Anti-beta(2)-glycoprotein I antibodies in children with atopic dermatitis

beta(2)-Glycoprotein I (beta(2)GPI) appears to be the major antigen for antiphospholipid antibodies (aPL) in patients with antiphospholipid syndrome (APS). In early infancy, virtually all children initiate transient immune response to non-pathogenic nutritional antigens, which fails to terminate in children with atopic diseases. To examine the possibility that a prolonged immune response to beta(2)GPI could also spread to the human protein, antibodies against human beta(2)GPI (anti-beta(2)GPI) were determined in 93 randomly selected children with different allergic diseases. A high frequency (42%) of IgG anti-beta(2)GPI was found in children with atopic dermatitis (AD), but not in those with other allergic diseases. Anti-beta(2)GPI in children with AD were exclusively of the IgG1 subclass and bound to bovine beta(2)GPI as well, but not to either beta(2)GPI combined with the phospholipid cardiolipin. The epitopes were identified in domain V of beta(2)GPI and the antibody binding was abolished upon the specific proteolytic cleavage of the phospholipid-binding C-terminal loop in domain V of beta(2)GPI. These results indicated that the epitopes for anti-beta(2)GPI in children with AD most likely resided in close vicinity of the phospholipid-binding site of beta(2)GPI. The epitopic difference from anti-beta(2)GPI in APS may explain presumed non-thrombogenicity of anti-beta(2)GPI in children with AD.     

Antibodies against annexin A5: detection pitfalls and clinical associations

Antiphospholipid syndrome (APS) has been defined as a clinical and laboratory entity. Laboratory criteria include the presence of anticardiolipin antibodies (aCL) and/or lupus anticoagulant (LA), collectively termed as antiphospholipid antibodies (aPL). However, there has been a rising interest in antibodies against so-called protein cofactors, particularly in beta(2)-glycoprotein I. In the early 90s, annexins were considered as target antigens for aPL, but at present the exact role of antibodies against annexins (aANX) remains puzzling. This review is concerned with annexin V or annexin A5 (ANXA5), a widespread member of the annexin family, and antibodies directed towards it. We have endeavoured to summarise essential information about the detection of anti-annexin V antibodies (aANXA5) and their clinical relevance. This review has also brought together some relevant published data concerning the structure, physiological role and therapeutic potential of ANXA5.     

Effects of ramipril in nondiabetic nephropathy: improved parameters of oxidatives stress and potential modulation of advanced glycation end products

Enhanced oxidative stress is involved in the progression of renal disease. Since angiotensin converting enzyme inhibitors (ACEI) have been shown to improve the antioxidative defence, we investigated, in patients with nondiabetic nephropathy, the short-term effect of the ACEI ramipril on parameters of oxidative stress, such as advanced glycation end products (AGEs), advanced oxidation protein products (AOPPs), homocysteine (Hcy), and lipid peroxidation products. Ramipril (2.5-5.0 mg/day) was administered to 12 newly diagnosed patients for 2 months and data compared with a patient group under conventional therapy (diuretic/beta-blockers) and with age- and sex-matched healthy subjects (CTRL). Patients had mild to moderate renal insufficiency and showed, in the plasma, higher fluorescent AGE and carboxymethyllysine (CML) levels, as well as elevated concentrations of AOPPs, lipofuscin and Hcy when compared with CTRL. Basal data of the patients on conventional therapy did not differ significantly from the ramipril group, except for higher Hcy levels in the latter. Administration of ramipril resulted in a drop in blood pressure and proteinuria, while creatinine clearance remained the same. The fluorescent AGEs exhibited a mild but significant decline, yet CML concentration was unchanged. The AOPP and malondialdehyde concentrations decreased, while a small rise in neopterin levels was evident after treatment. The mentioned parameters were not affected significantly in the conventionally treated patients. Evidence that ramipril administration results in a mild decline of fluorescent AGEs is herein presented for the first time. The underlying mechanism may be decreased oxidative stress, as indicated by a decline in AOPPs and malondialdehyde.     

Hyperferritinemia is Associated with Serologic Antiphospholipid Syndrome in SLE Patients

Ferritin may play a direct role on the immune system. We sought to determine if elevated levels of ferritin in lupus patients correlate with disease activity and organ involvement in a large cohort. Ferritin levels (gender and age adjusted) were assessed in 274 lupus serum samples utilizing the LIASON Ferritin automated immunoassay method. Significant disease activity was determined if European Consensus Lupus Activity Index (ECLAM)?>?2 or Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)?>?4. Utilizing an EXCEL database, we compared elevated ferritin levels to manifestations grouped by organ involvement, serology, and previous therapy. The patients were predominantly female (89%), median age was 37 years old, and disease duration was 10.6?±?7.7 years. Hyperferritinemia was found in 18.6% of SLE patients. Compared to subjects with normal ferritin levels, a significantly greater proportion of patients with hyperferritinemia had thrombocytopenia (15.4% vs. 33.3%, p?=?0.003) and lupus anticoagulant (11.3% vs. 29.0%, p?=?0.01). Additionally, compared to normoferritinemic subjects, hyperferritinemic subjects had significantly higher total aCL (99.7?±?369 vs. 30.9?±?17.3 GPI, p?=?0.02) and aCL IgM antibody levels (75.3?±?357.4 vs. 9.3?±?10.3 GPI, p?=?0.02), and marginally lower aCL IgG antibody levels (9.2?±?4.9 vs. 9.7?±?3.9 GPI, p?=?0.096). While the ECLAM score significantly correlated with hyperferritinemia (p?=?0.04), the SLEDAI score was marginally associated with hyperferritinemia (p?=?0.1). Serositis was marginally associated with hyperferritinemia, but not with other manifestations. An association with serologic APS was encountered. Hyperferritinemia was associated with thrombocytopenia, lupus anticoagulant, and anti-cardiolipin antibodies suggest that it may be an early marker for secondary antiphospholipid syndrome in SLE patients.     

Chromosomes 7,17 polysomies and overexpression of epidermal growth factor receptor and p53 protein in epithelial hyperplastic laryngeal lesions

PURPOSE: To visualize directly a sequence of genetic changes underlying the entire spectrum of epithelial hyperplastic laryngeal lesions (EHLL) and laryngeal cancer by the use of non-isotopic in situ hybridization (ISH) for chromosomes 7 and 17 in correlation with overexpression of p53 protein and epidermal growth factor receptor (EGFR). The specific aim was to compare the results and prognostic significance between the two types of EHLL: isolated, mainly atypical hyperplasia or risky epithelium, and EHLL associated with squamous cell carcinoma (SCC). PATIENTS AND METHODS: 59 tissue specimens of EHLL obtained from 34 patients, graded according to the Ljubljana classification into simple (SH), abnormal (AbH) and atypical hyperplasia (AtH), and carcinoma in situ (CIS) were included in the study. Non-fluorescent ISH for chromosomes 7 and 17 was performed by biotinylated alpha-satellite DNA probes. Immunohistochemical staining for EGFR and p53 protein was analyzed on the same tissue samples. RESULTS: Polysomy for both chromosomes increased in correlation with progressive grades of EHLL. The most important finding was the statistically significant difference in chromosome copy numbers between the isolated AtH and AtH associated with SCC. Overexpression of EGFR and p53 protein was found in 61 (36/59) and 52% (31/59) of cases, respectively. The immunoreactivity for both markers increased with the grade of lesions, but the staining pattern was not so uniform in isolated EHLL. On the other hand, the immunoreactivity was expressed more constantly in EHLL adjacent to SCC. CONCLUSIONS: Numerical changes in chromosomes 7 and 17 might be associated with an upregulation of EGFR and p53 genes, and could contribute to critical events in laryngeal carcinogenesis. For daily practice, the cytogenetic and immunohistochemical analyses could be of assistance in distinguishing between low- and high-risk groups of AtH. However, the isolated forms of atypical hyperplasia need considerable further study by evaluating genetic changes with the described methods regarding their ultimate transformation to carcinoma.     

Predictive model for estimating risk of crush syndrome: a data mining approach

BACKGROUND: There is no standard triage method for earthquake victims with crush injuries because of a scarcity of epidemiologic and quantitative data. We conducted a retrospective cohort study to develop predictive models based on clinical data for crush injury in the Kobe earthquake. METHODS: The medical records of 372 patients with crush injuries from the Kobe earthquake were retrospectively analyzed. Twenty-one risk factors were assessed with logistic regression analysis for three outcomes relating to crush syndrome. Two types of predictive triage models--initial evaluation in the field and secondary assessment at the hospital--were developed using logistic regression analysis. Classification accuracy, Brier score and area under the receiver operating characteristic curve (AUC) were used to evaluate the model. RESULTS: The initial triage model, which includes pulse rate, delayed rescue, and abnormal urine color, has an AUC of 0.73. The secondary model, which includes WBC, tachycardia, abnormal urine color, and hyperkalemia, shows an AUC of 0.76. CONCLUSIONS: These triage models may be especially useful to nondisaster experts for distinguishing earthquake victims at high risk of severe crush syndrome from those at lower risk. Application of the model may allow relief workers to better utilize limited medical and transportation resources in the aftermath of a disaster.     

Severe human granulocytic anaplasmosis transmitted by blood transfusion

A 36-year-old woman acquired severe human granulocytic anaplasmosis after blood transfusion following a cesarean section. Although intensive treatment with mechanical ventilation was needed, the patient had an excellent recovery. Disease caused by Anaplasma phagocytophilum infection was confirmed in 1 blood donor and in the transfusion recipient.