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The National Institute of Alcohol Abuse and Alcoholism (NIAAA) recently released a new definition of recovery from alcohol use disorder (AUD). A patient is considered recovered if they are remitted from DSM-5 AUD and report cessation of heavy drinking. The NIAAA has also recently proposed the Addictions Neuroclinical Assessment (ANA) to guide treatment research. Negative emotionality is one of three domains of the ANA and theory proposes that AUD is maintained by negative reinforcement via the relief of negative affect. The purpose of the current study was to examine: (1) the relationship of end-of-treatment negative emotionality and NIAAA recovery, and (2) the ability of NIAAA recovery at the end of treatment to predict three- and six-month drinking outcomes.At baseline and end-of-treatment, women and men (n = 181) in treatment for AUD completed measures of negative emotionality, drinking, and were assessed for DSM-5 AUD diagnostic criteria. At three- and six-months post-treatment, drinking was re-assessed.22.5% (n = 24) of participants met full criteria for NIAAA recovery at end-of-treatment. Lower levels of end of treatment negative emotionality were associated with increased odds of achieving NIAAA recovery. Meeting NIAAA recovery predicted greater percent days abstinent (PDA) and lower percent heavy drinking days (PHDD) at 3-months, but not at 6-months post-treatment.This study is among the first to report a relationship between the negative emotionality domain of the ANA and NIAAA recovery. Results underscore the importance of addressing negative emotionality in treatment. Findings also suggest that NIAAA recovery predicts positive short term drinking outcomes.

International audience; This paper presents a model-based approach for the fault diagnosis of three-cell power converters. The goal is to design a fault detection and isolation (FDI) scheme which diagnoses parametric and discrete faults. Parametric faults are characterized by abnormal changes in the capacitor value whereas a discrete fault affects a switching element and is characterized by an abrupt deviation of the dynamics of the system. The combined continuous and discrete diagnosers are used to detect and isolate the discrete and the parametric faults. The discrete diagnoser is based on an appropriate decomposition of the hybrid model of the three-cell converter. The continuous diagnoser is based on a set of residuals which enable a comparison between the measured and estimated values of each continuous variable. Some experiments are shown to prove the effectiveness of the proposed scheme.

Resume Introduction La pemphigoide est une dermatose bulleuse auto-immune caracterisee par la production d’anticorps diriges contre les composants des hemidesmosomes de la membrane basale. La physiopathologie du demasquage de ces antigenes est inconnue. La pemphigoide est plus frequente chez les personnes âgees, souvent debilitees. La prevalence des anticorps anti-antigene de la pemphigoide (anti-PB) est inconnue dans la population âgee indemne de manifestations dermatologiques evocatrices de pemphigoide. Nous avons etudie la prevalence d’anticorps anti-PBAg2 chez des personnes âgees indemnes de manifestations de pemphigoide et le lien entre la presence de ces anticorps et le diagnostic de demence. Patients et methodes Des personnes âgees (plus de 69 ans), sans aucune manifestation de pemphigoide, ont ete recrutees de facon consecutive dans des services de dermatologie ou de geriatrie (138 sujets). Chez chaque sujet etaient recueillies les prises medicamenteuses et un examen clinique etait realise avec calcul du MMS (Mini Mental Score). En fonction de leur MMS, les sujets etaient repartis en deux groupes. Le premier groupe etait compose de sujets sans demence (MMS > 24). Le second groupe etait compose de malades atteints de demence. Les anticorps anti-PBAg2 etaient doses dans les serums par la technique ELISA et par immunofluorescence indirecte et confirmes par un immunoblot. Les anticorps antinucleaires, utilises comme controle d’une reponse immune non specifique, etaient doses dans tous les serums. La prevalence de ces anticorps a ete comparee dans les deux groupes. Resultats Les deux groupes etaient comparables en âge, sexe, et presence de maladies dermatologiques (ulceres, escarres, erysipeles). Chaque groupe comportait 69 sujets. La prevalence globale des anticorps anti-PBAg2 chez ces personnes âgees indemnes de manifestations evoquant une pemphigoide etait de 3,6 p. 100. La presence des anticorps anti-PBAg2 etait associee au diagnostic de demence (p = 0,04 ; 0 p. 100 et 7 p. 100 dans les groupes 1 et 2, respectivement). Aucune association entre la presence d’anticorps anti-PBAg2 et les prises medicamenteuses ou une maladie dermatologique n’etait observee. La prevalence globale des anticorps antinucleaires etait de 14,5 p. 100 et proche dans les deux groupes. Discussion La presence des anticorps anti-PBAg2 pourrait etre associee au diagnostic de demence chez les personnes âgees.

To investigate the adjuvant effect of intestinal flora on macrophage-colony-stimulating factor-responsive macrophage progenitors from spleen and bone marrow, we compared progenitor numbers and phenotypic characteristics of in vitro matured macrophages in germ-free and flora-associated mice (conventional, Escherichia coli-monoassociated and conventionalized mice). The data obtained show that the flora affected differentially bone marrow and spleen progenitors. It increased the numbers of progenitors in the spleen but not in the bone marrow. It did not modify the expression of F4/80, Mac-1 and major histocompatibility complex (MHC) class II on bone-marrow-derived macrophages (BMDM), while it clearly up-regulated MHC class II expression on spleen-derived macrophages (SDM). This effect was more pronounced in flora-associated ex germ-free mice than in conventional mice and it was greatly enhanced in the absence of M-CSF. In vitro stimulation by lipopolysaccharide had no effect on marker expression of BMDM, while it decreased F4/80 and enhanced MHC class II molecules on SDM from germ-free and flora-associated mice. However, the expression of MHC class II remained lower in germ-free mice. Enhancement of MHC class II molecule expression on SDM may contribute to the protective role of flora, because successful immune responses are dependent on the expression of these molecules.

Characterization of the mle locus harboring the malolactic enzyme gene mleA and malate permease gene mleP from Leuconostoc oenos was completed in this study by mRNA analysis. Northern (RNA) blot experiments revealed a 2.6-kb transcript, suggesting an operon structure harboring mleA and mleP genes. Primer extension analysis showed that the mle operon has a single transcription start site located 17 nucleotides upstream of the ATG translation start site for the mleA gene. We found sequences, TTGACT and TATGAT (which are separated by 18 bp), that are closely related to the gram-positive and Escherichia coli consensus promoter sequences. Upstream of the mleA gene, an 894-bp open reading frame that transcribed divergently from the mle operon was found. Sequence analysis and expression in E. coli minicells suggest that this open reading frame encodes a polypeptide with an apparent molecular mass of 34 kDa belonging to the LysR-type regulatory protein family. Protein comparisons showed the highest level of identity with the MleR regulatory protein from Lactococcus lactis, which is involved in the expression of the malolactic genes in the presence of L-malate. However, the MleR-like protein of L. oenos seems different from the protein of Lactococcus lactis, since no regulation of the malolactic enzyme by L-malate was effective under our experimental conditions.

Using degenerated primers from conserved regions of the protein sequences of malic enzymes, we amplified a 324-bp DNA fragment by PCR from Leuconostoc oenos and used this fragment as a probe for screening a Leuconostoc oenos genomic bank. Of the 2,990 clones in the genomic bank examined, 7 with overlapping fragments were isolated by performing colony hybridization experiments. Sequencing 3,453 bp from overlapping fragments revealed two open reading frames that were 1,623 and 942 nucleotides long and were followed by a putative terminator structure. The first deduced protein (molecular weight, 59,118) is very similar (level of similarity, 66%) to the malolactic enzyme of Lactococcus lactis; as in several malic enzymes, highly conserved protein regions are present. The synthesis of a protein with an apparent molecular mass of 60 kDa was highlighted by the results of labelling experiments performed with Escherichia coli minicells. The gene was expressed in E. coli and Saccharomyces cerevisiae and conferred "malolactic activity" to these species. The second open reading frame encodes a putative 34,190-Da protein which has the characteristics of a carrier protein and may have 10 membrane-spanning segments organized around a central hydrophilic core. Energy-dependent L-[14C]malate transport was observed with E. coli dicarboxylic acid transport-deficient mutants carrying the malate permease-expressing vector. Our results suggest that in Leuconostoc oenos the genes that encode the malolactic enzyme and a malate carrier protein are organized in a cluster.

Preventive intraperitoneal trehalose dimycolate (TDM) treatment of mice, inoculated with encephalomyocarditis (EMC) virus by the same route, caused restriction of virus growth in the peritoneum, which was correlated to IFN production in peritoneal fluids prior to infection. Peritoneal macrophages from TDM-treated mice (TDM-PM) spontaneously secreted IFN-alpha/beta in large amounts. By their supernatants, TDM-PM could transfer an antiviral state against EMC virus to permissive resident peritoneal macrophages from control mice. IFN-alpha/beta produced by TDM-PM was found to be involved in this transfer activity. TDM-PM also exerted a strong antiviral effect on EMC virus-infected L-929 cells, which increased with time and the macrophage-target cell ratio. This activity also occurred by an IFN-alpha/beta-dependent mechanism. These data point to the role of IFN-alpha/beta production prior to EMC virus infection in the antiviral activities of TDM-PM and, more generally, in the outcome of viral infection.

In this paper, a circuit analysis of the electromagnetic interference filter used in a variable-speed drive is carried out in order to predict the resonance frequencies of its magnetic near-field radiations. The parasitic elements of the filter's components are determined by measurements and a model of the filter integrating these parasitics elements is proposed. It is used to calculate the input impedance and the transfer functions of the filter in common and differential modes. In parallel, magnetic near-field measurements were performed and the frequencies corresponding to a maximal radiation are related to the resonance frequencies of the transfer function.

Preventive treatment of mice with trehalose 6,6' dimycolate (TDM), an immunomodulator of bacterial origin, enhances their resistance to encephalomyocarditis (EMC) virus infection. The protective effect of TDM is totally abolished by the injection of silica particles in mice, demonstrating the role of macrophages in the antiviral action of TDM. In vitro, peritoneal macrophages from mice treated with TDM (TDM-PM) exhibit an intrinsic antiviral activity against EMC virus, while resident peritoneal macrophages (RES-PM) are permissive to this virus. Greater amounts of interferon are detected in supernatants of cultures of TDM-PM than of RES-PM. Neutralization of interferon (IFN) by addition in vitro of anti-IFN alpha/beta serum markedly reduces the antiviral activity of TDM-PM. These results indicate that interferon alpha/beta is involved in the intrinsic anti-EMC virus activity of peritoneal macrophages from mice treated with TDM.

In this paper, we perform magnetic near field measurements with a test bench. The probe used is sufficiently large to keep a good sensitivity. The measurement step equal to the probe radius lets to have a reasonable measurement time. The spatial step is shortened by a data post-processing technique derive from image restoration domain.

Pemphigoid is a form of auto-immune bullous dermatosis characterised by the production of antibodies directed against components of hemidesmosomes in the basal membrane. The physiopathological process responsible for unmasking of these antigens is unknown. Pemphigoid is more common in elderly subjects and is most often seen in debilitated subjects. The prevalence of pemphigoid anti-pemphigoid antibodies (anti-PB) is not known in the elderly population presenting no dermatological signs evocative of the disease. We studied the prevalence of anti-PBAg2 antibodies in elderly subjects with no signs of pemphigoid as well as in the correlation between the presence of these antibodies and diagnosis of dementia.Elderly subjects (aged over 69 years) with no signs of pemphigoid were recruited consecutively in dermatology and geriatrics departments (138 subjects). Details of concomitant medication were recorded for all subjects and clinical examination was performed with calculation of MMS (Mini Mental Score). The subjects were then divided into two groups based on MMS score. The first group comprised subjects without dementia (MMS24) while the second comprised subjects with dementia. Serum anti-PBAg2 antibodies were determined by ELISA and indirect immunofluorescence with confirmation by Western blot. Antinuclear antibodies, used as a control for non-specific immune response, were assayed in all serum samples. The prevalence of these antibodies was compared between the two groups.The two groups were comparable in terms of age, sex and presence of dermatological diseases (ulcers, bedsores, erysipelas). Each group comprised 69 subjects. The overall presence of anti-PBAg2 antibodies in subjects with no signs are suggestive of pemphigoid was 3.6%. Presence of anti-PBAg2 antibodies was associated with diagnosis of dementia (p=0.04; 0% and 7% in groups 1 and 2, respectively). No correlation was seen between the presence of anti-PBAg2 antibodies and concomitant medication or dermatological disease. The overall prevalence of antinuclear antibodies was 14.5% and the figure was similar between the two groups.The presence of anti-PBAg2 could be associated with the diagnosis of dementia in elderly subjects.

The aim of this paper is to describe the new developments of the thin wire method (TWM) applied to the study of various PCB shapes in power electronics, Labarre et al. (1998). We detail the new approach which is based on determining the per-unit-length resistance and internal inductance parameters. We present a new formulation of mutual partial inductance. (2 pages)

The purpose of this study was to evaluate the immunomodulatory activity of a peptide derived from bovine beta-casein (beta-CN), the beta-CN (193-209) peptide, on mouse macrophages that were obtained either from germfree (GF) or from human flora-associated (HF) mice. Macrophages were derived from bone marrow (BMDM) in the presence of recombinant macrophage colony-stimulating factor and exposed to the peptide or lipopolysaccharide (LPS). Membrane marker expression [F4/80, Mac-1, major histocompatibility complex (MHC) class II antigens] and phagocytic activity were assessed by flow cytometry. Production of tumor necrosis factor-alpha and interleukin (IL)-6 was measured by bioassays and production of IL-1alpha, IL-1beta and IL-12 by ELISA. The expression of cytokine mRNA was determined using semi-quantitative reverse transcription-polymerase chain reaction. The beta-CN (193-209) peptide up-regulated MHC class II antigen expression and phagocytic activity of BMDM from GF and HF mice. Its enhancing effect on phagocytosis was greater than that after LPS stimulation (P < 0.01). The peptide induced notable levels of cytokine mRNA in BMDM from GF and HF mice, but it was a significantly weaker inducer of cytokine secretion than LPS. Nevertheless, although flora implantation had no stimulatory influence on basal MHC class II and basal cytokine levels, cells from HF mice were more susceptible than those from GF mice to the peptide effects on these variables. These results indicate that the beta-CN (193-209) peptide could enhance antimicrobial activity of macrophages without proinflammatory effects.

Epidermis contains high amounts of IL-1. However, it is not clear whether IL-1 is a normal constituent of the epidermis or whether it is induced by continuous environmental stimulation of normal skin flora. These results show that the germ-free mouse epidermis contains IL-1 activity indicating that IL-1 is a normal constituent of this tissue. No difference in epidermal IL-1 activity was observed between the germ-free and the holoxenic mice. Keywords: Skin flora; Hairless mice; Interleukin 1; Axenic.

Besides its role as a barrier against potential pathogens, intestinal flora is presumed to protect the host by priming the immunological defense mechanisms. In this respect, the influence of intestinal flora on macrophage precursors was examined, and its modulating effect was compared on LPS-induced cytokine production by macrophages derived from bone marrow and spleen precursors (BMDM and SDM respectively). The regulation of IL-1, IL-6, TNF-alpha and IL-12 production in macrophages from germ-free and from three groups of flora-associated mice, conventional, conventionalized and E. coli-mono-associated mice, was investigated. The whole flora inhibited IL-1, TNF-alpha and IL-12 secretion by BMDM, whereas it had a stimulatory effect on IL-12 secretion by SDM. Implantation of E. coli alone enhanced cytokine secretion by BMDM but had a more limited effect than whole flora on SDM, enhancing only TNF-alpha and IL-12 secretion. Study of expression of mRNA showed a correlation with protein secretion for IL-6 but not for TNF-alpha and IL-1. IL-12 enhancement in BMDM seemed to be dependent on regulation of p35 mRNA expression while it was correlated to increased p40 mRNA expression in SDM. The results demonstrated that intestinal flora modulated bone marrow and spleen macrophage cytokine production in a differential manner and suggested a role for bacteria other than E. coli among the whole flora. The contrasting effects exerted by the intestinal flora on bone marrow and spleen precursors are an interesting observation in view of the different functions of these organs in immunity. The finding that intestinal flora enhanced IL-12 production in spleen is also potentially important since this cytokine is implicated in the determination of the relative levels of Th1 and Th2 responses and plays a pivotal role in host defense against intracellular microorganisms.

Peritoneal macrophages (PM) were isolated from mice treated with Dimycolate of Trehalose (TDM), a glycolipid extracted from the cell wall of Mycobacterium tuberculosis. PM from TDM-treated mice (TDM-PM) were shown to secrete consistent amount of IFN-gamma, which was not detectable in control Resident-PM (Res-PM), as revealed by ELISA. In addition, biologically active IFN was detected in the supernatants of TDM-PM, whereas no IFN production was found in those of control Res-PM. The addition of specific antisera to PM cultures revealed the simultaneous production of both type I and II IFNs in TDM-PM cultures. No reciprocal regulation in the production of IFN-gamma and IFN-alpha/beta was found in these cultures. In parallel, nitric oxide (NO) production was measured in TDM-PM cultures by detecting nitrites (NO2-). TDM-PM cultures accumulated high amounts of NO2- which decreased to the level of Res-PM in the presence of NMMA, an inhibitor of NO-synthases. In vitro, neither type I nor type II IFNs were involved in the stimulation of NO production. The capacity of macrophages to simultaneously secrete IFN-gamma, IFN-alpha/beta and NO upon in vivo TDM-treatment could be of particular relevance for the defense process of innate immunity in which macrophages play a crucial role.

IgG antibodies to cardiolipin and beta 2-glycoprotein I were looked for using an enzyme-linked immunosorbent assay (ELISA) in 19 patients with giant cell arteritis (meeting 1990 American College of Rheumatology criteria), including 16 with concomitant polymyalgia rheumatica (meeting Bird's criteria) and in three patients with isolated polymyalgia rheumatica. IgG anti-cardiolipin antibodies were demonstrated in eight patients (36%) and IgG anti-beta 2-glycoprotein I antibodies in two patients (9%) including one without anti-cardiolipin antibodies. Titers of anti-cardiolipin antibodies ranged from 27 to 190 units of IgG antiphospholipid antibodies (UGPL) (mean 71 UGPL). Of the eight patients with anti-cardiolipin antibodies, two had giant cell arteritis without polymyalgia rheumatica and six had polymyalgia rheumatica with clinical (n = 2) or histologic (n = 4) evidence of giant cell arteritis. None of the three patients with polymyalgia rheumatica but no giant cell arteritis had anti-cardiolipin or anti-beta 2 glycoprotein I antibodies. The VDRL was negative in the 14 patients who had this test. Tests for lupus anticoagulant were performed routinely, always with negative results. Among giant cell arteritis patients, those who tested positive for anticardiolipin antibody had significantly higher values for the erythrocyte sedimentation rate (p0.006) and for serum C-reactive protein (p0.03) and fibrinogen values (p = 0.05), and a trend toward higher platelet counts, as compared to those who tested negative for anticardiolipin antibody. The mean daily prednisone dose at the time of sampling was significantly lower in giant cell arteritis patients with anti-cardiolipin antibodies (p0.05); this difference may account for the apparent correlation between anti-cardiolipin antibodies and laboratory markers for inflammation. These data, as well as findings from serial measurements, suggest that anti-cardiolipin antibodies are present early in the course of giant cell arteritis and disappear within a few weeks of initiation of corticosteroid therapy in a dose of more than 25 mg prednisone per day. In this study, only one patient without anticardiolipin antibodies developed a cerebrovascular accident. Positive tests for anti-cardiolipin antibody or anti-beta 2 glycoprotein I antibody in a patient with polymyalgia rheumatica suggest a diagnosis of concomitant giant cell arteritis, which is usually symptomatic.

Nitric oxide (NO) generated by two NO donors (sodium nitroprusside or S-nitroso-L-glutathione) was shown to exert a dose-dependent inhibition of encephalomyocarditis virus growth in L-929 cells. This activity was not due to the cytotoxic or direct virucidal effects of NO donors. L-929 cells were shown to produce NO endogenously, but this low level of production did not counter encephalomyocarditis virus replication.

Bartonella (Rochalimaea) henselae causes a variety of diseases, including bacillary angiomatosis, peliosis hepatis, lymphadenitis, aseptic meningitis with bacteremia, and cat-scratch disease (CSD). Cases of B. henselae-related disease were collected from September 1991 through November 1993. Patients with suspected CSD, unexplained fever and lymphadenitis, or suspected B. henselae infection who were seen in the Infectious Diseases Clinic at Wilford Hall Medical Center (Lackland Air Force Base, TX) underwent physical and laboratory examinations. In addition to three previously described cases, 23 patients with R. henselae-related infection were identified. The patients included 19 immunocompetent individuals presenting with lymphadenitis (11), stellate neuroretinitis (5), Parinaud's oculoglandular syndrome with retinitis (1), chronic fatigue syndrome-like disease (1), and microbiologically proven adenitis without the presence of immunofluorescent antibodies to B. henselae (1) and four patients infected with human immunodeficiency virus type 1 presenting with isolated lymphadenitis (1), diffuse upper-extremity adenitis (1), neuroretinitis (1), and aseptic meningitis (1). A couple with neuroretinitis and their pet cat, a persistently fatigued patient, and a patient with Parinaud's oculoglandular syndrome were shown to have bacteremia. Tissue cultures were positive for B. henselae in three recent cases of adenitis. Twenty-two patients were exposed to cats. This series further demonstrates the similarities between B. henselae-related diseases and CSD and identifies several new syndromes due to B. henselae.

Beginning in 1991, case reports of coccidioidomycosis in California increased dramatically, pursuant to a variety of natural and demographic factors. This highly infectious fungal disease with propensity to disseminate widely, mimic other conditions, and cause pathology at locations distant in place and time is readily treatable if recognized at an early stage. The concentration of military bases in endemic areas and the mobility of military personnel suggest a heightened potential for case presentations elsewhere and a need for elevated diagnostic suspicion on the part of military physicians worldwide. We review three cases of disseminated disease recently referred to our facility.

Idiopathic livedo reticularis can be a sign of systemic disease since certain complications are frequently associated: cerebral thrombotic events in Sneddon's syndrome, necrotic ulcerations of the lower limbs. Antiphospholipid antibodies have been found in 0 to 85 p. 100 of patients with Sneddon's syndrome and anti-beta 2-glycoprotein 1 antibodies in 65 p. 100 of a series of 20 cases with Sneddon's syndrome. The aim of our study was to determine the prevalence of anti-beta 2-glycoprotein 1 antibodies in idiopathic livedo reticularis.Twelve patients in a series of 17 with idiopathic livedo reticularis seen between 1981 and 1992 were studied progressively. All underwent a clinical examination and simple laboratory tests with search for anticardiolipin antibodies, lupus type circulating anticoagulant and anti-beta 2-glycoprotein 1 antibodies.Eight of our 12 patients (60 p. 100) were positive for anti-beta 2-glycoprotein 1 antibodies, 3 of whom also had episodes of thrombosis similar to those described in antiphospholipid syndrome. Only one of the 8 patients also had anticardiolipin antibodies and no chronic manifestation of thrombosis.beta 2-glycoprotein 1 is a cofactor which increases anticardiolipin antibody adhesion to cardiolipin in ELISA. Anti-beta 2-glycoprotein 1 antibodies are associated with thrombosis and antiphospholipid antibodies with lupus. Our results would suggest that the prevalence of anti-beta 2-glycoprotein 1 antibodies is high in idiopathic livedo, but, due to the small number of patients, do not allow confirmation that anti-beta 2-glycoprotein 1 antibodies are associated with thrombosis. Anti-beta 2-glycoprotein 1 antibody assay would be justified in routine evaluation of patients with livedo and at follow-up examinations.

Tuberculous spondylitis (Pott's disease) is an uncommon complication of Mycobacterium tuberculosis infection that may have serious consequences if the diagnosis is missed or delayed. A case of tuberculous spondylitis in a military dependent is presented. Clinical presentation, radiologic findings, laboratory findings, and treatment are discussed.

Antiphospholipid antibodies (APL) are associated with venous and arterial thrombosis in SLE patients. Various thrombotic and non-thrombotic neurological manifestations have been reported in SLE but whether or not they are related to the presence of APL antibodies remains uncertain. To assess the possible association between neurological involvement in SLE and APL antibodies, IgG anticardiolipin antibodies (IgG ACL) were looked for using an ELISA technique in 92 consecutive SLE patients seen over a one-year period. Other APL determinations included VDRL and lupus anticoagulant (LAC) testing using APTT and the diluted thromboplastin time. Twenty-four SLE patients presented with neurological manifestations (40 episodes): 15/24 (62.5%) were found positive for APL antibodies (11 VDRL, 8 LAC, 7 ACL antibodies) versus 22/68 patients (32%) without neurological symptoms (p0.01). APL antibodies antedated neurological symptoms in 13/16 cases. Neurological manifestations were subsequently divided into 3 groups: thrombotic (n = 14), psychosis and convulsions (n = 15), miscellaneous (n = 10). No correlation was found between APL antibodies and any of the 3 subgroups. Among patients with neurological SLE, APL antibodies were present in two with valvular heart disease, as well as in seven with a history of either deep vein thrombosis, livedo reticularis or miscarriage. Among 7 patients with thrombocytopenia and neurological symptoms, 6 had APL antibodies. These data suggest that APL syndrome is associated with neuro-ophthalmological manifestations of SLE regardless of whether or not the mechanism of neurological involvement is thrombotic. SLE patients with APL antibodies may be at risk for future neurological manifestations. However, it is still questionable that APL positivity has definite therapeutic consequences.

The effect of bacterial flora on cytokine production from resident peritoneal macrophages was investigated in the mouse. The production of IL-1, IL-6 and TNF-alpha was determined in germ-free, and "conventionalized" mice, as well as in monoxenic mice implanted with either the Gram-negative bacterium E. coli, or the Gram-positive organism Bifidobacterium bifidum. Macrophages from the "conventionalized" mice produced significantly more IL-1 and IL-6 in vitro than those of the germ-free mice. IL-1 and IL-6 production from germ-free mice implanted with E. coli was comparable to that from "conventionalized" mice. However, implantation with Bifidobacterium bifidum did not increase production of these two cytokines above levels observed for macrophages from the germ-free mice. A little TNF-alpha was produced by only the macrophages from the "conventionalized" and monoxenic mice implanted with E. coli. Soon after implantation, the bacterial flora stimulated cytokine production by mouse peritoneal macrophages and our results suggest that Gram negative bacteria are the most efficient stimulus for this production.

The production of superoxide anions (superoxide) from alveolar macrophages stimulated or not with opsonized zymosan was investigated in the mouse after acute oral administration of alcohol (6.5 g/kg). Superoxide production was assayed using a nitroblue tetrazolium (NBT) reduction and chemiluminescence assay. In the absence of opsonized zymosan, superoxide concentration was not affected 1 h after ethanol treatment but was significantly increased 15 and 24 h after treatment. In the presence of opsonized zymosan, a biphasic response was observed. Superoxide production was significantly reduced 1 and 3 h after administration but was increased 15 and 24 h after treatment. One hour after treatment, the percentage of cells that phagocytized opsonized zymosan and reduced NBT was significantly decreased, whereas 24 h after alcohol treatment, phagocytosis was normal and the percentage of cells reducing NBT was significantly increased. The activity of cytosolic superoxide dismutase from alveolar macrophages was not altered 1 h after administration but was significantly reduced 24 h later. Considering the functions of alveolar macrophages in the defense of the lung, these alterations in the production of reactive oxygen species after ingestion of alcohol could explain why alcoholics are more sensitive to pulmonary infections. J. Leukoc. Biol. 53: 93–98; 1993.

The efficacy of ampicillin bound to polyisohexylcyanoacrylate nanoparticles was studied in vitro in mouse peritoneal macrophages infected with Listeria monocytogenes. Nanoparticles containing ampicillin 1 mg/L were more effective after 30 h than free ampicillin at the same concentration, with viable counts of 3.68 and 5.43 log10 cfu/mL, respectively. The nanoparticles acted on the intracellular bacteria after a lag period of 6-9 h; this time was apparently required for the degradation of the polymer. At the doses used in these experiments, empty nanoparticles had neither an anti-listeria nor a cytotoxic effect.

The purposes of this study were to test the pharmacokinetics and renal and otologic tolerances of a once-daily regimen of netilmicin and teicoplanin administered intramuscularly, alone or in combination (4.5 and 6 mg/kg, respectively), for 7 days in 30 healthy male volunteers. Teicoplanin induced only a mild increase in enzymuria. Nephrotoxicity was moderate and reversible with netilmicin; there was increased enzymuria and alteration in diluting ability, without significant changes in urinary β2-microglobulin levels, concentrating ability, and glomerular filtration rate. Ototoxicity was not detected in any of the subjects. Our results suggest that (1) teicoplanin and netilmicin given once daily induced only slight, reversible tubular damage, without any sign of ototoxicity; (2) their combination was not more toxic; and (3) clinical studies can be envisaged to evaluate the efficacy and tolerance of once-daily regimens in long-term treatment. Clinical Pharmacology and Therapeutics (1988) 44, 458–466; doi:10.1038/clpt.1988.180

Aerosol treatment with RU 41821, a glycoprotein extract from Klebsiella pneumoniae, was tested in mice for its effect on the kinetics of the induction of bronchoalveolar cells (i.e., alveolar macrophages, monocytes, lymphocytes, and polymorphonuclear leukocytes). RU 41821 led to an increase in the total number of bronchoalveolar cells. The largest increase was observed for polymorphonuclear leukocytes, and more moderate increases occurred in the numbers of alveolar macrophages, monocytes, and lymphocytes. The alveolar macrophages recruited in response to RU 41821 were activated, as indicated by luminol-dependent chemiluminescence in response to stimulation by opsonized zymosan. The effects of five RU 41821 aerosol treatments and those of a single treatment were further examined in vivo by aerosol infection of mice inoculated with a mouse-pathogenic influenza virus. The maximum protective effect was obtained after five once-a-day treatments and was correlated with the largest increase in the total number of bronchoalveolar cells.

Thyroxine-binding prealbumin (TBPA) seems to be more useful than other biochemical markers for the detection of subclinical protein-energy malnutrition. Accordingly, one can question whether its sensitivity to nutritional supply could be used in healthy populations for the discrimination of groups with low or high energy intakes; if such were the case, could TBPA serve as an index of overnutrition? In order to answer these questions, we measured TBPA circulating levels in three groups of healthy French subjects from a working population, with relatively low, medium or high levels of energy intake. We also observed the correlations of this protein with nutrient intakes and with some biological parameters related to the general nutritional status of the subjects. The observed figures did not support the hypothesis that TBPA could be used to discriminate healthy subjects with relatively low or high energy intake nor as an index of overnutrition. This study disclosed a positive relation of TBPA with alcohol consumption and related parameters such as body mass index or gamma-glutamyl transferase as well as a negative one with alpha 2-globulin and gamma-globulin. Other investigators have found similar results in chronic alcoholics, surgical patients, or patients suffering from severe illnesses such as cancer. Here, the study population consisted of adult men, neither undernourished nor suffering from any severe pathology and who could not be considered excessive drinkers. Positive relations were also observed between TBPA and apolipoprotein A1 and HDL cholesterol levels, which are negatively associated with coronary heart disease risk.

The specificity of various monoclonal antidigitoxin antibodies was characterized using 6 cardiac glycoside analogs. Spleen cells from BALB/c mice, immunized with BSA- or KLH-digitoxin conjugates, were fused with NS1 myeloma cells, and antibody-producing hybrids were identified by radioimmunoassay. Twenty-one monoclonal antidigitoxin-specific antibodies were obtained, 10 of which were cloned and characterized for affinity and specificity. All the antibodies had a high affinity constant, ranging from 8.10(8) to 2.5.10(10) 1/M. On the basis of their binding specificities, the antibodies could be classified into 3 groups: the first contained 7 antibodies exhibiting high cross reactivity (42-100%) with digitoxigenin, whereas the second and third groups did not recognize this analog (cross-reactivity of 1%). In the former group, the absence of the sugar moiety only slightly affected the binding reaction, although for the two other groups, this structure did appear to be involved in antibody recognition. Changes in the functional groups of the hapten molecule led to considerable changes in the antibody-antigen reaction. For all the antibodies except one, saturation of the lactone ring considerably affected binding. These results demonstrated that monoclonal antibodies of different specificities with respect to both the steroid backbone and the sugar moiety of digitoxin can be induced using a digitoxin-protein conjugate.

RU 41740, an immunomodulating compound extracted from Klebsiella pneumoniae, was previously shown to enhance mice resistance to bacterial and viral lung infections. To explore lung defense mechanisms, we studied the influence of RU 41740 aerosol treatment on the bronchoalveolar cell populations. Five successive daily RU 41740 aerosol treatments induced a large accumulation of leukocytes in the lungs 4h after the last treatment. Polymorphonuclear leukocytes predominated. The numbers of lymphocytes and monocytes rose significantly. A single RU 41740 aerosol treatment significantly raised the number of polymorphonuclears only. A luminol-dependent chemiluminescence assay was used to test the effect of RU 41740 on the opsonized zymosan induced response of alveolar macrophages. In vitro, addition of RU 41740 enhanced this chemiluminescence. After a single RU 41740 aerosol treatment of mice, the chemiluminescence of purified alveolar macrophages from these mice increased significantly. The protective effect of five daily RU 41740 aerosol treatments against influenza virus infection was believed to be due to the great intensity of the cellular response and the polymorphonuclear influx. The alveolar macrophage activation observed might also explain the enhanced resistance of mice to influenza virus infection.

One of the most important therapeutic goal in anorexia nervosa is to define with the patient a body weight to obtain. To do so, objective criteria are needed. For this purpose, we studied in a longitudinal way, 9 nutritional parameters in 23 patients with anorexia nervosa, as compared with 23 age - and sex - matched patients with Crohn's disease: body weight, tricep's skinfolds, mid-arm muscle circumferences; serum albumin, prealbumin, transferrin, hemoglobin, cholesterol; urinary creatinine and calcium, magnesium, zinc and copper serum levels and urinary outputs. Despite losses of body weight, of lean body mass and of fatty mass higher in patients with anorexia nervosa than in those with Crohn's disease, the former had higher nutritional protein's serum levels than the latter. These nutritional protein markers were not in anorexia nervosa different from normal values. In anorexia patients, zinc and copper serum levels and urinary outputs were very low. This study suggests that nutritional protein markers of hepatic synthesis are not sensitive markers for malnutrition evaluation and can not be used to follow renutrition efficacy.

Variations in plasma thyroxine-binding prealbumin (TBPA) were investigated in 15 well-nourished patients who underwent minor orthopaedic surgery and resumed normal oral feeding on the first post-operative day. TBPA fluctuations were analysed together with those of other nutritional and inflammatory markers including albumin (ALB), some acute-phase reactant proteins, C-reactive protein (CRP), orosomucoid also named alpha 1-acid-glycoprotein (alpha 1GP), alpha 1-antitrypsin (alpha 1AT) as well as cortisol and haematocrit. Measurements were conducted the day before operation, after the administration of anaesthesia, 2 h after the patient regained consciousness and then daily for a period of one week (days 1 to 7). Assays showed that TBPA and ALB levels began to decline by day 1 reaching minimum values by day 3 (with 35 and 15 per cent total decreases respectively compared to the initial levels). CRP levels began to rise on day 1 reaching maximum levels by day 2, alpha 1 GP and alpha 1 AT started to increase on day 1 and 2 respectively and displayed maximum concentrations by day 3. Cortisol, on the other hand, showed a rapid, yet short-lived increase after the patient regained consciousness on the day of operation. Haematocrit levels decreased from day 1 to day 3 and these low values were maintained until the end of the study. Aside from cortisol and CRP, the initial levels of the other parameters were not yet restored by day 7. These results show that despite an early return to normal oral feeding in post-operative patients, the commonly observed pattern of variation in TBPA levels persisted, indicating that such a pattern seems to be mainly influenced by stress-induced post-operative responses rather than by nutritional supply.