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1.
Scand J Rheumatol ; 51(2): 110-119, 2022 Mar.
Article in English | MEDLINE | ID: mdl-34251963

ABSTRACT

OBJECTIVE: To investigate aspects of validity and reliability of the Swedish version of the Self-Efficacy for Managing Chronic Disease (SEMCD-Swe) scale in systemic sclerosis (SSc). METHOD: A forward-backward translation procedure was used. Content validity was assessed through interviews with 11 people with SSc and 10 healthcare professionals. Construct validity, internal consistency, test-retest reliability, and floor and ceiling effects were evaluated in 104 SSc patients. RESULTS: The content validity of the SEMCD-Swe was interpreted as satisfactory, but some adjustments were made to increase the understanding. Confirmatory factor analysis supported a single-factor structure. Moderate to strong correlations between the SEMCD-Swe and Scleroderma Health Assessment Questionnaire; Multidimensional Assessment of Fatigue; Patient Health Questionnaire-8 (rs = -0.4 to -0.7), and RAND-36 subscales (rs = 0.5 to 0.7) were found. Weak correlations were found between SEMCD-Swe and modified Rodnan skin score; and disease severity of peripheral vascular and lung (rs = -0.1 to -0.2) and kidney (rs = 0.1) systems (Medsger severity scale). Cronbach's alpha was sufficient (0.85) and corrected item-to-total correlations were good (≥ 0.50). The intraclass correlation coefficient for the total score was sufficient (0.82). No floor or ceiling effects were found. CONCLUSION: Support for construct validity was indicated, as the SEMCD-Swe in SSc show a single-factor structure and is more strongly associated with pain, fatigue, depressive symptoms, interferences with daily activities, disability, and quality of life than with disease severity. Our results also indicate support for content validity and reliability. However, the responsiveness of the SEMCD-Swe needs to be tested.


Subject(s)
Scleroderma, Systemic , Self Efficacy , Chronic Disease , Fatigue/complications , Humans , Psychometrics , Quality of Life , Reproducibility of Results , Scleroderma, Systemic/complications , Surveys and Questionnaires , Sweden
2.
Int Immunopharmacol ; 90: 107226, 2021 Jan.
Article in English | MEDLINE | ID: mdl-33316742

ABSTRACT

Rituximab is widely used in the treatment of haematological malignancies, including chronic lymphocytic leukaemia (CLL), the most common leukaemia in adults. However, some patients, especially those with high tumour burden, develop cytokine release syndrome (CRS). It is likely that more patients will develop therapy-linked CRS in the future due to the implementation of other immunotherapies, such as CAR T-cell, for many malignancies. Current methods for CRS risk assessment are limited, hence there is a need to develop new methods. To better recapitulate an in vivo setting, we implemented a unique human whole blood "loop" system to study patient-specific immune responses to rituximab in blood derived from CLL patients. Upon rituximab infusion, both complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC) profiles were evident in CLL patient blood, coincident with CLL cell depletion. Whereas B cell depletion is induced in healthy persons in the blood loop, only patients display B cell depletion coupled with CRS. With the exception of one donor who lacked NK cells, all other five patients displayed variable B cell depletion along with CRS profile. Additionally, inhibition of CDC or ADCC via either inhibitors or antibody Fc modification resulted in skewing of the immune killing mechanism consistent with published literature. Herein we have shown that the human whole blood loop model can be applied using blood from a specific indication to build a disease-specific CRS and immune activation profiling ex vivo system. Other therapeutic antibodies used for other indications may benefit from antibody characterization in a similar setting.


Subject(s)
Antineoplastic Agents, Immunological/therapeutic use , Leukemia, Lymphocytic, Chronic, B-Cell/immunology , Rituximab/therapeutic use , Aged , Aged, 80 and over , Antirheumatic Agents , B-Lymphocytes/immunology , Blood Cell Count , Complement Activation , Cytokine Release Syndrome/etiology , Cytokine Release Syndrome/immunology , Cytokines/blood , Cytotoxicity, Immunologic , Female , Humans , Immunoglobulin Fc Fragments/immunology , Killer Cells, Natural , Leukemia, Lymphocytic, Chronic, B-Cell/complications , Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy , Leukocyte Count , Male
3.
Physiother Theory Pract ; 35(1): 80-93, 2019 Jan.
Article in English | MEDLINE | ID: mdl-29482403

ABSTRACT

Physiotherapists are facing complex health challenges in the treatment of persons suffering from long-lasting musculoskeletal disorders and mental health problems. Basic Body Awareness Therapy (BBAT) is a physiotherapy approach within the movement awareness domain developed to bridge physical, mental, and relational health challenges. The purpose of this study was to reach a consensus on core phenomena and statements describing BBAT. A consensus-building process was conducted using the nominal group technique (NGT). Twenty-one BBAT experts from 10 European countries participated in a concentrated weekend workshop of 20 hours. All participants signed informed consent. Participants reached a consensus on 138 core phenomena, clustered in three overarching categories: clinical core, historical roots, and research and evaluation phenomena. Of the 106 clinical core phenomena, the participants agreed on three categories of phenomena: movement quality, movement awareness practice, and movement awareness therapy and pedagogy. Furthermore, the participants reached 100 percent consensus on 16 of 30 statements describing BBAT. This study provides a consensus on core phenomena and statements describing BBAT. The data reveal phenomena implemented when promoting movement quality through movement awareness. Data provide clarity in some aspects of the vocabulary as fundamental theory. Further reearch will be developed.


Subject(s)
Awareness , Movement , Physical Therapy Modalities , Humans
4.
NPJ Precis Oncol ; 2: 18, 2018.
Article in English | MEDLINE | ID: mdl-30182064

ABSTRACT

Development of antibody drugs against novel targets and pathways offers great opportunities to improve current cancer treatment. We here describe a phenotypic discovery platform enabling efficient identification of therapeutic antibody-target combinations. The platform utilizes primary patient cells throughout the discovery process and includes methods for differential phage display cell panning, high-throughput cell-based specificity screening, phenotypic in vitro screening, target deconvolution, and confirmatory in vivo screening. In this study the platform was applied on cancer cells from patients with Chronic Lymphocytic Leukemia resulting in discovery of antibodies with improved cytotoxicity in vitro compared to the standard of care, the CD20-specific monoclonal antibody rituximab. Isolated antibodies were found to target six different receptors on Chronic Lymphocytic Leukemia cells; CD21, CD23, CD32, CD72, CD200, and HLA-DR of which CD32, CD200, and HLA-DR appeared as the most potent targets for antibody-based cytotoxicity treatment. Enhanced antibody efficacy was confirmed in vivo using a patient-derived xenograft model.

5.
J Intern Med ; 279(4): 347-57, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26709197

ABSTRACT

The remarkable clinical heterogeneity in chronic lymphocytic leukaemia (CLL) has highlighted the need for prognostic and predictive algorithms that can be employed in clinical practice to assist patient management and therapy decisions. Over the last 20 years, this research field has been rewarding and many novel prognostic factors have been identified, especially at the molecular genetic level. Whilst detection of recurrent cytogenetic aberrations and determination of the immunoglobulin heavy variable gene somatic hypermutation status have an established role in outcome prediction, next-generation sequencing has recently revealed novel mutated genes with clinical relevance (e.g. NOTCH1, SF3B1 and BIRC3). Efforts have been made to combine variables into prognostic indices; however, none has been universally adopted. Although a unifying model for all groups of patients and in all situations is appealing, this may prove difficult to attain. Alternatively, focused efforts on patient subgroups in the same clinical context and at certain clinically relevant 'decision points', that is at diagnosis and at initiation of first-line or subsequent treatments, may provide a more accurate approach. In this review, we discuss the advantages and disadvantages as well as the clinical applicability of three recently proposed prognostic models, the MD Anderson nomogram, the integrated cytogenetic and mutational model and the CLL-international prognostic index. We also consider future directions taking into account novel aspects of the disease, such as the tumour microenvironment and the dynamics of (sub)clonal evolution. These aspects are particularly relevant in view of the increasing number of new targeted therapies that have recently emerged.


Subject(s)
Leukemia, Lymphoid/diagnosis , Decision Support Techniques , Genes, p53/genetics , Humans , Leukemia, Lymphoid/genetics , Mutation , Prognosis
6.
Eur J Phys Rehabil Med ; 51(4): 405-21, 2015 Aug.
Article in English | MEDLINE | ID: mdl-25573599

ABSTRACT

BACKGROUND: Systemic sclerosis (SSc) is an autoimmune disease where thickening of the skin can lead to reduced body function and limitations in activities. Severe forms can also affect and seriously damage inner organs. Patient-centred rehabilitation emphasises considerations of patients' background, experience and behavior which highlights the need to know if patient-reported outcome measures (PROMs) include such personal factors. AIM: To identify and describe personal factors in the experiences of functioning and health of persons with SSc and to examine if and to what extent PROMs in SSc research cover these factors. DESIGN: Data from a qualitative study with focus group interviews were analysed. PROMs in SSc research were identified in a literature review between 2008-2013. SETTING: Participants were recruited from outpatient clinics at rheumatology department. POPULATION: Sixty-three patients with SSc from four European countries participated. METHODS: Data from interviews were analysed using a structure of personal factors developed by Geyh et al. Identified PROMs were analysed and linked to main concepts, related to the personal factors, found in the interview data. RESULTS: Nineteen main concepts were related to the area "patterns of experience and behaviour" in the personal factor structure, 16 to "thoughts and beliefs", nine to "feelings", one to "motives" and one to "personal history and biography", respectively. Among the 35 PROMs identified, 15 did not cover any of the identified concepts. Concepts within the area "feelings" were mostly covered by the PROMs. Five of the PROMs covered "patterns of experience and behaviour", while "motives" and "personal history and biography" were not covered at all. Four of the identified PROMs covered concepts within the areas "feelings", "thoughts and beliefs" and "patterns of experience and behaviour" in the same instrument. The Illness Cognition Questionnaire and Illness Behaviour Questionnaire were such PROMs. CONCLUSION: Patterns of experience and behaviour had the highest number of concepts related to personal factors, but few of the PROMs in SSc research covered these factors. Only a few PROMs covered several personal factors areas in the same instrument. CLINICAL REHABILITATION IMPACT: The results would be of value when developing core sets for outcome measurements in SSc.


Subject(s)
Disability Evaluation , Multicenter Studies as Topic , Patient Outcome Assessment , Qualitative Research , Scleroderma, Systemic/rehabilitation , Europe , Humans
7.
J Evol Biol ; 25(5): 961-71, 2012 May.
Article in English | MEDLINE | ID: mdl-22435643

ABSTRACT

Prezygotic isolation due to habitat choice is important to many models of speciation-with-gene-flow. Habitat choice is usually thought to occur through positive preferences of organisms for particular environments. However, avoidance of non-natal environments may also play a role in choice and have repercussions for post-zygotic isolation that preference does not. The recent host shift of Rhagoletis pomonella (Diptera: Tephritidae) from downy hawthorn, Crataegus mollis, to introduced apple, Malus domestica, in the eastern United States is a model for speciation-with-gene-flow. However, the fly is also present in the western United States where it was likely introduced via infested apples ≤ 60 years ago. R. pomonella now attacks two additional hawthorns in the west, the native C. douglasii (black hawthorn) and the introduced C. monogyna (English ornamental hawthorn). Flight tunnel tests have shown that western apple-, C. douglasii- and C. monogyna-origin flies all positively orient to fruit volatile blends of their respective natal hosts in flight tunnel assays. Here, we show that these laboratory differences translate to nature through field-trapping studies of flies in the state of Washington. Moreover, western R. pomonella display both positive orientation to their respective natal fruit volatiles and avoidance behaviour (negative orientation) to non-natal volatiles. Our results are consistent with the existence of behaviourally differentiated host races of R. pomonella in the west. In addition, the rapid evolution of avoidance behaviour appears to be a general phenomenon for R. pomonella during host shifts, as the eastern apple and downy hawthorn host races also are antagonized by non-natal fruit volatiles.


Subject(s)
Avoidance Learning , Behavior, Animal/physiology , Discrimination, Psychological/physiology , Fruit/chemistry , Odorants , Tephritidae/physiology , Animals , Crataegus/chemistry , Female , Gene Flow , Genetic Speciation , Male , Malus/chemistry , Olfactory Perception , Species Specificity , Volatile Organic Compounds/chemistry , Volatilization , Washington
8.
Musculoskeletal Care ; 10(1): 1-12, 2012 Mar.
Article in English | MEDLINE | ID: mdl-22009870

ABSTRACT

UNLABELLED: Systemic lupus erythematosus (SLE) is a chronic disease which can affect any organ, and the impact of the condition will affect each person differently. There are few qualitative studies including the experiences of both women and men with a diagnosis of SLE corresponding to the American College of Rheumatology (ACR) criteria where both negative and positive impacts of the disease have been presented. PURPOSE: The aim was to describe how patients with established SLE experience their illness in everyday life, including both negative and positive aspects. METHOD: Four focus group interviews were conducted with 16 women and three men with SLE according to ACR criteria, with varied disease activity and no or little organ damage. The interviews were tape recorded, transcribed verbatim and analysed using qualitative content analysis. RESULTS: Two themes emerged: multifaceted uncertainty contained the categories 'an unreliable body', 'obtrusive pain and incomprehensible fatigue', 'mood changes and worries', 'reliance on medication and health care'; Focus on health and opportunities included 'learning process implying personal strength', 'limitations and possibilities in activities and work', 'a challenge to explain and receive support' and 'living an ordinary life incorporating meaningful occupations'. CONCLUSIONS: While we expected to find a mainly negative impact, positive aspects were also described. Our findings were complex and showed that patients with established SLE can experience both uncertainty and opportunities. This highlights the importance for healthcare professionals of gaining a better understanding of patients' uncertainty, to enable them to support patients, allowing them to focus on health and opportunities. Measurement instruments that capture different aspects of uncertainty and opportunities needs to be developed.


Subject(s)
Lupus Erythematosus, Systemic/psychology , Activities of Daily Living , Adult , Affect , Aged , Aged, 80 and over , Fatigue/etiology , Female , Focus Groups , Humans , Lupus Erythematosus, Systemic/complications , Male , Middle Aged , Pain/etiology , Uncertainty
9.
Indoor Air ; 21(6): 454-61, 2011 Dec.
Article in English | MEDLINE | ID: mdl-21615502

ABSTRACT

UNLABELLED: Several studies have found that indoor air quality (IAQ) in schools is often poor and may affect the health of the pupils. Building ventilation is a means to reduce pollutants indoors, but different designs should be evaluated for their effectiveness in different environments. In a field experiment performed at four classrooms in one school building, air was supplied either in the mixing or in the displacement mode, and we collected information on exposures, pupils' perception of IAQ and climate, and health symptoms and performed clinical examinations. The room temperature, relative humidity, concentration of CO2, and cat allergen were measured at the breathing height and were similar during each ventilation mode. The children perceived IAQ were similar in the two ventilation regimes, and there were few differences in symptom reports or clinical parameters. However, the pupils reported more eye symptoms during displacement ventilation. PRACTICAL IMPLICATIONS: Both mixing and displacement ventilation may be appropriate in school classrooms as long as the overall design, ventilation rates, and maintenance of systems are satisfactory.


Subject(s)
Air Pollution, Indoor/analysis , Schools , Students , Ventilation/methods , Air Movements , Allergens/immunology , Allergens/metabolism , Animals , Carbon Dioxide/analysis , Cats , Child , Child, Preschool , Humans , Humidity , Perception , Risk Factors , Temperature , Ventilation/instrumentation , Ventilation/standards
10.
Scand J Rheumatol ; 37(4): 269-77, 2008.
Article in English | MEDLINE | ID: mdl-18612927

ABSTRACT

OBJECTIVE: The aim was to translate, test, and describe aspects of reliability and validity of the Fatigue Severity Scale (FSS) in Swedish (FSS-Swe) in patients with systemic lupus erythematosus (SLE). METHODS: Patients with stable SLE, low or moderate disease activity, and low organ damage were included. Forward and back translations of the FSS were performed. Construct validity was tested with 32 women using a first Swedish translation. Feasibility, ceiling and floor effects, internal consistency, test-retest reliability, and content validity were tested on a slightly modified final version of the FSS-Swe in a non-selected group of patients (n = 23). RESULTS: There were correlations (p< or =0.05) between the FSS-Swe and overall disease activity according to the Systemic Lupus Activity Measure (SLAM) (r(s) = 0.48) and the SLAM Visual Analogue Scale (SLAM-VAS) (r(s) = 0.46); between the FSS-Swe and eight subscales of the Swedish 36-Item Medical Outcomes Study Short-Form Health Survey (SF-36) (r(s) = -0.41 to -0.65) and between the FSS-Swe and age (r(s) = -0.35). All patients answered all FSS-Swe questions at both test and retest. There was one ceiling effect in one question on one occasion. The Kolmogorov-Smirnov test indicated normal distribution. Cronbach's alpha was 0.94 and corrected item-to-total correlation exceeded 0.3. There were no significant systematic test-retest differences, and the median-weighted kappa coefficient was 0.75. Twenty patients understood the questions in FSS-Swe, 18 considered they were relevant, reflected their fatigue, and that none should be excluded. Five items were suggested to be included. CONCLUSIONS: The FSS-Swe supports construct validity, is feasible, has no important ceiling or floor effects, has satisfactory internal consistency, substantial test-retest reliability, and satisfactory content validity in the SLE patients studied. However, its sensitivity to change needs to be tested.


Subject(s)
Fatigue/physiopathology , Lupus Erythematosus, Systemic/physiopathology , Severity of Illness Index , Adult , Female , Humans , Male , Middle Aged , Reproducibility of Results , Sweden
11.
Acta Psychiatr Scand ; 114(4): 274-81, 2006 Oct.
Article in English | MEDLINE | ID: mdl-16968365

ABSTRACT

OBJECTIVE: To evaluate "need-specific treatment" of first episode schizophrenia syndrome patients. METHOD: Sixty-one consecutive first episode schizophrenia syndrome patients were followed over 3 years. They were compared with a Historical "treatment as usual" group (n = 41) and a Prospective group from a high quality social and biological psychiatry centre (n = 25). RESULTS: Symptomatic and functional outcome was significantly better compared with the Historical group and equal with the Prospective group. During the first year, the direct costs for in- and out-patient care per patient in the Parachute project were less than half of those in the Prospective group. CONCLUSION: The study confirms the feasibility, clinically and economically, with a large scale application of "need-specific treatments" for first episode psychotic patients.


Subject(s)
Mental Health Services/economics , Schizophrenia/economics , Schizophrenia/therapy , Adult , Ambulatory Care/economics , Cohort Studies , Episode of Care , Feasibility Studies , Female , Follow-Up Studies , Health Care Costs , Hospitalization/economics , Humans , Male , Prospective Studies , Schizophrenia/epidemiology , Sweden/epidemiology , Time Factors
12.
Radiat Environ Biophys ; 45(1): 55-62, 2006 May.
Article in English | MEDLINE | ID: mdl-16552570

ABSTRACT

The aim of this study is to investigate if 1,800 MHz radiofrequency electromagnetic fields (RF-EMF) can induce reactive oxygen species (ROS) release and/or changes in heat shock protein 70 (Hsp70) expression in human blood cells, using different exposure and co-exposure conditions. Human umbilical cord blood-derived monocytes and lymphocytes were used to examine ROS release after exposure to continuous wave or different GSM signals (GSM-DTX and GSM-Talk) at 2 W/kg for 30 or 45 min of continuous or intermittent (5 min ON/5 min OFF) exposure. The cells were exposed to incubator conditions, to sham, to RF-EMF, or to chemicals in parallel. Cell stimulation with the phorbol ester phorbol-12-myristate-13-acetate (PMA; 1 microM) was used as positive control for ROS release. To investigate the effects on Hsp70 expression, the human monocytes were exposed to the GSM-DTX signal at 2 W/kg for 45 min, or to heat treatment (42 degrees C) as positive control. ROS production and Hsp70 expression were determined by flow cytometric analysis. The data were compared to sham and/or to control values and the statistical analysis was performed by the Student's t-test (P<0.05). The PMA treatment induced a significant increase in ROS production in human monocytes and lymphocytes when the data were compared to sham or to incubator controls. After continuous or intermittent GSM-DTX signal exposure (2 W/kg), a significantly different ROS production was detected in human monocytes if the data were compared to sham. However, this significant difference appeared due to the lowered value of ROS release during sham exposure. In human lymphocytes, no differences could be detected if data were compared either to sham or to incubator control. The Hsp70 expression level after 0, 1, and 2 h post-exposure to GSM-DTX signal at 2 W/kg for 1 h did not show any differences compared to the incubator or to sham control.


Subject(s)
Electromagnetic Fields , HSP70 Heat-Shock Proteins/physiology , Monocytes/radiation effects , Reactive Oxygen Species , Antigens, CD/biosynthesis , Antigens, Differentiation, T-Lymphocyte/biosynthesis , Dose-Response Relationship, Radiation , Flow Cytometry , Humans , Immunophenotyping , Lectins, C-Type , Lymphocytes/metabolism , Monocytes/metabolism , Radio Waves , Tetradecanoylphorbol Acetate/pharmacology , Umbilical Cord/radiation effects , Umbilical Veins/cytology
13.
Toxicol Lett ; 161(1): 73-82, 2006 Feb 08.
Article in English | MEDLINE | ID: mdl-16153791

ABSTRACT

The contemporary urban environment has become increasingly complex in its composition, leading to discussions regarding possible novel health effects. Two factors that recently have received considerable attention are ultrafine particles (UFP; <0.1 microm) produced by combustion processes and emissions from wireless communication devices like mobile phones that emit in the radio-frequency (RF) part of the spectrum. Several studies have shown biological effects of both these exposures in various cell systems. Here we investigate if exposure to UFP (12-14 nm, 100 microg/ml) and RF-electromagnetic fields (EMF; 2 W/kg specific absorption rate (SAR); continuous wave (CW) or modulated (217Hz or GSM-nonDTX)), alone or in combination influences levels of the superoxide radical anion or the stress protein heat-shock protein (Hsp70) in the human monocyte cell line Mono Mac 6. Heat treatment (42-43 degrees C, 1h) was used as positive control for both stress reaction and for heat development in the RF exposure setup. Our results clearly show that Mono Mac 6 cells are capable to internalise UFP, and that this phagocytic activity is connected to an increased release of free radicals. This increase (40-45% above negative control) is stronger than the effect of heat treatment. On the other hand, none of the employed RF exposures showed any effects on free radical levels. Co-exposure of RF and UFP did not potentiate the UFP effect either. Our investigations showed a significantly increased Hsp70 expression level by heat treatment in a time-dependent manner, whereas UFP, RF, or UFP+RF were without any effect. Therefore, we conclude that in the investigated Mono Mac 6 cells, RF exposure alone or in combination with UFP cannot influence stress-related responses.


Subject(s)
Free Radicals/metabolism , HSP70 Heat-Shock Proteins/biosynthesis , Radio Waves , Blotting, Western , Cell Line, Tumor , Cytochromes c/metabolism , Electromagnetic Fields , Flow Cytometry , Hot Temperature , Humans , In Vitro Techniques , Particle Size , Phagocytosis/radiation effects , Superoxides/metabolism , Time Factors
14.
Acta Psychiatr Scand ; 106(4): 276-85, 2002 Oct.
Article in English | MEDLINE | ID: mdl-12225494

ABSTRACT

OBJECTIVE: Implementing a system designed to treat first episode psychotic (FEP) patients. METHOD: Every FEP patient (n=253) from a catchment area of 1.5 million inhabitants were asked to participate in this 5-year project. One historical (n=71) and one prospective (n=64) FEP group were used for comparisons. RESULTS: A total of 175 patients (69%) were followed up through the first year of treatment. Global Assessment of Functioning (GAF) values were significantly higher than in the historical comparison group but similar to the prospective group. Psychiatric in-patient care was lower as was prescription of neuroleptic medication. Satisfaction with care was generally high in the Parachute group. Access to a small overnight crisis home was associated with higher GAF. CONCLUSION: It is possible to successfully treat FEP patients with fewer in-patient days and less neuroleptic medication than is usually recommended, when combined with intensive psychosocial treatment and support.


Subject(s)
Mental Health Services/standards , Psychotic Disorders/rehabilitation , Antipsychotic Agents/therapeutic use , Brief Psychiatric Rating Scale , Follow-Up Studies , Hospitalization/statistics & numerical data , Humans , Prospective Studies , Psychotic Disorders/diagnosis , Psychotic Disorders/drug therapy , Severity of Illness Index , Social Support , Sweden , Treatment Outcome
15.
J Exp Bot ; 53(370): 883-90, 2002 Apr.
Article in English | MEDLINE | ID: mdl-11912231

ABSTRACT

Much controversy exists about whether or not NH(+)(4) is translocated in the xylem from roots to shoots. In this paper it is shown that such translocation can indeed take place, but that interference from other metabolites such as amino acids and amines may give rise to large uncertainties about the magnitude of xylem NH(+)(4) concentrations. Elimination of interference requires sample stabilization by, for instance, formic acid or methanol. Subsequent quantification of NH(+)(4) should be done by the OPA-fluorometric method at neutral pH with 2-mercaptoethanol as the reducing agent since this method is sensitive and reliable. Colorimetric methods based on the Berthelot reaction should never be used, as they are prone to give erroneous results. Significant concentrations of NH(+)(4), exceeding 1 mM, were measured in both xylem sap and leaf apoplastic solution of oilseed rape and tomato plants growing with NO(-)(3) as the sole N source. When NO(-)(3) was replaced by NH(+)(4), xylem sap NH(+)(4) concentrations increased with increasing external concentrations and with time of exposure to NH(+)(4). Up to 11% of the translocated N was constituted by NH(+)(4). Glutamine synthetase (GS) incorporates NH(+)(4) into glutamine, but root GS activity and expression were repressed when high levels of NH(+)(4) were supplied. Ammonium concentrations measured in xylem sap sampled just above the stem base were highly correlated with NH(+)(4) concentrations in apoplastic solution from the leaves. Young leaves tended to have higher apoplastic NH(+)(4) concentrations than older non-senescing leaves. The flux of NH(+)(4) (concentration multiplied by transpirational water flow) increased with temperature despite a decline in xylem NH(+)(4) concentration. Retrieval of leaf apoplastic NH(+)(4) involves both high and low affinity transporters in the plasma membrane of mesophyll cells. Current knowledge about these transporters and their regulation is discussed.


Subject(s)
Cation Transport Proteins , Plant Proteins , Plant Structures/metabolism , Plants/metabolism , Quaternary Ammonium Compounds/metabolism , Amines/metabolism , Amino Acids/metabolism , Biological Transport/drug effects , Carrier Proteins/genetics , Cell Wall/metabolism , Gene Expression Regulation, Plant/drug effects , Glutamic Acid/pharmacology , Glutamine/pharmacology , Nitrates/pharmacology , Plants/genetics , Quaternary Ammonium Compounds/analysis , Quaternary Ammonium Compounds/pharmacology
16.
Pharmacol Toxicol ; 89(1): 56-64, 2001 Jul.
Article in English | MEDLINE | ID: mdl-11484911

ABSTRACT

Chlorinated fatty acids represent a recently discovered group of potentially hazardous organochlorine pollutants in the environment. The ability of human cells to incorporate and metabolise this type of fatty acids has never been investigated. The aim of the present study was, therefore, to investigate if two human cell lines, INT 407 and SH-SY5Y, incorporate and metabolise extracellular dichlorostearic acid. Cells were incubated with 9,10-dichlorostearic acid for 24 hr, and the amounts of chlorinated fatty acids in cells and culture medium analysed every two days for up to 6 or 10 days. Lipids were separated by solid phase extraction, transesterified to fatty acid methyl esters, and analysed by gas chromatography in combination with a halogen specific detector (GC/XSD). Dichlorostearic acid, dichloropalmitic acid and dichloromyristic acid were found in phospholipids and in neutral lipids of the INT 407 cells. Both cell lines secreted considerable amounts of dichloromyristic acid into the culture medium. Cellular or secreted metabolites shorter than dichloromyristic acid were not found. Taken together, the results suggest that human cells may (1) incorporate chlorinated fatty acids into membrane lipids and storage lipids, (2) metabolise cellular dichlorostearic acid to dichloropalmitic acid and dichloromyristic acid by B-oxidation; but that further metabolism is hindered, possibly because of the chlorine atoms, and (3) remove formed dichloromyristic acid by secretion. The removal of cellular dichloromyristic acid might represent an important cellular defence mechanism and deserves further investigations.


Subject(s)
Fatty Acids/metabolism , Hydrocarbons, Chlorinated/metabolism , Cell Line , Humans , Intestinal Mucosa/metabolism , Neuroblastoma/metabolism
17.
Cell Biol Int ; 25(9): 901-7, 2001.
Article in English | MEDLINE | ID: mdl-11518497

ABSTRACT

Jurkat E6-1 cells obtained from three different sources were compared with respect to intracellular calcium response to a 50 Hz, 0.15 mT, magnetic field, to treatment with poly-L-lysine and to protein expression at the cell surface. The fura-2 single cell measurements were a replication study performed by three members of our group. The cells responded to the applied magnetic fields, although the percentage of responding cells was lower than in earlier studies. The geomagnetic field was backed off without changing the outcome of the intracellular calcium measurements. Fluorometric analyses showed no difference between the E6-1 cells obtained from three sources with respect to the expression of cell surface marker molecules. The addition of the cell adhesive peptide, poly-L-lysine, did not itself cause any effects on the intracellular calcium concentration.


Subject(s)
Calcium/metabolism , Electromagnetic Fields , T-Lymphocytes/metabolism , Antigens, Differentiation, T-Lymphocyte/analysis , Fluorescent Dyes/chemistry , Fluorometry , Fura-2/chemistry , Humans , Jurkat Cells , Polylysine/pharmacology , Reproducibility of Results , T-Lymphocytes/drug effects
18.
Bioelectrochemistry ; 53(1): 73-8, 2001 Jan.
Article in English | MEDLINE | ID: mdl-11206927

ABSTRACT

The human T cell line Jurkat registers a sinusoidal extremely low frequency (ELF), 0.10 mT magnetic fields (MFs) at the level of the plasma membrane. In this study, the protein tyrosine phosphorylation (PY) of two membrane-associated proteins in Jurkat cells were examined following a short-term MFs exposure, the zeta chains and the Src kinases p56lck. These proteins are interesting to study since the earliest biochemical event upon T cell receptor (TcR) activation is PY of the zeta chains. These signalling chains in the TcR complex was assessed using Western blotting and the activation of the p56lck kinase was analysed by in vitro kinase assay. The MFs exposure of Jurkat for 5 min activated p56lck and resulted in PY of zeta. These findings are in line with earlier reports on how MFs exposure affects signal transduction in Jurkat.


Subject(s)
Lymphocyte Specific Protein Tyrosine Kinase p56(lck)/radiation effects , Magnetics , Receptors, Antigen, T-Cell/radiation effects , Blotting, Western , Humans , Jurkat Cells/radiation effects , Kinetics , Lymphocyte Specific Protein Tyrosine Kinase p56(lck)/metabolism , Membrane Proteins/radiation effects , Phosphorylation/radiation effects , Receptors, Antigen, T-Cell/metabolism , Signal Transduction/radiation effects
20.
Int J Pharm ; 202(1-2): 141-9, 2000 Jul 20.
Article in English | MEDLINE | ID: mdl-10915937

ABSTRACT

Powders absorb water by both capillary imbibition and swelling. The capillary process is almost instantaneous but swelling occurs over a period of time. An isothermal transient ionic current technique was used in this study to characterise the instantaneous absorption properties (rate and capacity) of a few selected pharmaceutical excipients. The results indicate that the instantaneous and long term water absorption properties of pharmaceutical powders can differ considerably. The rate of instantaneous water absorption appears to correlate with the total surface area while the absorption capacity correlates more with the porosity of the powder.


Subject(s)
Excipients/pharmacokinetics , Powders/pharmacokinetics , Absorption/drug effects
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