Affinity of C-reactive protein toward FcgammaRI is strongly enhanced by the gamma-chain

C-reactive protein (CRP), the prototype human acute phase protein, is widely regarded as a key player in cardiovascular disease, but the identity of its cellular receptor is still under debate. By using ultrasensitive confocal imaging analysis, we have studied CRP binding to transfected COS-7 cells expressing the high-affinity IgG receptor FcgammaRI. Here we show that CRP binds to FcgammaRI on intact cells, with a kd of 10+/-3 micromol/L. Transfection of COS-7 cells with a plasmid coding for both FcgammaRI and its functional counterpart, the gamma-chain, markedly increases CRP affinity to FcgammaRI, resulting in a kd of 0.35+/-0.10 micromol/L. The affinity increase results from an approximately 30-fold enhanced association rate coefficient. The pronounced enhancement of affinity by the gamma-chain suggests its crucial involvement in the CRP receptor interaction, possibly by mediating interactions between the transmembrane moieties of the receptors. Dissociation of CRP from the cell surfaces cannot be detected throughout the time course of several hours and is thus extremely slow. Considering the pentameric structure of CRP, this result indicates that multivalent binding and receptor clustering are crucially involved in the interaction of CRP with nucleated cells.     

Bone mineral density of the lumbar spine in children and adolescents with celiac disease on a gluten-free diet in São Paulo, Brazil

BACKGROUND: To compare bone mineral density (BMD) in children and adolescents with celiac disease (CD) and control subjects and to evaluate diet adequacy and calcium metabolism in patients with CD. METHODS: Thirty patients with asymptomatic CD (17 children, 13 adolescents), on a gluten-free diet, and 23 healthy subjects were studied. BMD of the lumbar spine (dual energy x-ray absorptiometry) was performed on all patients and control subjects. In patients, food diaries for nine nonconsecutive days were obtained and analyzed. In patients, laboratory tests pertaining to calcium balance were obtained. RESULTS: The mean weight and height of the adolescents with CD were lower than those of control subjects (weight: 45.8 +/- 10.5 kg v 55.3 +/- 10.5 kg, P = 0.037; height: 153.0 +/- 11.0 cm v 167 +/- 12.0 cm, P = 0.007). The mean BMD in adolescents with CD was significantly lower than that of the control subjects (0.917 +/- 0.116 g/cm2 v 1.060 +/- 0.158 g/cm2, P = 0.015), whereas no significant difference was found between children with CD and control subjects (P = 0.595). A multiple-regression model shows that increases in BMD relative to height were lower in adolescents with CD than in control subjects. The proportion of adolescents who had started a gluten-free diet after 2 years of age was higher than that of children with CD (P < 0.001). High percentages of magnesium, calcium, and phosphorous deficiencies were present in CD patients' diets. The serum levels of ionized and total calcium and parathormone were normal. CONCLUSIONS: The BMD of adolescents with CD was lower than that of the control subjects, whereas no difference was found between the BMD of children with CD and that of control subjects.     

Emergence of rifampicin resistance in methicillin-resistant Staphylococcus aureus isolated at a Turkish university hospital

Twenty-three rifampicin-resistant methicillin-resistant Staphylococcus aureus (MRSA) isolated in three wards at a university hospital in Turkey between June, 2000, and February, 2001, were studied for their genetic relatedness using a combination of antibiogram, coagulase serotyping, coagulase gene polymorphism (coa-RFLP), and pulsed-field gel electrophoresis (PFGE). They all expressed high-level rifampicin resistance (MIC, >256 mg/L) and were resistant to gentamicin, kanamycin, amikacin, ciprofloxacin, tetracycline, and cadmium acetate and were susceptible to fusidic acid, vancomycin, trimethoprim, and mupirocin. They belonged to the same coagulase serotype (serotype IV) and had identical coa-RFLP patterns. In contrast, PFGE generated nine banding patterns designated type A, types A1-A5, B, C, and D. The most common PFGE pattern (type A) and its subtypes (types A1-A5) were seen in 20 (87%) of the 23 isolates in the three wards. The results demonstrated the acquisition of rifampicin resistance by different MRSA clones and the spread of one clone among patients in the three wards.     

Immunohistochemical expression of estrogen and progesterone receptors in endometrial polyps and adjacent endometrium in postmenopausal women

OBJECTIVE: To detect the presence of estrogen (ER) and progesterone (PR) receptors in endometrial polyps and adjacent endometrium in postmenopausal women. METHODS: Forty-four consecutively enrolled postmenopausal patients were submitted to operative hysteroscopy. These patients had diagnosed benign endometrial polyp. The presence of ER and PR was determined in endometrial samples and polyps by immunohistochemical method and the slides were evaluated using a semiquantitative analysis. RESULTS: In the glandular epithelium, the median of the ER score was 7.0 in the polyps and 5.0 in the endometrium (P<0.0001) and the median of the PR was 6.0 in the polyps and 4.0 in the endometrium (P<0.0001). In the stroma, the median of the ER score was 6.0 in the polyps and 5.0 in the endometrium (P=0.021) and the median of the PR score was 4.0 in the polyps and 4.5 in the endometrium (P=0.34 ). CONCLUSIONS: Our data suggests that steroids receptors present a crucial role in the phisiopathology of the endometrial polyps in postmenopausal women, specially the estrogen receptors.     

Genetic lineages of community-associated methicillin-resistant Staphylococcus aureus in Kuwait hospitals

Twenty-six community-associated methicillin-resistant Staphylococcus aureus (CAMSRA) isolates were characterized by pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST) and screened for accessory gene regulator (agr), capsular polysaccharide (cap), and Panton-Valentine leucocidin (PVL) genes. They exhibited five PFGE patterns (types A to E). The majority were PFGE type A (12 isolates) or type B (8 isolates). MLST showed that PFGE type A isolates belonged to sequence type 80 (ST80), while the PFGE type B isolates were ST30. The ST80 and ST30 clones contained agr allotype 3, cap type 8, and PVL. The results showed that two internationally recognized CAMRSA clones are dominant in Kuwait hospitals.     

Treatment of epilepsy in childhood

OBJECTIVE: Due to the development of new antiepileptic drugs, epilepsy treatment has presented substantial progress in the last decade. In spite of presenting more adequate profile, these drugs have not shown better efficiency in seizure control than the traditional drugs. The objective of this revision is to provide up-to-date data for the treatment of epilepsy in childhood and the role of the new antiepileptic drugs. SOURCES: Bibliographic review has been performed at Medline for the last 10 years, and the most pertinent papers and abstracts presented in International Epilepsy Meetings were selected. SUMMARY OF THE FINDINGS: The new antiepileptic drugs could be indicated in the treatment of some specific epileptic syndromes. Serious side effects have been described with the use of these drugs. CONCLUSIONS: The traditional drugs must be considered as the primary choice in the treatment of ordinary epilepsy.     

Alpha‐melanocyte stimulating hormone ameliorates disease activity in an induced murine lupus‐like model

Alpha‐melanocyte stimulating hormone (α‐MSH) is a neuropeptide exhibiting anti‐inflammatory activity in experimental models of autoimmune diseases. However, no studies thus far have examined the effects of α‐MSH on systemic lupus erythematosus (SLE). This study aimed to determine the effects of an α‐MSH agonist in induced murine lupus. Here we employed female Balb/cAn mice in which lupus was induced by pristane. Groups of lupus animals were treated daily with the α‐MSH analogue [Nle4, DPhe7]‐α‐MSH (NDP–MSH) (1·25 mg/kg) injected intraperitoneally or saline for 180 days. Normal animals comprised the control group. Arthritis incidence, plasma immunoglobulin (Ig)G isotypes, anti‐nuclear antibodies (ANA) and plasma cytokines were evaluated. Renal function was assessed by proteinuria and histopathological lesion. Glomerular levels of IgG, α‐smooth muscle actin (α‐SMA), inducible nitric oxide synthase (iNOS), C3, CD3, melanocortin receptors (MCR)1, corticotrophin‐releasing factor (CRF) and α‐MSH was estimated by immunohistochemistry. When compared with normal controls, lupus animals exhibited increased arthritis, IgG levels, ANA, interleukin (IL)‐6, IL‐10, proteinuria and mesangial cell proliferation together with glomerular expression of α‐SMA and iNOS. Glomerular expression of MCR1 was reduced in lupus animals. NDP‐MSH treatment reduced arthritis scores by 70% and also diminished IgG1 and IgG2a levels and ANA incidence. In the glomerulus, NDP–MSH treatment reduced cellularity by 50% together with reducing IgG deposits, and expression levels of α‐SMA, iNOS and CRF were also all decreased. Taken together, our results suggest for the first time that α‐MSH treatment improves several parameters of SLE disease activity in mice, and indicate that this hormone is an interesting potential future treatment option.