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PubMed1996

Binding of autoantibodies is not restricted to desmosomes in pemphigus vulgaris: comparison of 14 cases of pemphigus vulgaris and 10 cases of pemphigus foliaceus studied by western immunoblot and immunoelectron microscopy.

Pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are autoimmune blistering diseases characterized by a loss of cell-cell adhesion and by autoantibodies directed against epidermal cadherins. PF antigen has been established as desmoglein I which is located strictly on the desmosome, whereas the precise ultrastructural localization of PV antigen remains unclear and controversial to date. To further investigate this question, we compared the location of immune deposits in 14 patients with PV and 10 patients with PF by both direct and indirect immunoelectron microscopy (IEM). Inclusion criteria were based upon clinical features, histological level of cleavage and characterization of circulating antibodies by Western blot on epithelial bovine tongue extracts. IEM was performed on unfixed 0.7-mm slices of skin for the direct technique or on normal skin for the indirect technique using peroxidase labelling. In PF, by both direct and indirect IEM, immune deposits were located on the extracellular part of desmosomes (desmoglea) in all the samples studied. In PV, by both direct and indirect IEM, deposits were situated on the desmoglea and along large portions of the keratinocyte membrane without desmosomal structures in 15 of the 18 samples studied and only on the desmoglea in 3 samples. These results suggest that, in contrast to PF, the target antigen in PV is not always restricted to desmosomes. As various types of adherens junctions have been reported to mediate cell adhesion in the epidermis, the PV antigen could be a component of desmosomes and of other focal adhesions.

Adult↗

PubMed1994

Dietary protein deficiency affects n-3 and n-6 polyunsaturated fatty acids hepatic storage and very low density lipoprotein transport in rats on different diets.

Fatty livers and the similarity between the skin lesions in kwashiorkor and those described in experimental essential fatty acid (EFA) deficiency have led to the hypothesis that protein and EFA deficiencies may both occur in chronic malnutrition. The relationship between serum very low density lipoprotein (VLDL) and hepatic lipid composition was studied after 28 d of protein depletion to determine the interactions between dietary protein levels and EFA availability. Rats were fed purified diets containing 20 or 2% casein and 5% fat as either soybean oil rich in EFA, or salmon oil rich in eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids, or hydrogenated coconut oil poor in EFA. Animals were divided into six groups, SOC (20% casein + 5% soybean oil), SOd (2% casein + 5% soybean oil), COC (20% casein + 5% hydrogenated coconut oil), COd (2% casein + 5% hydrogenated coconut oil), SAC (20% casein + 5% salmon oil) and SAd (2% casein + 5% salmon oil). After 28 d, liver steatosis and reduced VLDL-phospholipid contents (P < 0.001) were observed in protein-deficient rats. In protein deficiency, triacylglycerol and phospholipid fatty acid compositions in both liver and VLDL showed a decreased polyunsaturated-to-saturated fatty acid ratio. This ratio was higher with the salmon oil diets and lower with the hydrogenated coconut oil diets. Furthermore, independent of the oil in the diet, protein deficiency decreased linoleic and arachidonic acids in VLDL phospholipids. Conversely, despite decreased proportions of EPA at low protein levels, DHA levels remained higher in rats fed salmon oil diets.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1990

Experimental studies on the angiogenic activity of the detached retina.

Angiogenic activity of the retina in experimentally induced retinal detachment in cats was examined using the corneal micropocket technique and chorioallantoic membrane assay. The results of these studies indicate that the detached retina possesses higher angiogenic activity than the normal, attached retina. This suggests that disturbances in the nourishment by the choroid of outer retinal layers may play a role in the pathogenesis of ocular neovascularization.

Allantois↗

PubMedDate not supplied

Disseminated infection with Saccharomyces kluyveri in a patient with AIDS.

A 47-year-old man with acquired immune deficiency syndrome was found to have disseminated Saccharomyces kluyveri infection. The yeast was isolated from blood and cerebro-spinal fluid. An autopsy revealed the presence of the microorganism in many organs including liver, kidneys, pancreas, spleen, lung, and brain. The case confirms a potential pathogenicity of yeasts of the genus Saccharomyces in patients with profound immune deficiency, especially in advanced HIV infection.

AIDS-Related Opportunistic Infections↗

PubMed1994

[Inflammatory type of epidermolysis bullosa acquisita].

Epidermolysis bullosa acquisita (EBA) is an autoimmune subepidermal blistering disease, which can present in various clinical forms. We report on a 73-year-old male patient with the inflammatory type of EBA, which is clinically similar to bullous pemphigoid. Histological examination revealed subepidermal blister formation, and direct immunofluorescence of perilesional skin revealed a linear deposition of IgG and C3 at the basement membrane. Indirect immunofluorescence with 0.9% NaCl-separated human skin as substrate showed the presence of circulating antibodies binding to the base of the artificial blister at a titre of 1:320. Indirect immunoelectronmicroscopy revealed immune deposits localized in the area of the sublamina densa. Immunoblotting of dermal extracts disclosed binding of serum antibodies to a 290-kDa protein. Systemic therapy with diaminodiphenyl sulphone, initially in combination with corticosteroids, resulted in complete healing of the skin lesions. With reference to this case report, we discuss the clinical pictures possible in EBA, the differential diagnosis and the treatment options.

Aged↗

PubMed2005

Prognosis of cocaine body-packers.

OBJECTIVE: To study the prognosis and complications of cocaine body-packing (concealment of cocaine in the body for transportation between countries). DESIGN: We retrospectively reviewed the files of all cocaine body-packers hospitalized during a 4-year period in a medico-judiciary emergency unit. Subjects included in the survey were identified from the hospital databases using ICD-10 codes. SETTING: The Medico-Judiciary Emergency Unit of Hôtel-Dieu university hospital in Paris is a unique medical and surgical emergency unit receiving all patients in legal custody arrested at the two Paris international airports and suspected of body-packing. PATIENTS: All the cases of cocaine body-packers (n=581) hospitalized between January 1999 and December 2002 were studied. They had been arrested at Paris airports while arriving from drug-producing countries. RESULTS: The mean number of carried packets was 70.0+/-20.4 (range 18-150). The mean duration of hospitalization was 5.0+/-1.6 days (range 1-18). No complication occurred in 573 body-packers cases. Eight subjects developed a complication requiring admission to an intensive care unit: six acute cocaine intoxications due to packet rupture and two intestinal occlusions. No one died. Surgical treatment was necessary in six cases. CONCLUSIONS: Good prognosis observed in these body-packers cases is due to the careful monitoring of asymptomatic patients, allowing early detection and treatment of complications. Surgical removal of the packets when complication occurs is warranted.

Adult↗

PubMed2006

B-type natriuretic peptide and weaning from mechanical ventilation.

OBJECTIVE: Cardiac function and volume status could play a critical role in the setting of weaning failure. B-type natriuretic peptide (BNP) is a powerful marker of cardiac dysfunction. We assessed the value of BNP during the weaning process. DESIGN, SETTING AND PATIENTS: One hundred and two consecutive patients considered ready to undergo a 1-h weaning trial (T-piece or low-pressure support level) were prospectively included in a medical intensive care unit of a university hospital. Weaning was considered successful if the patient passed the trial and sustained spontaneous breathing for more than 48 h after extubation. INTERVENTIONS: Plasma BNP was measured just before the trial in all patients, and at the end of the trial in the first 60 patients. RESULTS: Overall, 42 patients (41.2%) failed the weaning process (37 patients failed the trial and 5 failed extubation). Logistic regression analysis identified high BNP level before the trial and the product of airway pressure and breathing frequency during ventilation as independent risk factors for weaning failure. BNP values were not different at the end of the trial. In nine of the patients in whom the weaning process failed, it succeeded on a later occasion after diuretic therapy. Their BNP level before weaning decreased between the two attempts (517 vs 226 pg/ml, p=0.01). In survivors, BNP level was significantly correlated to weaning duration (rho=0.52, p<0.01). CONCLUSIONS: Baseline plasma BNP level before the first weaning attempt is higher in patients with subsequent weaning failure and correlates to weaning duration.

Aged↗

PubMed2003

The effect of diffusion, depolymerization and nucleation promoting factors on actin gel growth.

In eukaryotic cells, localized actin polymerization is able to deform the plasma membrane and push the cell forward. Depolymerization of actin filaments and diffusion of actin monomers ensure the availability of monomers at sites of polymerization, and therefore these processes must play an active role in cellular actin dynamics. Here we reveal experimental evidence that actin gel growth can be limited by monomer diffusion, consistent with theoretical predictions. We study actin gels formed on beads coated with ActA (and ActA fragments), the bacterial factor responsible for actin-based movement of Listeria monocytogenes. We observe a saturation of gel thickness with increasing bead radius, the signature of diffusion control. Data analysis using an elastic model of actin gel growth gives an estimate of 2x10(-8) cm(-2) s(-1) for the diffusion coefficient of actin monomers through the gel, ten times less than in buffer, and in agreement with literature values in bulk cytoskeleton, providing corroboration of our model. The depolymerization rate of actin filaments and the elastic modulus of the gel are also evaluated. Furthermore, we qualitatively examine the different actin gels produced when ActA fragments interact with either VASP or the Arp2/3 complex.

Actin-Related Protein 2↗

PubMed1998

Acting on actin: the electric motility assay.

We have developed a novel technique which allows one to direct the two dimensional motion of actin filaments on a myosin coated sheet using a weak electric field parallel to the plane of motion. The filament velocity can be increased or decreased, and even reversed, as a function of orientation and strength of the field. PMMA (poly(methylmethacrylate)) gratings, which act as rails for actin, allow one for the first time to explore three quadrants of the force velocity diagram. We discuss effective friction, duty ratio and stall force at different myosin densities. A discontinuity in the velocity force relationship suggests the existence of dynamical phase transition.

Actins↗

PubMed2000

Measurement of the elasticity of the actin tail of Listeria monocytogenes.

We report biophysical experiments performed on the bacterium Listeria monocytogenes, a model system to study actin-based motility. Using optical tweezers and electrophoresis experiments, we find that the bacterium is firmly attached to its tail, and we demonstrate that the tail responds as an elastic gel when deformed. We have measured its elastic modulus at a value of 10(3)-10(4) Pa, which is 10 times higher than the rigidity of the eukaryotic cytoplasm. These results demonstrate that the bacterium and its tail form a very robust system, consistent with the steadyness of the motion observed in vivo. We propose an elastic model for the propulsion mechanism which takes into account the connection and thus the interaction between the actin filaments. It provides a generic description of the various aspects of actin-tail based movements.

Actins↗

PubMed2004

Fish protein improves blood pressure but alters HDL2 and HDL3 composition and tissue lipoprotein lipase activities in spontaneously hypertensive rats.

The two-month effects of dietary fish protein and casein on VLDL, HDL(2) and HDL(3) compositions and hepatic lipase (HTGL) and tissue lipoprotein lipase (LPL) activities were examined in spontaneously hypertensive rats (SHR) at 4 wk of age. After 2 mo of experiment, the fish protein diet induced lower blood pressure (-14 %) as compared to casein. Liver triacylglycerol and total cholesterol concentrations were 1.37- and 1.71-fold lower in the fish protein group than in the casein group, respectively. Total cholesterol concentration in plasma was also diminished by fish protein (-21 %) and was reflected in HDL(2) fraction (-44 %). SHR fed the fish protein diet as compared with those fed casein, showed a significantly low HDL(3) particle number, as measured by diminished HDL(3) mass and apo A-I. The consumption of fish protein did not affect VLDL particle number, but significantly decreased VLDL-triacylglycerol (-32 %) and adipose tissue total lipid concentrations as compared to casein. This was accompanied by diminished HTGL and adipose tissue LPL activities (-10%, -91%, respectively). These data demonstrate that fish protein plays an antihypertensive role and reduces plasma and tissue lipid concentrations. Thus, a fish protein intake might be beneficial for patients with hypertension.

Animals↗

PubMed2005

Intravenous immunoglobulin in neurological disorders: a mechanistic perspective.

Intravenous immunoglobulin (IVIg) has been used in the treatment of primary and secondary antibody deficiencies for over 25 years. It is a safe preparation with no long-term side effects. IVIg was first demonstrated to be effective in autoimmune disorders, two decades ago, in the treatment of acute immune thrombocytopenia. Since then, the therapeutic efficacy of IVIg has been established in Guillain Barré syndrome (GBS), chronic inflammatory demyelinating polyneuropathy (CIDP), myasthenia gravis (MG), dermatomyositis (DM), Kawasaki syndrome and the prevention of graft-versus-host disease in recipients of allogeneic bone marrow transplants and reported in a large number of other autoimmune and systemic inflammatory conditions.

Animals↗

PubMed1999

Immunoelectron microscopic study of the conjunctiva in cicatricial pemphigoid.

BACKGROUND: Immune deposits can be found on the conjunctival basement membrane zone of patients affected by cicatricial pemphigoid using immunofluorescence technique. The purpose of this study was to perform direct immunoelectron microscopy on the conjunctiva of patients with scarring conjunctivitis associated with cicatricial pemphigoid. METHODS: Conjunctival and skin biopsies were performed in six patients who presented with presumed autoimmune cicatrizing conjunctivitis associated with cicatricial pemphigoid. Specimens were processed for direct immunofluorescence and direct immunoelectron microscopy. RESULTS: Direct immunofluorescence was positive in all skin samples and in three of six conjunctival samples. Direct immunoelectron microscopy showed immune deposits in the lamina lucida and the lamina densa of all skin and conjunctival samples. CONCLUSIONS: Direct immunoelectron microscopy can be performed on the conjunctiva. It shows the precise localization of cicatricial pemphigoid target antigens within the conjunctival basement membrane zone.

Aged↗

PubMed1998

Axial and transverse stiffness measures of cochlear outer hair cells suggest a common mechanical basis.

The function of the hearing organ is based on mechanical processes occurring at the cellular level. The mechanical properties of guinea-pig isolated sensory cells were investigated using two different techniques. The stiffness of the outer hair cells along the longitudinal axis was measured by compressing the cell body using stiffness-calibrated quartz fibres. For cells with a mean length of 69 micron, the mean axial compression stiffness was 1. 1+/-0.8 mN/m (+/-SD). There was an inverse relation between stiffness and cell length. The stiffness of the cell membrane perpendicular to the longitudinal axis of the sensory cell was measured by indenting the cell membrane with a known force. The mean lateral indentation stiffness was 3.3+/-1.5 mN/m (+/-SD) for cells with a mean length of 64 microm. Longer cells were less stiff than short cells. Modelling the hair cell as a shell with bending resistance, finite element calculations demonstrated that the axial compression stiffness correlated well with the lateral indentation stiffness, and that a simple isotropic model is sufficient to explain the experimental observations despite the different stress strain states produced by the two techniques. The results imply that the two different stiffness properties may originate from the same cytoskeletal structures. It is suggested that the mechanical properties of the outer hair cells are designed to influence the sound-induced motion of the reticular lamina. In such a system, stiffness changes of the outer hair cell bodies could actively control the efficiency of the mechanical coupling between the basilar membrane and the important mechanoelectrical transduction sites at the surface of the hearing organ.

Animals↗

PubMed1998

Low birth weight at term impairs cord serum lipoprotein compositions and concentrations.

UNLABELLED: The purpose of this study was to determine the effect of low birth weight at term on serum lipoproteins. Lipid and apolipoprotein (apo) contents were investigated in cord sera of small-for-gestational-age (SGA) newborns at term (2290 g +/- 33 g) and compared with those of appropriate-for-gestational-age (AGA) newborns (3570 g +/- 93 g). In SGA newborns, VLDL amounts were twofold higher, whereas LDL, HDL2 and HDL3 contents were lower than in AGA newborns (-38%, -44% and -42%, respectively). VLDL-triacylglycerols (TG), apo B-100 and apo E were higher, while VLDL-apo C-II values were 39% lower in SGA newborns compared with those of AGA newborns. In SGA newborns, HDL2-apolipoprotein, phospholipid and cholesteryl ester levels were respectively reduced to 70%, 50% and 40% compared with AGA values. HDL3-apolipoprotein and phospholipid contents were also decreased in SGA newborns (-43% and -60%, respectively). The different HDL2 and HDL3-apolipoproteins (apo A-I, A-II, C-III and E) were significantly decreased in SGA newborns. CONCLUSION: Intra-uterine growth retardation was accompanied by alterations in apolipoproteins and lipid compositions in the four lipoprotein fractions, which may impair lipid metabolism. Follow up studies on lipoprotein patterns in SGA infants are required to investigate whether such abnormalities at birth lead to diseases in adulthood.

Apolipoproteins↗

PubMed1999

Changes in serum lipid and lipoprotein concentrations and compositions at birth and after 1 month of life in macrosomic infants of insulin-dependent diabetic mothers.

The aim of this study was to determine whether macrosomia related to maternal diabetes alters lipoprotein metabolism and whether these abnormalities still persist or regress after 1 month of life. Serum lipoprotein compositions and concentrations as well as serum lipid fatty acid compositions were investigated in macrosomic infants (birth weight = 4840 +/- 105 g at term) of insulin-dependent diabetic mothers at birth and after 1 month of life, and were compared to those of control infants (birth weight = 3400 +/- 198 g at term) of healthy mothers. Compared to controls, at birth, macrosomic newborns had higher serum lipids, apolipoprotein A-I and B-100, and lipoprotein (very low density lipoprotein, low density lipoprotein, high density lipoprotein-2 and high density lipoprotein-3) levels. Higher percentages of C18:2n-6 in serum triacylglycerols, phospholipids and cholesteryl esters were also observed. At day 30, in macrosomics, serum triacylglycerol, apo B-100, very low density lipoprotein and low density lipoprotein levels were still significantly higher. C18:2n-6 and C18:3n-3 contents in serum phospholipids, triacylglycerols and cholesteryl esters were reduced while C20:4n-6 and C22:6n-3 contents in serum phospholipids and cholesteryl esters were enhanced, compared to control values. Macrosomia was associated with alterations in lipoprotein compositions and concentrations at birth, some of which persisted after 1 month of life, and might play a role in the pathogenesis of diabetes and atherosclerosis in adult life.

Case-Control Studies↗

PubMed2005

Carotenoids modulate the trade-off between egg production and resistance to oxidative stress in zebra finches.

The allocation of resources to reproduction and survival is a central question of studies of life history evolution. Usually, increased allocation to current reproduction is paid in terms of reduced future reproduction and/or decreased survival. However, the proximal mechanisms underlying the cost of reproduction are poorly understood. Recently, it has been shown that increased susceptibility to oxidative stress might be one of such proximate links between reproduction and self-maintenance. Organisms possess a range of antioxidant defenses, including endogenously produced molecules (e.g., enzymes) and compounds ingested with food (e.g., carotenoids). If reproductive effort increases the production of reactive oxygen species, the availability of antioxidant defenses may partly or fully counteract the free-radical damages. One could, therefore, expect that the trade-off between reproduction and oxidative stress is modulated by the availability of antioxidant defenses. We tested this hypothesis in zebra finches. We manipulated reproductive effort by either allowing or preventing pairs to breed. Within each breeding or non-breeding group, the availability of antioxidant compounds was manipulated by supplementing or not supplementing the drinking water with carotenoids. We found that although birds in the breeding and non-breeding groups did not differ in their resistance to oxidative stress (the breakdown of red blood cells submitted to a controlled free-radical attack), one aspect of breeding effort (i.e., the number of eggs laid by birds in both breeding and non-breeding groups) was negatively correlated with resistance to oxidative stress only in birds that did not benefit from a carotenoid-supplemented diet. This result therefore suggests that carotenoid availability can modulate the trade-off between reproduction and resistance to oxidative stress.

Animals↗

PubMed2005

Immunomodulation of autoimmune and inflammatory diseases with intravenous immunoglobulin.

Intravenous immunoglobulin (IVIg) has been used in the treatment of primary and secondary antibody deficiencies for over two decades. Since the early 1980s, the therapeutic efficacy of IVIg has been established in idiopathic thrombocytopenic purpura, Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy, myasthenia gravis, dermatomyositis and Kawasaki syndrome, and the prevention of graft versus host disease in recipients of allogeneic bone marrow transplants. Its use has also been reported in a large number of other autoimmune and systemic inflammatory conditions. In this review, we discuss the mechanisms by which IVIg exerts immunomodulatory effects in immune pathologies.

Antigen-Presenting Cells↗