Analysis of spacing in a periodic pattern

Colonies of hydroids exhibit periodic biological patterns. Polyps form on stolons at fixed distances, obeying distinct rules. The spacing mechanism is based on inhibition emanating from existing polyps, predominantly from the head of the polyp. Removal of polyps from young colonies reduces the distance between initiating polyps and newly formed polyps to 50% of the normal values. Head removal suffices to obtain an almost identical reduction. Polyp enlargement which increases the distance between the inhibition-emitting head and the stolon tissue reduces the intrastolonal range of inhibition. In the stolon tissue, decrease of inhibitory activity occurs. An increase in the stolon/polyp ratio of a colony reduces bud distances. The decay is, in part, due to loss of inhibitory activity into the external medium: if colonies are incubated in conditioned culture medium derived from crowded colonies having normally large interpolyp distances, bud distances increase in test colonies. The effectiveness of transfer of inhibitory activity from tissue into the medium depends on culture conditions. If convection is increased by agitation of the culture medium, the distances between polyp and bud decreases; viscosity enhancement of the culture medium reduces convection and bud distances become larger. This effect is compensated for by additional agitation of the viscosity enhanced culture medium. Our results support the idea that a lateral inhibition mechanism controls polyp spacing in the stolon and that inhibition is based on diffusible inhibitory compounds.     

Shiny spheres of placozoans (Trichoplax) function in anti-predator defense

Abstract. When individual placozoans, Trichoplax adhaerens , were fed to polyps of the hydroid Podocoryna carnea , the polyps became paralyzed in all 27 trials. In one instance the hydroid polyp died and in five instances a fragment of the placozoan survived. The time to recovery from paralysis varied with the relative size of the polyp and the placozoan. Placozoans were disassociated into separate cells and then reaggregated by centrifugation to produce pellets of tissue lacking the vesicles called shiny spheres, normally abundant in the upper epithelium. We fed pellets of two size classes to the hydroid polyps. When the placozoan pellet was smaller than the hydroid, paralysis was eliminated in nine of ten trials. When the placozoan pellet was comparable in size to the polyp, paralysis occurred but the recovery time was substantially reduced, compared with trials in which polyps were fed intact placozoans possessing shiny spheres. These results support a function of shiny spheres in anti-predator defense.     

Deprived TLR9 Expression in Apparently Healthy Nasal Mucosa Might Trigger Polyp-Growth in Chronic Rhinosinusitis Patients

Background

The origin of nasal polyps in chronic rhinosinusitis is unknown, but the role of viral infections in polyp growth is clinically well established. Toll-like receptors (TLRs) have recently emerged as key players in our local airway defense against microbes. Among these, TLR9 has gained special interest in viral diseases. Many studies on chronic rhinosinusitis with nasal polyps (CRSwNP) compare polyp tissue with nasal mucosa from polyp-free individuals. Knowledge about changes in the turbinate tissue bordering the polyp tissue is limited.

Objectives

To analyse the role of TLR9 mediated microbial defense in tissue bordering the polyp.

Methods

Nasal polyps and turbinate tissue from 11 patients with CRSwNP and turbinate tissue from 11 healthy controls in total were used. Five biopsies from either group were analysed immediately with flow cytometry regarding receptor expression and 6 biopsies were used for in vitro stimulation with a TLR9 agonist, CpG. Cytokine release was analysed using Luminex. Eight patients with CRSwNP in total were intranasally challenged with CpG/placebo 24 hours before surgery and the biopsies were collected and analysed as above.

Results

TLR9 expression was detected on turbinate epithelial cells from healthy controls and polyp epithelial cells from patients, whereas TLR9 was absent in turbinate epithelial cells from patients. CpG stimulation increased the percentage cells expressing TLR9 and decreased percentage cells expressing VEGFR2 in turbinate tissue from patients. After CpG stimulation the elevated levels of IL-6, G-CSF and MIP-1β in the turbinate tissue from patients were reduced towards the levels demonstrated in healthy controls.

Conclusion

Defects in the TLR9 mediated microbial defense in the mucosa adjacent to the anatomic origin of the polyp might explain virus induced polyp growth. CpG stimulation decreased VEGFR2, suggesting a role for CpG in polyp formation. The focus on turbinate tissue in patients with CRSwNP opens new perspectives in CRSwNP-research.     

Ubiquitin ligase A20 regulates p53 protein in human colon epithelial cells

Background

Intestinal polyps may further develop into colon cancer; the pathogenesis is not clear. The p53 gene is an important anti-cancer gene in the body, which is suppressed in cancer. The ubiquitin E3 ligase A20 (A20) plays a role in regulating the activities of epithelial cells. This study was designed to investigate the role of the colon polyp epithelium-derived A20 in the pathogenesis of colon cancer.

Results

Eighty-eight colon cancer patients and 136 colon polyp patients were recruited into this study. Human colon cancer tissue, the epithelium of adenomas polyp and hyperplastic polyp showed high levels of A20, which had a positive correlation with the cancerous tendency of colon polyps. The levels of A20 were much higher in the adenomas and hyperplastic polyps than that in the inflammatory polyps; the latter showed less cancerous tendency. A20 bound p53 to form complexes in colon cancer tissue and colon polyps. Over expression of A20 suppresses P53 protein levels in the HEK293 cells.

Conclusions

A20 may play an important role in the cancerous tendency of colon polyposis.     

Hematic infiltrates and the expression of HLA-DR antigens in naso-sinusoidal polyps of the fibrous type

In this study fibrous nasal polyps, obtained from four patients, were analyzed by means of immunocytochemical methods for the presence of interstitial hematic cell infiltrate and HLA-DR molecule expression. This histologic type accounted for 36.4% of nasal polyps studied. Our results demonstrated that cells belonging to monocyte-macrophage lineage were mainly detected within fibrous and edematous zones (greater than 50%), whereas T cells were found within the subepithelial peripheral connective tissue (greater than 60%). Surface and gland epithelial cells appeared to be more intensely stained for HLA-DR molecules than nasal epithelium of normal subjects, thus indicating that the intensity of HLA-DR molecule expression correlated with the presence of a hematic cell infiltrate. Nasal polyps are a frequent pathology whose etiology has not yet been completely clarified. The present study provides additional information about the fibrous polyp structure and can support some speculations on the nasal polyp etiology.     

Iron concentrations in intestinal cancer tissue and in colon and rectum polyps

A prospective randomized trial was used to determine iron concentrations in intestinal cancer tissue and colorectum polyps. We investigated the possible difference between the concentrations of iron, ferritin, albumin, and hemoglobin in the serum of patients with colorectal cancer and polyps. We also determined the relationship between the iron and ferritin levels in cancer tissue, the localization of neoplasms, and the stage of their development. The study comprises 67 patients with colorectum cancer and 42 patients with colon and rectum polyps. The metal was determined by using the total-reflection X-ray fluorescence (TRXRF) method. The mean concentration of iron in colorectal cancer equaled 46.1 μg/g of the tissue and was higher than in the case of polyps (43.2 μg/g). The mean serum iron level in patients with colorectal cancer was statistically lower than in the serum of patients with polyp and in the control group (54.5, 91.3, and 108.0 μg/g, respectively). The determined average concentration of ferritin in the serum of patients with colorectal cancer equaled 60.4 μg/g and was statistically lower than the level of this enzyme in the serum of patients with polyps (85.2 μg/g) and in the control group (102.0 μg/g). There was no difference between the serum albumin and hemoglobin concentrations in patients with colorectal cancer, polyps, and the control. There was no difference in the levels of iron and ferritin depending on the location of the neoplasm and the stage of its development. Also, there was no difference between the concentrations of iron in the cancer tissue of malignant and benign tumors after taking into consideration sex and age of patients. During the examination we determined significantly higher concentrations of iron in the cancer tissue and not in the polyp. The low levels of iron in the serum of patients with malignant tumor may increase colorectal cancer risk.     

THE COORDINATION OF POTENTIAL PACEMAKERS IN THE HYDROID TUBULARIA

Sectioning experiments and electrical recording indicate thatthere are many potential pacemakers in polyps of the hydroidTubularia. Functionally the pacemakers are organized primarilyinto pacemaker systems, groups within which there is tight coupling.The different pacemaker systems of a polyp are loosely coupledto one another. There are two principal systems in Tubularia,one in the polyp neck (the NP system) and one in the hydranth(the HP system). In addition, there are pacemakers controllingactivities of individual tentacles. Activity in the NP systemis usually not associated with observable polyp behavior. HPsystem activity is correlated with behavioral responses termedconcerts. Concerts are probably digestive activities; they resultin the mixing of food being digested and the distribution ofthe products of this digestion. The NP systems of polyps ona colony are loosely coupled to one another through one of thethree conducting systems found in Tubularia stalks. The loosecoupling between NP systems of polyps on a colony and the loosecoupling between NP and HP systems within single polyps resultsin there being some coordination of concert activity throughouta colony.     

Telomerase activity is not related to life history stage in the jellyfish Cassiopea sp.

The polyp (scyphistoma) of the jellyfish Cassiopea sp. can be maintained in culture for a long time, as polyps repeatedly reproduce asexually via formation of vegetative buds or propagules. The medusa, which is the sexually reproducing stage, typically has a relatively short life span. As a first step to understand the difference in life spans of the polyp and medusa stages of Cassiopea sp., we measured telomerase activity in different life cycle stages. We found telomerase activity in tissues of aposymbiotic polyps and propagules and symbiotic ephyrae (newly budded medusae) and adult medusae. No significant difference in telomerase activity was found between polyps and the bell region of the medusae. The cloned elongation products of the stretch PCR contained the TTAGGG repeats suggesting that the jellyfish has the ‘vertebrate’ telomere motif (TTAGGG)_n. This is the first study to show that somatic tissues of both polyp and medusa stages of a cnidarian had telomerase activity. Telomerase activity in somatic tissues may be related to the presence of multipotent interstitial cells and high regenerative capacity of cnidarians.     

Intraspecific contact and egg production in the massive coral Goniastrea aspera in Okinawa, subtropical Japan

The effect of intraspecific contact (Contact) on egg production was examined in the massive coral Goniastrea aspera in Okinawa, subtropical Japan. The contact was non-aggressive without damaging soft tissues each other. Within Contact colonies, polyp volume, polyp fertility (%polyps with gonad), and NE/PV (number of eggs per polyp volume) were significantly smaller in marginal (Mg) polyps without direct intraspecific contact than other polyps, but no difference was found between non-marginal and Mg-Contact (marginal with direct intraspecific contact) polyps. Comparisons of non-marginal polyps (non-marginal and Mg-Contact polyps were combined in Contact colonies) between Non-Contact and Contact colonies showed that fertility and NE/PV were significantly larger in Contact colonies than in Non-Contact colonies, but polyp volume were not different significantly. Further analyses dividing colonies at Non-Contact maturation colony size (60 polyps) revealed that fertility and NE/PV were significantly larger in Contact colonies than in Non-Contact colonies only in the small colonies (<60 polyps), indicating that the intraspecific contact promoted sexual maturation at smaller colony size; one polyped Contact coral was also reproductive. The lack of correlation between polyp volume and NE/PV in the small Contact colonies, and the similarity of NE/PV in non-marginal and Mg-Contact polyps within a colony, suggest that the maturation at smaller size in Contact colonies is realized by reproductive integration of polyps at the colony level. The present results show that size-structured populations such as colonial corals may show phenotypic diversity in key demographic parameters, such as reproductive output, dependent on ecological conditions.     

First experience in clinical application of hyperspectral endoscopy for evaluation of colonic polyps

Early detection and resection of adenomatous polyps prevents their progression to colorectal cancer (CRC), significantly improving patient outcomes. Polyps are typically identified and removed during white-light colonoscopy. Unfortunately, the rate of interval cancers that arise between CRC screening events remains high, linked to poor visualization of polyps during screening and incomplete polyp removal. Here, we sought to evaluate the potential of a hyperspectral endoscope (HySE) to enhance polyp discrimination for detection and resection. We designed, built and tested a new compact HySE in a proof-of-concept clinical study. We successfully collected spectra from three tissue types in seven patients undergoing routine colonoscopy screening. The acquired spectral data from normal tissue and polyps, both pre- and post- resection, were subjected to quantitative analysis using spectral angle mapping and machine learning, which discriminated the data by tissue type, meriting further investigation of HySE as a clinical tool.     

Structure and signaling in polyps of a colonial hydroid

Abstract. After feeding, polyps of colonial hydroids contract regularly, dispersing food throughout the colony via the gastrovascular fluid. Such contractions may trigger signaling pathways that allow colonies to grow in an adaptive manner, i.e., to initiate development of more polyps in food‐rich areas and to suppress polyp development in food‐poor areas. In this context, we investigated the structure and potential signaling of the junction between polyps and stolons in colonies of the hydroid Podocoryna carnea. Using transmission electron microscopy, we found that the density of mitochondrion‐rich epitheliomuscular cells was low in polyp and stolon tissues except at or near the polyp‐stolon junction, where many of these mitochondrion‐rich cells occur in ectodermal tissue. In vivo fluorescence microscopy suggests that these mitochondria are a principal source of the metabolic signals of the colony. Both native fluorescence of NAD(P)H and fluorescence from peroxides (visualized with H₂DCFDA) co‐localize to this region of the polyp. Rhodamine 123 fluorescence suggests that both these metabolic signals emanate from mitochondria. To test whether such metabolic signals may be involved in colony pattern formation, inbred lines of P. carnea were used. Colonies of a runner‐like inbred line grow with widely spaced polyps and long stolonal connections, much like wild‐type colonies in a food‐poor environment. Colonies of a sheet‐like inbred line grow with closely spaced polyps and short stolonal connections, similar to wild‐type colonies in a food‐rich environment. Polyp‐stolon junctions in runner‐like and sheet‐like colonies were imaged for the fluorescence of H₂DCFDA. Densitometric analysis of this signal indicates that the mitochondria in epitheliomuscular cells of runner‐like polyps emit greater amounts of peroxides. Because peroxides and other reactive oxygen species are frequently intermediaries in metabolic signaling pathways, we suspect that such signaling may indeed occur at polyp‐stolon junctions, affecting colony pattern formation in these inbred lines and possibly in hydroid colonies in general.     

Signaling pathways of heat- and hypersalinity-induced polyp bailout in Pocillopora acuta

Polyp bailout is a drastic response to acute stress where coral coloniality breaks down and polyps detach. We induced polyp bailout in Pocillopora acuta with heat stress and tested for differential gene expression using RNAseq and a qPCR assay. Furthermore, we induced polyp bailout with hypersalinity and compared the results to identify stressor-independent signals and pathways active during polyp bailout. Both stressors led to the onset of polyp bailout and the detachment of vital polyps. We observed activation of microbe-associated molecular pattern receptors and downstream signaling pathways of the innate immune system. Further, we detected growth factors and genes active during Wnt-signaling potentially contributing to wound healing, regeneration, and proliferation. Upregulation of several genes encoding for matrix metalloproteinases and the fibroblast growth factor signaling pathway are the most likely involved in the remodeling of the extracellular matrix, as well as in the detachment of polyps from the calcareous skeleton during polyp bailout. Expression of genes of interest in our qPCR assay of vital polyps from our heat-stress experiment, showed a trend for a normalization of gene expression after polyp bailout. Our results provide new insights into the signaling cascades leading to the observed physiological responses during polyp bailout. Comparison between the two stressors showed that certain signaling pathways are independent of the stressor and suggested that polyp bailout is a general response of corals to acute stress. Furthermore, immune system responses during polyp bailout indicate that microbe-associated partners of corals may lead to the polyp bailout response.

     

Alteration of mitochondrial DNA sequence and copy number in nasal polyp tissue

This study was designed to investigate the possibility that mtDNA mutations might arise in inflammatory or chronically damaged nasal polyp tissue from 23 patients. Thirteen patients (57%) displayed nasal polyp tissue-specific mtDNA mutations in the hypervariable segment of the control region and cytochrome b gene, which were not found in the corresponding blood cells and/or adjacent normal tissue. Nasal polyp tissue-specific length heteroplasmic mutations were also detected in nucleotide position (np) 303–315 homopolymeric poly C track (39%), np 514–523 CA repeats (17%) and np 16184–16193 poly C track (30%). The average mtDNA copy number was about three times higher in nasal polyp tissue than in the corresponding peripheral blood cells and adjacent non-polyp tissues. The level of reactive oxygen species (ROS) was significantly higher in the nasal polyp tissues compared to those from the corresponding samples. High level of ROS in nasal polyp tissue may contribute to development of mtDNA mutations, which may play a crucial role in the vicious cycle of pathophysiology of nasal polyps.     

Benign epithelial gastric polyps--frequency,location, and age and sex distribution

Prospective investigation has been undertaken with the aim to study the frequency, location and age and sex distribution of various histological types of benign gastric epithelial polyps. Histological type--adenomatous, hyperplastic and fundic gland polyps--was diagnosed on the basis of at least three histological samples taken from the polyp. Biopsy samples were also taken from the antrum and the body of the stomach so that gastritis could be graded and classified, and the presence of H. pylori could be determined by histology. All 6,700 patients, who had undergone upper gastrointestinal endoscopy in a one-year period, participated in this study. Among them 42 benign gastric epithelial polyp were found in 31 patients: adenomatous gastric polyps in 7 patients, hyperplastic gastric polyp in 21 and fundic gland polyp in 3 patients. All patients with hyperplastic polyps had chronic active superficial gastritis, whereas most of the patients with adenomatous polyps had a chronic atrophic gastritis with high prevalence of intestinal metaplasia. Among 21 patients with hyperplastic gastric polyps, 16 (76%) patients were positive for H. pylori infection in contrast to only 2 patients (29%) with adenomatous gastric polyps and 1 patient (33%) with fundic gland polyp. Presented data indicates that hyperplastic gastric polyps are the most common and they are associated with the presence of chronic active superficial gastritis and concomitant H. pylori infection. Adenomatous polyps are rarer and they tend to be associated with chronic atrophic gastritis and intestinal metaplasia. Fundic gland polyp is the rarest type of gastric polyps.     

Colon cancer specific nuclear matrix protein alterations in human colonic adenomatous polyps

Most colon cancers arise within preexisting adenomatous polyps or adenomas. The slow evolution from the non-invasive premalignant lesion, the adenomatous polyp, to invasive cancer supports a strategy of early detection. Recently, we identified unique nuclear matrix proteins (NMPs) specific for colon cancer (CC2, CC3, CC4, CC5). Most of the NMPs identified are common to all cell types, but several identified NMPs are tissue and cell line specific. The objective of this study is to describe and characterize the NMP profile of premalignant adenomatous colon polyps. Specifically when in the adenoma-carcinoma sequence four specific colon cancer NMPs, previously described, appear. Using two-dimensional (2-D) gel analysis 20 colon polyps (one juvenile polyp, six tubular adenoma (TA), seven tubulovillous adenoma (TVA), six TVA with focal high-grade dysplasia (HGD), were analyzed for the presence of four (CC2, CC3, CC4, CC5) specific NMPs. CC2 was not seen in any of the premalignant polyps. CC5 was present in only two premalignant TVA with HGD and in one TA. CC3 and CC4 were present in most adenomas. None of the NMPs were seen in the juvenile polyp, which is not considered to be a precursor of colon cancer. CC2 and CC5 are NMPs expressed at the junction of an advanced adenoma and invasive colorectal cancer. CC3 and CC4 are expressed earlier in the evolution of adenomatous polyps. Development of an assay to these proteins may serve as a new method for early detection of colorectal cancer.     

Myb expression is higher in malignant human colonic carcinoma and premalignant adenomatous polyps than in normal mucosa.

Expression of the protooncogene c-Myb protein was assessed in normal mucosa and in tumor samples resected from six patients. We found that the tumor samples always expressed higher levels of full length Myb protein than the normal tissue. This contrasts with the situation in c-myb-associated hemopoietic malignancies of the mouse and chicken, in which Myb proteins are generally amino or carboxyl truncated. Tissues from five patients with colonic adenomatous polyps were also examined and found to express levels of Myb that were, in general, intermediate between those found in normal tissues and tumors. Of particular interest is that the more dysplastic polyps displayed higher Myb levels. In one patient with carcinoma and multiple colonic polyps, some polyps had intermediate levels of Myb, whereas one polyp with carcinoma in situ expressed tumor-like levels of Myb. To directly test the hypothesis that Myb expression may be important in determining the rate of colonic cell proliferation, we examined three colonic carcinoma cell lines and one polyp cell line. We found that the cell lines with the most rapid doubling times exhibited the highest Myb levels. In addition, we show that antisense myb oligonucleotides retard the proliferation of one of these colonic cell lines which expresses the highest level of Myb.     

Alkaline phosphatases and adenylate cyclase in the normal and desensitized rat small intestine after acute cholera toxin challenge: a histochemical study

The effect of cholera toxin (CT)-challenge on histochemically demonstrable activities of adenylatecyclase and alkaline phosphatase was investigated in rat small intestine, using an intestinal loop model. CT-challenge increased the activities of adenylatecyclase and alkaline phosphatases within 15 minutes, and the changes were confined to enterocytes in the upper third parts of the villi. There was no change in the staining of the crypt cells. There was an increased basal activity of both adenylatecyclase and alkaline phosphatases in animals desensitized to cholera toxin by multiple peroral exposures. CT-challenge in the desensitized rats did not further increase the enzyme activity. It is concluded that desensitization to secretagogues induces profound alterations in the cell systems responsible for fluid secretion.     

Rh-I-UEA-1 polymerized liposomes target and image adenomatous polyps in the APC(Min/+) mouse using optical colonography

Mutated adenomatous polyposis coli (APC) genes predispose transformations to neoplasia, progressing to colorectal carcinoma. Early detection facilitates clinical management and therapy. Novel lectin-mediated polymerized targeted liposomes (Rh-I-UEA-1), with polyp specificity and incorporated imaging agents were fabricated to locate and image adenomatous polyps in APC(Min/+) mice. The biomarker α-L-fucose covalently joins the liposomal conjugated lectin Ulexeuropaeus agglutinin (UEA-1), via glycosidic linkage to the polyp mucin layer. Multispectral optical imaging (MSI) corroborated a global perspective of specific binding (rhodamine B 532 nm emission, 590-620 nm excitation) of targeted Rh-I-UEA-1 polymerized liposomes to polyps with 1.4-fold labeling efficiency. High-resolution coregistered optical coherence tomography (OCT) and fluorescence molecular imaging (FMI) reveal the spatial correlation of contrast distribution and tissue morphology. Freshly excised APC(Min) bowels were incubated with targeted liposomes (UEA-1 lectin), control liposomes (no lectin), or iohexol (Omnipaque) and imaged by the three techniques. Computed tomographic quantitative analyses did not confirm that targeted liposomes more strongly bound polyps than nontargeted liposomes or iohexol (Omnipaque) alone. OCT, with anatomic depth capabilities, along with the coregistered FMI, substantiated Rh-I-UEA-1 liposome binding along the mucinous polyp surface. UEA-1 lectin denotes α-l-fucose biomarker carbohydrate expression at the mucin glycoprotein layer; Rh-I-UEA-1 polymerized liposomes target and image adenomatous polyps in APC(Min) mice.     

Effect of exercise on biological pathways in ApcMin/+ mouse intestinal polyps

Many epidemiological studies have demonstrated that level of exercise is associated with reduced colorectal cancer risk. Treadmill training can decrease Apc(Min/+) mouse intestinal polyp number and size, but the mechanisms remain unclear. Understanding the molecular changes in the tumor following exercise training may provide insight on the mechanism by which exercise decreases Apc(Min/+) mouse polyp formation and growth. The purpose of this study was to determine if exercise can modulate Apc(Min/+) mouse intestinal polyp cellular signaling related to tumor formation and growth. Male Apc(Min/+) mice were randomly assigned to control (n = 20) or exercise (n = 20) treatment groups. Exercised mice ran on a treadmill at a moderate intensity (18 m/min, 60 min, 6 days/wk, 5% grade) for 9 wk. Polyps from Apc(Min/+) mice were used to quantify markers of polyp inflammation, apoptosis, and beta-catenin signaling. Exercise decreased the number of macrophages in polyps by 35%. Related to apoptosis, exercise decreased the number of terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)-positive cells by 73% in all polyps. Bax protein expression in polyps was decreased 43% by exercise. beta-Catenin phosphorylation was elevated 3.3-fold in polyps from exercised mice. Moderate-intensity exercise training alters cellular pathways in Apc(Min/+) mouse polyps, and these changes may be related to the exercise-induced reduction in polyp formation and growth.