Cataract surgery in the nanophthalmic eye.
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Cataract Extraction↗
Biomedical subjects
A A Osman
Publications and source records attributed to A A Osman.
Neurological disease-associated autoantibodies against an unknown protein encoded by a RES4-22 homologous gene.
Screening a human small intestinal library with human serum yielded a clone which encoded a protein res4-22 the gene of which was highly homologous to a recently described gene located in the Huntington's disease locus. Autoantibodies against res4-22 (anti-res4-22), mainly of the immunoglobulin (Ig)A type, were detected in patients with neurological disorders at a higher frequency (18.4%) than in healthy blood donors (8.0%). In neurological patients with cerebral ischaemia anti-res4-22 was found significantly more often (47.4%) than in the total group of neurological patients. Anti-res4-22 positive sera showed significantly more frequently myelin staining in cerebellum and nerve sections than anti-res4-22 negative sera. Our findings demonstrate a new species of human autoantibodies against a newly described protein the function of which is still unknown.
Autoantibodies↗
A monoclonal antibody that recognizes a potential coeliac-toxic repetitive pentapeptide epitope in gliadins.
OBJECTIVES: Antibodies that detect coeliac-toxic prolamins from wheat, barley and rye are important tools for controlling the diet of coeliac disease patients. Recently, a monoclonal antibody R5 that recognizes wheat gliadin, barley hordein and rye secalin equally was described. In this study, the epitope recognized by R5 was investigated. METHODS: Both a phage-displayed heptapeptide library and overlapping peptides spanning the sequence of alpha- and gamma-type gliadins (pepscan) were screened for binding of R5. RESULTS: Both techniques yielded comparable pentapeptide consensus sequences (phage display QXPW/FP; pepscan QQPFP). According to recent observations, this peptide stretch may be of key importance in the pathogenicity of coeliac disease. This sequence occurs repetitively in prolamins (in gamma- and omega-type prolamins more frequently than in alpha-type prolamins) together with several homologous peptide stretches, which are recognized less strongly. CONCLUSIONS: R5 seems to be a good candidate for the specific detection of putative coeliac disease-active sequences in prolamins and thus represents a valuable tool for the quality control of gluten-free food.
Amino Acid Sequence↗
Callitrichid nutrition and food sensitivity.
Captive callitrichids are prone to developing intestinal problems. Their captive and natural diets differ enormously, and diet has been suggested to play a major role in wasting marmoset syndrome. Proteins in wheat, soy and milk are included in callitrichid diets of most colonies and have been linked to an immune reaction in Saguinus oedipus and Callithrix jacchus. In the present study of 23 males and females of the two species, wheat protein was tested but soy and milk products were excluded. One group had wheat and the other had rice in their diet. Blood samples and biopsies from the colon were taken. Results showed changes in the colon and an immune reaction to gliadin, a wheat protein related to coeliac disease in humans. A further immune reaction was also observed. Suggestions for further study and exclusion of cereal in the diet of these small, New World primates are discussed.
Animals↗
Exercise training increases ERK2 activity in skeletal muscle of obese Zucker rats.
Acute exercise and training increase insulin action in skeletal muscle, but the mechanism responsible for this effect is unknown. Activation of the insulin receptor initiates signaling through both the phosphatidylinositol (PI) 3-kinase and the mitogen-activated protein kinase [MAPK, also referred to as extracellular signal-regulated kinases (ERK1/2)] pathways. Acute exercise has no effect on the PI3-kinase pathway signaling elements but does activate the MAPK pathway, which may play a role in the adaptation of muscle to exercise. It is unknown whether training produces a chronic effect on basal activity or insulin response of the MAPK pathway. The present study was undertaken to determine whether exercise training improves the activity of the MAPK pathway or its response to insulin in obese Zucker rats, a well-characterized model of insulin resistance. To accomplish this, obese Zucker rats were studied by using the hindlimb perfusion method with or without 7 wk of treadmill training. Activation of the MAPK pathway was determined in gastrocnemius muscles exposed in situ to insulin. Compared with lean Zucker rats, untrained obese Zucker rats had reduced basal and insulin-stimulated activities of ERK2 and its downstream target p90 ribosomal S6 kinase (RSK2). Seven weeks of training significantly increased basal and insulin-stimulated ERK2 and RSK2 activities, as well as insulin stimulation of MAPK kinase activity. This effect was maintained for at least 96 h in the case of ERK2. The training-induced increase in basal ERK2 activity was correlated with the increase in citrate synthase activity. Therefore, 7 wk of training increases basal and insulin-stimulated ERK2 activity. The increase in basal ERK2 activity may be related to the response of muscle to training.
Animals↗
B cell epitopes of gliadin.
A phage displayed dodecapeptide library and synthetic octapeptides spanning the complete sequence of alpha- and gamma-type gliadin and overlapping in six amino acids (pepscan) were screened for binding to human gliadin antibodies (AGA). Phage display experiments led to four sequences recognized with significantly higher frequency by sera with raised IgA-AGA titres than by control sera. All these peptides contained the core sequence PEQ. Pepscan experiments revealed binding of AGA to five prominent regions: (i) QXQPFP (binding to IgG and IgA, X representing P, Q, and L); (ii) IPEQ (IgG) and WQIPEQ (IgA); (iii) FFQP (IgG) and QGXFQP (IgA, X representing F and S); (iv) PQQLPQ (IgG and IgA), all in alpha-type gliadin; and (v) QPQQPF (IgG and IgA) in gamma-type gliadin. In two of the sequences (QPQQPF and QQQPFP), substitution of Q by E resulting in QPEQPF and QEQPFP, respectively, increased significantly binding of AGA from sera of patients with biopsy-proven or suspected coeliac disease (CoD), all positive for endomysium antibodies (EmA). In contrast, binding of sera with high AGA titre from EmA-negative patients (CoD and dermatitis herpetiformis excluded) was not enhanced by this substitution. Thus, AGA directed against these modified epitopes can be regarded as specific for CoD. This is the first study demonstrating that deamidation of gliadin improves reactivity of AGA of CoD patients.
Amino Acid Sequence↗
Evidence for existence of coeliac disease autoantigens apart from tissue transglutaminase.
BACKGROUND: The pathogenesis of coeliac disease (CD) and of dermatitis herpetiformis (DH) is strongly associated with production of autoantibodies, defined by indirect immunohistology. Recently, tissue transglutaminase (tTG) was identified as a prominent autoantigen. It would be important to investigate if further molecules apart from tTG are involved in autoimmunity. METHODS: Tissue sections of human foetal intestine were used to compare the distribution of tTG with the autoantibody binding patterns of 14 sera samples from patients with CD or DH. Double label experiments were performed using monoclonal as well as polyclonal tTG antibodies (anti-tTG) and patient sera. The staining was investigated by using conventional light and confocal laser scanning microscopy. RESULTS: Most autoantibody binding sites were matched by tTG. Further, the binding of autoantibodies could be inhibited by preincubation with monoclonal anti-tTG. However, in nine serum samples (64%) autoantibody staining suggested a few distinct binding sites apart from tTG. In three sera (21 %) autoantibody binding fibres were detected which definitely did not match monoclonal anti-tTG signals. Distinctly stained fibres were confirmed by applying polyclonal anti-tTG. This indicates the existence of autoantigenic epitopes not related to tTG.
Animals↗
Regulation of MAP kinase pathway activity in vivo in human skeletal muscle.
Insulin and exercise potently stimulate glucose metabolism and gene transcription in vivo in skeletal muscle. A single bout of exercise increases the rate of insulin-stimulated glucose uptake and metabolism in skeletal muscle in the postexercise period. The nature of the intracellular signaling mechanisms that control responses to exercise is not known. In mammalian tissues, numerous reports have established the existence of the mitogen-activated protein (MAP) kinase signaling pathway that is activated by a variety of growth factors and hormones. This study was undertaken to determine how a single bout of exercise and physiological hyperinsulinemia activate the MAP kinase pathway. The euglycemic-hyperinsulinemic clamp and cycle ergometer exercise techniques combined with percutaneous muscle biopsies were used to answer this question. In healthy subjects, within 30 min, insulin significantly increased MAP kinase [isoforms p42(MAPK) and p44(MAPK) (ERK1 and ERK2)] phosphorylation (141 +/- 2%, P < 0.05) and activity (177 +/- 5%, P < 0.05), and the activity of its upstream activator MEK1 (161 +/- 16%, P < 0.05). Insulin also increased the activity of the MAP kinase downstream substrate, the p90 ribosomal S6 kinase 2 (RSK2) almost twofold (198 +/- 45%, P < 0.05). In contrast, a single 30-min bout of moderate-intensity exercise had no effect on the MAP kinase pathway activation from MEK to RSK2 in muscle of healthy subjects. However, 60 min of exercise did increase extracellular signal-related kinase activity. Therefore, despite similar effects on glucose metabolism after 30 min, insulin and exercise regulate the MAP kinase pathway differently. Insulin more rapidly activates the MAP kinase pathway.
Adult↗
Safety of intrauterine device insertion by trained nurse-midwives in the Sudan.
Insertion of intrauterine devices (IUDs) by trained health workers other than physicians is increasing, particularly in developing countries. Twenty nurse-midwives in government service in the Sudan, called health visitors (HVs), were trained to provide intrauterine contraceptives in a research project designed to evaluate the safety of insertion of IUDs by medical personnel who are not physicians. After training, they inserted 763 IUDs. Independent evaluation of 520 clients was conducted by gynecologists who found that only six devices (1.2%) had been incorrectly inserted. Outcomes for clients of the health visitors, with respect to perforations, infections, expulsions, and pregnancies, compared well with those of eight physicians who participated in the study. The research strongly supports the concept of nurse-midwife training for IUD insertion. This would greatly expand the availability of family planning services and would conserve physician time and skills for problem cases.
Consumer Product Safety↗
IgA-gliadin antibodies, IgA-containing circulating immune complexes, and IgA glomerular deposits in wasting marmoset syndrome.
BACKGROUND: Marmosets in captivity are highly susceptible to wasting marmoset syndrome (WMS), the aetiology of which is still not fully determined. METHODS: The level of IgA-gliadin antibodies (IgA-AGA), of IgA-containing circulating immune complexes (IgA-CIC), and the degree of glomerular IgA deposits were compared between marmosets suffering from WMS and animals not affected by the disorder. RESULTS: Both IgA-AGA and IgA-CIC were demonstrable in all groups of monkeys investigated. IgA-AGA and IgA-CIC were significantly higher in monkeys with WMS than in non-affected animals. There was a significant correlation between the glomerular IgA-deposition and titre of IgA-AGA. The group of marmosets strongly positive for glomerular IgA deposits comprised significantly more animals suffering from WMS than the group without deposits. In the diet of the animals a considerable amount of gliadin-like cereal proteins was assayed. CONCLUSIONS: There are several parallels between the human disorders (coeliac disease and IgA-nephropathy/Berger's disease) and the changes observed in WMS. It should be further investigated if WMS in marmosets is a suitable animal model for both human diseases.
Animals↗
Use of the phage display technique for detection of epitopes recognized by polyclonal rabbit gliadin antibodies.
A random phage heptapeptide library was screened with rabbit antibodies against wheat flour proteins comprising gliadins and a small amount of low molecular weight glutenins (gli/glu). Gli/glu antibodies isolated from the sera selected different consensus sequences (CS). All CS contained tri- to pentapeptide stretches homologous to gli/glu sequences (proposed epitopes). In alpha- and gamma-type gliadins, these sequences are clustered in the N-terminal region recently suspected to be toxic for humans with celiac disease. Peptides with CS were synthesized and checked for reactivity. Only immune and no control rabbit sera reacted with synthetic peptides. One of eight human sera containing gliadin antibodies was reactive as well (4/8 peptides) but control sera were negative. Thus the phage display technique is useful for epitope screening of polyclonal antibodies even in the case of a group of homologous but diverse antigens.
Amino Acid Sequence↗
Role of tissue transglutaminase in gliadin binding to reticular extracellular matrix and relation to coeliac disease autoantibodies.
On different tissue sections, binding of gliadin to reticular matrix components was observed which was Ca2+-dependent, inhibited by Cu2+ and Zn2+ ions, by putrescine, and by preincubation with antibodies against tissue transglutaminase (tTG) suggesting that binding of gliadin is mediated by tTG. tTG was able to bind to gliadin and fibronectin fixed to microplates. Furthermore, tTG mediated binding of gliadin to fibronectin coated to microplates. On tissue sections, treatment with sera containing coeliac disease autoantibodies yielded staining patterns very similar to that of bound gliadin. Dual label experiments by means of conventional and laser scanning microscopy revealed that most of autoantibody binding sites are matched by bound gliadin. However, lack of competition between gliadin and autoantibody binding hints to ligands in very close vicinity of this enzyme. Furthermore, there were several autoantibody binding regions which did not bind gliadin. This implies the existence of further autoantigenic epitopes not related to tTG.
Animals↗
Epitope mapping by screening of phage display libraries of a monoclonal antibody directed against the receptor binding domain of human alpha2-macroglobulin.
The human proteinase inhibitor, alpha2-macroglobulin (a2-M), inhibits a large number of proteinases. Alpha2-M-proteinase complexes are rapidly cleared from the circulation by binding to a cellular receptor (alpha2-M-R/LRP) via the receptor binding domain (RBD) which is made up of a 20 kDa C-terminal stretch of the 180 kDa monomer of the inhibitor. A monoclonal antibody (mab alpha-1) has been described which reacts with the receptor-recognizable form of the inhibitor, the so called transformed alpha2-M (a2-Mt). By screening of a phage display library an epitope in the RBD of the inhibitor was identified that reacts with mab alpha-1. Out of 25 phage clones a heptapeptide sequence (S-x1-x2-D-x3-x4-K) was obtained containing identical amino acids in three positions. A consensus peptide (S-R-S-D-P-P-K) was synthesized and found to displace alpha2-Mt from binding to mab alpha-1 and to receptor. The specificity of competition was demonstrated by a reversed peptide and a control antibody. By structural comparison it was found that the consensus heptapeptide mimics a discontinuous conformationally constrained epitope present in the RBD of the inhibitor. This is the first report describing the detection of discontinuous epitopes by phage display using a short linear peptide.
Amino Acid Sequence↗
Effect of gamma-interferon on binding of gliadin and other food peptides to the human intestinal cell line HT-29.
gamma-Interferon is one of the main cytokines released during activation of intestinal lymphocytes in coeliac patients. The question has never been addressed whether gamma-interferon influences binding of gliadin and other food peptides to human enterocytes. Therefore, the human intestinal epithelial cell line HT-29 was cultured with gliadin, casein, beta-lactoglobulin and ovalbumin, with or without gamma-interferon, and peptide binding to cells was determined by flow cytometry and fluorescence microscopy. gamma-Interferon stimulated gliadin binding by a factor of 4. Binding was saturable with half maximal binding at 0.15 mg/ml. For maximal binding, an incubation of at least 24 h was necessary. gamma-Interferon increased binding of beta-lactoglobulin and casein, too, but inhibited that of ovalbumin. Binding of gliadin was inhibited by the other peptides. Under the conditions of ongoing mucosal inflammatory reactions and release of gamma-interferon, enhanced binding may trigger intestinal lymphocytes, increase secretion of cytokines and thus induce a vicious circle.
Caseins↗
The IgA subclass distributions of endomysium and gliadin antibodies in human sera are different.
Subclass distributions of total IgA, IgA gliadin antibodies and IgA endomysium antibodies were investigated in 26 sera of patients with coeliac disease or dermatitis herpetiformis by means of enzyme immunoassay and fluorescence microscopy. Eight-point-three percent of total IgA belonged to the IgA2 subclass. The fraction of IgA2 gliadin antibodies amounted to 30.6% of IgA gliadin antibodies and was significantly different from the proportion of total IgA2. The relative percentage of IgA2 endomysium antibodies was very close to that of total IgA2 in serum (6.2%) and significantly lower than that of IgA2 gliadin antibodies. The results suggest an intestinal origin of gliadin antibodies. Different subclass distribution of IgA endomysium antibodies may be due to extraintestinal production or to the different nature of the endomysium antigen eliciting a more prominent IgA1 response than gliadin.
Antibodies↗
Isolation of antigens recognized by coeliac disease autoantibodies and their use in enzyme immunoassay of endomysium and reticulin antibody-positive human sera.
Components were isolated from rat liver, sheep lung, rhesus and orang-utan intestine. In enzyme immunoassay, these components detected 57%, 72%, 84% and 88% of human sera containing endomysium and reticulin antibodies (EmA and ARA). At most, 7% of EmA/ARA-negative sera reacted with the antigens. The spectrum of EmA/ARA-positive sera reactive with the various components was different but overlapping. When the antigens of sheep lung and orang-utan intestine were used as a cocktail, 98% of EmA/ARA-positive sera (45/46), but only 2% of control sera (1/46) were detected. The isolated antigens from sheep lung and monkey intestines were able to absorb EmA and ARA from human sera and thus should be suspected to contain the epitopes recognized by EmA and ARA, whereas the rat liver component did not bind. Therefore, the spectrum of autoantibodies in coeliac disease might comprise more than that covered by the terms EmA and ARA. The N-terminal amino acid sequence of some of the antigens was homologous with casein, gliadin, fibrinogen, and collagen.
Amino Acid Sequence↗
Septic sacroiliitis.
The authors treated 31 patients with septic arthritis of the sacroiliac joint (14 patients with tuberculosis, 7 acute staphylococcal, 6 gonococcal, and 4 typhoid). The clinical presentation was vague and nonspecific, but most patients reported buttock pain, low back pain and difficulty walking. In 28 patients, the diagnosis was established after clinical examination, bone scans, hematologic investigations, and blood cultures. The diagnosis was established through arthrocentesis of the sacroiliac joint in 9 patients. In 3 patients, there was a delay in diagnosis. Twenty-nine patients improved on a conservative regimen of bed rest and antibiotics. Two patients required open drainage because of a large buttock abscess that was secondary to tuberculosis sarcoiliitis.
Adolescent↗
Investigation of gliadin binding to different selected proteins using a biotin-streptavidin system.
Using a biotin streptavidin system 12 out of 19 different test proteins were found to bind to gliadin, with casein, fibrinogen, and fibronectin showing the strongest association. Binding was demonstrable using different gliadin subfractions and enzymatic digests. There was no consistent effect of several carbohydrates on binding. Binding of most proteins to gliadin was diminished slightly by removal of Ca2+ and strongly by dioxane, ethylene glycol, Triton X-100, and Tween 20. The results suggest a non-selective association between gliadin and the proteins investigated, mainly due to hydrophobic interactions, which might be of significance in intestinal pathobiochemistry, e.g. disease.
Animals↗