Circulating interleukin 10 and interleukin-6 serum levels in rheumatoid arthritis patients treated with methotrexate or gold salts: Preliminary report

In order to evaluate the relationship between serum concentrations of interleukin-10 (IL-10), IL-6, and acute phase proteins in rheumatoid arthritis (RA) patients treated with methotrexate (MTX) or intramuscular gold (IMG) we determined IL-10, IL-6, C-reactive protein (CRP), alpha-1-acid glycoprotein (AGP) and alpha-1-antichymotrypsin (ACT) in the sera of 35 RA patients. IL-10 and IL-6 levels were evaluated using an enzyme-linked immunoassay (ELISA). AGP and ACT level were measured using rocket immunoelectrophoresis. IL-10 serum level was not increased in RA patients as compared to controls (58.7 ± 18.1 pg/ml vs. 57.2 ± 11.9 pg/ml). IL-6 level was significantly elevated (91.6 ± 46.9 pg/ml vs. 45 ± 19 pg/ml, p < 0.05). CRP was significantly increased as compared to healthy controls (35 ± 19 mg/l vs. 3 ± 2 mg/l, p < 0.05). Patients treated with MTX or IMG presented an increased level of IL-10 and decreased amounts of IL-6, as compared to those treated with NSAID only. However, only changes between patients treated with IMG and NSAID were found to be statistically significant. A good negative correlation between IL-10 and IL-6 serum level was found (r = –0.75, p < 0.05). A positive significant correlation between IL-6 serum level and CRP (r = 0.62, p < 0.05), AGP (r = 0.78, p < 0.05) and ACT (r = 0.45, p < 0.05) was established. On the other hand, a negative correlation between IL-10 and serum level of CRP (r = –0.76, p < 0.05), AGP (r = –0.64, p < 0.05) and ACT (r = –0.38, p < 0.05) was also observed. Moreover, these relationships were maintained when patients treated with MTX, IMG, or NSAID were analyzed independently. According to the data thus far obtained, it seems that IL-10 decreases IL-6 production, and thereby indirectly affects the acute phase response, decreasing CRP, AGP, and ACT concentration in RA patients.Abbreviations ACT -1-antichymotrypsin - AGP ₁-acid glycoprotein - APP acute phase protein - CRP C-reactive protein - CSF colony stimulating factor - IFN interferon - IL interleukin - IMG intramuscular gold - MTX methotrexate - NSAID non-steroidal anti-inflammatory drug - RA rheumatoid arthritis     

Pathologic explanation for postoperative obstipation in Hirschsprung's disease revealed with monoclonal antibody staining

Until now, no pathologic explanation could be found for the postoperative obstipation occurring in some patients with intestinal aganglionosis. Twenty-two of 108 infants treated for intestinal aganglionosis suffered from postoperative obstipation. Resected material from these 22 patients and from 17 control subjects was investigated with monoclonal anti-neurofilament antibody staining. An abnormal staining pattern was revealed in 18 of the constipated patients. Consequently, this new immunohistochemical staining technic has revealed a hitherto unsuspected cause for postoperative obstipation in aganglionosis. The monoclonal antibody may provide early warning of such postoperative constipation.     

Elektronenmikroskopische Befunde an inneren Organen bei Morbus Fabry

Zusammenfassung Es werden elektronenmikroskopische Beobachtungen zur Lokalisation und zur Feinstruktur der Glykolipideinschlüsse in verschiedenen inneren Organen bei Morbus Fabry berichtet. Die intrazellulÄren und extrazellulÄren Einschlüsse bestehen aus vielschichtig lamellÄren Membransystemen in konzentrischer und exzentrischer sowie in stapeiförmiger paralleler Anordnung. Diese lamellÄre Anordnung ist charakteristisch für flüssigkristalline Phasen von Phospholipid-Wasser-Systemen. Erstmalig werden ultrastrukturelle Befunde an den inneren Organen einer erkrankten Frau mitgeteilt. Demzufolge lassen sich bei heterozygoten Frauen gleiche Glykolipidablagerungen wie bei homozygoten MÄnnern nachweisen. Die Beziehung der Glykolipideinschlüsse zu den Lysosomen wird erörtert.

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Electron microscopic observations in internal organs in morbus fabry

Summary Electron microscopic findings are reported on the localization and fine structure of glycolipid inclusions in different organs (heart, kidney, lymph nodes, arterial blood vessels, pancreas) in Fabry's disease in a female. The intracellular and extracellular inclusions were made up of multilamellar membraneous systems in concentric, excentric, and parallel arrangement. This fine structure is characteristic of liquid-crystalline phases of phospholipid-water systems.The same type of inclusions are found in the internal organs of heterozygotic women as in homozygotic men. The relationship between the glycolipid inclusions and the lysosomes is discussed.

Herrn Prof. Dr. F. Bolck, Direktor des Pathologischen Instituts der Friedrich-Schiller-UniversitÄt Jena, zum 60. Geburtstag gewidmet.     

Quantification of HIV-1 p24 by a highly improved ELISA: an alternative to HIV-1 RNA based treatment monitoring in patients from Abidjan, C?te d'Ivoire.

BACKGROUND: Quantification of HIV-1 RNA remains difficult to implement in Africa. Simple and inexpensive tests for antiretroviral treatment (ART) monitoring are needed. OBJECTIVE: To evaluate an HIV-1 p24 ELISA, which combines efficient virus disruption, heat-denaturation and signal amplification, in a West African setting. STUDY DESIGN: Eighty-six HIV-1 infected patients from Abidjan, C?te d'Ivoire, were tested for p24, HIV-1 RNA, and CD4+ count at baseline, and twice within 8 months after ART initiation. RESULTS: All patients responded to ART with a minimal HIV-1 RNA drop of 0.5 log(10) at first follow-up. Forty-one (47.7%) then rebounded >0.5 log(10) or persisted above 1000 copies/mL by week 24. The predicted baseline concentration of p24 corresponding to 100,000 copies/mL of HIV-1 RNA, above which ART is recommended, was 4546 fg/mL (95% confidence interval 3148-6566). A prediction model of virologic failure, occurring after an initial response to ART, correctly classified 84% of patients using baseline p24, p24 change on therapy, and achievement of undetectable p24 as explanatory variables. The model and further bootstrap evaluation suggested a good ability to discriminate between sustained or failing virologic response to ART. CONCLUSION: HIV-1 p24 and RNA based-ART monitoring in a low-resource country dominated by HIV-1 CRF02 AG appeared comparable.     

Detection of ophthalmic arterial doppler signals with Behcet disease using multilayer perceptron neural network

Doppler ultrasound is known as a reliable technique, which demonstrates the flow characteristics and resistance of ophthalmic arteries. In this study, ophthalmic arterial Doppler signals were obtained from 106 subjects, 54 of whom suffered from ocular Behcet disease while the rest were healthy subjects. Multilayer perceptron neural network (MLPNN) employing delta-bar-delta training algorithm was used to detect the presence of ocular Behcet disease. Spectral analysis of the ophthalmic arterial Doppler signals was performed by least squares (LS) autoregressive (AR) method for determining the MLPNN inputs. The MLPNN was trained with training set, cross validated with cross validation set and tested with testing set. All these data sets were obtained from ophthalmic arteries of healthy subjects and subjects suffering from ocular Behcet disease. Performance indicators and statistical measures were used for evaluating the MLPNN. The correct classification rate was 96.43% for healthy subjects and 93.75% for unhealthy subjects suffering from ocular Behcet disease. The classification results showed that the MLPNN employing delta-bar-delta training algorithm was effective to detect the ophthalmic arterial Doppler signals with Behcet disease.     

Sequence of a novel HLA-A*0301 intronic variant (A*03010103)

We report here the full-length sequence of a novel HLA-A*0301 allele, A*03010103, which differs from A*03010101 by a single nucleotide substitution (G>T) at position 492 within intron 2. The variant was originally identified by Reference Strand-mediated Conformational Analysis (RSCA) and was confirmed by cloning and sequencing. The difference in RSCA mobility between A*03010101 and A*03010103 demonstrates the sensitivity of RSCA to detect single nucleotide polymorphisms.     

Autoimmunity and inflammation due to a gain-of-function mutation in phospholipase C gamma 2 that specifically increases external Ca2+ entry

The identification of specific genetic loci that contribute to inflammatory and autoimmune diseases has proved difficult due to the contribution of multiple interacting genes, the inherent genetic heterogeneity present in human populations, and a lack of new mouse mutants. By using N-ethyl-N-nitrosourea (ENU) mutagenesis to discover new immune regulators, we identified a point mutation in the murine phospholipase Cg2 (Plcg2) gene that leads to severe spontaneous inflammation and autoimmunity. The disease is composed of an autoimmune component mediated by autoantibody immune complexes and B and T cell independent inflammation. The underlying mechanism is a gain-of-function mutation in Plcg2, which leads to hyperreactive external calcium entry in B cells and expansion of innate inflammatory cells. This mutant identifies Plcg2 as a key regulator in an autoimmune and inflammatory disease mediated by B cells and non-B, non-T haematopoietic cells and emphasizes that by distinct genetic modulation, a single point mutation can lead to a complex immunological phenotype.     

The pathogenesis of molybdenum cofactor deficiency, its delay by maternal clearance, and its expression pattern in microarray analysis

Molybdenum cofactor (Moco)-deficiency is a lethal autosomal recessive disease, for which until now no effective therapy is available. The biochemical hallmark of this disorder is the inactivity of the Moco-dependent sulfite oxidase, which results in elevated sulfite and diminished sulfate levels throughout the organism. In humans, Moco-deficiency results in neurological damage, which is apparent in untreatable seizures and various brain dysmorphisms. We have recently described a murine model for Moco-deficiency, which reflects all enzyme and metabolite changes observed in the patients, and an efficient therapy using a biosynthetic precursor of Moco has been established in this animal model. We now analyzed these mice in detail and excluded morphological brain damage, while expression analysis with microarrays indicates a massive cell death program. This neuronal damage appears to be triggered by elevated sulfite levels and is ameliorated in affected embryos by maternal clearance.