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Background: Low-dose computed tomography (lung cancer screening) can reduce lung cancer-specific mortality by 20-24%. Based on this evidence, the United States Preventive Services Task Force recommends annual lung cancer screening for asymptomatic high-risk individuals. Despite this recommendation, utilization is low (3-20%). Lung cancer screening may be particularly beneficial for African American patients because they are more likely to have advanced disease, lower survival, and lower screening rates compared to White individuals. Evidence points to multilevel approaches that simultaneously address multiple determinants to increase screening rates and decrease lung cancer burden in minoritized populations. This study will test the effects of provider- and patient-level strategies for promoting equitable lung cancer screening utilization., Methods: Guided by the Health Disparities Research Framework and the Practical, Robust Implementation and Sustainability Model, we will conduct a quasi-experimental study with four primary care clinics within a large health system (MedStar Health). Individuals eligible for lung cancer screening, defined as 50-80 years old, ≥ 20 pack-years, currently smoking, or quit < 15 years, no history of lung cancer, who have an appointment scheduled with their provider, and who are non-adherent to screening will be identified via the EHR, contacted, and enrolled (N = 184 for implementation clinics, N = 184 for comparison clinics; total N = 368). Provider participants will include those practicing at the partner clinics (N = 26). To increase provider-prompted discussions about lung screening, an electronic health record (EHR) clinician reminder will be sent to providers prior to scheduled visits with the screening-eligible participants. To increase patient-level knowledge and patient activation about screening, an inreach specialist will conduct a pre-visit phone-based educational session with participants. Patient participants will be assessed at baseline and 1-week post-visit to measure provider-patient discussion, screening intentions, and knowledge. Screening referrals and screening completion rates will be assessed via the EHR at 6 months. We will use mixed methods and multilevel assessments of patients and providers to evaluate the implementation outcomes (adoption, feasibility, acceptability, and fidelity)., Discussion: The study will inform future work designed to measure the independent and overlapping contributions of the multilevel implementation strategies to advance equity in lung screening rates., Trial Registration: ClinicalTrials.gov, NCT04675476. Registered December 19, 2020., (© 2024. The Author(s).)

Magnetic particle imaging (MPI) is an imaging modality to quantitatively determine the three-dimensional distribution of magnetic nanoparticles (MNPs) administered as a tracer into a biological system. Magnetic particle spectroscopy (MPS) is the zero-dimensional MPI counterpart without spatial coding but with much higher sensitivity. Generally, MPS is employed to qualitatively evaluate the MPI capability of tracer systems from the measured specific harmonic spectra. Here, we investigated the correlation of three characteristic MPS parameters with the achievable MPI resolution from a recently introduced procedure based on a two-voxel-analysis of data taken from the system function acquisition that is mandatory in Lissajous scanning MPI. We evaluated nine different tracer systems and determined their MPI capability and resolution from MPS measurements and compared the results with MPI phantom measurements., Competing Interests: The authors declare no conflict of interest., (This journal is © The Royal Society of Chemistry.)

For the preclinical development of magnetic particle imaging (MPI) in general, and the exploration of possible new clinical applications of MPI in particular, tailored MPI tracers with surface properties optimized for the intended use are needed. Here we present the synthesis of magnetic multicore particles (MCPs) modified with polyethylene glycol (PEG) for use as blood pool MPI tracers. To achieve the stealth effect the carboxylic groups of the parent MCP were activated and coupled with pegylated amines (mPEG-amines) with different PEG-chain lengths from 2 to 20 kDa. The resulting MCP-PEG variants with PEG-chain lengths of 10 kDa (MCP-PEG10K after one pegylation step and MCP-PEG10K2 after a second pegylation step) formed stable dispersions and showed strong evidence of a successful reaction of MCP and MCP-PEG10K with mPEG-amine with 10 kDa, while maintaining their magnetic properties. In rats, the mean blood half-lives, surprisingly, were 2 and 62 min, respectively, and therefore, for MCP-PEG10K2, dramatically extended compared to the parent MCP, presumably due to the higher PEG density on the particle surface, which may lead to a lower phagocytosis rate. Because of their significantly extended blood half-life, MCP-PEG10K2 are very promising as blood pool tracers for future in vivo cardiovascular MPI.

Magnetic Particle Imaging (MPI) is a new imaging modality, which maps the distribution of magnetic nanoparticles (MNP) in 3D with high temporal resolution. It thus may be suited for cardiovascular imaging. Its sensitivity and spatial resolution critically depend on the magnetic properties of MNP. Therefore, we used novel multicore nanoparticles (MCP 3) for in-vivo MPI in rats and analyzed dose requirements, sensitivity and detail resolution. 8 rats were examined using a preclinical MPI scanner (Bruker Biospin GmbH, Germany) equipped with a separate receive coil. MCP 3 and Resovist were administered intravenously (i.v.) into the rats' tail veins at doses of 0.1, 0.05 and 0.025 mmol Fe/kg followed by serial MPI acquisition with a temporal resolution of 46 volumes per second. Based on a qualitative visual scoring system MCP 3-MPI images showed a significantly (P ≤ 0.05) higher image quality than Resovist-MPI images. Morphological features such as vessel lumen diameters (D L ) of the inferior vena cava (IVC) and abdominal aorta (AA) could be assessed along a 2-cm segment in mesenteric area only after administration of MCP 3 at dosages of 0.1, 0.05 mmol Fe/kg. The mean D L  ± SD estimated was 2.7 ± 0.6 mm for IVC and 2.4 ± 0.7 mm for AA. Evaluation of D L of the IVC and AA was not possible in Resovist-MPI images. Our results show, that MCP 3 provide better image quality at a lower dosage than Resovist. MCP 3-MPI with a clinically acceptable dose of 0.05 mmol Fe/kg increased the visibility of vessel lumens compared to Resovist-based MPI towards possible detection of vascular abnormalities such as stenosis or aneurysms, in vivo.

Magnetic particle imaging (MPI) is a new imaging technique that detects the spatial distribution of magnetic nanoparticles (MNP) with the option of high temporal resolution. MPI relies on particular MNP as tracers with tailored characteristics for improvement of sensitivity and image resolution. For this reason, we developed optimized multicore particles (MCP 3) made by coprecipitation via synthesis of green rust and subsequent oxidation to iron oxide cores consisting of a magnetite/maghemite mixed phase. MCP 3 shows high saturation magnetization close to that of bulk maghemite and provides excellent magnetic particle spectroscopy properties which are superior to Resovist ® and any other up to now published MPI tracers made by coprecipitation. To evaluate the MPI characteristics of MCP 3 two kinds of tube phantoms were prepared and investigated to assess sensitivity, spatial resolution, artifact severity, and selectivity. Resovist ® was used as standard of comparison. For image reconstruction, the regularization factor was optimized, and the resulting images were investigated in terms of quantifying of volumes and iron content. Our results demonstrate the superiority of MCP 3 over Resovist ® for all investigated MPI characteristics and suggest that MCP 3 is promising for future experimental in vivo studies.

Synthesis of novel magnetic multicore particles (MCP) in the nano range, involves alkaline precipitation of iron(II) chloride in the presence of atmospheric oxygen. This step yields green rust, which is oxidized to obtain magnetic nanoparticles, which probably consist of a magnetite/maghemite mixed-phase. Final growth and annealing at 90°C in the presence of a large excess of carboxymethyl dextran gives MCP very promising magnetic properties for magnetic particle imaging (MPI), an emerging medical imaging modality, and magnetic resonance imaging (MRI). The magnetic nanoparticles are biocompatible and thus potential candidates for future biomedical applications such as cardiovascular imaging, sentinel lymph node mapping in cancer patients, and stem cell tracking. The new MCP that we introduce here have three times higher magnetic particle spectroscopy performance at lower and middle harmonics and five times higher MPS signal strength at higher harmonics compared with Resovist®. In addition, the new MCP have also an improved in vivo MPI performance compared to Resovist®, and we here report the first in vivo MPI investigation of this new generation of magnetic nanoparticles.

Background: Pharmacokinetic studies and histological detection of superparamagnetic iron oxide nanoparticles (SPIO) in biomedical research are limited due to a high iron background especially in pathological tissues., Objective: The suitability of doping the iron oxide cores of SPIO with europium (Eu) was tested for improved histologic detection and for quantitative analysis without changing their properties as probes for magnetic resonance imaging (MRI). A special variant of SPIO, so called very small superparamagnetic iron oxide nanoparticles (VSOP), was used for this approach., Methods: VSOP, stabilized by a citrate coating, were synthesized with and without addition of Eu (Eu-VSOP and VSOP, respectively). MR signal enhancing effects of Eu-VSOP and VSOP were studied in vitro. Cellular uptake of Eu-VSOP and VSOP was examined in RAW264.7 cells. For Eu-VSOP, fluorescence microscopy and spectrophotometry were used. Eu fluorescence was enhanced by means of an antenna system. For VSOP, Prussian blue staining and photometry using the phenanthroline method were applied. Results for both VSOP variants were compared., Results: Eu-VSOP and VSOP did not differ with respect to MR signal enhancing effects nor to uptake characteristics in the RAW264.7 cell experiments. Fluorescence microscopy detects Eu-VSOP with higher sensitivity compared to light microscopy using Prussian blue staining. In microscopy as well as in the analytical quantification using fluorescence, detection of Eu-VSOP is not contaminated by Fe background., Conclusions: Doping the VSOP with Eu allows for their improved detection by fluorescence microscopy and quantitative analysis without changing their cellular uptake characteristics or their MR signal enhancing effects and thus would allow for a multimodal approach for studying their pharmacokinetics and biodistribution in experimental research.

As emerging responsive materials, ferrogels have demonstrated significant potential for applications in areas of engineering to regenerative medicine. Promising techniques to study the behavior of magnetic nanoparticles (MNPs) in such matrices include magnetic particle spectroscopy (MPS) and magnetorelaxometry (MRX). This work investigated the magnetic response of gelatin-based ferrogels with increasing temperatures, before and after high energy crosslinking. The particle response was characterized by the nonlinear magnetization using MPS and quasistatic magnetization measurements as well as MRX to discriminate between Néel and Brownian relaxation mechanisms. The effective magnetic response of MNPs in gelatin was suppressed, indicating that the magnetization of the ferrogels was strongly influenced by competing dipole-dipole interactions. Significant changes in the magnetic behavior were observed across the gelatin sol-gel transition, as influenced by the matrix viscosity. These relaxation processes were modeled by Fourier transformation of the Langevin function, combined with a Debye term for the nonlinear magnetic response, for single core MNPs embedded in matrices of changing viscosities. Using high energy electron irradiation as a crosslinking method, modified ferrogels exhibited thermal stability on a range of timescales. However, MRX relaxation times revealed a slight softening around the gelatin sol-gel transition felt by the smallest particles, demonstrating a high sensitivity to observe local changes in the viscoelasticity. Overall, MPS and MRX functioned as non-contact methods to observe changes in the nanorheology around the native sol-gel transition and in crosslinked ferrogels, as well as provided an understanding of how MNPs were integrated into and influenced by the surrounding matrix.

The development of iron oxide nanoparticles for biomedical applications requires accurate histological evaluation. Prussian blue iron staining is widely used but may be unspecific when tissues contain substantial endogenous iron. Here we tested whether microscopy by laser ablation coupled to inductively coupled plasma mass spectrometry (LA-ICP-MS) is sensitive enough to analyze accumulation of very small iron oxide particles (VSOP) doped with europium in tissue sections. For synthesis of VSOP, a fraction of Fe3+ (5 wt%) was replaced by Eu3+, resulting in particles with 0.66 mol% europium relative to iron (Eu-VSOP) but with otherwise similar properties as VSOP. Eu-VSOP or VSOP was intravenously injected into ApoE-/- mice on Western cholesterol diet and accumulated in atherosclerotic plaques of these animals. Prussian blue staining was positive for ApoE-/- mice with particle injection but also for controls. LA-ICP-MS microscopy resulted in sensitive and specific detection of the europium of Eu-VSOP in liver and atherosclerotic plaques. Furthermore, calibration with Eu-VSOP allowed calculation of iron and particle concentrations in tissue sections. The combination of europium-doped iron oxide particles and LA-ICP-MS microscopy provides a new tool for specific and quantitative analysis of particle distribution at the tissue level and allows correlation with other elements such as endogenous iron.

To further optimize citrate-stabilized VSOPs (very small iron oxide particles, developed for MR angiography) for identification of atherosclerotic plaques, we modified their surface during synthesis using eight other acids for electrostatic stabilization. This approach preserves effective production for clinical application. Five particles were suitable to be investigated in targeting plaques of apoE(-/-) mice. Accumulation was evaluated by ex vivo MRI, TEM, and quantitatively by magnetic particle spectroscopy (MPS). Citric- (VSOP), etidronic-, tartaric-, and malic-acid-coated particles accumulated in atherosclerotic plaques with highest accumulation for VSOP (0.2‰ of injected dose). Targets were phagolysosomes of macrophages and of altered endothelial cells. In vivo MRI with VSOP allowed for definite plaque identification. Prussian blue staining revealed abundant endogenous iron in plaques, indistinguishable from particle iron. In apoE(-/-) mice, VSOPs are still the best anionic iron oxide particles for imaging atherosclerotic plaques. MPS allows for quantification of superparamagnetic nanoparticles in such small specimens., From the Clinical Editor: The presence of vulnerable plaques in arteries is important for the prediction of acute coronary events. VSOP (very small iron oxide particles, developed for MR angiography) have been shown to be very sensitive in identifying atherosclerotic plaques. The authors studied here further modification to the surface of VSOP during synthesis and compared their efficacy., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Unlabelled: The coupling of polyethylene glycol (PEG) to proteins (PEGylation) has become a standard method to prolong blood circulation of imaging probes and other proteins, liposomes, and nanoparticles. However, concerns have arisen about the safety of PEG, especially with respect to its poor biodegradability and antibody formation, including new evidence about preformed anti-PEG antibodies in a quarter of healthy blood donors. Here, we apply a new hydrophilic polypeptide XTEN to extend the blood half-life of an imaging probe. As an example, we chose annexin A5 (AnxA5), a recombinant 35-kD protein extensively used for the in vitro and in vivo detection of apoptosis, that has a blood half-life of less than 7 min in mice, limiting its accumulation in target tissues and therefore limiting its utility as an imaging reagent., Methods: The sequence of XTEN was developed by Volker Schellenberger and colleagues by evolutionary in vitro optimization to yield PEG-like properties but provides several key advantages in comparison to PEG. The DNA of a 288-amino-acid version of XTEN with an additional N-terminal cysteine for site-directed coupling was fused to AnxA5 (XTEN-AnxA5). The fusion protein could be highly expressed in Escherichia coli and efficiently purified using XTEN conveniently as a purification tag. It was labeled with a thiol-reactive fluorescent dye and via a chelator with a radionuclide., Results: SPECT/CT imaging revealed a blood half-life of about 1 h in mice, markedly longer than the 7-min blood half-life for unmodified AnxA5, which should allow improved imaging of target tissues with low perfusion. In comparison to AnxA5, XTEN-AnxA5 demonstrated a substantially higher accumulation in tumors under chemotherapy in near-infrared fluorescence imaging., Conclusion: The presented method allows the expression and production of high amounts of long-circulating XTEN-AnxA5 without the necessity of PEGylation, thereby simplifying the synthesis while avoiding labeling-induced inactivation of AnxA5 and potential adverse effects of PEG. It is readily applicable to other recombinant protein or peptide-based imaging probes and allows fine-tuning of the desired blood half-life, because longer XTEN variants yield longer blood half-lives.

Magnetic particle imaging (MPI) is a new imaging technique for visualizing the three-dimensional distribution of superparamagnetic iron oxide nanoparticles with specific properties (MPI tracers). Initial results obtained with MPI using superparamagnetic iron oxide as blood pool markers suggest that the method has great potential for cardiovascular imaging. Conversely, no clinically approved MPI tracers currently exist that could be used to exploit this potential of MPI. This article describes thermal decomposition and coprecipitation, two relevant methods for synthesizing and optimizing superparamagnetic iron oxide nanoparticles for MPI. Furthermore it summarizes the recent literature on MPI tracers and explores what can be learned from structural studies with Resovist(®) for novel synthesis approaches.

Retention of gadolinium (Gd) in biological tissues is considered an important cofactor in the development of nephrogenic systemic fibrosis (NSF). Research on this issue has so far focused on the stability of Gd-based contrast media (GdCM) and a possible release of Gd³⁺ from the complex. No studies have investigated competing chelators that may occur in vivo. We performed proton T(1) -relaxometry in solutions of nine approved GdCM and the macromolecular chelator heparin (250 000 IU per 10 ml) without and with addition of ZnCl₂. For the three linear, nonspecific GdCM complexes, Omniscan®, OptiMARK® and Magnevist®, 2 h of incubation in heparin at 37 °C in the presence of 2.0 mm ZnCl₂ led to an increase in T₁-relaxivity by a factor of 7.7, 5.6 and 5.1, respectively. For the three macrocyclic complexes, Gadovist®, Dotarem® and Prohance®, only a minor increase in T₁-relaxivity by a factor of 1.5, 1.6 and 1.7 was found, respectively. Without addition of ZnCl₂, no difference between the two GdCM groups was observed (factors of 1.4, 1.2, 1.1, 1.3, 1.5 and 1.4, respectively). The increase in T₁-relaxivities observed for linear GdCM complexes may be attributable to partial transchelation with formation of a macromolecular Gd-heparin complex. For comparison, mixing of GdCl₃ and heparin results in a 8.7-fold higher T₁-relaxivity compared with a solution of GdCl₃ in water. Heparin is a glycosaminoglycan (GAG) and as such occurs in the human body as a component of the extracellular matrix. GAGs generally are known to be strong chelators. Gd³⁺ released from chelates of GdCM might be complexed by GAGs in vivo, which would explain their retention in biological tissues. Plasma GAG levels are elevated in end-stage renal disease; hence, our results might contribute to the elucidation of NSF., (Copyright © 2012 John Wiley & Sons, Ltd.)

Background: Annexin A5 (anxA5) has been found useful for molecular imaging of apoptosis and other biological processes., Methods: Here, we report an optimised two-step synthesis of annexin A5-diethylene triamine pentaacetic acid (DTPA) (anxA5-DTPA) for positron emission tomography (PET) and single-photon emission computed tomography (SPECT) imaging with a single purification step. The use of a recombinant annexin A5 (cys-anxA5) with a single thiol group allowed regionally specific coupling, without affecting the binding domain of cys-anxA5., Results: The metal complexing capacity of anxA5-DTPA was investigated by labelling with 111In3+ and Eu3+. Binding of modified anxA5-DTPA to apoptotic cells was tested in competition experiments with a fluorescent anxA5 derivative (anxA5-FITC) using flow cytometry and compared with that of wildtype anxA5 or non-binding anxA5-DTPA (M1234-anxA5-DTPA). The binding affinity to apoptotic cells of the anxA5-DTPA conjugate does not differ from that of wildtype anxA5., Conclusions: This two-step synthesis of annexin A5-DTPA resulted in biologically active anxA5-DTPA, which can be labelled with radionuclides for use in SPECT and PET imaging.

Background: The purpose of the study was to identify and to profile alcohol-related attendances to emergency rooms (ERs) of 11 hospitals of various medical specialties covering a large urban population, to assess risk factors associated with short-stay cases, repeat attendances and higher degree of alcohol consumption and to estimate their impact on the alcohol-related burden at ERs., Methods: A 6-months study was carried out to obtain clinical and administrative data on single and multiple attendances at ERs in 11 governmental acute hospitals in a large city in Germany. All alcohol-related attendances at ERs of study hospitals were eligible. A broad definition of alcohol-related attendances independently from alcohol diagnosis and various demographic, clinical and administrative measures were used. Odds ratios for the associations of these measures with duration of stay, repeat attendances and higher degrees of alcohol consumption were derived from multivariate binomial and multinomial logistic regression models., Results: 1,748 patients with symptoms of alcohol consumption or withdrawal (inclusion rate 83.8%) yielded 2,372 attendances (3% of all medical admissions), and resulted in 12,629 inpatient-days. These patients accounted for 10.7 cases per 1,000 inhabitants. The average duration of inpatient stay was 10 days. 1,451 of all patients (83%) presented once, whereas the median of repeat attendances was three for the remaining 297 patients. Short-stay cases (<24 hours) were significantly linked with male gender, alcohol misuse, trauma (or suspicion of a trauma) and medical specialties. Increased levels of alcohol consumption at first attendance were significantly associated with repeat attendances in due course. In a multinomial logistic regression model higher degrees of alcohol consumption were significantly associated with male gender, trauma, short-stays, attendance outside regular working time, and with repeat attendances and self-discharge., Conclusion: Apart from demographic factors, the alcohol-related clinical burden is largely determined by short-stay cases, repeat attendances and cases with higher levels of alcohol consumption at first attendance varying across medical specialties. These findings could be relevant for the planning of anti-alcoholic interventions at ERs.

When irradiating under high voltage condition, verification photographs prove to be difficult to take if the Gantry position is not aligned to 0 degree respectively 180 degrees, since the patient is being irradiated diagonally. Under these conditions it is extremely difficult to align the X-ray-cartridge vertically to the central beam of the therapeutic radiation. This results in, amongst others, misprojections, so that definite dimensions of portrayed organ structures become practical impossible to determine. This paper presented describes how we have solved these problems on our high voltage units (tele-gamma cobalt unit and linear-accelerator). By using simple accessories, determination of dimensions of organ structures, as shown on the verification photographs, are made possible. We illustrate our method by using the so-called tangential fields technique when irradiating mamma carcinoma.

Pseudocysts, fistulae and abscesses are common complications of acute and acute-recurrent pancreatitis. Extension of necrosis and pseudocysts occur along anatomically determined structures. Extension of pancreatic necrosis into the mediastinum is rare. One such case is described. Possible mechanisms for the occurrence of acute and relapsing pancreatitis are discussed.

Excretory urography has been the most important examination in retroperitoneal fibrosis (RPF). Medial deviation of the ureters at the level of the lower lumbar spine with hydronephrosis and dilatation of the upper part of the ureters have been considered diagnostic of RPF. Nowadays RPF can be easily recognized via CT studies, provided if appears as a mass. However, often CT studies do not detect PRF in spite of the presence of characteristic urographic changes and although RPF has been diagnosed microscopically. RPF involves the vascular system, too, and the visualization of compression or occlusion especially of the inferior vena cava or the iliac veins is also helpful in the diagnosis of RPF. In this paper we describe a case of RPF (diagnosis was confirmed histopathologically) with characteristic urographic changes, but no evidence of retroperitoneal mass. However, in this case RPF had led to a circumscribed phlebectasis of perivesical veins, which we demonstrated via CT and angiography.

Excretory urography has been one of the most helpful tools in diagnosis of retroperitoneal fibrosis (RPF). Ventro-medial deviation of the ureters at the level of lower lumbar spine with urinary obstruction and pointed clinical stenosis of the upper part of the ureters have been considered diagnostic of RPF. It can be easily forgotten that RPF can become clinically apparent as vascular disease. Various types of RPF appearances will be discussed in the light of two examples.

A female infant already as a newborn progressively developed nutritional disturbances, metabolic acidosis, muscular hypotension and other neurologic changes, and on its 20th day of life suffered from an acute cardiac and respiratory insufficiency due to pericardial effusions causing cardiac tamponade. In spite of intensive care including mechanical ventilation the child died on the 58th day of life. Cardiac changes and cranial CT-scans are demonstrated. The characteristic symptomatology as well as blood chemistry led to the tentative diagnosis of Leigh's disease. Postmortem examination confirmed this diagnosis.

Flow phenomena can cause artifacts that may simulate thrombosis. The differentiation between thrombus and flow phenomenon can be made by delayed scans and certain CT-findings in thrombosis that may not be found in pseudothrombosis.

C1 and C1 activity measurements were performed with EA and EAC4 prepared with rabbit anti-Forssman IgG or IgM and were compared to measurements with EA and EAC4 prepared with mouse monoclonal IgG2b and IgM anti-DNP antibodies on cells coupled with TNP: the amount of TNP per cell was optimal for antibody activity. No differences were found in the ability of EAC4 made with poly- or monoclonal IgM to measure C1 activity; in contrast, monoclonal IgM was capable of activating only about 30% of C1 when compared to activation by polyclonal IgM. Monoclonal vs polyclonal IgGs behaved in a similar manner but they were detecting only 50% of C1 or C1 activity when compared to IgM of the appropriate class. It was concluded that monoclonal antibodies were capable of generating EAC4 intermediate, and that the ability of monoclonal antibodies in the EAC4 complex to bind C1 and to detect C1 activity is not significantly different from that of polyclonal antibodies but that monoclonal antibodies are less efficient in activating C1 than polyclonal antibodies.

Complement (C)-dependent hemolytic dose-response curves of anti-TNP IgG2b and IgM monoclonal antibodies as a function of TNP density were analyzed: sheep red cells coupled with TNP served as targets. Under conditions when equal numbers of either IgG2b or IgM anti-TNP antibodies were taken up by cells with various TNP densities, both antibodies showed optimal activity at a hapten density of approximately 10(6) TNP/E with regard to C-mediated lysis. These results were similar to those obtained with polyclonal antibodies. The effectiveness of monoclonal antibodies in utilizing guinea pig or mouse C was also investigated. IgM anti-TNP monoclonal antibodies lysed E-TNP in the presence of guinea pig C, but failed to produce lysis in the presence of mouse C. Two monoclonal IgG1 (anti-TNP and anti-SRBC) and an IgG2a anti-TNP antibody failed to produce hemolysis in the presence of guinea pig and mouse C. IgG2b monoclonal antibodies, whether directed against TNP or Forssman antigen, activated guinea pig and, to a lesser extent, mouse C. Finally, monoclonal anti-TNP IgG3 antibodies exhibited a low but measurable hemolytic activity with guinea pig C (10-20 times below that of IgG2b).

The differential diagnosis of angiomyolipomas is an manifold as their angiographic appearances. The differentiation of this renal hamartoma from its most important differential diagnosis, carcinoma of the kidney, is possible only occasionally even when one includes epidemiological, clinical and angiographic findings, CT, in the other hand, provides certain pre-operative diagnosis in most cases by showing portions of the tumour of fat density. In any case, surgical treatment should be carried out, but the actual procedure will be significantly influenced. Demonstration of a benign space-occupying lesion allows one to plan a procedure which will preserve the kidney.

Sheep erythrocytes were coupled with trinitophenyl sulphonate, sensitized with anti-TNP (or-DNP) IgM monoclonal antibodies, and exposed to components of the classical pathway of complement activation. When human fibronectin (FN) was added after C1q, but before addition of C1r and C1s (subunits of the first complement component), inhibition of haemolytic activity was observed which was strictly dependent upon the dose of FN. When FN was added after addition of C1 (reconstituted from C1q, C1r and C1s), the haemolytic activity of complement was not affected by the presence of FN. These data suggest that FN binds on C1q by interfering with C1r and C1s fixation. In addition, FN was unable to displace the activated subcomponents (C1r and C1s) from their binding site on C1q. When using other systems (sheep erythrocytes sensitized with anti-Forssman IgM monoclonal antibodies), the quantity of FN required to inhibit complement haemolytic activity was greater than in the TNP system. In normal plasma, there is a 50-fold excess of FN compared to free C1q.