) as was graft survival (94% sirolimus vs. 92% tacrolimus, p = 0.95). The incidence of clinical acute rejection was 10% in the tacrolimus group and 13% in the sirolimus group (p = 0.58). There was no difference in mean GFR measured by iothalamate clearance between the tacrolimus and sirolimus groups at 1 year (61 +/- 19 mL/min vs. 63 +/- 18 mL/min, p = 0.57) or 2 years (61 +/- 17 mL/min vs. 61 +/- 19 mL/min, p = 0.84). At 1 year, chronicity using the Banff schema showed no difference in interstitial, tubular or glomerular changes, but fewer chronic vascular changes in the sirolimus group. This study shows that a CNI-free regimen using sirolimus-MMF-prednisone produces similar acute rejection rates, graft survival and renal function 1-2 years after transplantation compared to tacrolimus-MMF-prednisone.


Subject(s)
Calcineurin Inhibitors , Graft Rejection/prevention & control , Immunosuppressive Agents/therapeutic use , Kidney Transplantation , Sirolimus/therapeutic use , Tacrolimus/therapeutic use , Adult , Aged , Aged, 80 and over , Female , Follow-Up Studies , Glomerular Filtration Rate/drug effects , Glomerular Filtration Rate/physiology , Graft Rejection/mortality , Graft Rejection/physiopathology , Graft Survival/drug effects , Humans , Male , Middle Aged , Prospective Studies , Survival Rate , Time Factors , Treatment Outcome
17.
Apoptosis ; 10(4): 831-40, 2005 Aug.
Article in English | MEDLINE | ID: mdl-16133873

ABSTRACT

Akt-mediated phosphorylation of forkhead transcription factors is linked to growth factor-stimulated cell survival. We investigated whether the survival activity of insulin-like growth factor-I (IGF-I) in SH-SY5Y human neuroblastoma (NBL) cells is associated with phosphorylation and/or localization changes in forkhead proteins. IGF-I induced phosphorylation of Erks (p42/p44), FKHR (FOXO1a) (Ser 253), FKHRL1 (FOXO3a) (Ser 256), and Akt (Ser 473). PI3-K inhibitor, LY294002, reduced IGF-I-stimulated phosphorylation of FKHR, FKHRL1, and Akt, but did not affect Erk phosphorylation. Using a GFP-FKHR construct, FKHR imported into the nucleus during growth factor withdrawal-induced apoptosis. In addition, IGF-I rescue from serum withdrawal-induced apoptosis is associated with a rapid export of GFP-FKHR into the cytoplasm. Leptomycin B, an inhibitor of Crm1-mediated nuclear export, decreased the level of FKHRL1 phosphorylation in the presence of IGF-I in vector and FKHR overexpressing cells, but had no effect on the phosphorylation status of FKHR. In addition, leptomycin B prevented IGF-I stimulated nuclear export of GFP-FKHR. These studies show IGF-I phosphorylation of FKHR and FKHRL1 via a PI3-K-dependent pathway in NBL cells.


Subject(s)
Cell Nucleus/drug effects , Cell Nucleus/metabolism , Forkhead Transcription Factors/metabolism , Insulin-Like Growth Factor I/pharmacology , Neuroblastoma/metabolism , Neuroblastoma/pathology , Apoptosis/drug effects , Cell Line, Tumor , Enzyme Activation/drug effects , Forkhead Box Protein O1 , Forkhead Box Protein O3 , Forkhead Transcription Factors/genetics , Gene Expression/drug effects , Humans , Neuroblastoma/enzymology , Phosphatidylinositol 3-Kinases/metabolism , Phosphorylation/drug effects , Protein Transport/drug effects , Recombinant Fusion Proteins/metabolism , Subcellular Fractions/drug effects
18.
Transplant Proc ; 35(3 Suppl): 125S-127S, 2003 May.
Article in English | MEDLINE | ID: mdl-12742483

ABSTRACT

INTRODUCTION: With the introduction of new immunosuppressive medicines, it has become possible to determine the extent to which nephrotoxic medicines contribute to CAN. The aim of this study is to compare the safety and efficacy of calcineurin inhibitor (CI) free immunosuppression in a prospective, randomized trial comparing sirolimus-mycophenolate mofetil (MMF)-prednisone to tacrolimus- MMF-prednisone. METHODS: Patients are randomized at the time of transplant to receive either tacrolimus (target level 12 to 15 ng/mL in the first month) or sirolimus (target level 12 to 18 ng/mL in the first month). All patients also receive MMF (750 mg bid) and prednisone tapered to 10 mg/d by 3 months and thymoglobulin induction (1.5 mg/kg/d on days 0, 1, 2, 4 and 6). RESULTS: At this point we have 4-month follow-up in 85 patients. The acute rejection rate is 7.5% (3/40) in the tacrolimus group and 6.7% (3/45) in the sirolimus group. We have discontinued sirolimus in eight patients so far, with wound complications being the most common indication. Renal function appears to be better in the sirolimus group at 1 month after transplantation, but the difference is not statistically significant. CONCLUSIONS: While longer follow-up is needed, these results demonstrate that total avoidance of CI can be achieved with extremely low acute cellular rejection rates using sirolimus-based immunosuppression in combination with thymoglobulin, MMF, and prednisone.


Subject(s)
Calcineurin Inhibitors , Kidney Transplantation/immunology , Kidney Transplantation/physiology , Mycophenolic Acid/analogs & derivatives , Sirolimus/therapeutic use , Drug Therapy, Combination , Follow-Up Studies , Glomerular Filtration Rate , Graft Rejection/immunology , Graft Rejection/prevention & control , Humans , Immunosuppressive Agents/adverse effects , Immunosuppressive Agents/therapeutic use , Kidney Transplantation/pathology , Muromonab-CD3/therapeutic use , Mycophenolic Acid/therapeutic use , Prednisone/therapeutic use , Time Factors , Transplantation, Homologous/pathology
19.
Transplantation ; 75(4): 560-1, 2003 Feb 27.
Article in English | MEDLINE | ID: mdl-12605128

ABSTRACT

Systemic amyloidosis results from the deposition of insoluble protein fibrils in various organs and tissues. To date, several different proteins have been associated with amyloid fibril formation, including immunoglobulin light chain, serum amyloid A protein, and transthyretin. Recent reports have shown that variant fibrinogen chains can form amyloid in certain kindreds. Hepatic transplantation has previously been reported in the treatment of hereditary amyloidosis associated with variant transthyretin proteins, which are mainly synthesized in the liver. This article reports the first use and long-term follow-up of combined hepatic and renal transplantation in the successful treatment of two patients with hereditary fibrinogen amyloidosis. Both patients experienced sustained improvement in renal function and nutritional status at 61/2 years and 28 months of follow-up, respectively. Orthotopic liver transplantation is effective and potentially curative treatment of hereditary fibrinogen amyloidosis.


Subject(s)
Amyloidosis, Familial/metabolism , Amyloidosis, Familial/surgery , Fibrinogen/metabolism , Liver Transplantation , Family Health , Follow-Up Studies , Humans , Male , Middle Aged
20.
Transplantation ; 72(10): 1671-5, 2001 Nov 27.
Article in English | MEDLINE | ID: mdl-11726830

ABSTRACT

BACKGROUND: Solitary pancreas transplants, both pancreas transplant alone (PTA) and pancreas after kidney (PAK), have higher rejection rates and lower graft survivals than simultaneous pancreas-kidney transplants (SPK). The aim of this study is to compare three different antibody induction regimens in solitary pancreas transplant recipients and to assess the role of surveillance pancreas biopsies in the management of these patients. METHODS: Solitary pancreas transplant recipients between 01/98 to 02/00 (n=29) received induction with either daclizumab (1 mg/kg on day 0, 7, 14), OKT 3 (5 mg/day x0-7), or thymoglobulin (1.5 mg/kg/day x0-10). Maintenance immunosuppression was similar for the three groups. All rejections were biopsy-proven either by surveillance/protocol or when clinically indicated. RESULTS: The 1-year graft survival was 89.3% overall and 91.7% in the thymoglobulin group. Thymoglobulin significantly decreased rejection in the first 6 months when compared with OKT3 or daclizumab (7.7 vs. 60 vs. 50%). Acute rejections were seen on surveillance biopsies in the absence of biochemical abnormalities in 40% of patients. CONCLUSIONS: Thymoglobulin induction regimen led to a low incidence of acute rejection and a high rate of graft survival in solitary pancreas transplants. In addition, surveillance biopsies were useful in the detection of early acute rejection in the absence of biochemical abnormalities.


Subject(s)
Antilymphocyte Serum/therapeutic use , Graft Rejection/prevention & control , Immunosuppressive Agents/therapeutic use , Pancreas Transplantation/immunology , Adult , Antibodies, Monoclonal/therapeutic use , Antibodies, Monoclonal, Humanized , Biopsy , Daclizumab , Female , Graft Survival , Humans , Immunoglobulin G/therapeutic use , Kidney Transplantation , Male , Muromonab-CD3/therapeutic use , Pancreas/pathology
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