Immunohistochemical study of stromal and vascular components of tonsillar polyps: high endothelial venules as participants of the polyp`s lymphoid tissue

Tonsillar polyps are nonneoplastic lesions usually composed of variable amounts of lymphoid and vascular and connective tissues. All of them are generally assumed to be hamartomatous proliferations, but the profile of vascular and connective components has yet to be explored. The vascular system of the tonsils is complex and includes highly specialized structures (i.e., high endothelial venules (HEVs)) involved in lymphocyte homing into lymphoid tissues. In 14 tonsillar polyps and 26 control tonsils, an immunohistochemical study was performed using CD34 (blood vessels and HEVs), MECA-79 (HEVs), D2-40 (lymphatic vessels), Ki-67, collagens I and III, fibronectin, and tenascin-C. The polyps showed increased total lymphatic area, whereas the number of blood vessels and lymphatics and the blood vascular area did not differ significantly from those of control tonsils. Rare Ki-67+ endothelial cells were found. In the polyps, we detected, possibly for the first time, HEVs amid lymphoid tissue, and that the amount of the latter correlated positively with HEV density. The polyps also presented lesser amounts of fibronectin and collagens I and III than in normal tonsils, which were distributed in a disorganized fashion. Tenascin-C expression was uncommon in the polyps and control tonsils. Tonsillar polyps are composed of disorganized connective tissue and lymphatic channels which can be considered hamartomatous proliferations. However, the lymphoid component is possibly reactive due to its relationship with the HEVs. The highly differentiated phenotype of the HEVs and their complex biology are not in agreement with what would be expected for a component of hamartomatous nature.

Emerging technologies for the prevention of dental caries. Are current methods of prevention sufficient for the high risk patient?

Fluorides and chlorhexidine are technologies that are 65 and 40 years old, respectively. This overview argues that current methods of caries prevention are not effective for the high caries risk patient. In this review examples, arguments and recommendations are provided to address the high caries risk patient that include: failure of comprehensive chemical modalities treatments to address the high caries risk patient; ecological alteration - would this be an effective approach?; and biomaterials and oral microbiome research to address the high caries risk patient.

Inducible nitric oxide synthase-deficient mice show exacerbated inflammatory process and high production of both Th1 and Th2 cytokines during paracoccidioidomycosis

Paracoccidioidomycosis, the major systemic mycosis in Latin America, is caused by fungus Paracoccidioides brasiliensis. To analyze the influence of inducible nitric oxide synthase (iNOS) in this disease, iNOS-deficient (iNOS(-/-)) and wild-type (WT) mice were infected intravenously with P. brasiliensis 18 isolate. We found that, unlike WT mice, iNOS(-/-) mice did not control fungal proliferation, and began to succumb to infection by day 50 after inoculation of yeast cells. Typical inflammatory granulomas were found in WT mice, while, iNOS(-/-) mice presented incipient granulomas with intense inflammatory process and necrosis. Additionally, splenocytes from iNOS(-/-) mice did not produce nitric oxide, however, their proliferative response to Con-A was impaired, just like infected WT mice. Moreover, infected iNOS(-/-) mice presented a mixed pattern of immune response, releasing high levels of both Th1 (IL-12, IFN-gamma and TNF-alpha) and Th2 (IL-4 and IL-10) cytokines. These data suggest that the enzyme iNOS is a resistance factor during paracoccidioidomycosis by controlling fungal proliferation, by influencing cytokines production, and by appeasing the development of a high inflammatory response and consequently formation of necrosis. However, iNOS-derived nitric oxide seems not being the unique factor responsible for immunosuppression observed in infections caused by P. brasiliensis. (c) 2008 Elsevier Masson SAS. All rights reserved.

Ultrasonic Chemical Vapor Deposition-coated Tip versus High- and Low-speed Carbide Burs for Apicoectomy: Time Required for Resection and Scanning Electron Microscopy Analysis of the Root-end Surfaces

This study compared ultrasonic chemical vapor deposition (CVD)-coated tip (CVDentus #8.1117-1; Clorovale Diamantes Ind. e Com. Ltda Epp, Sao Jose dos Campos, SP, Brazil) versus high-speed (#FG700L) and low-speed (#699) carbide burs for apicoectomy, evaluating the time required for resection and analyzing the root-end surfaces by scanning electron microscopy. Thirty extracted human premolars had the canals instrumented and obturated and were randomly assigned to 3 groups (n = 10), according to the instrument used for root-end resection. The time required for resection of the apical 2 mm of each root was recorded. The resected apical segments were dried, sputter coated with gold, and examined with a scanning electron microscope at X 350 magnification. A four-point (0-3) scoring system was used to evaluate the apical surface smoothness. The results were analyzed statistically by the Kruskal-Wallis test and two-by-two comparisons analyses were performed using the Miller test. The significance level was set at 5%. Root-end resection with the high-speed bur was significantly faster (p < 0.05) compared with the low-speed bur and CVD tip. The carbide burs produced significantly smoother root-end surfaces than the CVD tip (p < 0.05). The low-speed bur produced the smoothest root-end surfaces, whereas the roughest and most irregular root ends (p < 0.05) were obtained with the CVD tip. However, no statistically significant difference (p > 0.05) was found between the high- and low-speed burs regarding the surface roughness of the resected root ends (p > 0.05). In conclusion, under the tested conditions, ultrasonic root-end resection took a longer time and resulted in rougher surfaces compared with the use of carbide burs at both high and low speed. (J Endod 2009;35:265-268)

A nanometre-scale non-periodic structural variation in high temperature superconducting ceramics and the implications for properties

Non-periodic structural variation has been found in the high T-c cuprates, YBa2Cu3O7-x and Hg0.67Pb0.33Ba2Ca2Cu3O8+delta, by image analysis of high resolution transmission electron microscope (HRTEM) images. We use two methods for analysis of the HRTEM images. The first method is a means for measuring the bending of lattice fringes at twin planes. The second method is a low-pass filter technique which enhances information contained by diffuse-scattered electrons and reveals what appears to be an interference effect between domains of differing lattice parameter in the top and bottom of the thin foil. We believe that these methods of image analysis could be usefully applied to the many thousands of HRTEM images that have been collected by other workers in the high temperature superconductor field. This work provides direct structural evidence for phase separation in high T-c cuprates, and gives support to recent stripes models that have been proposed to explain various angle resolved photoelectron spectroscopy and nuclear magnetic resonance data. We believe that the structural variation is a response to an opening of an electronic solubility gap where holes are not uniformly distributed in the material but are confined to metallic stripes. Optimum doping may occur as a consequence of the diffuse boundaries between stripes which arise from spinodal decomposition. Theoretical ideas about the high T-c cuprates which treat the cuprates as homogeneous may need to be modified in order to take account of this type of structural variation.

Electron beam current loss at the high-vacuum-high-pressure boundary in the environmental scanning electron microscope

A significant loss in electron probe current can occur before the electron beam enters the specimen chamber of an environmental scanning electron microscope (ESEM). This loss results from electron scattering in a gaseous jet formed inside and downstream (above) the pressure-limiting aperture (PLA), which separates the high-pressure and high-vacuum regions of the microscope. The electron beam loss above the PLA has been calculated for three different ESEMs, each with a different PLA geometry: an ElectroScan E3, a Philips XL30 ESEM, and a prototype instrument. The mass thickness of gas above the PLA in each case has been determined by Monte Carlo simulation of the gas density variation in the gas jet. It has been found that the PLA configurations used in the commercial instruments produce considerable loss in the electron probe current that dramatically degrades their performance at high chamber pressure and low accelerating voltage. These detrimental effects are minimized in the prototype instrument, which has an optimized thin-foil PLA design.

Marine macroalgal biodiversity hotspots: why is there high species richness and endemism in southern Australian marine benthic flora?

The southern Australian marine macroalgal flora has the highest levels of species richness and endemism of any regional macroalgal flora in the world. Analyses of species composition and distributions for the southern Australian flora have identified four different floristic elements, namely the southern Australian endemic element, the widely distributed temperate element, the tropical element and a cold water element. Within the southern Australian endemic element, four species distribution patterns are apparent, thought to largely result from the Jurassic to Oligocene fragmentation of East Gondwana, the subsequent migration of Tethyan ancestors from the west Australian coast and the later invasion of high latitude Pacific species. Climatic deterioration from the late Eocene to the present is thought responsible for the replacement of the previous tropical south coast flora by an endemic temperate flora which has subsequently diversified in response to fluctuating environmental conditions, abundant rocky substrata and substantial habitat heterogeneity. High levels of endemism are attributed to Australia's long isolation and maintained, as is the high species richness, by the lack of recent mass extinction events. The warm water Leeuwin Current has had profound influence in the region since the Eocene, flowing to disperse macroalgal species onto the south coast as well as ameliorating the local environment. It is now evident that the high species richness and endemism we now observe in the southern Australian marine macroalgal flora can be attributed to a complex interaction of biogeographical, ecological and phylogenetic processes over the last 160 million years.

High doses of dexamethasone induce increased beta-cell proliferation in pancreatic rat islets

Rafacho A, Cestari TM, Taboga SR, Boschero AC, Bosqueiro JR. High doses of dexamethasone induce increased beta-cell proliferation in pancreatic rat islets. Am J Physiol Endocrinol Metab 296: E681-E689, 2009. First published January 21, 2009; doi:10.1152/ajpendo.90931.2008.-Activation of insulin signaling and cell cycle intermediates is required for adult beta-cell proliferation. Here, we report a model to study beta-cell proliferation in living rats by administering three different doses of dexamethasone (0.1, 0.5, and 1.0 mg/kg ip, DEX 0.1, DEX 0.5, and DEX 1.0, respectively) for 5 days. Insulin sensitivity, insulin secretion, and histomorphometric data were investigated. Western blotting was used to analyze the levels of proteins related to the control of beta-cell growth. DEX 1.0 rats, which present moderate hyperglycemia and marked hyperinsulinemia, exhibited a 5.1-fold increase in beta-cell proliferation and an increase (17%) in beta-cell size, with significant increase in beta-cell mass, compared with control rats. The hyperinsulinemic but euglycemic DEX 0.5 rats also showed a significant 3.6-fold increase in beta-cell proliferation. However, DEX 0.1 rats, which exhibited the lowest degree of insulin resistance, compensate for insulin demand by improving only islet function. Activation of the insulin receptor substrate 2/phosphatidylinositol 3-kinase/serine-threoninekinase/ribosomalprotein S6 kinase pathway, as well as protein retinoblastoma in islets from DEX 1.0 and DEX 0.5, but not in DEX 0.1, rats was also observed. Therefore, increasing doses of dexamethasone induce three different degrees of insulin requirement in living rats, serving as a model to investigate compensatory beta-cell alterations. Augmented beta-cell mass involves beta-cell hyperplasia and, to a lower extent, beta-cell hypertrophy. We suggest that alterations in circulating insulin and, to a lesser extent, glucose levels could be the major stimuli for beta-cell proliferation in the dexamethasone-induced insulin resistance.

Features of colorectal cancers with high-level microsatellite instability occurring in familial and sporadic settings

High-level microsatellite instability (AISI-H) is demonstrated in 10 to 15% of sporadic colorectal cancers and in most cancers presenting In the inherited condition hereditary nonpolyposis colorectal cancer (HNPCC). Distinction between these categories of MSI-H cancer is of clinical importance and the aim of this study was to assess clinical, pathological, and molecular features that might he discriminatory. One hundred and twelve MSI-H colorectal cancers from families fulfilling the Bethesda criteria were compared with 57 sporadic MSI-H colorectal cancers. HNPCC cancers presented at a lower age (P < 0.001) with no sporadic MSI-H cancer being diagnosed before the age of 57 years. MSI was less extensive in HNPCC cancers with 72% microsatellite markers showing band shifts compared with 87% in sporadic tumors (P < 0.001). Absent immunostaining for hMSH2 was only found in HNPCC tumors. Methylation of bMLH1 was observed in 87% of sporadic cancers but also in 55% of HNPCC tumors that showed loss of expression of hMLH1 (P = 0.02). HNPCC cancers were more frequently characterized by aberrant beta -catenin immunostaining as evidenced by nuclear positivity (P < 0.001). Aberrant p53 immunostaining was infrequent in both groups. There were no differences with respect to 5q loss of heterozygosity or codon 12 K-ras mutation, which were infrequent in both groups. Sporadic MSI-H cancers were more frequently heterogeneous (P < 0.001), poorly differentiated (P = 0.02), mucinous (P = 0.02), and proximally located (P = 0.04) than RNPCC tumors. In sporadic MSI-H cancers, contiguous adenomas were likely to be serrated whereas traditional adenomas were dominant in HNPCC. Lymphocytic infiltration was more pronounced in HNPCC but the results did not reach statistical significance. Overall, HNPCC cancers were more like common colorectal cancer in terms of morphology and expression of beta -catenin whereas sporadic MSI-H cancers displayed features consistent with a different morphogenesis. No individual feature was discriminatory for all RN-PCC cancers. However, a model based on four features was able to classify 94.5% of tumors as sporadic or HNPCC. The finding of multiple differences between sporadic and familial MSI-H colorectal cancer with respect to both genotype and phenotype is consistent with tumorigenesis through parallel evolutionary pathways and emphasizes the importance of studying the two groups separately.

Proliferation, apoptosis, and survival in high-level microsatellite instability sporadic colorectal cancer

Sporadic colorectal cancer (CRC) characterized by high-level DNA microsatellite instability (MSI-H) has a favorable prognosis. The reason for this MSI-H survival advantage is not known. The aim of this study was to correlate proliferation, apoptosis, and prognosis in CRC stratified by MSI status. The proliferative index (PI) was measured by immunohistochemical staining with the Ki-67 antibody in a selected series of 100 sporadic colorectal cancers classified according to the level of MSI as 31 MSI-H, 29 MSI-Low (MSI-L), and 40 microsatellite stable (MISS). The Ki-67 index was significantly higher in MSI-H cancers (P < 0.0001) in which the PI was 90.1 1.2% (mean +/- SE) compared with 69.5 +/- 3.1 % and 69.5 +/- 2.3 % in MSI-L and MSS subgroups, respectively. There was a positive linear correlation between the apoptotic index (AI) and PI (r = 0.51; P < 0.001), with MSI-H cancers demonstrating an increased AI:PI ratio indicative of a lower index of cell production. A high PI showed a trend toward predicting improved survival within MSI-H cancers (P = 0.09) but did not predict survival in MSI-L or MSS cancers. The Al was not associated with survival in any MSI subgroup. In conclusion, this is the first study to show that sporadic MSI-H cancers are characterized by a higher AL:PI ratio and increased proliferative activity compared with MSI-L and MSS cancers, and that an elevated PI may confer a survival advantage within the MSI-H subset.

High frequency of low-level microsatellite instability in early colorectal cancer

Molecular events in early colorectal cancers (CRCs) have not been well elucidated because of the low incidence of early CRCs in clinical practice. Therefore, we studied 104 sporadic early CRCs with invasion limited to submucosa compared with 116 advanced CRCs. Loss of heterozygosity as well as microsatellite instability (MSI) status was examined. A significantly high frequency of low-level MSI (MSI-L) phenotype was detected in early CRCs (51.0%) compared with advanced CRCs (25.9%; P = 0.0001). In early and advanced CRCs, samples with MSI-L phenotype differed from microsatellite stable (MSS) phenotype with respect to loss of heterozygosity at 1p32 and 8p12-22. MSI-L is a frequent genetic event in early CRCs and may be a novel pathway in colorectal carcinogenesis distinct from both MSI-H and MSS.

High concentration of residual aluminum oxide on titanium surface inhibits extracellular matrix mineralization

In the present study we characterized titanium (Ti) surfaces submitted to different treatments and evaluated the response of osteoblasts derived from human alveolar bone to these surfaces. Five different surfaces were evaluated: ground (G), ground and chemical etched (G1-HF for 60 s), sand blasted (SB-Al2O3 particles 65 pm), sand blasted and chemical etched (SLA1-HF for 60 s and SLA2-HF for 13 s). Surface morphology was evaluated under SEM and roughness parameters by contact scanning instrument. The presence of Al2O3 was detected by EDS and the amount calculated by digital analyses. Osteoblasts, were cultured on these surfaces and it was evaluated: cell adhesion, proliferation, and viability, alkaline phosphatase activity, total protein content, and matrix mineralization formation. Physical and chemical treatments produced very different surface morphologies. Al2O3 residues were detected on SB and SLA2 surfaces. Only matrix mineralization formation was affected by different surface treatments, being increased on rough surface (SLA1) and reduced on surface with high amount of Al2O3 residues (SB). On the basis of these findings, it is possible to conclude that high concentration of residual Al2O3 negatively interfere with the process of matrix mineralization formation in contact with Ti implant surfaces. (C) 2008 Wiley Periodicals, Inc. J Biomed Mater Res 87A: 588-597, 2008

Timing and duration of the last interglacial inferred from high resolution U-series chronology of stalagmite growth in Southern Hemisphere

High-precision Th-230-U-238 ages for a stalagmite from Newdegate Cave in southern Tasmania, Australia define a rare record of precipitation between 100 and 155 ka before the present. The fastest stalagmite growth occurred between 129.2 +/- 1.6 and 122.1 +/- 2.0 ka (similar to 61.5 mm/ka), coinciding with a time of prolific coral growth from Western Australia (128-122 ka). This is the first high-resolution continental record in the Southern Hemisphere that can be compared and correlated with the marine record. Such correlation shows that in southern Australia the onset of full interglacial sea level and the initiation of highest precipitation on land were synchronous. The stalagmite growth rate between 129.2 and 142.2 ka (similar to 5.9 mm/ka) was lower than that between 142.2 and 154.5 ka (similar to 18.7 mm/ka), implying drier conditions during the Penultimate Deglaciation, despite rising temperature and sea level. This asymmetrical precipitation pattern is caused by latitudinal movement of subtropical highs and an associated Westerly circulation, in response to a changing Equator-to-Pole temperature gradient. Both marine and continental records in Australia strongly suggest that the insolation maximum between 126 and 128 ka at 65 degreesN was directly responsible for the maintenance of full Last Interglacial conditions, although the triggers that initiated Penultimate Deglaciation (at similar to 142 ka) remain unsolved. (C) 2001 Elsevier Science B.V. All rights reserved.

Integrating high and moderate spatial resolution image data to estimate forest age structure

The collection of spatial information to quantify changes to the state and condition of the environment is a fundamental component of conservation or sustainable utilization of tropical and subtropical forests, Age is an important structural attribute of old-growth forests influencing biological diversity in Australia eucalypt forests. Aerial photograph interpretation has traditionally been used for mapping the age and structure of forest stands. However this method is subjective and is not able to accurately capture fine to landscape scale variation necessary for ecological studies. Identification and mapping of fine to landscape scale vegetative structural attributes will allow the compilation of information associated with Montreal Process indicators lb and ld, which seek to determine linkages between age structure and the diversity and abundance of forest fauna populations. This project integrated measurements of structural attributes derived from a canopy-height elevation model with results from a geometrical-optical/spectral mixture analysis model to map forest age structure at a landscape scale. The availability of multiple-scale data allows the transfer of high-resolution attributes to landscape scale monitoring. Multispectral image data were obtained from a DMSV (Digital Multi-Spectral Video) sensor over St Mary's State Forest in Southeast Queensland, Australia. Local scene variance levels for different forest tapes calculated from the DMSV data were used to optimize the tree density and canopy size output in a geometric-optical model applied to a Landsat Thematic Mapper (TU) data set. Airborne laser scanner data obtained over the project area were used to calibrate a digital filter to extract tree heights from a digital elevation model that was derived from scanned colour stereopairs. The modelled estimates of tree height, crown size, and tree density were used to produce a decision-tree classification of forest successional stage at a landscape scale. The results obtained (72% accuracy), were limited in validation, but demonstrate potential for using the multi-scale methodology to provide spatial information for forestry policy objectives (ie., monitoring forest age structure).

Ultracentrifugal studies of the effect of molecular crowding by trimethylamine N-oxide on the self-association of muscle glycogen phosphorylase b

The suitability of sedimentation equilibrium for characterizing the self-association of muscle glycogen phosphorylase b has been reappraised. Whereas sedimentation equilibrium distributions for phosphorylase b in 40 mM Hepes buffer (pH 6.8) supplemented with 1 mM AMP signify a lack of chemical equilibrium attainment, those in buffer supplemented additionally with potassium sulfate conform with the requirements of a dimerizing system in chemical as we:ll as sedimentation equilibrium. Because the rate of attainment of chemical equilibrium under the former conditions is sufficiently slow to allow resolution of the dimeric and tetrameric enzyme species by sedimentation velocity, this procedure has been used to examine the effects of thermodynamic nonideality arising from molecular crowding try trimethylamine N-oxide on the self-association behaviour of phosphorylase b. In those terms the marginally enhanced extent of phosphorylase b self-association observed in the presence of high concentrations of the cosolute is taken to imply that the effects of thermodynamic nonideality on the dimer-tetramer equilibrium are being countered by those displacing the T reversible arrow R isomerization equilibrium for dimer towards the smaller, nonassociating T state. Because the R state is the enzymically active form, an inhibitory effect is the predicted consequence of molecular crowding by high concentrations of unrelated solutes. Thermodynamic nonideality thus provides an alternative explanation for the inhibitory effects of high concentrations of glycerol, sucrose and ethylene glycol on phosphorylase b activity, phenomena that have been attributed to extremely weak interaction of these cryoprotectants with the T state of the enzyme.