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At least 469 records · Page 26Linked to original sources

Value of fine needle aspiration biopsy of salivary gland masses in clinical decision-making.

The accuracy of fine needle aspiration biopsy (FNAB) in the diagnosis of salivary tumors has been well established. This study was undertaken to determine the impact of FNAB on patient management. One hundred one patients underwent FNAB of major salivary gland masses. The physician's initial clinical impression was compared with the FNAB diagnosis and the final diagnosis in each case. Forty patients had solitary masses thought to be benign tumors other than Warthin's tumors. FNAB in 13 of these patients (33%) yielded a diagnosis permitting modification of the planned procedure. The diagnosis of Warthin's tumor was suspected clinically in 23 patients. In nine of these patients (39%), FNAB resulted in a different diagnosis. Of the 10 patients believed to have malignant tumors, using FNAB, 1 was found to have sialadenitis and 1 a lymphoma. Overall, FNAB resulted in a change in the clinical approach to 35% of the patients. We recommend the performance of FNAB in almost all patients with salivary masses.

Adenolymphoma↗

Phylogeny of New World arenaviruses based on the complete coding sequences of the small genomic segment identified an evolutionary lineage produced by intrasegmental recombination.

Previous studies suggested that the small genomic segments (S-RNA) of the South American arenaviruses (SA-AVs) represent three phylogenetic lineages (designated A, B, and C) and indicated that the S-RNA of Whitewater Arroyo virus (WWAV) (a North American arenavirus [NA-AV]) is a product of genetic recombination between a lineage A and lineage B virus. The purpose of this study was to extend our knowledge on the phylogenetic relationships between WWAV, the two other NA-AVs (Tamiami and bear canyon), and the 15 SA-AVs. Therefore, we determined the complete sequence of the S-RNA of nine arenaviruses previously uncharacterized or sequenced only partially. Phylogenetic analyses of the two complete coding regions indicated that the S-RNA of the three NA-AVs have descended from a single ancestral virus, which was the product of recombination between a lineage A and lineage B arenavirus. No such evidence for genetic recombination was found in cupixi virus (a novel arenavirus isolated from a wild rodent captured in Northeastern Brazil) or the 14 other SA-AVs. The recombinant nature of the S-RNA of NA-AVs distinguishes them from the SA-AVs, and thus, indicates that the NA-AVs represent a fourth phylogenetic lineage in the Tacaribe serocomplex.

Amino Acid Sequence↗

Lovastatin and phospholipase Cgamma regulate constitutive and protein kinase C dependent integrin mediated interactions of human T-cells with collagen.

We previously reported that human interleukin (IL)-2 dependent T cell lines derived from very late antigen (VLA)-1(+) CD45RO(+) peripheral blood (PB) T-cells adhere constitutively to collagen type IV, whereas lines from VLA-1(-) PB lymphocytes (L) adhere weakly. Here we report that the latter are induced to adhere by phorbol 12-myristate 13-acetate (PMA). Both PMA dependent and constitutive adhesion, including that of a Herpes Virus Saimiri (HVS) infected CD4(+)VLA-1(+) clone (HVST) were inhibited by anti-VLA-1 monoclonal antibodies (mAb), by inhibitors of phospholipase C (PLC)gamma and by lovastatin but not by a MEK1 inhibitor, whereas only PMA induced adhesion was blocked by inhibition of protein-kinase (PK) C. Furthermore, lovastatin enhanced PLCgamma and anti VLA-1 mAb blockade, and its effect was not reversed by mevalonic acid (MVA). Lovastatin also inhibited interferon (IFN)gamma secretion by T cells triggered with anti-CD3 and in cells detaching from collagen IV. These results suggest new ways for functional modulation of activated T-cells interacting with collagen.

Cell Adhesion↗

Pharmacological characterisation of the beta-adrenoceptor expressed by human lung mast cells.

The nonselective beta-adrenoceptor agonist, isoprenaline (pD2; 8.8 +/- 0.2), and selective beta2-adrenoceptor agonists, clenbuterol (9.2 +/- 0.4) and salbutamol (7.1 +/- 0.1), inhibited the immunoglobulin E-mediated release of histamine from human lung mast cells in a concentration-dependent manner. The beta2-adrenoceptor-selective antagonist, ICI118551 (erythro-(+/- )-1-(7-methylindan-4-yloyl)-3-isopropylaminobutan-2-ol HCl), antagonised the isoprenaline inhibition of histamine release from human lung mast cells with high affinity (apparent pK(B); 9.5 +/- 0.2), whereas high concentrations of the beta1-adrenoceptor-selective antagonist, CGP20712A (2-hydroxy-5-(2-(hydroxy-3-(4((1-methyl-4-trifluoromethyl)-1-H-imidazol-2-yl)-phenoxy)-propyl)-aminoethoxyl)-benzamide), were required to reverse the isoprenaline inhibition (apparent pK(B); 6.5 +/- 0.3). Radioligand binding studies using [125I]-iodocyanopindolol ([125I]CYP) were performed on membranes derived from purified mast cells (>90% purity). Binding of [125I]CYP to mast cell membranes was displaced from a single binding site with a high affinity for ICI118551 (pK(i); 8.9 +/- 0.1) and low affinity for CGP20712A (pK(i); 6.0 +/- 0.03), indicative of a homogeneous population of beta2-adrenoceptors. In contrast, in human lung membranes, these antagonists displaced [125I]CYP from two sites indicative of a heterogeneous population of beta1-adrenoceptors (20%) and beta2-adrenoceptors (80%). These data indicate that the beta-adrenoceptor expressed by human lung mast cells and mediating inhibition of mediator release from these cells is the beta2-adrenoceptor.

Adrenergic beta-Agonists↗

Behavioral consequences of congenital rubella.

Psychiatric and behavioral consequences of congenital rubella are reported for 243 children studies during the preschool period, and for 205 of these who were re-examined at ages 8 to 9. At preschool 37% were retarded, with the skew toward severe and profound; 15% had reactive behavior disorder and 7% had autism. At school age retardation diminished to 25%, but neurotic problems and behavioral pathology due to neurologic damage both increased. There were two remissions and three new instances of autism.

Autistic Disorder↗

Temperament of asthmatic children. A preliminary study.

The temperamental profile of a group of 12 asthmatic children between 3 and 7 years of age was compared to those of two comparison groups, each consisting of 12 normal well children and 12 children of the same age range with chronic eczema, allergic rhinitis, or both, but without asthma. The children with asthma differed significantly from the comparison groups in their temperamental profile, which was characterized by lower rhythmicity (reguluarity), lower adaptability, lower intensity of reaction, lower mood value, and lower persistence. The results indicate the need for further longitudinal studies of large populations of children with asthma to explore the implications and behavioral consequences of "the asthma temperament, and its interaction with other developmental factors.

Asthma↗

Urothelium derived inhibitory factor and cross-talk among receptors in the trigone of the bladder of the pig.

PURPOSE: In the dome of the bladder of the pig muscarinic receptor stimulation has been shown to release a factor from the urothelium that exerts an inhibitory effect on the underlying smooth muscle. We examined whether the urothelium in the trigone of the bladder also releases this factor, identified which receptors stimulate its release and investigated possible cross-talk among these receptor systems in the trigone. MATERIALS AND METHODS: Paired longitudinal strips of pig bladder were isolated, the urothelium was removed from 1 strip per pair and tissues were set up in gassed Krebs solution at 37C. Cumulative concentration-response curves to carbachol, phenylephrine or histamine were constructed. In some tissues a second phenylephrine curve was constructed in the presence of 1 microM. carbachol or 1 microM. histamine. In a further group of tissues the second phenylephrine curve was constructed in the presence of 1 microM. carbachol and 1 microM. atropine or 1 microM. histamine and 100 nM. mepyramine. RESULTS: In the presence of an intact urothelium contractile responses to carbachol and histamine but not to phenylephrine were depressed. In the presence of 1 microM. carbachol or 1 microM. histamine the responses of intact urothelium strips to phenylephrine were significantly depressed. This effect was absent in the presence of atropine and mepyramine, respectively. CONCLUSIONS: Carbachol and histamine induce the release of a urothelium derived inhibitory factor in the bladder trigone. The factor appears to mediate cross-talk between these systems and the alpha-adrenoceptor system in this region of the bladder.

Animals↗

Identification of beta-adrenoceptor subtypes in lower urinary tract of the female pig.

PURPOSE: We investigated the presence and functional role of beta-adrenoceptor subtypes in the bladder base and proximal urethra of the female pig. MATERIALS AND METHODS: Saturation experiments were done with 7 concentrations (0.25 to 16 nM.) of [(3)H]-dihydroalprenolol (NEN Life Science Products, Boston, Massachusetts). Competition experiments with [(3)H]-dihydroalprenolol were performed with unlabeled antagonists (beta1 selective CGP20712A, beta2 selective ICI118551 and beta3 selective SR59230A). In functional studies concentration-relaxation curves to the beta3-agonist BRL37344 were obtained and antagonist affinities for SR59230A were determined. RESULTS: CGP20712A displaced [(3)H]-dihydroalprenolol with low affinity, suggesting that beta1-adrenoceptors were not present. Displacement with ICI118551 in the bladder base and urethra best fitted a 2-site model with 20% and 28% high affinity sites (beta2), respectively. Displacement experiments with SR59230A in the bladder base demonstrated that 59% of binding sites had high affinity (beta3). In the urethra displacement with SR59230A best fitted a 1-site model but with a pK(i) of 7.2 that was intermediate between that expected for beta2 and beta3-adrenoceptors. In functional studies BRL37344 induced relaxation with pEC50 values of 5.5 and 8, and a maximum relaxation response relative to 30 microM. isoprenaline of 79% and 90% in the bladder base and urethra, respectively. The affinity value of SR59230A for the response to BRL37344 was 7.87 and 7.71 in the bladder base and urethra, respectively, which were intermediate between those of beta2 and beta3-adrenoceptors. CONCLUSIONS: Apparently beta3-adrenoceptors are the predominant beta-adrenoceptor subtype present in the lower urinary tract of the pig.

Adrenergic beta-Agonists↗

Evolutionary relationship between Old World West Nile virus strains. Evidence for viral gene flow between Africa, the Middle East, and Europe.

Little is known about the genetic relationships between European and other Old-World strains of West Nile virus (WNV) and persistence of WNV North of Mediterranean. We characterized the complete genomes of three WNV strains from France (horse-2000), Tunisia (human-1997) and Kenya (mosquito-1998), and the envelope, NS3 and NS5 genes of the Koutango virus. Phylogenetic analyses including all available full-length sequences showed that: (1) Koutango virus is a distant variant of WNV; (2) the three characterized strains belong to lineage 1, clade 1a; (3) the Tunisian strain roots the lineage of viruses introduced in North America. We established that currently available partial envelope sequences do not generate reliable phylogenies. Accordingly, establishing a large WNV sequence database is pivotal for the understanding of spatial and temporal epidemiology of this virus. For rapid completion of that purpose, colinearized E-NS3-NS5 gene sequences were shown to constitute a valuable surrogate for complete sequences.

Africa↗

Growth factors in lung development.

Organized and coordinated lung development follows transcriptional regulation of a complex set of cell-cell and cell-matrix interactions resulting in a blood-gas interface ready for physiologic gas exchange at birth. Transcription factors, growth factors, and various other signaling molecules regulate epithelial-mesenchymal interactions by paracrine and autocrine mechanisms. Transcriptional control at the earliest stages of lung development results in cell differentiation and cell commitment in the primitive lung bud, in essence setting up a framework for pattern formation and branching morphogenesis. Branching morphogenesis results in the formation of the conductive airway system, which is critical for alveolization. Lung development is influenced at all stages by spatial and temporal distribution of various signaling molecules and their receptors and also by the positive and negative control of signaling by paracrine, autocrine, and endocrine mechanisms. Lung bud formation, cell differentiation, and its interaction with the splanchnic mesoderm are regulated by HNF-3beta, Shh, Nkx2.1, HNF-3/Forkhead homolog-8 (HFH-8), Gli, and GATA transcription factors. HNF-3beta regulates Nkx2.1, a transcription factor critical to the formation of distal pulmonary structures. Nkx2.1 regulates surfactant protein genes that are important for the development of alveolar stability at birth. Shh, produced by the foregut endoderm, regulates lung morphogenesis signaling through Gli genes expressed in the mesenchyme. FGF10, produced by the mesoderm, regulates branching morphogenesis via its receptors on the lung epithelium. Alveolization and formation of the capillary network are influenced by various factors that include PDGF, vascular endothelial growth factor (VEGF), and retinoic acid. Epithelial-endothelial interactions during lung development are important in establishing a functional blood-gas interface. The effects of various growth factors on lung development have been demonstrated by gain- or loss-of-function studies in null mutant and transgenic mice models. Understanding the role of growth factors and various other signaling molecules and their cellular interactions in lung development will provide us with new insights into the pathogenesis of bronchopulmonary dysplasia and disorders of lung morphogenesis.

Gene Expression Regulation, Developmental↗

Muscarinic receptor subtypes and management of the overactive bladder.

Anticholinergic agents are the most widely used therapy for urge incontinence despite exerting adverse effects, such as constipation, tachycardia, and dry mouth, that limit their use. These adverse effects result from a lack of selectivity for the bladder over other organs. Although M2-muscarinic receptors are the predominant cholinoreceptor present in urinary bladder, the smaller population of M3-receptors appears to be the most functionally important and mediates direct contraction of the detrusor muscle. M2-receptors modulate detrusor contraction by several mechanisms and may contribute more to contraction of the bladder in pathologic states, such as bladder denervation or spinal cord injury. Prejunctional inhibitory M2-receptors or M4-receptors and prejunctional facilitatory M1-muscarinic receptors in the bladder have also been reported, but their relevance to the clinical effectiveness of muscarinic antagonists is unknown. In clinical studies, tolterodine, a nonselective muscarinic antagonist, has been reported to be equally effective to oxybutynin but to induce less dry mouth. Controlled-release and intravesical, intravaginal, and rectal administrations of oxybutynin have all been reported to cause fewer adverse effects. Conversely, darifenacin, a new M3-selective antagonist, has been reported to have selectivity for the bladder over the salivary gland in vivo. Whether M3-selective or nonselective muscarinic antagonists will be the most clinically effective for the overactive bladder-preserving the best balance between efficacy and tolerability-has yet to be established, and comparative clinical trials between compounds, such as darifenacin (M3 selective) and tolterodine (nonselective) will be required.

Cholinergic Antagonists↗

The isolation and nucleotide sequence of a cDNA encoding the T cell surface protein T4: a new member of the immunoglobulin gene family.

The surface glycoproteins T4 and T8 define different functional subsets of T lymphocytes and may act as recognition molecules mediating appropriate interactions between the T cell and its target. Previously we employed gene transfer and subtractive hybridization to isolate a T8 cDNA; now we have isolated and sequenced a cDNA clone encoding the T4 molecule. The deduced protein sequence reveals that T4 is an integral membrane protein that shares significant amino acid and structural homologies with members of the immunoglobulin supergene family. The overall structure of T4 consists of an N-terminal variable (V)-like domain, a joining (J)-like region, a third extracellular domain, a membrane-spanning region homologous to class II MHC beta-chains, and a highly charged cytoplasmic domain. Comparison of the protein sequences deduced from the T4 and T8 cDNAs reveals structural similarities consistent with their postulated role as recognition molecules, as well as differences suggesting that the two proteins recognize different structures on the target cell.

Amino Acid Sequence↗

Allelic inactivation regulates olfactory receptor gene expression.

We suggest a model in which a hierarchy of controls is exerted on the family of odorant receptor genes to assure that a sensory neuron expresses a single receptor from a family of 1000 genes. We propose that a cis-regulatory element directs the stochastic expression of only one gene from a large array of linked receptor genes. Moreover, only one allelic array encoding multiple receptor genes is active in an individual neuron. We demonstrate that in a neuron expressing a given receptor, expression derives exclusively from one allele. In addition, we observe that alleles encoding the odorant receptors are replicated asynchronously, a phenomenon consistently associated with allelic inactivation. This model, involving inactivation of one allelic array and cis control of the active array, provides a mechanism such that individual neurons express one or a small number of receptors.

Alleles↗