Immunopathology of ocular sarcoidosis

Summary Sarcoidosis is a multisystem disease characterized by enhanced immune responses at sites of involvement. To elucidate the immunopathogenesis of ophthalmic lesions, cell infiltrates in biopsies from conjunctiva and other tissues involved (lungs, lymph nodes, skin) were studied in 26 patients with active sarcoidosis in order to define the surface phenotype and the distribution of cells in granulomatous lesions. Biopsy specimens were also stained for detection of immunoglobulins, complement and fibrinogen deposits. The data demonstrate a lymphocytes/macrophages interaction in the central core of granulomatous areas as the crucial event that initiates the maintains the state of inflammation: at all sites of disease activity is present a compartmentalization of T-cells expressing a helper-related phenotype which account for the great majority of infiltrating cells both in the early lesions (aggregate of macrophages surrounded by lymphocytic infiltrate) and in well-organized sarcoid granulomata. The presence of plasma cells and immunoglobulin deposits may represent an epiphenomenon in line with the helper infiltration, suggesting a local hyper-reactivity of the B-cells immune system. This study suggests some immunopathogenetic mechanisms leading to the formation and growth of conjunctival sarcoid granulomata.     

Action of 2-hydroxy-4,6-dimethoxyacetophenone isolated from Sebastiania schottiana

The inhibitory action of the major constituent of Sebastiania schottiana (Euphorbiaceae), 2-hydroxy-4,6-dimethoxyacetophenone (xanthoxyline) on contractions induced by agonists and electrical stimulation of smooth and cardiac muscle preparations was analysed. Xanthoxyline (30 to 300 microM) inhibited contractions of the rat uterus, guinea-pig ileum, and urinary bladder induced by several agonists in a non-competitive, non-selective, concentration-related manner, with the IC50's ranging between 47 and 190 microM. Twitches evoked by electrical-stimulation of strips of guinea-pig longitudinal ileum, urinary bladder, dog ureter, and rat left atrium were also inhibited dose-dependently by cumulative additions of xanthoxyline (IC50's between 50 and 480 microM). Xanthoxyline was found to be a potent inhibitor of spontaneous contractions of the circular smooth muscle layer of the dog ureter, yielding an IC50 of 54 microM. Repeated washing of all preparations completely reversed the inhibitory effects of xanthoxyline. Therefore, it appears that xanthoxyline induces a direct and non-selective inhibition of contractions triggered by agonists or electrical stimulation of smooth and cardiac muscle preparations. The elucidation of the mechanism(s) by which xanthoxyline induced muscle relaxation requires further investigations.     

Epidemiologic surveillance of congenital abnormalities using the EUROCAT Register

The EUROCAT programme is a concerted action of the European Economic Community for the epidemiologic surveillance of congenital anomalies. Surveillance is based on a network of regional registries coordinated by a central registry. The programme started in 1979 and by 1987, 23 centres were participating, covering together more than 300,000 births per year. The surveillance process implies the selection of the anomalies possibly associated with environmental teratogens or mutagens, the definition of abnormal variations in the rate of these anomalies (the alarms), the establishment of base-line rate and the continuous monitoring of rate. The programme is evaluated by reference to four criteria: the sensitivity of the system in detecting teratogens or mutagens, the specificity of alarms, the rapidity in warning of alarm and in investigating their causes, and the programme efficiency expressed as its cost-utility ratio.     

Implantation of the inflatable penile prosthesis AMS 700 CX

The paper demonstrate the surgical approach used by the authors to implant the AMS 700CX penile prosthesis. Pre- and postoperative management are also discussed.     

Lipoid Proteinosis: Case Report

A 20-month-old Kuwaiti girl had manifestations of lipoid proteinosis, a rare autosomal recessive disorder seen more commonly in Caucasians. This condition is diagnosed based on clinical, histopathologic, and ultrastructural criteria. Its biochemical and genetic aspects are still poorly understood.     

Immunochemical characterization of the formyl peptide receptor moieties on human neutrophils.

The neutrophil (PMN) receptor for formylated peptides such as N-formyl-l-methionyl-l-leucyl-l-phenylalanine (FMLP) is involved in binding and subsequent response to certain chemotactic stimuli. The receptor on human PMN has been reported to consist of several glycoprotein components, ranging in size from 43-94 kDa. Furthermore, FMLP receptors on human PMN have been shown to contain both high and low affinity states. In this study, the receptor was purified by subjecting solubilized PMN plasma membrane components to FMLP-affinity chromatography, and was found to be comprised of four components, one of 68 kDa, and the others of 94, 48, and approximately 40 kDa. Only the 68, the 94, and the approximately 40 kDa components specifically bound a radioiodinated FMLP analogue. To further characterize these components, a battery of monoclonal antibodies reactive against the FMLP receptor was prepared. Seven monoclonal antibodies were selected on the basis of their reactivity with the 68 kDa receptor component. Some of these antibodies also cross-react with the 48 kDa component, suggesting that the 68 and the 48 kDa receptor moieties are immunologically related. These antibodies reacted with normal human neutrophils, but not with lymphocytes, or unstimulated HL-60 cells. Furthermore, the presence of 20 nmol of FMLP inhibited the binding of five of the anti-receptor antibodies to whole PMN. These results suggest that the epitopes recognized by these five antibodies may possibly be involved in FMLP binding.     

Kinetic aspects of release of fibrinopeptides AP and AY by human alpha-thrombin

The time-dependent release by human alpha-thrombin of the physiological variants of fibrinopeptide A, i.e. fibrinopeptide A-3-phosphate (FPAP) and des-Ala-fibrinopeptide A (FPAY), has been measured in order to study the kinetic pathway for their hydrolysis. The best-fit kinetic model for the release of FPAP and FPAY is consistent with a simple pseudo first-order reaction, as observed with FPA. These findings indicate that FPAP and FPAY are also released from intact fibrinogen before release of FPB. The values of the specificity constants, i.e. k(at)/Km, for the enzymatic reaction between thrombin and the various alpha-chains showed that AP alpha- and AY alpha-chain are hydrolyzed with a 0.2-and 0.4-fold higher specificity constant respectively than that of A alpha-chain. Such minor differences observed with the various chains suggest that the 1-3 NH2-terminal residues of the chain do not significantly contribute to the catalytic efficiency of thrombin toward the alpha-chains of fibrinogen.     

Effect of mast cell chymase on the morphology of thyroid cells in vitro.

We studied the effect of mast cell chymase on the thyroid cells in culture. Rat serosal mast cells, similar functionally to connective tissue mast cells, were obtained after lavage of the peritoneal cavity and lyzed by freezing. The resulting lysate was used as crude enzyme preparation. Mast cell chymase was purified from the crude preparation by anion exchange chromatography. Crude and purified chymase incubated with thyroid cells induced cellular retraction, the appearance of long processes and gradual cell detachment from the substratum. The effect of the enzyme was not cytotoxic. The immunofluorescence studies of thyroid cells showed a decreased amount of polymerized actin and tubulin after incubation with chymase. Neutral protease inhibitor abolished the effect of crude and purified chymase on thyroid cell morphology. The above findings suggest that mast cell chymase may have a function in the control of cell morphology and cell-matrix interaction.     

Correlations between follicular fluid steroid analysis and maturity and cytogenetic analysis of human oocytes that remained unfertilized after in vitro fertilization.

OBJECTIVE: Is there any correlation between follicular fluid (FF) steroid levels and the occurrence of cytogenetic abnormalities in unfertilized human oocytes? DESIGN: Cytogenetic analysis was carried out on 397 oocytes, and the steroid content of 104 corresponding FF was analyzed using high-pressure liquid chromatography. Ovarian stimulation was performed by clomiphene citrate and human menopausal gonadotropin (hMG) or by hMG combined with a gonadotropin-releasing hormone agonist (GnRH-a) pretreatment. RESULTS: Oocyte maturity was correlated with an increasing FF progestin content and a significant decrease of androstenedione (A) levels. Chromosomal analysis revealed 84 of all oocytes to be abnormal (polyploid or aneuploid and/or prematurely condensed chromosomes present). In this group, A levels and A to estradiol ratios were significantly higher. Although progestin levels were higher in GnRH-a/hMG cycles, the incidence of oocyte normality was not different between the two stimulation schemes. More abnormal oocytes were found in patients with good sperm morphology. CONCLUSIONS: Oocyte abnormality correlates with higher A levels in the corresponding FF. Oocyte fertilization is also determined by intrinsic oocytic factors other than maturity.