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1.
Z Rheumatol ; 80(2): 132-139, 2021 Mar.
Article in English | MEDLINE | ID: mdl-32676754

ABSTRACT

Despite widespread recommendations for involving patient research partners (PRPs), there is little information about how patients have been involved in research. Our aim was to describe and assess the contributions of four PRPs in a project on communication-skills training funded by Deutsche Rheuma-Liga Bundesverband e. V. (German League Against Rheumatism [GLR] is a patient organisation for people with rheumatic and musculoskeletal diseases). The PRPs' participation was beneficial with regards to content and organisation. Thanks to their participation, we could enlarge our sample by over a third, and they contributed their own ideas to the training. Four PRPs added their perspective of various regional organisations. Outside this project, they were also very active within GLR and experienced in managing their rheumatic disease. To achieve more representativeness, future studies might also employ strategies to engage individuals with less experience in dealing with their disease, e.g. newly diagnosed patients. While the collaboration between PRPs and researchers proved very successful, more regular discussions about tasks and responsibilities would be worthwhile.


Subject(s)
Communication , Musculoskeletal Diseases , Rheumatic Diseases , Humans , Rheumatic Diseases/diagnosis , Rheumatic Diseases/therapy
2.
Patient Educ Couns ; 100(4): 667-672, 2017 04.
Article in English | MEDLINE | ID: mdl-27839889

ABSTRACT

OBJECTIVE: The aim of the present study is to describe and analyse significant factors of disease-related everyday communication of persons with RMDs in a nationwide project in Germany funded by the Deutsche Rheumaliga Bundesverband e.V. (German League against Rheumatism). METHODS: In this participatory research project four persons with RMDs are involved. An online questionnaire addressing context, difficulties, and burden of disease-related everyday communication was answered by 1.015 persons with RMDs. Social and communication skills were recorded by questionnaires to capture social insecurity and patient communication competence. RESULTS: More than half of the participants reported difficulties in disease-related conversations across various situations. The majority of these persons suffer from this experience particularly in conversations at the work environment or with staff members of authorities. They feel unconfident especially in situations which require saying "no". Furthermore, compared to the general population persons with RMDs have more anxiety about contact with others. CONCLUSION: Strengthening the social skills of persons with RMDs in conversations related to everyday situations can promote a self-determined life and contribute to the maintenance of social participation. PRATICE IMPLICATIONS: Based on the results, a communication skills training for persons with RMDs will be developed.


Subject(s)
Communication , Musculoskeletal Diseases/psychology , Rheumatic Diseases/psychology , Social Participation , Adolescent , Adult , Aged , Community-Based Participatory Research , Female , Humans , Male , Middle Aged
3.
Article in English | MEDLINE | ID: mdl-27482937

ABSTRACT

The focus of the study is the analysis of changes in health-related quality of life in various cancer entities during and after an inpatient rehabilitation programme. In a multicentre longitudinal study, a total of 211 cancer patients (breast cancer: N = 84; prostate cancer: N = 90; colon cancer: N = 37) were asked about their quality of life (EORTC QLQ-C30; HADS) at the beginning, the end and 3 months after the end of the rehabilitation programme. In different domains of quality of life significant and mostly clinically relevant improvements were found during rehabilitation. The breast and prostate cancer patients improved most in emotional functioning, colon cancer patients in global quality of life. With regard to the severity of symptoms, the fatigue burden improved in breast and colon cancer patients, nausea in the prostate cancer patients. However, they are increases 3 months after rehabilitation. Functional burdens improved 3 months after the end of rehabilitation in the physical domain for all cancer patients. For breast cancer patients, emotional functioning decreased significantly 3 months after rehabilitation. An inpatient oncological rehabilitation programme can lead to an improvement in quality of life.


Subject(s)
Breast Neoplasms/rehabilitation , Colonic Neoplasms/rehabilitation , Health Status , Prostatic Neoplasms/rehabilitation , Quality of Life , Adult , Aged , Breast Neoplasms/complications , Breast Neoplasms/physiopathology , Breast Neoplasms/psychology , Colonic Neoplasms/complications , Colonic Neoplasms/physiopathology , Colonic Neoplasms/psychology , Emotions , Fatigue/etiology , Fatigue/physiopathology , Female , Hospitalization , Humans , Longitudinal Studies , Male , Middle Aged , Nausea/etiology , Nausea/physiopathology , Prostatic Neoplasms/complications , Prostatic Neoplasms/physiopathology , Prostatic Neoplasms/psychology , Severity of Illness Index
4.
Rehabilitation (Stuttg) ; 55(5): 319-325, 2016 Oct.
Article in German | MEDLINE | ID: mdl-27728939

ABSTRACT

Background: The social network is one of the most significant resources during the course of the rehabilitation. However, there is a lack of short instruments in questionnaire format for the assessment of social relations in the chronically ill. We therefore developed a network generator (NWG), and tested its performance in patients with different diseases during medical rehabilitation. Methods: We tested its reliability, validity and acceptance in 882 inpatients participating in medical rehabilitation programs (cancer N=290, musculoskeletal diseases N=292, and psychosomatic diseases N=300). Findings: The NWG provides clear information about different aspects of the social network of these subgroups with satisfying psychometric characteristics. Conclusions: The NWG can be applied as short assessment of positive social relationships that, in practice, are important resources during the whole rehabilitation process of the chronically ill.


Subject(s)
Chronic Disease/psychology , Chronic Disease/rehabilitation , Psychometrics/methods , Rehabilitation/classification , Social Support , Surveys and Questionnaires , Chronic Disease/epidemiology , Female , Germany/epidemiology , Humans , Male , Middle Aged , Rehabilitation/statistics & numerical data , Reproducibility of Results , Sensitivity and Specificity
5.
Z Rheumatol ; 73(1): 11-9, 2014 Feb.
Article in German | MEDLINE | ID: mdl-24402233

ABSTRACT

Positive therapeutic effects on the work force participation derived from international clinical trials may not be directly transferable to the community based care in Germany. Therefore recent changes of data regarding sick leave (SL), work disability pension (WDP) and employment from the social insurance and from the national database of the German collaborative arthritis centers were analyzed covering a time period of at least 10 years. Health insurance data showed a steeper decline in the average duration of SL caused by rheumatoid arthritis (RA), ankylosing spondylitis (AS) and systemic lupus erythematosus (SLE) compared with all other diseases. In RA patients from the collaborative arthritis centers the mean duration of SL was much more reduced than the average duration of SL for members of the compulsory health insurance. The proportion of gainfully employed RA patients in collaborative arthritis centers has particularly increased in women. According to data from the pension insurance fund less incident cases of WDP due to RA, AS, and SLE have been observed than WDP caused by all other diseases. Thus different nationwide data show positive changes of the work force participation of individuals suffering from inflammatory rheumatic diseases in Germany.


Subject(s)
Disability Evaluation , Employment/statistics & numerical data , Insurance, Disability/statistics & numerical data , National Health Programs/statistics & numerical data , Rheumatic Diseases/epidemiology , Rheumatic Diseases/rehabilitation , Sick Leave/statistics & numerical data , Adult , Age Distribution , Aged , Databases, Factual , Employment/economics , Employment/trends , Female , Germany/epidemiology , Humans , Incidence , Insurance, Disability/economics , Insurance, Disability/trends , Male , Middle Aged , National Health Programs/economics , National Health Programs/trends , Prevalence , Rheumatic Diseases/economics , Risk Factors , Sex Distribution , Sick Leave/economics , Sick Leave/trends , Workload/economics , Workload/statistics & numerical data , Young Adult
7.
Rehabilitation (Stuttg) ; 50(3): 186-94, 2011 Jun.
Article in German | MEDLINE | ID: mdl-21626466

ABSTRACT

BACKGROUND: An aftercare programme following medical rehabilitation may be beneficial in order to reinforce and stabilize the positive effects of rehabilitation and to encourage individual health-related modifications of behaviour and lifestyle. Medical rehabilitation and the aftercare programme of the German Pension Insurance Fund primarily are intended to sustain earning capacity. As part of an evaluation of the Intensified Rehabilitation Aftercare Programme (IRENA) established by the German Pension Insurance Fund, work-related aspects in orthopaedic patients were analyzed based on various data sources. Firstly, the significance of institutional and individual conditions for utilization of IRENA alongside work was of interest. Secondly, the IRENA participants' judgements of the changes of work-related parameters due to the programme were examined, differentiating specifically by extent of earning capacity impairments as well as by particular work problems. METHODS: The data set used for the analysis is composed of person-related routine data of the German Pension Insurance Fund relative to IRENA records of the year 2007 (n=30 663), interview data from orthopaedic rehabilitation centres providing IRENA (n=225), and questionnaires of IRENA participants (n=750) that were either collected during a broad evaluation of the IRENA programme or provided by the German Pension Insurance Fund. RESULTS: The results show that the compatibility of IRENA and work is facilitated by the institutional conditions. However, differences between inpatient and outpatient settings have to be recognized. The possibilities to participate in IRENA throughout the day frequently are more diverse in an outpatient setting. In contrast to inpatient centres, outpatient rehabilitation centres see clearly better chances for patients to return to work and to participate in IRENA alongside. With respect to the work-related parameters (work ability, periods of sick leave), clear improvements were reported by participants from the start of rehabilitation to the survey time after the end of IRENA. Particular work problems were reported by 33% of the IRENA participants. The work ability at the end of rehabilitation was found to have been the essential factor for improvement of work ability following IRENA. Particular work problems, however, had no influence, these individuals profited from IRENA to an equal extent. CONCLUSIONS: Institutional and individual view show that IRENA is compatible with utilization alongside work. Also, IRENA combined with prior medical rehabilitation will bring about subjective improvements in health and work-related parameters.


Subject(s)
Aftercare/organization & administration , Musculoskeletal Diseases/rehabilitation , Occupational Diseases/rehabilitation , Occupational Medicine/organization & administration , Rehabilitation, Vocational/methods , Rehabilitation/organization & administration , Germany , Humans , Models, Organizational
10.
Cell Biol Int ; 25(1): 43-9, 2001.
Article in English | MEDLINE | ID: mdl-11237407

ABSTRACT

The Th1--Th2 balance plays a pivotal role in determining the outcome of an immune response to an infectious organism. It is proposed that during HIV infection, disease progression is characterized by a loss of Th1 activity, a shift to a more 'allergic' Th2-type response and hence loss of cytotoxic cell activity against infected host cells. This study was undertaken to investigate this balance in three groups of individuals: HIV-negative volunteers (n=10), a group of HIV-infected patients on no therapy (n=10) as well as a group of patients managed with a mixture of plant sterols/sterolins (n=9). In parallel, their response to mitogens and the subsequent expression of the activation antigen CD69 was measured. This study was conducted by three-colour flow cytometry in order to obviate the less sensitive cytokine secretion assays that have yielded controversial results. The results indicate that HIV-infected patients on no therapy exhibit a pre-dominant Th2 response (IL-4 secretion), whereas those on the sterol/sterolin mixture exhibit a beneficial Th1 response (IFN-gamma). Surprisingly, in both patient groups, the expression of CD69 was abnormally low when compared to the uninfected volunteers, implying that chronic activation is already present in vivo. It appears that the detrimental Th2 driven response might be swung to the more beneficial Th1 response with the immune modulatory sterols/sterolin mixture. Clinical use of this mixture in HIV infection has yielded results which corroborate the above observations in that patients using the plant sterol/sterolin mixture maintain their CD4 cell numbers over an extended period of time in the absence of any anti-retroviral therapy.


Subject(s)
ATP-Binding Cassette Transporters/therapeutic use , HIV Seropositivity/blood , Lipoproteins/therapeutic use , Phytosterols/therapeutic use , Th1 Cells/metabolism , Th2 Cells/metabolism , ATP Binding Cassette Transporter, Subfamily G, Member 5 , Antigens, CD/blood , Antigens, Differentiation, T-Lymphocyte/blood , CD4-Positive T-Lymphocytes/metabolism , Cells, Cultured , Cytokines/blood , Flow Cytometry , HIV Infections/drug therapy , Humans , Interferon-gamma/blood , Interleukin-4/blood , Lectins, C-Type , Th1 Cells/drug effects , Th2 Cells/drug effects , Time Factors
11.
Klin Oczna ; 102(2): 85-8, 2000.
Article in Polish | MEDLINE | ID: mdl-10932886

ABSTRACT

PURPOSE: Research was aimed at comparison of isolation methods as well as determination of growth and differentiation dynamics of rabbit corneal epithelium (CE) in vitro. Adhesion, growth and differentiation of CE cells growing on collagen membranes were evaluated. MATERIAL AND METHODS: Research was performed on the cells of rabbit corneal epithelium isolated mechanically or enzymatically (Dispase II) from comeas excised at the edge of limbus. CE cells were cultured in media with high or low contents of calcium, with addition of FCS, insulin, cholera toxin and EGF. RESULTS: In comparison with mechanical isolation, enzymatic isolation yielded 4-5 times more living undifferentiated (CE) cells. The highest dynamics of in vitro growth was observed in primary cultures in low-calcium medium supplemented with the above substances. After 20 population doublings cells were differentiated and died. Only few cells on collagen membranes adhered to the collagen but did not enter division. CONCLUSIONS: Current research allowed for determination of methodology for CE excision and isolation. Optimal conditions for in vitro growth have been established. Growth dynamics and proliferation of CE in vitro have been evaluated. Growth of CE on standard collagen membrane has not been observed.


Subject(s)
Cornea/cytology , Animals , Cell Culture Techniques , Epithelial Cells , Rabbits
12.
Cell Biol Int ; 23(1): 51-60, 1999.
Article in English | MEDLINE | ID: mdl-10527548

ABSTRACT

We examined the effects of lovastatin, a common anti-atherosclerotic drug and a blocker of the cell cycle, on the process of mitosis. It is known that lovastatin induces an arrest or a retardation of the cell cycle in many cell types not only at the G(1)phase, but also at the G(2)/M transition. After 24-48 h incubation of epithelial PtK(2), T24, HeLa cells and fibroblastic L929 cells in the presence of 1. 0-60.0 microm lovastatin, diverse mitotic perturbations have been observed. The most noteworthy phenomena recorded were prometaphase retardation and chromosome lagging during metaphase and anaphase. After the recovery in lovastatin-free media, the cells continued mitosis without any disturbances. Mevalonic acid prevented the effects of lovastatin. We conclude that the effects were specific for lovastatin-induced inhibition of mevalonic acid synthesis. Immunofluorescence studies with anticentromeric antibodies suggested that one of the possible causes of the lovastatin-induced mitotic disorder could be an interference with the development and function of the centromeres.


Subject(s)
Anticholesteremic Agents/pharmacology , Lovastatin/pharmacology , Mitosis/drug effects , Cell Line , Centromere/drug effects , Fluorescent Antibody Technique , HeLa Cells , Humans , Mevalonic Acid/metabolism
13.
Int J Sports Med ; 20(4): 258-62, 1999 May.
Article in English | MEDLINE | ID: mdl-10376483

ABSTRACT

A pilot study was undertaken to investigate the effects of the intake of capsules containing the plant sterols and sterolins (BSS:BSSG mixture) on selected immune parameters of volunteers participating in an ultra-marathon in Cape Town, South Africa. Those runners having received active capsules (n=9) showed less neutrophilia, lymphopenia and leukocytosis when compared to their counterparts having received placebo capsules (n=8): the placebo treated individuals showed significant increases in their total white blood cell numbers as well as in their neutrophils (p=0.03 and 0.03 respectively). Furthermore, statistically significant increases within lymphocyte subsets were observed in the runners having received the active capsules: CD3+ cells increased (p=0.02) as did CD4+ cells (p=0.03). In parallel, the BSS:BSSG capsules decreased the plasma level of IL6 in the runners using the active capsules (p=0.08) and significantly decreased the cortisol: DHEAs ratio (p=0.03), suggesting that these volunteers had less of an inflammatory response and were less immune suppressed during the post-marathon recovery period. These findings justify further investigations into the use of the phytosterols to prevent the subtle immunosuppression associated with excessive physical stress.


Subject(s)
Exercise/physiology , Immunosuppression Therapy , Inflammation , Phytosterols/pharmacology , Sitosterols/pharmacology , Adult , Blood Cell Count , Dietary Supplements , Female , Humans , Leukocytosis , Lymphocyte Subsets , Lymphopenia , Male , Middle Aged , Neutrophils , Phytosterols/administration & dosage , Sitosterols/administration & dosage
14.
Altern Med Rev ; 4(3): 170-7, 1999 Jun.
Article in English | MEDLINE | ID: mdl-10383481

ABSTRACT

Beta-sitosterol (BSS) and its glycoside (BSSG) are sterol molecules which are synthesized by plants. When humans eat plant foods phytosterols are ingested, and are found in the serum and tissues of healthy individuals, but at concentrations orders of magnitude lower than endogenous cholesterol. Epidemiological studies have correlated a reduced risk of numerous diseases with a diet high in fruits and vegetables, and have concluded that specific molecules, including b-carotene, tocopherols, vitamin C, and flavonoids, confer some of this protective benefit. However, these epidemiologic studies have not examined the potential effect that phytosterols ingested with fruits and vegetables might have on disease risk reduction. In animals, BSS and BSSG have been shown to exhibit anti-inflammatory, anti-neoplastic, anti-pyretic, and immune-modulating activity. A proprietary BSS:BSSG mixture has demonstrated promising results in a number of studies, including in vitro studies, animal models, and human clinical trials. This phytosterol complex seems to target specific T-helper lymphocytes, the Th1 and Th2 cells, helping normalize their functioning and resulting in improved T-lymphocyte and natural killer cell activity. A dampening effect on overactive antibody responses has also been seen, as well as normalization of the DHEA:cortisol ratio. The re-establishment of these immune parameters may be of help in numerous disease processes relating to chronic immune-mediated abnormalities, including chronic viral infections, tuberculosis, rheumatoid arthritis, allergies, cancer, and auto-immune diseases.


Subject(s)
Adjuvants, Immunologic/therapeutic use , Sitosterols/immunology , Animals , Cats , HIV Infections/therapy , Humans , Immune Tolerance/drug effects , Sitosterols/therapeutic use , Tuberculosis, Pulmonary/therapy
15.
Klin Oczna ; 100(6): 355-8, 1998.
Article in Polish | MEDLINE | ID: mdl-10067060

ABSTRACT

PURPOSE: Morphological characteristics of established cell line (RtCE) derived from rat anterior corneal epithelium. MATERIAL AND METHODS: Morphology of cultured RtCE cells was evaluated by light and electron microscopy. Anterior corneal epithelium of rat served as control. RESULTS: Both in light and electron microscope we observed morphological similarity with anterior corneal epithelium (several layers of cells, numerous desmosomal connections). Moreover, similar morphological changes were observed in relation to the control material, i.e. degeneration and flattening of cells in superficial layers. CONCLUSIONS: The morphological analysis of RtCE cell line proves its usefulness for further cytomorphological, cytogenetical and functional analyses, as well as for evaluation of influence of different physico-chemical and biological factors on growth and regeneration of corneal epithelium in vitro.


Subject(s)
Cornea/ultrastructure , Epithelial Cells/ultrastructure , Animals , In Vitro Techniques , Male , Rats
16.
J Theor Biol ; 185(2): 255-62, 1997 Mar 21.
Article in English | MEDLINE | ID: mdl-9344725

ABSTRACT

Behavioural synchronization means that the behaviour of several individuals is related in time. They may show the same behaviour either at the same time (synchrony) or explicitly at different moments (anachrony). Here, a procedure is presented, which not only allows quantitative investigation of behavioural synchronization in groups of any size, but also a separate evaluation with respect to each individual and behaviour pattern. The method distinguishes between the purely descriptive degree of concurrence and the degree of synchrony, which takes into account synchrony or anachrony occurring by chance on the basis of particular behaviour frequencies. Some recommendations for the application of the procedure are given and its limitations discussed. Copyright 1997 Academic Press Limited

17.
Int J Tuberc Lung Dis ; 1(6): 518-22, 1997 Dec.
Article in English | MEDLINE | ID: mdl-9487449

ABSTRACT

OBJECTIVE: To evaluate the adjuvant effect of beta-sitosterol and its glucoside in the treatment of culture proven pulmonary tuberculosis (PTB). DESIGN: A blinded randomised placebo-controlled trial in culture proven drug sensitive PTB. Patients were hospitalised for the duration of treatment and evaluated at monthly intervals with regard to sputum culture positivity, chest radiography, weight gain, Mantoux test response, routine haematology and liver functions. STATISTICAL EVALUATION: General linear models for repeated measures (SAS GLM package) compared the interaction effects, group effects and time effects of findings in 19 patients receiving sitosterols with those in 18 patients receiving a placebo (talcum powder). Absolute values and change from baseline values were evaluated, although only the latter are reported. RESULTS: Weight gain was significantly greater in the sitosterol group (mean weight gain 8.9 kg) than the placebo group (mean gain 6.1 kg) (P = 0.0023 group effects; P = 0.0001 for time effects). Speed of achieving culture negativity, radiological improvement and induration on Mantoux testing was similar in the two groups. Change in lymphocyte counts from baseline was significantly higher in the sitosterol group (P = 0.0001 and P = 0.0001 for group and time effects) as was the increase in eosinophil counts (P = 0.0001 and P = 0.0137 for group and time effects). CONCLUSION: The study has shown significantly improved weight gain and higher lymphocyte and eosinophil counts in PTB patients receiving sitosterols in addition to an efficacious antituberculosis regimen. Sitosterols and their possible mode of action should now be evaluated in larger numbers of tuberculosis patients and in diseases with a similar immunopathogenesis.


Subject(s)
Sitosterols/therapeutic use , Tuberculosis, Pulmonary/drug therapy , Adjuvants, Immunologic/therapeutic use , Adult , Antitubercular Agents/therapeutic use , Humans , Leukocyte Count , Male , Tuberculosis, Pulmonary/blood , Weight Gain
18.
Z Rheumatol ; 56(6): 334-41, 1997 Dec.
Article in English | MEDLINE | ID: mdl-9487649

ABSTRACT

We examined to what extent patients with fibromyalgia differ from painfree control subjects in the perception and processing not only of somatosensory but also of external stimuli. For this purpose the acoustic perception of 30 patients with fibromyalgia was compared with that of 36 generally pain-free age and gender matched subjects. The groups were also controlled for organic disease of pathological dysfunction of the ear and auditory nerves. Thresholds of unpleasantness and hearing thresholds were determined autiometrically for various frequencies. In addition the participants rated their experience of daily noise, vulnerability to acoustic stress, and functional and affective complaints associated with fibromyalgia. As expected the results show reduced unpleasantness thresholds for all frequencies and a nonsymptomatic hearing loss for higher frequencies. The elevated hearing threshold correlated significantly with experience of noise at the place of work, which was also elevated in the fibromyalgia group. Generalized pain had a high impact on the interaction between threshold of unpleasantness and daily noise experience. We interpret the differences in thresholds of hearing and of unpleasantness in patients with fibromyalgia as a form of either preconscious or conscious acts to protect against disturbing stimulation. Our results support the notion of a generalized disturbancy of perceptual thresholds in patients with fibromyalgia not restricted to the perception of pain.


Subject(s)
Arousal/physiology , Auditory Perceptual Disorders/physiopathology , Auditory Threshold/physiology , Fibromyalgia/physiopathology , Adult , Audiometry, Pure-Tone , Auditory Perceptual Disorders/diagnosis , Bone Conduction/physiology , Female , Fibromyalgia/diagnosis , Hearing Loss, High-Frequency/diagnosis , Hearing Loss, High-Frequency/physiopathology , Humans , Male , Middle Aged , Noise , Pitch Perception/physiology , Reference Values , Vestibulocochlear Nerve/physiopathology
19.
Behav Processes ; 39(2): 161-76, 1997 Feb.
Article in English | MEDLINE | ID: mdl-24896963

ABSTRACT

In isolated pairs of the biparental convict cichlid (Cichlasoma nigrofasciatum) caring for fry, pairbonds can be broken by removal of the fry. Within three hours, the mates of many pairs become so mutually aggressive that the female finally flees from her larger mate, who chases her. The pairbond is mended within seconds upon re-introduction of the fry. Yet removal of young leaves some pairs little or not at all affected. They seem to have more stable pairbonds. Multiple regression of data from 39 pairs on a quantitative measure of pairbond destruction revealed support for the so-called parity-hypothesis, which holds that a cichlid pair is compatible only when the female's aggressiveness compensates for her smaller size. The size of the female relative to the male's, and her aggressiveness relative to his in the undisturbed situation, proved positive predictors of pair stability in the fry stage. Thus the same factors which have earlier been shown to favour pair formation in other biparental cichlids seem also responsible for pair stability in a later stage of the reproductive cycle.

20.
Eur J Cell Biol ; 71(3): 311-8, 1996 Nov.
Article in English | MEDLINE | ID: mdl-8929570

ABSTRACT

HeLa cells growing in vitro were treated with the peptidyl aldehyde inhibitor of the chymotrypsin-like activity of the proteasome N-benzyloxycarbonyl-Ile-Glu(O-t-butyl)-Ala-leucinal (PSI). Immunofluorescence studies of treated cells revealed the formation of massive perinuclear aggregates rich in ubiquitin and proteasomal antigens, which on the ultrastructural level appeared as perinuclear aggregates of electron-dense material, usually in the vicinity of Golgi cisternae. Histochemical studies disclosed that these cells contained protein-rich perinuclear aggregates detected by amido black staining, while unusual accumulations of lipids, carbohydrates, or nucleic acids were not present. Inhibition of protein synthesis by cycloheximide prevented the formation of aggregates, whereas microtubule disruption by nocodazole induced a dispersion of the aggregates. We hypothesize that aggregates induced by PSI treatment correspond to accumulations of proteasome-substrate complexes in a well-defined region, where the proteolytic processes of the ubiquitin-proteasome pathway seem to be somehow centered. We propose to call this region the proteolysis center.


Subject(s)
Chymotrypsin/metabolism , Cysteine Endopeptidases/metabolism , Multienzyme Complexes/metabolism , Ubiquitins/pharmacology , Blotting, Western , Cycloheximide/pharmacology , Electrophoresis, Polyacrylamide Gel , Fluorescent Antibody Technique, Indirect , HeLa Cells , Humans , Microscopy, Electron , Microtubules/drug effects , Nocodazole/pharmacology , Proteasome Endopeptidase Complex
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