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1.
Oper Orthop Traumatol ; 32(5): 433-439, 2020 Oct.
Article in German | MEDLINE | ID: mdl-31754746

ABSTRACT

OBJECTIVE: Surgical refixation intends to restore the continuity of the hamstrings and anatomically reattach the torn tendons. INDICATIONS: In patients with 2­tendon tear/ruptur with more than 2 cm retraction or with complete 3­tendon tears, surgical fixation should be performed. CONTRAINDICATIONS: Massive obesity, immobility. SURGICAL TECHNIQUE: Surgery is performed via a transverse skin incision in the gluteal fold. Refixation of the torn tendons is achieved by means of suture anchors on the footprint of the ischial tuberosity. POSTOPERATIVE MANAGEMENT: Postoperative treatment should be performed with a hip joint orthosis for 6 weeks, accompanied by physiotherapy. RESULTS: Regarding surgical treatment, positive results are clearly described in the literature. Of the 31 patients who underwent surgery between 2010 and 2018, 90 % were satisfied with the surgical results 1 year postoperatively and 75 % reached their previous activity level.


Subject(s)
Hamstring Muscles , Tendon Injuries , Humans , Muscle, Skeletal , Suture Anchors , Tendon Injuries/diagnostic imaging , Tendon Injuries/surgery , Treatment Outcome
3.
Orthopade ; 48(1): 84-91, 2019 Jan.
Article in German | MEDLINE | ID: mdl-30574674

ABSTRACT

STUDY DESIGN: Prospective clinical cohort study (data collection); expert opinion (recommendation development). OBJECTIVES: Treatment options for nonsurgical and surgical management of osteoporotic vertebral body fractures differ widely. Based on the current literature, the knowledge of the experts, and their classification for osteoporotic fractures (OF classification), the Spine Section of the German Society for Orthopaedics and Trauma has now introduced general treatment recommendations. METHODS: A total of 707 clinical cases from 16 hospitals were evaluated. An OF classification-based score was developed for guidance in the option of nonsurgical versus surgical management. For every classification type, differentiated treatment recommendations were deduced. Diagnostic prerequisites for reproducible treatment recommendations were defined: conventional X­rays with consecutive follow-up images (standing position whenever possible), magnetic resonance imaging, and computed tomography scans. OF classification allows for upgrading of fracture severity during the course of radiographic follow-up. The actual classification type is decisive for the score. RESULTS: A score of less than 6 points advocates nonsurgical management; in cases with more than 6 points, surgical management is recommended. The primary goal of treatment is fast and painless mobilization. Because of the expected comorbidities in this age group, minimally invasive procedures are preferred. As a general rule, stability is more important than motion preservation. It is mandatory to restore the physiological loading capacity of the spine. If the patient was in a compensated unbalanced state at the time of fracture, reconstruction of the individual prefracture sagittal profile is sufficient. The instrumentation technique has to account for compromised bone quality. We recommend the use of cement augmentation or high purchase screws. The particular situations of injuries with neurological impairment, the necessity to fuse, multiple level fractures, consecutive and adjacent fractures and fractures in ankylosing spondylitis are addressed separately. CONCLUSIONS: The therapeutic recommendations presented here provide a reliable and reproducible basis to decide for the treatment choices available. However, intermediate clinical situations with a score of 6 points remain, allowing for both nonsurgical and surgical options. As a result, individualized treatment decisions may still be necessary. In the subsequent step, the recommendations presented will be further evaluated in a multicentre controlled clinical trial.


Subject(s)
Orthopedics , Osteoporotic Fractures , Cohort Studies , Fractures, Compression , Humans , Prospective Studies , Spinal Fractures , Treatment Outcome
4.
Unfallchirurg ; 114(1): 9-16, 2011 Jan.
Article in German | MEDLINE | ID: mdl-21246343

ABSTRACT

This paper gives recommendations for treatment of thoracolumbar and lumbar spine injuries. The recommendations are based on the experience of the involved spine surgeons, who are part of a study group of the "Deutsche Gesellschaft für Unfallchirurgie" and a review of the current literature. Basics of diagnostic, conservative, and operative therapy are demonstrated. Fractures are evaluated by using morphologic criteria like destruction of the vertebral body, fragment dislocation, narrowing of the spinal canal, and deviation from the individual physiologic profile. Deviations from the individual sagittal profile are described by using the monosegmental or bisegmental end plate angle. The recommendations are developed for acute traumatic fractures in patients without severe osteoporotic disease.


Subject(s)
Lumbar Vertebrae/injuries , Lumbar Vertebrae/surgery , Spinal Fusion/standards , Spinal Injuries/therapy , Thoracic Vertebrae/injuries , Thoracic Vertebrae/surgery , Vertebroplasty/standards , Germany , Humans , Minimally Invasive Surgical Procedures/standards , Practice Guidelines as Topic
5.
Unfallchirurg ; 113(4): 308-12, 2010 Apr.
Article in German | MEDLINE | ID: mdl-20195841

ABSTRACT

QUESTION: Fractures of the ankle joint belong to the most often occurring injuries. The aftercare in plaster lasts several weeks and is problematic especially in elderly patients. METHODS: In a retrospective study patients over the age of 50 years who underwent surgical treatment of ankle fractures and early functional mobilization were examined in a follow-up. The range of motion, the circumferential measurements and the radiological course were examined by comparing preoperative and postoperative X-ray images after 13-24 months. The subjective results were collected using the Olerud-Molander score (OMS). RESULTS: A total of 30 out of 42 patients who qualified for the follow-up were included in the study. The distribution of the gender was equal as was the right/left distribution and the mean age was 68 years. The magnitude of movement and comparison between the two sides showed no significant differences. The average score for subjective satisfaction was 90 in the OMS. The radiological results showed few changes and no deviations from the axis. No redislocations or implant fractures could be observed. Early functional full weight-bearing showed satisfactory preliminary results. CONCLUSION: This treatment concept can be recommended because patient comfort is increased and the risk of immobilization is excluded.


Subject(s)
Ankle Injuries/physiopathology , Ankle Injuries/surgery , Fibula/injuries , Fracture Fixation, Internal/methods , Postoperative Complications/physiopathology , Weight-Bearing/physiology , Age Factors , Aged , Ankle Injuries/diagnostic imaging , Bone Plates , Bone Screws , Female , Fibula/diagnostic imaging , Fibula/surgery , Follow-Up Studies , Fracture Healing/physiology , Humans , Male , Middle Aged , Patient Satisfaction , Postoperative Complications/diagnostic imaging , Radiography , Retrospective Studies
6.
Unfallchirurg ; 112(6): 565-74, 2009 Jun.
Article in German | MEDLINE | ID: mdl-19436981

ABSTRACT

BACKGROUND: In Hannover and in nationwide contingency plans there are clear instructions for the medical care of mass casualties which are designed to cope with 50 to a maximum of 200 patients. Disaster simulations and practical exercises in Hannover regarding EXPO 2000 and the FIFA World Cup 2006 showed a very good and effective prehospital treatment and management up to a number of about 200 patients. Due to infrastructural settings a scenario with up to 1,000 (MANV IV) patients in the region of Hannover was beyond the capacity of existing concepts for the management of mass casualties, which comprised initial medical care at the on-site treatment area and subsequent transport to local or regional hospitals for definitive management. A new practicable and well trained model was necessary to improve the hospital admission and primary treatment capacity (Erstversorgungsklinik--EVK). In the case of MANV IV it was proposed that the tasks of on-site treatment area should be concentrated on triage and the stabilization of severely injured victims with immediate transport to special primary care hospitals. The main task of these hospitals was further stabilization of patients for inhospital care or further transport to other special facilities. METHODS: The main aim of the study was, after the initial trauma scenario, to provide the logistical and personal background for the fastest possible advanced life support and the further treatment of more than 60 severely injured patients at a city hospital with trauma centre level I experience. The timescale from the first alarm until the hospital was ready for action was approximately 60 min. To gain knowledge about the regional implementation of the whole logistic scenario in the case of MANV IV and to practice detailed questioning, a major casualty training was needed. This resulted in a large targeted disaster medical training with a realistic situation simulation on the 25.03.2006 including the Diakoniekrankenhaus Friederikenstift under the aspect of a special primary care hospital (EVK) working at full capacity. RESULTS: The AWD arena in Hannover was the site of a simulated major casualty event resulting in 620 patients with various penetrating or blunt trauma injuries. Within 60 min of the first alarm call the admission and casualty treatment capacity at the Diakoniekrankenhaus Friederikenstift was increased up to approximately 60 patients including 30 ventilated patients. After initial inspection of 78 patients according to the ATLS criteria advanced life support was performed (airway management, volume resuscitation, basic diagnostic and surgical techniques) by flexible treatment teams (including physicians of all other faculties) in 3 treatment corridors within 135 min. Of the patients 69 were admitted to the wards and intensive care units, 5 were discharged after ambulant treatment and 3 patients were transferred to an eye and ENT hospital. Of the patients 10 had already been intubated on arrival, another 6 patients were intubated in the treatment corridors. Simulations of 4 urgent laparatomies, 2 trepanations, 1 artery seam, osteosynthesis of 3 perforating fractures was performed in the operating theatre. A total of 6 extremity fractures were immobilized by a fixateur externe, 7 chest tubes were placed and 43 surgical wound dressings were performed in the treatment corridors. There was no significant shortage of logistical or personal resources. CONCLUSION: In a major disaster with more than 200 seriously injured patients the EVK model is a practicable and regional well tried solution that could increase the capacity of hospital admissions and advanced trauma life support, regardless of the type of casualty, season or weather conditions. It is possible to reduce the interval to advanced trauma life support, temporary fracture stabilization (damage control) and definitive surgical care by means of rapid and targeted utilization of resources and manpower. Physicians involved in the initial treatment play a key role and have to be highly trained (ATLS). The EVK model is variable and can easily be established and adapted to regional conditions at basic regional hospitals as well as at level I trauma centers.


Subject(s)
Disaster Planning/organization & administration , Emergency Service, Hospital/organization & administration , Mass Casualty Incidents , Primary Health Care/organization & administration , Triage/organization & administration , Germany
7.
Unfallchirurg ; 112(2): 211-6, 2009 Feb.
Article in German | MEDLINE | ID: mdl-19212740

ABSTRACT

BACKGROUND: The German Association of Trauma Surgery has developed a concept for the quality-assured care of severely injured patients; this concept includes the establishment of trauma networks. In this study, hospitals and emergency services in Lower Saxony were asked about their demands on the Hannover regional trauma network. MATERIALS AND METHODS: Trauma departments in Lower Saxony and adjoining federal states were asked to self-assess their level of trauma care. The demands of emergency services and trauma departments on the trauma network were also ascertained. RESULTS: Responses to the questionnaire were received from 70.2% of trauma departments and 11.5% of emergency services organizations. Of these, 46.9% of the trauma departments classified themselves as a "center of basic care", 50.0% as a "regional trauma center", and 3.1% as a "national trauma center". Compared with the regional trauma centers, centers of basic care requested fast transfers of patients to a trauma center significantly more often, whereas trauma centers desired more educational activities. CONCLUSION: The demands of trauma centers on a trauma network correspond with the aims formulated by the German Association of Trauma Surgery. These demands depend on the level of trauma care provided. Close cooperation with emergency services is essential to strengthen collaboration within the trauma network.


Subject(s)
Community Health Planning/organization & administration , Community Networks/organization & administration , Delivery of Health Care/organization & administration , Organizational Objectives , Traumatology/organization & administration , Germany , Surveys and Questionnaires
8.
Unfallchirurg ; 110(8): 675-83, 2007 Aug.
Article in German | MEDLINE | ID: mdl-17497119

ABSTRACT

BACKGROUND: This study was initiated to evaluate early results of a locked screw plate for unilateral fixation of bicondylar fractures of the tibial plateau. Emphasis was laid on malreduction, secondary loss of reduction, union rate, and infection. MATERIAL AND METHODS: A case series of patients with AO/ASIF 41-C type fractures treated with the less invasive stabilization system for the proximal lateral tibia (LISS PLT) were prospectively followed up until 11-13 months after surgery. Malreduction and malalignment were defined as an intra-articular step-off of 2 mm or more or as a malalignment in the frontal or sagittal plane of more than 5 degrees. RESULTS: Sixty-eight patients with 69 fractures were involved. Fourteen fractures were open. Primary bone grafting was performed in 13 patients. Significant malreduction was seen in 16 patients. Sixty-two (91%) patients returned for follow-up. All but one fracture healed eventually. The number of infections was low (4 superficial, 1 deep). Nine patients had a significant loss of reduction. Of 54 patients outcome scores were good to excellent in 47 patients on the Lysholm score (average 87.2) and in 44 patients on the Rasmussen score (average 26.7). CONCLUSION: We concluded that unilateral locked screw plating is a good alternative in the treatment of problematic fractures of the tibial plateau that are associated with soft tissue damage and metaphyseal comminution. The reduction technique for exact alignment is demanding.


Subject(s)
Bone Plates , Fracture Fixation, Internal/instrumentation , Fractures, Open/surgery , Knee Injuries/surgery , Tibial Fractures/surgery , Adolescent , Adult , Aged , Aged, 80 and over , Female , Follow-Up Studies , Fractures, Open/diagnostic imaging , Humans , Knee Injuries/diagnostic imaging , Male , Middle Aged , Postoperative Complications/diagnostic imaging , Postoperative Complications/etiology , Postoperative Complications/surgery , Prospective Studies , Radiography , Reoperation , Soft Tissue Injuries/diagnostic imaging , Soft Tissue Injuries/surgery , Surgical Wound Infection/diagnostic imaging , Surgical Wound Infection/etiology , Surgical Wound Infection/surgery , Tibial Fractures/diagnostic imaging
9.
Chirurg ; 78(1): 40-6, 2007 Jan.
Article in German | MEDLINE | ID: mdl-16998660

ABSTRACT

PURPOSE: In this prospective study, complications observed after angularly stable proximal humerus plate fixation (locking proximal humerus plate) were analysed by deriving specific therapies. PATIENTS: Fifty patients (median age 65 years, range 25-84 years, 39 female, 11 male) with displaced proximal humerus fractures (seven single, 36 double, and seven triple fractures) were evaluated 3, 6, and 12 months after angularly stable plate fixation using a standard protocol. RESULTS: Age- and gender-matched median constant scores 12 months postoperatively showed for the three fracture types 86, 87, and 55 points and complication rates of 14, 19, and 100%, respectively. There were seven primary and seven secondary implant displacements, five humeral head necroses, four osseous malalignments, two nonunions, two deep infections, and one heterotopic ossification. Nine reoperations were required in six patients: implant removal (n=3), reosteosynthesis (n=2), revision because of nonunion (n=2), and deep infection (n=2). CONCLUSIONS: Differentiated analysis of complications and the development of specific prevention and therapeutic strategies considering surgical technique, implant, fracture morphology, and humeral head perfusion minimize the rate of complications observed after angularly stable locking proximal humerus plate fixation.


Subject(s)
Bone Plates , Bone Screws , Equipment Failure , Fracture Fixation, Internal/instrumentation , Postoperative Complications/surgery , Shoulder Fractures/surgery , Adult , Aged , Aged, 80 and over , Device Removal , Female , Follow-Up Studies , Fracture Healing , Humans , Male , Middle Aged , Postoperative Complications/diagnosis , Radiography , Recovery of Function , Reoperation , Shoulder Fractures/diagnostic imaging
10.
Ultraschall Med ; 27(4): 364-7, 2006 Aug.
Article in German | MEDLINE | ID: mdl-16596510

ABSTRACT

AIM: To correlate findings of hip ultrasound on day 4-10 of life with sex, intrauterine position and a positive family history for congenital hip anomalies. METHODS: The SNiP-study ( Survey of Neonates In Pommerania) registered 2256 neonates (2030 term, 226 preterm) between May 2002 and March 2004. Hip ultrasound results of 1043 term and since October 2003 33 preterm neonates were analysed. Time of ultrasound was day 4-10 after birth. Preterm neonates were examined when reaching their corrected term gestational age. Ultrasound was applied with a 7.5 MHz linear scanner and results were classified according to Graf. Chi-square and Fishers exact test were used for statistical analysis. RESULTS: 4.9 % of the screened hips were classified as IIc or higher, 3.1 % were unilateral and 1.7 % bilateral. Incidence was significantly higher (p < 0.023) in females (6.6 %) than in males (3.2 %). There was no significant difference in intrauterine position or positive family history for hip anomalies with 3.7 % for mothers, 1.2 % of fathers and 2.4 % of siblings positive. There was a higher incidence for congenital hip dysplasia in preterms with 6.1 %, which is not significant due to the limited number. DISCUSSION: Current screening methods miss up to 18 % of newborns with severe hip dysplasia. We were able to demonstrate that screening for congenital hip dysplasia with ultrasound is a diagnostic tool even during the first days of life. There is a significantly higher incidence of congenital hip dysplasia in females, but in contrast to other studies we found no significant difference in intrauterine position or familial history. Earlier diagnosis and therapy on the base of relevant risk factors might correspond with an improved prognosis and outcome. Further studies are warranted to evaluate the significance in preterm neonates.


Subject(s)
Hip Dislocation, Congenital/diagnostic imaging , Hip Dislocation, Congenital/genetics , Female , Hip Dislocation, Congenital/embryology , Hip Dislocation, Congenital/epidemiology , Humans , Incidence , Infant, Newborn , Male , Pregnancy , Sex Characteristics , Siblings , Ultrasonography, Prenatal
11.
J Orthop Trauma ; 18(8): 546-51, 2004 Sep.
Article in English | MEDLINE | ID: mdl-15475851

ABSTRACT

OBJECTIVE: To compare the vertical subsidence in a bicondylar tibial plateau fracture model stabilized either by a unilateral locked screw plate (LSP) or by double plating. DESIGN: Biomechanical cadaver study. INTERVENTION: A 41-C1 fracture model was created in eight pairs of fresh-frozen human cadaver tibiae. Stabilization was performed either by open reduction and internal fixation (ORIF) using a lateral L-buttress plate and a medial four-hole, one-third tubular antiglide-plate or by a lateral LSP. Four load levels (400N, 800N, 1200N, 1600N), each with five cycles, were consecutively applied to the medial plateau. MAIN OUTCOME MEASUREMENTS: The vertical plastic deformation at the end of each cycle was the main parameter of interest. Statistical analysis was performed with the two-way ANOVA test for repeated measurements. Each individual loading level was analyzed separately using Student t test. RESULTS: In one pair, both fixation techniques failed at the first loading cycle of 1200N. One ORIF fixation failed at the first loading cycle of 1600N. The average plastic vertical subsidence was 0.40 mm (LSP) and 0.25 mm (ORIF) at 400N (P = 0.291), 0.83 mm (LSP) and 0.81 mm (ORIF) at 800N (P = 8.82), 1.06 mm (LSP) and 0.96 mm (ORIF) at 1200N (P = 0.98), and 1.54 mm (LSP) and 1.14 mm (ORIF) at 1600N (P = 0.53). Vertical subsidence depended on the applied load (P = 0.002), but not on the method of fixation (P = 0.236). CONCLUSION: Both fixation techniques have a high resistance to vertical subsidence even with loads exceeding the average body weight. No statistically significant difference was seen between the two methods of fixation.


Subject(s)
Bone Screws , Fracture Fixation/methods , Internal Fixators , Tibial Fractures/surgery , Aged , Aged, 80 and over , Biomechanical Phenomena , Equipment Design , Female , Fracture Fixation/instrumentation , Humans , Male , Middle Aged , Minimally Invasive Surgical Procedures/instrumentation , Minimally Invasive Surgical Procedures/methods
12.
Zentralbl Chir ; 129 Suppl 1: S98-100, 2004 May.
Article in German | MEDLINE | ID: mdl-15168301

ABSTRACT

Open fractures are complex injuries affecting the integrity of bones and adjacent soft tissue. The therapeutic goals in dealing with open fractures should consist of primary osteosynthesis in conjunction with functional reconstruction of soft tissue. In a period over 2 years, 26 patients were treated with extensive trauma in an interdisciplinary approach. These patients suffered from open fractures type 2 and 3. All patients were treated by primary osteosynthesis, and temporary wound closure with V.A.C.-system. Definitive wound closure was achieved by day 31 after injury. In contrast to a review of the pertinent literature we report the successful free tissue transfer in 21 patients during the critical period between 72 hours and several months preceded by the use of V.A.C.-system for the temporary coverage of open wounds.


Subject(s)
Debridement/instrumentation , Emergencies , External Fixators , Fractures, Open/surgery , Multiple Trauma/surgery , Occlusive Dressings , Soft Tissue Injuries/surgery , Suture Techniques/instrumentation , Adult , Equipment Design , Fluorocarbon Polymers , Fracture Fixation, Internal , Humans , Male , Microcomputers , Reoperation/instrumentation , Surgery, Computer-Assisted/instrumentation , Surgical Flaps , Vacuum , Wound Healing/physiology
13.
J Orthop Trauma ; 18(2): 102-5, 2004 Feb.
Article in English | MEDLINE | ID: mdl-14743030

ABSTRACT

The application of the pelvic clamp as a tool for emergency stabilization of unstable pelvic ring fractures has proved to be a life-saving procedure. Using correct technique, the pelvic clamp can be applied within a few minutes after the patient's admission. To avoid severe complications (eg, pin perforation into the pelvis) during the application, anatomic landmarks for the correct pin placement have to be defined. The surface landmarks that are presently recommended for the correct pin placement are not always reliably found due to deformation of the body surface caused by swelling and hematoma. Our experience with 43 emergency applications of the pelvic C-clamp showed that reliable anatomic landmarks on the bony surface of the innominate bone could be identified to ensure correct pin placement. The ideal insertion point of the pins is an anatomic region on the lateral cortex of the ileum, where an easily palpable "groove" is formed by angulations of the lateral cortex of the iliac wing. Being increasingly used as an entry point for percutaneous transiliosacral screw fixations of sacroiliac joint injuries and sacral fractures, this region, which is close to the sacroiliac joint, represents an ideal point for maximum compression of the posterior pelvic ring. With the described technique, this "groove" can be identified easily even in emergency situations by blunt palpation with an instrument, avoiding the time-consuming use of a fluoroscope in most cases.


Subject(s)
Fractures, Closed/surgery , Pelvic Bones/anatomy & histology , Pelvic Bones/injuries , Surgical Instruments , Emergency Medical Services , Humans
15.
Int Orthop ; 26(5): 278-82, 2002.
Article in English | MEDLINE | ID: mdl-12378353

ABSTRACT

We examined 25 different threaded cups using a specific biomechanical procedure. Great differences between the tested cups concerning their biomechanical parameters could be found. There is some evidence that the design of several cups might be inappropriate for stable acetabular fixation, and this may be the reason for early loosening. The new procedure is the first to allow biomechanical assessment of threaded cups by using quantified data, which correspond to long-term stability of the cup.


Subject(s)
Hip Prosthesis , Acetabulum , Biomechanical Phenomena , Humans , In Vitro Techniques , Prosthesis Design , Surface Properties , Torque
16.
Injury ; 32 Suppl 3: SC55-63, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11888195

ABSTRACT

In recent years, the technique of surgical stabilization in the distal femur has changed. This change decreased the number of non unions and the need for bone grafting. Minimally invasive surgical techniques with a submuscular plate placement have replaced the emphasis on anatomical reduction in the shaft area. Reconstruction of complex articular injuries has been simplified by more direct visualization of the articular surface with the lateral peripatellar approach. Problems remaining are surgical technique and implant considerations. The Less Invasive Stabilization System (LISS) simplifies the surgical technique for percutaneous plate osteosynthesis. An insertion guide is used to insert monocortical, self-tapping screws through a stab incision. A thread in the plate provides the angular stability for the anchoring of these screws. In extra-articular fractures and simple intra-articular fractures, the distal femoral nail permits intramedullary stabilization. A spiral blade improves fixation of the distal femoral condylar block. Despite the enhanced surgical technique and implant possibilities, a great number of patients show a functional deficiency. These are particularly patients with complex intra-articular fractures. The 'fatigue failure' of the osteoporotic implant-bone construct is a problem in elderly patients. The LISS represents a good option to avoid the addition of bone cement to an osteosynthesis.


Subject(s)
Bone Plates/standards , Bone Screws/standards , Femoral Fractures/surgery , Fracture Fixation, Intramedullary/methods , Adult , Aged , Female , Femoral Fractures/complications , Follow-Up Studies , Humans , Male , Minimally Invasive Surgical Procedures/methods , Treatment Outcome
17.
J Immunol ; 155(12): 5557-65, 1995 Dec 15.
Article in English | MEDLINE | ID: mdl-7499838

ABSTRACT

A proteoglycan had been isolated from the conditioned media of a human osteosarcoma cell line and had tentatively been named proteoglycan-100 (PG-100) because of the size of its core glycoprotein. Amino acid sequencing of the purified proteoglycan and cDNA analysis were consistent with the assumption that PG-100 is identical with the proteoglycan form of CSF-1 (or macrophage colony-stimulating factor). PG-100 induced mouse macrophage differentiation. Proliferation of macrophages was stimulated in a dose-dependent manner. On a molar basis, however, about 100- to 300-fold higher doses of PG-100 than of recombinant human (rh)CSF-1 were required for the half-maximal growth-stimulating effect. Upon enzymatic removal of the glycosaminoglycan chain, the purified core protein exhibited higher activity, but was still about 20-fold less active than rhCSF-1. Incubation of the purified proteoglycan for 48 h at 37 degrees C led to the formation of a glycosaminoglycan-free 50-kDa fragment either by autoproteolysis or by the action of a protease not yet identified. The purified fragment exhibited almost the same biologic activity as rhCSF-1. The glycosaminoglycan chain of the growth factor was not only shown to inhibit CSF-1 activity but also to increase the stability of the core protein when the CSF-1-producing osteosarcoma cells were maintained in a collagen lattice. These findings provide a link between a soluble, highly active cytokine and its extracellular matrix storage form of comparatively low activity.


Subject(s)
Chondroitin Sulfates/chemistry , Macrophage Colony-Stimulating Factor/chemistry , Macrophage Colony-Stimulating Factor/physiology , Proteoglycans/chemistry , Amino Acid Sequence , Base Sequence , Biglycan , Blotting, Northern , Decorin , Endopeptidases , Extracellular Matrix Proteins , Humans , Macrophage Activation/physiology , Macrophage Colony-Stimulating Factor/biosynthesis , Molecular Sequence Data , Osteosarcoma , Proteoglycans/physiology , Recombinant Proteins/biosynthesis , Tumor Cells, Cultured
18.
Cell Immunol ; 153(2): 505-15, 1994 Feb.
Article in English | MEDLINE | ID: mdl-7907005

ABSTRACT

The CD4-positive bovine serum albumin (BSA)-specific Ts cell clone BVI/5 from a CBA/J mouse tolerized to low doses of BSA induces specific unresponsiveness in the T helper (Th) cell population. Tolerance induction can be measured in vitro in proliferation assays using specific Th cell clones or antigen-primed lymph node cells (LNC) and determined in vivo by the failure to produce hapten-specific antibodies. Using the BSA-specific Th cell clone 83/1 as a target one observes in addition 51Cr-release in a 16-hr long-term assay but finds no effect in a typical 6-hr T cell cytotoxicity test. BVI/5 Ts cells do not produce interleukin-2 but otherwise express a Th1 profile. The suppression of proliferation of 83/1 Th cells is partly due to interferon-gamma (IFN-gamma). But lysis of 83/1 Th cells as well as suppression of BSA-specific LNC proliferation needs direct cell contact between BVI/5 Ts cells and their targets. Cell lysis and suppression of LNC cannot be simulated by IFN-gamma, by the combination of IFN-gamma and TNF, or by BVI/5 supernatants. Thus mediators cannot account for specific suppression by BVI/5 Ts cells in polyclonal in vitro responses from LNC and are probably not responsible for the induction of in vivo unresponsiveness. Instead the data show that BVI/5 Ts cells induce apoptosis-like DNA fragmentation in cloned BSA-specific 83/1 Th cells and in LNC from BSA-primed mice. Apoptosis can also be visualized as chromatin condensation in the LNC population. Macrophages have been excluded as targets. It can further be demonstrated that BVI/5 Ts cells express perforin and granzyme A on activation. Thus they are equipped with the effector molecules for target cell destruction. We consider BVI/5 Ts cells to be representative of a regulatory T cell inducing specific unresponsiveness in peripheral lymphoid organs.


Subject(s)
CD4-Positive T-Lymphocytes/immunology , DNA Damage/immunology , T-Lymphocytes, Helper-Inducer/immunology , T-Lymphocytes, Regulatory/immunology , Animals , Antigens , Apoptosis/immunology , Clone Cells/immunology , Cytotoxicity, Immunologic , Gene Expression , Granzymes , Immune Tolerance , Interleukin-2/genetics , Lymphocyte Activation , Macrophages/immunology , Male , Membrane Glycoproteins/genetics , Mice , Mice, Inbred CBA , Perforin , Pore Forming Cytotoxic Proteins , Serine Endopeptidases/genetics , Serum Albumin, Bovine/immunology , T-Lymphocytes, Helper-Inducer/metabolism
19.
Int Immunol ; 4(7): 755-64, 1992 Jul.
Article in English | MEDLINE | ID: mdl-1386751

ABSTRACT

The ability of macrophages to stimulate immune responses is heterogeneous and may have influence on the type of the developing immune response. Therefore, in an attempt to define different functional states of mouse macrophages, we made use of the two macrophage growth factors: macrophage colony stimulating factor (M-CSF) and granulocyte macrophage colony stimulating factor (GM-CSF). Generation of macrophages from freshly isolated bone marrow cells in the presence of GM-CSF results in a population expressing profound antigen presenting function for mouse TH1 cells, resulting in strong lymphokine production and proliferation of the T cells. Furthermore, high amounts of a novel soluble cytokine active on mouse TH1 cells are generated during the interaction of TH1 cells with macrophages elicited with GM-CSF. In contrast, macrophages grown from bone marrow cells for at least 14 days in the presence of M-CSF express only minimal antigen-presenting function for TH1 cells. Treatment of such macrophages for 24 h with either IFN-gamma or GM-CSF allows the distinction between two further functional states. Those treated with IFN-gamma efficiently presented antigen towards TH1 cells. The T cells produced large amounts of lymphokines and proliferate well. However, synthesis of the novel soluble cytokine (active on TH1 cells) was not detectable. The generation of this mediator requires a short-term treatment with GM-CSF of macrophages developed in the presence of M-CSF prior to their interaction with TH1 cells.


Subject(s)
Antigen-Presenting Cells/immunology , Macrophages/immunology , T-Lymphocytes, Helper-Inducer/immunology , Animals , Antigen-Presenting Cells/drug effects , Bone Marrow/drug effects , Bone Marrow/immunology , Bone Marrow Cells , Granulocyte-Macrophage Colony-Stimulating Factor/pharmacology , In Vitro Techniques , Interleukin-2/biosynthesis , Lymphocyte Activation , Lymphokines/biosynthesis , Macrophage Colony-Stimulating Factor/pharmacology , Macrophages/drug effects , Mice , T-Lymphocytes, Helper-Inducer/drug effects
20.
Eur J Immunol ; 20(9): 2035-40, 1990 Sep.
Article in English | MEDLINE | ID: mdl-2145173

ABSTRACT

Besides the signal generated in a T lymphocyte after triggering the T cell receptor (TcR), most lymphocytes need a "second signal" to become fully activated. The necessity and nature of the "second signal" differs between different types of T cells. At the level of CD4-positive T helper lymphocytes interleukin 1 (IL 1) serves as "second signal" for those of the TH2 subtype (IL4, 5, 6 producer) but not for those of the TH1 subtype (IL 2, IFN-gamma producer). This correlates with the absence of the IL 1 receptor at the surface of TH1 clones. We report herein the further purification of T cell stimulating factor (TSF), a soluble mediator involved in the proliferation of TH1 lymphocytes. A preparation free of detectable IL 1, 2, 4 and IL 6 activity could act as "second signal" required for the growth of TH1 lymphocytes in a TcR-mediated, as well as a TcR-independent activation system. In addition, we suggest that IL 1 can influence the proliferation of TH1 clones in an indirect way, probably via the induction of TSF in accessory cells.


Subject(s)
Interleukin-1/pharmacology , T-Lymphocytes, Helper-Inducer/immunology , Animals , Antibodies, Monoclonal/immunology , Antigen-Presenting Cells/physiology , Antigens, Differentiation, T-Lymphocyte/physiology , CD3 Complex , Interleukin-1/analysis , Interleukin-1/isolation & purification , Lymphocyte Activation , Macrophage Colony-Stimulating Factor/pharmacology , Macrophages/physiology , Mice , Mice, Inbred BALB C , Receptors, Antigen, T-Cell/physiology , Receptors, Interleukin-2/physiology
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