[DRESS syndrome with bilateral panuveitis, elevated intraocular pressure, and HHV-6 reactivation: a case report]. / DRESS syndrome associé à une pan-uvéite bilatérale: à propos d'un cas.

INTRODUCTION: DRESS syndrome (drug rash or reaction with eosinophilia and systemic symptoms) is a rare but life-threatening drug hypersensitivity syndrome with a potential viral cofactor. The syndrome is characterized by rash, fever, hematological disorders (eosinophilia, lymphocytosis), and systemic symptoms (adenopathy, multiorgan involvement). CASE REPORT: We report the first description of acute bilateral panuveitis with elevated intraocular pressure associated with anticonvulsant-induced DRESS syndrome, hypogammaglobulinemia, and HHV-6 reactivation in a 63-year-old-woman. Complete general and ophthalmological recovery was obtained 4 weeks after the end of anticonvulsant drug exposure without corticosteroid prescription, with the patient remaining free of disease after 6 months. DISCUSSION: Our data suggest that uveitis may be one of multivisceral involvements described in drug hypersensitivity syndrome. The data also suggest that HHV-6 may play a role in the complex pathogenesis of DRESS as well as in the development of immune inflammatory disorders such as bilateral panuveitis with elevated intraocular pressure and alteration of retinal and choroidal circulation in this patient.

[Isolated occlusion of a cilioretinal artery]. / Occlusion isolée d'une artère cilio-rétinienne.

PURPOSE: Isolated cilioretinal artery occlusion is uncommon but has characteristic features. Based on a case report and a review of the literature, we present the clinical findings and angiographic particularities of this syndrome and discuss controversial pathophysiological data. CASE REPORT AND METHOD: A 56-year-old man had sudden visual loss in the right eye estimated at 3/10 P10. Fundus examination showed areas of retinal interpapillomacular infarction due to cilioretinal artery occlusion. Fluorescein angiography demonstrated delayed filling and emptying of this artery. Left fundus examination was normal. RESULTS: Systemic examinations revealed severe hypertension (240/130) rapidly controlled with a two-drug regimen. The clinical course was good with normalization of fundus and angiography, and visual recovery to 8/10 P3 with a small absolute paracentral scotoma. DISCUSSION: The few cases described would offer an explanation of the low prevalence of cilioretinal arteries and the more frequent association with central retina venous obstruction which can mask arterial occlusion. A relative reversible occlusion explains the generally good prognosis especially if the capillary network is not affected by the occluded artery as was observed in our case. CONCLUSION: Although diagnosis of isolated cilioretinal artery occlusion is made without difficulty, the underlying pathogenic mechanism remains difficult to explain due to the various phenomena revealed by the increased arterial pressure.

[A case of conjunctival raspberry tumor of viral origin]. / Une tumeur framboisée conjonctivale d'origine virale.

We describe the clinical and histopathological findings of a conjunctival papilloma due to papillomavirus. The therapeutic method applied was excision plus cryotherapy. These lesions are known to recur, and papillomavirus DNA sequences are present in several cases of conjunctival dysplasia and carcinoma. Using biological molecular methods (in situ hybridization, Southern blot hybridization, and particularly polymerase chain reaction), more than 60 Human Papillomavirus have currently been reported. This new detection techniques improve the possibility of findings HPV infection, and increase the interest for this virus extremely widely distributed in man.

[Macular complications of synthetic antimalarials. Apropos of a case]. / Complications maculaires des antipaludéens de synthèse. A propos d'une observation.

The clinico-pathological findings in a 17-year-old girl with an "oeil de boeuf" maculopathy are reported together with the aetiological elements involved (hereditary or toxic maculopathy). The case was a second stage typical maculopathy due to antimalarial drugs. These patients were particularly susceptible, probably because of impaired renal function, since the total dose absorbed (140 g. chloroquine) was low. Ophthalmologic monitoring is required to prevent intoxication. Clinical examination, angiography and automatic perimetry and contrast sensitivity test are needed to detect the first effect of toxicity.

Identification of an IP3 receptor in endothelial cells.

In this study we have used saponin to permeabilize bovine endothelial cell membranes in order to directly test the involvement of IP3 in regulating internal Ca2+ release. Our results indicate that the release of internal Ca2+ occurs as early as 1-3 seconds after IP3 addition. This IP3-induced internal Ca2+ release can be inhibited by heparin (an IP3 receptor antagonist). Further binding of [3H]IP3 to saponin-permeabilized bovine endothelial cells reveals the presence of a single, high affinity class of IP3 receptor with a dissociation constant (Kd) of approximately 0.50 (+/- 0.03) nM. Using a panel of monoclonal and polyclonal antibodies against IP3 receptor, we have established that the bovine endothelial cell IP3 receptor (approximately 260 kDa) displays immunological cross-reactivity with the rat brain IP3 receptor. Immunofluorescence data indicates that the IP3 receptor is preferentially located at the perinuclear region of the cells. In addition, PCR analysis of first-strand cDNAs from both bovine endothelial cells and rat brain tissues reveals that the IP3 receptor transcript in bovine endothelial cells belongs to the short non-neuronal form and not the long neuronal form detected in rat brain tissue. These findings suggest that the IP3 receptor in endothelial cells is both structurally and functionally analogous to that reported in non-neuronal cell systems and probably plays an important role in agonist-induced endothelial cell activation.

A CD44-like endothelial cell transmembrane glycoprotein (GP116) interacts with extracellular matrix and ankyrin.

We used complementary biochemical and immunological techniques to establish that an endothelial cell transmembrane glycoprotein, GP116, is a CD44-like molecule and binds directly both to extracellular matrix components (e.g., hyaluronic acid) and to ankyrin. The specific characteristics of GP116 are as follows: (i) GP116 can be surface labeled with Na 125I and contains a wheat germ agglutinin-binding site(s), indicating that it has an extracellular domain; (ii) GP116 displays immunological cross-reactivity with a panel of CD44 antibodies, shares some peptide similarity with CD44, and has a similar 52-kDa precursor molecule, indicating that it is a CD44-like molecule; (iii) GP116 displays specific hyaluronic acid-binding properties, indicating that it is a hyaluronic acid receptor; (iv) GP116 can be phosphorylated by endogenous protein kinase C activated by 12-O-tetradecanoylphorbol-13-acetate and by exogenously added protein kinase C; and (v) GP116 and a 20-kDa tryptic polypeptide fragment of GP116 from the intracellular domain are capable of binding the membrane-cytoskeleton linker molecule, ankyrin. Furthermore, phosphorylation of GP116 by protein kinase C significantly enhances GP116 binding to ankyrin. Together, these findings strongly suggest that phosphorylation of the transmembrane glycoprotein GP116 (a CD44-like molecule) by protein kinase C is required for effective GP116-ankyrin interaction during endothelial cell adhesion events.

Role of Ca2+ in the regulation of hormone receptor exposure during lymphocyte activation.

Ca2+ is known to be required for mitogen-mediated lymphocyte activation. In order to further define the regulatory role of Ca2+, we have examined the activation events which occur following treatment with ionomycin (a Ca2+ ionophore), as compared to those occurring following concanavalin A (Con A) treatment of mouse splenic T-lymphocytes. Our results indicate that ionomycin and Con A induce the exposure of both interleukin-2 (IL-2) and insulin receptors on the surface of the lymphocytes within the first 5 min of treatment. The exposed insulin and IL-2 receptors have the following properties: (1) they consist of both high- and low-affinity receptors; and (2) they appear on the cell surface in small clusters (i.e., patches) or, occasionally, a large aggregate (i.e., cap). c-myc gene expression and DNA synthesis occur in both the ionomycin and Con A-treated lymphocytes when either IL-2 or insulin is present in the culture medium. Furthermore, the exposure of both hormone receptors can be inhibited by either EGTA (a Ca2+ chelator), bepridil (a Ca2+ channel blocker), W-7 (a calmodulin antagonist) or cytochalasin D (a microfilament inhibitor). Treatment with these inhibitors also blocks the expression of c-myc gene and DNA synthesis which occur at later times during IL-2 and insulin-induced activation of ionomycin- and Con A-treated lymphocytes. These findings suggest that a Ca2+ and calmodulin-mediated contractile system is involved in the exposure of certain hormone receptors which appear to be required for complete lymphocyte activation.

Electric stimulation of human fibroblasts causes an increase in Ca2+ influx and the exposure of additional insulin receptors.

Previously we reported that treating human fibroblasts in cell culture with high-voltage, pulsed galvanic stimulation (HVPGS) can significantly increase cellular protein and DNA synthesis (Bourguignon and Bourguignon: FASEB J., 1:398-402, 1987). In this study we have identified two of the early cellular events which occur following exposure to HVPGS: 1) an increase in Ca2+ uptake from the external medium and 2) an increase in the number of insulin receptors on the fibroblast cell surface. The increase in Ca2+ uptake begins within the first minute of electric stimulation while increased insulin binding is not detected until the second minute of stimulation. The HVPGS-induced increase in insulin binding can be inhibited by bepridil, a specific Ca2+ channel blocker, suggesting that the Ca2+ influx is required for the exposure of additional insulin receptors on the cell surface. Furthermore, we have determined that the addition of insulin to electrically stimulated cultures results in 1) an immediate, second increase in Ca2+ uptake and 2) significant increases in both protein and DNA synthesis compared to cells which were not stimulated. All three of these insulin-dependent effects are also inhibited by bepridil. Based on these results, we propose that HVPGS initially triggers the opening of voltage-sensitive calcium channels in the fibroblast plasma membrane. The increased level of intracellular Ca2+ then induces the exposure of additional insulin receptors, the fibroblasts will significantly increase both protein and DNA synthesis.

[Campylobacter pylori: diagnostic value of the urease test during endoscopy]. / Le Campylobacter pylori: valeur diagnostique de l'uréase test pratiqué en salle d'endoscopie.

The aims of this prospective study were a) to evaluate the diagnostic value of the urease test for the detection of C. pylori in gastric biopsy specimens, b) to specify the prevalence of C. pylori in a sample of 74 patients from the Grenoble area undergoing upper gastrointestinal endoscopy, c) to analyze the density of bacteria according to the biopsy site (antrum, body, edges of ulcer), d) to demonstrate any possible correlation between the histologic state of the antral and body mucosa and the presence of C. pylori. An antral biopsy was taken for the urease test during endoscopy. Biopsies were also taken from the body, the antrum and the edges of gastric or duodenal ulcers for bacterial and histologic studies, and urease test in the bacterial laboratory. The sensitivity and the specificity of the urease test during endoscopy varied according to the delay in observation of the color change. They were 0.81 and 0.84, respectively, at 2 h 30. The sensitivity and specificity of the urease test in the bacterial laboratory were 0.67 and 0.95, respectively, for the same delay. The global prevalence of C. pylori was 51 p. 100: it was 42 p. 100 in the absence of ulcer, 67 p. 100 in the presence of gastric ulcer, and 71 p. 100 in the presence of duodenal ulcer (p less than 0.05 compared to the group without ulcer).(ABSTRACT TRUNCATED AT 250 WORDS)

Lymphocyte activation and capping of hormone receptors.

In this study both a ligand-dependent treatment [concanavalin A (Con A)] and a ligand-independent treatment [high-voltage pulsed galvanic stimulation (HVPGS)] have been used to initiate lymphocyte activation via a transmembrane signaling process. Our results show that both treatments cause the exposure of two different hormone [insulin and interleukin-2 (IL-2)] receptors within the first 5 min of stimulation. When either insulin or IL-2 is present in the culture medium, the stimulated lymphocytes undergo the following responses: (1) increased free intracellular Ca2+ activity; (2) aggregation of insulin or IL-2 receptors into patch/cap structures; (3) tyrosine-kinase-specific phosphorylation of a 32-kd membrane protein; and finally (4) induction of DNA synthesis. Further analysis indicates that hormone receptor capping is inhibited by (1) cytochalasin D, suggesting the involvement of microfilaments; (2) sodium azide, indicating a requirement for ATP production; and (3) W-5, W-7, and W-12 drugs, implying a need for Ca2+/calmodulin activity. Treatment with these metabolic or cytoskeletal inhibitors also prevents both the tyrosine-kinase-specific protein phosphorylation and DNA synthesis which normally follow hormone receptor capping. Double immunofluorescence staining shows that actomyosin, Ca2+/calmodulin, and myosin light-chain kinase are all closely associated with the insulin and IL-2 receptor cap structures. These findings strongly suggest that an actomyosin-mediated contractile system (regulated by Ca2+, calmodulin, and myosin light-chain kinase in an energy-dependent manner) is required not only for the collection of insulin and IL-2 receptors into patch and cap structures but also for the subsequent activation of tyrosine kinase and the initiation of DNA synthesis. We, therefore, propose that the exposure and subsequent patching/capping of at least one hormone receptor are required for the activation of mouse splenic T-lymphocytes.

Electric stimulation of protein and DNA synthesis in human fibroblasts.

Human fibroblast cell cultures were employed as a model system to rapidly examine several potentially important variables involved in the use of high-voltage, pulsed galvanic stimulation (HVPGS) to increase the healing rate of soft tissue injuries. Fibroblasts were grown on Millipore filters and exposed to HVPGS of various voltages and pulse rates for 20 min in a rectangular, plastic chamber filled with growth medium. Filters with attached cells were placed either in the center of the chamber or close to the positive or negative electrode. Protein synthesis and DNA synthesis were monitored after stimulation using the radioactively labeled precursors, [3H]proline and [3H]thymidine, respectively. The major results obtained in this study are as follows: 1) the rates of both protein and DNA synthesis can be significantly increased by specific combinations of HVPGS voltage and pulse rate; 2) maximum stimulation of protein and DNA synthesis was obtained at 50 and 75 V, respectively, with a pulse rate of 100 pulses/s and the cells located near the negative electrode; and 3) exposure to HVPGS intensities greater than 250 V (at all pulse rates and locations within the chamber) is inhibitory for both protein and DNA synthesis. In view of the results obtained in preliminary clinical studies on the use of HVPGS for the treatment of dermal ulcers, it appears that similar voltages, pulse rates, and relative electrode location may be required for maximum acceleration of human skin wound healing.

Prevalence of anti-Legionella antibodies in a healthy population and in patients with tuberculosis or pneumonia.

The prevalence of antibodies to 13 antigens of Legionellaceae were compared in three populations: 583 blood donors, 140 tuberculosis patients and 66 patients with acute non Legionellosis pneumonia. Antibody levels were determined by indirect immunofluorescence (IFA) using formalized antigens prepared from bacteria developed in embryonated hen yolk sac. The very weak prevalence of anti L. pneumophila antibodies in a healthy population [almost nil for serogroups 2, 3, 4 and 5; 1.5% for serogroup 6, maximum of 2.5% for serogroup 1 (titres of 16)] confirms the positive and presumptive criteria that have been recommended by Centers for Disease Control (CDC). But as regards the other Legionellae studied, these criteria cannot be applied owing to the prevalences that are higher in healthy populations (until 14.5% with levels of 16-32 and 1% with levels of 64-128 for L. bozemanii) and clearly amplified in tuberculosis patients and in acute pneumonia. Although the significance of these antibodies remains to be discussed, with formalized antigens, it seems reasonable as regards these species to assign a threshold of 256 for the presumptive and positive criteria following seroconversion.

Prevalence of anti-Legionella antibodies in a healthy population and in patients with tuberculosis or pneumonia.

The prevalence of antibodies to 13 Legionella antigens was compared in three populations: 583 blood donors, 140 tuberculosis patients and 66 patients with acute non-legionellosis pneumonia. Antibody levels were determined by indirect immunofluorescence (IFA) using formalin-fixed antigens prepared from bacteria developed in embryonated hen yolk sac. The very weak prevalence of anti-L. pneumophila antibodies in a healthy population [almost 0 for serogroups (SG) 2, 3, 4 and 5; 1.5% for SG 6 and a maximum of 2.5% for SG 1 at a titer of 1: 16] confirms the criteria that have been recommended by the Centers for Disease control, USA. For the other legionellae studied, these criteria cannot be applied due to a higher prevalence in healthy populations (14.5% with levels of 1: 16-32 and 1% with levels of 1: 64-128 for L. bozemanii and progressively decreasing by as much as 2% for the other species: L. micdadei, L. longbeachae, L. gormanii, L. dumoffii and L. jordanis), in tuberculosis patients (12.1% with a level at 1: 64-128 for L. bozemanii, and for the same titer, 9.2% for L. gormanii, 5.7% for L. micdadei, 5% for L. longbeachae 2), and also in acute pneumonia (2 to 3.3% with levels of 1: 64-128 for L. longbeachae 1 and 2, L. jordanis, L. dumoffii, L. micdadei and L. bozemanii). Although the significance of these prevalences remains to be discussed, with formalin-fixed antigens, it seems reasonable for these species to assign a threshold of 1: 256 for the presumptive serodiagnosis following seroconversion.

Lower Spine Screening in the Shooting Sports.

In brief: Rifle and pistol shooters often experience low back pain during or after competition. As a first step in determining the extent and possible causes of such pain, a questionnaire and a rapid screening test for posture and flexibility were designed and administered to 80 shooters. It was found that 78% of the shooters had experienced back pain during competition and 63% had experienced pain afterward. Of the 11 posture and flexibility tests, only the results of Ober's test for tightness of the iliotibial band and tensor fascia lata muscle correlated significantly with reported back pain.

Phorbol ester-induced phosphorylation of a transmembrane glycoprotein (GP 180) in human blood platelets.

In this study we have used (phorbol-12-O-tetradecanoylphorbol 13-acetate) and its biologically inactive analogue, 4 alpha-phorbol 12,13-didecanoate), to investigate platelet protein phosphorylation with special emphasis on the properties of a membrane protein-cytoskeleton (transmembrane) complex during platelet activation. Our data indicate that phorbol-12-O-tetradecanoylphorbol 13-acetate (but not 4 alpha-phorbol 12,13-didecanoate) induces both a specific platelet shape change and the preferential phosphorylation of a 180-kDa protein (presumably due to the activation of protein kinase C on the cytoplasmic side of the membrane). Further analysis reveals that the 180-kDa protein can be iodinated by lactoperoxidase and is sensitive to trypsin treatment, indicating exposure of this protein on the outer cell surface. The 180-kDa protein has also been found to contain wheat germ agglutinin-binding sites. All evidence indicates that the 180-kDa polypeptide is a transmembrane glycoprotein and, most importantly, that this protein is found to be preferentially accumulated into a specific membrane-cytoskeleton complex during activation via phorbol-12-O-tetradecanoylphorbol 13-acetate treatment. We believe that the observed phosphorylation of this protein may be closely related to the formation of a complex between several membrane proteins and the cytoskeleton during the initial stages of platelet activation.

Phosphorylation of a tropomyosin-like (30 KD) protein during platelet activation.

In this study, we have used the tumor promoter 12-o-tetradecanoylphorbol-13-acetate (TPA), as well as its biologically inactive analogue 4 alpha-phorbol 12,13-didecanoate (4 alpha-PDD), to investigate platelet protein phosphorylation and its possible correlation with platelet activation. Our data show that TPA, but not 4 alpha-PDD, induces a preferential phosphorylation of a 30,000 dalton (30 KD) protein. This phosphoprotein is found to be physically associated with an actomyosin-containing platelet cytoskeleton complex. Further analysis using both standard two-dimensional gel electrophoresis and one-dimensional urea-SDS gel electrophoresis reveals that this 30 KD protein has several tropomyosin-like properties. Most importantly, the degree of TPA-induced phosphorylation of the 30 KD protein is directly proportional to the extent of platelet granule release and the shape change of the platelet, as well as to the degree of aggregation. We speculate that this phosphorylated tropomyosinlike protein may play a pivotal role in the regulation of actomyosin-mediated platelet contractility, which has been previously implicated in a variety of platelet functions.