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1.
J Eur Acad Dermatol Venereol ; 37(7): 1406-1414, 2023 Jul.
Article in English | MEDLINE | ID: mdl-36950970

ABSTRACT

BACKGROUND: The Localized Scleroderma Quality of Life Instrument (LoSQI) is a disease-specific patient-reported outcome (PRO) measure designed for children and adolescents with localized scleroderma (LS; morphea). This tool was developed using rigorous PRO methods and previously cognitively tested in a sample of paediatric patients with LS. OBJECTIVE: The purpose of this study was to evaluate the psychometric properties of the LoSQI in a clinical setting. METHODS: Cross-sectional data from four specialized clinics in the US and Canada were included in the analysis. Evaluation included reliability of scores, internal structure of the survey, evidence of convergent and divergent validity, and test-retest reliability. RESULTS: One hundred and ten patients with LS (age: 8-20 years) completed the LoSQI. Both exploratory and confirmatory factor analysis supported the use of two sub-scores: Pain and Physical Functioning, and Body Image and Social Support. Correlations with other PRO measures were consistent with pre-specified hypotheses. LIMITATIONS: This study did not evaluate longitudinal validity or responsiveness of scores. CONCLUSION: Results from a representative sample of children and adolescents with LS continue to support the validity of the LoSQI when used in a clinical setting. Future work to evaluate the responsiveness is ongoing.


Subject(s)
Quality of Life , Scleroderma, Localized , Adolescent , Humans , Child , Young Adult , Adult , Reproducibility of Results , Cross-Sectional Studies , Patient Reported Outcome Measures , Psychometrics/methods , Surveys and Questionnaires
4.
Br J Dermatol ; 183(4): 692-701, 2020 10.
Article in English | MEDLINE | ID: mdl-31955419

ABSTRACT

BACKGROUND: Paediatric localized scleroderma (LS) can negatively impact health-related quality of life (HRQoL) by causing skin fibrosis, abnormal limb development, disfigurement, and side-effects from immunosuppressive treatment. Studies to date have rarely included qualitative data gathered directly from paediatric patients with LS. OBJECTIVES: To assess the impact of LS on HRQoL among affected youth and their caregivers using qualitative description. METHODS: Youth with all subtypes of LS and their caregivers were purposively sampled to participate in age-appropriate focus groups (younger children, early adolescents, adolescents). Each group started with a drawing exercise followed by in-depth discussion of topics including skin symptoms (e.g. itch, pain, tightness), functional impairment, physical appearance, family and peer relationships, and treatment burden. Focus groups were transcribed verbatim and co-coded, with adjudication of differentially applied codes. The study findings were triangulated via comparison with adult reports and published literature. RESULTS: Eleven youth aged 9-16 years and 16 caregivers participated in three focus groups each. Major identified areas of impact included uncomfortable skin symptoms, physical functioning limitations, extracutaneous manifestations, body image, bullying and teasing, unwanted questioning from others, and treatment side-effects and burden. CONCLUSIONS: This is the first qualitative study of HRQoL in LS to include all major LS subtypes. We identified domains of HRQoL impacted by LS, some of which replicate earlier findings and some of which were novel. As impact also changed with developmental stage, our findings support the need for ongoing, formal evaluation of HRQoL in children and adolescents with LS. What is already known about this topic? Paediatric localized scleroderma (LS) negatively impacts health-related quality of life (HRQoL) via skin fibrosis, musculoskeletal and other extracutaneous manifestations from the disease process, and side-effects of systemic immunosuppression. The full impact of LS and its treatment on HRQoL is incompletely understood, with only one published qualitative study of youth with LS, which was limited to facial involvement. There are no qualitative studies of HRQoL in other LS subtypes to date. What does this study add? This is the first qualitative evaluation of HRQoL in youth with LS inclusive of all disease subtypes. Our study confirms that LS affects HRQoL across multiple distinct domains, including uncomfortable skin sensations, impacts on body image, bullying and teasing from peers, unwanted intrusive questioning, physical limitations, extracutaneous manifestations and high treatment burden. These results indicate the need for ongoing clinical assessment of paediatric patients in these domains. What are the clinical implications of the work? These results support the need to care for patients with LS holistically by synthesizing cutaneous, musculoskeletal and extracutaneous disease assessments with multidimensional evaluation of psychosocial impact and adverse effects of treatments. The development of an LS-specific HRQoL measure would advance such efforts.


Subject(s)
Quality of Life , Scleroderma, Localized , Adolescent , Adult , Body Image , Caregivers , Child , Focus Groups , Humans
5.
Br J Dermatol ; 182(3): 625-635, 2020 03.
Article in English | MEDLINE | ID: mdl-31498874

ABSTRACT

BACKGROUND: According to current standards, no existing patient-reported outcome (PRO) measures have high-quality validity evidence for use with individuals diagnosed with paediatric localized scleroderma (LS). This severely hinders patient-centred LS-focused research, including much needed clinical trials. OBJECTIVES: To develop a valid health-related quality of life measure for individuals with paediatric LS and to qualitatively evaluate its content validity using a patient-centred approach. METHODS: Previously collected qualitative data from youth with LS and their caregivers was used to develop items. The resulting item set was administered in a clinical setting to participants aged 8-18 years old. Cognitive interviews were used to evaluate time to survey completion, readability/understanding of the items, appropriateness of the recall period and construct representation. RESULTS: Seventeen children and adolescents with LS participated in the study. Interviews supported readability, understanding of the items and appropriateness of the recall period in individuals > 10 years old. Revisions were made to simplify the instructions and to be more inclusive of different subtypes of LS. Three items were added to improve content representation. CONCLUSIONS: Content validity was supported by the patient-centred development process of the outcome measure and via direct feedback from individuals with LS and their families. Although an important first step, the resulting PRO, termed the Localized Scleroderma Quality of Life Instrument, should be further evaluated in a larger sample before being implemented. What's already known about this topic? No current health-related quality of life (HRQoL) measures have been created using direct input from children and adolescents with localized scleroderma (LS). When compared with qualitative reports of HRQoL impact in youth with all LS subtypes, no existing patient-reported outcome (PRO) measures have appropriate content validity for individuals with paediatric LS. What does this study add? This study proposes a novel LS-specific PRO and is the first qualitative assessment of content validity for any PRO measure in this population. Results from cognitive interviews with children and adolescents support the content validity of the newly developed item set and its ability to capture HRQoL impact in a clinical context. What are the clinical implications of this work? Incorporating a content-valid PRO of HRQoL impact into clinical practice would allow for the valid, ongoing capture of patient experience in LS. Although content validity is an important and necessary step in the process of evaluating validity, items within this novel measure will undergo additional psychometric evaluation before implementation in research and clinical settings.


Subject(s)
Quality of Life , Scleroderma, Localized , Adolescent , Child , Humans , Patient Reported Outcome Measures , Psychometrics , Qualitative Research , Reproducibility of Results , Scleroderma, Localized/therapy , Surveys and Questionnaires
6.
Transplant Proc ; 51(4): 1263-1267, 2019 May.
Article in English | MEDLINE | ID: mdl-31101211

ABSTRACT

Thoracic organ transplantation made a fresh start in Hungary with the first double lung transplant in December 2015. This major leap in Hungarian transplantation was preceded by almost 10 years of preparation, new infrastructure development, and structural changes not only at the organizational level but in human resources as well. In the following years, until recently, altogether 47 lung transplants were performed on 24 men and 23 women. The underlying pathologies were as follows: chronic obstructive pulmonary disease, 25; cystic fibrosis, 11; idiopathic pulmonary fibrosis, 7; as well as other diseases, including bronchiectasis, eosinophilic granuloma, lymphangioleiomyomatosis, and primary pulmonary hypertension in 4 cases. The youngest recipient was 13 and the oldest was 65 years old. Overall survival rates at 30 days and at 1 year were 96% and 82%, respectively. No patients were lost in the cystic fibrosis and other diseases group, whereas the 1-year survival rates of the chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis groups were 73% and 71%, respectively. The results show the robustness and viability of the program, although there is still opportunity for further improvement. In this short paper, we summarize the fields of possible further cooperation of thoracic and cardiac teams as well as future challenges facing the new Hungarian lung transplant program.


Subject(s)
Cardiology , Lung Diseases/surgery , Lung Transplantation/methods , Lung Transplantation/statistics & numerical data , Adolescent , Adult , Aged , Female , Humans , Hungary , Male , Middle Aged , Surgeons , Survival Rate , Young Adult
7.
Transplant Proc ; 51(4): 1296-1298, 2019 May.
Article in English | MEDLINE | ID: mdl-31101218

ABSTRACT

Lung transplant is an effective way to treat many end-stage lung diseases. However, one of the main barriers of allograft organ transplant is still the immunologic rejection of transplanted tissue, which is a response of the HLA molecules. Rejection is a complex process involving both T-cell-mediated delayed-type hypersensitivity reactions and antibody-mediated hypersensitivity reactions to histocompatibility molecules on foreign grafts. We report the case of a 25-year-old female patient with cystic fibrosis who underwent 2 lung transplants because of her initial diagnosis and appearance of bronchiolitis obliterans syndrome after the first transplant. Only 13 months after the second transplant, despite the therapies applied, a new rejection occurred associated with high mean fluorescent intensity donor-specific antibody levels, which resulted later in the death of the patient. The present case draws attention to the importance of matching HLA molecules between donor and recipient in addition to immunosuppressive therapy.


Subject(s)
Cystic Fibrosis/surgery , Graft Rejection/immunology , Lung Transplantation/adverse effects , Reoperation/adverse effects , Adult , Bronchiolitis Obliterans/etiology , Bronchiolitis Obliterans/surgery , Female , HLA Antigens/immunology , Humans , Transplantation, Homologous/adverse effects
8.
Br J Dermatol ; 180(5): 1183-1189, 2019 05.
Article in English | MEDLINE | ID: mdl-30315656

ABSTRACT

BACKGROUND: Localized scleroderma (LS) is an autoimmune condition of the skin and underlying tissue. Active or recurring disease can lead to cumulative tissue damage, especially in paediatric-onset disease. OBJECTIVES: To highlight the rate of relapse of LS activity in a cohort of paediatric patients and to evaluate for potential clinical and laboratory predictors of disease relapse. METHODS: Clinical and laboratory data were gathered prospectively. Patients were categorized as experiencing relapse or not, and clinical and laboratory parameters were compared. A logistic regression was fit to predict odds of relapse while controlling for multiple predictors. A subgroup of patients was also evaluated to determine the average time from treatment completion to relapse. RESULTS: Seventy-seven patients were followed for the identified study duration of > 2 years and had achieved disease remission, with 35 (45%) experiencing LS relapse. Patients who were older at disease onset, antinuclear antibody (ANA) positive and without an extracutaneous manifestation (ECM) were more likely to relapse. All three variables remained significant in the multivariable logistic regression model. Results of the subgroup mirrored the larger sample. The average time between treatment completion and relapse was 21 months. CONCLUSIONS: Assessment of patients with LS experiencing a relapse of disease activity has shown older age of initial LS onset and ANA positivity to be potential markers for risk of relapse. Patients meeting these parameters may require greater clinical vigilance. The presence of one or more ECM may be protective. Clinicians treating patients with LS should provide significant long-term follow-up to monitor for relapse.


Subject(s)
Antibodies, Antinuclear/blood , Medication Adherence/statistics & numerical data , Scleroderma, Localized/diagnosis , Adolescent , Age of Onset , Antibodies, Antinuclear/immunology , Child , Child, Preschool , Cohort Studies , Disease Progression , Female , Glucocorticoids/therapeutic use , Humans , Male , Methotrexate/therapeutic use , Prognosis , Prospective Studies , Recurrence , Registries/statistics & numerical data , Remission Induction/methods , Retrospective Studies , Scleroderma, Localized/blood , Scleroderma, Localized/drug therapy , Scleroderma, Localized/immunology
9.
Transplant Proc ; 49(7): 1535-1537, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28838435

ABSTRACT

The first successful lung transplantation was done in 1963 by James Hardy in the United States. The Vienna Lung Transplant program was launched in 1989 by Professor Walter Klepetko, and in 1996 lung transplantation became available in this center also for Hungarian patients. By 2013, conditions for full-scale Hungarian lung transplantation program were ripe. The Hungarian government invested 3 million Euros for infrastructural developments that made the operation and the perioperative care available. Besides funding, the professional training of medical personnel was also essential for this program to start. Hungarian specialists have had internship opportunities to study all aspects of lung transplantation at the Thoracic Surgery Department in Vienna. After successful preparations, the first lung transplantation in Hungary was performed on December 12, 2015.


Subject(s)
Lung Transplantation , Program Development , Humans , Hungary , Program Evaluation
12.
Pharmazie ; 59(5): 412-6, 2004 May.
Article in English | MEDLINE | ID: mdl-15212312

ABSTRACT

In vitro and in vivo anti-inflammatory properties and soft characteristics of etiprednol dicloacetate (BNP-166) a new steroid, which has been developed for the treatment of asthma, were investigated in this study. The compound effectively decreased cytokine production in lipopolysaccharide stimulated lymphocytes and attenuated lectin-induced proliferation of blood mononuclear cells in tissue culture. In an animal model of allergen sensitized and challenged Brown Norway rats, using topical treatment, etiprednol dicloacetate substantially attenuated the extent of allergen induced bronchoalveolar fluid eosinophilia. At every examined parameter its pharmacological effects were comparable to those of budesonide. By means of in vitro biological and analytical methods the soft character of BNP-166 was also investigated. The anti-inflammatory effect of etiprednol dicloacetate in vitro was shown to be the function of the quantity of serum components, present in the assay. This loss of activity was most likely the result of the fast metabolism of etiprednol dicloacetate, which in the presence of sera could have been demonstrated by LC/MS/MS. Our data indicate that the significant local effect of the compound will very likely be accompanied with a drastically reduced systemic activity indicating an encouraging selectivity of the pharmacological action of etiprednol dicloacetate.


Subject(s)
Adrenal Cortex Hormones/pharmacology , Anti-Asthmatic Agents/pharmacology , Anti-Inflammatory Agents , Adrenal Cortex Hormones/pharmacokinetics , Animals , Anti-Asthmatic Agents/pharmacokinetics , Biotransformation , Bronchoalveolar Lavage Fluid/cytology , Budesonide/pharmacology , Cell Division/drug effects , Cell Line , Chromatography, Liquid , Enzyme-Linked Immunosorbent Assay , Granulocytes/drug effects , Humans , Interleukin-1/biosynthesis , Lectins/pharmacology , Lipopolysaccharides/pharmacology , Male , Mass Spectrometry , Monocytes/drug effects , Monocytes/metabolism , Rats , Rats, Inbred BN , Tumor Necrosis Factor-alpha/metabolism
13.
Biochem Soc Trans ; 30(2): 55-61, 2002 Apr.
Article in English | MEDLINE | ID: mdl-12023824

ABSTRACT

The conformation of Ca2+/calmodulin changes from extended when free in solution to compact when bound in peptide complexes. The extent and kinetics of calmodulin compaction in association with Ca2+/calmodulin-dependent protein kinases (CaMKs), as well as target peptides, were investigated by fluorescence, resonance energy transfer and stopped-flow kinetics. Compaction of Ca2+/calmodulin labelled with resonance energy-transfer probes in association with target peptides was rapid (>350 s(-1)). With the target enzymes smooth-muscle myosin light-chain kinase, CaMKIV and CaMKII, the rates of calmodulin compaction were one-two orders of magnitude lower compared with those of the peptides and in the case of alphaCaMKII, ATP binding and Thr(286) auto-phosphorylation were required for calmodulin compaction. In the absence of nucleotides, Ca2+/calmodulin bound to alphaCaMKII in extended conformations, initially probably attached by one lobe only. Kinetic data suggest that in the activation process of Ca2+/calmodulin-dependent protein kinases, productive as well as unproductive complexes are formed. The formation of productive complexes with Ca2+/calmodulin thus may determine the rate of activation.


Subject(s)
Calcium-Calmodulin-Dependent Protein Kinases/metabolism , Calmodulin/chemistry , Calmodulin/metabolism , Animals , Calcium-Calmodulin-Dependent Protein Kinase Type 2 , Calcium-Calmodulin-Dependent Protein Kinase Type 4 , Enzyme Activation , In Vitro Techniques , Kinetics , Macromolecular Substances , Muscle, Smooth/metabolism , Myosin-Light-Chain Kinase , Protein Conformation
14.
Biochemistry ; 40(49): 14878-90, 2001 Dec 11.
Article in English | MEDLINE | ID: mdl-11732908

ABSTRACT

The activation mechanism of Ca(2+)/calmodulin-dependent protein kinase II (alphaCaMKII) is investigated by steady-state and stopped-flow fluorescence spectroscopies. Lys(75)-labeled TA-cal [Török, K., and Trentham, D. R. (1994) Biochemistry 33, 12807-12820] is used to measure binding events, and double-labeled AEDANS,DDP-T34C/T110/C-calmodulin [Drum et al. (2000) J. Biol. Chem. 275, 36334-36340] (DA-cal) is used to detect changes in calmodulin conformation. Fluorescence quenching of DA-cal attributed to resonance energy transfer is related to the compactness of the calmodulin molecule. Interprobe distances are estimated by lifetime measurements of Ca(2+)/DA-cal in complexes with unphosphorylated nucleotide-free, nucleotide-bound, and Thr(286)-phospho-alphaCaMKII as well as with alphaCaMKII-derived calmodulin-binding peptides in the presence of Ca(2+). These measurements show that calmodulin can assume at least two spectrally distinct conformations when bound to alphaCaMKII with estimated interprobe distances of 40 and 22-26 A. Incubation with ATP facilitates the assumption of the most compact conformation. Nonhydrolyzable ATP analogues partially replicate the effects of ATP, suggesting that while the binding of ATP induces a conformational change, Thr(286)-autophosphorylation is probably required for the transition of calmodulin into its most compact conformer. The rate constant for the association of Ca(2+)/TA-cal with alphaCaMKII is estimated as 2 x 10(7) M(-1) s(-1) and is not substantially affected by the presence of ATP. The rate of net calmodulin compaction measured by Ca(2+)/DA-cal is markedly slower, occurring with a rate constant of 2.5 x 10(6) M(-1) s(-1), suggesting that unproductive complexes may play a role in the activation mechanism.


Subject(s)
Adenosine Triphosphate/metabolism , Brain/enzymology , Calcium-Calmodulin-Dependent Protein Kinases/metabolism , Calmodulin/metabolism , Adenosine Triphosphate/analogs & derivatives , Animals , Brain/metabolism , Calcium/metabolism , Calcium-Calmodulin-Dependent Protein Kinase Type 2 , Calcium-Calmodulin-Dependent Protein Kinases/genetics , Energy Transfer , Enzyme Activation , Humans , Ligands , Protein Binding , Protein Conformation , Spectrometry, Fluorescence
15.
Int J Obes Relat Metab Disord ; 25(7): 966-70, 2001 Jul.
Article in English | MEDLINE | ID: mdl-11443493

ABSTRACT

OBJECTIVE: To assess cardiorespiratory exercise function in obese children with and without metabolic syndrome (MS). DESIGN: Comparing three groups of subjects with different cardiovascular risk profiles. SUBJECTS: Twenty-two MS (body weight (mean+/-s.d.) 97.3+/-15.3 kg; age (mean+/-s.d.) 14.2+/-1.9 y), 17 obese (82.6+/-15.7 kg; 14.2+/-2.6 y) and 29 normal weight control (64.3+/-8.5 kg; 15.3+/-1.0 y) boys. MEASUREMENTS: Exercise duration (ED), resting heart rate (HR(0)), peak heart rate (HR(peak)), physical working capacity at 170 beat/min (PWC-170), peak oxygen consumption (VO(2peak)) and the lactic acidosis threshold (LAT) were determined on treadmill, using a continuous ramp protocol. RESULTS: ED (MS (mean+/-s.d.); 655+/-86 s; obese 703+/-64 s; control 750+/-0 s) in absolute value and PWC-170 normalised for body weight (139+/-40 w; 177+/-40 w; 211+/-40 w) were significantly shorter and lower in the MS group, as compared to obese and control groups (P<0.05). VO(2peak) (2.2+/-0.4 l/min; 2.4+/-0.5 l/min; 2.9+/-0.4 l/min) and LAT (1.3+/-0.4 l/min; 1.5+/-0.4 l/ min; 1.8+/-0.4 l/min) normalised for body weight, were significantly shorter and lower in the MS group, as compared to control group (P<0.05). HR(0) was significantly higher (P<0.05) in MS group than in obese and control groups (88+/-12 bpm; obese 78+/-10 bpm; 73+/-10 bpm). CONCLUSION: Cardiorespiratory exercise performance capacity in MS boys are reduced. It still remains to be elucidated whether the metabolic alterations or the decreased physical activity is responsible for the observed reduction in cardiorespiratory performance.


Subject(s)
Exercise/physiology , Heart Rate/physiology , Insulin Resistance , Obesity/physiopathology , Oxygen Consumption/physiology , Acidosis, Lactic , Adolescent , Cardiovascular Diseases , Case-Control Studies , Cohort Studies , Humans , Lipids/blood , Male , Risk Factors
16.
J Exp Bot ; 52(355): 215-21, 2001 Feb.
Article in English | MEDLINE | ID: mdl-11283165

ABSTRACT

A calmodulin like domain protein kinase (CPK) homologue was identified in alfalfa and termed MsCPK3. The full-length sequence of cDNA encoded a 535 amino acid polypeptide with a molecular weight of 60.2 kDa. The deduced amino acid sequence showed all the conserved motifs that define other members of this kinase family, such as serine-threonine kinase domain, a junction region and four potential Ca2+ -binding EF sites. The recombinant MsCPK3 protein purified from E. coli was activated by Ca2+ and inhibited by calmodulin antagonist (W-7) in in vitro phosphorylation assays. The expression of MsCPK3 gene increased in the early phase of the 2,4-D induced alfalfa somatic embryogenesis. Heat shock also activated this gene while kinetin, ABA and NaCl treatment did not result in MsCPK3 mRNA accumulation. The data presented suggest that the new alfalfa CPK differs in stress responses from the previously described homologues and in its potential involvement in hormone and stress-activated reprogramming of developmental pathways during somatic embryogenesis.


Subject(s)
Calcium-Calmodulin-Dependent Protein Kinases/genetics , Medicago sativa/enzymology , 2,4-Dichlorophenoxyacetic Acid/pharmacology , Abscisic Acid/pharmacology , Amino Acid Sequence , Cells, Cultured , Cloning, Molecular , DNA, Plant , Elongation Factor 2 Kinase , Escherichia coli/genetics , Genes, Plant , Heat-Shock Proteins/metabolism , Indoleacetic Acids/pharmacology , Medicago sativa/genetics , Molecular Sequence Data , Phosphorylation , Plant Growth Regulators/pharmacology , RNA, Plant , Recombinant Proteins/genetics , Sequence Analysis, DNA , Sequence Homology, Amino Acid , Signal Transduction
17.
J Mol Biol ; 308(1): 1-8, 2001 Apr 20.
Article in English | MEDLINE | ID: mdl-11302701

ABSTRACT

The subunit stoichiometry and symmetry of the neuronal alpha-calmodulin-dependent protein kinase II (alphaCaMKII) is investigated in this report to understand the structural basis of its regulation and mechanism at the molecular level. Two preparations are studied, alphaCaMKII obtained by overexpression in baculovirus-transfected insect cells and CaMKII isolated from rat forebrain. The structures, are studied by electron microscopy and image analysis. Single-particle analysis of individual molecular images reveals a molecule with a circular outline and pronounced 6-fold rotational symmetry of the central part. The central part has an outer radius of approximately 6 nm and is composed of six lobes grouped around a hollow centre. The outer ring extends to approximately 15 nm and consists of 12 apparent domains. These data are interpreted in terms of a three-dimensional model of the alphaCaMKII complex consisting of 12 subunits, each corresponding to a single alphaCaMKII polypeptide chain. The inner ring corresponding to approximately one-third of the molecular mass of the complex is made up of the C-terminal association domains. The 12 association domains are arranged in two concentric hexagonal rings at different axial levels and in rotational register. The outer ring corresponding to the remaining molecular mass of the complex is made up of the 12 N-terminal catalytic domains located at an axial level halfway between the two levels of the association domains. The 6-fold symmetry of stacked association domains may derive from subunit arrangements corresponding to either the C6 or the D6 point group symmetries. The symmetry and the resulting subunit arrangement define the pattern and extent of regulatory autophosphorylation within the alphaCaMKII complex.


Subject(s)
Brain/enzymology , Calcium-Calmodulin-Dependent Protein Kinases/chemistry , Animals , Baculoviridae/genetics , Calcium-Calmodulin-Dependent Protein Kinase Type 2 , Calcium-Calmodulin-Dependent Protein Kinases/genetics , Calcium-Calmodulin-Dependent Protein Kinases/metabolism , Catalytic Domain , Image Processing, Computer-Assisted , Isoenzymes/chemistry , Isoenzymes/genetics , Isoenzymes/metabolism , Microscopy, Electron , Models, Molecular , Molecular Weight , Phosphorylation , Protein Structure, Quaternary , Protein Subunits , Rats , Recombinant Proteins/chemistry , Recombinant Proteins/metabolism , Rotation
18.
Plant J ; 24(4): 437-46, 2000 Nov.
Article in English | MEDLINE | ID: mdl-11115125

ABSTRACT

Rapid accumulation of toxic products from reactions of reactive oxygen species (ROS) with lipids and proteins significantly contributes to the damage of crop plants under biotic and abiotic stresses. Here we have identified a stress-activated alfalfa gene encoding a novel plant NADPH-dependent aldose/aldehyde reductase that also exhibited characteristics of the homologous human enzyme. The recombinant alfalfa enzyme is active on 4-hydroxynon-2-enal, a known cytotoxic lipid peroxide degradation product. Ectopic synthesis of this enzyme in transgenic tobacco plants provided considerable tolerance against oxidative damage caused by paraquat and heavy metal treatment. These transformants could also resist a long period of water deficiency and exhibited improved recovery after rehydration. We found a reduced production of lipid peroxidation-derived reactive aldehydes in these transformed plants under different stresses. These studies reveal a new and efficient detoxification pathway in plants.


Subject(s)
Aldehyde Reductase/metabolism , Lipid Peroxidation , Nicotiana/metabolism , Plants, Toxic , Adaptation, Physiological/genetics , Aldehyde Reductase/drug effects , Aldehyde Reductase/genetics , Aldehydes/metabolism , Amino Acid Sequence , Gene Expression Regulation, Enzymologic/drug effects , Medicago sativa/cytology , Medicago sativa/drug effects , Medicago sativa/enzymology , Molecular Sequence Data , Oxidative Stress , Plants, Genetically Modified , Recombinant Fusion Proteins/genetics , Recombinant Fusion Proteins/metabolism , Sequence Homology, Amino Acid , Nicotiana/genetics , Water/pharmacology
19.
Int J Obes Relat Metab Disord ; 24(12): 1573-8, 2000 Dec.
Article in English | MEDLINE | ID: mdl-11126208

ABSTRACT

OBJECTIVE: The present study was performed to investigate the efficacy and safety of a caffeine/ephedrine (CE) mixture in obese adolescents. SUBJECTS: Thirty-two (m/f = 16/16) obese children were included into the study. They were treated by diet (calculated daily energy requirement minus 500 kcal) and either CE or placebo (PL) for 20 weeks in a randomized double-blind placebo-controlled trial. Those weighing less than 80 kg took one tablet three times (100 mg/10 mg), whereas those weighing more than 80 kg took two tablets three times per day. There were three dropouts (girls) from the PL group. The age, weight body mass index (BMI) values (mean (range)) of the PL and CE groups were 16.0 (14.3-17.6) and 16.0 (14.2-17.7) y, 103.0 (77.2-126.4) and 104.8 (69.8-150.2) kg, 35.2 (28.3-42.3) and 36.5 (31.3-51.8) kg/m2, respectively. RESULTS: The decrease in relative body weight, BMI and body fat (measured by bioelectric impedance) was significantly (P < 0.05) greater in the CE group (mean +/- s.d.; 14.4 +/- 10.5%, 2.9 +/- 1.9 kg/m2, 6.6 +/- 6.0 kg) than in the PL group (2.2 +/- 5.8%, 0.5 +/- 1.6 kg/m2, 0.5 +/- 2.7 kg). Relative body weight decreased by more than 5% in 81% of the CE group, out only in 31% of the PL group. Adverse events were negligible and did not differ between the CE and PL groups. Withdrawal symptoms were mild, transient and their frequency and severity were not different between the placebo and active groups. CONCLUSION: According to the present pilot study, CE can be a safe and effective compound for the treatment of obesity in adolescents.


Subject(s)
Caffeine/administration & dosage , Ephedrine/administration & dosage , Obesity/drug therapy , Adipose Tissue , Adolescent , Apolipoproteins B/blood , Blood Pressure , Body Composition , Caffeine/adverse effects , Caffeine/therapeutic use , Double-Blind Method , Electric Impedance , Energy Intake , Ephedrine/adverse effects , Ephedrine/therapeutic use , Female , Heart Rate , Humans , Male , Obesity/diet therapy , Obesity/physiopathology , Placebos , Substance Withdrawal Syndrome , Weight Loss
20.
Lipids ; 35(11): 1179-84, 2000 Nov.
Article in English | MEDLINE | ID: mdl-11132177

ABSTRACT

Previously we reported significantly higher values of gamma-linolenic acid (GLA, 18:3n-6), dihomo-gamma-linolenic acid (DHGLA, 20:3n-6), and arachidonic acid (20:4n-6) in plasma lipid classes in obese children than in nonobese controls. In the present study, fatty acid composition of plasma phospholipids (PL) and sterol esters (STE) was determined by high-resolution capillary gas-liquid chromatography in obese children with and without metabolic cardiovascular syndrome [MCS: defined as simultaneous presence of (i) dyslipidemia, (ii) hyperinsulinemia, (iii) hypertension, and.(iv) impaired glucose tolerance] and in nonobese controls. Fatty acid composition of PL and STE lipids did not differ between obese children without MCS and controls. Obese children with MCS exhibited significantly lower linoleic acid (LA, 18:2n-6) values in PL (17.43 [2.36], % wt/wt, median [range from the first to the third quartile]) than obese children without MCS (19.14 [3.49]) and controls (20.28 13.80]). In contrast, PL GLA values were significantly higher in obese children with (0.13 [0.08]) than in those without MCS (0.08 [0.04]), whereas STE GLA values were higher in obese children with MCS (1.04 [0.72]) than in controls (0.62 [0.48]). DHGLA values in PL were significantly higher in obese children with MCS (4.06 [0.74]) than in controls (2.69 [1.60]). The GLA/LA ratio was significantly higher, whereas the AA/DHGLA ratio was significantly lower in obese children with MCS than in obese children without MCS and in controls. In this study, LA metabolism was affected only in obese children with but not in those without MCS. In obese children with MCS, delta6-desaturase activity appeared to be stimulated, whereas delta5-desaturase activity appeared to be inhibited. Disturbances in LA metabolism may represent an additional health hazard within the multifaceted clinical picture of MCS.


Subject(s)
Fatty Acids, Unsaturated/blood , Lipids/blood , Microvascular Angina/blood , Obesity/blood , Adolescent , Case-Control Studies , Child , Chromatography, Gas , Female , Humans , Lipids/chemistry , Male
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