[Effectiveness of sacral neuromodulation in patients with Parkinson's disease]. / Efficacité de la neuromodulation sacrée chez le patient parkinsonien.

INTRODUCTION: The urinary disorders of the patients with Parkinson's disease are complex and have a negative impact on their quality of life. None of therapy is considered effective ; whether drug or surgical. Sacral neuromodulation, recommended in other neurological pathologies such as multiple sclerosis, has never been studied in the patients with Parkinson's disease. The objective of our study is to assess the efficacy of sacral neuromodulation in the patients with Parkinson's disease. MATERIAL AND METHOD: Multicentric retrospective cohort study, of 22 parkinsonian patients who underwent a sacral neuromodulation test. Epidemiological, clinical and urodynamic data were collected for each patient. A long-term effectiveness telephone survey was conducted. RESULTS: Twenty two patients with Parkinson's disease had a sacral neuromodulation test. 17/22 (77%) had Idiopathic Parkinson's Disease and 5/22 (23%) had Systematized Multi Atrophy. Clinically, the indication for the sacral neuromodulation test was overactive bladder in 68% of the cases. Urodynamically, detrusor hyperactivity is found in 12 patients (8 MPI, 4 AMS). Sacral neuromodulation was effective in only 7 patients (6 MPI and 1 AMS). Rather, the profile of the patient in whom NMS is effective is female, mature, and with PID. The long-term effectiveness of NMS is disappointing. Only 2 permanently implanted patients retained urinary benefit. CONCLUSION: NMS improves urinary symptoms in the patients with Parkinson's disease in 32% of cases. It fluctuates over time and loses its effectiveness in the long term.

[Renal Trauma]. / Traumatismes du rein.

INTRODUCTION: Renal traumas are common, observed in 10% of patients with abdominal trauma. Most renal traumas are blunt, resulting from a direct hit or from an abrupt deceleration. MATERIAL AND METHODS: We realized a synthesis of renal trauma management for nurses. RESULTS: Clinical presentation often encompasses gross hematuria and lumbar pain. The best diagnostic tool is computed tomography (CT) urogram. Based on CT urogram images, renal traumas are classified according to the American Association for the Surgery of Trauma (AAST) classification in five grades of increasing severity. The management is conservative in the vast majority of cases and has been largely simplified over the past few years, being now mostly based on observation. Radiological interventional and endoscopic procedures are used only in very selected cases and surgical exploration has become extremely rare. CONCLUSION: The prognosis has also considerably improved and renal trauma rarely result in death or loss of the kidney nowadays.

Giant optical polarisation rotations induced by a single quantum dot spin.

In the framework of optical quantum computing and communications, a major objective consists in building receiving nodes implementing conditional operations on incoming photons, using a single stationary qubit. In particular, the quest for scalable nodes motivated the development of cavity-enhanced spin-photon interfaces with solid-state emitters. An important challenge remains, however, to produce a stable, controllable, spin-dependent photon state, in a deterministic way. Here we use an electrically-contacted pillar-based cavity, embedding a single InGaAs quantum dot, to demonstrate giant polarisation rotations induced on reflected photons by a single electron spin. A complete tomography approach is introduced to extrapolate the output polarisation Stokes vector, conditioned by a specific spin state, in presence of spin and charge fluctuations. We experimentally approach polarisation states conditionally rotated by [Formula: see text], π, and [Formula: see text] in the Poincaré sphere with extrapolated fidelities of (97 ± 1) %, (84 ± 7) %, and (90 ± 8) %, respectively. We find that an enhanced light-matter coupling, together with limited cavity birefringence and reduced spectral fluctuations, allow targeting most conditional rotations in the Poincaré sphere, with a control both in longitude and latitude. Such polarisation control may prove crucial to adapt spin-photon interfaces to various configurations and protocols for quantum information.

Phase-diverse Fresnel coherent diffractive imaging of malaria parasite-infected red blood cells in the water window.

Phase-diverse Fresnel coherent diffractive imaging has been shown to reveal the structure and composition of biological specimens with high sensitivity at nanoscale resolution. However, the method has yet to be applied using X-ray illumination with energy in the so-called 'water-window' that lies between the carbon and oxygen K edges. In this range, differences in the strength of the X-ray interaction for protein based biological materials and water is increased. Here we demonstrate a proof-of-principle application of FCDI at an X-ray energy within the water-window to a dehydrated cellular sample composed of red blood cells infected with the trophozoite stage of the malaria parasite, Plasmodium falciparum. Comparison of the results to both optical and electron microscopy shows that the correlative imaging methods that include water-window FCDI will find utility in studying cellular architecture.

Borylation directed borylation of N-alkyl anilines using iodine activated pyrazaboles.

Doubly electrophilic pyrazabole derivatives (pyrazabole = [H2B(µ-C3N2H3)]2) combined with one equiv. of base effect the ortho-borylation of N-alkyl anilines. Initial studies found that the bis(trifluoromethane)sulfonimide ([NTf2]-) pyrazabole derivative, [H(NTf2)B(µ-C3N2H3)]2, is highly effective for ortho-borylation, with this process proceeding through N-H borylation and then ortho C-H borylation. The activation of pyrazabole by I2 was developed as a cheaper and simpler alternative to using HNTf2 as the activator. The addition of I2 forms mono or ditopic pyrazabole electrophiles dependent on stoichiometry. The ditopic electrophile [H(I)B(µ-C3N2H3)]2 was also effective for the ortho-borylation of N-alkyl-anilines, with the primary C-H borylation products readily transformed into pinacol boronate esters (BPin) derivatives. Comparison of borylation reactions using the di-NTf2-and the diiodo-pyrazabole congeners revealed that more forcing conditions are required with the latter. Furthermore, the presence of iodide leads to competitive formation of side products, including [HB(µ-C3N2H3)3BH]+, which are not active for C-H borylation. Using [H(I)B(µ-C3N2H3)]2 and 0.2 equiv. of [Et3NH][NTf2] combines the higher yields of the NTf2 system with the ease of handling and lower cost of the iodide system generating an attractive process applicable to a range of N-alkyl-anilines. This methodology represents a metal free and transiently directed C-H borylation approach to form N-alkyl-2-BPin-aniline derivatives.

[Factors related to success in the prosthetic fitting of lower limb amputees from vascular etiology]. / Factores relacionados con el éxito en la protetización de amputados de extremidad inferior de etiología vascular.

OBJECTIVE: Restoring the ambulation ability with prostheses in lower limb amputeesis essential to improve their functional independence. The aim of this study was to determine the factors involved in achieving prosthesis fitting in vascular amputees. MATERIAL AND METHOD: Observational longitudinal study of patients with major lower limb amputation of vascular etiology performed from April 1st 2017 to April 1st 2020. The following variables were compared between the group of patients who were prosthetized and those who were not: age, gender, body-mass index, comorbidity (Charlson index), independence in the activities of daily living (Barthel index) and ambulation ability (FAC test) before and a year after the amputation. The prosthetic use after a year was measured with the Houghton scale. RESULTS: A total of 80 patients were amputated with a mean age of 70.5 years old, 78.8% were male. The amputation level was supracondilealin 42 patients and infracondilealin 38 patients. The number of prosthetized patients was 35. The variables related to the possibility of prosthesis fitting were: younger age (P=0.020), less comorbidity (P=0.000), infracondileal amputation (P=0.024) and greater functional independence and ambulation ability prior to amputation (P=0.000). After a year 22 patients had died, only one of those who had been prosthetized. CONCLUSIONS: Although there are no clear recommendations to determine which amputees should be prosthetic fitting, in our patients the presence of fewer comorbidities and a good previous functional situation, younger age and infracondileal amputation, are related to greater success in achieving this objective.

Comparison between laser speckle contrast imaging and laser Doppler imaging to assess skin blood flow in humans.

OBJECTIVE: We tested the linearity between skin blood flux recorded with laser speckle contrast imaging (LSCI) and laser Doppler imaging (LDI), comparing different ways of expressing data. A secondary objective was to test within-subject variability of baseline flux with the two techniques. METHODS: We performed local heating at 36, 39, 42, and 44°C on the forearm of healthy volunteers, and measured cutaneous blood flux with LDI and LSCI. Biological zero (BZ) was obtained by occluding the brachial artery. We expressed data as raw arbitrary perfusion units (APUs) and as a percentage increase from baseline (%BL), with and without subtracting BZ. Inter-site variability was expressed as a within subject coefficient of variation (CV). RESULTS: Twelve participants were enrolled. Inter-site variability at baseline was lower with LSCI (CV=9.2%) than with LDI (CV=20.7%). We observed an excellent correlation between both techniques when data were expressed as raw APUs or APU-BZ (R=0.90; p<0.001). The correlation remained correct for %BL (R=0.77, p<0.001), but decreased for %BL-BZ (R=0.44, p=0.003). Bland-Altman plots revealed a major proportional bias between the two techniques. CONCLUSION: This study suggests that skin blood flux measured with LSCI is linearly related to the LDI signal over a wide range of perfusion. Subtracting BZ does not affect this linearity but introduces variability in baseline flux, thus decreasing the correlation when data are expressed as a function of baseline. Finally, systematic bias makes it impossible to assimilate arbitrary perfusion units provided by the two systems.

Skin microdialysis coupled with laser speckle contrast imaging to assess microvascular reactivity.

OBJECTIVE: Laser speckle contrast imaging (LSCI) can be used to assess real-time responses of skin microcirculation to pharmacological interventions. The main objective of this study was to determine whether intradermal or subdermal microdialysis fiber insertion, coupled with skin flux recording using LSCI, can be used to assess baseline cutaneous flux and the post-occlusive reactive hyperemic response. The microdialysis sites were compared to control area without microdialysis fibers. METHODS: One dermal and two subdermal microdialysis fibers were randomly inserted in the right forearm skin of six healthy volunteers. We performed consecutively tests of post-occlusive hyperemia, infusion of 29 mM sodium nitroprusside (SNP), local thermal hyperemia at 43°C and a second 29 mM SNP infusion at the end of the experiment. RESULTS: Two hours after fiber insertion, cutaneous vascular conductances (CVC) at the subdermal fiber sites were not different from their respective control regions of interest, while at the dermal site CVC remained higher (0.48+/-0.15 versus 0.37+/-0.1 PU.mm Hg(-1), P=0.003). The peak CVC and area under the curve observed during post-occlusive reactive hyperemia were similar at all fiber sites and their respective controls. We observed a similar increase in CVC using 29 mM SNP infusion, 40 min local heating at 43°C, and their combination. Finally, physiological and pharmacological responses of the subdermal sites were reproducible in terms of amplitude, whether expressed as raw CVC or as % CVCmax. CONCLUSIONS: We showed that studying skin microvascular physiological or pharmacological responses using inserted subdermal microdialysis fibers coupled with LSCI is feasible and reproducible, and provides two-dimensional information. This technique will be useful for future mechanistic studies of skin microcirculation.

Reproducibility and methodological issues of skin post-occlusive and thermal hyperemia assessed by single-point laser Doppler flowmetry.

OBJECTIVE: The primary objective of this study was to evaluate 1-week reproducibility of post-occlusive reactive hyperemia (PORH) and local thermal hyperemia (LTH) assessed by single-point laser-Doppler flowmetry (LDF) on different skin sites. We also evaluated spatial reproducibility of both tests on the forearm. Finally, we assessed the influence of mental stress and room temperature variations on PORH and LTH. METHODS: We performed PORH and LTH assessing skin blood flow on the forearm and on the finger pad with LDF. We repeated the sequence 1 week later. We also performed PORH and LTH during mental stress (Stroop test) and at room temperatures of 21 degrees C and 27 degrees C. Data were expressed as cutaneous vascular conductance (CVC), as a function of baseline and as a function of 44 degrees C vasodilation (%CVC(44)). Reproducibility was expressed as within subject coefficients of variation (CV) and intra-class correlation coefficients (ICC). RESULTS: Fourteen Caucasian healthy volunteers were recruited. Median age was 25 (2.7) and 50% were female. Median body mass index was 21.2 (5). PORH was reproducible on the finger, whether expressed as raw CVC (CV=25%; ICC=0.56) or as %CVC(44) (CV=24%; ICC=0.60). However, PORH showed poor reproducibility on the forearm. In the same way, LTH was reproducible on the finger pad when expressed as CVC (CV=17%; ICC=0.81) but not on the forearm. Spatial reproducibility was poor on the forearm. Elevated room temperature (27 degrees C) affected PORH and LTH on the finger pad (p<0.05) but not on the forearm. CONCLUSION: Single-point LDF is a reproducible technique to assess PORH and LTH on the finger pad when data are expressed as raw CVC or %CVC(44). On the forearm, however, it shows great inter-day variability, probably due to spatial variability of capillary density. These results highlight the need for alternative techniques on the forearm.

Excellent reproducibility of laser speckle contrast imaging to assess skin microvascular reactivity.

OBJECTIVE: We compared the inter-day reproducibility of post-occlusive reactive hyperemia (PORH) assessed by single-point laser Doppler flowmetry (LDF) and laser speckle contrast analysis (LSCI), and the reproducibility of local thermal hyperemia (LTH) assessed by LDF, laser Doppler imaging (LDI) and LSCI. We also tested whether skin blood flow assessment by LDF and by LSCI are correlated. METHODS: Skin blood flow was evaluated during PORH and LTH using LDF, LDI (for LTH only) and LSCI on the forearms of healthy volunteers, at a 7day interval. Data are expressed as cutaneous vascular conductance (CVC), as a function of baseline and scaled to the thermal plateau. Reproducibility is expressed as within subject coefficients of variation (CV, in %) and intra-class correlation coefficients (ICC). RESULTS: Twenty-eight healthy participants were enrolled in this study. The reproducibility of the PORH peak CVC was better when assessed with LSCI compared to LDF (CV=8%; ICC=0.76 and CV=30%; ICC=0.54, respectively). Inter-day reproducibility of the LTH plateau was better when assessed with LSCI or LDI than LDF (CV=15%, ICC=0.66; CV=17%, ICC=0.51 and CV=42%, ICC=0.28 respectively). Finally, we observed significant correlation between simultaneous LDF and LSCI measurements of the PORH peak CVC (R=0.54; p=0.001). CONCLUSION: The recently developed LSCI technique showed very good inter-day reproducibility for assessing PORH and LTH. Moreover, we showed significant correlation between LSCI and single-point LDF for PORH. However, more data are needed to evaluate the linearity between the LSCI signal and skin blood flow.

[Vertical dimension in the treatment of the edentulous patient]. / Dimensions verticales en prothèse complète.

Determining and recording appropriate occlusal vertical dimension (OVD) in the treatment of the edentulous patient is an important but critical procedure in practice. Incorrect determination of the OVD may result in failure of complete denture treatment. Many methods have been advocated to determine the vertical dimension in edentulous patients. However, there is no single precise scientific method for determining the correct OVD. These methods include the use of physiologic rest position, swallowing, phonetic, aesthetic, facial measurements. A combination of some of them is recommended for a simplified clinical determination. Moreover, the application of several accepted tests is advocated to verify the established OVD.

Sequential generation of linear cluster states from a single photon emitter.

Light states composed of multiple entangled photons-such as cluster states-are essential for developing and scaling-up quantum computing networks. Photonic cluster states can be obtained from single-photon sources and entangling gates, but so far this has only been done with probabilistic sources constrained to intrinsically low efficiencies, and an increasing hardware overhead. Here, we report the resource-efficient generation of polarization-encoded, individually-addressable photons in linear cluster states occupying a single spatial mode. We employ a single entangling-gate in a fiber loop configuration to sequentially entangle an ever-growing stream of photons originating from the currently most efficient single-photon source technology-a semiconductor quantum dot. With this apparatus, we demonstrate the generation of linear cluster states up to four photons in a single-mode fiber. The reported architecture can be programmed for linear-cluster states of any number of photons, that are required for photonic one-way quantum computing schemes.

Effects of menstrual cycle, oral contraception, and training on exercise-induced changes in circulating DHEA-sulphate and testosterone in young women.

The objective of this study was to ascertain the effects of menstrual cycle, oral contraception, and training status on the exercise-induced changes in circulating DHEA-sulphate and testosterone in young women. Twenty-eight healthy women were assigned to an untrained group (n = 16) or a trained group (n = 12) depending on their training background. The untrained group was composed of nine oral contraceptive users (OC+) and seven eumenorrheic women (OC-). The trained group was composed of OC+ subjects only. All the OC+ subjects were taking the same low-dose oral contraception. Three laboratory sessions were organised in a randomised order: a prolonged exercise test until exhaustion, a short-term exhaustive exercise test, and a control session. Blood specimens were collected before, during and after the exercise tests and at the same time of the day during the control session. Basal circulating testosterone was significantly lower in trained as compared to untrained subjects. In all subjects, the prolonged exhaustive exercise induced a significant increase in circulating DHEA-s and testosterone. The short-term exercise induced a significant increase in circulating DHEA-s in untrained eumenorrheic and in trained OC users only. Menstrual phases in OC- did not influence the responses. It was found that exhaustive physical exercise induced an increase in circulating DHEA-s and testosterone in young women. Oral contraception may limit short-term exercise-induced changes.

Chordin is underexpressed in ovarian tumors and reduces tumor cell motility.

Ovarian cancers mostly derive from the monolayer epithelium that covers the ovary. There are currently very few molecular clues to the etiology of this cancer. Bone morphogenetic proteins (BMPs) are required for follicular development and female fertility and are expressed in the ovarian surface epithelium (OSE). We previously reported the expression of human chordin (CHRD), a BMP extracellular regulator, in the ovary. Here we show that CHRD is underexpressed in epithelium ovary cancer and epithelial cancer cell lines as compared with normal tissues and OSE, respectively. Besides, we detected BMP expression in all ovarian cell lines analyzed. To determine the functional relevance of the absence of CHRD mRNA in tumors and cancer cell lines, we studied the effects of CHRD on two cancer cell lines, BG1 and PEO14. Migratory and invasive properties were greatly reduced, whereas cell adhesion to the support was enhanced. In addition, we detected chordin (Chrd) expression in OSE of rat ovaries in a pattern similar to that of BMP4. Altogether, these results suggest that CHRD could participate in regulating BMP activity in normal OSE physiology, and that its mis-expression in OSE may facilitate cancer incidence and/or progression.

Diagnostic strategy for growth hormone deficiency: relevance of IGF-1 determination as a screening test.

BACKGROUND: Adult growth hormone (GH) deficiency must be diagnosed before prescribing therapeutic recombinant human GH. We studied the clinical relevance of a diagnostic strategy for growth hormone deficiency (GHD) using IGF-1 determination as a first step. METHODS: In 2000 and 2001, we tested 142 adult patients with hypothalamo-pituitary disorders for somatotropic function using Insulin Tolerance Test (ITT), the reference test for the diagnosis of GHD, with concomitant Insulin-like growth factor-1 (IGF-1) determination, a marker of somatotropic function. Patients were classified as GHD (peak GH concentration<3 ng/ml with the ITT) or normal. SETTING: Monocenter prospective study in a tertiary referral center. RESULTS: GHD was diagnosed in 61 subjects. Using a ROC curve, a threshold IGF-1 concentration of 175 ng/ml yielded a negative predictive value of 89+/-5%. A diagnostic strategy with IGF-1 determination as the first step followed by ITT for patients with an IGF-1 concentration below 175 ng/ml missed five of the 61 GHD patients, avoided 46/142 ITT and reduced the cost of diagnosis by 15%. CONCLUSION: We propose the use of a strategy consisting of IGF-1 determination followed, if below 175 ng/ml by confirmatory ITT to diagnose GHD in adults.

Pain and Vertebral Dysfunction in Dry Immersion: A Model of Microgravity Simulation Different from Bed Rest Studies.

BACKGROUND: Astronauts frequently experience back pain during and after spaceflight. The aim of this study was to utilize clinical methods to identify potential vertebral somatic dysfunction (VD) in subjects exposed to dry immersion (DI), a model of microgravity simulation. METHOD: The experiment was performed in a space research clinic, respecting all the ethical rules, with subjects completing three days of dry immersion (n = 11). Assessments of VD, spine height, and back pain were made before and after simulated microgravity. RESULTS: Back pain was present in DI with great global discomfort during the entire protocol. A low positive correlation was found (Pearson r = 0.44; P < 0.001) between VD before DI and pain developed in the DI experiment. CONCLUSIONS: There is a specific location of pain in both models of simulation. Our analysis leads to relativizing constraints on musculoskeletal system in function of simulation models. This study was the first to examine manual palpation of the spine in a space experience. Additionally, osteopathic view may be used to select those individuals who have less risk of developing back pain.

Factores relacionados con el éxito en la protetización de amputados de extremidad inferior de etiología vascular / Factors related to success in the prosthetic fitting of lower limb amputees from vascular etiology

Objetivos: Recuperar la capacidad de deambulación con prótesis en los amputados de extremidad inferior es fundamental para mejorar su independencia funcional. El objetivo de este trabajo ha sido conocer qué factores intervienen en conseguir la protetización de pacientes amputados vasculares. Material y método: Estudio longitudinal observacional de los pacientes con amputación mayor de extremidad inferior de etiología vascular realizada desde el 1 de abril de 2017 hasta el 1 de abril de 2020. Se compararon las siguientes variables entre los pacientes que fueron protetizados y los que no: edad, sexo, índice de masa corporal, comorbilidades (escala de Charlson), independencia en las actividades de la vida diaria básicas (índice de Barthel) y capacidad de marcha (FAC) previas y al año de la amputación. La utilización de la prótesis al año se midió con el instrumento de Houghton. Resultados: Fueron amputados 80 pacientes con una edad media de 70,5 años, el 78,8% eran varones. El nivel de amputación fue supracondíleo en 42 pacientes y en 38 infracondíleo; se protetizaron 35. Las variables relacionadas con la posibilidad de protetización fueron la menor edad (p=0,020), presentar menos comorbilidad (p=0,00), la amputación infracondílea (p=0,024) y tener una mayor independencia funcional y de marcha previas a la amputación (p=0,00). Al año habían fallecido 22 pacientes, solo uno de los que fueron protetizados. Conclusión: Aunque no existen unas recomendaciones claras para determinar qué amputado ha de ser protetizado, en nuestros pacientes, tener menos comorbilidades, una buena situación funcional previa, menor edad y un nivel de amputación infracondíleo se relacionaron con un mayor éxito en conseguir dicho objetivo.(AU)

Objective: Restoring the ambulation ability with prostheses in lower limb amputeesis essential to improve their functional independence. The aim of this study was to determine the factors involved in achieving prosthesis fitting in vascular amputees. Material and method: Observational longitudinal study of patients with major lower limb amputation of vascular etiology performed from April 1st 2017 to April 1st 2020. The following variables were compared between the group of patients who were prosthetized and those who were not: age, gender, body-mass index, comorbidity (Charlson index), independence in the activities of daily living (Barthel index) and ambulation ability (FAC test) before and a year after the amputation. The prosthetic use after a year was measured with the Houghton scale. Results: A total of 80 patients were amputated with a mean age of 70.5 years old, 78.8% were male. The amputation level was supracondilealin 42 patients and infracondilealin 38 patients. The number of prosthetized patients was 35. The variables related to the possibility of prosthesis fitting were: younger age (P=0.020), less comorbidity (P=0.000), infracondileal amputation (P=0.024) and greater functional independence and ambulation ability prior to amputation (P=0.000). After a year 22 patients had died, only one of those who had been prosthetized. Conclusions: Although there are no clear recommendations to determine which amputees should be prosthetic fitting, in our patients the presence of fewer comorbidities and a good previous functional situation, younger age and infracondileal amputation, are related to greater success in achieving this objective.(AU)

The human chordin gene encodes several differentially expressed spliced variants with distinct BMP opposing activities.

During early embryogenesis of both vertebrates and invertebrates, antagonism between bone morphogenetic proteins (BMPs) and several unrelated secreted factors including Chordin (Chd) is a general mechanism by which the dorso-ventral axis is established. High affinity binding of Chd sequesters the BMP ligands in the extracellular space, preventing interactions with their membrane receptors. Another level of regulation consists in processing of vertebrate Chd or its Drosophila counterpart Sog by astacine metalloproteases like Xolloid-BMP-1/Tolloid, respectively, which releases an active BMP. Recently, it was shown that cleavage of Sog by Tolloid could generate novel BMP inhibitory activity and that sog is also capable of stimulation of BMP activity in a tolloid-dependant way. Activity and/or cleavage of Chd/Sog are influenced by other secreted factors like twisted gastrulation. In this study, we have cloned cDNAs of the human chordin gene (CHRD) and characterized alternative splice variants that code for C-truncated forms of the protein. We have found that CHRD is expressed in fetal as well as in adult tissues with relatively high levels in liver, cerebellum and female genital tract, suggesting functions in late embryogenesis and adult physiology. We also show that spliced variants are present with specific patterns in various tissues. When tested in an axis-duplication assay in Xenopus, we find that these variants can antagonize BMP activity. Altogether, these results suggest that, in addition to processing by metalloproteases, alternative splicing (AS) is another mechanism by which sub-products of CHRD can be generated to influence BMP activity in different developmental and physiological situations.

Associated complement C3b. Towards an understanding of its intracellular modifications.

Covalent Superose microspheres-bound C3b was used as a model system to simplify the analysis of antigen-bound C3b modifications during antigen processing. The model was set up using purified C3 and Superose-bound trypsin. C3b was covalently bound to Superose through an ester link, as indicated by lability to hydroxylamine treatment at alkaline pH. C3b-Superose was incubated with L subcellular fraction, enriched in endosomes/lysosomes, purified from U937 cell line. Two types of limited activities on the C3b-Superose model system were detected: (i) a proteolytic activity cleaving C3b into mainly a C3c-like fragment which was released and a C3d-like fragment of apparent M(r) 32 kDa which remained bound to Superose through the original ester link; (ii) an esterolytic activity cleaving the ester bond and releasing C3b. Inhibition experiments pointed to the involvement of serine, aspartyl and cysteine proteases. Cathepsin B appeared most probably as one of the major proteases of L fraction catalysing the proteolysis of the C3b-bound. Kinetic studies were in favour of a good stability on the ester bond, supporting an effective role of C3b as a chaperone during the extracellular and intracellular travel of C3b-bound antigen.