Anti-citrullinated heat shock protein 90 antibodies identified in bronchoalveolar lavage fluid are a marker of lung-specific immune responses

Previous work has demonstrated a correlation between serum anti-citrullinated HSP90 antibodies and rheumatoid arthritis-associated interstitial lung disease (RA-ILD). To further investigate this potential pathogenic relationship, we used ELISA-based techniques to assess anti-citrullinated HSP90 antibody profiles in bronchoalveolar lavage fluid (BALF) of patients with different stages of RA-ILD. 9/21 RA-derived BALF specimens demonstrated IgG and/or IgA antibodies targeting citrullinated HSP90 proteins/peptides, highlighting disease specific responses (with a predilection for RA-ILD) that did not occur in IPF patients (0/5) or healthy control subjects (0/5). Comparison of antibody profiles between BALF and matching serum specimens revealed various recognition patterns favoring predominant production of anti-citrullinated HSP90 antibodies within the lung microenvironment—further supporting the connection between this antibody specificity and parenchymal lung disease. Equally important, qualitative as well as quantitative differences in anti-citrullinated HSP90 profiles between BALF and serum indicate that the lung plays a direct role in shaping the immune repertoire of RA/RA-ILD.     

Specific allergens enhance elastase release in stimulated neutrophils from asthmatic patients

BACKGROUND: The presence of the three forms of IgE receptor - the heterotrimeric high-affinity receptor for IgE (Fc(epsilon)RI), the low-affinity receptor for IgE (Fc(epsilon)RII/CD23) and the Mac-2/IgE-binding protein (epsilonBP) - has been demonstrated on human neutrophils. We have previously shown that specific allergens are able to activate functional responses by neutrophils from allergic patients sensitized to those allergens. Neutrophils are present at the sites of allergic inflammation. The primary (azurophilic) granules of neutrophils contain a variety of enzymes, such as elastase, that might potentiate inflammation. It is not known whether specific allergens are able to elicit elastase release by neutrophils from allergic patients. In addition, we attempted to evaluate the relationship between neutrophil degranulation and lung function of the patients, measured as FEV(1). METHODS: Neutrophils were challenged in vitro with the specific allergens that produced clinical symptoms in asthmatic patients. The cells were also challenged with allergen to which the patients were not sensitive. Neutrophils from normal subjects were challenged with allergens as control. RESULTS: The in vitro challenge of neutrophils with allergens to which the patients were sensitive elicited a release of elastase by these cells. The in vitro activation of neutrophils was highly allergen specific; allergens other than those accounting for clinical symptoms did not evoke elastase release, and allergens were ineffective on neutrophils from healthy donors. A significant inverse correlation was observed between elastase release and patients' lung function, measured as FEV(1). CONCLUSION: An IgE-dependent mechanism might promote elastase release by neutrophils at allergic sites. There is a significant inverse relationship between levels of elastase released by neutrophils from allergic patients and lung function, as assessed by FEV(1).     

Enhanced number and activity of mitochondria in multiple sclerosis lesions

Mitochondrial dysfunction has been implicated in the development and progression of multiple sclerosis (MS) lesions. Mitochondrial alterations might occur as a response to demyelination and inflammation, since demyelination leads to an increased energy demand in axons and could thereby affect the number, distribution and activity of mitochondria. We have studied the expression of mitochondrial proteins and mitochondrial enzyme activity in active demyelinating and chronic inactive MS lesions. Mitochondrial protein expression and enzyme activity in active and chronic inactive MS lesions was investigated using (immuno)histochemical and biochemical techniques. The number of mitochondria and their co‐localization with axons and astrocytes within MS lesions and adjacent normal‐appearing white matter (NAWM) was quantitatively assessed. In both active and inactive lesions we observed an increase in mitochondrial protein expression as well as a significant increase in the number of mitochondria. Mitochondrial density in axons and astrocytes was significantly enhanced in active lesions compared to adjacent NAWM, whereas a trend was observed in inactive lesions. Complex IV activity was strikingly up‐regulated in MS lesions compared to control white matter and, to a lesser extent, NAWM. Finally, we demonstrated increased immunoreactivity of the mitochondrial stress protein mtHSP70 in MS lesions, particularly in astrocytes and axons. Our data indicate the occurrence of severe mitochondrial alterations in MS lesions, which coincides with enhanced mitochondrial oxidative stress. Together, these findings support a mechanism whereby enhanced density of mitochondria in MS lesions might contribute to the formation of free radicals and subsequent tissue damage. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Missing information in statewide and national cancer databases: Correlation with health risk factors,geographic disparities,and outcomes

Objective

The objectives of this study were to analyze factors associated with outcomes and missing data in women with epithelial ovarian cancer using institutional, state and national databases.

Alendronate treatment for infants with osteogenesis imperfecta: demonstration of efficacy in a mouse model

Recent non-placebo-controlled studies of the bisphosphonate pamidronate have shown it to be effective in reducing fractures and improving bone density in infants and children with osteogenesis imperfecta (OI). To evaluate the effects of bisphosphonate treatment in a controlled study, the oim/oim mouse model of OI was studied. Nursing infant mouse pups (approximately 2 wk old) with moderate to severe OI (oim/oim mouse) and age- and background-matched control mice (+/+) were treated either with the third-generation bisphosphonate alendronate (ALN), or with saline. Fracture risk, bone quality, and growth were evaluated over a 12-wk treatment period. ALN at a dose of 0.03 mg/kg/d or saline was administered via s.c. injection to infant oim/oim and wild-type (+/+) mice from 2 to 14 wk of age (n = 20 per subgroup). The average number of fractures sustained by the ALN-treated oim/oim mice was reduced significantly compared with the untreated oim/oim mice (0.7 +/- 0.7 fractures/mouse versus 2.0 +/- 0.2 fractures/mouse). Bone density increased significantly in the femur and the spine with treatment (2.0 +/- 0.5 versus 1.2 +/- 0.5 in femur and 2.1 +/- 0.5 versus1.6 +/- 0.5 in spine). Histologic evaluation revealed the percentage of metaphyseal tibial bone increased significantly with treatment in both +/+ and oim/oim mice. Mechanical testing revealed an increase in structural stiffness for both treated +/+ and oim/oim mice compared with untreated animals. None of the material properties examined were significantly altered with treatment, nor was spinal curvature affected. Weight gain and long bone growth were comparable in the treated and untreated oim/oim mice. In wild-type mice, femur lengths were significantly shorter in the treated mice compared with untreated counterparts. This animal study demonstrates that treatment of OI in mice as early as 2 wk of age with ALN appears to be effective in reducing fractures and increasing bone properties. Based on the data from this study, ALN therapy in infants with OI should prove to be effective.     

Structural Characteristics and Development of Ampullary Organs in Acipenser naccarii

Ampullary organs of Acipenser naccarii sturgeons were examined by optical and electronic microscopy (transmission electron microscopy and scanning electron microscopy) from hatching until 1 month later when the juvenile phase is completely established. It was observed that, when A. naccarii begins to feed actively, the ultrastructural characteristics of ampullary organs already correspond to those of adult animals. These organs may, therefore, be functional and, together with taste buds, facilitate food search after exhaustion of yolk sac food reserves. Mature ampullary organs of A. naccarii are formed by an ampulla that communicates with the exterior by means of a short channel. These ampullae correspond to the sensory portion of these receptors and are formed by two cell types: receptor cells and support cells. Receptor cells present a kinocilium on their free surface and establish ribbon synapses with axon nerve endings that arise from the underlying conjunctive tissue. Support cells enclose receptor cells, bear stereocilia and occasional cilia, and are of a secretory nature. The mucus associated with ampullary organs mainly comprises neutral mucopolysaccharides, whereas mucopolysaccharides are usually acid in other fish groups. Anat Rec, 290:1178–1189, 2007. © 2007 Wiley‐Liss, Inc.     

Antimicrobial resistance of Salmonella serotypes isolated from slaughter-age pigs and environmental samples

The aim of this study was to determine the antimicrobial resistance patterns of Salmonella strains isolated from slaughter-age pigs and environmental samples collected at modern swine raising facilities in Brazil. Seventeen isolates of six serotypes of Salmonella enterica subsp. enterica were isolated out of 1,026 collected samples: Salmonella Typhimurium (1), Salmonella Agona (5), Salmonella Sandiego (5), Salmonella Rissen (1), Salmonella Senftenberg (4), and Salmonella Javiana (1). Resistance patterns were determined to extended-spectrum penicillin (ampicillin), broad-spectrum cephalosporins (cefotaxime and ceftriaxone), aminoglycosides (streptomycin, neomycin, gentamicin, amikacin, and tobramycin), narrow-spectrum quinolone (nalidixic acid), broad-spectrum quinolone (ciprofloxacin and norfloxacin), tetracycline, trimethoprim, and chloramphenicol. Antimicrobial resistance patterns varied among serotypes, but isolates from a single serotype consistently showed the same resistance profile. All isolates were resistant to tetracycline, streptomycin, and nalidixic acid. One isolate, Salmonella Rissen, was also resistant to cefotaxime and tobramycin. All serotypes were susceptible to ceftriaxone, norfloxacin, ciprofloxacin, ampicillin, gentamicin, and chloramphenicol. The high resistance to tetracycline and streptomycin may be linked to their common use as therapeutic drugs on the tested farms. No relation was seen between nalidixic acid and fluoroquinolone resistance.     

Clonal proliferation of cyclin D1-positive mantle lymphocytes in an asymptomatic patient: an early-stage event in the development or an indolent form of a mantle cell lymphoma?

Mantle cell lymphoma (MCL) is a B-cell neoplasm with a relatively aggressive clinical course. There is a very small subgroup of patients who present with atypical lymphocytes in peripheral blood, with or without lymphocytosis, lymphadenopathy, or splenomegaly, and with an indolent clinical course. They frequently show mutated IgV(H) genes and CD5 negativity. We report an asymptomatic elderly patient who presented with a single submandibular lymphadenopathy. The biopsy showed immunophenotype and t(11;14)(q13;q32) consistent with MCL. The abnormal lymphoid population was also detected in peripheral blood and bone marrow. The patient has remained asymptomatic for 5 years without receiving any therapy. It is uncertain whether these cases represent an early-stage event in the development or an indolent form of MCL. The existence of such asymptomatic patients with an indolent clinical course should induce a strict clinical judgment in terms of therapeutic decisions.     

Olfactory discrimination and incentive value of non copulating and sexually sluggish male rats

Some apparently healthy male rats fail to copulate despite being tested on repeated occasions with receptive females and are called non copulating (NC) rats. NC rats sniff and lick the female genitals, and show normal erectile and ejaculatory functions and hormonal levels. Sexually sluggish (S) male rats take a long time to ejaculate or sometimes they don't achieve ejaculation when tested repeatedly with receptive females. The aim of the present study was to determine if NC and S males can discriminate sexually relevant olfactory cues such as urine from estrous or anestrous female and urine from sexually experienced males. We also tested odors like amyl acetate and mint using an olfactory discrimination test. In a second experiment we evaluated if a sexually receptive female has a preference for a copulating (C) male, for a NC male, or for a S male in a sexual incentive motivation test. This would let us determine if a NC and an S male are equally attractive than a C male to a sexually receptive female. The olfactory test revealed that C, NC and S males have the same ability to discriminate sexually relevant odors. As well, all males clearly discriminate non sexual odors like amyl acetate and mint suggesting that NC and S male rats do not have alterations in their olfactory system. With respect to the sexual incentive motivation test, females spend the same time in the incentive zone of the NC and C males. As well, females spent the same time in the incentive zone of S and C males. These results demonstrate that NC, S and C males are equally attractive to receptive females.