Juvenile idiopathic arthritis of the knee: is contrast needed to score disease activity when using an augmented MRI protocol comprising PD-weighted sequences?

OBJECTIVE: To compare unenhanced versus enhanced knee joint magnetic resonance imaging (MRI) to assess disease activity of juvenile idiopathic arthritis (JIA). METHODS: Fifty-three knee joint MRI examinations were performed on a 3-Tesla system in 27 patients (age: 11.40 ± 3.61 years; 21 females, 6 males). MRI protocols comprised PD-weighted sequences in addition to the widely used standard protocol. JIA subgroups comprised oligoarticular arthritis (n = 16), extended oligoarthritis (n = 6), rheumatoid factor-negative polyarticular arthritis (n = 3), enthesitis-related arthritis (n = 1), and psoriatic arthritis (n = 1). MR images were retrospectively analyzed by 3 experienced radiologists in two readings, using JAMRIS (juvenile arthritis MRI scoring) system and a modified IPSG (international prophylaxis study group) classification. In the first reading session, only unenhanced MR images were evaluated. In a second reading session, all images before and after contrast medium application were included. In order to avoid bias, an interval of at least 2 weeks was set between the two readings. The clinical JADAS10 (juvenile arthritis disease activity score) was calculated including clinical assessment and laboratory workup and correlated with MRI scores. Statistical analysis comprised Pearson's correlation for correlating two scoring results of unenhanced and the enhanced MRI, intra-class correlation coefficient (ICC) for inter- and intra-reader agreement. Diagnostic accuracy was calculated using ROC (receiver operating characteristics) curve analysis. RESULTS: Inter-reader agreement determined by ICC for unenhanced and enhanced MRI scores for IPSG was moderate (0.65, 95% CI 0.51-0.76, and 0.62, 95% CI 0.48-0.75) and high for JAMRIS (0.83, 95% CI 0.75-0.89, and 0.82, 95% CI 0.74-0.89). Intra-reader agreement was good to very good for JAMRIS (0.85 95% CI 0.81-0.88, 0.87 95% CI 0.83-0.89 and 0.96 95% CI 0.92-0.98) and IPSG (0.76 95% CI 0.62-0.86, 0.86 95% CI 0.77-0.92 and 0.92 95% CI 0.86-0.96). Scores of unenhanced MRI correlated with contrast-enhanced MRI: JAMRIS (r = 0.97, R2 = 0.93, p < 0.01), modified IPSG (r = 0.95, R2 = 0.91, p < 0.01). When using JADAS10 as a reference standard, moderate accuracy for both unenhanced and enhanced MRI scores was noted: JAMRIS (AUC = 0.68, 95% CI 0.51-0.85, and AUC = 0.66, 95% 0.49-0.82), IPSG score (AUC = 0.68, 95% 0.50-0.86, and AUC = 0.61, 95% 0.41-0.81). CONCLUSIONS: Our results suggest that contrast agent application could be omitted in JIA patients with an augmented knee MRI protocol comprising PD-weighted sequence. KEY POINTS: • Unenhanced MRI can detect disease activity of the knee joint in patients with JIA with equally high accuracy compared to contrast-enhanced MRI. • The intra- and inter-reader agreement was high for unenhanced and enhanced MRI JAMRIS scores, which indicate relatively good applicability of the scoring system, even for less experienced readers. • When using the clinical JADAS10 as a reference standard for the detection of disease activity, moderate accuracy for both unenhanced and enhanced MRI scores, both JAMRIS and IPSG, was noted, which might be caused by the fact that the majority of patients had either no or minimal clinical disease activity.

[Glucocorticoid-induced osteoporosis-Focus treatment (part 2)]. / Glukokortikoid-induzierte Osteoporose ­ Fokus Therapie (Teil 2).

The following substances are approved for the treatment of glucocorticoid-induced osteoporosis: the oral bisphosphonates alendronate and risedronate, the intravenous bisphosphonate zoledronate, the RANKL antibody denosumab as antiresorptive substances and teriparatide as osteoanabolic substance. In comparison to placebo a reduction of vertebral fractures is proven for all mentioned substances. Thereby, teriparatide is more effective than alendronate and risedronate with respect to the reduction of vertebral fractures. The severity of osteoporosis, especially the presence of osteoporotic fractures, the approach of treatment (preventive or curative) and contraindications are factors that are important for the differentiated application of the mentioned substances. Furthermore, it must be noted that the effect of osteoanabolic treatment must be stabilized by a subsequent antiresorptive treatment and that after termination of antiresorptive treatment with denosumab a temporary bisphosphonate treatment is required to prevent a rebound phenomenon.

[Glucocorticoid-induced osteoporosis-Focus treatment (part 1)]. / Glukokortikoid-induzierte Osteoporose ­ Fokus Therapie (Teil 1).

With a fracture prevalence of 30-50%, glucocorticoid (GC)-induced osteoporosis is one of the most important comorbidities in inflammatory rheumatic diseases. Because of a reduction of bone quality with a lack of correlation with bone mineral density, the fracture risk during long-term GC treatment is not sufficiently represented by the currently available methods of osteodensitometry and therefore underestimated. According to the Confederation for Osteology (DVO) guidelines, a baseline osteological diagnosis including osteodensitometry is indicated in all postmenopausal women and in men aged 60 years and older who receive or are scheduled to receive GC at a dose of ≥ 2.5 mg prednisolone equivalent/day for > 3 months. Basic measures in GC-treated patients include vitamin D and calcium supplementation as well as measures to promote muscle strength and coordination and to prevent falls. The indications for a specific osteological treatment depend on the calculated GC dose, age, sex, and other fracture risk factors in addition to bone mineral density and prevalent fractures.

[Imaging of tumor predisposition syndromes]. / Bildgebung bei Tumorprädispositionssyndromen.

CLINICAL ISSUE: Tumor predisposition syndromes (TPS) are a heterogeneous group of genetic cancers. About 10% of the approximately 2200 malignancies in the childhood in Germany develop due to an inherited disposition, whereby TPS may be underdiagnosed. The focus of this review is set on imaging of Li-Fraumeni syndrome, neurofibromatoses, tuberous sclerosis, overgrowth, and neuroendocrine syndromes. STANDARD RADIOLOGICAL METHODS: In order to detect tumors at an early stage, screening at specific time intervals for each TPS are required. Ultrasonography and magnetic resonance imaging (MRI), especially whole-body MRI, are particularly important imaging modalities. METHODOLOGICAL INNOVATIONS: Innovative MRI techniques can increase image quality and patient comfort. MRI acquisition time can be significantly reduced through optimized acceleration factors, motion robust radial sequences and joint acquisition and readout of multiple slices during excitation. Thus, shorter MRI examinations can be performed in younger children without anesthesia. PRACTICAL RECOMMENDATION: Regular screening with ultrasound and MRI can reduce the morbidity and mortality of the patients affected with TPS.

[Specialist training situation in rheumatology from a trainer's perspective]. / Weiterbildungssituation in der Rheumatologie aus Sicht der Weiterbilder.

This article focuses on the training situation of rheumatologists from the perspective of trainers regarding the existing and potentially increasing deficits of specialists for internal medicine and rheumatology. According to the new regulations defining the rheumatologist training, a substantial part of the training schedule is required to be completed in a hospital setting in order to become a specialist rheumatologist. In this context, the increased training capacity necessitates additional hospital training positions. In addition, the rheumatology residents desire a structured training program. Significantly, the work-life balance is an important factor to make working as a specialist for internal medicine and rheumatology more attractive.

[Analysis of referral diagnoses to the rheumatology department]. / Analyse der Zuweisungsdiagnose in die internistische Rheumatologie.

BACKGROUND: The initial presentation of patients with symptoms indicative of a rheumatic disease is in most cases not directly to a rheumatologist. This study evaluated the following questions: I. Which medical specialists refer patients to a department of rheumatology? II. Evaluation of the accordance of the presumptive referral diagnosis and the final diagnosis by a rheumatologist. METHODS: A total of 947 patients (279 men and 668 women) who initially presented to a university hospital for rheumatological diagnostics were included in the study. The referring medical specialist fields were identified. Furthermore, a kappa analysis was performed to evaluate the accordance of the presumptive referral diagnosis and the final diagnosis generated after a rheumatological evaluation of the patients. RESULTS: Of the referrals 73% were initiated by general practitioners or internists functioning as general practitioners. The other referrers were 5% specialists in internal medicine (excluding rheumatology), 4% orthopedic/trauma surgeons, 1% other surgeons and 4% other specialist fields. A rheumatological diagnosis was made in 58% of the patients and rheumatological inflammatory joint diseases (26%), collagenosis (14%) and vasculitides (5%) were the most frequently diagnoses. The accordance of the presumptive diagnosis of the general practitioners and the final diagnosis after rheumatological evaluation was a kappa coefficient of κ = 0.304. Lower kappa values were evaluated for orthopedic surgeons (κ = 0.277) and other specialists (κ = 0.200). CONCLUSION: The referrals to a rheumatology institution were frequently initiated by general practitioners and internists functioning as general practitioners. In this context the presumptive diagnosis of general practitioners showed a low accordance with the final rheumatological diagnosis. In contrast, a detailed presumptive diagnosis is desirable for optimal use of the limited resources for rheumatological care.

[Future of rheumatologists: what are the perspectives? : Survey of resident physicians in rheumatology in middle Germany]. / Rheumatologin/Rheumatologe in spe: Wie geht es weiter? : Befragung der rheumatologischen Assistenzärzte und -ärztinnen in Mitteldeutschland.

BACKGROUND AND OBJECTIVE: The work environment for rheumatologists has significantly changed over the last years. The healthcare of patients with rheumatic diseases is at risk due to the age structure of specialized rheumatologists in middle Germany and the limited availability of training positions for rheumatologists. In this context, it is important to have detailed information on the resident physicians in rheumatology concerning their own visions regarding their future professional career. MATERIAL AND METHODS: A questionnaire was sent to resident physicians in 25 rheumatology training hospitals in the middle of Germany (Saxony, Saxony-Anhalt and Thuringia). The questionnaire was completed and returned by 27 participants (17 women and 10 men). RESULTS: Most of the participants (60%) aimed to qualify as a specialist in internal medicine followed by a specialization in rheumatology (altogether training for a minimum of 8 years). After finishing training 44% would prefer to work in an outpatient setting while 30% planned to work in a combined outpatient and clinical setting. Of the participants 48% would prefer to work as part-time rheumatologists and 74% (women 94% and men 40%) were interested in employment in an outpatient medical healthcare center. The compatibility of family and work as well as the work-life balance was considered to be highly relevant for the future professional life. CONCLUSION: Less than half of the participants intended to work exclusively in an outpatient setting after completing the training in rheumatology. In addition, the participants preferred a part-time employment with compatibility of professional and private life. Consequently, alternative models of employment should be created in rheumatology to be attractive for future physicians. On the other hand, the study revealed that the independent rheumatological practice has a lower priority for the young rheumatologists taking part in this survey.

MRI of cystic fibrosis lung manifestations: sequence evaluation and clinical outcome analysis.

AIM: To evaluate different magnetic resonance imaging (MRI) sequences for diagnosis of pulmonary manifestations of cystic fibrosis (CF) in comparison to chest computed tomography (CT), including an extended outcome analysis. MATERIALS AND METHODS: Twenty-eight patients with CF (15 male, 13 female, mean age 30.5±9.4 years) underwent CT and MRI of the lung. MRI (1.5 T) included different T2- and T1-weighted sequences: breath-hold HASTE (half Fourier acquisition single shot turbo spin echo) and VIBE (volumetric interpolated breath-hold examination, before and after contrast medium administration) sequences and respiratory-triggered PROPELLER (periodically rotated overlapping parallel lines with enhanced reconstruction) sequences with and without fat signal suppression, and perfusion imaging. CT and MRI images were evaluated by the modified Helbich and the Eichinger scoring systems. The clinical follow-up analysis assessed pulmonary exacerbations within 24 months. RESULTS: The highest concordance to CT was achieved for the PROPELLER sequences without fat signal suppression (concordance correlation coefficient CCC of the overall modified Helbich score 0.93 and of the overall Eichinger score 0.93). The other sequences had the following concordance: PROPELLER with fat signal suppression (CCCs 0.91 and 0.92), HASTE (CCCs 0.87 and 0.89), VIBE (CCCs 0.84 and 0.85) sequences. In the outcome analysis, the combined MRI analysis of all five sequences and a specific MRI protocol (PROPELLER without fast signal suppression, VIBE sequences, perfusion imaging) reached similar correlations to the number of pulmonary exacerbations as the CT examinations. CONCLUSION: An optimum lung MRI protocol in patients with CF consists of PROPELLER sequences without fat signal suppression, VIBE sequences, and lung perfusion analysis to enable high diagnostic efficacy and outcome prediction.

Trends in incidence and medical resource utilisation in patients with chronic lymphocytic leukaemia: insights from the UK Clinical Practice Research Datalink (CPRD).

Chronic lymphocytic leukaemia (CLL) is the most common leukaemia in European adults. We aimed to evaluate time trends in CLL incidence and medical resource utilisation of CLL patients in the UK. We conducted a retrospective, observational cohort analysis using the UK Clinical Practice Research Datalink (CPRD) comprising mainly primary care data. We included adult patients with newly diagnosed CLL between January 2000 and June 2012. Descriptive and trend analyses of CLL incidence and medical resource utilisation were performed. A total of 2576 patients with CLL met the eligibility criteria. At diagnosis, the majority of patients (71.7 %) were above 65 years of age. The European age-standardised CLL incidence rate in the CPRD was 6.2/100,000 (95 % confidence interval [CI] 6.0, 6.5/100,000) person-years. There was no statistically significant increase over time. The CLL patients had on average 74.6 general practitioner visits during a median follow-up of 3.3 years. Between 2000 and 2012, the average number of recorded hospitalisations and referrals per year corrected for duration of follow-up significantly (p < 0.001) increased by 8.1 % (95 % CI 6.8 %, 9.3 %) and 16.4 % (95 % CI 15.4 %, 17.3 %), respectively. Referrals and hospitalisations in the second year compared to the first year following the CLL diagnosis significantly decreased. CLL incidence rates in the CPRD were stable over the period from 2000 to 2012. Medical resource utilisation in UK primary care was well documented, but further research is needed to describe secondary and tertiary care medical resource utilisation e.g. chemotherapy administration, which is inadequately captured in the CPRD.

Impact of genetic variability and treatment-related factors on outcome in early breast cancer patients receiving (neo-) adjuvant chemotherapy with 5-fluorouracil, epirubicin and cyclophosphamide, and docetaxel.

To assess the impact of patient-related factors, including genetic variability in genes involved in the metabolism of chemotherapeutic agents, on breast cancer-specific survival (BCSS) and recurrence-free interval (RFI). We selected early breast cancer patients treated between 2000 and 2010 with 4-6 cycles of (neo-)adjuvant 5-fluorouracil, epirubicin, and cyclophosphamide (FEC) or 3 cycles FEC followed by 3 cycles docetaxel. Tumor stage/subtype; febrile neutropenia and patient-related factors such as selected single nucleotide polymorphisms and baseline laboratory parameters were evaluated. Multivariable Cox regression was performed. Of 991 patients with a mean follow-up of 5.2 years, 152 (15.3 %) patients relapsed and 63 (6.4 %) patients died. Advanced stage and more aggressive subtype were associated with poorer BCSS and RFI in multivariable analysis (p < 0.0001). Associations with worse BCSS in multivariable analysis were: homozygous carriers of the rs1057910 variant C-allele in CYP2C9 (hazard ratio [HR] 30.4; 95 % confidence interval [CI] 6.1-151.5; p < 0.001) and higher white blood cell count (WBC) (HR 1.2; 95 % CI 1.0-1.3; p = 0.014). The GT genotype of the ABCB1 variant rs2032582 was associated with better BCSS (HR 0.5; 95 % CI 0.3-0.9, p = 0.021). Following associations with worse RFI were observed: higher WBC (HR 1.1; 95 % CI 1.0-1.2; p = 0.026), homozygous carriers of the rs1057910 variant C-allele in CYP2C9 (HR 10.9; 95 % CI 2.5-47.9; p = 0.002), CT genotype of the CYBA variant rs4673 (HR 1.8; 95 % CI 1.2-2.7; p = 0.006), and G-allele homozygosity for the UGT2B7 variant rs3924194 (HR 3.4; 95 % CI 1.2-9.7, p = 0.023). Patient-related factors including genetic variability and baseline white blood cell count, impacted on outcome in early breast cancer.

Renal ablation in patients with end-stage renal disease.

BACKGROUND: Transarterial catheter embolization of the kidneys (TAE) is a minimally invasive, image-guided procedure. In this study outcome and TAE-related complications of the patients who underwent TAE of the kidneys were evaluated retrospectively. PATIENTS AND METHODS: Between August 2003 and August 2009, 11 patients underwent selective percutaneous transarterial renal embolization for end stage renal disease associated with uncontrolled hypertension, nephrotic syndrome, bleeding or malignancy. TAE of renal arteries was performed using different embolization agents. RESULTS: Successful renal embolization was possible in all 21 kidneys. All patients became anuric. Non-target embolization was not detectable. Nevertheless, all patients developed some degree of postembolization symptoms including nausea, vomiting, fever or pain. A typical finding after embolization was an increase in the C-reactive protein. CONCLUSIONS: Renal embolization is rarely done but should be considered as an alternative to surgical nephrectomy in patients with end stage renal disease due to the lesser invasiveness. Our study confirms the safety and effectivity of percutaneous renal embolization in patients with ESRD. We were able to control the hypertension, nephrotic syndrome, and bleeding caused by ESRD.

Transarterial catheter embolization of a sarcoma for preoperative conditioning.

This paper presents a case of an undifferentiated pleomorphic sarcoma/NOS (not otherwise specified; former pleomorphic - storiform malignant fibrous histiocytoma) of the lower leg, of a huge tumor causing ulceration of the cutaneous surface. To improve preoperative conditions, selective transarterial devascularization of the tumor feeders was performed. At operation the tumor was completely ischaemic allowing for clear tumor demarcation with little blood loss during surgery.

Whole-body MRI: a powerful alternative to bone scan for bone marrow staging without radiation and gadolinium enhancer.

PURPOSE: Whole-body magnetic resonance imaging (WB-MRI) is a radiation-free alternative to the 99mTc-HDP bone scan (BS) for the detection of bone metastasis. The major drawback is the long examination time and application of gadolinium enhancer. The aim of this study is to analyze (i) the performance of WB-MRI versus the BS and (ii) the diagnostic benefit of gadolinium (WB-MRI + Gd) compared to a non-enhanced protocol (NE WB-MRI). METHODS AND MATERIALS: 1256 eligible WB-MRI scans were analyzed retrospectively with a single inclusion criterion, a clinical 12-month follow-up or a biopsy as ground truth. N = 285 patients received both a WB-MRI and a BS within 12 months. All the patients were imaged with a coronal T1w and a STIR, and n = 528 (42%) received an additional T1w-mDixon with gadoteridol (0.1 mmol Gd-DTPA/kg). RESULTS: From 1256 eligible patients, n = 884 (70%) had breast cancer as a primary disease, n = 101(8%) prostate cancer, and n = 77(6%) lung cancer. The sensitivity (Se) and negative predictive value (NPV) of the WB-MRI was 98/99%, significantly higher compared to BS with 82/89%, P < 0.001 Mc Nemar's test. The specificity (Spe) and positive predictive value (PPV) of the WB-MRI and BS was 85/82% and 91/86%, respectively. The interobserver agreement between WB-MRI and BS was 71%, Cohen's kappa 0.42. Analysis of the added diagnostic value of gadolinium revealed Se/Spe/PPV/NPV of 98/93/92/98% for the NE WB-MRI and 99/93/85/100% for the WM-MRI + Gd, P > 0.05 binary logistic regression with Fischer's exact test. CONCLUSION: WB-MRI exceeds the sensitivity of BS without compromising the specificity, even after omitting the gadolinium enhancer.

Magnetic resonance imaging diagnosis: incomplete ossification of the humeral condyle in a German shepherd dog.

Clinical signs, radiological, arthroscopic findings and magnetic resonance imaging features of a male German shepherd dog with incomplete ossification of the humeral condyle are described. The dog showed recurrent left forelimb lameness and pain on elbow palpation. In routine radiographs, the lesion was obscured. In oblique radiographs, a radiolucent line was detected, and magnetic resonance imaging clearly demonstrated a defect in the humeral condyle. However, arthroscopy showed no changes or discontinuity of the humeral cartilage. Incomplete ossification of the humeral condyle may be underrepresented in conventional, routine studies because if there is concurrent additional elbow pathology (for example fragmented coronoid process), treatment may lead to clinical improvement and further diagnostic techniques may not be performed. The benefit of magnetic resonance imaging in this case is demonstrated.

Effects of long-term immobilisation on cortical bone mass after traumatic amputation of the phalanges estimated by digital X-ray radiogrammetry.

UNLABELLED: Osteopenia of the cortical and trabecular bone partition is a common finding after immobilisation. Digital X-ray radiogrammetry (DXR) seems to quantify cortical demineralisation caused by circular saw amputation already few days after accident. INTRODUCTION: The study analyses the extent of demineralisation caused by immobilisation in patients with digital amputation after a circular saw injury, and elucidates the period of time which discloses a significant deprivation of bone mineral density estimated at the metacarpalia II-IV using DXR. METHODS: Twenty-eight patients with digital amputations underwent measurements of bone mineral density, cortical thickness, bone width and metacarpal index using DXR-technology in a follow-up up to 902 days. RESULTS: The data showed a significant decline of bone mineral density (-10.47%), the metacarpal index (-4.38%), the bone width (-12.06%) and the cortical thickness (-7.04%) after trauma-related amputation. The cortical demineralisation of the metacarpals could already be revealed in two patients after the second day, according to the amputation of phalanges (-3.65%). CONCLUSIONS: The inhibition of the periosteal bone formation detected by DXR-technique seems to be a specific finding caused by amputation, which thus differs from normal age-related (i.e., endosteal) bone loss and from demineralisation following acute immobilisation (i.e., trabecular osteopenia).

[Influence of body constitution on bone mineral density measured by digital radiogrammetry]. / Einfluss der Körperkonstitution auf die mittels digitaler Radiogrammetrie evaluierte Knochenmineraldichte.

PURPOSE: In addition to many established osteodensitometric techniques, digital radiogrammetry (DXR) is considered to be a reliable method for measuring the cortical bone mineral density (DXR-BMD). This study investigates the influence of body constitution on BMD of healthy adults as calculated by DXR. MATERIALS AND METHODS: In a prospective study, 246 adults without bone affecting diseases in their clinical history underwent DXR for analysis and calculations of bone mineral density and determination of metacarpal index (MCI) and porosity index (PI). Height, weight and body mass index (BMI) were recorded for each patient. RESULTS: For all individuals and for all BMI subgroups, both height (0.55 < R < 0.70, p < 0.01) and body weight (0.56 < R < 0.78, p < 0.01) correlated closely with DXR-BMD. Only in the over-weight group, no significant correlation was found between body weight and DXR-BMD. In addition, a significant reduction of the relative DXR-BMD and MCI values was observed between the over-weight and the under-weight group as well as between normal-weight and under-weight individuals (p < 0.01). Otherwise, cortical porosity decreased with increasing body weight. CONCLUSION: Similar to Dual Energy X-ray Absorptiometry-based studies (DXA), digital radiogrammetry measures an increase in BMD with increasing body weight. Therefore DXR, which provides a precise technique without influence of soft tissue, seems to be a promising technique for quantifying marginal alterations in cortical BMD as well for following the course of osteoporosis.

Irradiated homozygous TGF-beta1 knockout fibroblasts show enhanced clonogenic survival as compared with TGF-beta1 wild-type fibroblasts.

PURPOSE: To study the role of transforming growth factor beta1 (TGF-beta1) on cellular radiation sensitivity by analysing mouse lung fibroblasts of different TGF-beta1 genotypes. MATERIALS AND METHODS: Heterozygous TGF-beta1 knock-out mice were mated to produce offspring of different TGF-beta1 genotypes as confirmed by PCR-genotyping. Primary lung fibroblast populations were established from new-born animals of specific genotypes (TGF-beta1(+/+), TGF-beta1(+/-), TGF-beta1(-/-)). Production of TGF-beta1 was tested by ELISA. TGF-beta1 receptor-II mRNA expression was analysed by RT-PCR. Colony formation of untreated, TGF-beta1-treated and/or irradiated primary lung fibroblasts was determined under different medium conditions. RESULTS: Plating efficiencies under different medium conditions were independent of TGF-beta1 genotype. Production of TGF-beta1 correlated with the genotype: heterozygous TGF-beta1 knock-out fibroblasts (TGF-beta1(+/-)) produced 60-65% of wild-type (TGF-beta1(+/+) cells). As expected, homozygous TGF-beta1 knock-out fibroblasts (TGF-beta1(-/-)) did not produce TGF-beta1. Radiation exposure significantly enhanced TGF-beta1 production in TGF-beta1(+/+) cells by a factor of 2. No such stimulation was observed in TGF-beta1(+/-) cells. TGF-beta1(+/-) and especially TGF-beta1(-/-) cells were significantly more radioresistant than TGF-beta1(+/+) cells. TGF-beta1 treatment significantly reduced clonogenic survival for both TGF-beta1(+/+) and TGF-beta1(-/-) cells. TGF-beta1 treatment of TGF-beta1(-/-) cells resulted in an enhancement of radiation sensitivity. CONCLUSION: The data are the first direct evidence that TGF-beta1 is a major autocrine regulator of intrinsic radiation sensitivity of mouse lung fibroblasts.

Identification of two independent MHC class II antigens in a bovine lymphoblastoid cell line.

Bovine major histocompatibility complex (MHC) class II antigens were investigated using monoclonal antibodies (MoAbs) with known MHC class II specificities in other species. Thirty-four MoAbs were tested for reactivity with bovine peripheral blood mononuclear (PBM) cells and the bovine lymphoblastoid cell line, BL3, by flow cytometry. Twenty-seven of 31 MoAbs tested, reacted with BL3 cells, and 22 of 25 MoAbs tested with PBM cells were reactive. MoAbs that reacted with BL3 cells were used to immunoprecipitate class II molecules from BL3 lysate labeled with [35S]methionine. Using sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and autoradiography, many MoAbs were found to immunoprecipitate a single band of approximately 31,000 relative mass (Mr). MoAbs yielding successful immunoprecipitations and with known antigen specificity in other species were then used in sequential immunoprecipitations and two dimensional (2-D) non-equilibrium pH gradient electrophoresis (NEPHGE). The HLA-DR specific MoAb H4 and the predominantly HLA-DQ specific MoAb CC11.23 were used to identify the presence of two independent antigens in BL3 cell lysate. These class II molecules consist of alpha and beta chains.