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ARIA, a protein that stimulates acetylcholine receptor synthesis, also induces tyrosine phosphorylation of a 185-kDa muscle transmembrane protein.

Motoneurons promote the accumulation of acetylcholine receptors (AChRs) at developing neuromuscular synapses. The AChR-inducing activity protein ARIA, which is purified from chicken brain and increases the synthesis of AChRs in chicken myotubes, may play a crucial role in this process. Here we show that ARIA induces the rapid tyrosine phosphorylation of a M(r) 185,000 protein (p185) in muscle cells. Phosphorylation of p185 correlates with AChR induction at each stage of ARIA purification. Moreover, medium conditioned by spinal cord motoneurons stimulates AChR synthesis and p185 phosphorylation. Studies with membrane-impermeant reagents and 125I-labeled ARIA indicate that p185 is a transmembrane ARIA-receptor tyrosine kinase. Our data suggests that muscle AChR synthesis can be regulated through tyrosine phosphorylation.

Animals↗

Processing of ARIA and release from isolated nerve terminals.

The neuromuscular junction is a specialized synapse in that every action potential in the presynaptic nerve terminal results in an action potential in the postsynaptic membrane, unlike most interneuronal synapses where a single presynaptic input makes only a small contribution to the population postsynaptic response. The postsynaptic membrane at the neuromuscular junction contains a high density of neurotransmitter (acetylcholine) receptors and a high density of voltage-gated Na+ channels. Thus, the large acetylcholine activated current occurs at the same site where the threshold for action potential generation is low. Acetylcholine receptor inducing activity (ARIA), a 42 kD protein, that stimulates synthesis of acetylcholine receptors and voltage-gated Na+ channels in cultured myotubes, probably plays the same roles at developing and mature motor endplates in vivo. ARIA is synthesized as part of a larger, transmembrane, precursor protein called proARIA. Delivery of ARIA from motor neuron cell bodies in the spinal cord to the target endplates involves several steps, including proteolytic cleavage of proARIA. ARIA is also expressed in the central nervous system and it is abundant in the molecular layer of the cerebellum. In this paper we describe our first experiments on the processing and release of ARIA from subcellular fractions containing synaptosomes from the chick cerebellum as a model system.

Animals↗

Automated measurement of serum thyroxine with the "ARIA II," as compared with competitive protein binding and radioimmunoassay.

Two conventional serum thyroxine assays, run in separate laboratories, one by competitive protein binding and one by radioimmunoassay, were used to evaluate the automated ARIA II (Becton Dickinson Immunodiagnostics) serum thyroxine assay. Competitive protein binding as compared to ARIA II with 111 clinical serum samples gave a slope of 1.04 and a correlation coefficient of 0.94. The radioimmunoassay comparison to ARIA II with 53 clinical serum samples gave a slope of 1.05 and a correlation coefficient of 0.92. The ARIA II inter-assay coefficient of variation for 10 replicates of low, medium, and high thyroxine serum samples was 6.2, 6.0, and 2.9%, respectively, with an inter-assay coefficient of variation among 15 different assays of 15.5, 10.1, and 7.9%. The automated ARIA II, with a 2.2-min cycle per sample, gives results that compare well with those by manual methodology.

Antibody Specificity↗

Arias-Stella reaction in a cervicovaginal smear of a woman undergoing infertility treatment: a case report.

Arias-Stella reaction commonly is seen in gestational endometrium, but rarely is described outside the endometrium, particularly in nonpregnant women. Although the cytological diagnoses of Arias-Stella reaction by cervical Papanicolaou (Pap) smears in pregnant, postpartum, and postabortal women are documented, to our knowledge, this is the first report of Arias-Stella reaction in a cervicovaginal smear of a nonpregnant woman undergoing infertility treatment with clomiphene and beta-human chorionic gonadotropin (beta-HCG). The cytological features observed in this case were characteristic of Arias-Stella reaction but mimic malignancy leading to initial misinterpretation. It is of paramount importance to recognize this phenomenon in cervical Pap smears, especially in women receiving ovulation-inducing agents and exogenous hormonal treatment to avoid this potential cytological pitfall.

Adenocarcinoma↗

Pharmacologic and anti-IgE treatment of allergic rhinitis ARIA update (in collaboration with GA2LEN).

The pharmacologic treatment of allergic rhinitis proposed by ARIA is an evidence-based and step-wise approach based on the classification of the symptoms. The ARIA workshop, held in December 1999, published a report in 2001 and new information has subsequently been published. The initial ARIA document lacked some important information on several issues. This document updates the ARIA sections on the pharmacologic and anti-IgE treatments of allergic rhinitis. Literature published between January 2000 and December 2004 has been included. Only a few studies assessing nasal and non-nasal symptoms are presented as these will be discussed in a separate document.

Animals↗

Evaluation of an automated radioimmunoassay system: the ARIA II.

The ARIA II is an automated instrument for the quantitation by radioimmunoassay of the following constituents: digoxin, cortisol, thyroxine, T3 uptake, T3 RIA, estriol, and progesterone, its methodology uses a specific antibody covalently bonded to a solid support in a reusable antibody chamber. We evaluated the assay system for the first three constituents listed above. Coefficients of correlation with conventional manual methods were: thyroxine-0.9797; digoxin-0.9871; and cortisol-0.9727. Inter-assay variations using a commercially available tri-level control serum were as follows: thyroxine-5.4 to 10.3%; digoxin-3.7 to 6.3%; cortisol-5.2 to 8.4%. The ARIA II is not a discrete analyzer, and an estimate of carryover was significant only on low-to-high for the thyroxine assay. ARIA II assays are approximately one-half the cost of manual assays. Time studies indicate the ARIA II to be most suited to laboratories of low or moderate volume.

Autoanalysis↗

Arias-Stella reaction associated with cervical pregnancy. Report of a case with a cytologic presentation.

We report the case of an Arias-Stella reaction of the cervix presenting in the cervical smear from a 35-year-old woman who complained of heavy menstrual periods. The smear was originally reported as inconclusive. Colposcopy revealed an abnormal transformation zone extending out of range. Cervical conization was performed. Histologic examination revealed an ectopic cervical pregnancy associated with a cervical Arias-Stella reaction. The cytologic manifestations of the Arias-Stella reaction continue to cause diagnostic confusion with benign lesions and adenocarcinoma. We believe this to be the first reported case of a cervical Arias-Stella reaction associated with a cervical pregnancy; it should alert cytologists to the diagnostic implications.

Adenocarcinoma↗

Quantifying niche overlap and transgression in allopolyploid hybrids: Case study of Sorbus subgenus Aria.

BACKGROUND AND AIMS: Apomixis, the formation of seeds without recombination, facilitates adaptation and persistence under environmental change. By preserving hybrid genotypes over long time periods, apomixis may conserve adaptive trait combinations from parental niche margins. We tested whether apomictic entities occupy intermediate, marginal, or transgressive niche space relative to their parents and whether differentiation is associated with ploidy. METHODS: We studied polyploid Sorbus subgenus Aria in the Franconian Jura (Germany), comprising two progenitors Sorbus aria and S. collina, seven triploid entities, and a pool of genetically heterogenous individuals (single genotypes). Genetic structure was assessed using MIG-seq. Overall niche differentiation between parental taxa and hybrids was evaluated using Sørensen similarity of two-dimensional hypervolumes derived from principal component analysis (PCA) axes. Niche shifts were further analyzed using hypervolumes based on the three strongest PCA variables. Across 762 occurrences, observations ranged from 11 to 453 individuals per entity. KEY RESULTS: Environmental niche space was transgressive in three, significantly allocated towards the margins of parental niche space in one, while remaining intermediate in the other entities. Niche transgression occurred towards milder temperatures and drier conditions. Genetic analyses confirmed morphologically defined entities, although one morphotype was polyphyletic. Tetraploid S. collina significantly occupied warmer and wetter environments compared to other cytotypes. Triploids differed from S. aria along microtopographic gradients represented by the second PCA axis. CONCLUSIONS: Apomictic Sorbus entities show diverse strategies in niche occupation and can occupy environmental niche space at and beyond the limits of their parental taxa. Apomicts may conserve evolutionary adaptations at the edges of parental niche space that may otherwise be lost from, or fail to emerge in, the parental gene pool. Over long timescales these trait combinations may re-enter the parental gene pool through introgression, thereby reintroducing adaptations critical for survival under changing conditions.

Aria↗

"Arias-Stella reaction"-like changes in endocervical glandular epithelium in cervical smears during pregnancy and postpartum states--a potential diagnostic pitfall.

A wide spectrum of histologic changes has been described throughout the female genital tract during pregnancy and in the postpartum period. Of these, the endometrial glandular changes referred to as the Arias-Stella reaction have classically been a diagnostic pitfall in histologic sections. Pregnancy-related changes are also reflected in cytologic material obtained from the cervix and vagina. Both glandular and stromal alterations may be seen. The changes involving endocervical glandular epithelium are often alarming enough to cause diagnostic difficulties, especially when the history of pregnancy is not provided. We report 13 cases where marked glandular changes led to diagnostic misinterpretations. These were characterized by cyto- and karyomegaly, a high nuclear to cytoplasmic ratio, round to oval nuclei with smudgy chromatin imparting a ground glass appearance, frequent intranuclear inclusions, and vacuolated to dense variable cytoplasm. The cytologic diagnoses ranged from "glandular atypia" to "suspicious for adenocarcinoma." Follow-up was available in 11/13 cases. In 9/11 cases, subsequent cervical smears on multiple occasions were negative. Cervical biopsies and/or dilatation and curettage in 4/11 cases did not show significant glandular abnormalities. The glandular changes encountered in cytologic material were similar to those described histologically in the Arias-Stella reaction involving the cervix. This similarity and the fact that these changes disappeared upon termination of the pregnancy favors the presumption that they represent the Arias-Stella reaction. Awareness of these changes during pregnancy and postpartum may prevent interpretive errors and unnecessary surgical procedures.

Adolescent↗

Truncated form of pro-acetylcholine receptor-inducing activity (ARIA) induces AChR alpha-subunit but not AChE transcripts in cultured chick myotubes.

Acetylcholine receptor-inducing activity (ARIA) is a glycoprotein initially purified from chick brain based on its ability to increase the synthesis of acetylcholine receptor (AChR). We used reverse transcription-polymerase chain reaction (RT-PCR) to obtain a partial pro-ARIA cDNA clone from methonine-1 to serine-358 including the full functional sequence of ARIA. Northern blot analysis of mRNAs from the embryonic chick brain and muscle showed a transcript with a size of approximately 7.5 kb. The cloned cDNA was subcloned into an eukaryotic expression vector and stably transfected into human embryonic kidney 293 cells. The conditioned medium of the transfected cells was found to increase the level of transcript encoding for the alpha-subunit of AChR by approximately 4.4-fold, but not for acetylcholinesterase (AChE), in the cultured chick myotubes.

Acetylcholinesterase↗

Validation of the classification of ARIA (allergic rhinitis and its impact on asthma).

BACKGROUND: Allergic rhinitis is commonly divided into seasonal and perennial rhinitis. The recent Allergic Rhinitis and its Impact on Asthma (ARIA) workshop proposes to replace these terms by intermittent vs persistent rhinitis. METHODS: In order to test the new ARIA classification against the classical one used in medical practice in France, we designed two cross-sectional surveys: (i) a spring survey, where 1321 general practitioners enrolled 3026 patients consulting for seasonal allergic rhinitis and (ii) an autumn-winter survey, where 1346 doctors enrolled 3507 patients for perennial allergic rhinitis. Both doctors and patients filled out a specific questionnaire on allergic rhinitis. RESULTS: Focusing on the number of days per week and consecutive weeks per year, the patients described the duration of their symptoms (based on an auto-questionnaire). About 43.7% of the patients, classified by their doctor as seasonal, did in fact have persistent rhinitis, whereas 44.6% classified as perennial had intermittent rhinitis. CONCLUSIONS: The proposal of the ARIA expert panel defining the chronology of allergic rhinitis as number of days per week and consecutive weeks per year is likely to change daily physician practice.

Adult↗

Arias-Stella reaction in an adenomyomatous polyp of the uterus.

We describe a rare case of an Arias-Stella reaction in an adenomyomatous polyp of the endometrium found in the first trimester of pregnancy. A 33-year-old Japanese woman, gravida 1, para 1, presented for an initial prenatal examination at 6-week gestation; ultrasound revealed a myoma-like solid mass in the cervical canal. An abnormal Papanicolaou's smear (highly suspicious of adenocarcinoma) prompted the resection of this pedunculated polyp. Histologically, the musculature located in the center of the polyp was covered by the endometrium; numerous glands within both the endometrium and the musculature exhibited an Arias-Stella reaction. This explains the result of Papanicolaou's smear, because subsequent smears - both intrapartum and postpartum - were negative. To our knowledge, this is the first reported incident of an Arias-Stella reaction in an adenomyomatous polyp. This could be one of the diagnostic pitfalls in Papanicolaou's smears taken during pregnancy.

Adenocarcinoma↗

Arias-Stella reaction in fallopian tube epithelium. A light and electron microscopic study with a review of the literature.

Most pathologists are familiar with the Arias-Stella reaction in the endometrium, because it is seen in approximately 25% of curettage specimens during early pregnancy. However, the Arias-Stella reaction is exceedingly rare in the fallopian tube, and may be confused with herpetic infection or malignancy. This may result in unnecessary therapy. The authors present a case of Arias-Stella reaction in the fallopian tube and discuss the differential diagnosis of this condition.

Adult↗

ARIA: a neuromuscular junction neuregulin.

Motor neurons influence the expression and the distribution of acetylcholine receptors in skeletal muscle. Molecules that mediate this carefully choreographed interaction have recently been identified. One of them, ARIA, is a polypeptide purified from chicken brain on the basis of its ability to stimulate the synthesis of muscle acetylcholine receptors. The predicted amino acid sequence suggests that ARIA is synthesized as a transmembrane precursor protein and that it is a member of a family of ligands that activate receptor tyrosine kinases related to the epidermal growth factor receptor. Certain features of the ligand family (the neuregulins) and their receptors (erbBs) are reviewed. Evidence that ARIA plays an important role at developing and mature neuromuscularjunctions is discussed.

Animals↗

Arias-Stella atypia in a paratubal cyst: a rare phenomenon with potential diagnostic pitfalls.

BACKGROUND: Arias-Stella reaction is commonly encountered in the endometrium during the gestational period and puerperium. Similar changes in the tubal epithelium are exceedingly rare. The cytologic findings of this phenomenon have never been described before. CASE: Cytologic findings of Arias-Stella changes in the lining cells of a left paratubal cyst in a 41-year-old woman were examined. The smears showed occasional small clusters or isolated tubal epithelial cells consisting of a mixture of ciliated and secretory cells. Some of the ciliated cells showed a marked increase in nuclear and cytoplasmic volume and possessed coarse chromatin, prominent, angulated nucleoli, dense, amphophilic cytoplasm; and a discrete cell membrane. The nuclear membrane was still thin and regular, and these cells were mitotically inactive. The preservation of apical cilia in some of them ensured their benign nature. In some areas, clusters of secretory cells with an increase in both nuclear and cytoplasmic volume and ample, clear cytoplasm were also found. There were small, monolayered sheets of regular and benign-looking epithelial cells with a honeycomb arrangement, suggesting that the Arias-Stella atypia was focal. CONCLUSION: In view of the presence of scattered giant cells with coarse chromatin and angulated macronucleoli, a false positive cytologic diagnosis of malignancy can be made if one does not pay attention to the coexistence of apical cilia and other subtle changes, including the usual nuclear/cytoplasmic ratio, thin and regular nuclear membrane and absence of mitotic activity.

Adult↗

Cellular characteristics of Arias-Stella reaction in ectopic pregnancy. Immunocytochemical studies with epithelial membrane antigen and vimentin.

OBJECTIVE: Endometrial cytology in nine cases of ectopic pregnancy was examined in order to elucidate the cellular characteristics of the Arias-Stella reaction and decidual change. STUDY DESIGN: The cellular findings of epithelial and stromal cells were compared with histologic findings in each case. Furthermore, the immunocytochemical reactivity of each type of cell cluster-epithelial cells without atypia, epithelial cells with atypia, deep stromal cells and sheetlike stromal cells-to epithelial membrane antigen (EMA) or vimentin was investigated and compared with cytologic findings in smears stained with Papanicolaou stain. RESULTS: The distribution of each type of cell cluster correlated fairly well with the histologic findings on the endometrium. Immunocytochemical examination revealed that EMA expression coincided with cell origin identified by Papanicolaou stain. Epithelial cells with atypia, probably corresponding to the Arias-Stella reaction, frequently showed positive reactivity to antivimentin antibody as well as anti-EMA antibody. Endometrial stromal cells usually indicated negative reactivity to anti-EMA antibody. Deep stromal cells expressed vimentin, but sheetlike stromal cells, thought to be decidual cells, infrequently expressed vimentin. CONCLUSION: The Arias-Stella reaction may be the result of the regenerating and proliferating activity of endometrial glands. It is still controversial whether sheet-like stromal cells are identical to decidual cells.

Antibody Specificity↗

NOE assignment with ARIA 2.0: the nuts and bolts.

The assignment of nuclear Overhauser effect (NOE) resonances is the crucial step in determining the three-dimensional structure of biomolecules from nuclear magnetic resonance (NMR) data. Our program, Ambiguous Restraints for Iterative Assignment (ARIA), treats Noe assignment as an integral part of the structure determination process. This chapter briefly outlines the method and discusses how to carry out a complete structure determination project with the new version 2.0 of ARIA. Two new features greatly streamline the procedure: a new graphical user interface (GUI) and the incorporation of the data model of the Collaborative Computing Project for the NMR community (CCPN). The GUI supports the user in setting up and managing a project. The CCPN data model facilitates data exchange with a great variety of other programs. We give practical guidelines for how to use ARIA and how to analyze results.

Calibration↗

[Allergic Rhinitis and its Impact on Asthma (ARIA) in Latin America].

Allergic rhinitis is the commonest chronic respiratory disorder in children and young adults having an important impact for those suffering this condition, as well as for the public health. Allergic rhinitis is frequently associated to other co-morbidities, particularly asthma and conjunctivitis but, also, sinusitis and otitis media. Most of patients suffering rhinitis are cared by GPs and pediatricians and there are evidences that allergic rhinitis is undertreated, particularly the moderate/severe persistent forms. Clinical guidelines have become an important tool providing recommendations for diagnosis and treatment of different medical conditions. They help the process of decision making for GPs and pediatricians, and many of them, contain an update on basic science and epidemiology. In respiratory medicine, guidelines on asthma and rhinitis are available; however, they do not look at the patients globally and focus the disorder on an organ-specific basis without recommendations on co-morbidities. ARIA, Allergic rhinitis and its impact on asthma, has not been developed only to update specialists in allergy/immunology, otorhinolaryngology and neumology on rhinitis and its comorbidities but, also, to provide recommendations for non-specialists. A new classification and severity of allergic rhinitis is proposed replacing the classic perennial and seasonal forms for persistent and intermittent, mild to moderate/severe. ARIA is an initiative in collaboration with the World Health Organization and the master document has been endorsed by many national and international scientific societies and organizations. ARIA is an evidence-based document also stressing on pediatric aspects and providing recommendations for low-income countries.

Algorithms↗