Ceruloplasmin (CP), the major plasma anti-oxidant and copper transport protein, is synthesized in several tissues, including the brain. We compared regional brain concentrations of CP and copper ...between subjects with Alzheimer's disease (AD,
n = 12), Parkinson's disease (PD,
n = 14), Huntington's disease (HD,
n = 11), progressive supranuclear palsy (PSP,
n = 11), young adult normal controls (YC,
n = 6) and elderly normal controls (EC,
n = 7). Mean CP concentrations were significantly increased vs. EC (
P < 0.05) in AD hippocampus, entorhinal cortex, frontal cortex, and putamen, PD hippocampus, frontal, temporal, and parietal cortices, and HD hippocampus, parietal cortex, and substantia nigra. lmmunocytochemical staining for CP in AD hippocampus revealed marked staining within neurons, astrocytes, and neuritic plaques. Increased CP concentrations in brain in these disorders may indicate a localized acute phase-type response and/or a compensatory increase to oxidative stress.
The purpose of this study was to determine the effects of the Jones jig appliance on distal movement of maxillary molars and reciprocal effects on premolars and maxillary incisors. Cephalometric ...radiographs before and after orthodontic treatment of 72 consecutively treated patients, 46 females and 26 males, were measured to define treatment changes attributed to the Jones jig. Comparative measurements were made on a matched sample of 35 patients (20 females and 15 males) treated with cervical headgear by the same clinician. Both series of patients were treated to correct an Angle Class II molar relationship. The molar correction in the Jones jig patients consisted primarily of molar distal movement. Dental, soft tissue, and skeletal changes were evaluated and compared for significant differences between techniques. The results from the Jones jig sample showed the mean maxillary first molar distal movement was 2.51 mm, with distal tipping of 7.53°. The mean reciprocal mesial movement of the maxillary premolar was 2.0 mm, with mesial tipping of 4.76°. The maxillary first molar extruded 0.14 mm; the maxillary premolar extruded 1.88 mm. The maxillary second molars were also moved distally 2.02 mm and tipped distally 7.89°. The longitudinal assessment (initial to completion of orthodontic treatment) showed significant differences between the Jones jig sample and the cervical headgear sample for lower lip to E-line and SNA. The Jones jig sample showed a mean decrease in lower lip to E-line of 0.25 mm versus 1.20 mm (P <.0212) for the headgear sample. SNA decreased 0.40° for the Jones jig sample versus 1.20° (P <.0093) for the headgear sample. However, the Jones jig sample and cervical headgear sample did not show significant differences of the final position in either linear or angular measurements of the maxillary first molars and corresponding premolar-incisor anchor units. The Jones jig appliance demonstrated treatment results comparable with those of the sample treated with cervical headgear. The Jones jig sample demonstrated effective distal molar movement and maintenance of the Class I molar relationship. Advantages of the Jones jig include minimal dependence on patient compliance, ease of fabrication, and ease of buccal force application. (Am J Orthod Dentofacial Orthop 2000;118:526-34).
We report the results of an interdisciplinary collaboration formed to assess the sterilizing capabilities of the One Atmosphere Uniform Glow Discharge Plasma (OAUGDP). This newly-invented source of ...glow discharge plasma (the fourth state of matter) is capable of operating at atmospheric pressure in air and other gases, and of providing antimicrobial active species to surfaces and workpieces at room temperature as judged by viable plate counts. OAUGDP exposures have reduced log numbers of bacteria, Staphylococcus aureus and Escherichia coli, and endospores from Bacillus stearothermophilus and Bacillus subtilis on seeded solid surfaces, fabrics, filter paper, and powdered culture media at room temperature. Initial experimental data showed a two-log10 CFU reduction of bacteria when 2 x 10(2) cells were seeded on filter paper. Results showed > or = 3 log10 CFU reduction when polypropylene samples seeded with E. coli (5 x 10(4)) were exposed, while a 30 s exposure time was required for similar killing with S. aureus-seeded polypropylene samples. The exposure times required to effect > or = 6 log10 CFU reduction of E. coli and S. aureus on polypropylene samples were no longer than 30 s. Experiments with seeded samples in sealed commercial sterilization bags showed little or no differences in exposure times compared to unwrapped samples. Plasma exposure times of less than 5 min generated > or = 5 log10 CFU reduction of commercially prepared Bacillus subtilis spores (1 x 10(5)); 7 min OAUGDP exposures were required to generate a > or = 3 log10 CFU reduction for Bacillus stearothermophilus spores. For all microorganisms tested, a biphasic curve was generated when the number of survivors vs time was plotted in dose-response cures. Several proposed mechanisms of killing at room temperature by the OAUGDP are discussed.
The mosaic of autoimmunity Brickman, C M; Shoenfeld, Y
Scandinavian journal of clinical & laboratory investigation. Supplement,
2001, Letnik:
235
Journal Article
Recenzirano
Autoimmunity is a normal event, while autoimmune diseases result from an aberration of this normal phenomenon. The etiology of this switch is considered multifactorial with the final common pathway ...being the loss of normal self-tolerance in a particular organ or group of organs. Genetic, environmental, hormonal and immunologic factors (along with probably other yet unrecognised factors) are considered important in the development of these disorders. The particular autoimmune disease which any patient develops is most likely a result of which combination of factors the patient has accumulated. We begin with a brief review of immunobiology in order to arrive at a suitable definition of autoimmunity. This is followed by a concise description of the current theories regarding the development of autoimmune disease and the factors known to be associated with these illnesses. Concluding remarks address the factors that normally prevent the progression of autoimmunity to autoimmune disease and the application of current knowledge to future therapeutic approaches.
Complement activation is present in the brain in Alzheimer’s disease (AD), and C1q concentrations are decreased in AD cerebrospinal fluid (CSF). To determine whether concentrations of other ...complement proteins are also altered in AD CSF, we measured concentrations of C3a and SC5b-9 in CSF from patients with probable AD (
n = 19), normal aged controls (
n = 11), and normal younger controls (
n = 15). C3a concentrations were similar between AD and aged controls, but threefold higher than in younger controls (
p < 0.05 vs. both groups). A similar pattern was found with SC5b-9, though the increase was only twofold and statistically significant only for AD vs. younger controls. These results suggest that an increased generation of complement proteins in localized areas of the AD brain does not result in elevated concentrations of these proteins in CSF, compared with age-matched controls. Increased C3a (and, to a lesser extent, SC5b-9) in aged controls may be due to increased complement activation, increased central nervous system production, and/or blood–brain barrier leakage of these proteins.
We have examined the involvement of proteoglycan molecules in the induction of mesodermal tissue in Xenopus laevis embryos. Blastocoelic injections of the enzyme heparitinase at early blastula stages ...lead to gastrulation defects and to failures in the development of anterior embryonic structures. The period of sensitivity of embryos to this treatment suggests a possible role for these molecules during mesoderm induction. We show that heparan sulfate proteoglycans (HSPGs) and chondroitin sulfate proteoglycans are the predominant sulfated glycoconjugates synthesized in early Xenopus embryos and that HSPGs are degraded by blastocoelic injections of heparitinase. Further, bFGF induction of mesoderm in explants of Xenopus stage 8 embryonic animal cap tissue is blocked by heparitinase but not by Chondroitinase ABC, using three separate criteria of mesoderm induction. Since HSPGs present in blastula animal cap cells are digested by heparitinase under the culture conditions used in the mesoderm-induction assay, we suggest that cell-surface heparan sulfate proteoglycans are required for basic fibroblast growth factor-mediated mesoderm induction.
Translocation of intracellular components to the cell surface during the priming or apoptosis of polymorphonuclear leukocytes (PMN) is an important mechanism for interaction of antineutrophil ...cytoplasmic antibodies (ANCA) with these antigens. To test the capacity of apoptotic PMN to trigger production of ANCA, six groups of mice were immunized with either live or apoptotic lymphocytes, or with live, apoptotic, formalin-fixed, or lysed PMN. Mice immunized with both live and apoptotic neutrophils developed high titers of antibodies which gave a granular cytoplasmic immunofluorescent pattern. These antibodies were specific for lactoferrin and myeloperoxidase. Following a second intravenous infusion of apoptotic PMNs, mice developed anti-PR3 antibodies. Vasculitis lesions were not found in mice which developed ANCA. The ANCA-containing IgG fraction induced superoxide production by human PMNs. These results support the hypothesis that neutrophil-specific antigens presented on the cell membranes of apoptotic PMN may induce ANCA in the proper conditions.
Regulation of inflammatory responses is critical to progression of organ-specific autoimmune disease. Although many candidate cell types have been identified, immunoregulatory activity has rarely ...been directly assayed and never from the CNS. We have analyzed the regulatory capability of Gr-1high neutrophils isolated from the CNS of mice with experimental autoimmune encephalomyelitis. Proportions of neutrophils were markedly increased in the CNS of IFN-gamma-deficient mice. Strikingly, CNS-derived neutrophils, whether or not they derived from IFN-gamma-deficient mice, were potent suppressors of T cell responses to myelin or adjuvant Ags. Neutrophil suppressor activity was absolutely dependent on IFN-gamma production by target T cells, and suppression was abrogated by blocking NO synthase. These data identify an immunoregulatory capacity for neutrophils, and indicate that interplay between IFN-gamma, NO, and activated Gr-1high neutrophils within the target organ determines the outcome of inflammatory and potentially autoimmune T cell responses.
Although the pathophysiology of Alzheimer's disease (AD) and Parkinson's disease (PD) is unknown, altered brain antioxidative mechanisms have been found in both disorders. Ceruloplasmin (CP) and ...transferrin (TF) interact to limit concentrations of free ferrous iron (Fe2+), and thus play an important role in antioxidant defense in serum; both proteins are also produced in brain, where their significance as antioxidants is unknown. We quantified concentrations of CP and TF by immunoassay in AD (n = 17) and PD (n = 12) cerebrospinal fluid (CSF) to determine whether these proteins could serve as disease markers. CP was increased versus aged normal subjects (n = 11) in AD (p < 0.05) but not PD CSF, whereas TF concentrations did not differ between groups. CP levels have been reported to be elevated in some brain regions in AD, and increased CP in AD CSF may reflect this finding. Systemic inflammation and oxidative stress are major factors stimulating hepatic CP synthesis, and it remains to be determined whether increased CP concentrations in AD CSF and brain follow from similar mechanisms.
Nimesulide is a relatively new non-steroidal anti-inflammatory drug that is gaining popularity in many countries because it is a selective cyclooxygenase 2 inhibitor. Occasionally, treatment is ...associated with mild elevation of liver enzymes, which return to normal upon discontinuation of the drug. Several cases of nimesulide-induced symptomatic hepatitis were also recently reported, but these patients all recovered.
To report the characteristics of liver injury induced by nimesulide.
We report retrospectively six patients, five of them females with a median age of 59 years, whose aminotransferase levels rose after they took nimesulide for joint pains. In all patients nimesulide was discontinued, laboratory tests for viral and autoimmune causes of hepatitis were performed, and sufficient follow-up was available.
One patient remained asymptomatic. Four patients presented with symptoms, including fatigue, nausea and vomiting, which had developed several weeks after they began taking nimesulide (median 10 weeks, range 2-13). Hepatocellular injury was observed with median peak serum alanine aminotransferase 15 times the upper limit of normal (range 4-35), reversing to normal 2-4 months after discontinuation of the drug. The remaining patient developed symptoms, but continued taking the drug for another 2 weeks. She subsequently developed acute hepatic failure with encephalopathy and hepatorenal syndrome and died 6 weeks after hospitalization. In none of the cases did serological tests for hepatitis A, B and C, Epstein-Barr virus and cytomegalovirus, as well as autoimmune hepatitis reveal findings.
Nimesulide may cause liver damage. The clinical presentation may vary from abnormal liver enzyme levels with no symptoms, to fatal hepatic failure. Therefore, monitoring liver enzymes after initiating therapy with nimesulide seems prudent.
PDF
