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International audience; Fertility is of primary economic importance in dairy cattle and the most common reason for involuntary culling. However, standard fertility traits have very low heritability that renders genetic selection slow and difficult. In this study, we explored fertility from an endocrine standpoint. A total of 1,163 crossbred Holstein-Normande females in a 3-generation familial design were studied for progesterone level measured every 10 d to determine age at puberty (PUB) and commencement of postpartum luteal activity (CPLA). Genetic parameters were estimated using REML with WOMBAT software. The heritability estimates were 0.38 ± 0.10 and 0.16 ± 0.07 for PUB and CPLA, respectively. Moreover, the 2 traits were genetically correlated (0.45 ± 0.23), suggesting a partially common determinism. Because of the family structure, a linkage disequilibrium and linkage analysis approach was preferred over standard genome-wide association study to map genomic regions associated with these traits. Ten quantitative trait loci (QTL) were detected for PUB on chromosomes 1, 3, 11, 13, 14, 21, and 29, whereas 3 QTL were associated with CPLA on chromosomes 21 and 26. Only the QTL on chromosome 21 was common to both traits. Four functional candidate genes (NCOA2, GAS2, OVOL1, and FOSL1) were identified in the detected regions. These findings will contribute to a clearer understanding of fertility determinism and enhance the value of introducing endocrinological data in fertility studies.

International audience; Milk spontaneous lipolysis (SL) of milk triglycerides is induced by the lipoprotein lipase, a milk native enzyme, and leads to an accumulation of partial glycerides and free fatty acids that are responsible for the deterioration of the taste of milk products. The gene coding for diacylglycerol acyltransferase 1 (DGAT1), an enzyme implicated in triglycerides synthesis, has an important polymorphic site at the K232A locus. This gene is well known to modulate milk composition. No data are available on the effects of DGAT1 on SL. Thus, a trial was carried out to evaluate the effects of DGAT1 K232A polymorphism on milk SL upon milking frequency variations [once- (ODM) and twice-daily milking (TDM)]. Twenty-one cows were divided into 3 groups according their DGAT1 K232A genotype: 8 cows had the KK genotype of DGAT1 (KK cows), 8 had the KA genotype (KA cows), and 5 had the AA genotype (AA cows). The trial consisted in 3 successive periods: 3 wk of TDM, 3 of ODM, and 4 of TDM. Samples were collected for fat and protein contents, SL, fatty acid, and protein profiles determinations. The KK cows presented higher fat and protein contents, lower milk production, and higher κ-casein percentage. No significant difference in fatty acid composition was noted between groups. The SL was twice as high for KK cows in TDM situations (1.13 vs. 0.59 and 0.63 mEq/100 g of fat, respectively, for KK, KA, and AA cows during the first period of TDM, and 0.46 vs. 0.25 and 0.21 mEq/100 g of fat, respectively, for KK, KA, and AA during the second period of TDM). The SL remained sharply lower in TDM2 than in TDM1. During ODM, no difference in SL was found between groups and SL remained below 0.2 mEq/100 g of fat. These results demonstrate the existence of a correlation between DGAT1 genotypes and spontaneous lipolysis, in interaction with an environmental factor, milking frequency, although it has not been possible to clarify the causal mechanism at this stage.

International audience; Despite its potential utility for predicting cows' milk yield responses to once-daily milking (ODM), the genetic basis of cow milk trait responses to ODM has been scarcely if ever described in the literature, especially for short ODM periods. This study set out to (1) estimate the genetic determinism of milk yield and composition during a 3-wk ODM period, (2) estimate the genetic determinism of milk yield responses (i.e., milk yield loss upon switching cows to ODM and milk yield recovery upon switching them back to twice-daily milking; TDM), and (3) seek predictors of milk yield responses to ODM, in particular using the first day of ODM. Our trial used 430 crossbred Holstein × Normande cows and comprised 3 successive periods: 1 wk of TDM (control), 3 wk of ODM, and 2 wk of TDM. Implementing ODM for 3 wk reduced milk yield by 27.5% on average, and after resuming TDM cows recovered on average 57% of the milk lost. Heritability estimates in the TDM control period and 3-wk ODM period were, respectively, 0.41 and 0.35 for milk yield, 0.66 and 0.61 for milk fat content, 0.60 and 0.80 for milk protein content, 0.66 and 0.36 for milk lactose content, and 0.20 and 0.15 for milk somatic cell score content. Milk yield and composition during 3-wk ODM and TDM periods were genetically close (within-trait genetic correlations between experimental periods all exceeding 0.80) but were genetically closer within the same milking frequency. Heritabilities of milk yield loss observed upon switching cows to ODM (0.39 and 0.34 for milk yield loss in kg/d and %, respectively) were moderate and similar to milk yield heritabilities. Milk yield recovery (kg/d) upon resuming TDM was a trait of high heritability (0.63). Because they are easy to measure, TDM milk yield and composition and milk yield responses on the first day of ODM were investigated as predictors of milk yield responses to a 3-wk ODM to easily detect animals that are well adapted to ODM. Twice-daily milking milk yield and composition were found to be partly genetically correlated with milk yield responses but not closely enough for practical application. With genetic correlations of 0.98 and 0.96 with 3-wk ODM milk yield losses (in kg/d and %, respectively), milk yield losses on the first day of ODM proved to be more accurate in predicting milk yield responses on longer term ODM than TDM milk yield.

The goal of the FAZIA Collaboration is the design of a new-generation 4π detector array for heavy-ion collisions with radioactive beams. This article summarizes the main results of the R&D phase, devoted to the search for significant improvements of the techniques for charge and mass identification of reaction products. This was obtained by means of a systematic study of the basic detection module, consisting of two transmission-mounted silicon detectors followed by a CsI(Tl) scintillator. Significant improvements in ΔE-E and pulse-shape techniques were obtained by controlling the doping homogeneity and the cutting angles of silicon and by putting severe constraints on thickness uniformity. Purposely designed digital electronics contributed to identification quality. The issue of possible degradation related to radiation damage of silicon was also addressed. The experimental activity was accompanied by studies on the physics governing signal evolution in silicon. The good identification quality obtained with the prototypes during the R&D phase, allowed us to investigate also some aspects of isospin physics, namely isospin transport and odd-even staggering. Now, after the conclusion of the R&D period, the FAZIA Collaboration has entered the demonstrator phase, with the aim of verifying the applicability of the devised solutions for the realization of a larger-scale experimental set-up.

Chantier qualité GA; A current trend in the dairy industry is to reduce milk yield at the peak of lactation and improve lactation persistency. Lactation persistency is influenced by livestock management factors, such as feeding level or milking frequency, or by physiological status, including reproductive status or calving period. These factors modulate mammary gland apoptosis and tissue remodeling, which determine the rate of decline of milk yield after the lactation peak. Previous studies on lactating cows suggested that ovarian steroids have a negative effect on milk yield after the peak of lactation. In the present study, 4 Holstein x Normande crossbred multiparous cows were ovariectomized at the time of the lactation peak, and 5 cows underwent sham operations. All of the cows were maintained in lactation for 14 mo and milk yield was recorded daily. At slaughter, mammary epithelial cell apoptosis and mammary tissue remodeling were assessed. Ovariectomized cows had improved lactation persistency and presented an average daily milk gain of 2.5 kg compared with the sham-operated cows between mo 6 and 14 of lactation. The ovariectomy appears to have limited the decline in the milk yield after the peak of lactation by reducing mammary epithelial cell apoptosis [by reducing poly(adenosine diphosphate-ribose) polymerase expression] and mammary-tissue remodeling (by reducing matrix metalloproteinase activity). In conclusion, removal of ovarian secretion via ovariectomy improved the cows' lactation persistency.

Expérience GANIL; Current pulses induced in a silicon detector by 10 different heavy ion species at known energies around 10 AMeV have been sampled in time at high frequency. Their individual average shapes are quite well reproduced by a fit procedure based on our recent charge carrier collection treatment which considers the progressive extraction of the electrons and holes from the high carrier density zone along the ionizing particle track. This region is assumed to present a supplementary dielectric polarization and consequently a disturbe delectric field.The influence of the nature of the heavy ion on the values of the three fit parameters is analyzed.

INDRA, a new and innovative highly segmented detector for light charged particles and fragments is described. It covers geometrically 90% of the 4π solid angle and has very low detection thresholds. The detector, operated under vacuum, is axially symmetric and segmented in 336 independent cells allowing efficient detection of high multiplicity events. Nucleus identification down to very low energy threshold (≈ 1 A MeV) is achieved by using ionization chambers operated with low pressure C 3 F 8 gas. Residual energies are measured by a combination of silicon (300 μm thick) and cesium iodide (5 to 14 cm in length) detectors. Very forward angles are covered by fast counting phoswich scintillators (NE102/NE115). Charge resolution up to Z = 50 is achieved on a large energy dynamic range (5000 to 1 for silicon detectors). Isotopic separation is obtained up to Z = 3. The treatment of the signals is performed through specifically designed and highly integrated modules, most of which are in the new VXIbus standard. Full remote control of parameter settings, including visualization of signals, is thus allowed. The detector is continuously monitored with a laser source and electronic pulsers and is found stable over several days. Energy calibration procedures, making use of specific detectors and the ability of the GANIL accelerator to deliver secondary beams, have been developed. First experiments were performed in the spring of 1993.

The aim of this study was to investigate the effects of a severe nutrient restriction on mammary tissue morphology and remodeling, mammary epithelial cell (MEC) turnover and activity, and hormonal status in lactating dairy cows. We used 16 Holstein × Normande crossbred dairy cows, divided into 2 groups submitted to different feeding levels (basal and restricted) from 2 wk before calving to wk 11 postpartum. Restricted-diet cows had lower 11-wk average daily milk yield from calving to slaughter than did basal-diet cows (20.5 vs. 33.5 kg/d). Feed restriction decreased milk fat, protein, and lactose yields. Restriction also led to lower plasma insulin-like growth factor 1 and higher growth hormone concentrations. Restricted-diet cows had lighter mammary glands than did basal-diet cows. The total amount of DNA in the mammary gland and the size of the mammary acini were smaller in the restricted-diet group. Feed restriction had no significant effect on MEC proliferation at the time of slaughter but led to a higher level of apoptosis in the mammary gland. Gelatin zymography highlighted remodeling of the mammary extracellular matrix in restricted-diet cows. Udders from restricted-diet cows showed lower transcript expression of α-lactalbumin and kappa-casein. In conclusion, nutrient restriction resulted in lower milk yield in lactating dairy cows, partly due to modulation of MEC activity and a lower number of mammary cells. An association was found between feed restriction-induced changes in the growth hormone-insulin-like growth factor-1 axis and mammary epithelial cell dynamics.

International audience; The new challenges of the dairy industry require an accurate estimation of fine milk composition. The mid-infrared (MIR) spectrometry method appears to be a good, fast and cheap method for assessing milk fatty acid profile. Although partial least squares (PLS) regression is a very useful and powerful method to determine fine milk composition from the spectra, the estimations are not always very accurate and stable over time. Therefore a genetic algorithm (GA) combined with a PLS regression was used to produce models with a reduced number of wavelengths and a better accuracy. The results are a little sensitive to the choice of parameters in the algorithm. The number of wavelengths to consider is reduced substantially by 4 and accuracy is increased on average by 15%.

A new synthesis of trimethoprim is described, metalation of a pyrimidine has been used in the key step. An exceptional regioselectivity in the metalation of pyrimidine derivatives has been highlighted.

The DEL cell line isolated from a patient who died of malignant histiocytosis exhibits a reciprocal chromosomal translocation t(5;6)(5q35;6p21). The cells were analyzed for Ig(Jh), TCR beta-gene rearrangements and proto-oncogene expression pattern, using a panel of molecularly cloned probes that included c-fms, c-myc, c-myb, c-pim, c-fos, N-myc, c-sis, c-fgr as well as the virally derived probes v-ki-ras and v-src. Consistent levels of expression of c-fms, c-myc, c-myb, c-ki-ras and c-fgr were identified in cells from several in vitro passages as well as from the heterotransplanted tumors in nude mice. Transcripts homologous to the c-fos, c-src and c-sis were not observed. Southern blot study of DNA showed that the banding pattern of the screened proto-oncogenes was not altered. Furthermore, Southern blot analysis demonstrated monoallelic immunoglobulin heavy chain (IgJh) rearrangement but a normal germ-line configuration of the kappa light chain and TCR beta-genes. These results appear to imply that a T- or B-cell origin can be eliminated and that several activated proto-oncogenes, usually expressed in immature MPS cells (c-fms) and myeloblastic cells (c-fgr), may be implicated in the proliferative activity of the DEL cell line, the stem of which may be a primitive, ancestral myelomonocytic cell.

New charge and current-sensitive preamplifiers coupled to silicon detectors and devoted to studies in nuclear structure and dynamics have been developed and tested. For the first time shapes of current pulses from light charged particles and carbon ions are presented. Capabilities for pulse shape discrimination techniques are demonstrated., 14 pages, 12 figures, to be published in Nucl. Inst. Meth. A

In vitro explantation of 38 fragments of eosinophilic granuloma of bones was attempted. A satisfactory growth was obtained in nearly 90% of cases. This short-term culture maintained the ultrastructural characteristics and, to a lesser extent, the cytochemical features of the Langerhans cells, confirming the Langerhans cell origin of this cell proliferation. In addition, this procedure was able to demonstrate an immunodependent erythrophagocytosis (3/3) and a preferential fixation of labelled precursors (Glycerol, choline of lipid metabolism as well as labelled dopamine (2/2). All attempts to obtain a permanent cell line and graft to nude mice (even irradiated) failed. Under the in vitro conditions, the Langerhans cells do not divide up but can be readily identified up to 2 or 3 weeks. The contrast between the evident in vivo proliferation and the in vitro quiescent state suggests that some undetermined growth-factors targeted to the Langerhans cell system are missing in our commonly used culture media. The in vitro culture procedure could be of some help to their identification.

The production of TNF-alpha and IL-1 alpha and beta molecules has been shown to be associated with the proliferation and activation of cells of the monocyte/macrophage series, the intermediate steps in the synthesis of these molecules have been less investigated. Unstimulated and TPA stimulated DEL cells (a CD30-positive, t(5;6)(q35;p21) malignant histiocytosis cell line) were used to study the expression of TNF-alpha and IL-1 genes and to evaluate, by nuclear run-on assay and biological measurements, the control of their transcription and the level of protein production. To refine this analysis, the effects of cycloheximide and actinomycin D were also evaluated in this investigation. Following TPA stimulation, transcription of TNF-alpha (constitutively present) increased threefold as early as 30 mins and started decreasing by 24h. Cycloheximide superinduced the expression of TNF-alpha mRNA and, accordingly, the release of its protein. By contrast, transcription of IL-1 molecules appeared de novo and did not result in a biologically detectable protein. Measurements of RNA half line after actinomycin D indicated that TNF-a and IL-1 alpha mRNAs are not as stable as that of IL-1 beta. These results indicate that, despite their common synergistic activity, the transcriptional and post-transcriptional mechanisms regulating the synthesis of TNF-alpha and IL-1 alpha and IL-1 beta involve different pathways.

The stopping powers of gases have been measured for incident 24 MeV/u 238U and 29 MeV/u 208Pb projectiles using the LISE spectrometer at GANIL. The results show the persistence of the 20% gas-solid effect observed at lower energy. The effective charges derived from these measurements depend on the atomic number of the target in a way very similar to that observed for solid degraders.

Acute promyelocytic leukemia (APL) is thought to be caused by the t(15,17) translocation that fuses the PML gene to that of the retinoic acid receptor alpha (RAR alpha) and generates a PML/RAR alpha fusion protein. Yet, paradoxically, APL cells are exquisitely sensitive to retinoic acid (RA), as they terminally differentiate upon RA exposure. In this report, we have examined the expression of PML and PML/RAR alpha in normal and APL cells. By immunofluorescence or immunocytochemistry, we show that PML has a speckled nuclear pattern of expression that contrasts with that of PML/RAR alpha (mostly a micropunctuated nuclear pattern or a cytoplasmic localization). The APL- derived cell line NB4 that expresses both the PML and PML/RAR alpha genes also shows the fine micropunctuated nuclear pattern, suggesting a dominant effect of the fusion protein over the localization of wild- type PML. RA treatment of NB4 cells or clones expressing PML/RAR alpha gradually leads to a PML pattern before apparent morphologic maturation. In 14 untreated APL patients, the PML-reactive proteins were cytoplasmic (by immunocytochemistry) or both cytoplasmic and nuclear with a micropunctuated pattern (by immunofluorescence). Strikingly, in 4 patients, after 1 to 2 weeks of RA therapy, the speckled nuclear PML pattern reappeared concomitant with the onset of differentiation. These results establish that fusion of PML to RAR alpha results in an altered localization of PML that is reverted upon RA treatment. This observation, which highlights the importance of PML, is likely to be a key to unravelling the molecular mechanism of both leukemogenesis and RA-induced differentiation of APL.

Following exposure to phorbol ester (TPA), DEL cell line, a human malignant histiocytosis (MH) cell line, is able to differentiate along a macrophage phenotype and thus it provides a suitable model for analyzing the sequential and differential gene expression associated with monocyte/macrophage differentiation. C-myc, c-myb, c-fos, c-sis and c-fms expression were determined by Northern analysis at various times following TPA treatment. The results showed that TPA down-modulated the constitutive expression of c-myc, c-myb, and c-fms, mRNA to low but still detectable levels. Conversely, TPA-induced differentiation resulted in transient appearance of c-fos, whereas no change in the level of c-sis and actin transcripts were observed. Thus, the c-fms and c-sis genes appear to be regulated in a specific manner in this malignant histiocytosis derived cell line. Furthermore, these investigations demonstrated a constitutive CSF-1 gene expression which transiently increased at mRNA and also at protein level as evaluated by a murine bone marrow CFU bioassay. Through this drug-induced modulation, the DEL cell line offers an additional model for studying some of the subtle interrelations existing between a growth factor (CSF-1) and its receptor (c-fms) in the monocyte/macrophage system.

The clinicopathological data on 20 cases of malignant histiocytosis (MH) collected over a period of 30 years at the Hôpital des Enfants Malades (Paris) are reported. Childhood MH was characterized by disseminated, frequently tender lymphadenopathy (19/20), skin (8/20), bone (6/20), and soft tissue localizations (7/20). These features were usually accompanied by fever, deterioration of general condition, and hematological abnormalities including anemia, thrombocytopenia, and occasionally fibrinopenia. These manifestations were clinically suggestive of a diagnosis of a severe neoplastic blood disease, although this hypothesis was not entertained for a long time because of the initial absence of abnormal cells in the blood and bone marrow. MH was characterized by the proliferation of large "histiocyte-like," usually mononucleated cells. When suitable material was available, MH cells appeared to react positively with acid-phosphatase, alpha-naphthyl acetate esterase (ANAE), alpha-antichymotrypsin, and antibodies directed against EMA, HLA DR, CD25, CD30, CD68, and CD71. No B- and T-cell antigens (except for one case) have been detected. Due to the frequent abundance of accompanying granulocytes, lymphoid, and plasma cells, and the presence of areas of necrosis, an initial correct diagnosis of MH was often difficult to establish on skin (four cases), bone (two), and soft tissue (three) biopsies. In lymph nodes, the sinusoidal and perifollicular topography of cell proliferation represented a highly reliable morphological feature. A permanent cell line (DEL) was obtained from a pleural effusion showing a t(5;6)(q35;p21) translocation and a monoallelic immunoglobulin (IgjH) rearrangement and consistent levels of expression of c-fms, c-myc, c-myb, c-ki-ras and c-fgr. Since an identical 5q35 breakpoint has been reported in four other MH cell lines with a comparable phenotype and in several isolated published cases, this chromosomal abnormality provides a highly valuable argument for individualizing an authentic malignancy of the mononuclear phagocyte system (MPS) in childhood, among the rather heterogeneous group of the CD30+ anaplastic large cell lymphomas.

The histiocytic or lymphoid origin of human malignant histiocytosis is currently a subject of debate. The aim of this study was to investigate the in vitro effects of 12-O-tetradecanoylphorbol-13-acetate used as a differentiation inducer on the CD30, t(5;6)(q35;p21) DEL cell line, taken to be a reliable representative of the human malignant histiocytosis cell line. Treatment of DEL cells with 33 nM 12-O-tetradecanoylphorbol-13-acetate for 6-24 h resulted in cell surface attachment (up to 80%), decrease in dividing ability, enhancement of nitro blue tetrazolium reducing capacity (from 8 to 42%), occurrence of a limited immunodependent phagocytosis, and transient increase in expression of tumor necrosis factor alpha gene and in production of tumor necrosis factor alpha protein, whereas tumor necrosis factor beta remained undetectable. From these data, we can conclude that the malignant histiocytosis DEL cell line is not of lymphoid origin but stems from a myelomonocyte lineage.

Resume Nous presentons l'observation chez un africain, d'un cas clinique de rhinosclerome evoluant selon l'aspect clinique d'une tumeur extensive. Le role etiologique de Klebsiella rhinoscleromatis a pu etre affirme par l'observation directe de bacteries intracellulaires dans les tissus infectes et par l'isolement en culture de ce microorganisme. L'evolution clinique a ete favorable apres exerese chirurgicale et traitement antibiotique (gentamicine, trimethoprime-sulfamethoxazole). Les problemes poses par le diagnostic et le traitement de cette maladie rare sont discutes a la lumiere de cette observation.

Summary Expression of HLADR, I, i blood group antigen and T6 antigen were studied in Histiocytosis X cells and pulmonary alveolar macrophages using double labelling immunofluorescence technique or immuno-peroxydase procedure. Alveolar macrophages express simultaneously HLADR and i blood group antigen. Histiocytosis X cells, caracterized by HLADR and T6 antigens, and by their ultra-structural marker do not express i antigen. These results confirm the hypothesis that histiocytosis X cells constitute a specialized sub-population of the mononuclear phagocyte system.

Summary Histiocytosis X cells were demonstrated to react with T 6 antigen as well as with the M 1 and I 1 markers of monocytes using immuno-electron microscopy and double labeling immunofluorescence technique. The data confirm the close relationship existing between histiocytic X cells, Langerhans cells and dendritic cells, and suggest to consider the T 6 antigen either as an early differentiation marker of thymocytes or as a functional marker of Mononuclear Phagocyte System subpopulations.

A detection system consisting of a sectorised ionisation chamber coupled with parallel plate avalanche counters and plastic scintillator telescopes is described. The active area is 120 cm2 corresponding to angular apertures of 30° in plane and ±1° out of plane (experimental configuration). The sectorisation allows both an improved counting rate capability of the detector and a great versatility in its use. The addition of plastic scintillators in the rear part of the detector permits to enlarge the dynamic range of the charge measurement up to energetic light charged particles. A radial grid (θ grid) gives a precise in plane localisation (0.1°) while drift time measurement allows the determination of the out of plane coordinate. The energy resolution of the ionisation chamber is 1% for 120 MeV 32S and the energy loss resolution is 3–5% depending on the anode section considered. The charge resolution is therefore better than 1.8%.

Summary The ultrastructural and histochemical exploration of histiocytes X done by the means of Concanavalin A (Con A), peanut agglutinin (PNA) and BSPT demonstrate that the plasma membrane of histiocytes X shared some properties with all the other cells and is also specialized. The rod part of the X body has the same properties as the plasma membrane while its vesicular part differs and is closer to the inner membrane system of the cell. In consequence it is suggested that the rod part of the X body is a specialized pathway or shuttle for receptor linked glycoprotein exchanges in highly specialized cells.

Chantier qualité GA; International audience; Mid-infrared (MIR) spectrometry was used to estimate the fatty acid (FA) composition in cow, ewe, and goat milk. The objectives were to compare different statistical approaches with wavelength selection to predict the milk FA composition from MIR spectra, and to develop equations for FA in cow, goat, and ewe milk. In total, a set of 349 cow milk samples, 200 ewe milk samples, and 332 goat milk samples were both analyzed by MIR and by gas chromatography, the reference method. A broad FA variability was ensured by using milk from different breeds and feeding systems. The methods studied were partial least squares regression (PLS), first-derivative pretreatment + PLS, genetic algorithm + PLS, wavelets + PLS, least absolute shrinkage and selection operator method (LASSO), and elastic net. The best results were obtained with PLS, genetic algorithm + PLS and first derivative + PLS. The residual standard deviation and the coefficient of determination in external validation were used to characterize the equations and to retain the best for each FA in each species. In all cases, the predictions were of better quality for FA found at medium to high concentrations (i.e., for saturated FA and some monounsaturated FA with a coefficient of determination in external validation >0.90). The conversion of the FA expressed in grams per 100 mL of milk to grams per 100 g of FA was possible with a small loss of accuracy for some FA.

Lytic activity of eosinophilic granuloma and other tumours was studied in vitro on collagen substrate. Collagen degradation was measured through the release of hydroxyproline-rich peptides into the medium. The in vitro lytic action was at a maximum in the case of EG and was correlated with the presence of histiocytic cells.

Histochemical study combined with differential extractions of lipids from biopsy fragments in three cases of eosinophil granuloma reveals a great amount and variety of lipidic categories existing in histiocytosis X cells : sterids, fatty-acids, triacylglycerols, phosphoglycerids, cholino-phospholipids, sphingomyelins, glycolipids. Comparison of the lipidic content of histiocytosis X cells and that of normal histiocytes, showed a preponderance of cholesterol esters in histiocytosis X contrary to the normal macrophages and alteration in phospholipidic control of cholesterol esterification. This study confirms that the histiocytosis X cells have an active and probably preferential lipid metabolism, explaining the frequent xanthomatous changes of the lesions and the intense production of various cytoplasmic membranous structures.

Ultrastructural and immunohistochemical analysis of six specimens revealed for the first time a small number of Langerhans cells in non-neoplastic bronchial epithelium. These cells were usually found either interspersed perpendicularly between columnar epithelial cells or just above the basal lamina with extending cytoplasmic processes. Usually few Birbeck granules, especially located in the Golgi region, were present throughout the cytoplasm. Immunohistochemical studies were performed on semi-thin sections with a polyclonal anti-S-100 protein. The population of S-100 positive cells represented about 1% of all the epithelial cells. Not all ultrastructurally identified Langerhans cells were shown to be positive for S-100 antigen. Our results suggest that Langerhans cells could be a constant cellular constituent for the normal bronchial epithelium. The exact function of Langerhans cells in the respiratory epithelium remains to be investigated, but they may have an immunologic function, such as antigen presentation to T lymphocytes.

We have studied by ultrastructural histo-autoradiography, in a primary immunological response, the behavior of three types of guinea-pig histiocytic cells exposed to 125I-flagellin, lymph node histiocytes, alveolar macrophages and skin Langerhans cells, making use of the experimental model of Nossal et al. (1964). Whereas latero cave lymph node histiocytes exposed to 125I-flagellin by in vivo injection of the labelled antigen into the hind foot of the guinea-pig trap the flagellin as do 20% of alveolar macrophages incubated in vitro in a culture medium containing 125I-flagellin, skin Langerhans cells exposed in vivo (intradermal and hypodermal injection of the antigen) and in vitro, as was done for alveolar macrophages, are never labelled. These results suggest that, despite the fact that it belongs to the mononuclear phagocytic system, the Langerhans cell is not a common essentially phagocytic macrophage but represents a cell lineage involved in more complex immune reactions requiring the cooperation of sensitized lymphocytes.

Using 14C glycerol and 3H glycerol, in a study of lipid metabolism of two cases of eosinophilic granuloma of the bone, the authors point out that this precursor is preferentially but not electively incorporated by mononuclear cells. This fixation particularly concerns the big cells with numerous lipid droplets and few X bodies. The precursor is essentially involved in neutral lipid synthesis. As is the case with common macrophages, this lipid synthesis might express various states of cellular maturation and ageing.

The Langerhans cell system including the Langerhans cell (LC), the indeterminate epidermal cell, the lymphoid interdigitating cell, and the lymph veiled cell is nowadays considered as a very peculiar subpopulation of the mononuclear phagocyte system. The authors have tried in this review to point out the main salient features, the qualitative and quantitative variations of these cells during physiological, experimental and pathological processes.

Immunohistochemical study of 7 cases of histiocytosis X (HX) and of histologically normal skin shows that HX Langerhans cells react with Bl.49.9 monoclonal antibody which recognizes the Interleukin-2 receptor, whereas normal skin Langerhans cells do not. This reactivity suggest activation of HX Langerhans cells.

The anatomo-clinical investigation of a series of 12 cases of AIDS in infants, over two years in Hôpital des Enfants Malades (Paris) allows the following observations to be made: the frequency of materno-foetal contaminations (8/12); the relative shortness of the incubation period (3-6 months); the variable degree of the atrophy of the lymphoid tissues; the absence of vascular proliferation; the interest of demonstrating viral proteins associated with LAV virus (p 18) in imprecisely identifiable cells of lymphoid tissue; the severity of the thymic alterations, which are characterized less by a lymphocyte depletion than by a loss of the maturation of the epithelial tissue, which still preserves its hormone secretory properties.

Alveolar macrophages of non smoking and smoking human adults reduce BSPT salt spontaneously. The staining obtained is located on three cell membrane systems: the endoplasmic reticulum, the Golgi apparatus and the nuclear envelope. Methylene blue MB inhibits BSPT reduction. The smokers alvelolar macrophages have less positivity than those of the non smokers. The endogenous cell substrate revealed in this work is the initial common pathway of two different oxidative chains bounded to the microsome. One acts with cytochrome P 450 for chemical detoxification by hydroxylation, the other one acts with cytochrome B5 for lipid oxidation or peroxidation and both may be connected with the cell bactericidal system.

We have investigated the secretory function of cell suspensions from bone eosinophilic granulomas surgically collected in two patients with histiocytosis X. Unseparated cell preparations spontaneously produced interleukin 1 (IL-1) and prostaglandin E2 (PGE2). In order to ascertain that this secretion was due to the characteristic Langerhans cell-like histiocytosis X cells predominantly found in the bone lesions, we have purified T6+ cells by the use of a fluorescence-activated cell sorter. Such highly purified cell preparations were found to secrete IL-1 and PGE2 spontaneously in culture. Stimulation with endotoxins and treatment with interferon gamma (IFN gamma) revealed an intense IL-1 secretory function of histiocytosis X cells. Since both IL-1 and PGE2 are able to induce bone resorption in vitro, our findings are compatible with the hypothesis that histiocytosis X cells are responsible for the typical osteolytic lesion observed in histiocytosis X through the local secretion of these two mediators.

The stopping powers of six gaseous media have been measured for incident 40 MeV/u 125 Te heavy ions. The energylosses of ions in various ‘‘thicknesses’’ of gas have been accurately determined. The gases were confined in a cell. Theamount of matter traversed by the ions was determined from temperature and pressure measurements. The beamenergy before and after slowing down were measured using the LISE magnetic spectrometer at GANIL. These ex-perimental gas stopping powers are lower by about 10% than the corresponding tabulated values for solid media. Thismeans that the gas–solid e•ect is still significant at 40 MeV/u for Te ions. The projectile e•ective charges derived fromthese measurements depend on the target atomic number, thus confirming the trend observed in previous experimentsperformed with lighter ions or at lower energies. O 2000 Elsevier Science B.V. All rights reserved.Keywords: Slowing down; Heavy ions; Tellurium ions; 40 MeV/nucleon; Measured stopping powers; Gaseousdegraders; Gas-solid e•ect; E•ective-charge parametrization

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