Multiple sclerosis: cell-mediated immunity to human brain gangliosides

Cell-mediated immunity (CMI) to myelin components has been implicated in Multiple Sclerosis (MS) pathogenesis: two targets were suggested, Myelin Basic Protein with controversial results and, more recently, gangliosides. In order to investigate their possible involvement, we have performed Leukocyte Migration inhibition (LMI) tests in the presence of human brain gangliosides. Thirty nine MS patients (twenty four being "definite", according to McDonald and Halliday's classification), twenty nine patients with Other Neurological Diseases (OND), thirty six patients with Inflammatory diseases (ID) and forty healthy controls were tested. MS patients were divided into two groups, depending on the clinical stage of the disease. The mean migration inhibition percentage of the MS-attack group was found to be significantly different from the four others (p less than 0.01) (24.4 +/- 16.2 versus 10.9 +/- 8.5 in MS without attack, 4.4 +/- 12.9 in OND, 3.9 +/- 13.9 in ID and 11.1 +/- 12.1 in healthy subjects). LMI to gangliosides is therefore significantly increased during the attack stage in MS. These results support the notion of a Delayed Type Hypersensitivity to these glycolipids during the active stage of the disease.     

A role for hyaluronan in macrophage accumulation and collagen deposition after bleomycin-induced lung injury

Elevated concentrations of hyaluronan (HA) are associated with the accumulation of macrophages in the lung after injury. We have investigated the role of HA in the inflammatory and fibrotic responses to lung injury using the intratracheal instillation of bleomycin in rats as a model. After bleomycin-induced lung injury, both HA content in bronchoalveolar lavage (BAL) and staining for HA in macrophages accumulating in injured areas of the lung were maximal at 4 d. Increased HA in BAL correlated with increased locomotion of isolated alveolar macrophages. HA-binding peptide was able to specifically block macrophage motility in vitro. Importantly, systemic administration of HA-binding peptide to rats before injury not only decreased alveolar macrophage motility and accumulation in the lung, but also reduced lung collagen alpha (I) messenger RNA and hydroxyproline contents. We propose a model in which HA plays a critical role in the inflammatory response and fibrotic consequences of acute lung injury.     

Performance of a bimanual load-lifting task by parkinsonian patients.

Normal subjects and Parkinsonian patients performed a bimanual load lifting task. In this task, one "postural" forearm, held in a horizontal position while supporting a 1 kg weight, was unloaded either by the experimenter's hand (imposed unloading) or by the subject's other hand in response to a tone burst (voluntary unloading). The variables recorded were reaction time (RT: time interval between the tone and beginning of unloading) and movement time (MT: duration of the change in force measured by a force platform on the "postural" forearm). Elbow angle changes were also measured with a potentiometer. The EMG activity from brachioradialis of the "postural" arm and that from the biceps of the "active" arm were recorded. The Parkinsonian patients showed an increase in both RT and MT and an impairment of the co-ordination between movement and posture which was reflected in an increase in amplitude of the elbow rotation after voluntary unloading. Moreover, the decrease in EMG activity in the brachioradialis of the postural arm during unloading was less in Parkinsonian patients than in the normal group. This disorder of postural command was often accompanied by a lack of anticipatory EMG changes. Comparison between treated and non-treated patients showed that dopamine agonists brought about recovery of both RT and MT but did not improve postural co-ordination. The co-ordination was less impaired when the voluntary unloading was performed by the preferred hand. Several hypotheses are discussed concerning the mechanism underlying this impaired co-ordination.     

Intercomparison of calibration procedures for 192Ir HDR sources in Brazil

The lack of well established dosimetry protocols for HDR sources is a point of great concern regarding the uniformity of procedures within a particular country and worldwide. The main objective of this paper is to report the results from ten institutions of an intercomparison of calibration procedures for 192Ir HDR sources currently in use in Brazil. The treatment irradiator of one institution was calibrated by a reference system and used by all participants with their own measuring electrometers and ionization chambers under the same experimental conditions. Two methods were used: the calibration jig and the well-type ionization chamber. Each participant was allowed to use their own method and formalism. The results of this exercise were very positive since this was the first time in Brazil that a group of users gathered to share their experience and openly discuss the physical concepts behind the calibration procedures. The results were all within +/-3.0%, except one case where -4.6% was observed and later identified as a problem with the Nk value for x-rays. Though the magnitude of the deviations found was generally acceptable considering the diversity of formalisms currently in use, a proposal is now being prepared to be adopted as a national protocol. The identification of the institutions was left out for the sake of confidentiality.     

A novel immunization method to induce cytotoxic T-lymphocyte responses (CTL) against plasmid-encoded herpes simplex virus type-1 glycoprotein D

DNA molecules complexed with an asialoglycoprotein-polycation conjugate, consisting of asialoorosomucoid (ASOR) coupled to poly-L-lysine, can enter hepatocytes which bear receptors for ASOR. We used this receptor-mediated DNA delivery system to deliver plasmid DNA encoding glycoprotein D (gD) of herpes simplex virus type 1 to ASOR-positive cells. Maximum expression of gD protein was seen at 3 days after injection of this preparation in approximately 13% of cells from BALB/c mice [hepatocytes from mice injected intravenously (i.v.) or peritoneal exudate cells from mice injected intraperitoneally (i.p.)]. In comparison with mice injected with either the plasmid vector alone or the gD-containing plasmid uncomplexed to ASOR, mice immunized with gD-containing plasmid complexed with ASOR-poly-L-lysine induced marked antigen-specific CTL responses. BALB/c mice immunized with gD-DNA developed a T-cell-mediated CTL response against target cells expressing gD and MHC class II glycoproteins, but not against cells expressing only gD and MHC class I molecules. In C3H mice, gD-DNA induced a T-cell-mediated CTL response against target cells expressing gD and class I MHC molecules. Serum anti-gD antibody in low titers were produced in both strains of mice. DNA complexed with ASOR-poly-L-lysine induced CTL responses in mice.     

Orbital infarction and melting in a patient with systemic lupus erythematosus

OBJECTIVE: To present a patient with systemic lupus erythematosus who developed infarction and melting of the orbit secondary to her systemic disease. DESIGN: A case report. PARTICIPANT: A 61-year-old white woman with a 5-year history of systemic lupus erythematosus. METHODS: The patient presented with left orbital pain, limitation of extraocular movements, and a fistula from the ethmoid sinus to the upper eyelid. A detailed examination with computerized tomography, ultrasound, and a comprehensive medical evaluation with laboratory testing was performed. Histopathologic analysis with special stains of the orbital tissues was also performed. RESULTS: Histopathologic examination of the biopsy specimens revealed the features of an inflammatory process involving the orbit, similar to a panniculitis. These include a lymphocytic reaction with a predominance of plasma cells, vasculitis with occlusion, and thickening of the vessel walls, necrosis, and hyalinization of fat. CONCLUSION: This is a unique case in which infarction and melting of the entire orbital structures occurred in the presence of systemic lupus erythematosus. The underlying disease process is a lupus-related panniculitis. The authors stress that this is a very rare entity and that other diseases should be ruled out before entertaining this diagnosis.     

Phacotrabeculectomy versus two-stage operation: a matched study

BACKGROUND AND OBJECTIVE: To evaluate the efficacy and safety of phacoemulsification and foldable intraocular lens, combined with trabeculectomy (phacotrabeculectomy) in patients with coexisting cataract and glaucoma. PATIENTS AND METHODS: A total of 53 consecutive eyes which underwent phacotrabeculectomy and posterior chamber intraocular lens (PCIOL) were matched and compared with 53 eyes that had trabeculectomy followed by phacoemulsification and posterior chamber intraocular lens (mean interval 3.2 month). The 2 groups were first matched by diagnostic group and subsequently for the closest possible match with other successive variables, including age, gender, race and preoperative glaucoma medications. Mean intraocular pressure (IOP) reduction, visual acuity, antiglaucoma medications, and surgical success as well as complications were compared in both groups. RESULTS: Mean IOP reduction was 14.5+/-4.1 mmHg in the two-stage group compared to 15.1+/-3.9 in the phacotrabeculectomy group at 6 months follow-up (P<0.1) and 13.8+/-3.9 and 14.6+/-3.7 respectively at 1 year (P<0.1).Visual acuity and complications were comparable. CONCLUSION: Phacotrabeculectomy provides IOP control statistically comparable to two-stage surgery with earlier visual rehabilitation.     

Free versus liposome-encapsulated lignocaine hydrochloride topical applications.

The influence of encapsulating lignocaine hydrochloride, in a liposomal delivery system on its release from a topical formulation was studied. Liposomes were prepared from a mixture of L-alpha-dipalmitoylphosphatidyl choline (DPPC) and cholesterol in different molar ratios with or without charge inducing agents. The swelling time affording maximum entrapment was tested from 0-48 h at 53 degrees C. The percentage of drug entrapped in liposomes was found to be charge dependent and more pronounced for negatively charged liposomes. The amount of drug entrapped increased by increasing the ratio of cholesterol. The selected formulations were evaluated in vivo using the pin prick method. The results revealed localized and prolonged activity of lignocaine contained in liposomes when compared with an equivalent conventional topical application.