Mucosal immunity: The origin and migration patterns of cells in the secretory system.
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PURPOSE: To describe and characterize the primary lacrimal sac epithelial tumors of glandular origin, and to describe their possible source from glands in the lacrimal sac and nasolacrimal duct walls. METHODS: The authors conducted a clinicopathologic study on 14 patients with epithelial lacrimal sac tumors of possible glandular origin. In addition, they reviewed 35 surgical specimens of the lacrimal sac and nasolacrimal duct region and 13 cadaver specimens of the lacrimal sac region. RESULTS: Six of the tumors were benign: four were oncocytomas and two were pleomorphic adenomas. Eight of the tumors were malignant: three were oncocytic adenocarcinomas, three were adenoid cystic carcinomas, and two were adenocarcinomas. All tumors were from adults, ranging in age from 38 to 87 years. Twenty-eight of the 47 specimens of lacrimal sac and nasolacrimal duct region showed mixed glands of serous and mucous elements. CONCLUSIONS: Although rare, benign and malignant glandular lacrimal sac tumors should be considered in the differential diagnosis of lacrimal sac obstruction. Their possible origin is from the normal glands that exist under the lacrimal sac and nasolacrimal duct epithelium.
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Most animals that display a bilateral symmetry (bilaterians) share homologous regulatory genes involved in head development. Recently, homologues of several of these genes have been cloned from animals that are radially organized, such as coral, sea anemones, jellyfish or hydra (cnidarians). Surprisingly, some of these are expressed apically and/or during apical patterning in hydrozoans, suggesting that head patterning is much older than previously thought.
The gain, loss or modification of morphological traits is generally associated with changes in gene regulation during development. However, the molecular bases underlying these evolutionary changes have remained elusive. Here we identify one of the molecular mechanisms that contributes to the evolutionary gain of a male-specific wing pigmentation spot in Drosophila biarmipes, a species closely related to Drosophila melanogaster. We show that the evolution of this spot involved modifications of an ancestral cis-regulatory element of the yellow pigmentation gene. This element has gained multiple binding sites for transcription factors that are deeply conserved components of the regulatory landscape controlling wing development, including the selector protein Engrailed. The evolutionary stability of components of regulatory landscapes, which can be co-opted by chance mutations in cis-regulatory elements, might explain the repeated evolution of similar morphological patterns, such as wing pigmentation patterns in flies.
The MCM2-7 complex is believed to function as the eukaryotic replicative DNA helicase. It is recruited to chromatin by the origin recognition complex (ORC), Cdc6, and Cdt1, and it is activated at the G(1)/S transition by Cdc45 and the protein kinases Cdc7 and Cdk2. Paradoxically, the number of chromatin-bound MCM complexes greatly exceeds the number of bound ORC complexes. To understand how the high MCM2-7:ORC ratio comes about, we examined the binding of these proteins to immobilized linear DNA fragments in Xenopus egg extracts. The minimum length of DNA required to recruit ORC and MCM2-7 was approximately 80 bp, and the MCM2-7:ORC ratio on this fragment was approximately 1:1. With longer DNA fragments, the MCM2-7:ORC ratio increased dramatically, indicating that MCM complexes normally become distributed over a large region of DNA surrounding ORC. Only a small subset of the chromatin-bound MCM2-7 complexes recruited Cdc45 at the onset of DNA replication, and unlike Cdc45, MCM2-7 was not limiting for DNA replication. However, all the chromatin-bound MCM complexes may be functional, because they were phosphorylated in a Cdc7-dependent fashion, and because they could be induced to support Cdk2-dependent Cdc45 loading. The data suggest that in Xenopus egg extracts, origins of replication contain multiple, distributed, initiation-competent MCM2-7 complexes.
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All chordates share a basic body plan and many common features of early development. Anteroposterior (AP) regions of the vertebrate neural tube are specified by a combinatorial pattern of Hox gene expression that is conserved in urochordates and cephalochordates. Another primitive feature of Hox gene regulation in all chordates is a sensitivity to retinoic acid during embryogenesis, and recent developmental genetic studies have demonstrated the essential role for retinoid signalling in vertebrates. Two AP regions develop within the chordate neural tube during gastrulation: an anterior 'forebrain-midbrain' region specified by Otx genes and a posterior 'hindbrain-spinal cord' region specified by Hox genes. A third, intermediate region corresponding to the midbrain or midbrain-hindbrain boundary develops at around the same time in vertebrates, and comparative data suggest that this was also present in the chordate ancestor. Within the anterior part of the Hox-expressing domain, however, vertebrates appear to have evolved unique roles for segmentation genes, such as Krox-20, in patterning the hindbrain. Genetic approaches in mammals and zebrafish, coupled with molecular phylogenetic studies in ascidians, amphioxus and lampreys, promise to reveal how the complex mechanisms that specify the vertebrate body plan may have arisen from a relatively simple set of ancestral developmental components.
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As a result of an experiment in which the development of a mineral phase in the rabbit embryo was observed, a model is proposed to explain the mechanism that controls the place of precipitation of crystals in mineralizing tissue. The reaction-diffusion equations for the specified compounds are formulated and solved. Among a variety of compounds the concentrations of carbon dioxide, oxygen, HCO-3 ions, H+ ions, calcium, and inorganic phosphorus are evaluated. CO2, HCO-3 ions, and H+ ions, are distinguished due to their key role in the maintenance of the pH value. The local concentration of oxygen is the pivot factor that controls the metabolic rate, i.e., production of CO2. Next the supersaturation was estimated on the basis of the calculated values of pH and the concentrations of calcium and inorganic phosphorus. It is assumed that the synthesis of the organic matrix breaks the metastable equilibrium with respect to spontaneous precipitation and leads to the deposition of minerals. It was found that the geometry of the vasculature determines the shape of primitive trabecular bone (woven bone) while the value of the diffusion coefficient may be the key factor indicating the possibility of mineralization under the control of a living organism.
Using immunofluorescence microscopy, we observed that in several established cell culture lines derived from different nonepithelial tissues and species, cells spontaneously emerge, usually at low frequencies, which contain cytoplasmic structures decorated by antibodies specific for cytokeratins 8 and 18. This phenomenon was further examined at both the protein (gel electrophoreses of cytoskeletal proteins, followed by immunoblotting) and the RNA (Northern blots, "nuclear run-on" analysis, in situ hybridization) level. Positive cell lines included simian virus (SV40)-transformed human fibroblasts (HF-SV80, WI-38 VA13), human astrocytic glioma cells (U333 CG/343MG), rat (RVF-SMC) and hamster (BHK-21/13) cells derived from vascular smooth muscle and murine sarcoma MS-180 cells. In two cell lines (HF-SV80 and BHK-21/13), the frequency of the cytokeratin-containing cells and of the cytokeratin fibril arrays per cell was drastically increased upon treatment with 5-azacytidine. The structural appearance of the cytokeratins was variable in the different cell lines but could also differ among cells of the same culture: While small granular or comma-shaped structures or bizarrely shaped filament arrays prevailed in WI-38, RVF and normally grown BHK-21 cells, most of the other lines revealed extended normal-looking, fibrillar arrays. In one line (MS-180), the appearance of cytokeratins was associated with a morphological change, as it was only found in a subpopulation of cells that had lost their typical elongated and spindle-shaped phenotype and assumed a rounded ("coccoid") shape. Our results show that the expression of the genes encoding cytokeratins 8 and 18 is not necessarily restricted to programs of epithelial differentiation and that factors stochastically effective appear in cultured cell lines that allow the synthesis of these cytoskeletal components. Mechanisms possibly involved in this spontaneous and selective advent of cytokeratins 8 and 18 and implications for tumor diagnosis are discussed.
OBJECTIVE: To assess the prevalence and patterns of congenital heart defects in infants requiring hospital admission in a defined population and to determine the differences in ethnic groups. DESIGN: A three year retrospective analysis of all hospital admissions for paediatric congenital heart defects in a single centre. SETTING: Tertiary referral centre for infant cardiac services in the West Midlands region, United Kingdom. PATIENTS AND METHODS: Indian, Pakistani, Bangladeshi and other individuals from the Indian subcontinent constitute 5.8% of the total population of the West Midlands region. Some 9% of infants, however, are Asian because of a high birth rate. All infants with confirmed congenital heart defects resident in this region who required hospital admission between April 1990 and March 1993 were classified as Asians and non-Asian, mainly white, infants. RESULTS: Of 1111 infants with congenital heart defects born in the West Midlands and admitted to the hospital, 17.0% were Asian, significantly more than the percentage of Asian infants in the population (P < 0.0001). Asian infants had a higher proportion of complex congenital heart disease (7% v 2.1%, P < 0.001), whereas coarctation of the aorta was more common in non-Asian (3% v 9.1%, P = 0.003). Persistent arterial duct seemed to be more common in Asian children (16% v 10%, NS), but this group included preterm infants admitted for duct ligation. There was no significant difference between the two groups in the other nine categories of congenital heart defects. CONCLUSIONS: The estimated prevalence of congenital heart defects requiring hospital admission was higher in Asian infants than in non-Asian (9.45 per 1000 v 4.56 per 1000, P < 0.0001). Complex congenital heart defects were more common in Asian infants whereas coarctation of the aorta was more common in non-Asian.
Microsurgical anatomy for the pterional approach was studied regarding the origin and the course of the ophthalmic artery and the distal dural ring using human cadaveric specimens, with special reference to the surrounding bony structures. In 50 human adult formalin-fixed cadaveric cerebral hemispheres and 10 block specimens of the skull base region including the ophthalmic artery and the carotid dural ring were examined under magnification using an operating microscope. The ophthalmic artery originated from the intradural portion of the internal carotid artery (ICA), except in 5% where the ophthalmic artery originated extradurally. The extradural origin had two patterns: one was that the ophthalmic artery penetrated the bony optic strut (trans-optic strut pattern) and the other was that it coursed into the optic canal proximally to the optic strut without bone penetration (supra-optic strut pattern). The origin of the intradural ophthalmic artery was commonly located at the medial third of the superior wall of the ICA (78%). The ophthalmic artery was commonly taking an S-shaped course in the intradural portion and entered the optic canal over the optic strut. The distal dural ring was tightly adherent to the internal carotid artery; circumferential sectioning of the dural ring is required to mobilize the internal carotid artery. When approaching juxtadural ring ICA aneurysms via the pterional route, it is important to recognize the extradural origin, especially the trans-optic strut type, and to precisely understand the microsurgical anatomy around the dural ring.
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Bilateral symmetry is a hallmark of the Bilateria. It is achieved by the intersection of two orthogonal axes of polarity: the anterior-posterior (A-P) axis and the dorsal-ventral (D-V) axis. It is widely thought that bilateral symmetry evolved in the common ancestor of the Bilateria. However, it has long been known that members of the phylum Cnidaria, an outgroup to the Bilateria, also exhibit bilateral symmetry. Recent studies have examined the developmental expression of axial patterning genes in members of the phylum Cnidaria. Hox genes play a conserved role in patterning the A-P axis of bilaterians. Hox genes are expressed in staggered axial domains along the oral-aboral axis of cnidarians, suggesting that Hox patterning of the primary body axis was already present in the cnidarian-bilaterian ancestor. Dpp plays a conserved role patterning the D-V axis of bilaterians. Asymmetric expression of dpp about the directive axis of cnidarians implies that this patterning system is similarly ancient. Taken together, these result imply that bilateral symmetry had already evolved before the Cnidaria diverged from the Bilateria.
Male white rats divided in three groups on the basis of their behavior in the elevated plus-maze were subjected to 10-min cardiac arrest. Analysis of the results of their subsequent food and active avoidance conditioning revealed the effects of the following factors: (1) a factor of initial typological features of the higher nervous activity, (2) a factor of general brain mechanisms of postresuscitation, and (3) a factor of postresuscitation features in rats with different behaviors, which represented changes in different mechanisms of conditioned reflex performance in these animals.
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