Vocal fold submucosal infusion technique in phonomicrosurgery.

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Kass, E S; Hillman, R E; Zeitels, S M

1996-05-01

Phonomicrosurgery is optimized by maximally preserving the vocal fold's layered microstructure (laminae propriae). The technique of submucosal infusion of saline and epinephrine into the superficial lamina propria (SLP) was examined to delineate how, when, and why it was helpful toward this surgical goal. A retrospective review revealed that the submucosal infusion technique was used to enhance the surgery in 75 of 152 vocal fold procedures that were performed over the last 2 years. The vocal fold epithelium was noted to be adherent to the vocal ligament in 29 of the 75 cases: 19 from previous surgical scarring, 4 from cancer, 3 from sulcus vocalis, 2 from chronic hemorrhage, and 1 from radiotherapy. The submucosal infusion technique was most helpful when the vocal fold epithelium required resection and/or when extensive dissection in the SLP was necessary. The infusion enhanced the surgery by vasoconstriction of the microvasculature in the SLP, which improved visualization during cold-instrument tangential dissection. Improved visualization facilitated maximal preservation of the SLP, which is necessary for optimal pliability of the overlying epithelium. The infusion also improved the placement of incisions at the perimeter of benign, premalignant, and malignant lesions, and thereby helped preserve epithelium uninvolved by the disorder.

An IFNG SNP with an estrogen-like response element selectively enhances promoter expression in peripheral but not lamina propria T cells.

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Gonsky, R; Deem, R L; Bream, J H; Young, H A; Targan, S R

2006-07-01

This study examines mucosa-specific regulatory pathways involved in modulation of interferon-gamma (IFN-gamma) in lamina propria T cells. Previous studies identified mucosa-specific CD2 cis-elements within the -204 to -108 bp IFNG promoter. Within this region, a single-site nucleotide polymorphism, -179G/T, imparts tumor necrosis factor-alpha stimulation of IFNG in peripheral blood lymphocytes, and is linked with accelerated AIDS progression. We discovered a putative estrogen response element (ERE) introduced by the -179T, which displays selective activation in peripheral blood mononuclear cells (PBMC) vs lamina propria mononuclear cells (LPMC). Transfection of PBMC with constructs containing the -179G or -179T site revealed CD2-mediated enhancement of the -179T compared to -179G allele, although, in LPMC, a similar level of expression was detected. Electrophoretic mobility shift assay (EMSA) analysis demonstrated CD2-mediated nucleoprotein binding to the -179T but not the -179G in PBMC. In LPMC, binding is constitutive to both -179G and -179T regions. Sequence and EMSA analysis suggests that the -179T allele creates an ERE-like binding site capable of binding recombinant estrogen receptor. Estrogen response element transactivation is enhanced by CD2 signaling, but inhibited by estrogen in PBMC but not in LPMC, although expression of estrogen receptor was similar. This is the first report to describe a potential molecular mechanism responsible for selectively controlling IFN-gamma production in LPMC.

Adipose-Derived Mesenchymal Stem Cells in the Regeneration of Vocal Folds: A Study on a Chronic Vocal Fold Scar

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Angelou Valerie

2016-01-01

Full Text Available Background. The aim of the study was to assess the histological effects of autologous infusion of adipose-derived stem cells (ADSC on a chronic vocal fold scar in a rabbit model as compared to an untreated scar as well as in injection of hyaluronic acid. Study Design. Animal experiment. Method. We used 74 New Zealand rabbits. Sixteen of them were used as control/normal group. We created a bilateral vocal fold wound in the remaining 58 rabbits. After 18 months we separated our population into three groups. The first group served as control/scarred group. The second one was injected with hyaluronic acid in the vocal folds, and the third received an autologous adipose-derived stem cell infusion in the scarred vocal folds (ADSC group. We measured the variation of thickness of the lamina propria of the vocal folds and analyzed histopathologic changes in each group after three months. Results. The thickness of the lamina propria was significantly reduced in the group that received the ADSC injection, as compared to the normal/scarred group. The collagen deposition, the hyaluronic acid, the elastin levels, and the organization of elastic fibers tend to return to normal after the injection of ADSC. Conclusions. Autologous injection of adipose-derived stem cells on a vocal fold chronic scar enhanced the healing of the vocal folds and the reduction of the scar tissue, even when compared to other treatments.

Adipose-Derived Mesenchymal Stem Cells in the Regeneration of Vocal Folds: A Study on a Chronic Vocal Fold Scar

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Vassiliki, Kalodimou; Irini, Messini; Nikolaos, Psychalakis; Karampela, Eleftheria; Apostolos, Papalois

2016-01-01

Background. The aim of the study was to assess the histological effects of autologous infusion of adipose-derived stem cells (ADSC) on a chronic vocal fold scar in a rabbit model as compared to an untreated scar as well as in injection of hyaluronic acid. Study Design. Animal experiment. Method. We used 74 New Zealand rabbits. Sixteen of them were used as control/normal group. We created a bilateral vocal fold wound in the remaining 58 rabbits. After 18 months we separated our population into three groups. The first group served as control/scarred group. The second one was injected with hyaluronic acid in the vocal folds, and the third received an autologous adipose-derived stem cell infusion in the scarred vocal folds (ADSC group). We measured the variation of thickness of the lamina propria of the vocal folds and analyzed histopathologic changes in each group after three months. Results. The thickness of the lamina propria was significantly reduced in the group that received the ADSC injection, as compared to the normal/scarred group. The collagen deposition, the hyaluronic acid, the elastin levels, and the organization of elastic fibers tend to return to normal after the injection of ADSC. Conclusions. Autologous injection of adipose-derived stem cells on a vocal fold chronic scar enhanced the healing of the vocal folds and the reduction of the scar tissue, even when compared to other treatments. PMID:26933440

A mixed-effects model approach for the statistical analysis of vocal fold viscoelastic shear properties.

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Xu, Chet C; Chan, Roger W; Sun, Han; Zhan, Xiaowei

2017-11-01

A mixed-effects model approach was introduced in this study for the statistical analysis of rheological data of vocal fold tissues, in order to account for the data correlation caused by multiple measurements of each tissue sample across the test frequency range. Such data correlation had often been overlooked in previous studies in the past decades. The viscoelastic shear properties of the vocal fold lamina propria of two commonly used laryngeal research animal species (i.e. rabbit, porcine) were measured by a linear, controlled-strain simple-shear rheometer. Along with published canine and human rheological data, the vocal fold viscoelastic shear moduli of these animal species were compared to those of human over a frequency range of 1-250Hz using the mixed-effects models. Our results indicated that tissues of the rabbit, canine and porcine vocal fold lamina propria were significantly stiffer and more viscous than those of human. Mixed-effects models were shown to be able to more accurately analyze rheological data generated from repeated measurements. Copyright © 2017 Elsevier Ltd. All rights reserved.

IgA class switch occurs in the organized nasopharynx- and gut-associated lymphoid tissue, but not in the diffuse lamina propria of airways and gut.

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Shikina, Takashi; Hiroi, Takachika; Iwatani, Kohichi; Jang, Myoung Ho; Fukuyama, Satoshi; Tamura, Manabu; Kubo, Takeshi; Ishikawa, Hiromichi; Kiyono, Hiroshi

2004-05-15

Secretory IgA plays a crucial role in the host immune response as a first line of defense. A recent demonstration of in situ IgA class switching in intestinal lamina propria provided an opportunity to reconsider the model for the homing of IgA-committed B cells characterized by distinctive trafficking patterns to effector sites. Those effector sites depend on the organized mucosa-associated lymphoid tissues as their site of induction. In this report we show the preferential presence of IgM(+)B220(+) and IgA(+)B220(+) cells belonging to pre- and post-IgA isotype class-switched cells in the organized mucosa-associated lymphoid tissues, such as nasopharynx-associated lymphoid tissues, isolated lymphoid follicles, and Peyer's patches, and the defect of those populations in the diffuse effector tissues, such as the nasal passage and intestinal lamina propria. Consistent with these findings, the expressions of a series of IgA isotype class switch recombination-related molecules, including activation-induced cytidine deaminase, Ialpha-C micro circle transcripts, and Ialpha-C micro circle transcripts, were selectively detected in these organized mucosa-associated lymphoid structures, but not in the diffuse mucosal effector sites. Taken together, these findings suggest that IgA isotype class switching occurs only in the organized mucosa-associated lymphoid organs (e.g., nasopharynx-associated lymphoid tissues, isolated lymphoid follicles, and Peyer's patches), but not in the diffuse effector tissues of the upper respiratory and gastrointestinal tracts.

Collagen Content Limits Optical Coherence Tomography Image Depth in Porcine Vocal Fold Tissue.

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Garcia, Jordan A; Benboujja, Fouzi; Beaudette, Kathy; Rogers, Derek; Maurer, Rie; Boudoux, Caroline; Hartnick, Christopher J

2016-11-01

Vocal fold scarring, a condition defined by increased collagen content, is challenging to treat without a method of noninvasively assessing vocal fold structure in vivo. The goal of this study was to observe the effects of vocal fold collagen content on optical coherence tomography imaging to develop a quantifiable marker of disease. Excised specimen study. Massachusetts Eye and Ear Infirmary. Porcine vocal folds were injected with collagenase to remove collagen from the lamina propria. Optical coherence tomography imaging was performed preinjection and at 0, 45, 90, and 180 minutes postinjection. Mean pixel intensity (or image brightness) was extracted from images of collagenase- and control-treated hemilarynges. Texture analysis of the lamina propria at each injection site was performed to extract image contrast. Two-factor repeated measure analysis of variance and t tests were used to determine statistical significance. Picrosirius red staining was performed to confirm collagenase activity. Mean pixel intensity was higher at injection sites of collagenase-treated vocal folds than control vocal folds (P Fold change in image contrast was significantly increased in collagenase-treated vocal folds than control vocal folds (P = .002). Picrosirius red staining in control specimens revealed collagen fibrils most prominent in the subepithelium and above the thyroarytenoid muscle. Specimens treated with collagenase exhibited a loss of these structures. Collagen removal from vocal fold tissue increases image brightness of underlying structures. This inverse relationship may be useful in treating vocal fold scarring in patients. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2016.

Modulating Phonation Through Alteration of Vocal Fold Medial Surface Contour

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Mau, Ted; Muhlestein, Joseph; Callahan, Sean; Chan, Roger W.

2012-01-01

Objectives 1. To test whether alteration of the vocal fold medial surface contour can improve phonation. 2. To demonstrate that implant material properties affect vibration even when implant is deep to the vocal fold lamina propria. Study Design Induced phonation of excised human larynges. Methods Thirteen larynges were harvested within 24 hours post-mortem. Phonation threshold pressure (PTP) and flow (PTF) were measured before and after vocal fold injections using either calcium hydroxylapatite (CaHA) or hyaluronic acid (HA). Small-volume injections (median 0.0625 mL) were targeted to the infero-medial aspect of the thyroarytenoid (TA) muscle. Implant locations were assessed histologically. Results The effect of implantation on PTP was material-dependent. CaHA tended to increase PTP, whereas HA tended to decrease PTP (Wilcoxon test P = 0.00013 for onset). In contrast, the effect of implantation on PTF was similar, with both materials tending to decrease PTF (P = 0.16 for onset). Histology confirmed implant presence in the inferior half of the vocal fold vertical thickness. Conclusions Taken together, these data suggested the implants may have altered the vocal fold medial surface contour, potentially resulting in a less convergent or more rectangular glottal geometry as a means to improve phonation. An implant with a closer viscoelastic match to vocal fold cover is desirable for this purpose, as material properties can affect vibration even when the implant is not placed within the lamina propria. This result is consistent with theoretical predictions and implies greater need for surgical precision in implant placement and care in material selection. PMID:22865592

Expression and distribution of hyaluronic acid and CD44 in unphonated human vocal fold mucosa.

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Sato, Kiminori; Umeno, Hirohito; Nakashima, Tadashi; Nonaka, Satoshi; Harabuchi, Yasuaki

2009-11-01

The tension caused by phonation (vocal fold vibration) is hypothesized to stimulate vocal fold stellate cells (VFSCs) in the maculae flavae (MFe) to accelerate production of extracellular matrices. The distribution of hyaluronic acid (HA) and expression of CD44 (a cell surface receptor for HA) were examined in human vocal fold mucosae (VFMe) that had remained unphonated since birth. Five specimens of VFMe (3 adults, 2 children) that had remained unphonated since birth were investigated with Alcian blue staining, hyaluronidase digestion, and immunohistochemistry for CD44. The VFMe containing MFe were hypoplastic and rudimentary. The VFMe did not have a vocal ligament, Reinke's space, or a layered structure, and the lamina propria appeared as a uniform structure. In the children, HA was distributed in the VFMe containing MFe. In the adults, HA had decreased in the VFMe containing MFe. In both groups, the VFSCs in the MFe and the fibroblasts in the lamina propria expressed little CD44. This study supports the hypothesis that the tensions caused by vocal fold vibration stimulate the VFSCs in the MFe to accelerate production of extracellular matrices and form the layered structure. Phonation after birth is one of the important factors in the growth and development of the human VFMe.

Sex Hormone Receptor Expression in the Human Vocal Fold Subunits.

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Kirgezen, Tolga; Sunter, Ahmet Volkan; Yigit, Ozgur; Huq, Gulben Erdem

2017-07-01

The study aimed to evaluate the existence of sex hormone receptors in the subunits of vocal fold. This is a cadaver study. The androgen, estrogen, and progesterone receptors were examined in the epithelium (EP), superficial layer of the lamina propria (SLP), vocal ligament (VL), and macula flava (MF) of the vocal folds from 42 human cadavers (21 male, 21 female) by immunohistochemical methods. Their staining ratios were scored and statistically compared. The androgen receptor score was significantly higher for the MF than for the EP and SLP (P vocal fold, mostly in the MF and VLs. Copyright © 2017 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

Immunomodulation by Bifidobacterium infantis 35624 in the murine lamina propria requires retinoic acid-dependent and independent mechanisms.

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Patrycja Konieczna

Full Text Available Appropriate dendritic cell processing of the microbiota promotes intestinal homeostasis and protects against aberrant inflammatory responses. Mucosal CD103(+ dendritic cells are able to produce retinoic acid from retinal, however their role in vivo and how they are influenced by specific microbial species has been poorly described. Bifidobacterium infantis 35624 (B. infantis feeding to mice resulted in increased numbers of CD103(+retinaldehyde dehydrogenase (RALDH(+ dendritic cells within the lamina propria (LP. Foxp3(+ lymphocytes were also increased in the LP, while TH1 and TH17 subsets were decreased. 3,7-dimethyl-2,6-octadienal (citral treatment of mice blocked the increase in CD103(+RALDH(+ dendritic cells and the decrease in TH1 and TH17 lymphocytes, but not the increase in Foxp3(+ lymphocytes. B. infantis reduced the severity of DSS-induced colitis, associated with decreased TH1 and TH17 cells within the LP. Citral treatment confirmed that these effects were RALDH mediated. RALDH(+ dendritic cells decreased within the LP of control inflamed animals, while RALDH(+ dendritic cells numbers were maintained in the LP of B. infantis-fed mice. Thus, CD103(+RALDH(+ LP dendritic cells are important cellular targets for microbiota-associated effects on mucosal immunoregulation.

Eosinophils from Murine Lamina Propria Induce Differentiation of Naïve T Cells into Regulatory T Cells via TGF-β1 and Retinoic Acid.

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Hong-Hu Chen

Full Text Available Treg cells play a crucial role in immune tolerance, but mechanisms that induce Treg cells are poorly understood. We here have described eosinophils in lamina propria (LP that displayed high aldehyde dehydrogenase (ALDH activity, a rate-limiting step during all-trans retinoic acid (ATRA synthesis, and expressed TGF-β1 mRNA and high levels of ATRA. Co-incubation assay confirmed that LP eosinophils induced the differentiation of naïve T cells into Treg cells. Differentiation promoted by LP eosinophils were inhibited by blocked either TGF-β1 or ATRA. Peripheral blood (PB eosinophils did not produce ATRA and could not induce Treg differentiation. These data identifies LP eosinophils as effective inducers of Treg cell differentiation through a mechanism dependent on TGF-β1 and ATRA.

Cogels of Hyaluronic Acid and Acellular Matrix for Cultivation of Adipose-Derived Stem Cells: Potential Application for Vocal Fold Tissue Engineering

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Dongyan Huang

2016-01-01

Full Text Available Stem cells based tissue engineering has been one of the potential promising therapies in the research on the repair of tissue diseases including the vocal fold. Decellularized extracellular matrix (DCM as a promising scaffold has be used widely in tissue engineering; however, it remained to be an important issue in vocal fold regeneration. Here, we applied the hydrogels (hyaluronic acid [HA], HA-collagen [HA-Col], and HA-DCM to determine the effects of hydrogel on the growth and differentiation of human adipose-derived stem cells (hADSCs into superficial lamina propria fibroblasts. hADSCs were isolated and characterized by fluorescence-activated cell sorting. The results indicated that HA-DCM hydrogel enhanced cell proliferation and prolonged cell morphology significantly compared to HA and HA-Col hydrogel. Importantly, the differentiation of hADSCs into fibroblasts was also promoted by cogels of HA-Col and HA-DCM significantly. The differentiation of hADSCs towards superficial lamina propria fibroblasts was accelerated by the secretion of HGF, IL-8, and VEGF, the decorin and elastin expression, and the synthesis of chondroitin sulfate significantly. Therefore, the cogel of HA-DCM hydrogel was shown to be outstanding in apparent stimulation of hADSCs proliferation and differentiation to vocal fold fibroblasts through secretion of important growth factors and synthesis of extracellular matrix.

High- and ultrahigh-field magnetic resonance imaging of naïve, injured and scarred vocal fold mucosae in rats

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Kishimoto, Ayami Ohno; Kishimoto, Yo; Young, David L.; Zhang, Jinjin

2016-01-01

ABSTRACT Subepithelial changes to the vocal fold mucosa, such as fibrosis, are difficult to identify using visual assessment of the tissue surface. Moreover, without suspicion of neoplasm, mucosal biopsy is not a viable clinical option, as it carries its own risk of iatrogenic injury and scar formation. Given these challenges, we assessed the ability of high- (4.7 T) and ultrahigh-field (9.4 T) magnetic resonance imaging to resolve key vocal fold subepithelial tissue structures in the rat, an important and widely used preclinical model in vocal fold biology. We conducted serial in vivo and ex vivo imaging, evaluated an array of acquisition sequences and contrast agents, and successfully resolved key anatomic features of naïve, acutely injured, and chronically scarred vocal fold mucosae on the ex vivo scans. Naïve lamina propria was hyperintense on T1-weighted imaging with gadobenate dimeglumine contrast enhancement, whereas chronic scar was characterized by reduced lamina propria T1 signal intensity and mucosal volume. Acutely injured mucosa was hypointense on T2-weighted imaging; lesion volume steadily increased, peaked at 5 days post-injury, and then decreased – consistent with the physiology of acute, followed by subacute, hemorrhage and associated changes in the magnetic state of hemoglobin and its degradation products. Intravenous administration of superparamagnetic iron oxide conferred no T2 contrast enhancement during the acute injury period. These findings confirm that magnetic resonance imaging can resolve anatomic substructures within naïve vocal fold mucosa, qualitative and quantitative features of acute injury, and the presence of chronic scar. PMID:27638667

High- and ultrahigh-field magnetic resonance imaging of naïve, injured and scarred vocal fold mucosae in rats.

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Kishimoto, Ayami Ohno; Kishimoto, Yo; Young, David L; Zhang, Jinjin; Rowland, Ian J; Welham, Nathan V

2016-11-01

Subepithelial changes to the vocal fold mucosa, such as fibrosis, are difficult to identify using visual assessment of the tissue surface. Moreover, without suspicion of neoplasm, mucosal biopsy is not a viable clinical option, as it carries its own risk of iatrogenic injury and scar formation. Given these challenges, we assessed the ability of high- (4.7 T) and ultrahigh-field (9.4 T) magnetic resonance imaging to resolve key vocal fold subepithelial tissue structures in the rat, an important and widely used preclinical model in vocal fold biology. We conducted serial in vivo and ex vivo imaging, evaluated an array of acquisition sequences and contrast agents, and successfully resolved key anatomic features of naïve, acutely injured, and chronically scarred vocal fold mucosae on the ex vivo scans. Naïve lamina propria was hyperintense on T1-weighted imaging with gadobenate dimeglumine contrast enhancement, whereas chronic scar was characterized by reduced lamina propria T1 signal intensity and mucosal volume. Acutely injured mucosa was hypointense on T2-weighted imaging; lesion volume steadily increased, peaked at 5 days post-injury, and then decreased - consistent with the physiology of acute, followed by subacute, hemorrhage and associated changes in the magnetic state of hemoglobin and its degradation products. Intravenous administration of superparamagnetic iron oxide conferred no T2 contrast enhancement during the acute injury period. These findings confirm that magnetic resonance imaging can resolve anatomic substructures within naïve vocal fold mucosa, qualitative and quantitative features of acute injury, and the presence of chronic scar. © 2016. Published by The Company of Biologists Ltd.

High- and ultrahigh-field magnetic resonance imaging of naïve, injured and scarred vocal fold mucosae in rats

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Ayami Ohno Kishimoto

2016-11-01

Full Text Available Subepithelial changes to the vocal fold mucosa, such as fibrosis, are difficult to identify using visual assessment of the tissue surface. Moreover, without suspicion of neoplasm, mucosal biopsy is not a viable clinical option, as it carries its own risk of iatrogenic injury and scar formation. Given these challenges, we assessed the ability of high- (4.7 T and ultrahigh-field (9.4 T magnetic resonance imaging to resolve key vocal fold subepithelial tissue structures in the rat, an important and widely used preclinical model in vocal fold biology. We conducted serial in vivo and ex vivo imaging, evaluated an array of acquisition sequences and contrast agents, and successfully resolved key anatomic features of naïve, acutely injured, and chronically scarred vocal fold mucosae on the ex vivo scans. Naïve lamina propria was hyperintense on T1-weighted imaging with gadobenate dimeglumine contrast enhancement, whereas chronic scar was characterized by reduced lamina propria T1 signal intensity and mucosal volume. Acutely injured mucosa was hypointense on T2-weighted imaging; lesion volume steadily increased, peaked at 5 days post-injury, and then decreased – consistent with the physiology of acute, followed by subacute, hemorrhage and associated changes in the magnetic state of hemoglobin and its degradation products. Intravenous administration of superparamagnetic iron oxide conferred no T2 contrast enhancement during the acute injury period. These findings confirm that magnetic resonance imaging can resolve anatomic substructures within naïve vocal fold mucosa, qualitative and quantitative features of acute injury, and the presence of chronic scar.

Drug delivery system of basic fibroblast growth factor using gelatin hydrogel for restoration of acute vocal fold scar.

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Kobayashi, Toshiki; Mizuta, Masanobu; Hiwatashi, Nao; Kishimoto, Yo; Nakamura, Tatsuo; Kanemaru, Shin-Ichi; Hirano, Shigeru

2017-02-01

There continue to be therapeutic challenges in the management of vocal fold scarring. We previously showed that basic fibroblast growth factor (bFGF) injection has therapeutic potential for vocal fold scarring. However, the working time of bFGF is relatively short, and multiple injections were required in many cases to obtain the regenerative effect. An efficacious delivery system for bFGF has yet to be established. We designed a method of sustained drug delivery system (DDS) of bFGF by using a gelatin hydrogel. Hydrogel has been developed for targeted delivery and controlled release of bFGF. Hydrogel of the particle type is also injectable and commercially available. The current study aims to investigate the effects of a single injection of bFGF-DDS on acute vocal fold scarring using a canine model. Vocal folds from eight beagles were unilaterally scarred by stripping the lamina propria. One month later, hydrogels (0.5ml) containing 10μg of bFGF were injected into the scarred vocal folds of four beagles (FGF-hydrogel group). Saline (0.5ml) was injected into the other four beagles (sham group). Vibratory and histological examination of excised larynges was performed 5 months after treatment. Comparative analysis between the current data and our previous data with repeated injection of bFGF solution was also completed. Vibratory examination demonstrated significantly improved vibration in the bFGF hydrogel-treated group. Histological examination of the bFGF hydrogel group showed restoration of hyaluronic acid in the lamina propria as compared to sham. Comparison between the DDS system and our previous bFGF solution injection indicated better effects of the DDS system on vibratory amplitude. A single injection of bFGF hydrogel has regenerative effects on acute vocal fold scarring, which is at least similar to repeated injection of bFGF solution. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Use of Ulex europaeus agglutinin I (UEAI) to distinguish vascular and "pseudovascular" invasion in transitional cell carcinoma of bladder with lamina propria invasion.

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Larsen, M P; Steinberg, G D; Brendler, C B; Epstein, J I

1990-01-01

We used Ulex europaeus agglutinin I (UEAI)-immunoperoxidase staining of endothelium to study the accuracy of hematoxylin and eosin (H&E) diagnosis, occurrence, and significance of lymphvascular invasion in transitional cell carcinoma (TCC) of the bladder invading the lamina propria (Stage T1). Original histologic slides from cases (1967 to 1985) with and without vascular invasion were destained and restained with UEAI-immunoperoxidase. Only 5 of 36 biopsies originally diagnosed with lymphvascular invasion had tumor nests within endothelium-lined spaces. The 31 negative biopsies had extensive retraction artifacts lined by connective tissue and fibroblasts around tumor nests. Thirty-five control biopsies remained negative for lymphvascular invasion. Clinical follow-up of the five patients with proven lymphvascular invasion found three without progression of disease 3 to 10 yr postbiopsy, one dead of a local recurrence of TCC 1.67 yr postbiopsy, and one lost to follow-up. Based on this study, we feel that lymphvascular invasion by TCC in Stage T1 tumors is unusual, is frequently misdiagnosed on H&E stain, and does not necessarily portend a poor prognosis.

Temporalis Fascia Transplantation for Sulcus Vocalis and Vocal Fold Scar: Long-Term Outcomes.

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Karle, William E; Helman, Samuel N; Cooper, Amy; Zhang, Yuan; Pitman, Michael J

2018-04-01

Sulcus vocalis and vocal fold scar involve derangement of the superficial lamina propria of the vocal fold, which results in significant dysphonia. Many options exist for treatment, most of which have unsatisfactory and unpredictable outcomes. Autologous transplantation of temporalis fascia into the vocal fold (ATFV) has the potential to be a better treatment option, but long-term outcomes have not been well studied. Retrospective chart review and patient survey. Twenty-one patients diagnosed with vocal fold scar or sulcus vocalis and treated with ATFV with at least 1-year follow-up were included. Voice Handicap Index 10 (VHI-10) questionnaires were collected preoperatively and 6 months postoperatively. Patients were reached at the time of the study to complete another VHI-10 and a Likert scale survey. The mean decrease in VHI-10 scores between preoperation and 6 months postoperation was 8.35 ( P vocal fold for the treatment of vocal fold scar and sulcus vocalis is a safe surgery with good long-term outcomes and high patient satisfaction.

CXCL14-like Immunoreactivity Exists in Somatostatin-containing Endocrine Cells, and in the Lamina Propria and Submucosal Somatostatinergic Nervous System of Mouse Alimentary Tract.

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Suzuki, Hirohumi; Yamada, Kentaro; Matsuda, Yasuhiro; Onozuka, Minoru; Yamamoto, Toshiharu

2017-12-26

In the present study, we investigated the distribution of CXCL14 immunoreactive endocrine cells and neurons in mouse alimentary tract by immunohistochemistry. CXCL14 immunoreactive endocrine cells were found as closed-type cells in the stomach and open-type cells in the small intestine. The immunostaining of these endocrine cells corresponded with that of the somatostatin-containing endocrine cells. Only a few CXCL14 immunoreactive endocrine cells were seen in the large intestine. CXCL14 immunoreactive fibers were observed in the muscular layer from the stomach to the rectum with most abundance in the rectum. Many CXCL14 immunoreactive fibers were observed in the lamina propria and submucosal layer from the duodenum to the rectum with most abundance in the rectum; these fibers corresponded to the somatostatin-containing nerve fibers. Some CXCL14 immunoreactive neuronal somata that were also immuno-positive for somatostatin, were noted in the submucosal layer of the rectum. However, the remaining parts of the alimentary tract presented with almost negligible immunoreactive somata. The co-localization of CXCL14 and somatostatin suggests that CXCL14 contributes to the function of somatostatin, which include the inhibition of other endocrine and exocrine cells and the enteric nervous systems.

Histopathologic study of human vocal fold mucosa unphonated over a decade.

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Sato, Kiminori; Umeno, Hirohito; Ono, Takeharu; Nakashima, Tadashi

2011-12-01

Mechanotransduction caused by vocal fold vibration could possibly be an important factor in the maintenance of extracellular matrices and layered structure of the human adult vocal fold mucosa as a vibrating tissue after the layered structure has been completed. Vocal fold stellate cells (VFSCs) in the human maculae flavae of the vocal fold mucosa are inferred to be involved in the metabolism of extracellular matrices of the vocal fold mucosa. Maculae flavae are also considered to be an important structure in the growth and development of the human vocal fold mucosa. Tension caused by phonation (vocal fold vibration) is hypothesized to stimulate the VFSCs to accelerate production of extracellular matrices. A human adult vocal fold mucosa unphonated over a decade was investigated histopathologically. Vocal fold mucosa unphonated for 11 years and 2 months of a 64-year-old male with cerebral hemorrhage was investigated by light and electron microscopy. The vocal fold mucosae (including maculae flavae) were atrophic. The vocal fold mucosa did not have a vocal ligament, Reinke's space or a layered structure. The lamina propria appeared as a uniform structure. Morphologically, the VFSCs synthesized fewer extracellular matrices, such as fibrous protein and glycosaminoglycan. Consequently, VFSCs appeared to decrease their level of activity.

CD4+ T regulatory cells from the colonic lamina propria of normal mice inhibit proliferation of enterobacteria-reactive, disease-inducing Th1-cells from scid mice with colitis

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Gad, M; Brimnes, J; Claesson, Mogens Helweg

2003-01-01

Adoptive transfer of CD4+ T cells into scid mice leads to a chronic colitis in the recipients. The transferred CD4+ T cells accumulate in the intestinal lamina propria (LP), express an activated Th1 phenotype and proliferate vigorously when exposed ex vivo to enteric bacterial antigens. As LP CD4......+ T cells from normal BALB/c mice do not respond to enteric bacterial antigens, we have investigated whether colonic LP-derived CD4+ T cells from normal mice suppress the antibacterial response of CD4+ T cells from scid mice with colitis. LP-derived CD4+ T cells cocultured with bone marrow......-derived dendritic cells effectively suppress the antibacterial proliferative response of CD4+ T cells from scid mice with colitis. The majority of these LP T-reg cells display a nonactivated phenotype and suppression is independent of antigen exposure, is partly mediated by soluble factor(s) different from IL-10...

Stretch independent regulation of prostaglandin E(2) production within the isolated guinea-pig lamina propria.

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Nile, Christopher J; de Vente, Jan; Gillespie, James I

2010-02-01

To use an isolated preparation of the guinea-pig bladder lamina propria (LP) to investigate the effects of adenosine tri-phosphate (ATP) and nitric oxide (NO) on the release of prostaglandin E(2) (PGE(2)). The bladders of female guinea-pigs (200-400 g) were isolated and opened to expose the urothelial surface. The LP was dissected free of the underlying detrusor muscle and cut into strips from the dome to base. Strips were then incubated in Krebs buffer at 37 degrees C. Each tissue piece was then exposed to the stable ATP analogue, BzATP, and a NO donor, diethylamine-NONOate (DEANO), and the effect on PGE(2) output into the supernatant determined using the Parameter(TM) PGE(2) enzyme immunoassay kit (R & D Systems, Abingdon, UK). Experiments were repeated in the presence of purinergic receptor and cyclooxygenase (COX) enzymes, COX I and COX II, antagonists. The cellular location of COX I, COX II and neuronal NO synthase (nNOS) within the bladder LP was also determined by immunohistochemistry. PGE(2) production was significantly increased by BzATP. Antagonist studies showed the purinergic stimulation involved both P(2)X and P(2)Y receptors. The BzATP response was inhibited by the COX inhibitor indomethacin (COX I >COX II) but not by DUP 697 (COX II >COX I). Thus, BzATP stimulation occurs because of COX I stimulation. NO had no effect on PGE(2) production over the initial 10 min of an exposure. However, PGE(2) output was increased 100 min after exposure to the NO donor. In the presence of NO, the BzATP stimulation was abolished. Immunohistochemistry was used to confirm the location of COX I to the basal and inner intermediate urothelial layers and to cells within the diffuse layer of LP interstitial cells. In addition, nNOS was also located in the basal urothelial layers whilst COX II was found in the interstitial cell layers. There is complex interaction between ATP and NO to modulate PGE(2) release from the bladder LP in the un-stretched preparation. Such

Cross-sample validation provides enhanced proteome coverage in rat vocal fold mucosa.

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Nathan V Welham

2011-03-01

Full Text Available The vocal fold mucosa is a biomechanically unique tissue comprised of a densely cellular epithelium, superficial to an extracellular matrix (ECM-rich lamina propria. Such ECM-rich tissues are challenging to analyze using proteomic assays, primarily due to extensive crosslinking and glycosylation of the majority of high M(r ECM proteins. In this study, we implemented an LC-MS/MS-based strategy to characterize the rat vocal fold mucosa proteome. Our sample preparation protocol successfully solubilized both proteins and certain high M(r glycoconjugates and resulted in the identification of hundreds of mucosal proteins. A straightforward approach to the treatment of protein identifications attributed to single peptide hits allowed the retention of potentially important low abundance identifications (validated by a cross-sample match and de novo interpretation of relevant spectra while still eliminating potentially spurious identifications (global single peptide hits with no cross-sample match. The resulting vocal fold mucosa proteome was characterized by a wide range of cellular and extracellular proteins spanning 12 functional categories.

Single injection of basic fibroblast growth factor to treat severe vocal fold lesions and vocal fold paralysis.

Science.gov (United States)

Kanazawa, Takeharu; Komazawa, Daigo; Indo, Kanako; Akagi, Yusuke; Lee, Yogaku; Nakamura, Kazuhiro; Matsushima, Koji; Kunieda, Chikako; Misawa, Kiyoshi; Nishino, Hiroshi; Watanabe, Yusuke

2015-10-01

Severe vocal fold lesions such as vocal fold sulcus, scars, and atrophy induce a communication disorder due to severe hoarseness, but a treatment has not been established. Basic fibroblast growth factor (bFGF) therapies by either four-time repeated local injections or regenerative surgery for vocal fold scar and sulcus have previously been reported, and favorable outcomes have been observed. In this study, we modified bFGF therapy using a single of bFGF injection, which may potentially be used in office procedures. Retrospective chart review. Five cases of vocal fold sulcus, six cases of scars, seven cases of paralysis, and 17 cases of atrophy were treated by a local injection of bFGF. The injection regimen involved injecting 50 µg of bFGF dissolved in 0.5 mL saline only once into the superficial lamina propria using a 23-gauge injection needle. Two months to 3 months after the injection, phonological outcomes were evaluated. The maximum phonation time (MPT), mean airflow rate, pitch range, speech fundamental frequency, jitter, and voice handicap index improved significantly after the bFGF injection. Furthermore, improvement in the MPT was significantly greater in patients with (in increasing order) vocal fold atrophy, scar, and paralysis. The improvement in the MPT among all patients was significantly correlated with age; the MPT improved more greatly in younger patients. Regenerative treatments by bFGF injection—even a single injection—effectively improve vocal function in vocal fold lesions. 4 © 2015 The American Laryngological, Rhinological and Otological Society, Inc.

Microscopic Colitis Evolved Into Inflammatory Bowel Diseases Is Characterized by Increased Th1/Tc1 Cells in Colonic Mucosal Lamina Propria.

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Li, Ji; Yan, Yuchu; Meng, Ziran; Liu, Shuhong; Beck, Paul L; Ghosh, Subrata; Qian, Jiaming; Gui, Xianyong

2017-10-01

An association between microscopic colitis (MC), i.e., lymphocytic colitis (LC) and collagenous colitis (CC), and inflammatory bowel diseases (IBD) has been noticed. A subset of MC cases may evolve into IBD, and IBD in remission may present as MC in a histologic pattern. Moreover, MC and IBD may coexist in different regions of the bowel. A link between MC and IBD in their pathogenesis is, therefore, suggested. Abnormal mucosal immunity is likely the key. We reviewed 2324 MC cases in Calgary over 14 years and identified 20 cases evolved into IBD (IBD transformers). 13 of them were further investigated for colonic mucosal lamina propria mononuclear cells (LPMNCs), as opposed to 22 cases whose MC resolved. On their index colonic biopsy immunohistochemistry was performed to detect major T cell subsets characterized by key cytokines and master transcription factors (IFNγ and T-bet for Th1/Tc1, GATA-3 for Th2/Tc2, IL-17 and RORc for Th17/Tc17, FoxP3 for Treg/Tcreg) as well as TNFα + cells (partly representing Th1). LPMNCs positive for each marker were counted (average number per high-power field). IBD transformers had increased IFNγ + , T-bet + , TNF-α + , and GATA-3 + LPMNCs compared to the MC-resolved cases. The LC-to-IBD subgroup had increased IFNγ + and GATA-3 + cells compared to the LC-resolved subgroup. The CC-to-IBD subgroup had increased T-bet + , TNF-α + , and GATA-3 + cells compared to the CC-resolved subgroup. Among MC-resolved patients, more TNF-α + and RORc + cells were seen in LC than in CC. Th1/Tc1- and TNFα-producing cells, and likely a subset of Th2/Tc2 cells as well, may be involved in the MC-to-IBD transformation.

Regulatory role of NKG2D+ NK cells in intestinal lamina propria by secreting double-edged Th1 cytokines in ulcerative colitis.

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Wang, Fan; Peng, Pai-Lan; Lin, Xue; Chang, Ying; Liu, Jing; Zhou, Rui; Nie, Jia-Yan; Dong, Wei-Guo; Zhao, Qiu; Li, Jin

2017-11-17

The role of intestinal lamina propria (LP) NKG2D+ NK cells is unclear in regulating Th1/Th2 balance in ulcerative colitis (UC). In this study, we investigated the frequency of LP NKG2D+ NK cells in DSS-induced colitis model and intestinal mucosal samples of UC patients, as well as the secretion of Th1/Th2/Th17 cytokines in NK cell lines after MICA stimulation. The role of Th1 cytokines in UC was validated by bioinformatics analysis. We found that DSS-induced colitis in mice was characterized by a Th2-mediated process. In acute phrase, the frequency of LP NKG2D+ lymphocytes increased significantly and decreased in remission, while the frequency of LP NKG2D+ NK cells decreased significantly in acute phase and increased in remission. No obvious change was found in the frequency of total LP NK cells. Similarly, severe UC patients had a higher expression of mucosal NKG2D and a lower number of NKG2D+ NK cells than mild to moderate UC. In NK cell lines, the MICA stimulation could induce a predominant secretion of Th1 cytokines (TNF, IFN-γ). Furthermore, in bioinformatics analysis, mucosal Th1 cytokine of TNF, showed a double-edged role in UC when compared to the Th1-mediated disease of Crohn's colitis. In conclusion, LP NKG2D+ NK cells partially played a regulatory role in UC through secreting Th1 cytokines to regulate the Th2-predominant Th1/Th2 imbalance, despite of the concomitant pro-inflammatory effects of Th1 cytokines.

Insights into the role of elastin in vocal fold health and disease

Science.gov (United States)

Moore, Jaime

2011-01-01

Elastic fibers are large, complex and surprisingly poorly understood extracellular matrix (ECM) macromolecules. The elastin fiber, generated from a single human gene - elastin (ELN), is a self assembling integral protein that endows critical mechanic proprieties to elastic tissues and organs such as the skin, lungs, and arteries. The biology of elastic fibers is complex because they have multiple components, a tightly regulated developmental deposition, a multi-step hierarchical assembly and unique biomechanical functions. Elastin is present in vocal folds, where it plays a pivotal role in the quality of phonation. This review article provides an overview of the genesis of elastin and its wide- ranging structure and function. Specific distribution within the vocal fold lamina propria across the lifespan in normal and pathological states and its contribution to vocal fold biomechanics will be examined. Elastin and elastin-derived molecules are increasingly investigated for their application in tissue engineering. The properties of various elastin– based materials will be discussed and their current and future applications evaluated. A new level of understanding of the biomechanical properties of vocal fold elastin composites and their molecular basis should lead to new strategies for elastic fiber repair and regeneration in aging and disease. PMID:21708449

Quantification of change in vocal fold tissue stiffness relative to depth of artificial damage.

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Rohlfs, Anna-Katharina; Schmolke, Sebastian; Clauditz, Till; Hess, Markus; Müller, Frank; Püschel, Klaus; Roemer, Frank W; Schumacher, Udo; Goodyer, Eric

2017-10-01

To quantify changes in the biomechanical properties of human excised vocal folds with defined artificial damage. The linear skin rheometer (LSR) was used to obtain a series of rheological measurements of shear modulus from the surface of 30 human cadaver vocal folds. The tissue samples were initially measured in a native condition and then following varying intensities of thermal damage. Histological examination of each vocal fold was used to determine the depth of artificial alteration. The measured changes in stiffness were correlated with the depth of cell damage. For vocal folds in a pre-damage state the shear modulus values ranged from 537 Pa to 1,651 Pa (female) and from 583 Pa to 1,193 Pa (male). With increasing depth of damage from the intermediate layer of the lamina propria (LP), tissue stiffness increased consistently (compared with native values) following application of thermal damage to the vocal folds. The measurement showed an increase of tissue stiffness when the depth of tissue damage was extending from the intermediate LP layer downwards. Changes in the elastic characteristics of human vocal fold tissue following damage at defined depths were demonstrated in an in vitro experiment. In future, reproducible in vivo measurements of elastic vocal fold tissue alterations may enable phonosurgeons to infer the extent of subepithelial damage from changes in surface elasticity.

Functional histology of the macula flava in the human vocal fold--Part 1: its role in the adult vocal fold.

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Sato, Kiminori; Umeno, Hirohito; Nakashima, Tadashi

2010-01-01

This study aims to clarify the role of the maculae flavae (MFe) in the human adult vocal fold mucosa (VFM). Our current results concerning MFe in the human adult VFM are summarized. MFe were found to be composed of dense masses of vocal fold stellate cells (VFSCs) and extracellular matrices (EM), such as fibrous proteins and glycosaminoglycans, which are essential for the EM in the human VFM. VFSCs in the MFe demonstrated marked morphologic differences from conventional fibroblasts. They were irregular and stellate in shape and possessed slender cytoplasmic processes. They had well-developed intracellular organelles. A number of vesicles were present at the periphery of the cytoplasm. They constantly synthesized EM. The VFSCs possessed lipid droplets and stored vitamin A. VFSCs formed an independent cell category of cells in the human VFM. The VFSCs in aged adult MFe decreased their activity, and had abnormal metabolism. Human MFe including VFSCs seem to be involved in the metabolism of EM which are essential for the viscoelasticity of the lamina propria of the VFM, and to be responsible for maintaining the characteristic layered structure of the human VFM. Age-related changes in VFSCs were found to influence the metabolism of EM in the VFM. (c) 2010 S. Karger AG, Basel.

Reinke’s Edema: investigations on the role of MIB-1 and hepatocyte growth factor

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M. Artico

2010-07-01

Full Text Available Reinke’s edema is a benign disease of the human vocal fold, which mainly affects the sub-epithelial layer of the vocal fold. Micro­scopic observations show a strongly oedematous epithelium with loosened intercellular junctions, a disruption of the extracellular connections between mucosal epithelium and connective tissue, closely adherent to the thyroarytenoid muscle. Thickening of the basal layer of epithelium, known as Reinke’s space, high deposition of fibronectin and chronic inflammatory infiltration it is also visible. We analyzed, together with the hepatocyte growth factor (HGF, the expression level of MIB-1 in samples harvested from patients affected by Reinke’s edema, in order to define its biological role and consider it as a possible prognostic factor in the follow-up after surgical treatment. We observed a moderate expression of HGF in the lamina propria of the human vocal fold and in the basal membrane of the mucosal epithelium. Our finding suggests that this growth factor acts as an anti – fibrotic agent in Reinke’s space and affects the fibronectin deposition in the lamina propria. MIB-1, on the contrary, showed a weak expression in the basement membrane of the mucosal epithelium and a total absence in the lamina propria deep layer, thus suggesting that only the superficial layer is actively involved in the reparatory process with a high regenerative capacity, together with a high deposition of fibronectin. The latter is necessary for the cellular connections reconstruction, after the inflammatory infiltration.

Reinke's edema: investigations on the role of MIB-1 and hepatocyte growth factor.

Science.gov (United States)

Artico, M; Bronzetti, E; Ionta, B; Bruno, M; Greco, A; Ruoppolo, G; De Virgilio, A; Longo, L; De Vincentiis, M

2010-07-08

Reinke's edema is a benign disease of the human vocal fold, which mainly affects the sub-epithelial layer of the vocal fold. Microscopic observations show a strongly oedematous epithelium with loosened intercellular junctions, a disruption of the extracellular connections between mucosal epithelium and connective tissue, closely adherent to the thyroarytenoid muscle. Thickening of the basal layer of epithelium, known as Reinke's space, high deposition of fibronectin and chronic inflammatory infiltration it is also visible. We analyzed, together with the hepatocyte growth factor (HGF), the expression level of MIB-1 in samples harvested from patients affected by Reinke's edema, in order to define its biological role and consider it as a possible prognostic factor in the follow-up after surgical treatment. We observed a moderate expression of HGF in the lamina propria of the human vocal fold and in the basal membrane of the mucosal epithelium. Our finding suggests that this growth factor acts as an antifibrotic agent in Reinke's space and affects the fibronectin deposition in the lamina propria. MIB-1, on the contrary, showed a weak expression in the basement membrane of the mucosal epithelium and a total absence in the lamina propria deep layer, thus suggesting that only the superficial layer is actively involved in the reparatory process with a high regenerative capacity, together with a high deposition of fibronectin. The latter is necessary for the cellular connections reconstruction, after the inflammatory infiltration.

Videostroboscopic and morphological aspects of voice disturbances in patients with larynx atrophy and coexisting hypopharynx cancer

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Dawid Falkowski

2012-01-01

Full Text Available Vocal folds play a crucial role in voice production. The physiological vibrations of vocal folds depend on the unchanged multilayered structure of the vocal folds mucosa. Morphological changes of mucosa are the cause of voice quality disorders — dysphonia. The aim of this study was to determine the morphological base of dysphonia in patients with vocal folds atrophy. A group of 24 patients with larynx atrophy confirmed by endoscopic (VLS and stroboscopic (VLSS examination of the larynx was included in the study. The morphological assessment of the larynx mucosa was carried out with the use of the transmission electron microscopy (TEM. Ultramorphological examinations revealed changes in the epithelium, basal membrane and lamina propria of the vocal folds mucosa. An increased number of collagenous fibers, fibroblasts with signs of vacuolar degeneration inflammatory cells and a decreased number of blood vessels and pericytes were observed. Morphological changes found in the epithelium, basal membrane and lamina propria of the vocal folds mucosa were the cause of disorders of vocal folds vibrations registered in the stroboscopic examination of the larynx (VLSS. (Folia Histochemica et Cytobiologica 2011; Vol. 49, No. 4, pp. 659–663

Adapted to roar: functional morphology of tiger and lion vocal folds.

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Sarah A Klemuk

Full Text Available Vocal production requires active control of the respiratory system, larynx and vocal tract. Vocal sounds in mammals are produced by flow-induced vocal fold oscillation, which requires vocal fold tissue that can sustain the mechanical stress during phonation. Our understanding of the relationship between morphology and vocal function of vocal folds is very limited. Here we tested the hypothesis that vocal fold morphology and viscoelastic properties allow a prediction of fundamental frequency range of sounds that can be produced, and minimal lung pressure necessary to initiate phonation. We tested the hypothesis in lions and tigers who are well-known for producing low frequency and very loud roaring sounds that expose vocal folds to large stresses. In histological sections, we found that the Panthera vocal fold lamina propria consists of a lateral region with adipocytes embedded in a network of collagen and elastin fibers and hyaluronan. There is also a medial region that contains only fibrous proteins and hyaluronan but no fat cells. Young's moduli range between 10 and 2000 kPa for strains up to 60%. Shear moduli ranged between 0.1 and 2 kPa and differed between layers. Biomechanical and morphological data were used to make predictions of fundamental frequency and subglottal pressure ranges. Such predictions agreed well with measurements from natural phonation and phonation of excised larynges, respectively. We assume that fat shapes Panthera vocal folds into an advantageous geometry for phonation and it protects vocal folds. Its primary function is probably not to increase vocal fold mass as suggested previously. The large square-shaped Panthera vocal fold eases phonation onset and thereby extends the dynamic range of the voice.

Oral Serum-Derived Bovine Immunoglobulin/Protein Isolate Has Immunomodulatory Effects on the Colon of Mice that Spontaneously Develop Colitis.

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Anna Pérez-Bosque

Full Text Available Dietary immunoglobulin concentrates prepared from animal plasma can modulate the immune response of gut-associated lymphoid tissue (GALT. Previous studies have revealed that supplementation with serum-derived bovine immunoglobulin/protein isolate (SBI ameliorates colonic barrier alterations in the mdr1a-/- genetic mouse model of IBD. Here, we examine the effects of SBI on mucosal inflammation in mdr1a-/- mice that spontaneously develop colitis. Wild type (WT mice and mice lacking the mdr1a gene (KO were fed diets supplemented with either SBI (2% w/w or milk proteins (Control diet, from day 21 (weaning until day 56. Leucocytes in mesenteric lymph nodes (MLN and in lamina propria were determined, as was mucosal cytokine production. Neutrophil recruitment and activation in MLN and lamina propria of KO mice were increased, but were significantly reduced in both by SBI supplementation (p < 0.05. The increased neutrophil recruitment and activation observed in KO mice correlated with increased colon oxidative stress (p < 0.05 and SBI supplementation reduced this variable (p < 0.05. The Tact/Treg lymphocyte ratios in MLN and lamina propria were also increased in KO animals, but SBI prevented these changes (both p < 0.05. In the colon of KO mice, there was an increased production of mucosal pro-inflammatory cytokines such as IL-2 (2-fold, IL-6 (26-fold and IL-17 (19-fold, and of chemokines MIP-1β (4.5-fold and MCP-1 (7.2-fold. These effects were significantly prevented by SBI (p < 0.05. SBI also significantly increased TGF-β secretion in the colon mucosa, suggesting a role of this anti-inflammatory cytokine in the modulation of GALT and the reduction of the severity of the inflammatory response during the onset of colitis.

Increased intracellular Th1 cytokines in scid mice with inflammatory bowel disease

DEFF Research Database (Denmark)

Bregenholt, S; Claesson, Mogens Helweg

1998-01-01

Severe combined immunodeficient (scid) mice engrafted with small pieces of full thickness gut wall from immunocompetent syngenic donors develop a chronic and lethal colitis. Lymphocytes from the lamina propria of engrafted mice were analyzed for phorbol ester/ionomycin-induced cytokine production...... by intracellular staining. A 4-5-fold increase in the fraction of IFN-gamma-producing CD4+ lamina propria T cells was found in moderately and severely diseased mice when compared to healthy congenic C.B-17 control mice. The number of IL-2-producing T cells was increased by approximately 2-fold when comparing mice...... suffering from severe disease to healthy control mice. The fraction of TNF-alpha positive CD4+ T cells was increased by a factor of two in both moderately and severely diseased mice. When analyzing Th2 cytokines, it was found that the levels of IL-4-producing CD4+ T cells was not altered in diseased animals...

The Ability of Human Nasal Inferior Turbinate-Derived Mesenchymal Stem Cells to Repair Vocal Fold Injuries.

Science.gov (United States)

Kim, Choung-Soo; Choi, Hyunsu; Park, Ki Cheol; Kim, Sung Won; Sun, Dong-Il

2018-03-01

Objective This study investigated the ability of implanted human nasal inferior turbinate-derived mesenchymal stem cells (hTMSCs) to repair injured vocal folds. To this end, we used quantitative real-time polymerase chain reaction (PCR) to analyze the early phase of wound healing and histopathological analysis to explore the late phase of wound healing in xenograft animal models. Study Design Prospective animal study. Setting Research laboratory. Subjects and Methods The right-side lamina propria of the vocal fold was injured in 20 rabbits and 30 rats. Next, hTMSCs were implanted into half of the injured vocal folds (hTMSC groups). As a control, phosphate-buffered saline (PBS) was injected into the other half of the injured vocal folds (PBS groups). Rat vocal folds were harvested for polymerase chain reaction (PCR) at 1 week after injury. Rabbit vocal folds were evaluated endoscopically and the larynges harvested for histological and immunohistochemical examination at 2 and 8 weeks after injury. Results In the hTMSC group, PCR showed that hyaluronan synthase ( HAS) 1, HAS 2, and transforming growth factor ( TGF)-β1 were significantly upregulated compared with the PBS group. Procollagen type III ( COL III) messenger RNA expression was significantly upregulated in the PBS group compared with the normal group. Histological analyses showed that hTMSC administration afforded more favorable collagen and hyaluronic acid deposition than was evident in the controls. Implanted hTMSCs were observed in injured vocal folds 2 weeks after implantation. Conclusions Our results show that hTMSCs implantation into injured vocal folds facilitated vocal fold regeneration, with presenting antifibrotic effects.

The Insulator Protein SU(HW) Fine-Tunes Nuclear Lamina Interactions of the Drosophila Genome

NARCIS (Netherlands)

Van Bemmel, J.G.; Pagie, L.; Braunschweig, U.; Brugman, W.; Meuleman, W.; Kerkhoven, R.M.; Van Steensel, B.

2010-01-01

Specific interactions of the genome with the nuclear lamina (NL) are thought to assist chromosome folding inside the nucleus and to contribute to the regulation of gene expression. High-resolution mapping has recently identified hundreds of large, sharply defined lamina-associated domains (LADs) in

Abaxial growth and steric constraints guide leaf folding and shape in Acer pseudoplatanus.

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Couturier, Etienne; Brunel, Nicole; Douady, Stéphane; Nakayama, Naomi

2012-08-01

How leaf shape is regulated is a long-standing question in botany. For diverse groups of dicotyledon species, lamina folding along the veins and geometry of the space available for the primordia can explain the palmate leaf morphology. Dubbed the kirigami theory, this hypothesis of fold-dependent leaf shape regulation has remained largely theoretical. Using Acer pseudoplatanus, we investigated the mechanisms behind the two key processes of kirigami leaf development. Cytological examination and quantitative analyses were used to examine the course of the vein-dependent lamina folding. Surgical ablation and tissue culturing were employed to test the effects of physical constraints on primordia growth. The final morphology of leaves growing without steric constraints were predicted mathematically. The cytological examination showed that the lamina's abaxial side along the veins grows substantially more than the adaxial side. The abaxial hypergrowth along the veins and the lamina extension correlated with the lamina folding. When a primordium was released from the physical constraints imposed by the other primordia, it rapidly grew into the newly available space, while maintaining the curvature inward. The morphology of such a leaf was predicted to lack symmetry in the lobe shapes. The enhanced growth on the abaxial side of the lamina along the veins is likely to drive lamina folding. The surgical ablation provided clear support for the space-filling nature of leaf growth; thus, steric constraints play a role in determination of the shapes of folded leaves and probably also of the final leaf morphology.

Multimodal imaging of vocal fold scarring in a rabbit model by multiphoton microscopy

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Kazarine, Alexei; Bouhabel, Sarah; Douillette, Annie H.; Kost, Karen; Li-Jessen, Nicole Y. K.; Mongeau, Luc; Wiseman, Paul W.

2017-02-01

Vocal fold scarring as a result of injury or disease can lead to voice disorders which can significantly affect the quality of life. During the scarring process, the normally elastic tissue of the vocal fold lamina propria is replaced by a much stiffer collagen-based fibrotic tissue, which impacts the fold's ability to vibrate. Surgical removal of this tissue is often ineffective and can result in further scarring. Injectable biomaterials, a form of tissue engineering, have been proposed as a potential solution to reduce existing scars or prevent scarring altogether. In order to properly evaluate the effectiveness of these new materials, multiphoton microscopy emerges as an effective tool due to its intrinsic multiple label free contrast mechanisms that highlight extracellular matrix elements. In this study, we evaluate the spatial distribution of collagen and elastin fibers in a rabbit model using second harmonic generation (SHG), third harmonic generation (THG) and two photon autofluorescence (TPAF) applied to unlabeled tissue sections. In comparison to traditional methods that rely on histological staining or immunohistochemistry, SHG, THG and TPAF provide a more reliable detection of these native proteins. The evaluation of collagen levels allows us to follow the extent of scarring, while the presence of elastin fibers is thought to be indicative of the level of healing of the injured fold. Using these imaging modalities, we characterize the outcome of injectable biomaterial treatments in order to direct future treatments for tissue engineering.

Process of tight junction recovery in the injured vocal fold epithelium: Morphological and paracellular permeability analysis.

Science.gov (United States)

Suzuki, Ryo; Katsuno, Tatsuya; Kishimoto, Yo; Nakamura, Ryosuke; Mizuta, Masanobu; Suehiro, Atsushi; Yamashita, Masaru; Nakamura, Tatsuo; Tateya, Ichiro; Omori, Koichi

2018-04-01

The vocal fold epithelium that includes tight junction (TJ)-based barrier function protects underlying connective tissues from external insults. TJs play an important role to control paracellular permeability of not only solutes but also ions, and preserve the vocal fold homeostasis. However, the distribution of TJs and paracellular diffusion barrier across the entire vocal fold epithelium are still unknown. The aim of this study was to identify the distribution of TJs in the vocal fold epithelium and to characterize the recovery process of TJ-based paracellular diffusion barrier in a rat model of vocal fold injury. Animal experiments with controls. Normal and vocal fold-injured rats were used. Larynges were harvested for immunohistochemical examination of TJ proteins. For functional analysis, a tracer permeability assay was performed using EZ-Link Sulfo-NHS-LC-Biotin. TJ proteins occludin and zonula occludens 1 signals were localized to the junctional regions of the most luminal cell layers of the vocal fold epithelium. The injured region had been recovered with epithelium at 5 days postinjury, but the paracellular diffusion barrier assays revealed that biotinylation reagents diffused into the lamina propria at 5 days postinjury, and were blocked at the epithelium at 14 and 28 days postinjury. It was strongly suggested that TJs in the vocal fold epithelium exist at the junctional regions of the first layer of stratified squamous epithelium. TJ-based paracellular diffusion barrier following vocal fold injury is recovered by 14 days postinjury, and this period corresponds with the time course of structural changes in the regenerating epithelium layer. NA. Laryngoscope, 128:E150-E156, 2018. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

A comparison of mode of attachment and histopathogenicity of four tapeworm species representing two orders infecting the spiral intestine of the nurse shark, Ginglymostoma cirratum.

Science.gov (United States)

Borucinska, J; Caira, J N

1993-04-01

This study was undertaken to compare 2 species of Tetraphyllidea and 2 species of Trypanorhyncha with regard to the relationship between attachment structure morphology, mode of attachment, and tapeworm size, to damage at the sites of attachment in the Atlantic nurse shark, Ginglymostoma cirratum. Regions of the spiral intestine with worms attached were removed from 8 nurse sharks and sectioned according to conventional techniques. Sections of 5-50 specimens of each tapeworm species were examined. Regions of the spiral intestine devoid of worms were processed for characterization of the normal mucosa. The normal mucosa was found to consist of a folded surface covered with round-to-oval primary mucosal crypts. In the first 7 or 8 chambers of the spiral intestine the mucosal surface was thrown into secondary folds, forming ridges and secondary crypts. The primary mucosal crypts were lined with a single layer of columnar epithelium resting on a basement membrane. A highly cellular lamina propria and submucosa were found between the crypts and the muscularis mucosa. The small tetraphyllidean Pedibothrium brevispine was found with its scolex lying within the primary mucosal crypts with its hooks embedded in the basement membrane. Epithelial denudation was evident. The large tetraphyllidean Pedibothrium globicephalum was found with its bothridia engulfing large portions of the mucosa and its hooks embedded into the lamina propria. It was associated with moderate to severe mucosal necrosis. The small trypanorhynch Prochristianella tenuispine was found lying between the mucosal ridges in the secondary crypts with its tentacles either penetrating the epithelium, or occasionally, the lamina propria.(ABSTRACT TRUNCATED AT 250 WORDS)

Significance of host cell kinases in herpes simplex virus type 1 egress and lamin-associated protein disassembly from the nuclear lamina

International Nuclear Information System (INIS)

Leach, Natalie R.; Roller, Richard J.

2010-01-01

The nuclear lamina is thought to be a steric barrier to the herpesvirus capsid. Disruption of the lamina accompanied by phosphorylation of lamina proteins is a conserved feature of herpesvirus infection. In HSV-1-infected cells, protein kinase C (PKC) alpha and delta isoforms are recruited to the nuclear membrane and PKC delta has been implicated in phosphorylation of emerin and lamin B. We tested two critical hypotheses about the mechanism and significance of lamina disruption. First, we show that chemical inhibition of all PKC isoforms reduced viral growth five-fold and inhibited capsid egress from the nucleus. However, specific inhibition of either conventional PKCs or PKC delta does not inhibit viral growth. Second, we show hyperphosphorylation of emerin by viral and cellular kinases is required for its disassociation from the lamina. These data support hypothesis that phosphorylation of lamina components mediates lamina disruption during HSV nuclear egress.

The efficacy of a novel collagen-gelatin scaffold with basic fibroblast growth factor for the treatment of vocal fold scar.

Science.gov (United States)

Hiwatashi, Nao; Hirano, Shigeru; Mizuta, Masanobu; Kobayashi, Toshiki; Kawai, Yoshitaka; Kanemaru, Shin-Ichi; Nakamura, Tatsuo; Ito, Juichi; Kawai, Katsuya; Suzuki, Shigehiko

2017-05-01

Vocal fold scar remains a therapeutic challenge. Basic fibroblast growth factor (bFGF) was reported to have regenerative effects for vocal fold scar, although it has the disadvantage of rapid absorption in vivo. A collagen-gelatin sponge (CGS) can compensate for the disadvantage by providing a sustained release system. The current study evaluated the efficacy of CGS combined with bFGF on vocal fold scar, using rat fibroblasts for an in vitro model and a canine in vivo model. We prepared fibroblasts from scarred vocal folds (sVFs) in rats and showed that bFGF accelerated cell proliferation and suppressed expression levels of cleaved caspase 3 and α-smooth muscle actin. Has 1, Has 3, Fgf2, Hgf and Vegfa mRNA levels were significantly upregulated, while Col1a1 and Col3a1 were dose-dependently downregulated, with a maximum effect at 100 ng/ml bFGF. In an in vivo assay, 6 weeks after lamina propria stripping, beagles were divided into three groups: CGS alone (CGS group); CGS with bFGF (7 µg/cm 2 ; CGS + bFGF group); or a sham-treated group. Vibratory examination revealed that the glottal gap was significantly reduced in the bFGF group and the two implanted groups, whereas the CGS + bFGF group showed higher mucosal wave amplitude. Histological examination revealed significantly restored hyaluronic acid and elastin redistribution in the CGS + bFGF group and reductions in dense collagen deposition. These results provide evidence that CGS and bFGF combination therapy may have therapeutic potential and could be a promising tool for treating vocal fold scar. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

CD4+ T lymphocytes injected into severe combined immunodeficient (SCID) mice lead to an inflammatory and lethal bowel disease

DEFF Research Database (Denmark)

Claesson, Mogens Helweg; Rudolphi, A; Kofoed, S

1996-01-01

Transfer of 2 x 10(5) congenic or semiallogenic purified TCR alphabeta+ CD4+ T cells to SCID mice leads to an infiltration of the recipient gut lamina propria and epithelium with a donor-derived CD4+ T cell subset which induces a lethal inflammatory bowel disease (IBD) in the recipients....... In contrast, IBD was not observed in SCID mice transplanted with unfractionated splenic cells. The earliest detectable pathological changes after CD4+ T cell transfer were proliferation and hypertrophy of the entire colonic epithelial layer, including increased mitotic activity, increased expression...... plasma cells were present in the lamina propria of both the small and large intestine. We conclude that low numbers of intraveneously transferred CD4+ T cells induce IBD in SCID mice. In the late stages of CD4+ T cell-induced IBD, the colonic lamina propria becomes infiltrated with macrophages...

Identification of normal and cancerous human colorectal muscularis propria by multiphoton microscopy in different sections

International Nuclear Information System (INIS)

Zhou, Yi; Li, Lianhuang; Zhuo, Shuangmu; Zhu, Xiaoqin; Chen, Jianxin; Chen, Zhifen; Guan, Guoxian; Kang, Deyong

2016-01-01

Multiphoton microscopy (MPM) based on two-photon excited fluorescence (TPEF) and second harmonic generation (SHG) as a potential diagnostic tool is attractive. MPM can effectively provide information about morphological and biochemical changes in biological tissues at the molecular level. In this paper, we attempt to identify normal and cancerous human colorectal muscularis propria by multiphoton microscopy in different sections (both in transverse and longitudinal sections). The results show that MPM can display different microstructure changes in the transverse and longitudinal sections of colorectal muscularis propria. MPM also can quantitatively describe the alteration of collagen content between normal and cancerous muscle layers. These are important pathological findings that MPM images can bring more detailed complementary information about tissue architecture and cell morphology through observing the transverse and longitudinal sections of colorectal muscularis propria. This work demonstrates that MPM can be better for identifying the microstructural characteristics of normal and cancerous human colorectal muscularis propria in different sections. (paper)

Identification of normal and cancerous human colorectal muscularis propria by multiphoton microscopy in different sections

Science.gov (United States)

Zhou, Yi; Chen, Zhifen; Kang, Deyong; li, Lianhuang; Zhuo, Shuangmu; Zhu, Xiaoqin; Guan, Guoxian; Chen, Jianxin

2016-01-01

Multiphoton microscopy (MPM) based on two-photon excited fluorescence (TPEF) and second harmonic generation (SHG) as a potential diagnostic tool is attractive. MPM can effectively provide information about morphological and biochemical changes in biological tissues at the molecular level. In this paper, we attempt to identify normal and cancerous human colorectal muscularis propria by multiphoton microscopy in different sections (both in transverse and longitudinal sections). The results show that MPM can display different microstructure changes in the transverse and longitudinal sections of colorectal muscularis propria. MPM also can quantitatively describe the alteration of collagen content between normal and cancerous muscle layers. These are important pathological findings that MPM images can bring more detailed complementary information about tissue architecture and cell morphology through observing the transverse and longitudinal sections of colorectal muscularis propria. This work demonstrates that MPM can be better for identifying the microstructural characteristics of normal and cancerous human colorectal muscularis propria in different sections.

[Histopathological Study of the Relationship between Lymphoid Follicles and Different Endoscopic Types of Nodular Gastritis].

Science.gov (United States)

Nagata, Takuo; Ishitake, Hisahito; Shimamoto, Fumio; Tamura, Tadamasa; Matsumura, Kazunori; Sumii, Masaharu; Nakai, Shirou

2014-11-01

Nodular gastritis is characterized histologically by hyperplasia and enlargement of lymphoid follicles in the lamina propria. With the objective of elucidating the relationship between different endoscopic types of nodular gastritis and lymphoid follicles, distributions of lymphoid follicles in the lamina propria were investigated in young gastric cancer patients with nodular gastritis. For the study, whole-mucosal step sectioning of each resected stomach was performed, the densities of lymphoid follicles of all specimens were measured microscopically, and the horizontal and depth distributions were calculated. For assessment in the horizontal direction, density distribution diagrams of lymphoid follicles were created. For assessment in the depth direction, the different endoscopic types of nodular gastritis were compared in the five different analysis sites. In the assessment of the horizontal distribution, no characteristic distribution tendencies were observed in either the granular type group or the scattered type group; however, it was found that areas with relatively high densities of lymphoid follicles generally coincided with the areas where nodular gastritis was observed endoscopically. These results suggested that hyperplasia and aggregation of lymphoid follicles in the lamina propria are involved at the sites where nodular gastritis is observed endoscopically. In the assessment of the depth distribution, lymphoid follicles tended to be more unevenly distributed in the upper lamina propria in the granular type group than in the scattered type at the three different analysis sites where nodular gastritis was observed endoscopically. These results suggested the possibility of a granular type characteristic.

Endoscopic excavation for the treatment of small esophageal subepithelial tumors originating from the muscularis propria.

Science.gov (United States)

Ye, Li-ping; Zhu, Lin-hong; Zhou, Xian-bin; Mao, Xin-li; Zhang, Yu

2015-01-01

This study was designed to evaluate the safety and efficacy of endoscopic excavation for esophageal subepithelial tumors originating from the muscularis propria. Forty-five patients with esophageal subepithelial tumors originating from the muscularis propria were treated with endoscopic excavation between January 2010 and June 2012. The key steps were: (1) making several dots around the tumor; (2) incising the mucosa along with the marker dots, and then seperating the tumor from the muscularis propria by using a hook knife or an insulated-tip knife; (3) closing the artificial ulcer with clips after the tumor was removed. The mean tumor diameter was 1.1 ± 0.6 cm. Endoscopic excavation was successfully performed in 43 out of 45 cases (95.6%), the other 2 cases were ligated with nylon rope. During the procedure perforation occurred in 4 (8.9%) patients, who recovered after conservative treatment. No massive bleeding or delayed bleeding occurred. Histologic diagnosis was obtained from 43 (95.6%) patients. Pathological diagnoses of these tumors were leiomyomas (38/43) and gastrointestinal stromal tumors (5/43). Endoscopic excavation is a safe and effective method for the treatment of small esophageal subepithelial tumors originating from the muscularis propria.

An ultrastructural study of the effect of neomycin on the colon in the human subject and in the conventional and the germ-free mouse.

Science.gov (United States)

Aluwihare, A P

1971-05-01

An electron microscopic study of the colon of normal mice and human subjects and those treated with neomycin is reported; there is a close resemblance between the mouse and human colons. After rapid disinfection of the colon, there is epithelial cell damage due to a toxic effect of the drug, a reduction in epithelial turnover accompanying the change in flora, and an important reduction in the cellularity of the lamina propria mainly due to a reduction in inflammatory cells. The changes in the lamina propria probably represent changes in the antipathogenetic defences of the host.

Severe hypoplasia of the omasal laminae in a Japanese Black steer with chronic bloat--a case report.

Science.gov (United States)

Takagi, Mitsuhiro; Mukai, Shuhei; Fushimi, Yasuo; Matsushita, Kouhei; Miyoshi, Nobuaki; Yasuda, Nobuhiro; Kitajima, Hideo; Takamure, Senro; Matsushita, Toshihiko; Kitamura, Nobuo; Deguchi, Eisaburo

2007-12-01

An 11-month-old Japanese Black steer with chronic bloat underwent clinical and histological analyses. During the observation period, it showed normal appetite and fecal volume but persistent chronic bloat symptoms. Compared to controls, the steer's feces contained undigested large straws. Necropsy revealed normal rumen, reticulum, and abomasum but a small omasum. The rumen, reticulum, and abomasum mucosa was normal, with well-developed ruminal papillae. However, severe hypoplasia of the omasal laminae was observed along with hypoplasia reticular groove and ruminoreticular fold. The contents of the reticulum, omasum, and abomasums comprised undigested large sized hay particles. The omasum papillae showed no pathological abnormalities. This is a rare case of a steer with chronic bloat probably caused by severe hypoplasia of the omasal laminae.

Gut-associated lymphoid tissue contains the molecular machinery to support T-cell-dependent and T-cell-independent class switch recombination.

Science.gov (United States)

Barone, F; Patel, P; Sanderson, J D; Spencer, J

2009-11-01

A PRoliferation-Inducing Ligand (APRIL) is a secreted cytokine member of the tumor necrosis factor family. It is a B-cell survival factor that also induces class switch recombination (CSR) toward immunoglobulin A (IgA), independent of T cells. It is therefore an important contributor to the maintenance of the mucosal immunological barrier, which has been linked to a putative extrafollicular inductive phase of the IgA response in lamina propria. By immunohistochemistry (IHC) and quantitative real-time PCR (qRT-PCR) on microdissected tissue from normal human gut, we observed APRIL expression, together with TACI (transmembrane activator and CAML interactor) and BCMA (B-cell maturation antigen), in gut-associated lymphoid tissue (GALT), lamina propria, and in the epithelium of stomach, small and large intestine, and rectum. However, no activation-induced cytidine deaminase (AID) expression (an absolute requirement for class switching) was detected in lamina propria by IHC or qRT-PCR. APRIL and its receptors were only observed alongside AID in GALT, showing that GALT contains the apparatus to support both T-independent and T-dependent routes to IgA CSR.

Robust nuclear lamina-based cell classification of aging and senescent cells.

Science.gov (United States)

Righolt, Christiaan H; van 't Hoff, Merel L R; Vermolen, Bart J; Young, Ian T; Raz, Vered

2011-12-01

Changes in the shape of the nuclear lamina are exhibited in senescent cells, as well as in cells expressing mutations in lamina genes. To identify cells with defects in the nuclear lamina we developed an imaging method that quantifies the intensity and curvature of the nuclear lamina. We show that this method accurately describes changes in the nuclear lamina. Spatial changes in nuclear lamina coincide with redistribution of lamin A proteins and local reduction in protein mobility in senescent cell. We suggest that local accumulation of lamin A in the nuclear envelope leads to bending of the structure. A quantitative distinction of the nuclear lamina shape in cell populations was found between fresh and senescent cells, and between primary myoblasts from young and old donors. Moreover, with this method mutations in lamina genes were significantly distinct from cells with wild-type genes. We suggest that this method can be applied to identify abnormal cells during aging, in in vitro propagation, and in lamina disorders.

A macro- and light microscopical study of the pathology of Calicophoron microbothrium infection in experimentally infected cattle

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M. Mavenyengwa

2005-09-01

Full Text Available Twelve Tuli weaner steers aged 1 year were randomly subdivided into three groups of four animals and infected with different doses of Calicophoron microbothrium metacercariae. Each animal in Group I received a low dose (LD of 5 000 metacercariae, Group II a medium dose (MD of 15 000 metacercariae, Group III a high dose (HD of 25 000 metacercariae and one additional animal was kept as an uninfected control (C. After infection, one animal from each group was slaughtered on Day 28, 42, 56 and 84 post infection (pi and samples from the ileum, jejunum, duodenum, abomasum and the rumen were collected for histopathological and cytological examination. On Day 28 pi, the gross pathological lesions observed in the duodenum of the LD and the MD animals were similar and comprised duodenal thickening, corrugation, hyperaemia, petechiation and ulceration. In the HD animal the duodenal lesions were similar but more severe. The abomasal folds were severely oedematous in the MD group and nearly occluded the abomasal lumen. Moderate oedema of the abomasal folds was also present in the LD and HD animals. The gross pathological lesions regressed in all the infected groups with increasing age of infection and had disappeared completely by Day 56 pi. On Day 28 pi the histopathological lesions in the duodenum and jejunum of the LD and MD groups were similar, comprising subtotal villous atrophy, hyperplasia of Brunner's glands and Peyer's patches and moderate infiltration of eosinophils, mast cells and a few globule leukocytes, basophils and lymphocytes in the lamina propria. The HD group had total villous atrophy, severe hyperplasia and cystic dilatation of Brunner's glands, which had expanded to cover the entire submucosa. On Day 42 pi the histopathological lesions were still present in the MD and the HD groups comprising subtotal villous atrophy and hyperplasia of Brunner's glands. Heavy infiltrations of eosinophils, moderate amounts of mast cells and a few

Endoscopic full-thickness resection for gastric submucosal tumors arising from the muscularis propria layer.

Science.gov (United States)

Huang, Liu-Ye; Cui, Jun; Lin, Shu-Juan; Zhang, Bo; Wu, Cheng-Rong

2014-10-14

To evaluate the efficacy, safety and feasibility of endoscopic full-thickness resection (EFR) for the treatment of gastric submucosal tumors (SMTs) arising from the muscularis propria. A total of 35 gastric SMTs arising from the muscularis propria layer were resected by EFR between January 2010 and September 2013. EFR consists of five major steps: injecting normal saline into the submucosa; pre-cutting the mucosal and submucosal layers around the lesion; making a circumferential incision as deep as the muscularis propria around the lesion using endoscopic submucosal dissection and an incision into the serosal layer around the lesion with a Hook knife; a full-thickness resection of the tumor, including the serosal layer with a Hook or IT knife; and closing the gastric wall with metallic clips. Of the 35 gastric SMTs, 14 were located at the fundus, and 21 at the corpus. EFR removed all of the SMTs successfully, and the complete resection rate was 100%. The mean operation time was 90 min (60-155 min), the mean hospitalization time was 6.0 d (4-10 d), and the mean tumor size was 2.8 cm (2.0-4.5 cm). Pathological examination confirmed the presence of gastric stromal tumors in 25 patients, leiomyomas in 7 and gastric autonomous nerve tumors in 2. No gastric bleeding, peritonitis or abdominal abscess occurred after EFR. Postoperative contrast roentgenography on the third day detected no contrast extravasation into the abdominal cavity. The mean follow-up period was 6 mo, with no lesion residue or recurrence noted. EFR is efficacious, safe and minimally invasive for patients with gastric SMTs arising from the muscularis propria layer. This technique is able to resect deep gastric lesions while providing precise pathological information about the lesion. With the development of EFR, the indications of endoscopic resection might be extended.

Functional Characterization of Lamina X Neurons in ex-Vivo Spinal Cord Preparation

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Volodymyr Krotov

2017-11-01

Full Text Available Functional properties of lamina X neurons in the spinal cord remain unknown despite the established role of this area for somatosensory integration, visceral nociception, autonomic regulation and motoneuron output modulation. Investigations of neuronal functioning in the lamina X have been hampered by technical challenges. Here we introduce an ex-vivo spinal cord preparation with both dorsal and ventral roots still attached for functional studies of the lamina X neurons and their connectivity using an oblique LED illumination for resolved visualization of lamina X neurons in a thick tissue. With the elaborated approach, we demonstrate electrophysiological characteristics of lamina X neurons by their membrane properties, firing pattern discharge and fiber innervation (either afferent or efferent. The tissue preparation has been also probed using Ca2+ imaging with fluorescent Ca2+ dyes (membrane-impermeable or -permeable to demonstrate the depolarization-induced changes in intracellular calcium concentration in lamina X neurons. Finally, we performed visualization of subpopulations of lamina X neurons stained by retrograde labeling with aminostilbamidine dye to identify sympathetic preganglionic and projection neurons in the lamina X. Thus, the elaborated approach provides a reliable tool for investigation of functional properties and connectivity in specific neuronal subpopulations, boosting research of lamina X of the spinal cord.

Fate of the Molar Dental Lamina in the Monophyodont Mouse

Science.gov (United States)

Dosedělová, Hana; Dumková, Jana; Lesot, Hervé; Glocová, Kristýna; Kunová, Michaela; Tucker, Abigail S.; Veselá, Iva; Krejčí, Pavel; Tichý, František; Hampl, Aleš; Buchtová, Marcela

2015-01-01

The successional dental lamina (SDL) plays an essential role in the development of replacement teeth in diphyodont and polyphyodont animals. A morphologically similar structure, the rudimental successional dental lamina (RSDL), has been described in monophyodont (only one tooth generation) lizards on the lingual side of the developing functional tooth. This rudimentary lamina regresses, which has been proposed to play a role in preventing the formation of future generations of teeth. A similar rudimentary lingual structure has been reported associated with the first molar in the monophyodont mouse, and we show that this structure is common to all murine molars. Intriguingly, a lingual lamina is also observed on the non-replacing molars of other diphyodont mammals (pig and hedgehog), initially appearing very similar to the successional dental lamina on the replacing teeth. We have analyzed the morphological as well as ultrastructural changes that occur during the development and loss of this molar lamina in the mouse, from its initiation at late embryonic stages to its disappearance at postnatal stages. We show that loss appears to be driven by a reduction in cell proliferation, down-regulation of the progenitor marker Sox2, with only a small number of cells undergoing programmed cell death. The lingual lamina was associated with the dental stalk, a short epithelial connection between the tooth germ and the oral epithelium. The dental stalk remained in contact with the oral epithelium throughout tooth development up to eruption when connective tissue and numerous capillaries progressively invaded the dental stalk. The buccal side of the dental stalk underwent keratinisation and became part of the gingival epithelium, while most of the lingual cells underwent programmed cell death and the tissue directly above the erupting tooth was shed into the oral cavity. PMID:26010446

Size dependence of ozone lamina characteristics and their correlations

Czech Academy of Sciences Publication Activity Database

Križan, Peter; Laštovička, Jan; Kozubek, Michal

2015-01-01

Roč. 132, September (2015), s. 116-123 ISSN 1364-6826 R&D Projects: GA ČR GA15-03909S Institutional support: RVO:68378289 Keywords : ozone laminae * correlations among laminae * vertical resolution of ozone sonde measurements Subject RIV: DG - Athmosphere Sciences, Meteorology Impact factor: 1.463, year: 2015 http://www.sciencedirect.com/science/article/pii/S1364682615300055

A study on expression levels of matrix metalloproteinases and their ...

African Journals Online (AJOL)

Keywords: Ulcerative colitis, Matrix metalloproteinases, Tissue inhibitors of metalloproteinases, Lamina propria ... The symptoms of UC include diarrhea with blood, fever ..... Eisen A, Jeffrey J, Gross J. Human skin collagenase. Isolation and ...

Влияние токсиканта делагила на морфологические изменения в слизистой оболочке полости рта крыс при разном уровне поступления алиментарных полифенолов = The influence of the toxicant delagil on the morphological changes in the oral mucosa of rats in the different levels of receipts of alimentary polyphenols

Directory of Open Access Journals (Sweden)

Oleh Anatolievich Glazunov

2015-12-01

Summary The Aim of  study was to investigate the the influence of delagila on the morphological changes in the connective tissue of the lamina propria and the epithelium of the buccal mucosa of rats under conditions of normal receipts and deprivation of the animals plant foods. Materials and methods. In the experiment were taken 22 white rats, distributed in the following groups. 1st group (7 rats - intact; 2nd group (7 was obtained delagil per os at a dose of 5 mg / kg body weight of rats 5 times a week, against full vivarium ration. Rats of group 3 (8 was prepared delagil with the content on their diet, devoid of plant food. Time of the experiment was 60 days. Results and conclusions. The introduction on the background of a full ration of vivarium caused on the surface of the epithelial layer appearance of a gigant epithelial cells and swelling in the intercellular spaces. Chronic nutritional deprivation ratsof the plant polyphenols increased the sensitivity of the oral mucosa to the action delagila and caused a significant change in the epithelial layer of connective tissue in the lamina propria of the buccal mucosa of rats.   Key words: delagil, nutritional deficiency of polyphenols, epithelial layer, giant epithelial cells, mitotic process, the connective tissue of the lamina propria, destructive and inflammatory changes, white rats.

Histological analysis of trachea and lung of newborn dogs

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Andrezza Braga Soares da Silva

2016-11-01

Full Text Available The neonatology science is, in Veterinary Medicine, studying the post-birth to the development of certain characteristics of resistance, which for canines occurs until the second week of life. The newborn requires a precise approach given the particularities of their physiology and immunology extremely immature. The histological study elucidates problems morphological and functional abnormalities, as it provides a reliable and microscopic analysis. Aimed to analyze trachea and lung of newborn dogs through techniques of basic histology. We used five neonates that died postpartum. These were weighed, measured and dissected. Proceeded to the extraction of the trachea, bronchus and lung for submitting these samples to histological routine. The tracheal tissue presents a pseudostratified columnar ciliated epithelium with globet cells, a small amount of glands in the lamina propria and hyaline cartilage not fully developed. As regards the bronchial tissue may be observed well defined layers, pulmonary pseudostratified columnar ciliated epithelium with goblet cells in the lamina propria several bundles of smooth muscle and thick vascularized tissue. Likewise, the signs of bronchial cartilage present under development. The bronchioles also feature the common pulmonary epithelium and lamina propria also normal pens without smooth muscle. The bags alveolar lung cells showed typical. The lung tissues of newborn dogs present is still in development stage. It is possible to understand patterns of histogenesis and morphogenesis in newborn dogs.

The insulator protein SU(HW fine-tunes nuclear lamina interactions of the Drosophila genome.

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Joke G van Bemmel

Full Text Available Specific interactions of the genome with the nuclear lamina (NL are thought to assist chromosome folding inside the nucleus and to contribute to the regulation of gene expression. High-resolution mapping has recently identified hundreds of large, sharply defined lamina-associated domains (LADs in the human genome, and suggested that the insulator protein CTCF may help to demarcate these domains. Here, we report the detailed structure of LADs in Drosophila cells, and investigate the putative roles of five insulator proteins in LAD organization. We found that the Drosophila genome is also organized in discrete LADs, which are about five times smaller than human LADs but contain on average a similar number of genes. Systematic comparison to new and published insulator binding maps shows that only SU(HW binds preferentially at LAD borders and at specific positions inside LADs, while GAF, CTCF, BEAF-32 and DWG are mostly absent from these regions. By knockdown and overexpression studies we demonstrate that SU(HW weakens genome - NL interactions through a local antagonistic effect, but we did not obtain evidence that it is essential for border formation. Our results provide insights into the evolution of LAD organization and identify SU(HW as a fine-tuner of genome - NL interactions.

Radiologic study on lamina dura

Energy Technology Data Exchange (ETDEWEB)

Ahn, Hyung Kyu [Dept. of Radiology, College of Dentistry, Seoul National University, Seoul (Korea, Republic of)

1981-11-15

This study was performed to investigate the thickness of lamina dura of the human teeth in periodontal disease, which obtained from the intraoral roentgenograms of the 122 cases taken by bisecting technic. All films were divided into the different ages, the different sexes, and the different location of the different teeth. The obtained results were as follows: 1. Compared with the normal teeth, the thickness of lamina dura in periodontal disease is increased in all of different ages, sexes and teeth. 2. Generally, the alveolar crest portion is the thickest among the root surfaces, and midroot, apex followed, and the average thickness of the posterior teeth is thicker than that of anterior teeth. 3. The mean value of the whole maxillary teeth is almost same as that of mandibular teeth. 4. On the whole cases, the differences of male and female is about 0.01 mm, which is not a significant differences.

Radiologic study on lamina dura

International Nuclear Information System (INIS)

Ahn, Hyung Kyu

1981-01-01

This study was performed to investigate the thickness of lamina dura of the human teeth in periodontal disease, which obtained from the intraoral roentgenograms of the 122 cases taken by bisecting technic. All films were divided into the different ages, the different sexes, and the different location of the different teeth. The obtained results were as follows: 1. Compared with the normal teeth, the thickness of lamina dura in periodontal disease is increased in all of different ages, sexes and teeth. 2. Generally, the alveolar crest portion is the thickest among the root surfaces, and midroot, apex followed, and the average thickness of the posterior teeth is thicker than that of anterior teeth. 3. The mean value of the whole maxillary teeth is almost same as that of mandibular teeth. 4. On the whole cases, the differences of male and female is about 0.01 mm, which is not a significant differences.

Matrix expansion and syncytial aggregation of syndecan-1+ cells underpin villous atrophy in coeliac disease.

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Camilla Salvestrini

Full Text Available We studied the expression of sulphated glycosaminoglycans (GAGs in coeliac disease (CD mucosa, as they are critical determinants of tissue volume, which increases in active disease. We also examined mucosal expression of IL-6, which stimulates excess GAG synthesis in disorders such as Grave's ophthalmopathy.We stained archival jejunal biopsies from 5 children with CD at diagnosis, on gluten-free diet and challenge for sulphated GAGs. We then examined duodenal biopsies from 9 children with CD compared to 9 histological normal controls, staining for sulphated GAGs, heparan sulphate proteoglycans (HSPG, short-chain HSPG (Δ-HSPG and the proteoglycan syndecan-1 (CD138, which is expressed on epithelium and plasma cells. We confirmed findings with a second monoclonal in another 12 coeliac children. We determined mucosal IL-6 expression by immunohistochemistry and PCR in 9 further cases and controls, and used quantitative real time PCR for other Th17 pathway cytokines in an additional 10 cases and controls.In CD, HSPG expression was lost in the epithelial compartment but contrastingly maintained within an expanded lamina propria. Within the upper lamina propria, clusters of syndecan-1(+ plasma cells formed extensive syncytial sheets, comprising adherent plasma cells, lysed cells with punctate cytoplasmic staining and shed syndecan ectodomains. A dense infiltrate of IL-6(+ mononuclear cells was detected in active coeliac disease, also localised to the upper lamina propria, with significantly increased mRNA expression of IL-6 and IL-17A but not IL-23 p19.Matrix expansion, through syndecan-1(+ cell recruitment and lamina propria GAG increase, underpins villous atrophy in coeliac disease. The syndecan-1(+ cell syncytia and excess GAG production recapitulate elements of the invertebrate encapsulation reaction, itself dependent on insect transglutaminase and glutaminated early response proteins. As in other matrix expansion disorders, IL-6 is upregulated and

Matrix Expansion and Syncytial Aggregation of Syndecan-1+ Cells Underpin Villous Atrophy in Coeliac Disease

Science.gov (United States)

Salvestrini, Camilla; Lucas, Mark; Lionetti, Paolo; Torrente, Franco; James, Sean; Phillips, Alan D.; Murch, Simon H.

2014-01-01

Background We studied the expression of sulphated glycosaminoglycans (GAGs) in coeliac disease (CD) mucosa, as they are critical determinants of tissue volume, which increases in active disease. We also examined mucosal expression of IL-6, which stimulates excess GAG synthesis in disorders such as Grave's ophthalmopathy. Methods We stained archival jejunal biopsies from 5 children with CD at diagnosis, on gluten-free diet and challenge for sulphated GAGs. We then examined duodenal biopsies from 9 children with CD compared to 9 histological normal controls, staining for sulphated GAGs, heparan sulphate proteoglycans (HSPG), short-chain HSPG (Δ-HSPG) and the proteoglycan syndecan-1 (CD138), which is expressed on epithelium and plasma cells. We confirmed findings with a second monoclonal in another 12 coeliac children. We determined mucosal IL-6 expression by immunohistochemistry and PCR in 9 further cases and controls, and used quantitative real time PCR for other Th17 pathway cytokines in an additional 10 cases and controls. Results In CD, HSPG expression was lost in the epithelial compartment but contrastingly maintained within an expanded lamina propria. Within the upper lamina propria, clusters of syndecan-1+ plasma cells formed extensive syncytial sheets, comprising adherent plasma cells, lysed cells with punctate cytoplasmic staining and shed syndecan ectodomains. A dense infiltrate of IL-6+ mononuclear cells was detected in active coeliac disease, also localised to the upper lamina propria, with significantly increased mRNA expression of IL-6 and IL-17A but not IL-23 p19. Conclusions Matrix expansion, through syndecan-1+ cell recruitment and lamina propria GAG increase, underpins villous atrophy in coeliac disease. The syndecan-1+ cell syncytia and excess GAG production recapitulate elements of the invertebrate encapsulation reaction, itself dependent on insect transglutaminase and glutaminated early response proteins. As in other matrix expansion disorders

Histopathological and electron microscopic studies of lymphangiectasia of the small intestine in Behçet's disease

Science.gov (United States)

Asakura, Hitoshi; Morita, Akira; Morishita, Tetsuo; Tsuchiya, Masaharu; Watanabe, Yoonosuke; Enomoto, Yasuhiro

1973-01-01

The gastrointestinal involvement and immunological findings in 16 patients with Behçet's disease are described. Four of 15 biopsy specimens of jejunal mucosa showed marked lymphangiectasia in the lamina propria similar to the appearance which was thought to be a characteristic finding in protein-losing enteropathy. None of the patients had hypoproteinaemia. Increases in serum immunoglobulin IgA were proved in six of 15 cases; in IgM, five of 15; and in IgG, one of 15. Electron microscopic studies showed that there were thousands of precipitated lymph protein bodies in the extracellular spaces of the lamina propria. Ulcers and healed ulcers of the large intestine were studied by light microscopy. ImagesFig. 1Fig. 2Fig. 3Fig. 4Fig. 7Fig. 8Fig. 9 PMID:4700433

Diversity and functions of intestinal mononuclear phagocytes

DEFF Research Database (Denmark)

Joeris, Thorsten; Müller-Luda, K; Agace, William Winston

2017-01-01

The intestinal lamina propria (LP) contains a diverse array of mononuclear phagocyte (MNP) subsets, including conventional dendritic cells (cDC), monocytes and tissue-resident macrophages (mφ) that collectively play an essential role in mucosal homeostasis, infection and inflammation. In the curr......The intestinal lamina propria (LP) contains a diverse array of mononuclear phagocyte (MNP) subsets, including conventional dendritic cells (cDC), monocytes and tissue-resident macrophages (mφ) that collectively play an essential role in mucosal homeostasis, infection and inflammation....... In the current review we discuss the function of intestinal cDC and monocyte-derived MNP, highlighting how these subsets play several non-redundant roles in the regulation of intestinal immune responses. While much remains to be learnt, recent findings also underline how the various populations of MNP adapt...

Serotonin Immunoreactive Cells and Nerve Fibers in the Mucosa of ...

African Journals Online (AJOL)

hydroxytryptamine) immunoreactivity in the pyloric mucosa of the rat stomach. The immunoreactive elements included the endocrine cells, mast cells and mucosal nerve fibers in the lamina propria. The immunopositive endocrine cells were oval in ...

The diagnostic value of the alveolar lamina dura in generalised bone disease

International Nuclear Information System (INIS)

Kuhlencordt, J.; Kruse, H.P.; Franke, J.; Hamburg Univ.

1981-01-01

Changes in the alveolar lamina dura in 134 patients have been analysed. They included 32 cases with urolithiasis in whom generalised bone disease had been excluded, 37 cases of primary hyperparathyroidism, 31 cases of secondary hyperparathyroidism and 34 cases with primary osteoporosis. The state of the lamina dura was related to biochemical, radiological and histological findings in the various groups. The value of the lamina dura in the diagnosis of generalised skeletal abnormalities has been defined. (orig.) [de

Toughening MoSi2 with Niobium metal -- Effects of size and orientation of ductile laminae

International Nuclear Information System (INIS)

Shaw, L.; Abbaschian, R.

1994-01-01

Effects of size and orientation of ductile laminae on the toughness of brittle matrix composites have been evaluated using MoSi 2 composites reinforced with Nb laminae. Nb laminae with thicknesses ranging from 0.127 to 1.0 mm were hot pressed with MoSi 2 powder to prepare the composites. Toughness of the composites was measured using four-point bend test on chevron-notched specimens. It was found that the toughness of the composites increased with increasing size of the niobium laminae. Furthermore, toughening was observed at crack propagation directions perpendicular to the laminae plane, indicating that ductile laminae offer two dimensional toughening. A model based on the bridging contribution of the ductile phase has been proposed to analyze the chevron-notched specimens of the ductile-phase-reinforced brittle matrix composites. The analysis showed that the dependence of the toughness of the composites on the size and orientation of the ductile laminae could be interpreted in terms of their bridging capability and bending contributions

Layer-dependent role of collagen recruitment during loading of the rat bladder wall.

Science.gov (United States)

Cheng, Fangzhou; Birder, Lori A; Kullmann, F Aura; Hornsby, Jack; Watton, Paul N; Watkins, Simon; Thompson, Mark; Robertson, Anne M

2018-04-01

In this work, we re-evaluated long-standing conjectures as to the source of the exceptionally large compliance of the bladder wall. Whereas these conjectures were based on indirect measures of loading mechanisms, in this work we take advantage of advances in bioimaging to directly assess collagen fibers and wall architecture during biaxial loading. A custom biaxial mechanical testing system compatible with multiphoton microscopy was used to directly measure the layer-dependent collagen fiber recruitment in bladder tissue from 9 male Fischer rats (4 adult and 5 aged). As for other soft tissues, the bladder loading curve was exponential in shape and could be divided into toe, transition and high stress regimes. The relationship between collagen recruitment and loading curves was evaluated in the context of the inner (lamina propria) and outer (detrusor smooth muscle) layers. The large extensibility of the bladder was found to be possible due to folds in the wall (rugae) that provide a mechanism for low resistance flattening without any discernible recruitment of collagen fibers throughout the toe regime. For more extensible bladders, as the loading extended into the transition regime, a gradual coordinated recruitment of collagen fibers between the lamina propria layer and detrusor smooth muscle layer was found. A second important finding was that wall extensibility could be lost by premature recruitment of collagen in the outer wall that cut short the toe region. This change was correlated with age. This work provides, for the first time, a mechanistic understanding of the role of collagen recruitment in determining bladder extensibility and capacitance.

Contributions of the 12 neuron classes in the fly lamina to motion vision.

Science.gov (United States)

Tuthill, John C; Nern, Aljoscha; Holtz, Stephen L; Rubin, Gerald M; Reiser, Michael B

2013-07-10

Motion detection is a fundamental neural computation performed by many sensory systems. In the fly, local motion computation is thought to occur within the first two layers of the visual system, the lamina and medulla. We constructed specific genetic driver lines for each of the 12 neuron classes in the lamina. We then depolarized and hyperpolarized each neuron type and quantified fly behavioral responses to a diverse set of motion stimuli. We found that only a small number of lamina output neurons are essential for motion detection, while most neurons serve to sculpt and enhance these feedforward pathways. Two classes of feedback neurons (C2 and C3), and lamina output neurons (L2 and L4), are required for normal detection of directional motion stimuli. Our results reveal a prominent role for feedback and lateral interactions in motion processing and demonstrate that motion-dependent behaviors rely on contributions from nearly all lamina neuron classes. Copyright © 2013 Elsevier Inc. All rights reserved.

Morphometric study of uninvolved rectal mucosa 10 cm and 20 cm away from the malignant tumor.

Science.gov (United States)

Despotović, Sanja Z; Milićević, Novica M; Milosević, Dragoslav P; Despotović, Nebojsa; Erceg, Predrag; Bojić, Bozidar; Bojić, Danijela; Svorcan, Petar; Mihajlović, Gordana; Dorđević, Jelena; Lalić, Ivana M; Milićević, Zivana

2014-02-01

Recently, many details of the interplay between tumor cells and tumor-associated stromal elements leading to the progression of malignant disease were elucidated. In contrast, little is known about the role of uninvolved stromal tissue in the remote surrounding of the malignant tumor. Therefore, we performed a computer-aided morphometric study of rectal mucosa in samples taken 10 cm and 20 cm away from the malignant tumor during endoscopic examination of 23 patients older than 60 years. The samples of rectal mucosa from 10 healthy persons of corresponding age subjected to diagnostic rectoscopy during active screening for asymptomatic cancer were used as control. All structural elements of the rectal mucosa were studied and the number of nucleated cells in the lamina propria per 0.1 mm² of tissue was assessed. Our study revealed a reduced number of cells in the lamina propria of the rectal mucosa 10 cm and 20 cm away from the tumor lesion in both male and female patients. The decreased mucosal height and increased crypt number were registered in female patients 10 cm away from the tumor. The connective tissue of lamina propria showed a disorderly organization: the collagen fibers were frail, loosely arranged and signs of tissue edema were present. Small blood vessels and capillaries were much more frequently seen than in healthy tissue. Our results demonstrate the complex interactions between the cancer and remote mucosal tissue of the affected organ.

Reparo de esôfago cervical de cães com segmento intestinal livre autólogo desprovido de epitélio e de lâmina própria da túnica mucosa Canine cervical esophagus repair using of free autograft intestinal segment without epithelium and lamina propria of the mucosa

Directory of Open Access Journals (Sweden)

Patrícia Maria Coletto Freitas

2002-06-01

Full Text Available Doze cães foram separados em dois grupos de igual número e submetidos à remoção de um retalho de 3,0 x 3,5cm do esôfago cervical. A abertura foi ocluída com enxerto de segmento intestinal livre autólogo desprovido de epitélio e lâmina própria da túnica mucosa, com pontos simples separados por fio poliglactina 910. Os animais do grupo 1 foram observados durante 15 dias de pós-operatório, e os do grupo 2, durante 30 dias. Observou-se epitelização e discreta estenose no local do enxerto com invasão de tecido conjuntivo denso rico em fibras colágenas. O enxerto de segmento intestinal livre autólogo foi eficiente no reparo de rupturas do esôfago cervical de cães.Twelve dogs were allocated in two groups with same number of animals and submitted to removal of a 3.0 x 3.5cm piece of the cervical esophagus. The incision was occluded with a autograft of free intestinal segment without epithelium and lamina propria of the mucosa, with separate simples points using poliglactina 910 line. Animals of the group 1 were observed for 15 days post-surgery, and the animals from group 2, for 30 days. Epithelization and discreet stenosis in the place of the graft with invasion of dense conjunctive tissue, rich in collagen fibers was noticed. The autograft free intestinal segment was efficient in the repair of ruptures in the cervical segment of the canine esophagous.

The expression of receptors for estrogen and epithelial growth factor in the male rabbit prostate and prostatic urethra following castration

DEFF Research Database (Denmark)

Bødker, A; Balslev, E; Iversen, H G

1997-01-01

In the lower urinary tract of the male rabbit, estrogen receptors (ERs) are restricted to the urethra and the prostatic stroma. At present, the function of ERs in these tissues is not known. Epithelial growth factor (EGF) stimulates proliferation of epidermal and epithelial tissues, and several...... were included as controls. In the control group, ERs were found in the urothelial lining and lamina propria of the prostatic urethra, and in the prostatic stroma. EGF receptors were demonstrated in the epithelial lining of the prostatic urethra and the glandular epithelium of the prostate. Following...... castration, the expression of ERs, assessed as the increase in the number of positively stained specimens, increased significantly in the lamina propria of the prostatic urethra and the prostatic stroma. EGF receptor expression increased significantly in the epithelial lining of the prostatic urethra...

Quantification of the spatial organization of the nuclear lamina as a tool for cell classification

NARCIS (Netherlands)

Righolt, C.H.; Zatreanu, D.A.; Raz, V.

2013-01-01

The nuclear lamina is the structural scaffold of the nuclear envelope that plays multiple regulatory roles in chromatin organization and gene expression as well as a structural role in nuclear stability. The lamina proteins, also referred to as lamins, determine nuclear lamina organization and

Characterization of the surface and interfacial properties of the lamina splendens

Science.gov (United States)

Rexwinkle, Joe T.; Hunt, Heather K.; Pfeiffer, Ferris M.

2017-06-01

Joint disease affects approximately 52.5 million patients in the United States alone, costing 80.8 billion USD in direct healthcare costs. The development of treatment programs for joint disease and trauma requires accurate assessment of articular cartilage degradation. The articular cartilage is the interfacial tissue between articulating surfaces, such as bones, and acts as low-friction interfaces. Damage to the lamina splendens, which is the articular cartilage's topmost layer, is an early indicator of joint degradation caused by injury or disease. By gaining comprehensive knowledge on the lamina splendens, particularly its structure and interfacial properties, researchers could enhance the accuracy of human and animal biomechanical models, as well as develop appropriate biomimetic materials for replacing damaged articular cartilage, thereby leading to rational treatment programs for joint disease and injury. Previous studies that utilize light, electron, and force microscopy techniques have found that the lamina splendens is composed of collagen fibers oriented parallel to the cartilage surface and encased in a proteoglycan matrix. Such orientation maximizes wear resistance and proteoglycan retention while promoting the passage of nutrients and synovial fluid. Although the structure of the lamina splendens has been explored in the literature, the low-friction interface of this tissue remains only partially characterized. Various functional models are currently available for the interface, such as pure boundary lubrication, thin films exuded under pressure, and sheets of trapped proteins. Recent studies suggest that each of these lubrication models has certain advantages over one another. Further research is needed to fully model the interface of this tissue. In this review, we summarize the methods for characterizing the lamina splendens and the results of each method. This paper aims to serve as a resource for existing studies to date and a roadmap of the

Prognostic significance of epidermal growth factor receptor (EGFR) over expression in urothelial carcinoma of urinary bladder.

Science.gov (United States)

Hashmi, Atif Ali; Hussain, Zubaida Fida; Irfan, Muhammad; Khan, Erum Yousuf; Faridi, Naveen; Naqvi, Hanna; Khan, Amir; Edhi, Muhammad Muzzammil

2018-06-07

Epidermal growth factor receptor (EGFR) has been shown to have abnormal expression in many human cancers and is considered as a marker of poor prognosis. Frequency of over expression in bladder cancer has not been studied in our population; therefore we aimed to evaluate the frequency and prognostic significance of EGFR immunohistochemical expression in locoregional population. We performed EGFR immunohistochemistry on 126 cases of bladder cancer and association of EGFR expression with tumor grade, lamina propria invasion, deep muscle invasion and recurrence of disease was evaluated. High EGFR expression was noted in 26.2% (33 cases), 15.1% (19 cases) and 58.7% (74 cases) revealed low and no EGFR expression respectively. Significant association of EGFR expression was noted with tumor grade, lamina propria invasion, deep muscle invasion and recurrence status while no significant association was seen with age, gender and overall survival. Kaplan- Meier curves revealed significant association of EGFR expression with recurrence while no significant association was seen with overall survival. Significant association of EGFR overexpression with tumor grade, muscularis propria invasion and recurrence signifies its prognostic value; therefore EGFR can be used as a prognostic biomarker in Urothelial bladder carcinoma.

Medial depression with bony dehiscence of lamina papyracea as an anatomic variation: CT evaluation

International Nuclear Information System (INIS)

Na, Sun Young; Lee, Young Uk; Youn, Eun Kyung; Suh, Sang Gyung; Kim, Dong Hyun

1994-01-01

To evaluate the incidence and CT findings of the medial depression and bony dehiscence of lamina papyracea as an anatomic variation. 1472 PNS CTs of the patients with symptoms of chronic sinusitis were retrospectively evaluated. The total incidence of depressed lamina papyracea as an anatomic variation was 3.5%(52/1472) on PNS CT. There was a statistically significant correlation between the increasing age and the incidence of depressed lamina papyracea. Depression of lamina papyracea anterior to the basal lamella were more common than those of the posterior depression. Associated findings were herniation of adjacent fatty tissue in all cases and the medial bowing and hypertrophied configuration of the medial rectus muscle without significant herniation in 19 cases(34%). Nontraumatic, asymptomatic depression with bony dehiscence of lamina papyracea as an anatomic variation is not uncommon with the incidence of 3.5%. Recognition of its existence and degree may be helpful in avoiding various ocular complication during ethmoid surgery

Indian Hedgehog Suppresses a Stromal Cell–Driven Intestinal Immune Response

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B. Florien Westendorp

2018-01-01

Conclusions: We show that epithelium-derived Indian Hedgehog signals exclusively to fibroblasts in the intestine. Loss of Ihh leads to a rapid immune response with up-regulation of fibroblast-derived CXCL12, and migration of immune cells into the lamina propria.

Galanin-immunoreactivity identifies a distinct population of inhibitory interneurons in laminae I-III of the rat spinal cord

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Watanabe Masahiko

2011-05-01

Full Text Available Abstract Background Inhibitory interneurons constitute 30-40% of neurons in laminae I-III and have an important anti-nociceptive role. However, because of the difficulty in classifying them we know little about their organisation. Previous studies have identified 3 non-overlapping groups of inhibitory interneuron, which contain neuropeptide Y (NPY, neuronal nitric oxide synthase (nNOS or parvalbumin, and have shown that these differ in postsynaptic targets. Some inhibitory interneurons contain galanin and the first aim of this study was to determine whether these form a different population from those containing NPY, nNOS or parvalbumin. We also estimated the proportion of neurons and GABAergic axons that contain galanin in laminae I-III. Results Galanin cells were concentrated in laminae I-IIo, with few in laminae IIi-III. Galanin showed minimal co-localisation with NPY, nNOS or parvalbumin in laminae I-II, but most galanin-containing cells in lamina III were nNOS-positive. Galanin cells constituted ~7%, 3% and 2% of all neurons in laminae I, II and III, and we estimate that this corresponds to 26%, 10% and 5% of the GABAergic neurons in these laminae. However, galanin was only found in ~6% of GABAergic boutons in laminae I-IIo, and ~1% of those in laminae IIi-III. Conclusions These results show that galanin, NPY, nNOS and parvalbumin can be used to define four distinct neurochemical populations of inhibitory interneurons. Together with results of a recent study, they suggest that the galanin and NPY populations account for around half of the inhibitory interneurons in lamina I and a quarter of those in lamina II.

Genome-Nuclear Lamina Interactions Regulate Cardiac Stem Cell Lineage Restriction.

Science.gov (United States)

Poleshko, Andrey; Shah, Parisha P; Gupta, Mudit; Babu, Apoorva; Morley, Michael P; Manderfield, Lauren J; Ifkovits, Jamie L; Calderon, Damelys; Aghajanian, Haig; Sierra-Pagán, Javier E; Sun, Zheng; Wang, Qiaohong; Li, Li; Dubois, Nicole C; Morrisey, Edward E; Lazar, Mitchell A; Smith, Cheryl L; Epstein, Jonathan A; Jain, Rajan

2017-10-19

Progenitor cells differentiate into specialized cell types through coordinated expression of lineage-specific genes and modification of complex chromatin configurations. We demonstrate that a histone deacetylase (Hdac3) organizes heterochromatin at the nuclear lamina during cardiac progenitor lineage restriction. Specification of cardiomyocytes is associated with reorganization of peripheral heterochromatin, and independent of deacetylase activity, Hdac3 tethers peripheral heterochromatin containing lineage-relevant genes to the nuclear lamina. Deletion of Hdac3 in cardiac progenitor cells releases genomic regions from the nuclear periphery, leading to precocious cardiac gene expression and differentiation into cardiomyocytes; in contrast, restricting Hdac3 to the nuclear periphery rescues myogenesis in progenitors otherwise lacking Hdac3. Our results suggest that availability of genomic regions for activation by lineage-specific factors is regulated in part through dynamic chromatin-nuclear lamina interactions and that competence of a progenitor cell to respond to differentiation signals may depend upon coordinated movement of responding gene loci away from the nuclear periphery. Copyright © 2017 Elsevier Inc. All rights reserved.

Discrimination of cortical laminae using MEG.

Science.gov (United States)

Troebinger, Luzia; López, José David; Lutti, Antoine; Bestmann, Sven; Barnes, Gareth

2014-11-15

Typically MEG source reconstruction is used to estimate the distribution of current flow on a single anatomically derived cortical surface model. In this study we use two such models representing superficial and deep cortical laminae. We establish how well we can discriminate between these two different cortical layer models based on the same MEG data in the presence of different levels of co-registration noise, Signal-to-Noise Ratio (SNR) and cortical patch size. We demonstrate that it is possible to make a distinction between superficial and deep cortical laminae for levels of co-registration noise of less than 2mm translation and 2° rotation at SNR > 11 dB. We also show that an incorrect estimate of cortical patch size will tend to bias layer estimates. We then use a 3D printed head-cast (Troebinger et al., 2014) to achieve comparable levels of co-registration noise, in an auditory evoked response paradigm, and show that it is possible to discriminate between these cortical layer models in real data. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Cellular Evidence of Telocytes as Novel Interstitial Cells Within the Magnum of Chicken Oviduct.

Science.gov (United States)

Yang, Ping; Zhu, Xudong; Wang, Lingling; Ahmed, Nisar; Huang, Yufei; Chen, Hong; Zhang, Qian; Ullah, Shakeeb; Liu, Tengfei; Guo, Dawei; Brohi, Sarfaraz Ahmed; Chen, Qiusheng

2017-01-24

Telocytes are a novel type of interstitial cell that has been identified in many organs of mammals, but there is little information available on these cells in avian species. This study shows the latest findings associated with telocytes in the muscular layer and lamina propria of the magnum of chicken oviduct analyzed by transmission electron microscopy. Telocytes are characterized by telopodes, which are thin and long prolongations, and a small amount of cytoplasm rich with mitochondria. Spindle- or triangular-shaped telocytes were detected at various locations in the magnum. In the muscular layer, telocytes have direct connection with smooth muscle cells. The cell body of telocytes along with their long telopodes mainly exists in the interstitial space between the smooth muscle bundles, whereas large numbers of short telopodes are scattered in between the smooth muscle cells. In the lamina propria, extremely long telopodes are twisting around each other and are usually collagen embedded. Both in the lamina propria and muscular layer, telocytes have a close relationship with other cell types, such as immune cells and blood vessels. Telopodes appear with dichotomous branching alternating between the podom and podomer, forming a 3D network structure with complex homo- and heterocellular junctions. In addition, a distinctive size of the vesicles is visible around the telopodes and may be released from telopodes because of the close relation between the vesicle and telopode. All characteristics of telocytes in the magnum indicate that telocytes may play a potential, but important, role in the pathogenesis of oviduct diseases.

Morphologic observation of mucosa-associated lymphoid tissue in the large intestine of Bactrian camels (Camelus bactrianus).

Science.gov (United States)

ZhaXi, Yingpai; Wang, Wenhui; Zhang, Wangdong; Gao, Qiang; Guo, Minggang; Jia, Shuai

2014-07-01

The structure and distribution of the mucosa-associated lymphoid tissue (MALT) throughout the large intestine of 10 Bactrian camels were comparatively studied by anatomical and histological methods. The results showed that Peyer's patches (PPs) were mainly located on the mucosal surfaces of the entire ileocecal orifice, the beginning of the cecum and the first third of the colon. The shape of PPs gradually changed from "scrotiform" to "faviform" along the large intestine with the scrotiform PP as the major type in the ileocecal orifice. The distribution density also gradually decreased from the ileocecal orifice to the colon. The histological observations further revealed that the MALT in the form of PPs or isolated lymphoid follicles (ILF) and lamina propria lymphocytes was mainly present in the lamina propria and submucosa from the entire ileocecal orifice, where the muscularis mucosa is usually incomplete, to the colonic forepart. In addition, lymphoid tissue was much more abundant in the lamina propria and submucosa of the ileocecal orifice as compared to the cecum and colon. Statistically, the MALT of the ileocecal orifice contained a higher number of lymphoid follicles (37.7/10 mm(2) ) than that of the cecum, colon, or rectum (P lymphoid follicles were clearly visible. Together, our data suggest that the ileocecal orifice constitutes the main inductive site for the mucosal immunity in the large intestine of the Bactrian camel; and that scrotiform PPs are likely to the result of long-term adaptation of the Bactrian camel to the harsh living environment. © 2014 Wiley Periodicals, Inc.

Schellackia (Apicomplexa: Eimeriidae of the brazilian tree-frog, Phrynohyas venulosa (Amphibia: Anura from Amazonian Brazil

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I. Paperna

1995-10-01

Full Text Available Endogenous stages of a Schellackia species are described in histological sections of the intestine of the tree-frog, Phrynohyas venulosa, from North Brazil. Most oocysts sporulate within the epithelial cells of the gut, but a few were detected in the lamina propria.

Immunoglobulin leakiness in scid mice with CD4(+) T-cell-induced chronic colitis

DEFF Research Database (Denmark)

Brimnes, J; Reimann, J; Claesson, Mogens Helweg

2000-01-01

Inflammatory bowel disease in scid mice is initiated by transplantation of CD4(+) T-cells from immunocompetent syngenic donor mice. As the disease progresses, immunoglobulin (Ig)-containing cells appear in the gut lamina propria, suggesting that locally accumulating Ig may play a role in disease ...

TANZANIA JOURNAL OF SCIENCE VOLUME 35, 2009

African Journals Online (AJOL)

Mgina

Department of Anatomy/Histology, Muhimbili University College of Health Sciences ... immunoreactivity in the pyloric mucosa of the rat stomach. The immunoreactive elements included the endocrine cells, mast cells and mucosal nerve fibers in the lamina propria. The .... pancreatic secretion via a vagal cholinergic pathway ...

Susceptibility of porcine ileal enterocytes to the cytotoxin of Serpulina hyodysenteriae and the resolution of the epithelial lesions: an electron microscopic study.

Science.gov (United States)

Bland, A P; Frost, A J; Lysons, R J

1995-01-01

The cytotoxin from Serpulina hyodysenteriae was injected into ileal loops of eight germ-free pigs, and the effects on the villi were observed after 1, 3, and 18 hours of exposure. The mature vacuolated villus enterocytes of the proximal part of the absorptive villi were most susceptible to the lethal effects of the cytotoxin and were extensively exfoliated. The enterocytes at the base of the villi, the goblet cells, and the follicle-associated epithelium of the dome villi, particularly the M cells, were less affected. As the enterocytes were shed, the villi progressively shortened and the basement membrane became extensively folded. The absorptive villi were markedly stunted at 3 hours, and flattened globlet cells predominated at the site of restitution of the lesion. The myofibroblasts were also damaged, apparently subsequent to the exfoliation of the enterocytes. There was no further damage at 18 hours. The absorptive villi were stunted and were devoid of the large interstitial spaces of the normal lamina propria; the enterocytes were generally columnar, and at the apex of each villus there was an accumulation of goblet cells. There was a preponderance of M cells at the apices of the dome villi. Restitution of the lesions was not as rapid as observed in in vitro systems. The changes observed indicated that as the proximal enterocytes of the absorptive villi were shed, the loss of hydrostatic forces in the lamina propria allowed the myofibroblasts to collapse the villi by progressively retracting the basement membrane. This reduced the surface area to be covered during restitution. Resolution of the lesions was still incomplete after 18 hours.

Transient and Partial Nuclear Lamina Disruption Promotes Chromosome Movement in Early Meiotic Prophase.

Science.gov (United States)

Link, Jana; Paouneskou, Dimitra; Velkova, Maria; Daryabeigi, Anahita; Laos, Triin; Labella, Sara; Barroso, Consuelo; Pacheco Piñol, Sarai; Montoya, Alex; Kramer, Holger; Woglar, Alexander; Baudrimont, Antoine; Markert, Sebastian Mathias; Stigloher, Christian; Martinez-Perez, Enrique; Dammermann, Alexander; Alsheimer, Manfred; Zetka, Monique; Jantsch, Verena

2018-04-23

Meiotic chromosome movement is important for the pairwise alignment of homologous chromosomes, which is required for correct chromosome segregation. Movement is driven by cytoplasmic forces, transmitted to chromosome ends by nuclear membrane-spanning proteins. In animal cells, lamins form a prominent scaffold at the nuclear periphery, yet the role lamins play in meiotic chromosome movement is unclear. We show that chromosome movement correlates with reduced lamin association with the nuclear rim, which requires lamin phosphorylation at sites analogous to those that open lamina network crosslinks in mitosis. Failure to remodel the lamina results in delayed meiotic entry, altered chromatin organization, unpaired or interlocked chromosomes, and slowed chromosome movement. The remodeling kinases are delivered to lamins via chromosome ends coupled to the nuclear envelope, potentially enabling crosstalk between the lamina and chromosomal events. Thus, opening the lamina network plays a role in modulating contacts between chromosomes and the nuclear periphery during meiosis. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Nomenclature of Vertebral Laminae in Lizards, with Comments on Ontogenetic and Serial Variation in Lacertini (Squamata, Lacertidae).

Science.gov (United States)

Tschopp, Emanuel

2016-01-01

Vertebral laminae are bony ridges or sheets that connect important morphological landmarks on the vertebrae, like diapophyses or zygapophyses. They usually exhibit some serial variation throughout the column. A consistent terminology facilitates the morphological description of this variation, and the recognition of patterns that could be taxonomically significant and could serve as phylogenetic characters. Such a terminology was designed for saurischian dinosaurs, and has also been applied to other members of Archosauriformes. Herein, this terminology is applied for the first time to lizards (Squamata). Probably due to their generally smaller size compared to saurischian dinosaurs, lizards have less developed vertebral laminae. Some laminae could not be recognized in this group and others require new names to account for differences in basic vertebral morphology. For instance, the fusion of diapophysis and parapophysis in lacertids into a structure called synapophysis necessitates the creation of the new term synapophyseal laminae for both diapophyseal and parapophyseal laminae. An assessment of occurrence and serial variation in a number of lacertid species shows that some laminae develop throughout ontogeny or only occur in large-sized species, whereas the distribution of other laminae might prove to be taxonomically significant in future.

Nomenclature of Vertebral Laminae in Lizards, with Comments on Ontogenetic and Serial Variation in Lacertini (Squamata, Lacertidae.

Directory of Open Access Journals (Sweden)

Emanuel Tschopp

Full Text Available Vertebral laminae are bony ridges or sheets that connect important morphological landmarks on the vertebrae, like diapophyses or zygapophyses. They usually exhibit some serial variation throughout the column. A consistent terminology facilitates the morphological description of this variation, and the recognition of patterns that could be taxonomically significant and could serve as phylogenetic characters. Such a terminology was designed for saurischian dinosaurs, and has also been applied to other members of Archosauriformes. Herein, this terminology is applied for the first time to lizards (Squamata. Probably due to their generally smaller size compared to saurischian dinosaurs, lizards have less developed vertebral laminae. Some laminae could not be recognized in this group and others require new names to account for differences in basic vertebral morphology. For instance, the fusion of diapophysis and parapophysis in lacertids into a structure called synapophysis necessitates the creation of the new term synapophyseal laminae for both diapophyseal and parapophyseal laminae. An assessment of occurrence and serial variation in a number of lacertid species shows that some laminae develop throughout ontogeny or only occur in large-sized species, whereas the distribution of other laminae might prove to be taxonomically significant in future.

Intestinal T lymphocytes of different rat strains in immunotoxicity

NARCIS (Netherlands)

Bruder, M.C.; Spanhaak, S.; Bruijntjes, J.P.; Michielsen, C.P.P.C.; Vos, J.G.; Kuper, C.F.

1999-01-01

In order to study the intestinal mucosal immune cells, with emphasis on single T lymphocytcs, an inventory was made of single and organized lymphocytes in the epithelium and lamina propria of the small intestines of untreated Wistar, Fischer 344, and Lewis rats. The single and organized lymphocytes

Oral administration of kefiran induces changes in the balance of immune cells in a murine model.

Science.gov (United States)

Medrano, Micaela; Racedo, Silvia M; Rolny, Ivanna S; Abraham, Analía G; Pérez, Pablo F

2011-05-25

The aim of the present study was to evaluate the effect of the oral administration of kefiran on the balance of immune cells in a murine model. Six week old BALB/c mice were treated with kefiran (300 mg/L) for 0, 2 and 7 days. Kefiran treatment increased the number of IgA+ cells in lamina propria after 2 and 7 days. Percentage of B220+/MHCII(high) cells in mesenteric lymph nodes (2 days) and Peyer's patches (7 days) was higher compared to untreated control mice. An increase of macrophages (F4/80+ cells) was observed in lamina propria and peritoneal cavity (2 and 7 days). In contrast, at day 7, macrophage population decreased in Peyer's patches. These results show the ability of kefiran to modify the balance of immune cells in intestinal mucosa. This property could be highly relevant for the comprehension of the probiotic effect attributed to kefir.

Morphological study of the sensory innervation of the rat labial mucosa.

Science.gov (United States)

Yamamoto, T; Tazaki, M; Sakada, S

1986-02-01

The sensory innervation of the rat labial mucosa was investigated by means of methylene blue vital staining and osmic acid staining. Sensory receptors in this region were of three kinds (free nerve endings, encapsulated corpuscles and bush-like nerve endings) which constituted separate sensory units respectively. The encapsulated corpuscles were observed in the deep part of lamina propria, and distributed mainly in the margin of labial mucosa. Almost all (78.8%) of encapsulated corpuscles were of a simple type which had a non-branched axon terminal. No clew-like type corpuscles or glomerular-Meissner corpuscles were observed. The bush-like nerve endings were located in the lamina propria close to the epithelium, and localized in the central part of labial mucosa where the formation of papillae was remarkable. The density of the encapsulated corpuscles in the entire mucosa was 3.5-5.3/mm2, and that of the bush-like nerve endings in the densely distributed area was 38.9-60.6/mm2.

Mechanisms and timing of replacement dental lamina regression

Czech Academy of Sciences Publication Activity Database

Dosedělová, H.; Dumková, J.; Lesot, H.; Glocová, K.; Hampl, A.; Tucker, A.; Buchtová, Marcela

2013-01-01

Roč. 296, special feature (2013), s. 272-272 ISSN 1932-8486. [International Congress of Vertebrate Morphology /10./. 08.07.2013-12.07.2013, Barcelona] Institutional support: RVO:67985904 Keywords : dental lamina Subject RIV: FF - HEENT, Dentistry

Effects of the oral administration of the exopolysaccharide produced by Lactobacillus kefiranofaciens on the gut mucosal immunity.

Science.gov (United States)

Vinderola, Gabriel; Perdigón, Gabriela; Duarte, Jairo; Farnworth, Edward; Matar, Chantal

2006-12-01

The probiotic effects ascribed to lactic acid bacteria (LAB) and their fermented dairy products arise not only from whole microorganisms and cell wall components but also from peptides and extracellular polysaccharides (exopolysaccharides) produced during the fermentation of milk. There is a lack of knowledge concerning the immune mechanisms induced by exopolysaccharides produced by lactic acid bacteria, which would allow a better understanding of the functional effects described to them. The aim of this study was to investigate the in vivo immunomodulating capacity of the exopolysaccharide produced by Lactobacillus kefiranofaciens by analyzing the profile of cytokines and immunoglobulins induced at the intestinal mucosa level, in the intestinal fluid and blood serum. BALB/c mice received the exopolysaccharide produced by L. kefiranofaciens for 2, 5 or 7 consecutive days. At the end of each period of administration, control and treated mice were sacrificed and the numbers of IgA+ and IgG+ cells were determined on histological slices of the small and large intestine by immunofluorescence. Cytokines (IL-4, IL-6, IL-10, IL-12, IFNgamma and TNFalpha) were also determined in the gut lamina propria as well as in the intestinal fluid and blood serum. There was an increase of IgA+ cells in the small and large intestine lamina propria, without change in the number of IgG+ cells in the small intestine. This study reports the effects of the oral administration of the exopolysaccharide produced by L. kefiranofaciens in the number of IgA+ cells in the small and large intestine, comparing simultaneously the production of cytokines by cells of the lamina propria and in the intestinal fluid and blood serum. The increase in the number of IgA+ cells was not simultaneously accompanied by an enhance of the number of IL-4+ cells in the small intestine. This finding would be in accordance with the fact that, in general, polysaccharide antigens elicit a T-independent immune response. For

Suprihati and Yunus, Afr., J. Infect. Dis. (2018) 12(S): 104-110 https ...

African Journals Online (AJOL)

user1

2017-10-18

Oct 18, 2017 ... intensifying because of the increasing threat of drug resistance to anticoccidial agents. It is important, therefore, to develop a reliable ..... hemorrhage and complete desquamation of epithelium and edema of muscular tissue which agreed with the finding of Levine. (1985). The entire lamina propria revealed ...

The formation process of the flood type lamina in the Lake Mokoto, Hokkaido, Japan.

Science.gov (United States)

Seto, K.; Katsuki, K.; Takeshi, S.

2017-12-01

In the coastal area of the Sea of Okhotsk in the east part of Hokkaido located to subarctic zone, many brackish-water lakes are distributed. Lake Mokoto consist of organic mud with the lamination. The 09Mk-1C core at 2009. In the soft X-ray photograph, the cyclic lamina set is observed. The cyclic lamina set consists of low- and high-density lamina. According to the meteorological data in Abashiri region, the annually precipitation is high from August to September. Probably, the cyclic lamina set is formed by seasonal change of precipitation. In August 2016, it showed a precipitation of 425 mm which is about 4 times the average precipitation. In February 2017, the 10 cm class short core (17Mk-4SC core) was collected and the flood lamina was observed. Six layers showing different color were observed in top 6.5 cm. The first, third and fifth layers from the top are relatively light in color (L*value=17). The second, fourth and sixth layers are relatively dark in color (L*value=8). Thickness of the first to fourth layers is about 5 mm, but the thickness of the fifth layer reaches 4 cm. According to the observation of the soft X-ray photograph, the third and fifth layers were high-density lamina, and the others were low-density lamina. Because these layers were not observed in the 15Mk-3C core collected in March 2015, they were deposited after that. It is estimated that the third layer showing the high-density lamina is the sediment of the flood event in August 2016. This is supported by the fact that the total organic carbon (TOC) and total sulfur (TS) contents are diluted and the C/N ratio is relatively high value. Because this lamina is remarkable, it will be used as a future key bed. On the other hand, the fifth layer showing the high-density is a very thick. In this layer, the TS content is diluted and the C/N ratio is high, but the TOC content shows the highest value. This suggests that sediments with high TOC content flowed out from Mokoto River Basin. It has

Brilliant iridescence of Morpho butterfly wing scales is due to both a thin film lower lamina and a multilayered upper lamina.

Science.gov (United States)

Giraldo, M A; Stavenga, D G

2016-05-01

Butterflies belonging to the nymphalid subfamily, Morphinae, are famous for their brilliant blue wing coloration and iridescence. These striking optical phenomena are commonly explained as to originate from multilayer reflections by the ridges of the wing scales. Because the lower lamina of the scales of related nymphalid butterflies, the Nymphalinae, plays a dominant role in the wing coloration, by acting as a thin film reflector, we investigated single blue scales of three characteristic Morpho species: M. epistrophus, M. helenor and M. cypris. The experimental data obtained by spectrophotometry, scatterometry and scanning electron microscopy demonstrated that also in the Morpho genus the lower lamina of both the cover and ground scales acts as an optical thin film reflector, contributing importantly to the blue structural coloration of the wings. Melanin pigment has a contrast-enhancing function in a sub-class of ground scales.

Brilliant iridescence of Morpho butterfly wing scales is due to both a thin film lower lamina and a multilayered upper lamina

NARCIS (Netherlands)

Giraldo, M A; Stavenga, D G

2016-01-01

Butterflies belonging to the nymphalid subfamily, Morphinae, are famous for their brilliant blue wing coloration and iridescence. These striking optical phenomena are commonly explained as to originate from multilayer reflections by the ridges of the wing scales. Because the lower lamina of the

Experimental Investigations on the effect of Additive on the Tensile Properties of Fiber Glass Fabric Lamina

Science.gov (United States)

Nava Sai Divya, A.; Raghu Kumar, B., Dr; Lakshmi Narayana, G., Dr

2017-09-01

The main objective of this work is to investigate the effect of additives on tensile behaviour of fiber glass fabric at lamina level to explore an alternative skin material for the outer body of aerospace applications and machines. This experimental work investigates the effect of silica concentration in epoxy resin lapox L-12 on the tensile properties of glass fabric lamina of 4H-satin weave having 3.6 mm thickness. The lamina was prepared by using hand lay-up method and tests were conducted on it. Various tensile properties values obtained from experimentation were compared for four glass fiber lamina composites fabricated by adding the silica powder to resin bath. The effect of variations in silica concentration (0% SiO2, 5% SiO2, 10% SiO2 and 15% SiO2) on the tensile properties of prepared material revealed that maximum stiffness was obtained at 15% and yield strength at 10% SiO2 concentration in glass fiber lamina. Increasing the silica concentration beyond 10% had led to deterioration in the material properties. The experimentation that was carried out on test specimen was reasonably successful as the effect of silica powder as an additive in glass fiber lamina enhanced the mechanical properties up to certain limit. The underpinning microscopic behaviour at the source of these observations will be investigated in a follow up work.

Neutrophil migration through preexisting holes in the basal laminae of alveolar capillaries and epithelium during streptococcal pneumonia.

Science.gov (United States)

Walker, D C; Behzad, A R; Chu, F

1995-11-01

The purpose of this study was to determine whether or not there are preexisting holes in the endothelial and epithelial basal laminae of alveolar walls and to determine the path taken by neutrophils as they migrate from the capillaries to the airspace of the alveoli during inflammation. Using transmission electron microscopy and serial thin sections of normal rabbit and mouse lung, we have demonstrated the presence of slit-like holes in the capillary basal laminae and round holes in the basal laminae of type 2 pneumocytes. The slits in the capillary basal laminae were observed at the intersection of the thick and thin walls where endothelium, pericytes, and fibroblasts make close contact. The round holes in the type 2 cell basal laminae were observed at sites of close contact with fibroblasts. Neutrophils were observed to migrate through these slits and holes during streptococcal pneumonia in rabbit lungs. We conclude that during inflammation in the lung, migrating neutrophils displace pericytes and fibroblasts from the slits in the capillary basal lamina and then crawl through these slits into the alveolar interstitium. We postulate that neutrophils find their way to type 2 pneumocytes by following interstitial fibroblasts. We believe that neutrophils displace fibroblasts from their close contacts with the type 2 cells and then crawl through the holes in the basal lamina into the basal lateral space of the type 2 cells. From there, neutrophils migrate into the alveolar airspace.

Untitled

Indian Academy of Sciences (India)

The muscularis is in two layers, an inner longitudinal and an outer circular. Both have striated fibres. The proximal part of the oesophagus which lies outside the body cavity consists of four layers, mucosa, lamina propria, submucosa and muscularis. The distal part lying inside the body cavity has in addition a serous layer.

Electron microscopic observation of 137Cs-irradiated rat testis. Production of basal laminae for germ cells, despite their absence

International Nuclear Information System (INIS)

Sawada, Hajime; Esaki, Michiyo

2003-01-01

Whole body γ-ray irradiation of rats with caesium-137 ( 137 Cs) at embryonic day 20 induced marked reduction of the weight of the testis. Body weight and other tissues, however, seemed to remain normal. By light microscopy, complete loss of germ cells was observed in the testis. Other components, such as Sertoli cells and interstitial cells, seemed to be normal. The testes from day 8 postpartum rats contained very few spermatogonia compared with newborn rats, indicating loss of germ cells between days 0 and 8. In the adult, 137 Cs-irradiated testes showed two conspicuous features other than the loss of germ cells: empty vacuolar spaces between Sertoli cells and multilayered seminiferous tubule basal laminae (lamina densa). The junctional structures (ectoplasmic specializations) between Sertoli cells, however, seemed normal. The thickness of each layer of multilayered basal laminae was the same as that of normal rats and electron-lucent layers similar to lamina lucida were interposed between them. Of the empty vacuolar spaces between Sertoli cells, basal laminae bridge the gap. The basal laminae contained laminin, type IV collagen and heparan sulphate proteoglycan evenly distributed among layers, suggesting a normal composition. Rough estimation of the amount of basal laminae deposited in 137 Cs-irradiated rats indicates that it is within a range similar to that in normal testis. These features imply that Sertoli cells are, in part, determined perinatally to produce basal laminae for germ-line cells. (author)

Changes in the interstitial cells of Cajal and neuronal nitric oxide synthase positive neuronal cells with aging in the esophagus of F344 rats.

Science.gov (United States)

Kim, Hee Jin; Kim, Nayoung; Kim, Yong Sung; Nam, Ryoung Hee; Lee, Sun Min; Park, Ji Hyun; Choi, Daeun; Hwang, Young-Jae; Lee, Jongchan; Lee, Hye Seung; Kim, Min-Seob; Lee, Moon Young; Lee, Dong Ho

2017-01-01

The aging-associated cellular and molecular changes in esophagus have not been established, yet. Thus we evaluated histological structure, interstitial cells of Cajal (ICCs), neuronal nitric oxide synthase (nNOS)-positive cells, and contractility in the esophagus of Fischer 344 rat at different ages (6-, 31-, 74-weeks, and 2-years). The lamina propria thickness and endomysial area were calculated. The immunoreactivity of c-Kit, nNOS and protein gene product (PGP) 9.5 was counted after immunohistochemistry. Expression of c-Kit, stem cell factor (SCF), nNOS and PGP 9.5 mRNA was measured by real-time PCR, and expression of c-Kit and nNOS protein was detected by Western blot. Isovolumetric contractile force measurement and electrical field stimulation (EFS) were conducted. The lamina propria thickness increased (6 week vs 2 year, P = 0.005) and the endomysial area of longitudinal muscle decreased with aging (6 week vs 2 year, Pcells and c-Kit-immunoreactive areas declined with aging (6 week vs 2 year; Paging (6 week vs 2 year; P = 0.006, P = 0.001 and P = 0.006, respectively), while the change of PGP 9.5 mRNA expression was not significant. Western blot showed the significant decreases of nNOS and c-Kit protein expression with aging (6 week vs 2 year; P = 0.008 and P = 0.012, respectively). The EFS-induced esophageal contractions significantly decreased in 2-yr-old rat compared with 6-wk-old rats, however, L-NG-Nitroarginine methylester did not significantly increase the spontaneous and EFS-induced contractions in the 6-wk- and 2-yr-old rat esophagus. In conclusion, an increase of lamina propria thickness, a decrease of endomysial area, c-Kit, SCF and NOS expression with preserved total enteric neurons, and contractility in aged rat esophagus may explain the aging-associated esophageal dysmotility.

Crucial involvement of tumor-associated neutrophils in the regulation of chronic colitis-associated carcinogenesis in mice.

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Kun Shang

Full Text Available Ulcerative colitis (UC is a major form of chronic inflammation that can frequently progress to colon cancer. Several studies have demonstrated massive infiltration of neutrophils and macrophages into the lamina propria and submucosa in the progression of UC-associated colon carcinogenesis. Macrophages contribute to the development of colitis-associated colon cancer (CAC. However, the role of neutrophils is not well understood. To better understand the involvement of tumor-associated neutrophils (TANs in the regulation of CAC, we used a mouse CAC model produced by administering azoxymethane (AOM, followed by repeated dextran sulfate sodium (DSS ingestion. This causes severe colonic inflammation and subsequent development of multiple tumors in mice colon. We observed that colorectal mucosal inflammation became increasingly severe with AOM and DSS treatment. Macrophages infiltrated the lamina propria and submucosa, together with a marked increase in neutrophil infiltration. The chemokine CXCL2 increased in the lamina propria and submucosal regions of the colons of the treated mice, together with the infiltration of neutrophils expressing CXCR2, a specific receptor for CXCL2. This process was followed by neoplastic transformation. After AOM and DSS treatment, the mice showed enhanced production of metalloproteinase (MMP-9 and neutrophil elastase (NE, accompanied by excessive vessel generation and cell proliferation. Moreover, CXCL2 promoted neutrophil recruitment and induced neutrophils to express MMP-9 and NE in vitro. Furthermore, administration of neutrophil-neutralizing antibodies after the last DSS cycle markedly reduced the number and size of tumors and decreased the expression of CXCR2, CXCL2, MMP-9, and NE. These observations indicate a crucial role for TANs in the initiation and progression of CAC and suggest that the CXCL2-CXCR2 axis might be useful in reducing the risk of UC-associated colon cancer.

Cathaemasia hians infection in Black stork in Slovakia: morphological and histopathological study

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Königová A.

2015-12-01

Full Text Available Cathaemasia hians is an obligate trematode parasite of Black storks that are on the List of protected birds in Europe. In the present study, adult trematodes were isolated from the Black stork post mortem and morphological study revealed C. hians species. In total, 10 worms were found in the oesophagus and the ventriculus of the bird. Histopathological examination of the tissue samples of oesophagus, proventriculus and ventriculus was performed on paraffin sections using a set of staining procedures. The sporadic lesions were seen in the tela submucosa of oesophagus containing connective tissue mast cells, eosinophils and heterophils and some foci were surrounded by the fibrous tissue. In addition, a few inflammatory nodules had larval-like material inside, probably being of the same species. There were no visible morphological alterations in the epithelial layer of lamina propria mucosae of proventriculus, rich in goblet cells as well as in the tela submucosa. Majority of trematodes were localized in the ventriculus, where the lamina propria mucosae was damaged or disrupted sporadically. In these sites, in the tela submucosa, a various food-originated inorganic/organic material and eggs of C. hians were deposited, stimulating a weak inflammatory response. Nodules containing larvae were not observed in any of ventriculus tissue layers. This study demonstrated, for the first time, infection with adults of C. hians trematode in the Black stork nesting in Slovakia. The presence of larvae and eggs in the tissues of the upper gastrointestinal tract of bird was associated with mild inflammatory response but feeding behaviour of adult worms in the ventriculus probably contributed to the enhanced susceptibility of the lamina propria mucosae to mechanical damage by inorganic material. Although larval stages have not yet been documented in the intermediate hosts in Slovakia, our report indicates that the life cycle of C. hians might occur in Central

Crucial Involvement of Tumor-Associated Neutrophils in the Regulation of Chronic Colitis-Associated Carcinogenesis in Mice

Science.gov (United States)

Wang, Chen; Wang, Zhen; Gu, Hong-Yu; Du, Xiang; Zhou, Xiao-Yan; Zheng, Chun-Lei; Chi, Ya-Yun; Mukaida, Naofumi; Li, Ying-Yi

2012-01-01

Ulcerative colitis (UC) is a major form of chronic inflammation that can frequently progress to colon cancer. Several studies have demonstrated massive infiltration of neutrophils and macrophages into the lamina propria and submucosa in the progression of UC-associated colon carcinogenesis. Macrophages contribute to the development of colitis-associated colon cancer (CAC). However, the role of neutrophils is not well understood. To better understand the involvement of tumor-associated neutrophils (TANs) in the regulation of CAC, we used a mouse CAC model produced by administering azoxymethane (AOM), followed by repeated dextran sulfate sodium (DSS) ingestion. This causes severe colonic inflammation and subsequent development of multiple tumors in mice colon. We observed that colorectal mucosal inflammation became increasingly severe with AOM and DSS treatment. Macrophages infiltrated the lamina propria and submucosa, together with a marked increase in neutrophil infiltration. The chemokine CXCL2 increased in the lamina propria and submucosal regions of the colons of the treated mice, together with the infiltration of neutrophils expressing CXCR2, a specific receptor for CXCL2. This process was followed by neoplastic transformation. After AOM and DSS treatment, the mice showed enhanced production of metalloproteinase (MMP)-9 and neutrophil elastase (NE), accompanied by excessive vessel generation and cell proliferation. Moreover, CXCL2 promoted neutrophil recruitment and induced neutrophils to express MMP-9 and NE in vitro. Furthermore, administration of neutrophil-neutralizing antibodies after the last DSS cycle markedly reduced the number and size of tumors and decreased the expression of CXCR2, CXCL2, MMP-9, and NE. These observations indicate a crucial role for TANs in the initiation and progression of CAC and suggest that the CXCL2–CXCR2 axis might be useful in reducing the risk of UC-associated colon cancer. PMID:23272179

Physiologic TLR9-CpG-DNA interaction is essential for the homeostasis of the intestinal immune system.

Science.gov (United States)

Hofmann, Claudia; Dunger, Nadja; Doser, Kristina; Lippert, Elisabeth; Siller, Sebastian; Edinger, Matthias; Falk, Werner; Obermeier, Florian

2014-01-01

Cytosine-guanosine dinucleotide (CpG) motifs are immunostimulatory components of bacterial DNA and activators of innate immunity through Toll-like receptor 9 (TLR9). Administration of CpG oligodeoxynucleotides before the onset of experimental colitis prevents intestinal inflammation by enforcement of regulatory mechanisms. It was investigated whether physiologic CpG/TLR9 interactions are critical for the homeostasis of the intestinal immune system. Mesenteric lymph node cell and lamina propria mononuclear cell (LPMC) populations from BALB/c wild-type (wt) or TLR9 mice were assessed by flow cytometry and proteome profiling. Cytokine secretion was determined and nuclear extracts were analyzed for nuclear factor kappa B (NF-κB) and cAMP response-element binding protein activity. To assess the colitogenic potential of intestinal T cells, CD4-enriched cells from LPMC of wt or TLR9 donor mice were injected intraperitoneally in recipient CB-17 SCID mice. TLR9 deficiency was accompanied by slight changes in cellular composition and phosphorylation of signaling proteins of mesenteric lymph node cell and LPMC. LPMC from TLR9 mice displayed an increased proinflammatory phenotype compared with wt LPMC. NF-κB activity in cells from TLR9 mice was enhanced, whereas cAMP response-element binding activity was reduced compared with wt. Transfer of lamina propria CD4-enriched T cells from TLR9 mice induced severe colitis, whereas wt lamina propria CD4-enriched T cells displayed an attenuated phenotype. Lack of physiologic CpG/TLR9 interaction impairs the function of the intestinal immune system indicated by enhanced proinflammatory properties. Thus, physiologic CpG/TLR interaction is essential for homeostasis of the intestinal immune system as it is required for the induction of counterregulating anti-inflammatory mechanisms.

Spatial distribution and functional significance of leaf lamina shape in Amazonian forest trees

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A. C. M. Malhado

2009-08-01

Full Text Available Leaves in tropical forests come in an enormous variety of sizes and shapes, each of which can be ultimately viewed as an adaptation to the complex problem of optimising the capture of light for photosynthesis. However, the fact that many different shape "strategies" coexist within a habitat demonstrate that there are many other intrinsic and extrinsic factors involved, such as the differential investment in support tissues required for different leaf lamina shapes. Here, we take a macrogeographic approach to understanding the function of different lamina shape categories. Specifically, we use 106 permanent plots spread across the Amazon rainforest basin to: 1 describe the geographic distribution of some simple metrics of lamina shape in plots from across Amazonia, and; 2 identify and quantify relationships between key environmental parameters and lamina shape in tropical forests. Because the plots are not randomly distributed across the study area, achieving this latter objective requires the use of statistics that can account for spatial auto-correlation. We found that between 60–70% of the 2791 species and 83 908 individual trees in the dataset could be classified as having elliptic leaves (= the widest part of the leaf is on an axis in the middle fifth of the long axis of the leaf. Furthermore, the average Amazonian tree leaf is 2.5 times longer than it is wide and has an entire margin. Contrary to theoretical expectations we found little support for the hypothesis that narrow leaves are an adaptation to dry conditions. However, we did find strong regional patterns in leaf lamina length-width ratios and several significant correlations with precipitation variables suggesting that water availability may be exerting an as yet unrecognised selective pressure on leaf shape of rainforest trees. Some support was found for the hypothesis that narrow leaves are an adaptation to low nutrient soils. Furthermore, we found a strong correlation between

Mechanisms of nuclear lamina growth in interphase

Czech Academy of Sciences Publication Activity Database

Zhironkina, O.A.; Kurchashova, S.Y.; Pozharskaia, V.A.; Cherepanynets, V.D.; Strelkova, O.S.; Hozák, Pavel; Kireev, I.I.

2016-01-01

Roč. 145, č. 4 (2016), s. 419-432 ISSN 0948-6143 R&D Projects: GA ČR GA16-03403S Grant - others:Russian Fund for Basic Research(RU) 13-04-00885; Russian Fund for Basic Research(RU) 15-54-78077 Institutional support: RVO:68378050 Keywords : Nuclear lamina * Microdomains * Interphase * Nucleus * DNA replication * Cell cycle Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.553, year: 2016

The disruption of the epithelial mesenchymal trophic unit in COPD.

Science.gov (United States)

Behzad, Ali R; McDonough, John E; Seyednejad, Nazgol; Hogg, James C; Walker, David C

2009-12-01

Progression of COPD is associated with a measurable increase in small airway wall thickness resulting from a repair and remodeling process that involves fibroblasts of the epithelial mesenchymal trophic unit (EMTU). The present study was designed to examine the organization of fibroblasts within the lamina propria of small airways with respect to their contacts with the epithelium and with each other in persons with COPD. Transmission electron microcopy (TEM) and three-dimensional (3D) reconstructions of serial TEM sections were used to estimate the frequency and determine the nature of the contacts between the epithelium and fibroblasts within the EMTU in small airways from 5 controls (smokers with normal lung function), from 6 persons with mild (GOLD-1) and 5 with moderate (GOLD-2) COPD. In airways from control lungs fibroblasts make frequent contact with cytoplasmic extensions of epithelial cells through apertures in the epithelial basal lamina, but the frequency of these fibroblast-epithelial contacts is reduced in both mild and moderate COPD compared to controls (p < 0.01). The 3D reconstructions showed that the cytoplasmic extensions of lamina propria fibroblasts form a reticulum with fibroblast-fibroblast contacts in an airway from a control subject but this reticulum may be reorganized in airways of COPD patients. Development of COPD is associated with significant disruption of the EMTU due to a reduction of contacts between fibroblasts and the epithelium.

(Clarias gariepinus

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Lawrence Ezemonye

2010-01-01

Full Text Available Clarias gariepinus fingerlings exposed to lethal and sublethal concentrations of Gammalin 20 were investigated in a renewal static bioassay with particular reference to behaviour, survival, and histopathological changes. Early symptoms of gammalin 20 lethal poisoning were, respiratory distress, increased physical activity, convulsions, erratic swimming, loss of equilibrium, and increased breathing activity. Behavioural response was dose dependent and decreased with decreased concentration. The 96-hour lethal concentration (LC50 value was 30 ppb. Histopathological changes of the gill, liver, and intestinal tissues of fish treated with sublethal concentration of gammalin 20 for twelve weeks showed gill distortion and fusion of adjacent secondary lamella as a result of hyperplasia and excessive mucus accumulation. The liver showed swelling of hepatocytes with mild necrosis, pyknosis, and vacuolation, while the intestine showed yellow bodies of the lamina propria at the tip of the mucosal fold.

Histopathological Effects of Gammalin 20 on African Catfish (Clarias gariepinus)

International Nuclear Information System (INIS)

Ezemonye, L.; Ogbomida, T.E.

2010-01-01

Clarias gariepinus fingerlings exposed to lethal and sublethal concentrations of Gammalin 20 were investigated in a renewal static bioassay with particular reference to behaviour, survival, and histopathological changes. Early symptoms of gammalin 20 lethal poisoning were, respiratory distress, increased physical activity, convulsions, erratic swimming, loss of equilibrium, and increased breathing activity. Behavioural response was dose dependent and decreased with decreased concentration. The 96-hour lethal concentration (LC 50 ) value was 30 ppb. Histopathological changes of the gill, liver, and intestinal tissues of fish treated with sublethal concentration of gammalin 20 for twelve weeks showed gill distortion and fusion of adjacent secondary lamella as a result of hyperplasia and excessive mucus accumulation. The liver showed swelling of hepatocytes with mild necrosis, pyknosis, and vacuolation, while the intestine showed yellow bodies of the lamina propria at the tip of the mucosal fold. environmental monitoring hazardous substances like heavy metals, pesticides

Diagenetic variation at the lamina scale in lacustrine organic-rich shales: Implications for hydrocarbon migration and accumulation

Science.gov (United States)

Liang, Chao; Cao, Yingchang; Liu, Keyu; Jiang, Zaixing; Wu, Jing; Hao, Fang

2018-05-01

Lacustrine carbonate-rich shales are well developed within the Mesozoic-Cenozoic strata of the Bohai Bay Basin (BBB) of eastern China and across southeast Asia. Developing an understanding of the diagenesis of these shales is essential to research on mass balance, diagenetic fluid transport and exchange, and organic-inorganic interactions in black shales. This study investigates the origin and distribution of authigenic minerals and their diagenetic characteristics, processes, and pathways at the scale of lacustrine laminae within the Es4s-Es3x shale sequence of the BBB. The research presented in this study is based on thin sections, field emission scanning electron microscope (FESEM) and SEM-catholuminescence (CL) observations of well core samples combined with the use of X-ray diffraction (XRD), energy dispersive spectroscopy, electron microprobe analysis, and carbon and oxygen isotope analyses performed using a laser microprobe mass spectrometer. The dominant lithofacies within the Es4s-Es3x sequence are a laminated calcareous shale (LCS-1) and a laminated clay shale (LCS-2). The results of this study show that calcite recrystallization1 is the overarching diagenetic process affecting the LCS-1, related to acid generation from organic matter (OM) thermal evolution. This evolutionary transition is the key factor driving the diagenesis of this lithofacies, while the transformation of clay minerals is the main diagenetic attribute of the LCS-2. Diagenetic differences occur within different laminae and at variable locations within the same lamina level, controlled by variations in mineral composition and the properties of laminae interfaces. The diagenetic fluid migration scale is vertical and responses (dissolution and replacement) are limited to individual laminae, between zero and 100 μm in width. In contrast, the dominant migration pathway for diagenetic fluid is lateral, along the abrupt interfaces between laminae boundaries, which leads to the vertical

Glymphatic stasis at the site of the lamina cribrosa as a potential mechanism underlying open-angle glaucoma

NARCIS (Netherlands)

Wostyn, Peter; Killer, Hanspeter Esriel; De Deyn, Peter Paul

The underlying pathophysiology of primary open-angle glaucoma remains unclear, but the lamina cribrosa seems to be the primary site of injury, and raised intraocular pressure is a major risk factor. In recent years, a decreased intracranial pressure, leading to an abnormally high trans-lamina

Dietary cadmium and enteropathy in the Japanese quail: histochemical and ultrastructural studies

Energy Technology Data Exchange (ETDEWEB)

Richardson, M.E.; Fox, M.R.S.

1974-01-01

Cadmium was fed to young Japanese quail, at a level of 75 mg. per kg. of diet, from hatching to 4 weeks of age. Cadmium produced gross, microscopic, and ultrastructural lesions in the proximal small intestine of these quail, similar to those occurring in human malabsorption syndromes, celiac disease, nontropical sprue, and tropical sprue. The small intestines of the quail were dilated and thin walled. Villi were short and thick and had a dense cellular infiltrate in the lamina propria. The striated border was thin but stained for neutral mucopolysaccharides, as did the normal border. Some villi were covered with stratified epithelial cells. Hypertrophy and hyperplasia of goblet were seen, but the mucin stained for weakly acidic mucopolysaccharides, as did the normal cells. At the ultrastructural level, microvilli of both absorptive and goblet cells were markedly shortened, particularly near the tips of the villi. Absorptive cells were atrophic, and there was s diminution of the usual cellular organelles. Granular cisternae were long and tortuous, mitochondria were dense and small, and large lysosome-like bodies and large lipid droplets accumulated in the cytoplasm, but there was a decrease in the normal small, pale and dark lipid droplets. The cellular infiltrate of the lamina propria included groups of plasma cells with dilated cisternae. There were large, irregular, electron-dense bodies in the endothelium of large veins and degeneration of some nerve plexuses in the muscularis propria. 31 references, 21 figures.

Sensitization to epithelial antigens in chronic mucosal inflammatory disease. Characterization of human intestinal mucosa-derived mononuclear cells reactive with purified epithelial cell-associated components in vitro.

OpenAIRE

Roche, J K; Fiocchi, C; Youngman, K

1985-01-01

To explore the auto-reactive potential of cells infiltrating the gut mucosa in idiopathic chronic inflammatory bowel disease, intestinal lamina propria mononuclear cells (LPMC) were isolated, characterized morphologically and phenotypically, and evaluated for antigen-specific reactivity. The last was assessed by quantitating LPMC cytotoxic capabilities against purified, aqueous-soluble, organ-specific epithelial cell-associated components (ECAC) characterized previously. Enzyme-isolated infla...

Remodeling of the Nuclear Envelope and Lamina during Bovine Preimplantation Development and Its Functional Implications.

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Jens Popken

Full Text Available The present study demonstrates a major remodeling of the nuclear envelope and its underlying lamina during bovine preimplantation development. Up to the onset of major embryonic genome activation (MGA at the 8-cell stage nuclei showed a non-uniform distribution of nuclear pore complexes (NPCs. NPCs were exclusively present at sites where DNA contacted the nuclear lamina. Extended regions of the lamina, which were not contacted by DNA, lacked NPCs. In post-MGA nuclei the whole lamina was contacted rather uniformly by DNA. Accordingly, NPCs became uniformly distributed throughout the entire nuclear envelope. These findings shed new light on the conditions which control the integration of NPCs into the nuclear envelope. The switch from maternal to embryonic production of mRNAs was accompanied by multiple invaginations covered with NPCs, which may serve the increased demands of mRNA export and protein import. Other invaginations, as well as interior nuclear segments and vesicles without contact to the nuclear envelope, were exclusively positive for lamin B. Since the abundance of these invaginations and vesicles increased in concert with a massive nuclear volume reduction, we suggest that they reflect a mechanism for fitting the nuclear envelope and its lamina to a shrinking nuclear size during bovine preimplantation development. In addition, a deposit of extranuclear clusters of NUP153 (a marker for NPCs without associated lamin B was frequently observed from the zygote stage up to MGA. Corresponding RNA-Seq data revealed deposits of spliced, maternally provided NUP153 mRNA and little unspliced, newly synthesized RNA prior to MGA, which increased strongly at the initiation of embryonic expression of NUP153 at MGA.

The essential oil in lamina and petiole of heracleum-dissectum leaves

NARCIS (Netherlands)

Montanarella, L; Bos, R; Fisher, FC

The essential oils of lamina and petiole of Heracleum dissectum are described. Fifty-seven compounds have been identified by mass spectrometry and retention indices. Differences between the oils of the two organs were mainly quantitative.

Uso de carbonos pirolíticos (Durasphere no tratamento da insuficiência glótica: estudo experimental em cães Use of pyrolytic carbon coated beads (Durasphere to treat glottic failure: an experimental study in dogs

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Domingos Hiroshi Tsuji

2009-12-01

Full Text Available Nenhum tecido ou substância ideal foi encontrado para a injeção em pregas vocais. O objetivo deste estudo prospectivo foi avaliar o uso do Durasphere como substância de injeção na prega vocal canina. MATERIAIS E MÉTODOS: Em seis cães adultos foram injetados 0,3mL de Durasphere no terço médio da prega vocal direita no músculo tireoaritenoideo e 0,3mL de soro fisiológico na prega contralateral. Os animais foram sacrificados após 7 dias (três cães e 90 dias (três cães. Analisamos os processos inflamatórios no músculo vocal e na lâmina própria das pregas vocais. RESULTADOS: No músculo vocal com Durasphere havia uma inflamação significativamente maior que no músculo controle, formouse um infiltrado linfomononuclear moderado após 7 dias e leve após 90 dias. Não observamos formação de corpos estranhos ou granulomas. Já na lâmina própria houve um processo inflamatório leve nos dois grupos, sem diferença entre eles. CONCLUSÃO: Trata-se de uma substância com biocompatibilidade comprovada em humanos, com resultados preliminares e inéditos de sua injeção em pregas vocais caninas que causou um processo inflamatório moderado no músculo vocal após 7 dias e leve após 90 dias, sem formação de corpos estranhos ou granulomas.There is no ideal tissue or substance to be injected in the vocal folds. The objective of the present study was to assess the use of Durasphere in canine vocal fold injection. MATERIALS AND METHODS: in six adult dogs we injected 0.3 mL of Durasphere in the middle third of the thyroarytenoid muscle and 0.3 mL of saline solution in the contralateral vocal fold. The animals were slaughtered after seven days (three dogs and after 90 days (three dogs. We analyzed the inflammatory process in the vocal fold and in the lamina propria of the vocal folds. RESULTS: in the vocal muscle which received Durasphere there was a significantly more intense inflammation when compared to the control muscle - there was

In vitro activated CD4+ T cells from interferon-gamma (IFN-gamma)-deficient mice induce intestinal inflammation in immunodeficient hosts

DEFF Research Database (Denmark)

Bregenholt, S; Brimnes, J; Nissen, Mogens Holst

1999-01-01

To investigate the role of IFN-gamma in the immunopathogenesis of inflammatory bowel disease (IBD), severe combined immunodeficient (SCID) mice were transplanted with in vitro activated CD4+ T cells from either wild-type (WT) or IFN-gamma-deficient (IFN-gammaKO) BALB/c mice. In vitro, the two types...... of T cells displayed comparable proliferation rates and production of tumour necrosis factor-alpha (TNF-alpha), IL-2, IL-4 and IL-10 after concanavalin A (Con A) stimulation. When transplanted into SCID mice, WT CD4+ blasts induced a lethal IBD, whereas IFN-gammaKO blasts induced a less severe...... intestinal inflammation with moderate weight loss. Intracellular cytokine staining of lamina propria lymphocytes (LPL) revealed comparable fractions of CD4+ T cells positive for TNF-alpha, IL-2 and IL-10 in the two groups of transplanted SCID mice, whereas a two-to-three-fold increase in the fraction of IL-4...

Anastomotic stenosis of the descending colon caused by barium granuloma formation following barium peritonitis: report of a case.

Science.gov (United States)

Kitajima, Toshihiro; Tomizawa, Kenji; Hanaoka, Yutaka; Toda, Shigeo; Matoba, Shuichiro; Kuroyanagi, Hiroya; Oota, Yasunori

2014-11-01

Anastomotic stricture reportedly often recurs following barium peritonitis, regardless of whether the anastomotic diameter is initially sufficient. However, the causes of repetitive stricture have not been clarified. We report a case that suggests the pathophysiology of recurrent anastomotic strictures following barium peritonitis. The patient was a 39-year-old Japanese man with idiopathic perforation of the descending colon after undergoing an upper gastrointestinal barium contrast study. After emergency peritoneal lavage and diverting colostomy, created using the perforated region, the patient recovered uneventfully and 3 months later, the colostomy was closed and the perforated colon was resected. However, 7 months after colostomy closure, abdominal distention gradually developed, and colonoscopy revealed an anastomotic stricture. The patient was referred to our hospital where he underwent resection of the anastomotic stricture. The surgical specimen exhibited barium granulomas not only in the subserosa of the entire specimen, but also in the submucosa and lamina propria localized in the anastomotic site. These findings suggest that barium was embedded in the submucosa and lamina propria with manipulation of the stapled anastomosis and that the barium trapped in the anastomotic site caused persistent inflammation, resulting in an anastomotic stricture.

Evaluation of the shedding of Sarcocystis falcatula sporocysts in experimentally infected Virginia opossums (Didelphis virginiana).

Science.gov (United States)

Porter, R A; Ginn, P E; Dame, J B; Greiner, E C

2001-02-26

Five Virginia opossums (Didelphis virginiana) were fed muscles of brown-headed cowbirds (Molothrus ater) containing sarcocysts of Sarcocystis falcatula. Shedding of sporocysts was confirmed in all five opossums by fecal flotation. Counts were conducted daily for 2 weeks and then biweekly until the animals were euthanized and necropsied. The average prepatent period was 9.8 (7-16) days. The number of sporocysts shed varied greatly between the opossums with maximum mean shedding occurring at 71.6 (26-112) days post-infection (DPI). Average sporocyst production was 1480 sporocysts/gram of feces (SPG). Maximum output was 37,000 SPG. Average fecal yield in captivity was 17.5g of feces/day. Opossums shed 25,900 sporocysts/day (average) and a maximum of 647,500 sporocysts/day. All opossums shed sporocysts until time of euthanasia (46-200 DPI). Histologically, numerous sporocysts were present in the lamina propria at necropsy, primarily in the proximal half of the small intestine. Sporocysts were generally in clusters within the lamina propria of the luminal two-thirds of the villi. Sporocysts were found less frequently in the epithelium. No evidence of ongoing gametogony or other development was evident.

NLRP3 Controls the Development of Gastrointestinal CD11b+ Dendritic Cells in the Steady State and during Chronic Bacterial Infection

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Isabelle C. Arnold

2017-12-01

Full Text Available The gastric lamina propria is largely uncharted immunological territory. Here we describe the evolution and composition of the gastric, small intestinal, and colonic lamina propria mononuclear phagocyte system during the steady state and infection with the gastric pathogen Helicobacter pylori. We show that monocytes, CX3CR1hi macrophages, and CD11b+ dendritic cells are recruited to the infected stomach in a CCR2-dependent manner. All three populations, but not BATF3-dependent CD103+ DCs, sample red fluorescent protein (RFP+ Helicobacter pylori (H. pylori. Mice reconstituted with human hematopoietic stem cells recapitulate several features of the myeloid cell-H. pylori interaction. The differentiation in and/or recruitment to gastrointestinal, lung, and lymphoid tissues of CD11b+ DCs requires NLRP3, but not apoptosis-associated speck-like protein containing a carboxy-terminal CARD (ASC or caspase-1, during steady-state and chronic infection. NLRP3−/− mice fail to generate Treg responses to H. pylori and control the infection more effectively than wild-type mice. The results demonstrate a non-canonical inflammasome-independent function of NLRP3 in DC development and immune regulation.

Anterior lamina cribrosa surface position in idiopathic intracranial hypertension and glaucoma

DEFF Research Database (Denmark)

Villarruel, Jenni Martinez; Li, Xiao Q.; Bach-Holm, Daniella

2017-01-01

Purpose: To compare the anterior lamina cribrosa (LC) surface position in patients with idiopathic intracranial hypertension (IIH), primary open-angle glaucoma (high-tension glaucoma [HTG] and normal-tension glaucoma [NTG]), and healthy controls using enhanced depth imaging spectral-domain optical...

Pernicious anaemia and mucosal endocrine cell proliferation of the non-antral stomach.

OpenAIRE

Rode, J; Dhillon, A P; Papadaki, L; Stockbrügger, R; Thompson, R J; Moss, E; Cotton, P B

1986-01-01

There is a recognised association between pernicious anaemia and the development of gastric carcinoma, endocrine cell hyperplasia, and carcinoid tumour. Multiple endoscopic biopsies from the body mucosa of seven patients with pernicious anaemia showed small intestinal metaplasia with varying degrees of inflammation, fibrosis, and expansion of the lamina propria. Using conventional silver and lead stains, endocrine cells were inconspicuous. Staining for the general neural and neuroendocrine ma...

Microbial Communities and Their Predicted Metabolic Functions in Growth Laminae of a Unique Large Conical Mat from Lake Untersee, East Antarctica

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Hyunmin Koo

2017-08-01

Full Text Available In this study, we report the distribution of microbial taxa and their predicted metabolic functions observed in the top (U1, middle (U2, and inner (U3 decadal growth laminae of a unique large conical microbial mat from perennially ice-covered Lake Untersee of East Antarctica, using NextGen sequencing of the 16S rRNA gene and bioinformatics tools. The results showed that the U1 lamina was dominated by cyanobacteria, specifically Phormidium sp., Leptolyngbya sp., and Pseudanabaena sp. The U2 and U3 laminae had high abundances of Actinobacteria, Verrucomicrobia, Proteobacteria, and Bacteroidetes. Closely related taxa within each abundant bacterial taxon found in each lamina were further differentiated at the highest taxonomic resolution using the oligotyping method. PICRUSt analysis, which determines predicted KEGG functional categories from the gene contents and abundances among microbial communities, revealed a high number of sequences belonging to carbon fixation, energy metabolism, cyanophycin, chlorophyll, and photosynthesis proteins in the U1 lamina. The functional predictions of the microbial communities in U2 and U3 represented signal transduction, membrane transport, zinc transport and amino acid-, carbohydrate-, and arsenic- metabolisms. The Nearest Sequenced Taxon Index (NSTI values processed through PICRUSt were 0.10, 0.13, and 0.11 for U1, U2, and U3 laminae, respectively. These values indicated a close correspondence with the reference microbial genome database, implying high confidence in the predicted metabolic functions of the microbial communities in each lamina. The distribution of microbial taxa observed in each lamina and their predicted metabolic functions provides additional insight into the complex microbial ecosystem at Lake Untersee, and lays the foundation for studies that will enhance our understanding of the mechanisms responsible for the formation of these unique mat structures and their evolutionary significance.

Effects of the oral administration of the products derived from milk fermentation by kefir microflora on immune stimulation.

Science.gov (United States)

Vinderola, Gabriel; Perdigón, Gabriela; Duarte, Jairo; Farnworth, Edward; Matar, Chantal

2006-11-01

Nutritional status has a major impact on the immune system. Probiotic effects ascribed to fermented dairy products arise not only from whole microorganisms but also from metabolites (peptides, exopolysaccharides) produced during the fermentation. We recently demonstrated the immunomodulating capacity of kefir in a murine model. We now aimed at studying the immunomodulating capacity in vivo of the products derived from milk fermentation by kefir microflora (PMFKM) on the gut. BALB/c mice received the PMFKM for 2, 5 or 7 consecutive days. IgA+ and IgG+ cells were determined on histological slices of the small and large intestine. IL-4, IL-6, IL-10, IL-12, IFNgamma and TNFalpha were determined in the gut, intestinal fluid and blood serum. IL-6 was also determined in the supernatant of a primary culture of small intestine epithelial cells challenged with PMFKM. PMFKM up-regulated IL-6 secretion, necessary for B-cell terminal differentiation to IgA secreting cells in the gut lamina propria. There was an increase in the number of IgA+ cells in the small and large intestine. The increase in the number of IgA+ cells was accompanied by an increase in the number of IL-4+, IL-10+ and IL-6+ cells in the small intestine. Effects of PMFKM in the large intestine were less widely apparent than the ones observed at the small intestine lamina propria. All cytokines that increased in the small intestine lamina propria, also did so in blood serum, reflecting here the immunostimulation achieved in the gut mucosa. We observed that the PMFKM induced a mucosal response and it was able to up and down regulate it for protective immunity, maintaining the intestinal homeostasis, enhancing the IgA production at both the small and large intestine level. The opportunity exists then to manipulate the constituents of the lumen of the intestine through dietary means, thereby enhancing the health status of the host.

Direct and indirect pathways to lamina I in the medulla oblongata and spinal cord of the cat

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Holstege, Gert

1988-01-01

The pathways to lamina I in the medulla oblongata and spinal cord of the cat were traced using horse-radish-peroxidase (HRP) and autoradiographic techniques. The HRP results indicated that several neuronal cell groups in the brain stem and hypothalamus project to the spinal cord throughout its total length. The autoradiographic tracing results demonstrated that the strongest projections to lamina I are derived from the following four areas: the caudal nucleus raphe magnus (NRM), the ventral part of the caudal pontine and NRM, the contralaterally projecting lateral pontine or paralemniscal tegmentum, and the paraventricular nucleus of the hypothalamus. In addition, a limited, especially at lumbosacral levels, distinct projection to lamina I was found to originate in the most caudal part of the medullary tegmentum.

Effect of Lamina Thickness of Prepreg on the Surface Accuracy of Carbon Fiber Composite Space Mirrors

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Yang, Zhiyong; Tang, Zhanwen; Xie, Yongjie; Shi, Hanqiao; Zhang, Boming; Guo, Hongjun

2018-02-01

Composite space mirror can completely replicate the high-precision surface of mould by replication process, but the actual surface accuracy of the replication composite mirror always decreases. Lamina thickness of prepreg affects the layers and layup sequence of composite space mirror, and which would affect surface accuracy of space mirror. In our research, two groups of contrasting cases through finite element analyses (FEA) and comparative experiments were studied; the effect of different lamina thicknesses of prepreg and corresponding lay-up sequences was focused as well. We describe a special analysis model, validated process and result analysis. The simulated and measured surface figures both get the same conclusion. Reducing lamina thickness of prepreg used in replicating composite space mirror is propitious to optimal design of layup sequence for fabricating composite mirror, and could improve its surface accuracy.

Anterior lamina cribrosa insertion in primary open-angle glaucoma patients and healthy subjects.

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Kyoung Min Lee

Full Text Available To determine using swept-source optical coherence tomography (SS-OCT whether there are differences in the location of the anterior lamina cribrosa insertion (ALI in primary open-angle glaucoma (POAG patients and healthy subjects.Fifty three eyes from 53 patients with POAG, and 53 eyes from 53 age-matched healthy subjects were included prospectively in Seoul National University Bundang Hospital. Twelve radial line B-scans centered on the optic disc in every half-clock-hour meridian were acquired using SS-OCT. The ALI position was assessed by measuring two parameters: (1 ALI distance (ALID--the distance from the anterior scleral canal opening (ASCO to the ALI; and (2 marginal anterior lamina cribrosa surface depth (mALCSD--the perpendicular distance from the ASCO plane to the anterior lamina cribrosa surface. These parameters were compared between the two groups for each meridian.Both ALID (256 ± 54 vs. 209 ± 37 µm, mean ± SD, p < 0.001 and mALCSD (232 ± 63 vs. 187 ± 40 µm, p < 0.001 were significantly greater in the POAG group than in the normal group. The largest difference was observed at the 6.5 o'clock and 11.5 o'clock meridians for both ALID and mALCSD. Multiple regression analysis revealed a negative correlation between age and both ALID and mALCSD in the control group, and a negative correlation between mean deviation of the visual field test and both ALID and mALCSD in the POAG group.The ALI was displaced posteriorly in eyes with POAG compared to those of healthy controls. This finding suggests that the posteriorly located lamina cribrosa insertion is an important component of glaucomatous optic nerve excavation.

Traffic of antibody-secreting cells after immunization with a liposome-associated, CpG-ODN-adjuvanted oral cholera vaccine.

Science.gov (United States)

Somroop, Srinuan; Tongtawe, Pongsri; Chaisri, Urai; Tapchaisri, Pramuan; Chongsa-nguan, Manas; Srimanote, Potjanee; Chaicumpa, Wanpen

2006-12-01

An oral cholera vaccine made up of heat-treated recombinant cholera toxin (rCT), V. cholerae lipopolysaccharide (LPS), and recombinant toxin-co-regulated pili subunit A (rTcpA), entrapped in liposomes in the presence of unmethylated bacterial CpG-DNA (ODN#1826) was used to orally immunize a group of eight week old rats. A booster dose was given 14 days later. Control rats received placebo (vaccine diluent). The kinetics of the immune response were investigated by enumerating the antigen specific-antibody secreting cells (ASC) in the blood circulation and intestinal lamina propria using the ELISPOT assay and a histo-immunofluorescence assay (IFA), respectively. ASC of all antigenic specificities were detected in the blood of the vaccinated rats as early as two days after the booster dose. The numbers of LPS-ASC and TcpA-ASC in the blood were at their peak at day 3 post booster while the number of CT-ASC was highest at day 4 after the booster immunization. At day 13 post immunization, no ASC were detected in the blood. A several fold increase in the number of ASC of all antigenic specificities in the lamina propria above the background numbers of the control animals were found in all vaccinated rats at days 6 and 13 post booster (earlier and later time points were not studied). Vibriocidal antibody and specific antibodies to CT, LPS and TcpA were detected in 57.1% and 52.4%, 14.3%, and 19.0% of the orally vaccinated rats, respectively. The data indicated that rats orally primed with the vaccine could produce a rapid anamnestic response after re-exposure to the V. cholerae antigens. Thus, a single dose of the vaccine is expected to elicit a similar anamnestic immune response in people from cholera endemic areas who have been naturally primed to V. cholerae antigens, while two doses at a 14 day interval should be adequate for a traveler to a disease endemicarea.

Chemo preventive action of Liv.52 against radiation and cadmium induced histopathological changes in the jejunum of Swiss albino mice

International Nuclear Information System (INIS)

Purohit, R.K.; Sunita; Bhati, Sharwan; Isran, Rakesh; Ranga, Deepti; Meena, Dinesh; Pyarelal

2012-01-01

The present century has been an ever-increasing use of nuclear technologies in different fields raising the alarming problem of radiation hazards to living beings including man. An increasing body of evidence indicates that human activities are responsible for global climatic changes, which, in turn, may be directly or indirectly increasing human exposure to environmental hazards. On the other hand, all forms of cadmium are poisonous leading cadmium intoxication under appropriate circumstances. The interaction between radiation and other toxicants represents a field of immense potential importance as their total environmental burden may have greater effects than expected from the sum of their individual impact. In the present study six to eight weeks old male Swiss albino mice were exposed to 2.5 and 5.0 Gy of gamma rays with or without cadmium chloride treatment. The animals of experimental groups were administered Liv.52 for seven days prior to radiation or cadmium chloride treatment. After routine procedure of histology the histopathological changes were observed in the jejunum of Swiss albino mice. The changes included loosened sub-mucosa with hydropic degeneration. Lamina propria exhibited hydropic degeneration, abnormal mitotic figures, pyknotic nuclei and cytoplasmic degranulation in crypt cells, loosened tips and shortened villi. Leucocytic infiltration appeared in lamina propria. Few mitotic figures were observed during the early intervals but were not normal and resulted in mitotic death. Recovery started on day-14 in non-drug treated groups and day-7 in Liv.52 treated groups. After irradiation with various doses of gamma rays, histological changes depend upon the dose of radiation delivered. The important radio-lesions were looseness of musculature, hydropic degeneration in sub-mucosa and lamina propria, hyperaemia and haemorrhage in sub-mucosa, pyknotic cells, cytoplasmic degranulation and vacuolation, abnormal mitotic figures. Karyolysis, karyorrhexis

A Corner-Point-Grid-Based Voxelization Method for Complex Geological Structure Model with Folds

Science.gov (United States)

Chen, Qiyu; Mariethoz, Gregoire; Liu, Gang

2017-04-01

3D voxelization is the foundation of geological property modeling, and is also an effective approach to realize the 3D visualization of the heterogeneous attributes in geological structures. The corner-point grid is a representative data model among all voxel models, and is a structured grid type that is widely applied at present. When carrying out subdivision for complex geological structure model with folds, we should fully consider its structural morphology and bedding features to make the generated voxels keep its original morphology. And on the basis of which, they can depict the detailed bedding features and the spatial heterogeneity of the internal attributes. In order to solve the shortage of the existing technologies, this work puts forward a corner-point-grid-based voxelization method for complex geological structure model with folds. We have realized the fast conversion from the 3D geological structure model to the fine voxel model according to the rule of isocline in Ramsay's fold classification. In addition, the voxel model conforms to the spatial features of folds, pinch-out and other complex geological structures, and the voxels of the laminas inside a fold accords with the result of geological sedimentation and tectonic movement. This will provide a carrier and model foundation for the subsequent attribute assignment as well as the quantitative analysis and evaluation based on the spatial voxels. Ultimately, we use examples and the contrastive analysis between the examples and the Ramsay's description of isoclines to discuss the effectiveness and advantages of the method proposed in this work when dealing with the voxelization of 3D geologic structural model with folds based on corner-point grids.

Fine structure of subepithelial "free" and corpuscular trigeminal nerve endings in anterior hard palate of the rat.

Science.gov (United States)

Byers, M R; Yeh, Y

1984-01-01

Axonally transported protein labeled many trigeminal nerve endings in subepithelial regions of the anterior hard palate of the rat. Sensory endings were most numerous in the lamina propria near the tips of the palatal rugae where large connective tissue and epithelial papillae interdigitated. Two kinds of sensory ending were found there: "free" endings, and a variety of corpuscular endings. The "free" sensory endings consisted of bundles of unmyelinated axons separated from the connective tissue by relatively unspecialized Schwann cells covering part or all of their surface and a completely continuous basal lamina; they were commonly found running parallel to the epithelium or near corpuscular endings. The corpuscular sensory endings all had a specialized nerve form, specialized Schwann cells, and axonal fingers projecting into the corpuscular basal lamina or connective tissue. There were at least four distinct types of corpuscular ending: Ruffini-like endings were found among dense collagen bundles, and they had a flattened nerve ending with a flattened Schwann lamella on either side. Meissner endings had an ordered stack of flattened nerve terminals with flattened Schwann cells and much basal lamina within and around the corpuscle. Simple corpuscles were single nerve endings surrounded by several layers of concentric lamellar Schwann processes. Glomerular endings were found in lamina propria papillae or encircling epithelial papillae; they were a tangle of varied neural forms each of which had apposed flattened Schwann cells, and a layer of basal lamina of varied thickness. Fibroblasts often formed incomplete partitions around Meissner and simple corpuscles. The axoplasm of all kinds of subepithelial sensory endings contained numerous mitochondria and vesicles, as well as occasional multivesicular bodies and lysosomes; the axoplasm of all endings was pale with few microtubules and neurofilaments. The specialized lamellar Schwann cells had much pinocytotic

Disruption of basal lamina components in neuromotor synapses of children with spastic quadriplegic cerebral palsy.

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Karyn G Robinson

Full Text Available Cerebral palsy (CP is a static encephalopathy occurring when a lesion to the developing brain results in disordered movement and posture. Patients present with sometimes overlapping spastic, athetoid/dyskinetic, and ataxic symptoms. Spastic CP, which is characterized by stiff muscles, weakness, and poor motor control, accounts for ∼80% of cases. The detailed mechanisms leading to disordered movement in spastic CP are not completely understood, but clinical experience and recent studies suggest involvement of peripheral motor synapses. For example, it is recognized that CP patients have altered sensitivities to drugs that target neuromuscular junctions (NMJs, and protein localization studies suggest that NMJ microanatomy is disrupted in CP. Since CP originates during maturation, we hypothesized that NMJ disruption in spastic CP is associated with retention of an immature neuromotor phenotype later in life. Scoliosis patients with spastic CP or idiopathic disease were enrolled in a prospective, partially-blinded study to evaluate NMJ organization and neuromotor maturation. The localization of synaptic acetylcholine esterase (AChE relative to postsynaptic acetylcholine receptor (AChR, synaptic laminin β2, and presynaptic vesicle protein 2 (SV2 appeared mismatched in the CP samples; whereas, no significant disruption was found between AChR and SV2. These data suggest that pre- and postsynaptic NMJ components in CP children were appropriately distributed even though AChE and laminin β2 within the synaptic basal lamina appeared disrupted. Follow up electron microscopy indicated that NMJs from CP patients appeared generally mature and similar to controls with some differences present, including deeper postsynaptic folds and reduced presynaptic mitochondria. Analysis of maturational markers, including myosin, syntrophin, myogenin, and AChR subunit expression, and telomere lengths, all indicated similar levels of motor maturation in the two groups

Terminal-Nerve-Derived Neuropeptide Y Modulates Physiological Responses in the Olfactory Epithelium of Hungry Axolotls (Ambystoma mexicanum)

OpenAIRE

Mousley, Angela; Polese, Gianluca; Marks, Nikki J.; Eisthen, Heather L.

2006-01-01

The vertebrate brain actively regulates incoming sensory information, effectively filtering input and focusing attention toward environmental stimuli that are most relevant to the animal's behavioral context or physiological state. Such centrifugal modulation has been shown to play an important role in processing in the retina and cochlea, but has received relatively little attention in olfaction. The terminal nerve, a cranial nerve that extends underneath the lamina propria surrounding the o...

Transmission Electron Microscopy of the Gastrointestinal Tract of Nile Perch Lates niloticus

OpenAIRE

Namulawa, V. T; Kato, C. D; Nyatia, E; Rutaisire, J; Britz, P. J

2015-01-01

The ultrastructure of the gastrointestinal tract of Nile perch was described using Transmission Electron Microscopy standard procedures. Investigations revealed the presence of mucous cells, blood vessels and oil droplets plus several nerve cells and muscle bundles in the oral cavity. Further observations revealed columnar epithelial cells in the oesophagus, with a ragged surface, high electron dense cytoplasm, intercellular spaces, mitochondria and mucus granules. The lamina propria of the o...

Evaluation of the rostral projection of the sacral lamina as a component of degenerative lumbosacral stenosis in German shepherd dogs.

Science.gov (United States)

Saunders, Harvey; Worth, Andrew J; Bridges, Janis P; Hartman, Angela

2018-05-20

To determine the association between a greater rostral projection of the sacral lamina and clinical signs of cauda equina syndrome (CES) in German shepherd dogs (GSD) with presumptive degenerative lumbosacral disease (DLSS). Retrospective cohort study. One hundred forty-three GSD (125 police dogs and 18 pet dogs) presenting for either CES or prebreeding evaluation. Fifty-five were classified as affected by CES and diagnosed with DLSS, and 88 were classified as unaffected on the basis of clinical and imaging findings. The position of the rostral edge of the sacral lamina was measured from radiographs and/or computed tomography (CT) scans. This position was compared between affected and unaffected dogs. In dogs that underwent both radiography and CT scanning, the agreement between sacral lamina localization using each imaging modality was determined. Owners/handlers were contacted to determine whether dogs subsequently developed clinical signs compatible with CES at a mean of 29 months (unaffected). The sacral lamina did not extend as far rostrally in affected dogs, compared to unaffected dogs (P = .04). Among the 88 dogs unaffected by CES at initial evaluation, 2 developed clinical signs consistent with CES at follow-up. Rostral projection of the sacral lamina, previously proposed as a potential risk factor in dogs with CES due to lumbosacral degeneration, was not associated with a diagnosis of DLSS in this study; the opposite was true. Rostral projection of the sacral lamina may not be a predisposing factor in the development of CES due to DLSS in GSD. © 2018 The American College of Veterinary Surgeons.

Single‑shot lamina technique of paravertebral block as an adjunct to ...

African Journals Online (AJOL)

Thoracic paravertebral block can be employed as an alternative or an adjunct to general anesthesia (GA) for breast cancer surgery. There is no report of this new lamina technique for catheter placement in our environment. In low‑resource settings, potent opioids are lacking and the extended postoperative analgesia it ...

Relative Composition of Fibrous Connective and Fatty/Glandular Tissue in Connective Tissue Grafts Depends on the Harvesting Technique but not the Donor Site of the Hard Palate.

Science.gov (United States)

Bertl, Kristina; Pifl, Markus; Hirtler, Lena; Rendl, Barbara; Nürnberger, Sylvia; Stavropoulos, Andreas; Ulm, Christian

2015-12-01

Whether the composition of palatal connective tissue grafts (CTGs) varies depending on donor site or harvesting technique in terms of relative amounts of fibrous connective tissue (CT) and fatty/glandular tissue (FGT) is currently unknown and is histologically assessed in the present study. In 10 fresh human cadavers, tissue samples were harvested in the anterior and posterior palate and in areas close to (marginal) and distant from (apical) the mucosal margin. Mucosal thickness, lamina propria thickness (defined as the extent of subepithelial portion of the biopsy containing ≤25% or ≤50% FGT), and proportions of CT and FGT were semi-automatically estimated for the entire mucosa and for CTGs virtually harvested by split-flap (SF) preparation minimum 1 mm deep or after deepithelialization (DE). Palatal mucosal thickness, ranging from 2.35 to 6.89 mm, and histologic composition showed high interindividual variability. Lamina propria thickness (P >0.21) and proportions of CT (P = 0.48) and FGT (P = 0.15) did not differ significantly among the donor sites (anterior, posterior, marginal, apical). However, thicker palatal tissue was associated with higher FGT content (P tissue composition in the hard palate, DE-harvested CTG contains much larger amounts of CT and much lower amounts of FGT than SF-harvested CTG, irrespective of the harvesting site.

Genetic analysis of Enterobius vermicularis isolated from a chimpanzee with lethal hemorrhagic colitis and pathology of the associated lesions.

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Yaguchi, Yuji; Okabayashi, Sachi; Abe, Niichiro; Masatou, Haruhisa; Iida, Shinya; Teramoto, Isao; Matsubayashi, Makoto; Shibahara, Tomoyuki

2014-11-01

Human pinworms, Enterobius vermicularis, are normally recognized as minor pathogens. However, a fatal case of human pinworm infection has been reported in a nonhuman primate, a zoo reared chimpanzee. Here, we histopathologically examined the lesions in tissues from the deceased chimpanzee and genetically characterized the isolated worms to investigate the pathogenicity and determine the phylogeny. We identified ulcers deep in the submucosa where many parasites were found to have invaded the lamina propria mucosa or submucous tissue. An inflammatory reaction consisting mainly of neutrophils and lymphocytes but not eosinophils was observed around the parasites, and intense hemorrhage in the lamina propria was confirmed. The parasites were morphologically similar to E. vermicularis based on the shape of the copulatory spicules. Mitochondrial cytochrome c oxidase subunit 1 gene products were amplified from worm DNA by PCR and were genetically identified as E. vermicularis based on >98.7% similarity of partial sequences. Phylogenetic analysis revealed that the sequences clustered together with other chimpanzee E. vermicularis isolates in a group which has been referred to as type C and which differs from human isolates (type A). The samples were negative for bacterial pathogens and Entamoeba histolytica indicating that E. vermicularis could be pathogenic in chimpanzees. Phylogenetic clustering of the isolates indicated that the parasite may be host specific.

[The role of gut microbiota in the regulation of the immune response].

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Alarcón, Pedro; González, Margarita; Castro, Érica

2016-07-01

The gastrointestinal tract hosts around 10(14) bacterial microorganisms, in a constantly growing density from the stomach to the distal colon. This microbiota is composed by more than 500 species of bacteria, which are quickly acquired after birth, fairly stable during the host’s life, and essential for human homeostasis. These bacteria have important functions, such as stimulating the immune system, protecting the host from invading bacteria and viruses, and improving digestion, especially of complex carbohydrates. Also, the gut microbiota interacts directly with the immune system. However, the interaction of the intestinal epithelium and its microbiota with the immune system has yet to be fully understood. Secretory immunoglobulin A, produced by the plasma cells in Peyer’s patches and in the lamina propria, maintains non-invasive commensal bacteria and neutralize invasive pathogens. Dendritic cells migrate from the lamina propria of the secondary lymphoid organs to regulate gut immunity. They also have a key role maintaining luminal IgA and inducing the growth of regulatory T cells. Dendritic cells supervise the gut microenvironment too, keeping an immunological equilibrium and tolerance. The importance of the gut microbiota in regulating the immune system lies mostly in the homeostasis-or positive equilibrium. Thus, many diseases are a consequence of poor interactions or a loss of this equilibrium.

Phosphorylation of ERK in neurokinin 1 receptor-expressing neurons in laminae III and IV of the rat spinal dorsal horn following noxious stimulation

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Watanabe Masahiko

2007-02-01

Full Text Available Abstract Background There is a population of large neurons with cell bodies in laminae III and IV of the spinal dorsal horn which express the neurokinin 1 receptor (NK1r and have dendrites that enter the superficial laminae. Although it has been shown that these are all projection neurons and that they are innervated by substance P-containing (nociceptive primary afferents, we know little about their responses to noxious stimuli. In this study we have looked for phosphorylation of extracellular signal-regulated kinases (ERKs in these neurons in response to different types of noxious stimulus applied to one hindlimb of anaesthetised rats. The stimuli were mechanical (repeated pinching, thermal (immersion in water at 52°C or chemical (injection of 2% formaldehyde. Results Five minutes after each type of stimulus we observed numerous cells with phosphorylated ERK (pERK in laminae I and IIo, together with scattered positive cells in deeper laminae. We found that virtually all of the lamina III/IV NK1r-immunoreactive neurons contained pERK after each of these stimuli and that in the great majority of cases there was internalisation of the NK1r on the dorsal dendrites of these cells. In addition, we also saw neurons in lamina III that were pERK-positive but lacked the NK1r, and these were particularly evident in animals that had had the pinch stimulus. Conclusion Our results demonstrate that lamina III/IV NK1r-immunoreactive neurons show receptor internalisation and ERK phosphorylation after mechanical, thermal or chemical noxious stimuli.

Identification of sodium channel isoforms that mediate action potential firing in lamina I/II spinal cord neurons

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Smith Paula L

2011-09-01

Full Text Available Abstract Background Voltage-gated sodium channels play key roles in acute and chronic pain processing. The molecular, biophysical, and pharmacological properties of sodium channel currents have been extensively studied for peripheral nociceptors while the properties of sodium channel currents in dorsal horn spinal cord neurons remain incompletely understood. Thus far, investigations into the roles of sodium channel function in nociceptive signaling have primarily focused on recombinant channels or peripheral nociceptors. Here, we utilize recordings from lamina I/II neurons withdrawn from the surface of spinal cord slices to systematically determine the functional properties of sodium channels expressed within the superficial dorsal horn. Results Sodium channel currents within lamina I/II neurons exhibited relatively hyperpolarized voltage-dependent properties and fast kinetics of both inactivation and recovery from inactivation, enabling small changes in neuronal membrane potentials to have large effects on intrinsic excitability. By combining biophysical and pharmacological channel properties with quantitative real-time PCR results, we demonstrate that functional sodium channel currents within lamina I/II neurons are predominantly composed of the NaV1.2 and NaV1.3 isoforms. Conclusions Overall, lamina I/II neurons express a unique combination of functional sodium channels that are highly divergent from the sodium channel isoforms found within peripheral nociceptors, creating potentially complementary or distinct ion channel targets for future pain therapeutics.

Stochastic and cyclic deposition of multiple subannual laminae in an urban lake (Twin Lake, Golden Valley, Minnesota, USA)

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Myrbo, A.; Ustipak, K.; Demet, B.

2013-12-01

Twin Lake, a small, deep, meromictic urban lake in Minneapolis, Minnesota, annually deposits two to 10 laminae that are distinguished from one another by composition and resulting color. Sediment sources are both autochthonous and allochthonous, including pure and mixed laminae of authigenic calcite, algal organic matter, and diatoms, as well as at least three distinct types of sediment gravity flow deposits. Diagenetic iron sulfide and iron phosphate phases are minor components, but can affect color out of proportion to their abundance. We used L*a*b* color from digital images of a freeze core slab, and petrographic smear slides of individual laminae, to categorize 1080 laminae deposited between 1963 and 2010 CE (based on lead-210 dating). Some causal relationships exist between the ten categories identified: diatom blooms often occur directly above the debris of gravity flows that probably disrupt the phosphate-rich monimolomnion and fertilize the surface waters; calcite whitings only occur after diatom blooms that increase calcite saturation. Stochastic events, as represented by laminae rich in siliciclastics and other terrigenous material, or shallow-water microfossils and carbonate morphologies, are the dominant sediment source. The patterns of cyclic deposition (e.g., summer and winter sedimentation) that produce 'normal' varve couplets in some lakes are continually interrupted by these stochastic events, to such an extent that spectral analysis finds only a weak one-year cycle. Sediments deposited before about 1900, and extending through the entire Holocene sequence (~10m) are varve couplets interrupted by thick (20-90 cm) debris layers, indicating that gravity flows were lower in frequency but greater in magnitude before the historical period, probably due to an increased frequency of disturbance under urban land-use.

Detecção de receptor de ácido hialurônico em prega vocal humana por método imunohistoquímico Detection of hyaluronic acid receptor in human vocal folds by immunohistochemistry

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Luiz Henrique Fonseca Barbosa

2008-04-01

deep layers of the lamina propria. In the silanized slides we used immunohistochemistry, and evaluated the slides under light microscopy with 40x magnification, and the color changed to brown when there was a reaction with the receptor for hyaluronic acid. RESULTS: Immunohistochemical findings showed the presence of hyaluronic acid receptors in the epithelium covering the vocal fold, being more concentrated in the central region of the vocal fold. CONCLUSION: immunohistochemistry, used to assess the distribution of hyaluronic acid receptors in the central portion of the vocal fold, proved it to be present in the vocal fold epithelium and it prevailed in its middle third.

Plasma cell granuloma of lip

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B Sabarinath

2012-01-01

Full Text Available Plasma cells are medium-sized round-to-oval cells with eccentrically placed nuclei, usually found in the red pulp of the spleen, tonsils, medulla of the lymph nodes, nasal mucosa, upper airway, lamina propria of the gastrointestinal tract, and sites of inflammation. Plasma cell granuloma is a rare reactive tumor-like proliferation composed chiefly of plasmacytic infiltrate. Here, we present a case of plasma cell granuloma of lip in a female patient.

Tufting enteropathy with EpCAM mutation: case report

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Pêgas,Karla Lais; Cambruzzi,Eduardo; Ferrelli,Regis Schander; Silva,Carolina Soares da; Guedes,Renata Rostirola; Adami,Marina; Dias,Eduardo Montagner; Melere,Melina Utz; Ceza,Marilia Rosso; Steinhaus,Cintia; Epifanio,Matias; Salomon,Julie; Ferreira,Cristina Targa

2014-01-01

Tufting enteropathy (TE), also known as intestinal epithelial dysplasia (IED), is a rare congenital enteropathy related to an earlyonset of severe intractable diarrhea due to specific abnormalities of the intestinal epithelium and mutations of the EpCAM gene. TE is characterized by clinical and histological heterogeneity, such as with low or without mononuclear cell infiltration of the lamina propria, and abnormalities of basement membrane. TE can be associated with malformations, other epith...

Non-muscle invasive bladder cancer risk stratification

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Sumit Isharwal

2015-01-01

Conclusion: EORTC and CUETO risk tables are the two best-established models to predict recurrence and progression in patients with NMIBC though they tend to overestimate risk and have poor discrimination for prognostic outcomes in external validation. Future research should focus on enhancing the predictive accuracy of risk assessment tools by incorporating additional prognostic factors such as depth of lamina propria invasion and molecular biomarkers after rigorous validation in multi-institutional cohorts.

The nervus terminalis in the chick: a FMRFamide-immunoreactive and AChE-positive nerve.

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Wirsig-Wiechmann, C R

1990-07-16

The chick terminal nerve (TN) was examined by immunocytochemical and histochemical methods. Molluscan cardioexcitatory peptide-immunoreactive (FMRFamide-ir) and acetylcholinesterase (AChE)-positive TN perikarya and fibers were distributed along olfactory and trigeminal nerves. FMRFamide-ir TN fibers terminated in the olfactory lamina propria and epithelium and in ganglia along the rostroventral nasal septum. This initial description of several populations of avian TN neurons should provide the foundation for future developmental studies of this system.

GPCR-Mediated Signaling of Metabolites

DEFF Research Database (Denmark)

Husted, Anna Sofie; Trauelsen, Mette; Rudenko, Olga

2017-01-01

microbiota target primarily enteroendocrine, neuronal, and immune cells in the lamina propria of the gut mucosa and the liver and, through these tissues, the rest of the body. In contrast, metabolites from the intermediary metabolism act mainly as metabolic stress-induced autocrine and paracrine signals...... and obesity. The concept of key metabolites as ligands for specific GPCRs has broadened our understanding of metabolic signaling significantly and provides a number of novel potential drug targets....

[Histochemical detection of glycoproteins and glycosaminoglycans in the respiratory mucosa of albino rats during estrous cycle, pregnancy and puerperium].

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Pontes, P A; Simões, M J; Merzel, J

1989-11-01

In this work we attempted to detect, with histochemical methods, the possible modifications in the mucus of the respiratory mucosa of albino female rats during estral cycle, pregnancy and puerperium. Based on its results, it was possible to conclude that: a--There were no modifications in the nature of the epithelial and supraepithelial mucus during the studied periods: b--The Alcian Blue staining from lamina propria is absent during pregnancy and present during puerperium.

Abnormality of the spinal column in pediatric patients with lumbosacral spinal lipoma with special reference to CT findings of the lamina defects

International Nuclear Information System (INIS)

Yoshifuji, Kazuhisa; Ochi, Satoko; Koyanagi, Izumi; Houkin, Kiyohiro

2009-01-01

Lumbosacral spinal lipomas are usually associated with occult spinal dysraphism at the lumbosacral spine. During childfood, posterior arch defects in the lumbosacral spine are considered normal computed tomography (CT) findings because of the presence of interlaminar synchondrosis. In this study, we investigated the CT findings of the lumbosacral spine in the pediatric patients with lumbosacral spinal lipomas. We aimed to characterize the radiological features of the abnormal spinal column in case of spinal lipomas. Twenty-one patients (age, 1 month to 3 years) were enrolled in this study: 11 patients had conus lipoma; 10 patients, filum lipoma. All patients showed lamina defects of the lumbosacral spine on 3D-CT. The number of the defective laminae was significantly larger in the patients with conus lipomas than in those with filum lipomas. Although the appearance of lamina defects in the patients with filum lipoma was similar to the reported findings of defective laminae in normal children, these patients were characterized by mild scoliosis and asymmetry of the posterior arches localized in the lower sacrum and coccyx. On the other hand, the patients with conus lipoma were characterized by wider lamina defects that extended rostrally, 'open-door like' deformity of lamina, vertebral dysgenesis, thoracolumber scoliosis and heterotopic ossification. Such CT characterization of the abnormality of the lumbosacral spine in lipoma patients will be useful to differentiate the pathological spina bifida from the normal open posterior arches in childhood. (author)

Effects of collagen microstructure and material properties on the deformation of the neural tissues of the lamina cribrosa.

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Voorhees, A P; Jan, N-J; Sigal, I A

2017-08-01

It is widely considered that intraocular pressure (IOP)-induced deformation within the neural tissue pores of the lamina cribrosa (LC) contributes to neurodegeneration and glaucoma. Our goal was to study how the LC microstructure and mechanical properties determine the mechanical insult to the neural tissues within the pores of the LC. Polarized light microscopy was used to measure the collagen density and orientation in histology sections of three sheep optic nerve heads (ONH) at both mesoscale (4.4μm) and microscale (0.73μm) resolutions. Mesoscale fiber-aware FE models were first used to calculate ONH deformations at an IOP of 30mmHg. The results were then used as boundary conditions for microscale models of LC regions. Models predicted large insult to the LC neural tissues, with 95th percentile 1st principal strains ranging from 7 to 12%. Pores near the scleral boundary suffered significantly higher stretch compared to pores in more central regions (10.0±1.4% vs. 7.2±0.4%; p=0.014; mean±SD). Variations in material properties altered the minimum, median, and maximum levels of neural tissue insult but largely did not alter the patterns of pore-to-pore variation, suggesting these patterns are determined by the underlying structure and geometry of the LC beams and pores. To the best of our knowledge, this is the first computational model that reproduces the highly heterogeneous neural tissue strain fields observed experimentally. The loss of visual function associated with glaucoma has been attributed to sustained mechanical insult to the neural tissues of the lamina cribrosa due to elevated intraocular pressure. Our study is the first computational model built from specimen-specific tissue microstructure to consider the mechanics of the neural tissues of the lamina separately from the connective tissue. We found that the deformation of the neural tissue was much larger than that predicted by any recent microstructure-aware models of the lamina. These results

Effects Aerosol of Industrial Bleach and Detergent Mixture on Mucosa Layer and Lamina Mucosa Conjunctiva in Mice

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Gh. Vaezi

2013-06-01

Full Text Available Today bleach and detergents are being frequently used and some people use their mixture for more cleaning. Because of chemical interaction of bleach and detergent, chlorine gas was released and thereby it could be dangerous for human health. This study examined the effects of exposed toxic mixture of bleach and detergent on the Mucosa layer and Lamina mucosa conjunctiva in the mice. In this study, 42 adult male mice NMRI race weighing 35-40 gr and from age 8 to 10 weeks were divided into 6 experimental groups and one control group. Experimental groups 1-2-3 with the use of chamber, the exposed 20 minutes were exposed to spray the amount 1 cc of mixture of bleach and detergent by nebulizer. Experimental groups 4-5-6 were for 35 minutes to inhale the same amount of material. Mice killed at 24-48-72 hours after exposed and the Mucosa Layer and Lamina mucosa conjunctiva tissue was studied pathology. In the study of microscopic sections prepared of mouse mucosa layer and Lamina mucosa conjunctiva tissue experimental group comparison with the control group, significant decrease was observed in mucosa layer the have (p ≤ 0.001  and significant decrease was observed in the Lamina mucosa have(p ≤ 0. 01,  p ≤ 0.001. As a result, increasing the exposed time of mixing bleach and detergent, as time passed, increasing the tissue damage and changes.

Evaluation of architectural and histopathological biomarkers in the intestine of brown trout (Salmo trutta Linnaeus, 1758) challenged with environmental pollution.

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Barišić, Josip; Filipović Marijić, Vlatka; Mijošek, Tatjana; Čož-Rakovac, Rozelindra; Dragun, Zrinka; Krasnići, Nesrete; Ivanković, Dušica; Kružlicová, Dáša; Erk, Marijana

2018-06-14

In the present study novel histopathological approach, using fish intestine as a sensitive bioindicator organ of pollution impact in the freshwater ecosystem, was proposed. Histopathological alterations were compared between native brown trout (Salmo trutta Linnaeus, 1758) from the reference (Krka River spring) and pollution impacted location (influence of technological/municipal wastewaters and agricultural runoff near the Town of Knin) of the karst Krka River in Croatia. In brown trout from both locations, severe parasitic infestation with acanthocephalan species Dentitruncus trutae was found, enabling evaluation of acanthocephalan infestation histopathology, which indicated parasite tissue reaction in a form of inflammatory, necrotic and hyperplastic response that extended throughout lamina epithelialis mucosae, lamina propria, and lamina muscularis mucosae. New semi-quantitative histological approach was proposed in order to foresee alterations classified in three reaction patterns: control tissue appearance, moderate (progressive) tissue impairment and severe (regressive and inflammatory) tissue damage. The most frequent progressive alteration was hyperplasia of epithelium on the reference site, whereas the most frequent regressive alterations were atrophy and necrosis seen on the polluted site. Furthermore, histopathological approach was combined with micromorphological and macromorphological assessment as an additional indicator of pollution impact. Among 15 observed intestinal measures, two biomarkers of intestinal tissue damage were indicated as significant, height of supranuclear space (hSN) and number of mucous cells over 100 μm fold distance of intestinal mucosa (nM), which measures were significantly lower in fish from polluted area compared to the reference site. Obtained results indicated that combined histological and morphological approach on fish intestinal tissue might be used as a valuable biological tool for assessing pollution impact on

Cloacal morphology of Nothura maculosa (Temminck, 1815), Aves tinamiformes.

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de Oliveira, C A; Mahecha, G A

1996-10-01

Cloacae of male Nothura maculosa (spotted tinamous) were dissected and studied with routine histological and histochemical techniques. In the cloaca of this species the following cranio-caudally oriented regions can be recognized: the coprodeum, the urodeum and the proctodeum, separated by the coprourodeal and the uroproctodeal folds respectively. The coprodeum is an abrupt dilatation of the rectum which receives the ureters, contrary to other birds in which they open into the urodeum. The urodeum is the smallest compartment of the cloaca. Its wall presents the paracloacal vascular bodies and the ductus deferens receptacles which open into the ejaculatory fossa through a pair of papillae. The ejaculatory fossa forms the ventral floor of the urodeum and is characterized by the presence of a secretory epithelium and a lamina propria showing rich vascularization. The proctodeum is connected to the exterior through the cloacal opening and ventrally it presents the phallic structures and the proctodeal lamella. Its dorsolateral wall forms the cloacal bursa, its mucosa shows morphological variations depending on the degree of regression. Enclosing the uroproctodeal wall are the cloacal sphincter muscle and the skin.

Changes in the interstitial cells of Cajal and neuronal nitric oxide synthase positive neuronal cells with aging in the esophagus of F344 rats.

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Hee Jin Kim

Full Text Available The aging-associated cellular and molecular changes in esophagus have not been established, yet. Thus we evaluated histological structure, interstitial cells of Cajal (ICCs, neuronal nitric oxide synthase (nNOS-positive cells, and contractility in the esophagus of Fischer 344 rat at different ages (6-, 31-, 74-weeks, and 2-years. The lamina propria thickness and endomysial area were calculated. The immunoreactivity of c-Kit, nNOS and protein gene product (PGP 9.5 was counted after immunohistochemistry. Expression of c-Kit, stem cell factor (SCF, nNOS and PGP 9.5 mRNA was measured by real-time PCR, and expression of c-Kit and nNOS protein was detected by Western blot. Isovolumetric contractile force measurement and electrical field stimulation (EFS were conducted. The lamina propria thickness increased (6 week vs 2 year, P = 0.005 and the endomysial area of longitudinal muscle decreased with aging (6 week vs 2 year, P<0.001, while endomysial area of circular muscle did not significantly decrease. The proportions of NOS-immunoreactive cells and c-Kit-immunoreactive areas declined with aging (6 week vs 2 year; P<0.001 and P = 0.004, respectively, but there was no significant change of PGP 9.5-immunopositiviy. The expressions of nNOS, c-Kit and SCF mRNA also reduced with aging (6 week vs 2 year; P = 0.006, P = 0.001 and P = 0.006, respectively, while the change of PGP 9.5 mRNA expression was not significant. Western blot showed the significant decreases of nNOS and c-Kit protein expression with aging (6 week vs 2 year; P = 0.008 and P = 0.012, respectively. The EFS-induced esophageal contractions significantly decreased in 2-yr-old rat compared with 6-wk-old rats, however, L-NG-Nitroarginine methylester did not significantly increase the spontaneous and EFS-induced contractions in the 6-wk- and 2-yr-old rat esophagus. In conclusion, an increase of lamina propria thickness, a decrease of endomysial area, c-Kit, SCF and NOS expression with preserved

Ageing combines CD4 T cell lymphopenia in secondary lymphoid organs and T cell accumulation in gut associated lymphoid tissue.

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Martinet, Kim Zita; Bloquet, Stéphane; Bourgeois, Christine

2014-01-01

CD4 T cell lymphopenia is an important T cell defect associated to ageing. Higher susceptibility to infections, cancer, or autoimmune pathologies described in aged individuals is thought to partly rely on T cell lymphopenia. We hypothesize that such diverse effects may reflect anatomical heterogeneity of age related T cell lymphopenia. Indeed, no data are currently available on the impact of ageing on T cell pool recovered from gut associated lymphoid tissue (GALT), a crucial site of CD4 T cell accumulation. Primary, secondary and tertiary lymphoid organs of C57BL/6 animals were analysed at three intervals of ages: 2 to 6 months (young), 10 to 14 months (middle-aged) and 22 to 26 months (old). We confirmed that ageing preferentially impacted CD4 T cell compartment in secondary lymphoid organs. Importantly, a different picture emerged from gut associated mucosal sites: during ageing, CD4 T cell accumulation was progressively developing in colon and small intestine lamina propria and Peyer's patches. Similar trend was also observed in middle-aged SJL/B6 F1 mice. Interestingly, an inverse correlation was detected between CD4 T cell numbers in secondary lymphoid organs and colonic lamina propria of C57BL/6 mice whereas no increase in proliferation rate of GALT CD4 T cells was detected. In contrast to GALT, no CD4 T cell accumulation was detected in lungs and liver in middle-aged animals. Finally, the concomitant accumulation of CD4 T cell in GALT and depletion in secondary lymphoid organs during ageing was detected both in male and female animals. Our data thus demonstrate that T cell lymphopenia in secondary lymphoid organs currently associated to ageing is not sustained in gut or lung mucosa associated lymphoid tissues or non-lymphoid sites such as the liver. The inverse correlation between CD4 T cell numbers in secondary lymphoid organs and colonic lamina propria and the absence of overt proliferation in GALT suggest that marked CD4 T cell decay in secondary

Microchannel neural interface manufacture by stacking silicone and metal foil laminae

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Lancashire, Henry T.; Vanhoestenberghe, Anne; Pendegrass, Catherine J.; Ajam, Yazan Al; Magee, Elliot; Donaldson, Nick; Blunn, Gordon W.

2016-06-01

Objective. Microchannel neural interfaces (MNIs) overcome problems with recording from peripheral nerves by amplifying signals independent of node of Ranvier position. Selective recording and stimulation using an MNI requires good insulation between microchannels and a high electrode density. We propose that stacking microchannel laminae will improve selectivity over single layer MNI designs due to the increase in electrode number and an improvement in microchannel sealing. Approach. This paper describes a manufacturing method for creating MNIs which overcomes limitations on electrode connectivity and microchannel sealing. Laser cut silicone—metal foil laminae were stacked using plasma bonding to create an array of microchannels containing tripolar electrodes. Electrodes were DC etched and electrode impedance and cyclic voltammetry were tested. Main results. MNIs with 100 μm and 200 μm diameter microchannels were manufactured. High electrode density MNIs are achievable with electrodes present in every microchannel. Electrode impedances of 27.2 ± 19.8 kΩ at 1 kHz were achieved. Following two months of implantation in Lewis rat sciatic nerve, micro-fascicles were observed regenerating through the MNI microchannels. Significance. Selective MNIs with the peripheral nervous system may allow upper limb amputees to control prostheses intuitively.

Current practice and feasibility in microlaryngeal surgery: microsurgical pressing excision technique.

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Lee, Ka-Wo; Chiang, Feng-Yu

2009-12-01

Since the introduction of endolaryngeal microsurgery, several basic microsurgical techniques have been described for the removal of benign vocal fold lesions. These techniques include conventional incision or dissection, bimanual retraction and cutting, microflap technique and the CO2 laser. Until recently, only a few microsurgical methods have emerged as new choices for the treatment of benign vocal fold lesions. This article introduces an innovative method that can precisely remove benign sessile vocal fold lesions with epithelial keratosis or hyperplasia without jeopardizing the intermediate or deep layer of the lamina propria. Instead of using conventional vertically opening microinstruments, this microsurgical pressing excision technique (MPET) utilized two pairs of custom-made horizontally left-opening or right-opening, curved microscissors/curved cupped microforceps to remove right or left vocal fold lesions accordingly. Using one instrument at a time, the lesion was subsequently removed with the microscissors and microforceps in a press-evert-cut manner. Among a total of 553 cases, the treatment results were satisfactory, with 520 (94%) patients retaining a satisfactory/normal (G0) voice 2 months postoperatively. More importantly, no patient's voice was worse postoperatively. This technique has several advantages: utilizing one instrument at a time can maximize exposure of the narrow endoscopic view, adjusting the pressing force makes precise excision easy in a well controlled horizontal plane. The MPET is particularly useful for removing sessile vocal nodules (especially those with epithelial keratosis), epithelial hyperplasia and leukoplakia in patients with difficult endolaryngeal exposure. This could be a well tolerated and precise microsurgical technique.

Glymphatic stasis at the site of the lamina cribrosa as a potential mechanism underlying open-angle glaucoma.

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Wostyn, Peter; Killer, Hanspeter Esriel; De Deyn, Peter Paul

2017-07-01

The underlying pathophysiology of primary open-angle glaucoma remains unclear, but the lamina cribrosa seems to be the primary site of injury, and raised intraocular pressure is a major risk factor. In recent years, a decreased intracranial pressure, leading to an abnormally high trans-lamina cribrosa pressure difference, has gained interest as a new risk factor for glaucoma. New research now lends support to the hypothesis that a paravascular transport system is present in the eye analogous to the recently discovered 'glymphatic system' in the brain, which is a functional waste clearance pathway that promotes elimination of interstitial solutes, including β-amyloid, from the brain along paravascular channels. Given that β-amyloid has been reported to increase by chronic elevation of intraocular pressure in glaucomatous animal models and to cause retinal ganglion cell death, the discovery of a paravascular clearance system in the eye may provide powerful new insights into the pathophysiology of primary open-angle glaucoma. In this review, we provide a new conceptual framework for understanding the pathogenesis of primary open-angle glaucoma, present supporting preliminary data from our own post-mortem study and hypothesize that the disease may result from restriction of normal glymphatic flow at the level of the lamina cribrosa owing to a low intracranial pressure and/or a high trans-lamina cribrosa pressure gradient. If confirmed, this viewpoint could offer new perspectives for the development of novel diagnostic and therapeutic strategies for this devastating disorder. © 2017 Royal Australian and New Zealand College of Ophthalmologists.

Histogenesis of rumen in one-humped camel (Camelus dromedarius

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E. Salimi Naghani* and L. Akradi1

2012-05-01

Full Text Available The aim of this study was to follow several sequence histological changes that occur during the histogenesis of the rumen in one-humped camel (Camelus dromedarius. Histogenesis study was carried out on 66 fetuses of camel from 50th day of gestation until birth (390 days, according to the most relevant histo-differentiation characteristics of the rumen in fetuses, these were divided into four groups: group I (5-24 cm crown-rump length (C-RL; 50-140 days; group II (24-30 cm C-RL; 140-160 days; group III (30-60 cm C-RL; 160-250 days; group IV (60-108 cm C-RL; 250-390 days. At 50 days, the rumen consisted of four layers: the epithelial layer, propria-submucosa, tunica muscularis and serosa. The epithelium glandular region was pseudostratified and in non-glandular region was stratified. The muscularis mucosa was observed incompletely from 140 days between lamina propria and submucosa in glandular region of the rumen to the birth day. The primary lymphatic nodules appeared in lamina propria of glandular region of the rumen at 160 days of gestation. The epithelium of the glandular region in rumen was formed by a simple columnar layer at 250 days. In all groups, the tunica muscularis layer of rumen was increased with ruminal development, gradually. The non-glandular region of rumen was formed by a stratified epithelium and number of these cells increased with ruminal development. The lymphatic nodules and muscularis mucosa in non-glandular region did not observe in all groups. The study observations revealed that non-glandular region of the rumen in the fetuses of camel are less precocious than the rumen of the domestic ruminants.

Lamina specific loss of inhibition may lead to distinct neuropathic manifestations: a computational modeling approach

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Erick Javier Argüello Prada

Full Text Available Introduction It has been reported that inhibitory control at the superficial dorsal horn (SDH can act in a regionally distinct manner, which suggests that regionally specific subpopulations of SDH inhibitory neurons may prevent one specific neuropathic condition. Methods In an attempt to address this issue, we provide an alternative approach by integrating neuroanatomical information provided by different studies to construct a network-model of the SDH. We use Neuroids to simulate each neuron included in that model by adapting available experimental evidence. Results Simulations suggest that the maintenance of the proper level of pain sensitivity may be attributed to lamina II inhibitory neurons and, therefore, hyperalgesia may be elicited by suppression of the inhibitory tone at that lamina. In contrast, lamina III inhibitory neurons are more likely to be responsible for keeping the nociceptive pathway from the mechanoreceptive pathway, so loss of inhibitory control in that region may result in allodynia. The SDH network-model is also able to replicate non-linearities associated to pain processing, such as Aβ-fiber mediated analgesia and frequency-dependent increase of the neural response. Discussion By incorporating biophysical accuracy and newer experimental evidence, the SDH network-model may become a valuable tool for assessing the contribution of specific SDH connectivity patterns to noxious transmission in both physiological and pathological conditions.

Investigation in clinical potential of polarization sensitive optical coherence tomography in laryngeal tumor model study

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Zhou, Xin; Oak, Chulho; Ahn, Yeh-Chan; Kim, Sung Won; Tang, Shuo

2018-02-01

Polarization-sensitive optical coherence tomography (PS-OCT) is capable of measuring tissue birefringence. It has been widely applied to access the birefringence in tissues such as skin and cartilage. The vocal cord tissue consists of three anatomical layers from the surface to deep inside, the epithelium that contains almost no collagen, the lamina propria that is composed with abundant collagen, and the vocalis muscle layer. Due to the variation in the organization of collagen fibers, the different tissue layers show different tissue birefringence, which can be evaluated by PS-OCT phase retardation measurement. Furthermore, collagen fibers in healthy connective tissues are usually well organized, which provides relatively high birefringence. When the collagen organization is destroyed by diseases such as tumor, the birefringence of the tissue will decrease. In this study, a rabbit laryngeal tumor model with different stages of tumor progression is investigated ex-vivo by PS-OCT. The PS-OCT images show a gradual decrease in birefringence from normal tissue to severe tumor tissue. A phase retardation slope-based analysis is conducted to distinguish the epithelium, lamina propria, and muscle layers, respectively. The phase retardation slope quantifies the birefringence in different layers. The quantitative study provides a more detailed comparison among different stages of the rabbit laryngeal tumor model. The PS-OCT result is validated by the corresponding histology images of the same samples.

Langerhans cell histiocytosis of the urinary bladder in a patient with bladder cancer previously treated with intravesical Bacillus Calmette-Guérin therapy.

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Numakura, Satoe; Morikawa, Teppei; Ushiku, Tetsuo; Toyoshima, Toyoaki; Fukayama, Masashi

2014-02-01

We report an extremely rare case of Langerhans cell histiocytosis (LCH) of the urinary bladder. A 68-year-old man presented with gross hematuria. Cystoscopy showed multiple papillary tumors in the urinary bladder, and transurethral resection was performed. Pathological diagnosis was high-grade papillary urothelial carcinoma with lamina propria invasion. The patient received six treatments with intravesical Bacillus Calmette-Guérin (BCG) therapy. Seven months after surgery, follow-up cystoscopy showed three elevated lesions in the urinary bladder, two of which were identified histologically as recurrent urothelial carcinoma. Microscopic examination of the lesion at the anterior wall revealed diffuse infiltration of medium to large histiocytoid cells in the lamina propria, many of which had distorted nuclei and nuclear grooves. Dense eosinophilic infiltration was also observed. Immunohistochemically, the histiocytoid cells were diffusely positive for S-100 and CD1a, but negative for cytokeratin AE1/AE3 and melanosome-associated antigen recognized by HMB-45. Based on the histological and immunohistochemical features, we diagnosed the lesion as LCH of the urinary bladder. There was no evidence of recurrence of either bladder cancer or LCH after an 18-month follow-up. To avoid misdiagnosis, urologists and pathologists should be aware that LCH may develop in the urinary bladder after intravesical BCG therapy for bladder cancer. Copyright © 2013 Elsevier GmbH. All rights reserved.

Dendritic cells in Barrett's esophagus and esophageal adenocarcinoma.

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Bobryshev, Yuri V; Tran, Dinh; Killingsworth, Murray C; Buckland, Michael; Lord, Reginald V N

2009-01-01

Like other premalignant conditions that develop in the presence of chronic inflammation, the development and progression of Barrett's esophagus is associated with the development of an immune response, but how this immune response is regulated is poorly understood. A comprehensive literature search failed to find any report of the presence of dendritic cells in Barrett's intestinal metaplasia and esophageal adenocarcinoma and this prompted our study. We used immunohistochemical staining and electron microscopy to examine whether dendritic cells are present in Barrett's esophagus and esophageal adenocarcinoma. Immunohistochemical staining with CD83, a specific marker for dendritic cells, was performed on paraffin-embedded sections of Barrett's intestinal metaplasia (IM, n = 12), dysplasia (n = 11) and adenocarcinoma (n = 14). CD83+ cells were identified in the lamina propria surrounding intestinal type glands in Barrett's IM, dysplasia, and cancer tissues. Computerized quantitative analysis showed that the numbers of dendritic cells were significantly higher in cancer tissues. Double immunostaining with CD83, CD20, and CD3, and electron microscopy demonstrated that dendritic cells are present in Barrett's esophagus and form clusters with T cells and B cells directly within the lamina propria. These findings demonstrate that dendritic cells are present in Barrett's tissues, with a significant increase in density in adenocarcinoma compared to benign Barrett's esophagus. Dendritic cells may have a role in the pathogenesis and immunotherapy treatment of Barrett's esophagus and adenocarcinoma.

Mast cell-derived histamine mediates cystitis pain.

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Charles N Rudick

2008-05-01

Full Text Available Mast cells trigger inflammation that is associated with local pain, but the mechanisms mediating pain are unclear. Interstitial cystitis (IC is a bladder disease that causes debilitating pelvic pain of unknown origin and without consistent inflammation, but IC symptoms correlate with elevated bladder lamina propria mast cell counts. We hypothesized that mast cells mediate pelvic pain directly and examined pain behavior using a murine model that recapitulates key aspects of IC.Infection of mice with pseudorabies virus (PRV induces a neurogenic cystitis associated with lamina propria mast cell accumulation dependent upon tumor necrosis factor alpha (TNF, TNF-mediated bladder barrier dysfunction, and pelvic pain behavior, but the molecular basis for pelvic pain is unknown. In this study, both PRV-induced pelvic pain and bladder pathophysiology were abrogated in mast cell-deficient mice but were restored by reconstitution with wild type bone marrow. Pelvic pain developed normally in TNF- and TNF receptor-deficient mice, while bladder pathophysiology was abrogated. Conversely, genetic or pharmacologic disruption of histamine receptor H1R or H2R attenuated pelvic pain without altering pathophysiology.These data demonstrate that mast cells promote cystitis pain and bladder pathophysiology through the separable actions of histamine and TNF, respectively. Therefore, pain is independent of pathology and inflammation, and histamine receptors represent direct therapeutic targets for pain in IC and other chronic pain conditions.

The prognosis significance and application value of peritoneal elastic lamina invasion in colon cancer.

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Lu, Jun; Hu, Xiumei; Meng, Yutong; Zhao, Hongying; Cao, Qing; Jin, Mulan

2018-01-01

The aims of this study were to evaluate the associations between peritoneal elastic lamina invasion (ELI) and the clinicopathological prognostic factors of colon cancer, to evaluate the feasibility of ELI with use of an elastic stain to help diagnose serosal invasion of colon cancer in routine practice, so as to help us to provide a more accurate estimate for prognosis and stage of patients and a marker for postoperative treatment. 254 cases with colon cancer were included in the study. According to the presence of elastic lamina (EL) and elastic lamina invasion (ELI), all cases were divided into four groups: pT3 EL negative (pT3 EL (-)), pT3 ELI positive (pT3 ELI (+)), pT3 ELI negative (pT3 ELI (-)) and pT4a. Statistical analysis was used to analyze the relationship between elastic lamina invasion and other established adverse histologic features. The EL and ELI positive rates were 81.5% and 42.1% respectively. There were significant differences in mph node metastasis, venous invasion and tumor buds between pT3 ELI (-) and pT3 ELI (+), pT3 ELI (-) and pT4a. There was no significant difference in same factors between pT3 ELI (+) and pT4a. In pT3 stage, there were significant differences in lymph node metastasis, perineural invasion and tumor buds between EL (-) and ELI (+). There were no significant differences in same factors between EL (-) and ELI (-). EL was detected less frequently in right-sided tumors compared with left-sided tumors. ELI might be the prognostic factors of colon cancer with II stage and might be the marker of postoperative adjuvant chemotherapy. Patients with pT3 ELI (+) might have similar prognosis to patients with pT4a. For patients with pT3 colon cancer, EL(-) might have similar prognosis as ELI (-) and might take the same therapy. In addition, the right half colon EL positive rate was lower than the left colon. Elastic staining might be a useful tool to help determine the invasive depth and stage of colon cancer.

Clinical study of bilateral decompression via vertebral lamina fenestration for lumbar interbody fusion in the treatment of lower lumbar instability

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GUO, SHUGUANG; SUN, JUNYING; TANG, GENLIN

2013-01-01

The aim of this study was to observe the clinical effects of bilateral decompression via vertebral lamina fenestration for lumbar interbody fusion in the treatment of lower lumbar instability. The 48 patients comprised 27 males and 21 females, aged 47?72 years. Three cases had first and second degree lumbar spondylolisthesis and all received bilateral vertebral lamina fenestration for posterior lumbar interbody fusion (PLIF) using a threaded fusion cage (TFC), which maintains the three-column...

The Complexity of Folding Self-Folding Origami

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Stern, Menachem; Pinson, Matthew B.; Murugan, Arvind

2017-10-01

Why is it difficult to refold a previously folded sheet of paper? We show that even crease patterns with only one designed folding motion inevitably contain an exponential number of "distractor" folding branches accessible from a bifurcation at the flat state. Consequently, refolding a sheet requires finding the ground state in a glassy energy landscape with an exponential number of other attractors of higher energy, much like in models of protein folding (Levinthal's paradox) and other NP-hard satisfiability (SAT) problems. As in these problems, we find that refolding a sheet requires actuation at multiple carefully chosen creases. We show that seeding successful folding in this way can be understood in terms of subpatterns that fold when cut out ("folding islands"). Besides providing guidelines for the placement of active hinges in origami applications, our results point to fundamental limits on the programmability of energy landscapes in sheets.

Correlation of radiographic size and the presence of radiopaque lamina with histological findings in 70 periapical lesions.

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Carrillo, Celia; Penarrocha, Miguel; Ortega, Bárbara; Martí, Eva; Bagán, José Vicente; Vera, Francisco

2008-08-01

This study was conducted to relate the histological diagnosis of chronic inflammatory periapical lesions with the radiographic images of these lesions. A total of 70 biopsy specimens obtained during periapical surgery were stained with hematoxylin and eosin and examined under a microscope. Histological analysis established the diagnosis as granuloma, cyst, or scar tissue. The location of the lesion was recorded, as were the radiographic size (maximum and minimum diameter in mm and area in mm(2)) and the presence of radiopaque lamina around the lesion, using an image analyzing system. The distribution of the biopsy specimens was 65.7% granulomas, 25.7% scar tissue, and 8.6% cysts, 1 of which was a keratocyst. The largest lesions were cysts and epithelialized granulomas, with statistically significant differences. Radiopaque lamina was observed around 9 lesions; of these, only 2 were histologically diagnosed as cysts, with the rest as granulomas. Most of the apical lesions were granulomas. Cysts had the largest radiotransparent images; however, in the 70 cases studied, neither the radiographic size nor the presence of associated radiopaque lamina alone was sufficient to determine the type of lesion. Histological analysis is required.

Mucosal bridges of the upper esophagus after radiotherapy for Hodgkin's disease

International Nuclear Information System (INIS)

Papazian, A.; Capron, J.P.; Ducroix, J.P.; Dupas, J.L.; Quenum, C.; Besson, P.

1983-01-01

A 47-yr-old man developed dysphagia 4 yr after mediastinal radiotherapy for Hodgkin's disease. X-ray series, fiberoptic endoscopy, and computerized transverse tomography showed mucosal bridges in the upper esophagus. Histologically, these bridges were constituted from normal epithelium overlying a chronic inflammatory lamina propria, without evidence of Hodgkin's disease recurrence or of squamous cell carcinoma. Swallowing was improved by endoscopic electrocoagulation and Eder-Puestow dilatations. Several arguments favor the hypothesis that these mucosal bridges were the late sequelae of radiation esophagitis

Epithelial regeneration of transposed intestine after high doses of X irradiation

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Both, N.J. de; Vermey, M [Erasmus Universiteit, Rotterdam (Netherlands)

1976-01-01

The regeneration capacities of normal and transposed small bowel epithelium were compared in rats after applying high doses of x irradiation. It has been shown that the potency of the mucosa to regenerate was much higher than assumed and that the mucosa could regenerate after single doses varying from 2000 to 5000 R. Even in the villus epithelium and in flat epithelium covering infiltrates of the lamina propria cells survived, which were still able to resume proliferative activity several days after irradiation.

Epithelial regeneration of transposed intestine after high doses of X-irradiation

International Nuclear Information System (INIS)

Both, N.J. de; Vermey, M.

1976-01-01

The regeneration capacities of normal and transposed small bowel epithelium were compared in rats after applying high doses of X-irradiation. It has been shown that the potency of the mucosa to regenerate was much higher than assumed and that the mucosa could regenerate after single doses varying from 2000 to 5000 R. Even in the villus epithelium and in flat epithelium covering infiltrates of the lamina propria cells survived, which were still able to resume proliferative activity several days after irradiation. (author)

The Complexity of Folding Self-Folding Origami

Directory of Open Access Journals (Sweden)

Menachem Stern

2017-12-01

Full Text Available Why is it difficult to refold a previously folded sheet of paper? We show that even crease patterns with only one designed folding motion inevitably contain an exponential number of “distractor” folding branches accessible from a bifurcation at the flat state. Consequently, refolding a sheet requires finding the ground state in a glassy energy landscape with an exponential number of other attractors of higher energy, much like in models of protein folding (Levinthal’s paradox and other NP-hard satisfiability (SAT problems. As in these problems, we find that refolding a sheet requires actuation at multiple carefully chosen creases. We show that seeding successful folding in this way can be understood in terms of subpatterns that fold when cut out (“folding islands”. Besides providing guidelines for the placement of active hinges in origami applications, our results point to fundamental limits on the programmability of energy landscapes in sheets.

Oxytocin-induced antinociception in the spinal cord is mediated by a subpopulation of glutamatergic neurons in lamina I-II which amplify GABAergic inhibition

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Schlichter Rémy

2008-05-01

Full Text Available Abstract Background Recent evidence suggests that oxytocin (OT, secreted in the superficial spinal cord dorsal horn by descending axons of paraventricular hypothalamic nucleus (PVN neurons, produces antinociception and analgesia. The spinal mechanism of OT is, however, still unclear and requires further investigation. We have used patch clamp recording of lamina II neurons in spinal cord slices and immunocytochemistry in order to identify PVN-activated neurons in the superficial layers of the spinal cord and attempted to determine how this neuronal population may lead to OT-mediated antinociception. Results We show that OT released during PVN stimulation specifically activates a subpopulation of lamina II glutamatergic interneurons which are localized in the most superficial layers of the dorsal horn of the spinal cord (lamina I-II. This OT-specific stimulation of glutamatergic neurons allows the recruitment of all GABAergic interneurons in lamina II which produces a generalized elevation of local inhibition, a phenomenon which might explain the reduction of incoming Aδ and C primary afferent-mediated sensory messages. Conclusion Our results obtained in lamina II of the spinal cord provide the first clear evidence of a specific local neuronal network that is activated by OT release to induce antinociception. This OT-specific pathway might represent a novel and interesting therapeutic target for the management of neuropathic and inflammatory pain.

Current status of submucosal tunneling endoscopic resection for gastrointestinal submucosal tumors originating from the muscularis propria layer.

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Tan, Yuyong; Huo, Jirong; Liu, Deliang

2017-11-01

Gastrointestinal submucosal tumors (SMTs) have been increasingly identified via the use of endoscopic ultrasonography, and removal is often recommended for SMTs that are >2 cm in diameter or symptomatic. Submucosal tunneling endoscopic resection (STER), also known as submucosal endoscopic tumor resection, endoscopic submucosal tunnel dissection or tunneling endoscopic muscularis dissection, is a novel endoscopic technique for treating gastrointestinal SMTs originating from the muscularis propria layer, and has been demonstrated to be effective in the removal of SMTs with a decreased rate of recurrence by clinical studies. STER may be performed for patients with esophageal or cardia SMTs, and its application has expanded beyond these types of SMTs due to modifications to the technique. The present study reviewed the applications, procedure, efficacy and complications associated with STER.

Mucosal bridges of the upper esophagus after radiotherapy for Hodgkin's disease

Energy Technology Data Exchange (ETDEWEB)

Papazian, A.; Capron, J.P.; Ducroix, J.P.; Dupas, J.L.; Quenum, C.; Besson, P.

1983-05-01

A 47-yr-old man developed dysphagia 4 yr after mediastinal radiotherapy for Hodgkin's disease. X-ray series, fiberoptic endoscopy, and computerized transverse tomography showed mucosal bridges in the upper esophagus. Histologically, these bridges were constituted from normal epithelium overlying a chronic inflammatory lamina propria, without evidence of Hodgkin's disease recurrence or of squamous cell carcinoma. Swallowing was improved by endoscopic electrocoagulation and Eder-Puestow dilatations. Several arguments favor the hypothesis that these mucosal bridges were the late sequelae of radiation esophagitis.

Enteric alpha defensins in norm and pathology

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Lisitsyn Nikolai A

2012-01-01

Full Text Available Abstract Microbes living in the mammalian gut exist in constant contact with immunity system that prevents infection and maintains homeostasis. Enteric alpha defensins play an important role in regulation of bacterial colonization of the gut, as well as in activation of pro- and anti-inflammatory responses of the adaptive immune system cells in lamina propria. This review summarizes currently available data on functions of mammalian enteric alpha defensins in the immune defense and changes in their secretion in intestinal inflammatory diseases and cancer.

Mucous flow and ciliary activity in the trachea of rats exposed to pulmonary irritant gas

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Dalhamm, T; Rhodin, J

1956-01-01

Tracheal mucous secretion was increased in rats exposed to 10 ppM SO/sub 2/, 6 hr/day for 10 weeks. Mucous transport was decreased from 13.5 to 5 mm/min although ciliary beat remained a constant 1320 beats/min. The mucous layer was 5 times as thick as the normal ..mu..m. Histologically, cilia were generally unaffected whereas tracheal epithelium was irregular with deep crypts, and the lamina propria showed severe edema, fragmentation of collagen fibrils, and profuse vascularization with blood escaping perivascularly.

Connective tissue growth factor is necessary for retinal capillary basal lamina thickening in diabetic mice

NARCIS (Netherlands)

Kuiper, Esther J.; van Zijderveld, Rogier; Roestenberg, Peggy; Lyons, Karen M.; Goldschmeding, Roel; Klaassen, Ingeborg; van Noorden, Cornelis J. F.; Schlingemann, Reinier O.

2008-01-01

Experimental prevention of basal lamina (BL) thickening of retinal capillaries ameliorates early vascular changes caused by diabetes. Connective tissue growth factor (CTGF) is upregulated early in diabetes in the human retina and is a potent inducer of expression of BL components. We hypothesize

Boomerang deformity of cervical spinal cord migrating between split laminae after laminoplasty.

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Kimura, S; Gomibuchi, F; Shimoda, H; Ikezawa, Y; Segawa, H; Kaneko, F; Uchiyama, S; Homma, T

2000-04-01

Patients with cervical compression myelopathy were studied to elucidate the mechanism underlying boomerang deformity, which results from the migration of the cervical spinal cord between split laminae after laminoplasty with median splitting of the spinous processes (boomerang sign). Thirty-nine cases, comprising 25 patients with cervical spondylotic myelopathy, 8 patients with ossification of the posterior longitudinal ligament, and 6 patients with cervical disc herniation with developmental canal stenosis, were examined. The clinical and radiological findings were retrospectively compared between patients with (B group, 8 cases) and without (C group, 31 cases) boomerang sign. Moderate increase of the grade of this deformity resulted in no clinical recovery, although there was no difference in clinical recovery between the two groups. Most boomerang signs developed at the C4/5 and/or C5/6 level, where maximal posterior movement of the spinal cord was achieved. Widths between lateral hinges and between split laminae in the B group were smaller than in the C group. Flatness of the spinal cord in the B group was more severe than in the C group. In conclusion, the boomerang sign was caused by posterior movement of the spinal cord, narrower enlargement of the spinal canal and flatness of the spinal cord.

Basal lamina structural alterations in human asymmetric aneurismatic aorta

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M Cotrufo

2009-06-01

Full Text Available Basal lamina (BL is a crucial mechanical and functional component of blood vessels, constituting a sensor of extracellular microenvironment for endothelial cells and pericytes. Recently, an abnormality in the process of matrix microfibrillar component remodeling has been advocated as a mechanism involved in the development of aortic dilation.We focused our attention on BL composition and organization and studied some of the main components of the Extracellular Matrix such as Tenascin, Laminins, Fibronectin, type I, III and IV Collagens.We used surgical fragments from 27 patients, submitted to operation because of aortic root aneurysm and 5 normal aortic wall specimens from heart donors without any evidence for aneurysmal or atherosclerotic diseases of the aorta. Two samples of aortic wall were harvested from each patient, proximal to the sinotubular junction at the aortic convexity and concavity. Each specimen was processed both for immunohistochemical examination and molecular biology study.We compared the convexity of each aortic sample with the concavity of the same vessel, and both of them with the control samples. The synthesis of mRNA and the levels of each protein were assessed, respectively, by RTPCR and Western Blot analysis. Immunohistochemistry elucidated the organization of BL, whose composition was revealed by molecular biology. All pathological samples showed a wall thinner than normal ones. Basal lamina of the aortic wall evidentiated important changes in the tridimensional arrangement of its major components which lost their regular arrangement in pathological specimens. Collagen I, Laminin a2 chain and Fibronectin amounts decreased in pathological samples, while type IV Collagen and Tenascin synthesis increased. Consistently with the common macroscopic observation that ascending aorta dilations tend to expand asymmetrically, with prevalent involvement of the vessel convexity and relative sparing of the concavity, Collagen type

Comparative study of the organisation and phenotypes of bladder interstitial cells in human, mouse and rat.

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Gevaert, Thomas; Neuhaus, Jochen; Vanstreels, Els; Daelemans, Dirk; Everaerts, Wouter; Der Aa, Frank Van; Timmermans, Jean-Pierre; Roskams, Tania; Steiner, Clara; Pintelon, Isabel; De Ridder, Dirk

2017-12-01

With most research on interstitial cells (IC) in the bladder being conducted on animal models, it remains unclear whether all structural and functional data on IC from animal models can be translated to the human context. This prompted us to compare the structural and immunohistochemical properties of IC in bladders from mouse, rat and human. Tissue samples were obtained from the bladder dome and subsequently processed for immunohistochemistry and electron microscopy. The ultrastructural properties of IC were compared by means of electron microscopy and IC were additionally characterized with single/double immunohistochemistry/immunofluorescence. Our results reveal a similar organization of the IC network in the upper lamina propria (ULP), the deep lamina propria (DLP) and the detrusor muscle in human, rat and mouse bladders. Furthermore, despite several similarities in IC phenotypes, we also found several obvious inter-species differences in IC, especially in the ULP. Most remarkably in this respect, ULP IC in human bladder predominantly displayed a myoid phenotype with abundant presence of contractile micro-filaments, while those in rat and mouse bladders showed a fibroblast phenotype. In conclusion, the organization of ULP IC, DLP IC and detrusor IC is comparable in human, rat and mouse bladders, although several obvious inter-species differences in IC phenotypes were found. The present data show that translating research data on IC in laboratory animals to the human setting should be carried out with caution.

Broad MICA/B Expression in the Small Bowel Mucosa: A Link between Cellular Stress and Celiac Disease

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Allegretti, Yessica L.; Bondar, Constanza; Guzman, Luciana; Cueto Rua, Eduardo; Chopita, Nestor; Fuertes, Mercedes; Zwirner, Norberto W.; Chirdo, Fernando G.

2013-01-01

The MICA/B genes (MHC class I chain related genes A and B) encode for non conventional class I HLA molecules which have no role in antigen presentation. MICA/B are up-regulated by different stress conditions such as heat-shock, oxidative stress, neoplasic transformation and viral infection. Particularly, MICA/B are expressed in enterocytes where they can mediate enterocyte apoptosis when recognised by the activating NKG2D receptor present on intraepithelial lymphocytes. This mechanism was suggested to play a major pathogenic role in active celiac disease (CD). Due to the importance of MICA/B in CD pathogenesis we studied their expression in duodenal tissue from CD patients. By immunofluorescence confocal microscopy and flow cytometry we established that MICA/B was mainly intracellularly located in enterocytes. In addition, we identified MICA/B+ T cells in both the intraepithelial and lamina propria compartments. We also found MICA/B+ B cells, plasma cells and some macrophages in the lamina propria. The pattern of MICA/B staining in mucosal tissue in severe enteropathy was similar to that found in in vitro models of cellular stress. In such models, MICA/B were located in stress granules that are associated to the oxidative and ER stress response observed in active CD enteropathy. Our results suggest that expression of MICA/B in the intestinal mucosa of CD patients is linked to disregulation of mucosa homeostasis in which the stress response plays an active role. PMID:24058482

MHC class II+ (HLA-DP-like) cells in the cow reproductive tract: II. Immunolocalization of MHC class II+ cells in oviduct and vagina.

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Eren, U; Kum, S; Sandikçi, M; Eren, V; Ilhan, F

2009-08-01

The aim of this study was to determine and examine the distribution of major frequency MHC II+ cells in the oviduct and vagina of cows during the oestrous and dioestrus phases. Right oviduct (ampulla, isthmus) and vaginal samples taken from a total of twenty seven multiparous cows were used. Tissue samples were processed to obtain both cryostat and paraffin sections. Sections were stained immunocytochemically using StreptABC method using a specific monoclonal antibody to MHC II+ cell population. Intra-epithelial and subepithelial areas along with lamina propria, muscularis mucosae and serosa of both ampulla and isthmus and intra-epithelial/subepithelial areas and mucosae of vagina were examined for the presence of MHC II+ cells. The density of immune positive cells was determined using a subjective scoring system. MHC II+ cells were demonstrated in all areas examined in both oestrus and dioestrus. In oestrus, the density of MHC II+ cells decreased in subepithelial areas (in between the epithelial cells and the basal membrane) of isthmus, whereas the density of immune positive cells was increased in muscularis mucosae of isthmus (P < 0.05), lamina propria and muscularis mucosae of ampulla (P < 0.05) as well as in the mucosae of vagina (P

Association of Helicobacter pylori infection with gastroesophageal reflux disease

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Aswathy Chandramohan

2016-01-01

Full Text Available Introduction: The study was conducted to determine the association of Helicobactor pylori with endoscopic and histological parameters of gastroesophageal reflux disease (GERD. Materials and Methods: A cross-sectional study was undertaken. A total of 79 patients were evaluated prospectively in the endoscopic unit of a gastroenterology department for symptoms compatible with GERD. In all cases, routine endoscopy and Los Angeles grading of GERD were performed. In each subject, biopsies were taken from 3 cm above the squamocolumnar junction and from the antrum and assessed histologically. Results: Majority of the patients presented with complaints of heartburn (84.8% and regurgitation (75.9%. Nonerosive reflux disease was present in only five patients. Endoscopically, the remaining 74 cases were graded as follows: 25 had GERD A, 10 had GERD B, 35 had features of Barrett's esophagus, and 4 had miscellaneous findings. H. pylori positivity was present in 33.3% of patients with GERD A and 4.8% of those with GERD B. Majority of the histological parameters such as elongation of lamina propria papillae, intraepithelial inflammatory infiltrate, ballooning degeneration, lack of surface maturation, and dilatation and congestion of lamina propria capillaries did not show statistically significant association with H. pylori. The overall H. pylori prevalence was found to be 26.58% (21/79. Conclusion: On endoscopy, with the increased GERD severity, H. pylori incidence decreased. H. pylori was found to have no significant association with majority of the histological parameters.

Sensitive quantification of the HIV-1 reservoir in gut-associated lymphoid tissue.

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Morón-López, Sara; Puertas, Maria C; Gálvez, Cristina; Navarro, Jordi; Carrasco, Anna; Esteve, Maria; Manyé, Josep; Crespo, Manel; Salgado, Maria; Martinez-Picado, Javier

2017-01-01

The implementation of successful strategies to achieve an HIV cure has become a priority in HIV research. However, the current location and size of HIV reservoirs is still unknown since there are limited tools to evaluate HIV latency in viral sanctuaries such as gut-associated lymphoid tissue (GALT). As reported in the so called "Boston Patients", despite undetectable levels of proviral HIV-1 DNA in blood and GALT, viral rebound happens in just few months after ART interruption. This fact might imply that current methods are not sensitive enough to detect residual reservoirs. Showing that, it is imperative to improve the detection and quantification of HIV-1 reservoir in tissue samples. Herein, we propose a novel non-enzymatic protocol for purification of Lamina Propria Leukocytes (LPL) from gut biopsies combined to viral HIV DNA (vDNA) quantification by droplet digital PCR (ddPCR) to improve the sensitivity and accuracy of viral reservoir measurements (LPL-vDNA assay). Endoscopic ileum biopsies were sampled from 12 HIV-1-infected cART-suppressed subjects. We performed a DTT/EDTA-based treatment for epithelial layer removal followed by non-enzymatic disruption of the tissue to obtain lamina propria cell suspension (LP). CD45+ cells were subsequently purified by flow sorting and vDNA was determined by ddPCR. vDNA quantification levels were significantly higher in purified LPLs (CD45+) than in bulk LPs (pgut-associated viral sanctuaries, which might be used to evaluate any proposed eradication strategy.

Abortive Intestinal Infection With an Escherichia coli-Shigella flexneri Hybrid Strain

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Formal, Samuel B.; LaBrec, E. H.; Kent, T. H.; Falkow, S.

1965-01-01

Formal, Samuel B., (Walter Reed Army Institute of Research, Washington, D.C.), E. H. LaBrec, T. H. Kent, and S. Falkow. Abortive intestinal infection with an Escherichia coli-Shigella flexneri hybrid strain. J. Bacteriol. 89:1374–1382. 1965.—The mechanism of the apparent loss of virulence of an Escherichia coli-Shigella flexneri hybrid strain was studied. The parent Shigella strain caused a fatal enteric infection when fed to starved guinea pigs, and signs of dysentery followed its oral administration to monkeys. The hybrid strain failed to produce any apparent symptoms when fed to either of these species. The parent strain was shown to invade the intestinal mucosa of starved guinea pigs. This caused a severe inflammatory reaction in the lamina propria, which progressed to ulceration of the intestinal epithelium and resulted in death of the animal. The hybrid strain also invaded the intestinal mucosa and produced an inflammatory reaction. In this case, the inflammatory reaction subsided, the intestine returned to normal within 4 days after challenge, and the animal survived. Both fluorescent-antibody techniques and in vivo growth studies have shown that the hybrid strain can not maintain itself in the intestinal mucosa. Preliminary studies have indicated that a similar situation also exists in the monkey. It is concluded that the virulence of dysentery bacilli rests not only in the capacity to reach the lamina propria, but also in the ability to multiply in this region. Images PMID:14293011

Gnotobiotic IL-10; NF-kappaB mice develop rapid and severe colitis following Campylobacter jejuni infection.

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Elisabeth Lippert

2009-10-01

Full Text Available Limited information is available on the molecular mechanisms associated with Campylobacter jejuni (C. jejuni induced food-borne diarrheal illnesses. In this study, we investigated the function of TLR/NF-kappaB signaling in C. jejuni induced pathogenesis using gnotobiotic IL-10(-/-; NF-kappaB(EGFP mice. In vitro analysis showed that C. jejuni induced IkappaB phosphorylation, followed by enhanced NF-kappaB transcriptional activity and increased IL-6, MIP-2alpha and NOD2 mRNA accumulation in infected-mouse colonic epithelial cells CMT93. Importantly, these events were blocked by molecular delivery of an IkappaB inhibitor (Ad5IkappaBAA. NF-kappaB signalling was also important for C.jejuni-induced cytokine gene expression in bone marrow-derived dendritic cells. Importantly, C. jejuni associated IL-10(-/-; NF-kappaB(EGFP mice developed mild (day 5 and severe (day 14 ulcerating colonic inflammation and bloody diarrhea as assessed by colonoscopy and histological analysis. Macroscopic analysis showed elevated EGFP expression indicating NF-kappaB activation throughout the colon of C. jejuni associated IL-10(-/-; NF-kappaB(EGFP mice, while fluorescence microscopy revealed EGFP positive cells to be exclusively located in lamina propria mononuclear cells. Pharmacological NF-kappaB inhibition using Bay 11-7085 did not ameliorate C. jejuni induced colonic inflammation. Our findings indicate that C. jejuni induces rapid and severe intestinal inflammation in a susceptible host that correlates with enhanced NF-kappaB activity from lamina propria immune cells.

Antinociceptive action of oxytocin involves inhibition of potassium channel currents in lamina II neurons of the rat spinal cord

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Darbon Pascal

2009-11-01

Full Text Available Abstract Background Growing evidence in the literature shows that oxytocin (OT has a strong spinal anti-nociceptive action. Oxytocinergic axons originating from a subpopulation of paraventricular hypothalamic neurons establish synaptic contacts with lamina II interneurons but little is known about the functional role of OT with respect to neuronal firing and excitability. Results Using the patch-clamp technique, we have recorded lamina II interneurons in acute transverse lumbar spinal cord slices of rats (15 to 30 days old and analyzed the OT effects on action potential firing ability. In the current clamp mode, we found that bath application of a selective OT-receptor agonist (TGOT reduced firing in the majority of lamina II interneurons exhibiting a bursting firing profile, but never in those exhibiting a single spike discharge upon depolarization. Interestingly, OT-induced reduction in spike frequency and increase of firing threshold were often observed, leading to a conversion of the firing profile from repetitive and delayed profiles into phasic ones and sometimes further into single spike profile. The observed effects following OT-receptor activation were completely abolished when the OT-receptor agonist was co-applied with a selective OT-receptor antagonist. In current and voltage clamp modes, we show that these changes in firing are strongly controlled by voltage-gated potassium currents. More precisely, transient IA currents and delayed-rectifier currents were reduced in amplitude and transient IA current was predominantly inactivated after OT bath application. Conclusion This effect of OT on the firing profile of lamina II neurons is in good agreement with the antinociceptive and analgesic properties of OT described in vivo.

Metal X-ray microanalysis in the olfactory system of rainbow trout exposed to low level of copper

International Nuclear Information System (INIS)

Julliard, A.K.; Astic, L.; Saucier, D.

1995-01-01

It has recently been shown that a chronic copper exposure induces specific degeneration of olfactory receptor cells in rainbow trout; however, the exact mechanism of action of the metal is not yet known. Using X-ray microanalysis in transmission electron microscopy, we have studied the distribution of metal in the olfactory system of fish exposed for 15,30 and 60 days to 20 μg/l of copper. This was done in order to determine if it was accumulated in receptor cells and transported into the central nervous system via the olfactory nerve. No copper accumulation was detected either in the olfactory epithelium, in the olfactory nerve or in the olfactory bulb. The heavy metal was exclusively found within melanosomes of melanophores located in the lamina propria. After 60 days of exposure, the copper content in melanosomes was about two-fold higher than that in controls. As far as some morphological recovery took place in the olfactory organ during the metal exposure, which lets us suppose that some detoxication mechanism occurs, it could be suggested that metanophores might be somehow involved in such a mechanism. (authors). 57 refs., 15 figs

Bait-lamina assay as a tool to assess the effects of metal contamination in the feeding activity of soil invertebrates within a uranium mine area

International Nuclear Information System (INIS)

Andre, A.; Antunes, S.C.; Goncalves, F.; Pereira, R.

2009-01-01

As part of the tier 2 of a site-specific risk assessment, this study was the first reporting an intensive in situ application of the bait-lamina assay; two exposure periods (7 and 14 days) were tested during four seasons in ten different sites, within a uranium mine area and at two different depths. The most contaminated sites (by deposition of sludge from the effluent treatment pond) were discriminated after 14 days of exposure because extremely low percentages of feeding activity were recorded. Previous sub-lethal ecotoxicological assays, already had demonstrated that the habitat function of these soils is compromised. Nevertheless, seasonality has proved to have a significant influence on responses. Thus to strength conclusions about the impact of contaminants, the in situ bait-lamina assay should be performed on different annual seasons, at least for temperate regions. It was also found that some environmental parameters (e.g. soil moisture and litter) can act as confounding factors in the bait-lamina assay. - Bait-lamina assay for in situ evaluation of soil functions under site-specific risk assessments.

Using the trans-lamina terminalis route via a pterional approach to resect a retrochiasmatic craniopharyngioma involving the third ventricle.

Science.gov (United States)

Weil, Alexander G; Robert, Thomas; Alsaiari, Sultan; Obaid, Sami; Bojanowski, Michel W

2016-01-01

Retrochiasmatic craniopharyngiomas involving the anterior third ventricle are challenging to access. Although the pterional approach is a common route for suprasellar lesions, when the craniopharyngioma extends behind the chiasma into the third ventricle, access is even more difficult, and the lamina terminalis may offer a good working window. The translamina terminalis approach provides direct access to the retrochiasmatic portion of the tumor with minimal brain retraction and no manipulation of the visual nerves. In this video, we emphasize the utility of using the lamina terminalis corridor to resect the retrochiasmatic intraventricular portion of a craniopharyngioma. The video can be found here: https://youtu.be/hrLNC0hDKe4 .

Long-term trends in the northern extratropical ozone laminae with focus on European stations

Czech Academy of Sciences Publication Activity Database

Laštovička, Jan; Križan, Peter; Kozubek, Michal

2014-01-01

Roč. 120, December (2014), s. 88-95 ISSN 1364-6826 R&D Projects: GA MŠk LD12070; GA ČR GAP209/10/1792 Institutional support: RVO:68378289 Keywords : ozone laminae * long-term trends * atmospheric dynamics Subject RIV: DG - Athmosphere Sciences, Meteorology Impact factor: 1.474, year: 2014 http://www.sciencedirect.com/science/article/pii/S1364682614002119

Co-expression of GAD67 and choline acetyltransferase in neurons in the mouse spinal cord: A focus on lamina X.

Science.gov (United States)

Gotts, Jittima; Atkinson, Lucy; Yanagawa, Yuchio; Deuchars, Jim; Deuchars, Susan A

2016-09-01

Lamina X of the spinal cord is a functionally diverse area with roles in locomotion, autonomic control and processing of mechano and nociceptive information. It is also a neurochemically diverse region. However, the different populations of cells in lamina X remain to be fully characterised. To determine the co-localisation of the enzymes responsible for the production of GABA and acetylcholine (which play major roles in the spinal cord) in lamina X of the adult and juvenile mouse, we used a transgenic mouse expressing green fluorescent protein (GFP) in glutamate decarboxylase 67 (GAD67) neurons, combined with choline acetyltransferase (ChAT) immunohistochemistry. ChAT-immunoreactive (IR) and GAD67-GFP containing neurons were observed in lamina X of both adult and juvenile mice and in both age groups a population of cells containing both ChAT-IR and GAD67-GFP were observed in lumbar, thoracic and cervical spinal cord. Such dual labelled cells were predominantly located ventral to the central canal. Immunohistochemistry for vesicular acetylcholine transporter (VAChT) and GAD67 revealed a small number of double labelled terminals located lateral, dorsolateral and ventrolateral to the central canal. This study therefore describes in detail a population of ChAT-IR/GAD67-GFP neurons predominantly ventral to the central canal of the cervical, thoracic and lumbar spinal cord of adult and juvenile mice. These cells potentially correspond to a sub-population of the cholinergic central canal cluster cells which may play a unique role in controlling spinal cord circuitry. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Papillary cystitis mimicking transitional cell carcinoma : a case report

International Nuclear Information System (INIS)

Lee, Young Rae; Park, Chan Pil

1998-01-01

Polypoid cystitis is a rare entity and, to our knowledge, has not been described in the radiologic literature. It is frequently found in patients with indwelling catheters and is characterized by inflammation and edema of the lamina propria. We encountered a case of papillary cystitis which on a sonogram showed a solid mass with inhomogeneous internal echopattern; on CT, a poorly-defined inhomogeneous, dense, soft-tissue density mass with enhancement and perivesical extension; and on T2 weighted MR images an intermediate SI mass. (author). 6 refs., 1 fig

Differential effect of immune cells on non-pathogenic Gram-negative bacteria-induced nuclear factor-kappaB activation and pro-inflammatory gene expression in intestinal epithelial cells

DEFF Research Database (Denmark)

Haller, D.; Holt, L.; Parlesak, Alexandr

2004-01-01

stimulation, interleukin-8 (IL-8) mRNA accumulation is strongly induced in Escherichia coli- but not Bacteroides vulgatus-stimulated IEC cocultured with peripheral blood (PBMC) and lamina propria mononuclear cells (LPMC). The presence of PBMC triggered both E. coli- and B. vulgatus-induced mRNA expression...... in the presence of PBMC. Interestingly, B. vulgatus- and E. coli-derived lipopolysaccharide-induced similar IL-8 mRNA expression in epithelial cells after basolateral stimulation of HT-29/PBMC cocultures. Although luminal enteric bacteria have adjuvant and antigenic properties in chronic intestinal inflammation...

Nephroid metaplasia of the urinary tract. A survey of the literature, with the contribution of 5 new immunohistochemically studied cases, including one case examined by electron microscopy

DEFF Research Database (Denmark)

Sørensen, Flemming Brandt; Jacobsen, F; Nielsen, J B

1987-01-01

Nephroid metaplasia is an unusual lesion confined to the lamina propria of the lower urinary tract. It is defined by a characteristic histologic picture of tubular structures, formed by a single layer of cuboidal cells, surrounded by a thick basement membrane. Two main theories concerning...... the histogenesis of the condition have been proposed: embryonic origin, or metaplasia. Five cases of nephroid metaplasia were studied light-microscopically and by immunohistochemistry for the content of Tamm Horsfall's uromucoprotein. In addition, one case was examined by electron microscopy. The results were...

[Hereditary hemorrhagic telangiectasia presenting with hematuria and severe anemia].

Science.gov (United States)

Paz, A; Goren, E; Segal, M

1995-07-01

A patient with hereditary hemorrhagic telangiectasia was admitted with hematuria and severe anemia after mild recurrent episodes of epistaxis. Telangiectasias were found in the skin and buccal and nasal mucosa. No defect in the coagulation mechanism was found; thrombocyte count and function were normal. On cystoscopy, tortuous engorged vessels, some actively bleeding, were seen in the trigonal mucosa. Biopsy showed enlarged vessels in the lamina propria. Electrocoagulation of the bleeding vessels stopped hematuria, but 6 months later it recurred. This time Nd-YAG laser was used to stop the bleeding after electrocoagulation was ineffective.

Microstructure imaging of human rectal mucosa using multiphoton microscopy

Science.gov (United States)

Liu, N. R.; Chen, G.; Chen, J. X.; Yan, J.; Zhuo, S. M.; Zheng, L. Q.; Jiang, X. S.

2011-01-01

Multiphoton microscopy (MPM) has high resolution and sensitivity. In this study, MPM was used to image microstructure of human rectal mucosa. The morphology and distribution of the main components in mucosa layer, absorptive cells and goblet cells in the epithelium, abundant intestinal glands in the lamina propria and smooth muscle fibers in the muscularis mucosa were clearly monitored. The variations of these components were tightly relevant to the pathology in gastrointestine system, especially early rectal cancer. The obtained images will be helpful for the diagnosis of early colorectal cancer.

Flips for 3-folds and 4-folds

CERN Document Server

Corti, Alessio

2007-01-01

This edited collection of chapters, authored by leading experts, provides a complete and essentially self-contained construction of 3-fold and 4-fold klt flips. A large part of the text is a digest of Shokurov's work in the field and a concise, complete and pedagogical proof of the existence of 3-fold flips is presented. The text includes a ten page glossary and is accessible to students and researchers in algebraic geometry.

Mechanical properties of ramie fiber reinforced epoxy lamina composite for socket prosthesis

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Tresna Soemardi

2010-10-01

Full Text Available This paper presents an investigation into the application of natural fiber composite especially ramie fiber reinforced epoxy lamina composite for socket prosthesis. The research focuses on the tensile and shear strength from ramie fiber reinforced epoxy lamina composite which will be applied as alternative material for socket prosthesis. The research based on American Society for Testing Material (ASTM standard D 3039/D 3039M for tensile strength and ASTM D 4255/D 4255M-83 for shear strength. The ramie fiber applied is a fiber continue 100 % Ne14'S with Epoxy Resin Bakelite EPR 174 as matrix and Epoxy Hardener V-140 as hardener. The sample composite test made by hand lay up method. Multiaxial characteristic from ramie fiber reinforced epoxy composite will be compared with ISO standard for plastic/polymer for health application and refers strength of material application at Prosthetics and Orthotics. The analysis was completed with the mode of the failure and the failure criterion observation by using Scanning Electron Microscope (SEM. Based on results of the research could be concluded that ramie fiber reinforced epoxy composite could be developed further as the alternative material for socket prosthesis on Vf 40-50%. Results of the research will be discussed in more detail in this paper.

RNA folding: structure prediction, folding kinetics and ion electrostatics.

Science.gov (United States)

Tan, Zhijie; Zhang, Wenbing; Shi, Yazhou; Wang, Fenghua

2015-01-01

Beyond the "traditional" functions such as gene storage, transport and protein synthesis, recent discoveries reveal that RNAs have important "new" biological functions including the RNA silence and gene regulation of riboswitch. Such functions of noncoding RNAs are strongly coupled to the RNA structures and proper structure change, which naturally leads to the RNA folding problem including structure prediction and folding kinetics. Due to the polyanionic nature of RNAs, RNA folding structure, stability and kinetics are strongly coupled to the ion condition of solution. The main focus of this chapter is to review the recent progress in the three major aspects in RNA folding problem: structure prediction, folding kinetics and ion electrostatics. This chapter will introduce both the recent experimental and theoretical progress, while emphasize the theoretical modelling on the three aspects in RNA folding.

Casein kinase II protein kinase is bound to lamina-matrix and phosphorylates lamin-like protein in isolated pea nuclei

Science.gov (United States)

Li, H.; Roux, S. J.

1992-01-01

A casein kinase II (CK II)-like protein kinase was identified and partially isolated from a purified envelope-matrix fraction of pea (Pisum sativum L.) nuclei. When [gamma-32P]ATP was directly added to the envelope-matrix preparation, the three most heavily labeled protein bands had molecular masses near 71, 48, and 46 kDa. Protein kinases were removed from the preparation by sequential extraction with Triton X-100, EGTA, 0.3 M NaCl, and a pH 10.5 buffer, but an active kinase still remained bound to the remaining lamina-matrix fraction after these treatments. This kinase had properties resembling CK II kinases previously characterized from animal and plant sources: it preferred casein as an artificial substrate, could use GTP as efficiently as ATP as the phosphoryl donor, was stimulated by spermine, was calcium independent, and had a catalytic subunit of 36 kDa. Some animal and plant CK II kinases have regulatory subunits near 29 kDa, and a lamina-matrix-bound protein of this molecular mass was recognized on immunoblot by anti-Drosophila CK II polyclonal antibodies. Also found associated with the envelope-matrix fraction of pea nuclei were p34cdc2-like and Ca(2+)-dependent protein kinases, but their properties could not account for the protein kinase activity bound to the lamina. The 71-kDa substrate of the CK II-like kinase was lamin A-like, both in its molecular mass and in its cross-reactivity with anti-intermediate filament antibodies. Lamin phosphorylation is considered a crucial early step in the entry of cells into mitosis, so lamina-bound CK II kinases may be important control points for cellular proliferation.

An examination of the damage tolerance enhancement of carbon/epoxy using an outer lamina of spectra (R)

Science.gov (United States)

Lance, D. G.; Nettles, A. T.

1991-01-01

Low velocity instrumented impact testing was utilized to examine the effects of an outer lamina of ultra-high molecular weight polyethylene (Spectra) on the damage tolerance of carbon epoxy composites. Four types of 16-ply quasi-isotropic panels (0, +45, 90, -45) were tested. Some panels contained no Spectra, while others had a lamina of Spectra bonded to the top (impacted side), bottom, or both sides of the composite plates. The specimens were impacted with energies up to 8.5 J. Force time plots and maximum force versus impact energy graphs were generated for comparison purposes. Specimens were also subjected to cross-sectional analysis and compression after impact tests. The results show that while the Spectra improved the maximum load that the panels could withstand before fiber breakage, the Spectra seemingly reduced the residual strength of the composites.

Development of a Natural Language Processing Engine to Generate Bladder Cancer Pathology Data for Health Services Research.

Science.gov (United States)

Schroeck, Florian R; Patterson, Olga V; Alba, Patrick R; Pattison, Erik A; Seigne, John D; DuVall, Scott L; Robertson, Douglas J; Sirovich, Brenda; Goodney, Philip P

2017-12-01

To take the first step toward assembling population-based cohorts of patients with bladder cancer with longitudinal pathology data, we developed and validated a natural language processing (NLP) engine that abstracts pathology data from full-text pathology reports. Using 600 bladder pathology reports randomly selected from the Department of Veterans Affairs, we developed and validated an NLP engine to abstract data on histology, invasion (presence vs absence and depth), grade, the presence of muscularis propria, and the presence of carcinoma in situ. Our gold standard was based on an independent review of reports by 2 urologists, followed by adjudication. We assessed the NLP performance by calculating the accuracy, the positive predictive value, and the sensitivity. We subsequently applied the NLP engine to pathology reports from 10,725 patients with bladder cancer. When comparing the NLP output to the gold standard, NLP achieved the highest accuracy (0.98) for the presence vs the absence of carcinoma in situ. Accuracy for histology, invasion (presence vs absence), grade, and the presence of muscularis propria ranged from 0.83 to 0.96. The most challenging variable was depth of invasion (accuracy 0.68), with an acceptable positive predictive value for lamina propria (0.82) and for muscularis propria (0.87) invasion. The validated engine was capable of abstracting pathologic characteristics for 99% of the patients with bladder cancer. NLP had high accuracy for 5 of 6 variables and abstracted data for the vast majority of the patients. This now allows for the assembly of population-based cohorts with longitudinal pathology data. Published by Elsevier Inc.

Cholera toxin B subunit labeling in lamina II of spinal cord dorsal horn following chronic inflammation in rats.

Science.gov (United States)

Ma, Qing Ping; Tian, Li

2002-07-26

We have investigated the effect of inflammation on the labeling pattern of cholera toxin B subunit (CTB)-conjugated horseradish peroxidase, an A-fiber marker, by an intra-sciatic nerve injection of the tracer. Following chronic inflammation in one hind paw in rats, there was substantial CTB labeling in lamina II of the spinal dorsal horn, which is normally absent. However, there was no change in the labeling pattern of wheat germ agglutinin or fluoride resistant acid phosphatase/thiamine monophosphatase, two C-fiber markers. The CTB labeling in lamina II after peripheral nerve injury has been interpreted as central sprouting of A-fibers or uptake of the tracer by injured C-fibers. Our results suggest that chronic inflammation and nerve injury may share some common mechanisms in generating allodynia and hyperalgesia.

Isolation and characterization of populations of mature and immature rat colonocytes

International Nuclear Information System (INIS)

Ahnen, D.J.; Reed, T.A.; Bozdech, J.M.

1988-01-01

A nonenzymatic method is described for the isolation of viable populations of mature and immature rat colonocytes. Histology was used to monitor colonocyte dissociation and to systematically characterize the amount of cross-contamination between populations of mature luminal cells and immature crypt cells. The mature coloncytes were 87 ± 9% pure with respect to contamination from cells from the lower half of the colonic crypt, and the immature populations were 98% pure with respect to contamination with cells from the upper half of the colonic crypt. Neither population contained significant numbers of cells from the lamina propria. Cell viability and synthetic function were maintained from 10-12 h in short-term culture. Alkaline phosphatase activity was 1.59 ± 0.01-fold higher in the mature cells than in the immature cells, and in vivo [ 3 H]thymidine incorporation was 2.9 ± 0.4-fold greater in the immature than the mature populations. These studies demonstrate that highly enriched populations of mature and immature rat colonocytes that maintain viability and synthetic function in short-term culture can be prepared. The intrinsic rate of protein synthesis is higher in immature colonocytes, and a shift to synthesis of a higher percentage of fucoproteins occurs during colonocyte differentiation. In contrast to result in the small intestine, only modest gradients of differentiation markers and cell surface protein expression were observed between mature and immature colonocytes

Some Comparative Anatomical and Histological Studies on the Laryngeal Cartilages of Buffaloes, Camels and Donkeys

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Eman A. Eshra

2016-01-01

Full Text Available Comparative studies concerned the upper air ways of domestic animals are few. So this study was carried out to compare between the larynx of buffaloes, camels and donkeys. The present investigation was carried out on 39 larynxes, 13 larynxes (7 males, 6 females of each species. Ten heads from each species were used for gross anatomical study; the remained three heads were used for the histological study. Results revealed that, the laryngeal cartilages of the three species were consisted of three single cartilages; the thyroid, the cricoid and the epiglottis, and two paired cartilages; the arytenoid and the corniculate. The cuneiform cartilages were paired cartilages present only in the larynx of the donkey. Thyroid, arytenoid and cricoid cartilages were of hyaline type, while the epiglottis, cuniform and corniculate cartilages and the vocal process of the arytenoid cartilage were of elastic type. The laryngeal epithelium of aditus laryngis, greater part of epiglottis and vocal folds was lined by non-keratinized stratified squamous epithelium. The remained parts of laryngeal epithelium from base of epiglottis and entire parts caudal to vocal folds were lined by pseudostratified columnar ciliated epithelium with goblet cells. The laryngeal glands of lamina propria were of mixed types in buffaloes and donkeys but in camels it was pure mucous glands. This study will fill a gap in the field of comparative anatomy and help other clinical investigation applied on these animals.

Biointegration of the osteo-odonto lamina in the modified osteo-odonto keratoprosthesis: engineering of tissue to restore lost vision.

Science.gov (United States)

Sawatari, Yoh; Marx, Robert E; Perez, Victor L; Parel, Jean-Marie

2013-01-01

The modified osteo-odonto keratoprosthesis (MOOKP) is a biologic keratoprosthesis that is used to treat a severely scarred cornea. The procedure involves multiple stages, including the transplantation of buccal mucosa to the damaged ocular surface and the implantation of an osteo-odonto lamina with a mounted polymethylmethacrylate lens. Among the keratoprostheses currently available, the MOOKP has proven to be the most effective based on the number of patients who have undergone the procedure and the duration of documented follow-up. Upon successful biointegration of the osteo-odonto lamina, the keratoprosthesis is able to resist resorption, provide stability, and prevent bacterial invasion and epithelial ingrowth. The effectiveness of the MOOKP is dependent on the anatomic and physiologic characteristics of the dental tissues and periodontal ligament.

Histologic Anatomy of the Anterior Vagina and Urethra.

Science.gov (United States)

Mazloomdoost, Donna; Westermann, Lauren B; Mutema, George; Crisp, Catrina C; Kleeman, Steven D; Pauls, Rachel N

Vaginal and urethral histology is important to understanding the pathophysiology of the pelvic floor. En bloc removal of 4 female cadaveric pelvises was performed, with 18 to 25 serial sections obtained from each. The vaginal and urethral lengths were divided into distal and proximal sections; urethra was divided into anterior and posterior segments as well. Innervation and vasculature were qualified as small and large and quantified per high-power field. The mean vaginal length was 7.45 cm, and the mean urethral length was 3.38 cm. A distinct vaginal fibromuscular layer was noted, without evidence of a dense sheet of continuous collagen. An epithelial, lamina propria, and muscular layer surrounded the urethral lumen. Adipose and loose fibroconnective tissue separated the urethra from the anterior vagina in 41% of slides. Nerves and vasculature were concentrated in the lamina propria. More small nerves and vessels were grossly seen compared with larger counterparts in both the vagina and urethra. No significant differences in layer thickness, innervation, or vasculature were observed along the vaginal length. The posterior urethra had greater innervation than did the anterior (P = 0.012). The distal posterior urethra had more large vessels than did the proximal posterior urethra (P = 0.03). No other differences were noted in urethral sections. A vaginal fibromuscular layer was confirmed, refuting a true fascia. Innervation and vasculature were quantitatively the same along the anterior vagina. However, the posterior urethra had greater innervation than did anterior and is most innervated proximally. Nerve and vascular histology may relate to pelvic floor disorder etiology.

Short article: Relapsing Whipple's disease: a case report and literature review.

Science.gov (United States)

Ruggiero, Elena; Zurlo, Anna; Giantin, Valter; Galeazzi, Francesca; Mescoli, Claudia; Nante, Giovanni; Petruzzellis, Florinda; Manzato, Enzo

2016-03-01

Whipple's disease is a rare infection caused by Tropheryma whipplei, a Gram-negative Bacillus usually found in macrophages of the lamina propria of the small intestine. The typical clinical manifestations of classic Whipple's disease are diarrhea, weight loss, malabsorption, abdominal pain, and arthralgia. The disease's laboratory diagnosis is currently based on duodenal biopsy. Treatment generally includes primary therapy for 2 weeks with intravenous antibiotics capable of reaching high levels in the cerebrospinal fluid, such as ceftriaxone, usually followed by treatment with oral cotrimoxazole for 1 year. Early diagnosis should enable appropriate treatment and improves the prognosis, and prolonged antibiotic treatment often leads to complete remission. Our case report focuses on a 72-year-old man who had been passing watery stools for 1-2 months, accompanied by low-grade fever. He reported profound asthenia, a weight loss of about 3 kg, and loss of appetite. Thirty years earlier (in 1984), he had been working as a horse keeper at a University Department of Agricultural and Veterinary Studies, where he had contracted Whipple's disease. Laboratory tests and microbiological studies led to a diagnosis of recurrent Whipple's disease. Esophagogastroduodenoscopy was performed under deep sedation. Biopsy samples obtained from the stomach and duodenum were stained with hematoxylin and eosin, Giemsa, and periodic acid-Schiff to identify any accumulation of typical periodic acid-Schiff-positive macrophages in the lamina propria. A specific quantitative real-time PCR assay using specific oligonucleotide probes for targeting repeated sequences of Tropheryma whipplei was also performed to detect its DNA in the duodenum samples.

Protective efficacy of Emblica against radiation and lead induced changes in the Jejunum of Swiss Albino mice

International Nuclear Information System (INIS)

Purohit, R.K.; Meena, Dinesh; Issran, Rakesh; Pyarelal; Jangir, Ashok Kumar

2014-01-01

Recently, increased interest has developed on search for potential drugs of plant origin which can quench the radiation induced free radicals and eliminate oxygen with minimum side effects. In view of the fact, present study was planned to evaluate the protective efficacy of Emblica against radiation and lead induced changes in jejunum of mice. For the purpose, six to eight weeks old male Swiss albino mice were selected and divided into seven groups on the basis of radiation, lead, combined treatment and drug treated. The values of total proteins, cholesterol, acid phosphatase activity, alkaline phosphatase activity, DNA and RNA were estimated. The values of total proteins, cholesterol, DNA and RNA decreased whereas acid phosphatase and alkaline phosphatase activity increased. After irradiation with various doses of gamma rays, histological changes depend upon the dose of radiation delivered. The important radio-lesions were looseness of musculatrue, hydropic degeneration in submucosa and lamina propria, hyperaemia and haemorrhage in submucosa, pyknotic cells, cytoplasmic degranulation and vacuolation, abnormal mitotic figures. Karyolysis, karyorrhexis and chromatolysis were also observed in crypt cells. Shortening and breaking of villus tips, leucocytic infiltration in lamina propria and cell debris in intestinal lumen were also noted. The number of goblet cells per crypt section also decreased in all the experimental groups. The value of the experimental groups was significantly lower than that of the control group. The biochemical finding indicated the drug treated section of living tissue showed slightly/no degenerative changes. The drug treated groups demonstrating the ability of Aloe vera to inhibit oxidative stress thus preventing tissue injury. (author)

An experimental study on radiation hazard to lingual papillae of dogs

International Nuclear Information System (INIS)

Tomiyama, Motoya

1986-01-01

The dorsal membrane of the tongue was exposed to X-rays in a total dose of 30 Gy (10 Gy/day at intervals of 3 days) in 19 young dogs. Light microscopic (LM) and scanning electron microscopic (SEM) observations were made on the first, 3rd, 5th, 9th, 15th, 35th, and 60th days. The animals had physical signs, including slow movement, loss of appetite, eye mucus or secretion, and weakness, on Days 5 and 9. On Day 15, their signs began to be recovered. On Day 9, the mucous membrane of the tongue closest to the irradiation tube turned to yellowish-brown, where erosion formation, without lingual papillae or epithelial layers, was seen on LM. The lamina propria of mucous membrane where inflammatory cells had infiltrated was exposed. On SEM, the erosive region contained mixed these inflammatory cells and debris of the epithelial layers. Irregularly arranged connective tissues and congested and dilated blood vessels were seen over the lamina propria of mucous membrane with extending atrophied and striated muscular fibers. Scanning electron microscopy of the normal colored mucous membrane showed some morphological changes in the filiform and fungiform papillae. The taste buds of fungiform papillae decreased in number, and showed atrophied and vacuolized cells. On Day 15, the repair of the epithelial layers was seen. However, cells remained atrophied and were arranged irregularly. On Day 35, some taste buds had still inflammatory cells. Complete recovery was attained 60 days after irradiation. (Namekawa, K.)

A new problem in inflammatory bladder diseases: Use of mobile phones!

Directory of Open Access Journals (Sweden)

Orhan Koca

2014-08-01

Full Text Available Purpose Technological developments provide a lot of conveniences to our lives. This issue is one of the risks that arise along with these conveniences. In our study we tried to understand the impact of electromagnetic waves from mobile phones on bladder tissue. Materials and Methods Twenty-one adult male albino rats were divided into three equal groups. Group 1 was exposed to electromagnetic wave for 8 hours per day for 20 days and then their bladders were taken off immediately. Group 2 was firstly exposed to electromagnetic wave for 8 hours per day for 20 days then secondly another for 20 days without exposition to electromagnetic wave and then their bladders were taken off. Group 3 was the control group and they were not exposed to electromagnetic wave. Results Under microscopic examination of bladder tissue, in the first group severe inflammatory cell infiltration was seen in lamina propria and muscle layer in contrast to intact urothelium. In the second group mild inflammatory cell infiltration was seen in lamina propria and muscle layer. The mean scores for the three groups were 5.5 ± 2.5, 0.8 ± 1.3 and 1.2 ± 1.5 respectively. Mean score of group 1 was statistically higher than others (p = 0.001. Conclusion Intensive use of mobile phones has negative impact on bladder tissue as well as the other organs. Keeping a minimum level of mobile phone use makes it easy to be kept under control of diseases in which inflammation is an etiologic factor.

Covering folded shapes

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Oswin Aichholzer

2014-05-01

Full Text Available Can folding a piece of paper flat make it larger? We explore whether a shape S must be scaled to cover a flat-folded copy of itself. We consider both single folds and arbitrary folds (continuous piecewise isometries \\(S\\to\\mathbb{R}^2\\. The underlying problem is motivated by computational origami, and is related to other covering and fixturing problems, such as Lebesgue's universal cover problem and force closure grasps. In addition to considering special shapes (squares, equilateral triangles, polygons and disks, we give upper and lower bounds on scale factors for single folds of convex objects and arbitrary folds of simply connected objects.

Air mass origins and troposphere-to-stratosphere exchange associated with mid-latitude cyclogenesis and tropopause folding inferred from Be-7 measurements

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Kritz, Mark A.; Rosner, Stefan W.; Danielsen, Edwin F.; Selkirk, Henry B.

1991-01-01

The 1984 extratropical mission of NASA's Stratosphere-Troposphere Exchange Project (STEP) studied cross-jet transport in regions of cyclogenesis and tropopause folding. Correlations of Be-7, ozone, water vapor, and potential vorticity measured on a NASA U-2 research aircraft flying in high shear regions above the jet core are indicative of mixing between the cyclonic and the anticyclonic sides of the jet and are consistent with the hypothesis that small-scale entrainments of upper tropospheric air into the lower stratosphere during cyclogenesis are important in maintaining the vertical gradients of Be-7, ozone, water vapor and other trace constituents in the lower few kilometers of the midlatitude stratosphere. Correlations between Be-7, and ozone suggest a lower tropical stratospheric origin for the ozone-poor lamina observed above the jet core.

Tongue and Taste Organ Biology and Function: Homeostasis Maintained by Hedgehog Signaling.

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Mistretta, Charlotte M; Kumari, Archana

2017-02-10

The tongue is an elaborate complex of heterogeneous tissues with taste organs of diverse embryonic origins. The lingual taste organs are papillae, composed of an epithelium that includes specialized taste buds, the basal lamina, and a lamina propria core with matrix molecules, fibroblasts, nerves, and vessels. Because taste organs are dynamic in cell biology and sensory function, homeostasis requires tight regulation in specific compartments or niches. Recently, the Hedgehog (Hh) pathway has emerged as an essential regulator that maintains lingual taste papillae, taste bud and progenitor cell proliferation and differentiation, and neurophysiological function. Activating or suppressing Hh signaling, with genetic models or pharmacological agents used in cancer treatments, disrupts taste papilla and taste bud integrity and can eliminate responses from taste nerves to chemical stimuli but not to touch or temperature. Understanding Hh regulation of taste organ homeostasis contributes knowledge about the basic biology underlying taste disruptions in patients treated with Hh pathway inhibitors.

Identifying and quantifying the stromal fibrosis in muscularis propria of colorectal carcinoma by multiphoton microscopy

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Chen, Sijia; Yang, Yinghong; Jiang, Weizhong; Feng, Changyin; Chen, Zhifen; Zhuo, Shuangmu; Zhu, Xiaoqin; Guan, Guoxian; Chen, Jianxin

2014-10-01

The examination of stromal fibrosis within colorectal cancer is overlooked, not only because the routine pathological examinations seem to focus more on tumour staging and precise surgical margins, but also because of the lack of efficient diagnostic methods. Multiphoton microscopy (MPM) can be used to study the muscularis stroma of normal and colorectal carcinoma tissue at the molecular level. In this work, we attempt to show the feasibility of MPM for discerning the microstructure of the normal human rectal muscle layer and fibrosis colorectal carcinoma tissue practicably. Three types of muscularis propria stromal fibrosis beneath the colorectal cancer infiltration were first observed through the MPM imaging system by providing intercellular microstructural details in fresh, unstained tissue samples. Our approach also presents the capability of quantifying the extent of stromal fibrosis from both amount and orientation of collagen, which may further characterize the severity of fibrosis. By comparing with the pathology analysis, these results show that the MPM has potential advantages in becoming a histological tool for detecting the stromal fibrosis and collecting prognosis evidence, which may guide subsequent therapy procedures for patients into good prognosis.

Transforming growth factor-beta messenger RNA and protein in murine colitis

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Whiting, C V; Williams, A M; Claesson, Mogens Helweg

2001-01-01

Using a CD4+ T-cell-transplanted SCID mouse model of colitis, we have analyzed TGF-beta transcription and translation in advanced disease. By in situ hybridization, the epithelium of both control and inflamed tissues transcribed TGF-beta1 and TGF-beta3 mRNAs, but both were expressed significantly...... farther along the crypt axis in disease. Control lamina propria cells transcribed little TGF-beta1 or TGF-beta3 mRNA, but in inflamed tissues many cells expressed mRNA for both isoforms. No TGF-beta2 message was detected in either control or inflamed tissues. Immunohistochemistry for latent and active TGF...

Lymphangioma circumscriptum, angiokeratoma, or superficial vascular ectasia with epithelial hyperplasia?

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Katsoulas, Nikolaos; Tosios, Konstantinos I; Argyris, Prokopios; Koutlas, Ioannis G; Sklavounou, Alexandra

2014-08-01

We report a case of lymphangioma circumscriptum (cavernous lymphangioma with epithelial hyperplasia) in a 12-year-old girl, presenting as a papillary tumor on the right dorsal side of her tongue. Microscopic examination found cavernous vascular channels lined by a single layer of CD31(+), podoplanin-positive, CD34(-) endothelial cells that occupied the papillary lamina propria and were accompanied by epithelial hyperplasia. A review of the literature on oral vascular tumors with epithelial hyperplasia, namely, lymphangioma circumscriptum and angiokeratoma, provided information that draws into question the use of these terms. Copyright © 2014 Elsevier Inc. All rights reserved.

Tumour necrosis factor-alpha (TNF-alpha) transcription and translation in the CD4+ T cell-transplanted scid mouse model of colitis

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Williams, A M; Whiting, C V; Bonhagen, K

1999-01-01

The adoptive transfer of activated CD4+ alpha/beta T cell blasts from the spleens of immunocompetent C.B-17+/+ or BALB/cdm2 mice into C.B-17scid/scid (scid) mice induces a colitis in the scid recipient within 8 weeks, which progresses to severe disease within 16 weeks. T cells isolated from......-labelled riboprobes were used. The prominent myeloid cell infiltrate in diseased tissues comprised F4/80+, Mac-l+ macrophages, neutrophils, dendritic cells and activated macrophages. TNF-alpha transcription and translation were associated with activated macrophages in the lamina propria. Activated macrophages...

Large-segment tracheal resection and interannular anastomosis with a tension-release technique in the dog.

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Dallman, M J; Bojrab, M J

1982-02-01

Tracheal resection and anastomosis were done on 7 dogs, and a modified procedure to provide optimum first-intention healing, minimum connective tissue proliferation, and optimum epithelialization was used. To test the integrity of the technique at high incision-line tensile forces, 15 to 17 tracheal rings were excised. Excessive tracheal manipulation resulted in an increased amount of lamina propria and submucosa collagenous tissue, increased size and number of blood vessels, and increased leukocytic invasion. Criteria for a successful anastomosis were minimum postoperative coughing, good mucosal apposition and epithelialization, and tracheal lumen diameters that were at least 80% of the preoperative measurement.

Primary Malignant Melanoma of the Genitourinary Tract with Upper and Lower Tracts Involvement

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Broderick Sutton

2013-01-01

Full Text Available A 91-year-old female presented with lower extremity swelling and shortness of breath. Laboratory analysis revealed elevations in blood urea nitrogen and creatinine along with microscopic hematuria on urinalysis. Computed tomography imaging showed moderate right hydronephrosis with dilatation of the proximal ureter with a soft tissue density at a transition point. Endoscopic evaluation revealed multiple raised, fleshy, and hemorrhagic masses throughout the bladder which are present in both ureters. Biopsy of these lesions revealed malignant melanoma invading the lamina propria. No dermatologic lesions were identified suggesting a primary malignant melanoma of the genitourinary system.

Cloaca prolapse and cystitis in green iguana (Iguana iguana) caused by a novel Cryptosporidium species.

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Kik, Marja J L; van Asten, Alphons J A M; Lenstra, Johannes A; Kirpensteijn, Jolle

2011-01-10

Cryptosporidium infection was associated with colitis and cystitis in 2 green iguanas (Iguana iguana). The disease was characterized by a chronic clinical course of cloacal prolapses and cystitis. Histological examination of the gut and urinary bladder showed numerous Cryptosporidium developmental stages on the surface of the epithelium with mixed inflammatory response in the lamina propria. Cryptosporidium oocysts were visualised in a cytological preparation of the faeces. Based on the small subunit ribosomal RNA gene the cryptosporidia were characterized as belonging to the intestinal cryptosporidial lineage, but not to Cryptosporidium saurophilum or Cryptosporidium serpentis species. Copyright © 2010 Elsevier B.V. All rights reserved.

Vigas de madeira laminada colada com laminas pre-classificadas de eucalyptus grandis

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Grohmann, Sandra Zampieri

1998-01-01

Dissertação (Mestrado) - Universidade Federal de Santa Catarina, Centro Tecnologico Comprovar a viabilidade de realização e desempenho de vigas de madeira laminada colada de Eucalyptus grandis classificadas de acordo com sua rigidez cujas lâminas estão divididas em classes de resistência onde o parâmetro de comparação é o módulo de elasticidade longitudinal. Para isso caracterizou-se física e mecanicamente a madeira e fez-se a classificação das laminas em grupos de acordo com o módulo de e...

Vocal Fold Paralysis

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... here Home » Health Info » Voice, Speech, and Language Vocal Fold Paralysis On this page: What is vocal fold ... Where can I get additional information? What is vocal fold paralysis? Structures involved in speech and voice production ...

Effect of ethanolic seed extract of Caesalpinia bonducella on female reproductive system of albino rat: a focus on antifertility efficacy

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Lilaram

2012-10-01

Full Text Available Objective: To evaluate the effect of oral administration of the ethanolic seed extract of Caesalpinia bonducella on the reproductive system in Wistar female albino rat. Methods: The study was divided into four groups. The group I received distilled water and served as vehicle treated control. Groups II, III and IV were orally administered 100, 200 and 300 mg/kg body weight dose of seed extract respectively, for 10 consecutive days and subsequently euthanized twenty four hours after the last dose. Results: The treatment prolonged the length of estrous cycle with significant increase in the duration of diestrus stage. The analysis of the principal hormones viz. LH, FSH, estradiol and progesterone showed significantly decreased levels in dose-dependant manner. Ovarian and uterine weight was significantly reduced as compared to that of the control group. Histoarchitectural observations revealed follicular atresia and degeneration of corpora lutea in ovary. Oviduct showed degeneration of mucosal folds and epithelium cells. Uterus showed evidence of degeneration of endometrial epithelium and endometrial glands. Lamina propria and muscularis layer of vagina were found slightly disorganized. Conclusions: It can be concluded that significant decrease in the hormone levels, reproductive organs weight and alterations in histoarchitecture of reproductive organs might be due to antiestrogenic nature of seed extract.

Anatomy and histology of the reproductive tract of the female Babirusa (Babyrousa celebensis).

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Ziehmer, B; Ogle, S; Signorella, A; Knorr, C; Macdonald, A A

2010-07-15

The anatomy and histology of the female reproductive tract of the Indonesian wild pig Babyrousa celebensis was studied by means of reproductive tracts obtained from seven animals aged between two and 22 years of age. The ovary appeared to have the ability to ovulate up to four ova at one time. However, the combined ovarian output seemed to average 1.86 ova. Ovulation can take place at any time from puberty to old age (22 years). The opening to the uterine tube was indicated by a 'flower-like' array of tall, broad epithelial 'petals' arising from the luminal surface of the funnel. The mucosal surfaces of these structures were covered in a mixture of prominent ciliated cells and bulbous secretory cells. The uterine tube followed a tightly convoluted path to the tip of the uterine horn. The uterus was proportionately short. The anatomical construction of the uterus was similar to those of other suids in that the columnar endometrium was heavily folded, there was a rich supply of uterine glands in the lamina propria, and the uterus was provided with a good blood supply. The cervix was thick walled and had a spiral lumen. Copyright 2010 Elsevier Inc. All rights reserved.

Estimation of Lamina Stiffness and Strength of Quadriaxial Non-Crimp Fabric Composites Based on Semi-Laminar Considerations

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Yong Cao

2016-09-01

Full Text Available Quadriaxial non-crimp fabric (QNCF composites are increasingly being used as primary structural materials in aircraft and automotive applications. Predicting the mechanical properties of QNCF lamina is more complicated compared with that of unidirectional (UD composites, because of the knitting connection of different plies. In this study, to analyze the stiffness and strength of the QNCF composites, a novel modeling strategy for the meso-scale features is presented based on the semi-laminar assumption. Following the view of the mechanical properties of single composite lamina, the complex QNCF layer is decomposed into individual plies. Three different representative unit cells along fiber direction are selected to predict the mechanical performance of QNCF, including in-plane stiffness, damage initiation, and stiffness degradation. To validate the developed modeling strategy, the predictions are compared with existing experimental results, where a good agreement is presented on the prediction of in-plane stiffness and strength. Furthermore, the effect of in-plane fiber distortion, induced by the stitching yarn on the mechanical properties, is studied.

Consequences of bisphenol a perinatal exposure on immune responses and gut barrier function in mice.

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Malaisé, Yann; Ménard, Sandrine; Cartier, Christel; Lencina, Corinne; Sommer, Caroline; Gaultier, Eric; Houdeau, Eric; Guzylack-Piriou, Laurence

2018-01-01

The potent immunomodulatory effect of the endocrine disruptor bisphenol A during development and consequences during life span are of increasing concern. Particular interests have been raised from animal studies regarding the risk of developing food intolerance and infection. We aimed to identify immune disorders in mice triggered by perinatal exposure to bisphenol A. Gravid mice were orally exposed to bisphenol (50 μg/kg body weight/day) from day 15 of pregnancy until weaning. Gut barrier function, local and systemic immunity were assessed in adult female offspring. Mice perinatally exposed to bisphenol showed a decrease in ileal lysozyme expression and a fall of fecal antimicrobial activity. In offspring mice exposed to bisphenol, an increase in colonic permeability was observed associated with an increase in interferon-γ level and a drop of colonic IgA + cells and fecal IgA production. Interestingly, altered frequency of innate lymphoid cells type 3 occurred in the small intestine, with an increase in IgG response against commensal bacteria in sera. These effects were related to a defect in dendritic cell maturation in the lamina propria and spleen. Activated and regulatory T cells were decreased in the lamina propria. Furthermore, perinatal exposure to bisphenol promoted a sharp increase in interferon-γ and interleukin-17 production in the intestine and elicited a T helper 17 profile in the spleen. To conclude, perinatal exposure to bisphenol weakens protective and regulatory immune functions in the intestine and at systemic level in adult offspring. The increased susceptibility to inflammatory response is an interesting lead supporting bisphenol-mediated adverse consequences on food reactions and infections.

IL-9 antibody injection suppresses the inflammation in colitis mice

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Yuan, Aping [Laboratory of Molecular Cell Biology, Department of Chemistry, Biotechnology and Food Science, Norwegian University of Life Sciences, Ås (Norway); Research Group of Gastrointestinal Diseases, The Second Affiliated Hospital of Zhengzhou University, Henan (China); Yang, Hang; Qi, Haili; Cui, Jing; Hua, Wei; Li, Can; Pang, Zhigang; Zheng, Wei [Research Group of Gastrointestinal Diseases, The Second Affiliated Hospital of Zhengzhou University, Henan (China); Cui, Guanglin, E-mail: guanglin.cui@yahoo.com [Research Group of Gastrointestinal Diseases, The Second Affiliated Hospital of Zhengzhou University, Henan (China); Faculty of Health, Nord University at Levanger (Norway)

2015-12-25

Diverse T help (Th) cells play a crucial role in the processing and maintaining of chronic inflammation as seen in ulcerative colitis (UC). Th9, a novel subset of Th cells that primarily produces interleukin (IL)-9, has recently been associated with the development of inflammatory diseases. In this study, we evaluated the presentation of Th9 cells in inflamed tissues of human and experimental mouse UC, and examined the therapeutic efficiency of anti Th9 cytokine IL-9 in the experimental mouse UC. Using immunohistochemistry (IHC), we evaluated the presentation of Th9 cells labelled by transcriptional factor PU.1 in both human and dextran sulfate sodium (DSS) induced mouse colitis biopsies. The results showed that increased PU.1 positive Th9 cells were mainly located in the lamina propria in relative with the controls, intraepithelial Th9 cells can also be observed but at low density. Double IHCs revealed that most of PU.1 positive cells were CD3 positive lymphocytes in human UC specimens. Anti-IL-9 antibody injection for 2 weeks reduced the severity of inflammation in DSS induced colitis mice. Our results suggest that The Th9/IL-9 is involved in the pathogenesis of UC. - Highlights: • The density of novel PU.1 positive Th9 cells is significantly increased in both human and mouse colitis tissues. • PU.1 positive Th9 cells are predominately located in the inflamed lamina propria in both human and mouse colitis tissues. • Blocking of Th9 cytokine IL-9 by antibody injection suppresses the severity of inflammation in the bowel in colitis mice. • Novel Th9 cells contribute to the pathogenesis of UC.

IL-9 antibody injection suppresses the inflammation in colitis mice

International Nuclear Information System (INIS)

Yuan, Aping; Yang, Hang; Qi, Haili; Cui, Jing; Hua, Wei; Li, Can; Pang, Zhigang; Zheng, Wei; Cui, Guanglin

2015-01-01

Diverse T help (Th) cells play a crucial role in the processing and maintaining of chronic inflammation as seen in ulcerative colitis (UC). Th9, a novel subset of Th cells that primarily produces interleukin (IL)-9, has recently been associated with the development of inflammatory diseases. In this study, we evaluated the presentation of Th9 cells in inflamed tissues of human and experimental mouse UC, and examined the therapeutic efficiency of anti Th9 cytokine IL-9 in the experimental mouse UC. Using immunohistochemistry (IHC), we evaluated the presentation of Th9 cells labelled by transcriptional factor PU.1 in both human and dextran sulfate sodium (DSS) induced mouse colitis biopsies. The results showed that increased PU.1 positive Th9 cells were mainly located in the lamina propria in relative with the controls, intraepithelial Th9 cells can also be observed but at low density. Double IHCs revealed that most of PU.1 positive cells were CD3 positive lymphocytes in human UC specimens. Anti-IL-9 antibody injection for 2 weeks reduced the severity of inflammation in DSS induced colitis mice. Our results suggest that The Th9/IL-9 is involved in the pathogenesis of UC. - Highlights: • The density of novel PU.1 positive Th9 cells is significantly increased in both human and mouse colitis tissues. • PU.1 positive Th9 cells are predominately located in the inflamed lamina propria in both human and mouse colitis tissues. • Blocking of Th9 cytokine IL-9 by antibody injection suppresses the severity of inflammation in the bowel in colitis mice. • Novel Th9 cells contribute to the pathogenesis of UC.

Defining progression in nonmuscle invasive bladder cancer: it is time for a new, standard definition.

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Lamm, Donald; Persad, Raj; Brausi, Maurizio; Buckley, Roger; Witjes, J Alfred; Palou, Joan; Böhle, Andreas; Kamat, Ashish M; Colombel, Marc; Soloway, Mark

2014-01-01

Despite being one of the most important clinical outcomes in nonmuscle invasive bladder cancer, there is currently no standard definition of disease progression. Major clinical trials and meta-analyses have used varying definitions or have failed to define this end point altogether. A standard definition of nonmuscle invasive bladder cancer progression as determined by reproducible and reliable procedures is needed. We examine current definitions of nonmuscle invasive bladder cancer progression, and propose a new definition that will be more clinically useful in determining patient prognosis and comparing treatment options. The IBCG (International Bladder Cancer Group) analyzed published clinical trials and meta-analyses that examined nonmuscle invasive bladder cancer progression as of December 2012. The limitations of the definitions of progression used in these trials were considered, as were additional parameters associated with the advancement of nonmuscle invasive bladder cancer. The most commonly used definition of nonmuscle invasive bladder cancer progression is an increase in stage from nonmuscle invasive to muscle invasive disease. Although this definition is clinically important, it fails to include other important parameters of advancing disease such as progression to lamina propria invasion and increase in grade. The IBCG proposes the definition of nonmuscle invasive bladder cancer progression as an increase in T stage from CIS or Ta to T1 (lamina propria invasion), development of T2 or greater or lymph node (N+) disease or distant metastasis (M1), or an increase in grade from low to high. Investigators should consider the use of this new definition to help standardize protocols and improve the reporting of progression. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Identification and characterization of novel gut-associated lymphoid tissues in rat small intestine.

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Hitotsumatsu, Osamu; Hamada, Hiromasa; Naganuma, Makoto; Inoue, Nagamu; Ishii, Hiromasa; Hibi, Toshifumi; Ishikawa, Hiromichi

2005-10-01

The crypt lamina propria of the mouse small intestine has been shown to harbor multiple tiny clusters filled with c-kit- and interleukin 7 receptor (IL-7R)-positive lympho-hemopoietic cells (cryptopatches; CPs). However, it has remained an open question whether similar lymphoid tissue are present in the gastrointesitinal tract in other animals. In the present study, we investigated whether the small intestine of rats harbored lymphoid tissues similar to mouse CPs. Immunohistochemical and flow cytometric analyses were carried out using various antibodies, including those to c-kit and IL-7R molecules. Lymphocyte-filled villi (LFVs), populated predominantly with c-kit- and IL-7 receptor (IL-7R)-positive cells and less with T cell receptor (TCR)-alphabeta T cells were found throughout the small intestine of young adult rats. Although LFVs were absent from fetal rat intestine, they were first detected at around 2 weeks after birth. Notably, in most LFVs that settled in the antimesenteric wall of the small intestine in young adult rats, immunoglobulin M-positive B cells were also detectable at the bottom of the LFVs. In aged rats, lymphocytes in some LFVs displayed a different phenotype, comprising a large B-cell area that included a germinal center. Thus, these clusters represent the first description of isolated lymphoid follicles (ILFs) in the rat small intestine. The present study provides the first evidence for c-kit- and IL-7R-positive lymphocyte clusters in the rat small intestine. Our data also indicating that LFVs and ILFs may constitute novel organized gut-associated lymphoid tissues in lamina propria of the rat small intestine.

Comparative immunohistochemical characterization of interstitial cells in the urinary bladder of human, guinea pig and pig.

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Steiner, Clara; Gevaert, Thomas; Ganzer, Roman; De Ridder, Dirk; Neuhaus, Jochen

2018-05-01

Interstitial cells (ICs) are thought to play a functional role in urinary bladder. Animal models are commonly used to elucidate bladder physiology and pathophysiology. However, inter-species comparative studies on ICs are rare. We therefore analyzed ICs and their distribution in the upper lamina propria (ULP), the deeper lamina propria (DLP) and the detrusor muscular layer (DET) of human, guinea pig (GP) and pig. Paraffin slices were examined by immunohistochemistry and 3D confocal immunofluorescence of the mesenchymal intermediate filament vimentin (VIM), alpha-smooth muscle actin (αSMA), platelet-derived growth factor receptor alpha (PDGFRα) and transient receptor potential cation channel A1 (TRPA1). Image stacks were processed for analysis using Huygens software; quantitative analysis was performed with Fiji macros. ICs were identified by immunoreactivity for VIM (excluding blood vessels). In all species ≥ 75% of ULP ICs were VIM + /PDGFRα + and ≥ 90% were VIM + /TRPA1 + . In human and pig ≥ 74% of ULP ICs were VIM + /αSMA + , while in GP the percentage differed significantly with only 37% VIM + /αSMA + ICs. Additionally, over 90% of αSMA + ICs were also TRPA1 + and PDGFRα + in human, GP and pig. In all three species, TRPA1 + and PDGFRα + ICs point to an active role for these cells in bladder physiology, regarding afferent signaling processes and signal modification. We hypothesize that decline in αSMA-positivity in GP reflects adaptation of bladder histology to smaller bladder size. In our experiments, pig bladder proved to be highly comparable to human urinary bladder and seems to provide safer interpretation of experimental findings than GP.

Anterograde axonal transport and intercellular transfer of WGA-HRP in trigeminal-innervated sensory receptors of rat incisive papilla.

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Chan, K Y; Byers, M R

1985-04-08

The ultrastructure and identification of WGA-HRP-labeled sensory receptors in the rat incisive papilla (the most anterior part of hard palate) were studied using semiserial thin sections. Various sensory receptors were organized according to three locations: dome region (ventral), chemosensory corpuscle region (medial to orifice of incisive canal), and lateral labium (apposing the incisive canal). In the dome region, the sensory receptors were localized in three sensory zones that were associated with surface ridges (one medial and two lateral). In each of these zones, intraepithelial receptor axons and Merkel receptors occurred in the epithelium, while simple unencapsulated corpuscles, glomerular-Meissner corpuscles, and incisive (encapsulated) corpuscles occurred in the lamina propria. In the chemosensory corpuscle region, chemosensory corpuscles and intraepithelial receptor axons were located in the epithelium, and incisive corpuscles were present in the lamina propria. In the lateral labium, only intraepithelial receptor axons were prominent. In all these sensory receptors, the preterminal axons and axon terminals were labeled with the tracer protein. In addition, some nonneuronal cells closely associated with the axon terminals were selectively labeled, e.g., terminal Schwann cells, lamellar Schwann cells, Merkel cells, corpuscular basal cells and chemosensory cells. Other adjacent cells were not labeled, e.g., unspecialized epithelial cells, capsular cells, corpuscular sustentacular cells, and fibroblasts. In both labeled axons and cells, WGA-HRP was incorporated into vesicles, tubules, and vacuolar organelles. The specific intercellular transfer of tracer protein may indicate trophic interactions between axon terminals and support cells in sensory receptors. The specific organization of multiple sensory receptors in the rat incisive papilla may provide a useful alternative system for studying somatosensory physiology.

Systems Modeling of Interactions between Mucosal Immunity and the Gut Microbiome during Clostridium difficile Infection.

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Andrew Leber

Full Text Available Clostridium difficile infections are associated with the use of broad-spectrum antibiotics and result in an exuberant inflammatory response, leading to nosocomial diarrhea, colitis and even death. To better understand the dynamics of mucosal immunity during C. difficile infection from initiation through expansion to resolution, we built a computational model of the mucosal immune response to the bacterium. The model was calibrated using data from a mouse model of C. difficile infection. The model demonstrates a crucial role of T helper 17 (Th17 effector responses in the colonic lamina propria and luminal commensal bacteria populations in the clearance of C. difficile and colonic pathology, whereas regulatory T (Treg cells responses are associated with the recovery phase. In addition, the production of anti-microbial peptides by inflamed epithelial cells and activated neutrophils in response to C. difficile infection inhibit the re-growth of beneficial commensal bacterial species. Computational simulations suggest that the removal of neutrophil and epithelial cell derived anti-microbial inhibitions, separately and together, on commensal bacterial regrowth promote recovery and minimize colonic inflammatory pathology. Simulation results predict a decrease in colonic inflammatory markers, such as neutrophilic influx and Th17 cells in the colonic lamina propria, and length of infection with accelerated commensal bacteria re-growth through altered anti-microbial inhibition. Computational modeling provides novel insights on the therapeutic value of repopulating the colonic microbiome and inducing regulatory mucosal immune responses during C. difficile infection. Thus, modeling mucosal immunity-gut microbiota interactions has the potential to guide the development of targeted fecal transplantation therapies in the context of precision medicine interventions.

Histological changes caused by experimental Riedeliella graciliflora (Leg. Papilionoideae poisoning in cattle and laboratory animals Alterações histológicas na intoxicação experimental por Riedeliella graciliflora (Leg. Papilionoideae em bovinos e animais de laboratório

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Franklin Riet-Correa

2001-03-01

Full Text Available Tissues from cattle, mice, rats and guinea pigs experimentally intoxicated by Riedeliella graciliflora were studied histologically. Cattle lymph nodes, spleen, Peyer patches and peribronchial lymphoid tissues had diffuse necrosis of lymphocytes, mainly in the germinal centers of the follicles. This lesion was less severe in laboratory animals. All species had severe enteritis with infiltration of the lamina propria by mononuclear cells. Some cells in this infiltrate were necrotic. Degeneration and necrosis of the epithelial cells, mainly in the tip of the villi, and detachment of the epithelial lining from the lamina propria were also observed. In the liver the trabecular structure was disrupted and the hepatocytes had some degree of individual necrosis and degeneration. A tubular nephrosis was observed in the kidneys. Liver, lung, kidney, intestine and lymph nodes had different degrees of congestion. Those lesions are similar than those caused by Polygala klotzschii, a plant that contains 5-metoxi-podophyllotoxin.Foi realizado um estudo histológico de bovinos, camundongos, ratos e coelhos intoxicados experimentalmente por Riedeliella graciliflora. Em bovinos os gânglios linfáticos, baço, placas de Peyer e tecido peribronquial apresentavam necrose do tecido linfático, afetando, principalmente, os centros germinativos dos folículos. Esta lesão foi menos severa em animais de laboratório. Em todas as espécies havia severa enterite e infiltração da lâmina propria do intestino por células mononucleares. Algumas destas células estavam necróticas. Degeneração e necrose do epitélio, principalmente na superfície das vilosidades, e descamação das células epiteliais foram, também, observadas. No fígado havia desorganização da estrutura trabecular e alguns hepatócitos apresentavam-se degenerados ou necróticos. Os rins apresentavam nefrose tubular. Diferentes graus de congestão foram observados no fígado, pulmão, rins

Tufting enteropathy with EpCAM mutation: case report

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Karla Lais Pêgas

2014-06-01

Full Text Available Tufting enteropathy (TE, also known as intestinal epithelial dysplasia (IED, is a rare congenital enteropathy related to an earlyonset of severe intractable diarrhea due to specific abnormalities of the intestinal epithelium and mutations of the EpCAM gene. TE is characterized by clinical and histological heterogeneity, such as with low or without mononuclear cell infiltration of the lamina propria, and abnormalities of basement membrane. TE can be associated with malformations, other epithelial diseases, or to abnormal enterocytes development and/or differentiation. The authors report a case of a Brazilian child with TE associated with c.556-14A>G mutation in the EpCAM gene (NM_002354.2.

Fatal Ichthyocotylurus erraticus infestation in Inca terns (Larosterna inca) in a zoological collection.

Science.gov (United States)

Pieters, Wouter; Hoyer, Mark; Verstappen, Frank; Wolters, Marno; Ijzer, Jooske; de Jong, Sara; Cremers, Herman; Kik, Marja

2014-06-01

In a breeding group of Inca terns (Larosterna inca), 14 birds died without antemortem signs of illness. Other than a poor body condition and a bloody cloaca, no symptoms were observed. Gross necropsy revealed severe segmental hemorrhagic enteritis with intralesional trematodes in most birds. Histopathologic examination revealed infiltration of lymphocytes, plasma cells, and granulocytes in the lamina propria of the duodenum and cross-sections of trematodes in the lumen. The parasites were identified as Ichthyocotylurus erraticus, a trematode of fish-eating birds. The cause of the infestation most likely was the feeding of unfrozen fresh fish. We describe the first case of a lethal I. erraticus infestation in Inca terns.

Angled Growth of the Dental Lamina Is Accompanied by Asymmetrical Expression of the WNT Pathway Receptor Frizzled 6

Czech Academy of Sciences Publication Activity Database

Putnová, Iveta; Dosedělová, Hana; Bryja, V.; Landová, Marie; Buchtová, Marcela; Štembírek, Jan

2017-01-01

Roč. 8, č. 1 (2017), č. článku 29. ISSN 1664-042X R&D Projects: GA ČR(CZ) GP14-29273P Institutional support: RVO:67985904 Keywords : FZD6 * successional dental lamina * WNT signaling Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Developmental biology Impact factor: 4.134, year: 2016

[Effectiveness of posterior intrasegmental fixation with pedicle screw-lamina hook system in treatment of lumbar spondylolysis].

Science.gov (United States)

Zhou, Zhongjie; Song, Yueming; Zeng, Jiancheng; Liu, Hao; Liu, Limin; Kong, Qingquan; Li, Tao; Gong, Quan

2013-03-01

To investigate the effectiveness of posterior intrasegmental fixation with pedicle screw-lamina hook system and bone grafting for lumbar spondylolysis. Between January 2005 and October 2009, 22 patients with lumbar spondylolysis underwent posterior intrasegmental fixation with pedicle screw-lamina hook system and bone grafting. There were 19 males and 3 females with an average age of 18.4 years (range, 12-26 years). The main symptom was low back pain with an average disease duration of 16 months (range, 8-56 months). The visual analogue scale (VAS) was 6.0 +/- 1.2 and Oswestry disability index (ODI) was 72.0% +/- 10.0% preoperatively. The X-ray films showed bilateral spondylolysis at L4 in 9 cases and at L5 in 13 cases. The range of motion (ROM) at upper and lower intervertebral spaces was (11.8 +/- 2.8) degrees and (14.1 +/- 1.9) degrees, respectively. All incisions healed by first intention. All patients were followed up 12-45 months (mean, 25 months). Low back pain was significantly alleviated after operation. The VAS score (0.3 +/- 0.5) and ODI (17.6% +/- 3.4%) were significantly decreased at last follow-up when compared with preoperative scores (P spondylolysis, having a high fusion rate, low complication rate, and maximum retention of lumbar ROM.

Improving protein fold recognition by extracting fold-specific features from predicted residue-residue contacts.

Science.gov (United States)

Zhu, Jianwei; Zhang, Haicang; Li, Shuai Cheng; Wang, Chao; Kong, Lupeng; Sun, Shiwei; Zheng, Wei-Mou; Bu, Dongbo

2017-12-01

Accurate recognition of protein fold types is a key step for template-based prediction of protein structures. The existing approaches to fold recognition mainly exploit the features derived from alignments of query protein against templates. These approaches have been shown to be successful for fold recognition at family level, but usually failed at superfamily/fold levels. To overcome this limitation, one of the key points is to explore more structurally informative features of proteins. Although residue-residue contacts carry abundant structural information, how to thoroughly exploit these information for fold recognition still remains a challenge. In this study, we present an approach (called DeepFR) to improve fold recognition at superfamily/fold levels. The basic idea of our approach is to extract fold-specific features from predicted residue-residue contacts of proteins using deep convolutional neural network (DCNN) technique. Based on these fold-specific features, we calculated similarity between query protein and templates, and then assigned query protein with fold type of the most similar template. DCNN has showed excellent performance in image feature extraction and image recognition; the rational underlying the application of DCNN for fold recognition is that contact likelihood maps are essentially analogy to images, as they both display compositional hierarchy. Experimental results on the LINDAHL dataset suggest that even using the extracted fold-specific features alone, our approach achieved success rate comparable to the state-of-the-art approaches. When further combining these features with traditional alignment-related features, the success rate of our approach increased to 92.3%, 82.5% and 78.8% at family, superfamily and fold levels, respectively, which is about 18% higher than the state-of-the-art approach at fold level, 6% higher at superfamily level and 1% higher at family level. An independent assessment on SCOP_TEST dataset showed consistent

Non-cylindrical fold growth in the Zagros fold and thrust belt (Kurdistan, NE-Iraq)

Science.gov (United States)

Bartl, Nikolaus; Bretis, Bernhard; Grasemann, Bernhard; Lockhart, Duncan

2010-05-01

The Zagros mountains extends over 1800 km from Kurdistan in N-Iraq to the Strait of Hormuz in Iran and is one of the world most promising regions for the future hydrocarbon exploration. The Zagros Mountains started to form as a result of the collision between the Eurasian and Arabian Plates, whose convergence began in the Late Cretaceous as part of the Alpine-Himalayan orogenic system. Geodetic and seismological data document that both plates are still converging and that the fold and thrust belt of the Zagros is actively growing. Extensive hydrocarbon exploration mainly focuses on the antiforms of this fold and thrust belt and therefore the growth history of the folds is of great importance. This work investigates by means of structural field work and quantitative geomorphological techniques the progressive fold growth of the Permam, Bana Bawi- and Safeen- Anticlines located in the NE of the city of Erbil in the Kurdistan region of Northern Iraq. This part of the Zagros fold and thrust belt belongs to the so-called Simply Folded Belt, which is dominated by gentle to open folding. Faults or fault related folds have only minor importance. The mechanical anisotropy of the formations consisting of a succession of relatively competent (massive dolomite and limestone) and incompetent (claystone and siltstone) sediments essentially controls the deformation pattern with open to gentle parallel folding of the competent layers and flexural flow folding of the incompetent layers. The characteristic wavelength of the fold trains is around 10 km. Due to faster erosion of the softer rock layers in the folded sequence, the more competent lithologies form sharp ridges with steeply sloping sides along the eroded flanks of the anticlines. Using an ASTER digital elevation model in combination with geological field data we quantified 250 drainage basins along the different limbs of the subcylindrical Permam, Bana Bawi- and Safeen- Anticlines. Geomorphological indices of the drainage

Digital radiographic evaluation of alveolar bone loss, density and lamina dura integrity on post splinting mandibular anterior with chronic periodontitis

Science.gov (United States)

Rafini, F.; Priaminiarti, M.; Sukardi, I.; Lessang, R.

2017-08-01

The healing of periodontal splinting can be detected both with clinical and radiographic examination. In this study, the alveolar bone was evaluated by radiographic digital periapical analysis. Periodontal tooth splinting is periodontal support therapy used to prevent periodontal injury during repair and regeneration of periodontal therapy. Radiographic digital periapical analysis of alveolar bone in the mandibular anterior region with chronic periodontitis and 2/3 cervical bone loss after three months of periodontal splinting. Eighty four proximal site (43 mesial and 41 distal) from 16 patients with chronic periodontitis and treated with spinting were examined by taking periapical digital radiographic at day 1 and 91. The bone loss, bone density and utility of lamina dura were evaluated. The statistical analysis after three months evaluation using T-test for bone loss, Wilcoxon sign rank test for bone density and utility lamina dura showed no significantly differences (pchronic periodontitis with 2/3 alveolar bone loss after three months splinting.

Estimate of compressive strength of an unidirectional composite lamina using cross-ply and angle-ply laminates

OpenAIRE

Scafè, M.; Raiteri, G.; Brentari, A.; Dlacic, R.; Troiani, E.; Falaschetti, M. P.; Besseghini, E.

2014-01-01

In this work has been estimated the compressive strength of a unidirectional lamina of a carbon/epoxy composite material, using the cross-ply and angle-ply laminates. Over the years various methods have been developed to deduce compressive properties of composite materials reinforced with long fibres. Each of these methods is characterized by a specific way of applying load to the specimen. The method chosen to perform the compression tests is the Wyoming Combined Loading Compr...

The Risk of Vocal Fold Atrophy after Serial Corticosteroid Injections of the Vocal Fold.

Science.gov (United States)

Shi, Lucy L; Giraldez-Rodriguez, Laureano A; Johns, Michael M

2016-11-01

The aim of this study was to illustrate the risk of vocal fold atrophy in patients who receive serial subepithelial steroid injections for vocal fold scar. This study is a retrospective case report of two patients who underwent a series of weekly subepithelial infusions of 10 mg/mL dexamethasone for benign vocal fold lesion. Shortly after the procedures, both patients developed a weak and breathy voice. The first patient was a 53-year-old man with radiation-induced vocal fold stiffness. Six injections were performed unilaterally, and 1 week later, he developed unilateral vocal fold atrophy with new glottal insufficiency. The second patient was a 67-year-old woman with severe vocal fold inflammation related to laryngitis and calcinosis, Raynaud's phenomenon, esophagean dysmotility, sclerodactyly, and telangiectasia (CREST) syndrome. Five injections were performed bilaterally, and 1 week later, she developed bilateral vocal fold atrophy with a large midline glottal gap during phonation. In both cases, the steroid-induced vocal atrophy resolved spontaneously after 4 months. Serial subepithelial steroid infusions of the vocal folds, although safe in the majority of patients, carry the risk of causing temporary vocal fold atrophy when given at short intervals. Copyright © 2016 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

Activation of stretch-activated channels and maxi-K+ channels by membrane stress of human lamina cribrosa cells.

LENUS (Irish Health Repository)

Irnaten, Mustapha

2009-01-01

The lamina cribrosa (LC) region of the optic nerve head is considered the primary site of damage in glaucomatous optic neuropathy. Resident LC cells have a profibrotic potential when exposed to cyclical stretch. However, the mechanosensitive mechanisms of these cells remain unknown. Here the authors investigated the effects of membrane stretch on cell volume change and ion channel activity and examined the associated changes in intracellular calcium ([Ca(2+)](i)).

NoFold: RNA structure clustering without folding or alignment.

Science.gov (United States)

Middleton, Sarah A; Kim, Junhyong

2014-11-01

Structures that recur across multiple different transcripts, called structure motifs, often perform a similar function-for example, recruiting a specific RNA-binding protein that then regulates translation, splicing, or subcellular localization. Identifying common motifs between coregulated transcripts may therefore yield significant insight into their binding partners and mechanism of regulation. However, as most methods for clustering structures are based on folding individual sequences or doing many pairwise alignments, this results in a tradeoff between speed and accuracy that can be problematic for large-scale data sets. Here we describe a novel method for comparing and characterizing RNA secondary structures that does not require folding or pairwise alignment of the input sequences. Our method uses the idea of constructing a distance function between two objects by their respective distances to a collection of empirical examples or models, which in our case consists of 1973 Rfam family covariance models. Using this as a basis for measuring structural similarity, we developed a clustering pipeline called NoFold to automatically identify and annotate structure motifs within large sequence data sets. We demonstrate that NoFold can simultaneously identify multiple structure motifs with an average sensitivity of 0.80 and precision of 0.98 and generally exceeds the performance of existing methods. We also perform a cross-validation analysis of the entire set of Rfam families, achieving an average sensitivity of 0.57. We apply NoFold to identify motifs enriched in dendritically localized transcripts and report 213 enriched motifs, including both known and novel structures. © 2014 Middleton and Kim; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

Glycoprotein folding and quality-control mechanisms in protein-folding diseases

Directory of Open Access Journals (Sweden)

Sean P. Ferris

2014-03-01

Full Text Available Biosynthesis of proteins – from translation to folding to export – encompasses a complex set of events that are exquisitely regulated and scrutinized to ensure the functional quality of the end products. Cells have evolved to capitalize on multiple post-translational modifications in addition to primary structure to indicate the folding status of nascent polypeptides to the chaperones and other proteins that assist in their folding and export. These modifications can also, in the case of irreversibly misfolded candidates, signal the need for dislocation and degradation. The current Review focuses on the glycoprotein quality-control (GQC system that utilizes protein N-glycosylation and N-glycan trimming to direct nascent glycopolypeptides through the folding, export and dislocation pathways in the endoplasmic reticulum (ER. A diverse set of pathological conditions rooted in defective as well as over-vigilant ER quality-control systems have been identified, underlining its importance in human health and disease. We describe the GQC pathways and highlight disease and animal models that have been instrumental in clarifying our current understanding of these processes.

The pulmonary pseudonodule: Characteristic features of a normal variant due to a bone thickening at the junction of the laminae and posterior spine

International Nuclear Information System (INIS)

Homer, M.J.

1981-01-01

The normal thickening of bone at the junction of the laminae and posterior spine should not be confused with a patholigc process. Its appearance on the plain radiograph and computed tomography is pathognomonic. (orig.)

Irinotecan (CPT-11)-induced elevation of bile acids potentiates suppression of IL-10 expression

International Nuclear Information System (INIS)

Fang, Zhong-Ze; Zhang, Dunfang; Cao, Yun-Feng; Xie, Cen; Lu, Dan; Sun, Dong-Xue; Tanaka, Naoki; Jiang, Changtao; Chen, Qianming; Chen, Yu; Wang, Haina; Gonzalez, Frank J.

2016-01-01

Irinotecan (CPT-11) is a first-line anti-colon cancer drug, however; CPT-11-induced toxicity remains a key factor limiting its clinical application. To search for clues to the mechanism of CPT-11-induced toxicity, metabolomics was applied using ultra-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry. Intraperitoneal injection of 50 mg/kg of CPT-11 induced loss of body weight, and intestine toxicity. Changes in gallbladder morphology suggested alterations in bile acid metabolism, as revealed at the molecular level by analysis of the liver, bile, and ileum metabolomes between the vehicle-treated control group and the CPT-11-treated group. Analysis of immune cell populations further showed that CPT-11 treatment significantly decreased the IL-10-producing CD4 T cell frequency in intestinal lamina propria lymphocytes, but not in spleen or mesenteric lymph nodes. In vitro cell culture studies showed that the addition of bile acids deoxycholic acid and taurodeoxycholic acid accelerated the CPT-11-induced suppression of IL-10 secretion by activated CD4 + naive T cells isolated from mouse splenocytes. These results showed that CPT-11 treatment caused metabolic changes in the composition of bile acids that altered CPT-11-induced suppression of IL-10 expression. - Highlights: • CPT-11 is an effective anticancer drug, but induced toxicity limits its application in the clinic. • CPT-11 decreased IL-10-producing CD4 T cell frequency in intestinal lamina propria lymphocytes. • CPT-11 altered the composition of bile acid metabolites, notably DCA and TDCA in liver, bile and intestine. • DCA and TDCA potentiated CPT-11-induced suppression of IL-10 secretion by active CD4 + naive T cells.

Persistent changes in circulating and intestinal γδ T cell subsets, invariant natural killer T cells and mucosal-associated invariant T cells in children and adults with coeliac disease.

Science.gov (United States)

Dunne, Margaret R; Elliott, Louise; Hussey, Seamus; Mahmud, Nasir; Kelly, Jacinta; Doherty, Derek G; Feighery, Conleth F

2013-01-01

Coeliac disease is a chronic small intestinal immune-mediated enteropathy precipitated by exposure to dietary gluten in genetically predisposed individuals. The only current therapy is a lifelong gluten free diet. While much work has focused on the gliadin-specific adaptive immune response in coeliac disease, little is understood about the involvement of the innate immune system. Here we used multi-colour flow cytometry to determine the number and frequency of γδ T cells (Vδ1, Vδ2 and Vδ3 subsets), natural killer cells, CD56(+) T cells, invariant NKT cells, and mucosal associated invariant T cells, in blood and duodenum from adults and children with coeliac disease and healthy matched controls. All circulating innate lymphocyte populations were significantly decreased in adult, but not paediatric coeliac donors, when compared with healthy controls. Within the normal small intestine, we noted that Vδ3 cells were the most abundant γδ T cell type in the adult epithelium and lamina propria, and in the paediatric lamina propria. In contrast, patients with coeliac disease showed skewing toward a predominant Vδ1 profile, observed for both adult and paediatric coeliac disease cohorts, particularly within the gut epithelium. This was concurrent with decreases in all other gut lymphocyte subsets, suggesting a specific involvement of Vδ1 cells in coeliac disease pathogenesis. Further analysis showed that γδ T cells isolated from the coeliac gut display an activated, effector memory phenotype, and retain the ability to rapidly respond to in vitro stimulation. A profound loss of CD56 expression in all lymphocyte populations was noted in the coeliac gut. These findings demonstrate a sustained aberrant innate lymphocyte profile in coeliac disease patients of all ages, persisting even after elimination of gluten from the diet. This may lead to impaired immunity, and could potentially account for the increased incidence of autoimmune co-morbidity.

Irinotecan (CPT-11)-induced elevation of bile acids potentiates suppression of IL-10 expression

Energy Technology Data Exchange (ETDEWEB)

Fang, Zhong-Ze [Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD (United States); Department of Toxicology, School of Public Health, Tianjin Medical University, Tianjin (China); Joint Center for Translational Medicine, Dalian Institute of Chemical Physics, Chinese Academy of Sciences and First Affiliated Hospital of Liaoning Medical University, Dalian (China); Zhang, Dunfang [State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu (China); Cao, Yun-Feng [Joint Center for Translational Medicine, Dalian Institute of Chemical Physics, Chinese Academy of Sciences and First Affiliated Hospital of Liaoning Medical University, Dalian (China); Xie, Cen [Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD (United States); Lu, Dan [Department of Immunology, Tianjin Key Laboratory of Cellular and Molecular Immunology, Tianjin Medical University, Tianjin (China); Sun, Dong-Xue; Tanaka, Naoki; Jiang, Changtao [Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD (United States); Chen, Qianming; Chen, Yu [State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu (China); Wang, Haina [School of Pharmaceutical Sciences, Shandong University, Jinan (China); Gonzalez, Frank J., E-mail: gonzalef@mail.nih.gov [Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD (United States)

2016-01-15

Irinotecan (CPT-11) is a first-line anti-colon cancer drug, however; CPT-11-induced toxicity remains a key factor limiting its clinical application. To search for clues to the mechanism of CPT-11-induced toxicity, metabolomics was applied using ultra-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry. Intraperitoneal injection of 50 mg/kg of CPT-11 induced loss of body weight, and intestine toxicity. Changes in gallbladder morphology suggested alterations in bile acid metabolism, as revealed at the molecular level by analysis of the liver, bile, and ileum metabolomes between the vehicle-treated control group and the CPT-11-treated group. Analysis of immune cell populations further showed that CPT-11 treatment significantly decreased the IL-10-producing CD4 T cell frequency in intestinal lamina propria lymphocytes, but not in spleen or mesenteric lymph nodes. In vitro cell culture studies showed that the addition of bile acids deoxycholic acid and taurodeoxycholic acid accelerated the CPT-11-induced suppression of IL-10 secretion by activated CD4{sup +} naive T cells isolated from mouse splenocytes. These results showed that CPT-11 treatment caused metabolic changes in the composition of bile acids that altered CPT-11-induced suppression of IL-10 expression. - Highlights: • CPT-11 is an effective anticancer drug, but induced toxicity limits its application in the clinic. • CPT-11 decreased IL-10-producing CD4 T cell frequency in intestinal lamina propria lymphocytes. • CPT-11 altered the composition of bile acid metabolites, notably DCA and TDCA in liver, bile and intestine. • DCA and TDCA potentiated CPT-11-induced suppression of IL-10 secretion by active CD4{sup +} naive T cells.

CXCR3-dependent CD4⁺ T cells are required to activate inflammatory monocytes for defense against intestinal infection.

Directory of Open Access Journals (Sweden)

Sara B Cohen

Full Text Available Chemokines and their receptors play a critical role in orchestrating immunity to microbial pathogens, including the orally acquired Th1-inducing protozoan parasite Toxoplasma gondii. Chemokine receptor CXCR3 is associated with Th1 responses, and here we use bicistronic CXCR3-eGFP knock-in reporter mice to demonstrate upregulation of this chemokine receptor on CD4⁺ and CD8⁺ T lymphocytes during Toxoplasma infection. We show a critical role for CXCR3 in resistance to the parasite in the intestinal mucosa. Absence of the receptor in Cxcr3⁻/⁻ mice resulted in selective loss of ability to control T. gondii specifically in the lamina propria compartment. CD4⁺ T cells were impaired both in their recruitment to the intestinal lamina propria and in their ability to secrete IFN-γ upon stimulation. Local recruitment of CD11b⁺Ly6C/G⁺ inflammatory monocytes, recently reported to be major anti-Toxoplasma effectors in the intestine, was not impacted by loss of CXCR3. However, inflammatory monocyte activation status, as measured by dual production of TNF-α and IL-12, was severely impaired in Cxcr3⁻/⁻ mice. Strikingly, adoptive transfer of wild-type but not Ifnγ⁻/⁻ CD4⁺ T lymphocytes into Cxcr3⁻/⁻ animals prior to infection corrected the defect in inflammatory macrophage activation, simultaneously reversing the susceptibility phenotype of the knockout animals. Our results establish a central role for CXCR3 in coordinating innate and adaptive immunity, ensuring generation of Th1 effectors and their trafficking to the frontline of infection to program microbial killing by inflammatory monocytes.

Characterization of New Zealand White Rabbit Gut-Associated Lymphoid Tissues and Use as Viral Oncology Animal Model.

Science.gov (United States)

Haines, Robyn A; Urbiztondo, Rebeccah A; Haynes, Rashade A H; Simpson, Elaine; Niewiesk, Stefan; Lairmore, Michael D

2016-01-01

Rabbits have served as a valuable animal model for the pathogenesis of various human diseases, including those related to agents that gain entry through the gastrointestinal tract such as human T cell leukemia virus type 1. However, limited information is available regarding the spatial distribution and phenotypic characterization of major rabbit leukocyte populations in mucosa-associated lymphoid tissues. Herein, we describe the spatial distribution and phenotypic characterization of leukocytes from gut-associated lymphoid tissues (GALT) from 12-week-old New Zealand White rabbits. Our data indicate that rabbits have similar distribution of leukocyte subsets as humans, both in the GALT inductive and effector sites and in mesenteric lymph nodes, spleen, and peripheral blood. GALT inductive sites, including appendix, cecal tonsil, Peyer's patches, and ileocecal plaque, had variable B cell/T cell ratios (ranging from 4.0 to 0.8) with a predominance of CD4 T cells within the T cell population in all four tissues. Intraepithelial and lamina propria compartments contained mostly T cells, with CD4 T cells predominating in the lamina propria compartment and CD8 T cells predominating in the intraepithelial compartment. Mesenteric lymph node, peripheral blood, and splenic samples contained approximately equal percentages of B cells and T cells, with a high proportion of CD4 T cells compared with CD8 T cells. Collectively, our data indicate that New Zealand White rabbits are comparable with humans throughout their GALT and support future studies that use the rabbit model to study human gut-associated disease or infectious agents that gain entry by the oral route. © The Author 2016. Published by Oxford University Press on behalf of the Institute for Laboratory Animal Research. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Systemic and Terminal Ileum Mucosal Immunity Elicited by Oral Immunization With the Ty21a Typhoid Vaccine in HumansSummary

Directory of Open Access Journals (Sweden)

Jayaum S. Booth

2017-11-01

Full Text Available Background & Aims: Systemic cellular immunity elicited by the Ty21a oral typhoid vaccine has been extensively characterized. However, very limited data are available in humans regarding mucosal immunity at the site of infection (terminal ileum [TI]. Here we investigated the host immunity elicited by Ty21a immunization on terminal ileum–lamina propria mononuclear cells (LPMC and peripheral blood in volunteers undergoing routine colonoscopy. Methods: We characterized LPMC-T memory (TM subsets and assessed Salmonella enterica serovar Typhi (S Typhi–specific responses by multichromatic flow cytometry. Results: No differences were observed in cell yields and phenotypes in LPMC CD8+-TM subsets following Ty21a immunization. However, Ty21a immunization elicited LPMC CD8+ T cells exhibiting significant S Typhi–specific responses (interferon-γ, tumor necrosis factor-α, interleukin-17A, and/or CD107a in all major TM subsets (T-effector/memory [TEM], T-central/memory, and TEM-CD45RA+, although each TM subset exhibited unique characteristics. We also investigated whether Ty21a immunization elicited S Typhi–specific multifunctional effectors in LPMC CD8+ TEM. We observed that LPMC CD8+ TEM responses were mostly multifunctional, except for those cells exhibiting the characteristics associated with cytotoxic responses. Finally, we compared mucosal with systemic responses and made the important observation that LPMC CD8+ S Typhi–specific responses were unique and distinct from their systemic counterparts. Conclusions: This study provides the first demonstration of S Typhi–specific responses in the human terminal ileum mucosa and provides novel insights into the generation of mucosal immune responses following oral Ty21a immunization. Keywords: Lamina Propria Mononuclear Cells, Multifunctional T Cells, CD8+-T Memory Cells, Typhoid, Vaccines

Persistent changes in circulating and intestinal γδ T cell subsets, invariant natural killer T cells and mucosal-associated invariant T cells in children and adults with coeliac disease.

Directory of Open Access Journals (Sweden)

Margaret R Dunne

Full Text Available Coeliac disease is a chronic small intestinal immune-mediated enteropathy precipitated by exposure to dietary gluten in genetically predisposed individuals. The only current therapy is a lifelong gluten free diet. While much work has focused on the gliadin-specific adaptive immune response in coeliac disease, little is understood about the involvement of the innate immune system. Here we used multi-colour flow cytometry to determine the number and frequency of γδ T cells (Vδ1, Vδ2 and Vδ3 subsets, natural killer cells, CD56(+ T cells, invariant NKT cells, and mucosal associated invariant T cells, in blood and duodenum from adults and children with coeliac disease and healthy matched controls. All circulating innate lymphocyte populations were significantly decreased in adult, but not paediatric coeliac donors, when compared with healthy controls. Within the normal small intestine, we noted that Vδ3 cells were the most abundant γδ T cell type in the adult epithelium and lamina propria, and in the paediatric lamina propria. In contrast, patients with coeliac disease showed skewing toward a predominant Vδ1 profile, observed for both adult and paediatric coeliac disease cohorts, particularly within the gut epithelium. This was concurrent with decreases in all other gut lymphocyte subsets, suggesting a specific involvement of Vδ1 cells in coeliac disease pathogenesis. Further analysis showed that γδ T cells isolated from the coeliac gut display an activated, effector memory phenotype, and retain the ability to rapidly respond to in vitro stimulation. A profound loss of CD56 expression in all lymphocyte populations was noted in the coeliac gut. These findings demonstrate a sustained aberrant innate lymphocyte profile in coeliac disease patients of all ages, persisting even after elimination of gluten from the diet. This may lead to impaired immunity, and could potentially account for the increased incidence of autoimmune co-morbidity.

Folding of multidomain proteins: biophysical consequences of tethering even in apparently independent folding.

Science.gov (United States)

Arviv, Oshrit; Levy, Yaakov

2012-12-01

Most eukaryotic and a substantial fraction of prokaryotic proteins are composed of more than one domain. The tethering of these evolutionary, structural, and functional units raises, among others, questions regarding the folding process of conjugated domains. Studying the folding of multidomain proteins in silico enables one to identify and isolate the tethering-induced biophysical determinants that govern crosstalks generated between neighboring domains. For this purpose, we carried out coarse-grained and atomistic molecular dynamics simulations of two two-domain constructs from the immunoglobulin-like β-sandwich fold. Each of these was experimentally shown to behave as the "sum of its parts," that is, the thermodynamic and kinetic folding behavior of the constituent domains of these constructs seems to occur independently, with the folding of each domain uncoupled from the folding of its partner in the two-domain construct. We show that the properties of the individual domains can be significantly affected by conjugation to another domain. The tethering may be accompanied by stabilizing as well as destabilizing factors whose magnitude depends on the size of the interface, the length, and the flexibility of the linker, and the relative stability of the domains. Accordingly, the folding of a multidomain protein should not be viewed as the sum of the folding patterns of each of its parts, but rather, it involves abrogating several effects that lead to this outcome. An imbalance between these effects may result in either stabilization or destabilization owing to the tethering. Copyright © 2012 Wiley Periodicals, Inc.

Tissue distribution of epimucosally applied 3H DNFB: an autoradiographic study

International Nuclear Information System (INIS)

Warfvinge, G.; Larsson, Aa.

1988-01-01

The distribution of 3 H-labeled 2,4-dinitrofluorobenzene (DNFB) has been autoradiographically investigated in buccal mucosa after topical application to sensitized or nonsensitized rats. The rats were killed between 3 min and 24 h after challenge. No significant labeling pattern differences were found between plastic embedded and frozen sections. Surface epithelium was heavily labeled and labeled cells were observed in the lamina propria shortly (3-6 min) after application. These cells were clearly dendritic. Specific accumulation of hapten in epithelial Langerhans cells (LC) could not be clearly demonstrated. The connective tissue labeling gradually diminished and at 24 h post-elicitation, remaining label could be detected only in the epithelial surface layers. (author)

Cystoscopic optical coherence tomography for urinary bladder imaging in vivo

Science.gov (United States)

Wang, Z. G.; Adler, H.; Chan, D.; Jain, A.; Xie, H. K.; Wu, Z. L.; Pan, Y. T.

2006-02-01

This paper summarizes the development of new 2D MEMS mirrors and the pertinent modification to improve OCT endoscopic catheter packaging suitable for in vivo imaging diagnosis of bladder cancers. Comparative study of the newly developed endocopic OCT versus the bench-top OCT is presented. Results of in vivo OCT cystoscopy based on a porcine acute inflammation model are presented to compare time-domain OCT and spectral-domain OCT for in vivo imaging. In addition, results of spectral-domain Doppler OCT are presented to image blood flow in the lamina propria of the bladder. The results of our in vivo animal study using the presented OCT endoscope are discussed for potential problems in the future clinical applications.

Intestinal epithelium in inflammatory bowel disease

Directory of Open Access Journals (Sweden)

Mehmet eCoskun

2014-08-01

Full Text Available The intestinal epithelium has a strategic position as a protective physical barrier to luminal microbiota and actively contributes to the mucosal immune system. This barrier is mainly formed by a monolayer of specialized intestinal epithelial cells (IECs that are crucial in maintaining intestinal homeostasis. Therefore, dysregulation within the epithelial layer can increase intestinal permeability, lead to abnormalities in interactions between IECs and immune cells in underlying lamina propria, and disturb the intestinal immune homeostasis, all of which are linked to the clinical disease course of inflammatory bowel disease (IBD. Understanding the role of the intestinal epithelium in IBD pathogenesis might contribute to an improved knowledge of the inflammatory processes and the identification of potential therapeutic targets.

Pathogenicity of a strain of Yersinia pseudotuberculosis isolated from a pig with porcine colitis syndrome.

Science.gov (United States)

Neef, N A; Lysons, R J

1994-07-16

A strain of Yersinia pseudotuberculosis (NCTC 12718), isolated from a seven-week-old pig suffering from an ulcerative typhlocolitis, was inoculated orally into 16 growing pigs in two separate experiments. At necropsy 10 days later, typhlocolitis was present in nine of the pigs, and it was accompanied by diarrhoea in four cases. In both the original case and in the experimental pigs, the typhlocolitis was characterised by microabscesses of the lamina propria, frequently involving ulceration or erosion of the surface epithelium. The organism was of serotype IIa, which has not been isolated previously from pigs in the United Kingdom. Y pseudotuberculosis may be the aetiological agent responsible in some cases of porcine colitis syndrome.

Nuclear lamina and nuclear matrix organization in sperm pronuclei assembled in Xenopus egg extract.

Science.gov (United States)

Zhang, C; Jenkins, H; Goldberg, M W; Allen, T D; Hutchison, C J

1996-09-01

Nuclear lamina and matrices were prepared from sperm pronuclei assembled in Xenopus egg extracts using a fractionation and extraction procedure. Indirect immunofluorescence revealed that while chromatin was efficiently removed from nuclei during the extraction procedure, the distribution of lamins was unaffected. Consistent with this data, the amount of lamin B3, determined by immunoblotting, was not affected through the extraction procedure. Nuclear matrices were visualised in DGD sections by TEM. Within these sections filaments were observed both at the boundary of the nucleus (the lamina) and within the body of the nucleus (internal nuclear matrix filaments). To improve resolution, nuclear matrices were also prepared as whole mounts and viewed using field emission in lens scanning electron microscopy (FEISEM). This technique revealed two distinct networks of filaments. Filaments lying at the surface of nuclear matrices interconnected nuclear pores. These filaments were readily labelled with monoclonal anti-lamin B3 antibodies. Filaments lying within the body of the nuclear matrix were highly branched but were not readily labelled with antilamin B3 antibodies. Nuclear matrices were also prepared from sperm pronuclei assembled in lamin B3 depleted extracts. Using FEISEM, filaments were also detected in these preparations. However, these filaments were poorly organised and often appeared to aggregate. To confirm these results nuclear matrices were also observed as whole mounts using TEM. Nuclear matrices prepared from control nuclei contained a dense array of interconnected filaments. Many (but not all) of these filaments were labelled with anti-lamin B3 antibodies. In contrast, nuclear matrices prepared from "lamin depleted nuclei' contained poorly organised or aggregated filaments which were not specifically labelled with anti-lamin B3 antibodies.

Regulatory peptides in the upper respiratory system and oral cavity of man. An immunocytochemical and radioimmunological study

International Nuclear Information System (INIS)

Hauser-Kronberger, C.

1992-01-01

In the present study a dense network of peptide-immunoreactive nerve fibres in the upper respiratory system and the oral cavity of man was investigated. The occurrence, distribution and concentrations of regulatory peptide immunoreactivities in human nasal mucosa, soft palate, ventricular fold, vocal cord, epiglottis, subglottis, glandula submandibularis and glandula parotis were investigated using highly efficient immunocytochemical and radio-immunological methods. In the tissues investigated vasoactive intestinal polypeptide (VIP) and other derivatives from the VIP-precursor (peptide histidine methionine = PHM), prepro VIP (111-122)), neuropeptide tyrosine (NPY) and its C-flanking peptide (CPON), calcitonin gene-related peptide (CGRP), substance P, neurokinin A, bombesin-flanking peptide and somatostatin were detected. The regulatory peptides demonstrated also included the recently isolated peptides helospectin and pituitary adenylate cyclase activating peptide (PACAP). Single endocrine-like cells were for the first time demonstrated within the respiratory epithelium and in the lamina propria of the nasal mucosa and soft palate and in groups within ducts. Ultrastructural immunelectronmicroscopy was performed using an ABC-pre-embedding method. In addition, semithin Epon resin sections were immunostained. The concentrations of VIP, NPY, CGRP, substance P and neurokinin A were measured using radioimmunological methods. The peptide immunoreactivities demonstrated in a dense network of neuronal structures and endocrine cells give indication for the presence of a complex regulatory system with potent physiological mechanisms in the upper respiratory system and allocated tissues of man

Characterization of the early proliferative response of the rodent bladder to subtotal cystectomy: a unique model of mammalian organ regeneration.

Directory of Open Access Journals (Sweden)

Charles C Peyton

Full Text Available Subtotal cystectomy (STC; surgical removal of ∼75% of the rat urinary bladder elicits a robust proliferative response resulting in complete structural and functional bladder regeneration within 8-weeks. The goal of these studies was to characterize the early cellular response that mediates this regenerative phenomenon, which is unique among mammalian organ systems. STC was performed on eighteen 12-week-old female Fischer F344 rats. At 1, 3, 5 and 7-days post-STC, the bladder was harvested 2-hours after intraperitoneal injection of bromodeoxyuridine (BrdU. Fluorescent BrdU labeling was quantified in cells within the urothelium, lamina propria (LP, muscularis propria (MP and serosa. Cell location was confirmed with fluorescently co-labeled cytokeratin, vimentin or smooth muscle actin (SMA, to identify urothelial, interstitial and smooth muscle cells, respectively. Expression of sonic hedgehog (Shh, Gli-1 and bone morphogenic factor-4 (BMP-4 were evaluated with immunochemistry. Three non-operated rats injected with BrdU served as controls. Less than 1% of cells in the bladder wall were labeled with BrdU in control bladders, but this percentage significantly increased by 5-8-fold at all time points post-STC. The spatiotemporal characteristics of the proliferative response were defined by a significantly higher percentage of BrdU-labeled cells within the urothelium at 1-day than in the MP and LP. A time-dependent shift at 3 and 5-days post-STC revealed significantly fewer BrdU-labeled cells in the MP than LP or urothelium. By 7-days the percentage of BrdU-labeled cells was similar among urothelium, LP and MP. STC also caused an increase in immunostaining for Shh, Gli-1 and BMP-4. In summary, the early stages of functional bladder regeneration are characterized by time-dependent changes in the location of the proliferating cell population, and expression of several evolutionarily conserved developmental signaling proteins. This report extends

Glass ionomer application for vocal fold augmentation: Histopathological analysis on rabbit vocal fold.

Science.gov (United States)

Demirci, Sule; Tuzuner, Arzu; Callıoglu, Elif Ersoy; Yumusak, Nihat; Arslan, Necmi; Baltacı, Bülent

2016-04-01

The aim of this study was to investigate the use of glass ionomer cement (GIC) as an injection material for vocal fold augmentation and to evaluate the biocompatibility of the material. Ten adult New Zealand rabbits were used. Under general anesthesia, 0.1-cc GIC was injected to one vocal fold and the augmentation of vocal fold was observed. No injection was applied to the opposite side, which was accepted as the control group. The animals were sacrificed after 3 months and the laryngeal specimens were histopathologically evaluated. The injected and the noninjected control vocal folds were analyzed. The GIC particles were observed in histological sections on the injected side, and no foreign body giant cells, granulomatous inflammation, necrosis, or marked chronic inflammation were detected around the glass ionomer particles. Mild inflammatory reactions were noticed in only two specimens. The noninjected sides of vocal folds were completely normal. The findings of this study suggest that GIC is biocompatible and may be further investigated as an alternative injection material for augmentation of the vocal fold. Further studies are required to examine the viscoelastic properties of GIC and the long-term effects in experimental studies. NA. © 2015 The American Laryngological, Rhinological and Otological Society, Inc.

PREFACE Protein folding: lessons learned and new frontiers Protein folding: lessons learned and new frontiers

Science.gov (United States)

Pappu, Rohit V.; Nussinov, Ruth

2009-03-01

In appropriate physiological milieux proteins spontaneously fold into their functional three-dimensional structures. The amino acid sequences of functional proteins contain all the information necessary to specify the folds. This remarkable observation has spawned research aimed at answering two major questions. (1) Of all the conceivable structures that a protein can adopt, why is the ensemble of native-like structures the most favorable? (2) What are the paths by which proteins manage to robustly and reproducibly fold into their native structures? Anfinsen's thermodynamic hypothesis has guided the pursuit of answers to the first question whereas Levinthal's paradox has influenced the development of models for protein folding dynamics. Decades of work have led to significant advances in the folding problem. Mean-field models have been developed to capture our current, coarse grain understanding of the driving forces for protein folding. These models are being used to predict three-dimensional protein structures from sequence and stability profiles as a function of thermodynamic and chemical perturbations. Impressive strides have also been made in the field of protein design, also known as the inverse folding problem, thereby testing our understanding of the determinants of the fold specificities of different sequences. Early work on protein folding pathways focused on the specific sequence of events that could lead to a simplification of the search process. However, unifying principles proved to be elusive. Proteins that show reversible two-state folding-unfolding transitions turned out to be a gift of natural selection. Focusing on these simple systems helped researchers to uncover general principles regarding the origins of cooperativity in protein folding thermodynamics and kinetics. On the theoretical front, concepts borrowed from polymer physics and the physics of spin glasses led to the development of a framework based on energy landscape theories. These

Lamina Cribrosa Changes after Laser In Situ Keratomileusis in Myopic Eyes.

Science.gov (United States)

Lee, Soomin; Choi, Da Ye Diana; Lim, Dong Hui; Chung, Tae Young; Han, Jong Chul; Kee, Changwon

2018-04-01

To determine deep optic nerve head structure changes after transient intraocular pressure elevation during laser in situ keratomileusis (LASIK) for myopia. Enhanced depth imaging-optical coherence tomography was performed in each myopic eye that underwent LASIK surgery. Enhanced depth imaging-optical coherence tomography images were created at postoperative 1 day, 1 week, 2 weeks, and 1 month. Lamina cribrosa (LC) thickness, LC depth and prelaminar thickness at the superior, middle and inferior portions of the optic nerve head were measured by two investigators. Forty eyes in 40 patients were included in the present study. During follow-up, there were no significant differences in prelaminar thickness or LC depth. The LC demonstrated increased thickness at postoperative 1 day at all three locations (superior, middle, and inferior) (p LASIK surgery. However, the thickness will gradually return to baseline morphology. Temporary intraocular pressure increase during LASIK does not appear to induce irreversible LC thickness changes. © 2018 The Korean Ophthalmological Society.

Periodic folding of viscous sheets

Science.gov (United States)

Ribe, Neil M.

2003-09-01

The periodic folding of a sheet of viscous fluid falling upon a rigid surface is a common fluid mechanical instability that occurs in contexts ranging from food processing to geophysics. Asymptotic thin-layer equations for the combined stretching-bending deformation of a two-dimensional sheet are solved numerically to determine the folding frequency as a function of the sheet’s initial thickness, the pouring speed, the height of fall, and the fluid properties. As the buoyancy increases, the system bifurcates from “forced” folding driven kinematically by fluid extrusion to “free” folding in which viscous resistance to bending is balanced by buoyancy. The systematics of the numerically predicted folding frequency are in good agreement with laboratory experiments.

Spatial distribution of diffuse, primitive, and classic amyloid-beta deposits and blood vessels in the upper laminae of the frontal cortex in Alzheimer disease.

Science.gov (United States)

Armstrong, R A; Cairns, N J; Lantos, P L

1998-12-01

The spatial distribution of the diffuse, primitive, and classic amyloid-beta deposits was studied in the upper laminae of the superior frontal gyrus in cases of sporadic Alzheimer disease (AD). Amyloid-beta-stained tissue was counterstained with collagen IV to determine whether the spatial distribution of the amyloid-beta deposits along the cortex was related to blood vessels. In all patients, amyloid-beta deposits and blood vessels were aggregated into distinct clusters and in many patients, the clusters were distributed with a regular periodicity along the cortex. The clusters of diffuse and primitive deposits did not coincide with the clusters of blood vessels in most patients. However, the clusters of classic amyloid-beta deposits coincided with those of the large diameter (>10 microm) blood vessels in all patients and with clusters of small-diameter (upper cortical laminae.

Asymmetric hindwing foldings in rove beetles.

Science.gov (United States)

Saito, Kazuya; Yamamoto, Shuhei; Maruyama, Munetoshi; Okabe, Yoji

2014-11-18

Foldable wings of insects are the ultimate deployable structures and have attracted the interest of aerospace engineering scientists as well as entomologists. Rove beetles are known to fold their wings in the most sophisticated ways that have right-left asymmetric patterns. However, the specific folding process and the reason for this asymmetry remain unclear. This study reveals how these asymmetric patterns emerge as a result of the folding process of rove beetles. A high-speed camera was used to reveal the details of the wing-folding movement. The results show that these characteristic asymmetrical patterns emerge as a result of simultaneous folding of overlapped wings. The revealed folding mechanisms can achieve not only highly compact wing storage but also immediate deployment. In addition, the right and left crease patterns are interchangeable, and thus each wing internalizes two crease patterns and can be folded in two different ways. This two-way folding gives freedom of choice for the folding direction to a rove beetle. The use of asymmetric patterns and the capability of two-way folding are unique features not found in artificial structures. These features have great potential to extend the design possibilities for all deployable structures, from space structures to articles of daily use.

Quantification of fold growth of frontal antiforms in the Zagros fold and thrust belt (Kurdistan, NE Iraq)

Science.gov (United States)

Bretis, Bernhard; Bartl, Nikolaus; Graseman, Bernhard; Lockhart, Duncan

2010-05-01

The Zagros fold and thrust belt is a seismically active orogen, where actual kinematic models based on GPS networks suggest a north-south shortening between Arabian and Eurasian in the order of 1.5-2.5 cm/yr. Most of this deformation is partitioned in south-southwest oriented folding and thrusting with northwest-southeast to north-south trending dextral strike slip faults. The Zagros fold and thrust belt is of great economic interest because it has been estimated that this area contains about 15% of the global recoverable hydrocarbons. Whereas the SE parts of the Zagros have been investigated by detailed geological studies, the NW extent being part of the Republic of Iraq have experienced considerably less attention. In this study we combine field work and remote sensing techniques in order to investigate the interaction of erosion and fold growth in the area NE of Erbil (Kurdistan, Iraq). In particular we focus on the interaction of the transient development of drainage patterns along growing antiforms, which directly reflects the kinematics of progressive fold growth. Detailed geomorphological studies of the Bana Bawi-, Permam- and Safeen fold trains show that these anticlines have not developed from subcylindrical embryonic folds but they have merged from different fold segments that joined laterally during fold amplification. This fold segments with length between 5 and 25 km have been detected by mapping ancient and modern river courses that initially cut the nose of growing folds and eventually got defeated leaving behind a wind gap. Fold segments, propagating in different directions force rivers to join resulting in steep gorges, which dissect the merging fold noses. Along rapidly lateral growing folds (e.g. at the SE end of the Bana Bawi Anticline) we observed "curved wind gaps", a new type of abandoned river course, where form of the wind gap mimics a formed nose of a growing antiform. The inherited curved segments of uplifted curved river courses strongly

Optical coherence tomography for bladder cancer - ready as a surrogate for optical biopsy? - results of a prospective mono-centre study

Directory of Open Access Journals (Sweden)

Karl A

2010-03-01

OCT. Furthermore all invasive tumors were staged correctly by OCT regarding tumor growth beyond the lamina propria. There were no false negative lesions detected by OCT. Sensitivity of OCT for detecting the presence of a malignant lesion was 100% and sensitivity for detection of tumor growth beyond the lamina propria was 100% as well. Specificity of OCT for presence of malignancy was 65%, due to the fact that a number of lesions were interpreted as false positive by OCT. Conclusion As a minimally invasive technique, OCT proved to have extremely high sensitivity for detection of malignant lesions as well as estimation of whether a tumor has invaded beyond the lamina propria. However, specificity of OCT within the bladder was impaired (65%, possibly due to a learning curve and/or the relatively low spatial resolution and visualization depth of the OCT technology. Further studies and technical development are needed to establish an adequate surrogate for optical biopsy.

Cation-induced folding of alginate-bearing bilayer gels: an unusual example of spontaneous folding along the long axis.

Science.gov (United States)

Athas, Jasmin C; Nguyen, Catherine P; Kummar, Shailaa; Raghavan, Srinivasa R

2018-04-04

The spontaneous folding of flat gel films into tubes is an interesting example of self-assembly. Typically, a rectangular film folds along its short axis when forming a tube; folding along the long axis has been seen only in rare instances when the film is constrained. Here, we report a case where the same free-swelling gel film folds along either its long or short axis depending on the concentration of a solute. Our gels are sandwiches (bilayers) of two layers: a passive layer of cross-linked N,N'-dimethylyacrylamide (DMAA) and an active layer of cross-linked DMAA that also contains chains of the biopolymer alginate. Multivalent cations like Ca2+ and Cu2+ induce these bilayer gels to fold into tubes. The folding occurs instantly when a flat film of the gel is introduced into a solution of these cations. The likely cause for folding is that the active layer stiffens and shrinks (because the alginate chains in it get cross-linked by the cations) whereas the passive layer is unaffected. The resulting mismatch in swelling degree between the two layers creates internal stresses that drive folding. Cations that are incapable of cross-linking alginate, such as Na+ and Mg2+, do not induce gel folding. Moreover, the striking aspect is the direction of folding. When the Ca2+ concentration is high (100 mM or higher), the gels fold along their long axis, whereas when the Ca2+ concentration is low (40 to 80 mM), the gels fold along their short axis. We hypothesize that the folding axis is dictated by the inhomogeneous nature of alginate-cation cross-linking, i.e., that the edges get cross-linked before the faces of the gel. At high Ca2+ concentration, the stiffer edges constrain the folding; in turn, the gel folds such that the longer edges are deformed less, which explains the folding along the long axis. At low Ca2+ concentration, the edges and the faces of the gel are more similar in their degree of cross-linking; therefore, the gel folds along its short axis. An analogy

Spherical images and inextensible curved folding

Science.gov (United States)

Seffen, Keith A.

2018-02-01

In their study, Duncan and Duncan [Proc. R. Soc. London A 383, 191 (1982), 10.1098/rspa.1982.0126] calculate the shape of an inextensible surface folded in two about a general curve. They find the analytical relationships between pairs of generators linked across the fold curve, the shape of the original path, and the fold angle variation along it. They present two special cases of generator layouts for which the fold angle is uniform or the folded curve remains planar, for simplifying practical folding in sheet-metal processes. We verify their special cases by a graphical treatment according to a method of Gauss. We replace the fold curve by a piecewise linear path, which connects vertices of intersecting pairs of hinge lines. Inspired by the d-cone analysis by Farmer and Calladine [Int. J. Mech. Sci. 47, 509 (2005), 10.1016/j.ijmecsci.2005.02.013], we construct the spherical images for developable folding of successive vertices: the operating conditions of the special cases in Duncan and Duncan are then revealed straightforwardly by the geometric relationships between the images. Our approach may be used to synthesize folding patterns for novel deployable and shape-changing surfaces without need of complex calculation.

Lamina cribrosa position and Bruch's membrane opening differences between anterior ischemic optic neuropathy and open-angle glaucoma.

Science.gov (United States)

Rebolleda, Gema; Pérez-Sarriegui, Ane; Díez-Álvarez, Laura; De Juan, Victoria; Muñoz-Negrete, Francisco J

2018-06-01

To compare the optic nerve head morphology among primary open-angle glaucoma, non-arteritic anterior ischemic optic neuropathy eyes, their fellow healthy eyes and control eyes, using spectral-domain optical coherence tomography with enhanced depth imaging. Observational cross-sectional study including 88 eyes of 68 patients. In this study, 23 non-arteritic anterior ischemic optic neuropathy eyes, 17 fellow unaffected eyes, 25 primary open-angle glaucoma eyes, and 23 age-matched control eyes were included. Peripapillary retinal nerve fiber layer thickness and optic disk area were evaluated. Bruch's membrane opening diameter, optic cup depth, anterior lamina cribrosa depth, and prelaminar tissue thickness were assessed. Non-arteritic anterior ischemic optic neuropathy and primary open-angle glaucoma eyes had similar visual field mean deviation and peripapillary retinal nerve fiber layer thickness (P = 0.6 and P = 0.56, respectively). Bruch's membrane opening diameter was significantly larger in primary open-angle glaucoma eyes than in control eyes (P = 0.02). Lamina cribrosa and disk cup were deeper in eyes with primary open-angle glaucoma than both control and non-arteritic anterior ischemic optic neuropathy eyes (P open-angle glaucoma eyes than in non-arteritic anterior ischemic optic neuropathy eyes (P opening diameter was found in primary open-angle glaucoma eyes compared with control eyes. This issue has clinical implications because Bruch's membrane opening has been considered a stable reference for disk-related measures.

Atrophic rhinitis and other nasal lesions induced by a 1-month exposure of F344 rats to 0.25 or 0.5 ppm ozone

International Nuclear Information System (INIS)

Hotchkiss, J.A.; Harkema, J.R.; Wacnik, P.W.

1994-01-01

Ozone, the principal oxidant pollutant of photochemical smog, is a common inhaled toxicant for metropolitan area residents. The effects of acute and chronic ozone exposure on inflammatory cell influx, hyperplasia, and secretory cell metaplasia within the surface epithelium lining rat nasal airways have previously been reported. On the other hand, there is a paucity of data describing the effects of ozone exposure on the subepithelial tissues (i.e., lamina propria and bone) of nasal turbinates. However, recently, a significant decrease in nasal turbinate bone area in rats chronically exposed (20 mo) to 1 ppm ozone was reported. The purpose of the present study was to examine the effects of a 1-mo ozone exposure on subepithelial tissue compartments of maxilloturbinates in the anterior nasal cavity of rats

Database survey of anti-inflammatory plants in South America: a review.

Science.gov (United States)

de Morais Lima, Gedson Rodrigues; de Albuquerque Montenegro, Camila; de Almeida, Cynthia Layse Ferreira; de Athayde-Filho, Petrônio Filgueiras; Barbosa-Filho, José Maria; Batista, Leônia Maria

2011-01-01

Inflammation is a complex event linked to tissue damage whether by bacteria, physical trauma, chemical, heat or any other phenomenon. This physiological response is coordinated largely by a variety of chemical mediators that are released from the epithelium, the immunocytes and nerves of the lamina propria. However, if the factor that triggers the inflammation persists, the inflammation can become relentless, leading to an intensification of the lesion. The present work is a literature survey of plant extracts from the South American continent that have been reported to show anti-inflammatory activity. This review refers to 63 bacterial families of which the following stood out: Asteraceae, Fabaceae, Euphorbiaceae, Apocynaceae and Celastraceae, with their countries, parts used, types of extract used, model bioassays, organisms tested and their activity.

Bacterial invasion of the uterus and oviducts in bovine pyometra

DEFF Research Database (Denmark)

Karstrup, C. C.; Pedersen, H. G.; Jensen, Tim Kåre

2017-01-01

of bacterial pathogenicity and development of lesions, have not been investigated. Bacterial invasion of the uterus and oviducts was studied in 21 cows diagnosed with pyometra at the time of slaughter by applying fluorescence in situ hybridization using probes targeting 16S ribosomal RNA of Fusobacterium...... necrophorum, Porphyromonas levii, Trueperella pyogenes and the overall bacterial domain Bacteria. Fusobacterium necrophorum and P. levii were found to invade the endometrium, especially if the endometrium was ulcerated, and penetrated deep into the lamina propria. These species co-localized within the tissue...... thus indicating a synergism. Trueperella pyogenes did not invade the uterine tissue. In addition to endometrial lesions, most cows with pyometra also had salpingitis but without significant bacterial invasion of the oviductal wall....

Immunostaining for Homer reveals the majority of excitatory synapses in laminae I?III of the mouse spinal dorsal horn

OpenAIRE

Gutierrez-Mecinas, Maria; Kuehn, Emily D.; Abraira, Victoria E.; Polg?r, Erika; Watanabe, Masahiko; Todd, Andrew J.

2016-01-01

The spinal dorsal horn processes somatosensory information before conveying it to the brain. The neuronal organization of the dorsal horn is still poorly understood, although recent studies have defined several distinct populations among the interneurons, which account for most of its constituent neurons. All primary afferents, and the great majority of neurons in laminae I–III are glutamatergic, and a major factor limiting our understanding of the synaptic circuitry has been the difficulty i...

Low-Cost Intra-Articular Distraction Technique Using Kirschner Wires and a Toothed Lamina Spreader.

Science.gov (United States)

Shymon, Stephen Joseph; Harris, Thomas Gregory

We describe a low-cost (instrument cost) technique for joint distraction using 2 Kirschner wires and a toothed lamina spreader in lieu of a Hintermann distractor. The described technique allows for temporary intra-articular distraction and visualization and preservation of the articular surface with extra-articular instrumentation. The technique can also allow for closed reduction and percutaneous treatment in cases of soft tissue compromise. Additionally, the technique uses common orthopedic surgical instruments, leading to a minimal learning curve for novice surgeons. We have found this distraction technique to be most effective for intra-articular preparation of hindfoot and midfoot arthrodeses and for navicular fracture reduction. Copyright © 2016 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.

SVM-Fold: a tool for discriminative multi-class protein fold and superfamily recognition.

Science.gov (United States)

Melvin, Iain; Ie, Eugene; Kuang, Rui; Weston, Jason; Stafford, William Noble; Leslie, Christina

2007-05-22

Predicting a protein's structural class from its amino acid sequence is a fundamental problem in computational biology. Much recent work has focused on developing new representations for protein sequences, called string kernels, for use with support vector machine (SVM) classifiers. However, while some of these approaches exhibit state-of-the-art performance at the binary protein classification problem, i.e. discriminating between a particular protein class and all other classes, few of these studies have addressed the real problem of multi-class superfamily or fold recognition. Moreover, there are only limited software tools and systems for SVM-based protein classification available to the bioinformatics community. We present a new multi-class SVM-based protein fold and superfamily recognition system and web server called SVM-Fold, which can be found at http://svm-fold.c2b2.columbia.edu. Our system uses an efficient implementation of a state-of-the-art string kernel for sequence profiles, called the profile kernel, where the underlying feature representation is a histogram of inexact matching k-mer frequencies. We also employ a novel machine learning approach to solve the difficult multi-class problem of classifying a sequence of amino acids into one of many known protein structural classes. Binary one-vs-the-rest SVM classifiers that are trained to recognize individual structural classes yield prediction scores that are not comparable, so that standard "one-vs-all" classification fails to perform well. Moreover, SVMs for classes at different levels of the protein structural hierarchy may make useful predictions, but one-vs-all does not try to combine these multiple predictions. To deal with these problems, our method learns relative weights between one-vs-the-rest classifiers and encodes information about the protein structural hierarchy for multi-class prediction. In large-scale benchmark results based on the SCOP database, our code weighting approach

Quantification of Porcine Vocal Fold Geometry.

Science.gov (United States)

Stevens, Kimberly A; Thomson, Scott L; Jetté, Marie E; Thibeault, Susan L

2016-07-01

The aim of this study was to quantify porcine vocal fold medial surface geometry and three-dimensional geometric distortion induced by freezing the larynx, especially in the region of the vocal folds. The medial surface geometries of five excised porcine larynges were quantified and reported. Five porcine larynges were imaged in a micro-CT scanner, frozen, and rescanned. Segmentations and three-dimensional reconstructions were used to quantify and characterize geometric features. Comparisons were made with geometry data previously obtained using canine and human vocal folds as well as geometries of selected synthetic vocal fold models. Freezing induced an overall expansion of approximately 5% in the transverse plane and comparable levels of nonuniform distortion in sagittal and coronal planes. The medial surface of the porcine vocal folds was found to compare reasonably well with other geometries, although the compared geometries exhibited a notable discrepancy with one set of published human female vocal fold geometry. Porcine vocal folds are qualitatively geometrically similar to data available for canine and human vocal folds, as well as commonly used models. Freezing of tissue in the larynx causes distortion of around 5%. The data can provide direction in estimating uncertainty due to bulk distortion of tissue caused by freezing, as well as quantitative geometric data that can be directly used in developing vocal fold models. Copyright © 2016 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

Graph-representation of oxidative folding pathways

Directory of Open Access Journals (Sweden)

Kaján László

2005-01-01

Full Text Available Abstract Background The process of oxidative folding combines the formation of native disulfide bond with conformational folding resulting in the native three-dimensional fold. Oxidative folding pathways can be described in terms of disulfide intermediate species (DIS which can also be isolated and characterized. Each DIS corresponds to a family of folding states (conformations that the given DIS can adopt in three dimensions. Results The oxidative folding space can be represented as a network of DIS states interconnected by disulfide interchange reactions that can either create/abolish or rearrange disulfide bridges. We propose a simple 3D representation wherein the states having the same number of disulfide bridges are placed on separate planes. In this representation, the shuffling transitions are within the planes, and the redox edges connect adjacent planes. In a number of experimentally studied cases (bovine pancreatic trypsin inhibitor, insulin-like growth factor and epidermal growth factor, the observed intermediates appear as part of contiguous oxidative folding pathways. Conclusions Such networks can be used to visualize folding pathways in terms of the experimentally observed intermediates. A simple visualization template written for the Tulip package http://www.tulip-software.org/ can be obtained from V.A.

Understanding ensemble protein folding at atomic detail

International Nuclear Information System (INIS)

Wallin, Stefan; Shakhnovich, Eugene I

2008-01-01

Although far from routine, simulating the folding of specific short protein chains on the computer, at a detailed atomic level, is starting to become a reality. This remarkable progress, which has been made over the last decade or so, allows a fundamental aspect of the protein folding process to be addressed, namely its statistical nature. In order to make quantitative comparisons with experimental kinetic data a complete ensemble view of folding must be achieved, with key observables averaged over the large number of microscopically different folding trajectories available to a protein chain. Here we review recent advances in atomic-level protein folding simulations and the new insight provided by them into the protein folding process. An important element in understanding ensemble folding kinetics are methods for analyzing many separate folding trajectories, and we discuss techniques developed to condense the large amount of information contained in an ensemble of trajectories into a manageable picture of the folding process. (topical review)

Vocal fold injection medialization laryngoplasty.

Science.gov (United States)

Modi, Vikash K

2012-01-01

Unilateral vocal fold paralysis (UVFP) can cause glottic insufficiency that can result in hoarseness, chronic cough, dysphagia, and/or aspiration. In rare circumstances, UVFP can cause airway obstruction necessitating a tracheostomy. The treatment options for UVFP include observation, speech therapy, vocal fold injection medialization laryngoplasty, thyroplasty, and laryngeal reinnervation. In this chapter, the author will discuss the technique of vocal fold injection for medialization of a UVFP. Copyright © 2012 S. Karger AG, Basel.

Functional results after external vocal fold medialization thyroplasty with the titanium vocal fold medialization implant.

Science.gov (United States)

Schneider, Berit; Denk, Doris-Maria; Bigenzahn, Wolfgang

2003-04-01

A persistent insufficiency of glottal closure is mostly a consequence of a unilateral vocal fold movement impairment. It can also be caused by vocal fold atrophy or scarring processes with regular bilateral respiratory vocal fold function. Because of consequential voice, breathing, and swallowing impairments, a functional surgical treatment is required. The goal of the study was to outline the functional results after medialization thyroplasty with the titanium vocal fold medialization implant according to Friedrich. In the period of 1999 to 2001, an external vocal fold medialization using the titanium implant was performed on 28 patients (12 women and 16 men). The patients were in the age range of 19 to 84 years. Twenty-two patients had a paralysis of the left-side vocal fold, and six patients, of the right-side vocal fold. Detailed functional examinations were executed on all patients before and after the surgery: perceptive voice sound analysis according to the "roughness, breathiness, and hoarseness" method, judgment of the s/z ratio and voice dysfunction index, voice range profile measurements, videostroboscopy, and pulmonary function tests. In case of dysphagia/aspiration, videofluoroscopy of swallowing was also performed. The respective data were statistically analyzed (paired t test, Wilcoxon-test). All patients reported on improvement of voice, swallowing, and breathing functions postoperatively. Videostroboscopy revealed an almost complete glottal closure after surgery in all of the patients. All voice-related parameters showed a significant improvement. An increase of the laryngeal resistance by the medialization procedure could be excluded by analysis of the pulmonary function test. The results confirm the external medialization of the vocal folds as an adequate method in the therapy of voice, swallowing, and breathing impairment attributable to an insufficient glottal closure. The titanium implant offers, apart from good tissue tolerability, the

Basis for the Age-related Decline in Intestinal Mucosal Immunity

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Douglas L. Schmucker

2003-01-01

Full Text Available The elderly are characterized by mucosal immunosenescence and high rates of morbidity and mortality associated with infectious diseases of the intestinal tract. Little is known about how the differentiation of immunoglobulin A (IgA plasma cells in Peyer's patches (PPs and their subsequent homing to the small intestinal lamina propria (LP is affected by aging. Quantitative immunohistochemical analyses demonstrated a 2-fold increase in the number of IgA+ cells in the PPs, coupled with significant declines in the numbers of IgA+ and antibody-positive cells in the intestinal LP of senescent rats compared to young adult animals. These data suggest that aging diminishes the emigration of IgA immunoblasts from these lymphoid aggregates, as well as their migration to the intestinal LP. Flow cytometry and lymphocyte adoptive transfer studies showed 3- to 4-fold age-related declines in the homing of antibody-containing cells and mesenteric lymph node lymphocytes to the small intestines of rhesus macaques and rats, respectively. The number of peripheral blood IgA immunoblasts expressing the homing molecule α4β7 declined 30% in senescent rats. This was accompanied by a >17% decrease in the areal density of LP blood vessels staining positive for the cell adhesion molecule MAdCAM-1. Cumulatively, declines in expression of these homing molecules constitute a substantial age-related diminution of IgA immunoblast homing potential. In vitro antibody secretion by LP plasma cells, i.e. antibody secreted per antibody-positive cell, remains unchanged as a function of donor age. Intestinal mucosal immunosenescence is a consequence of reduced homing of IgA plasma cells to the intestinal LP as a result of declines in homing molecule expression.

Optical coherence tomography-enhanced microlaryngoscopy: preliminary report of a noncontact optical coherence tomography system integrated with a surgical microscope.

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Vokes, David E; Jackson, Ryan; Guo, Shuguang; Perez, Jorge A; Su, Jianping; Ridgway, James M; Armstrong, William B; Chen, Zhongping; Wong, Brian J F

2008-07-01

Optical coherence tomography (OCT) is a new imaging modality that uses near-infrared light to produce cross-sectional images of tissue with a resolution approaching that of light microscopy. We have previously reported use of OCT imaging of the vocal folds (VFs) during direct laryngoscopy with a probe held in contact or near-contact with the VFs. This aim of this study was to develop and evaluate a novel OCT system integrated with a surgical microscope to allow hands-free OCT imaging of the VFs, which could be performed simultaneously with microscopic visualization. We performed a prospective evaluation of a new method of acquiring OCT images of the VFs. An OCT system was successfully integrated with a surgical microscope to permit noncontact OCT imaging of the VFs of 10 patients. With this novel device we were able to identify VF epithelium and lamina propria; however, the resolution was reduced compared to that achieved with the standard contact or near-contact OCT. Optical coherence tomography is able to produce high-resolution images of vocal fold mucosa to a maximum depth of 1.6 mm. It may be used in the diagnosis of VF lesions, particularly early squamous cell carcinoma, in which OCT can show disruption of the basement membrane. Mounting the OCT device directly onto the operating microscope allows hands-free noncontact OCT imaging and simultaneous conventional microscopic visualization of the VFs. However, the lateral resolution of the OCT microscope system is 50 microm, in contrast to the conventional handheld probe system (10 microm). Although such images at this resolution are still useful clinically, improved resolution would enhance the system's performance, potentially enabling real-time OCT-guided microsurgery of the larynx.

A comparison of RNA folding measures

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Gardner Paul P

2005-10-01

Full Text Available Abstract Background In the last few decades there has been a great deal of discussion concerning whether or not noncoding RNA sequences (ncRNAs fold in a more well-defined manner than random sequences. In this paper, we investigate several existing measures for how well an RNA sequence folds, and compare the behaviour of these measures over a large range of Rfam ncRNA families. Such measures can be useful in, for example, identifying novel ncRNAs, and indicating the presence of alternate RNA foldings. Results Our analysis shows that ncRNAs, but not mRNAs, in general have lower minimal free energy (MFE than random sequences with the same dinucleotide frequency. Moreover, even when the MFE is significant, many ncRNAs appear to not have a unique fold, but rather several alternative folds, at least when folded in silico. Furthermore, we find that the six investigated measures are correlated to varying degrees. Conclusion Due to the correlations between the different measures we find that it is sufficient to use only two of them in RNA folding studies, one to test if the sequence in question has lower energy than a random sequence with the same dinucleotide frequency (the Z-score and the other to see if the sequence has a unique fold (the average base-pair distance, D.

RNAiFold: a web server for RNA inverse folding and molecular design.

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Garcia-Martin, Juan Antonio; Clote, Peter; Dotu, Ivan

2013-07-01

Synthetic biology and nanotechnology are poised to make revolutionary contributions to the 21st century. In this article, we describe a new web server to support in silico RNA molecular design. Given an input target RNA secondary structure, together with optional constraints, such as requiring GC-content to lie within a certain range, requiring the number of strong (GC), weak (AU) and wobble (GU) base pairs to lie in a certain range, the RNAiFold web server determines one or more RNA sequences, whose minimum free-energy secondary structure is the target structure. RNAiFold provides access to two servers: RNA-CPdesign, which applies constraint programming, and RNA-LNSdesign, which applies the large neighborhood search heuristic; hence, it is suitable for larger input structures. Both servers can also solve the RNA inverse hybridization problem, i.e. given a representation of the desired hybridization structure, RNAiFold returns two sequences, whose minimum free-energy hybridization is the input target structure. The web server is publicly accessible at http://bioinformatics.bc.edu/clotelab/RNAiFold, which provides access to two specialized servers: RNA-CPdesign and RNA-LNSdesign. Source code for the underlying algorithms, implemented in COMET and supported on linux, can be downloaded at the server website.

Kinetic partitioning mechanism of HDV ribozyme folding

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Chen, Jiawen; Gong, Sha; Wang, Yujie; Zhang, Wenbing, E-mail: wbzhang@whu.edu.cn [Department of Physics, Wuhan University, Wuhan, Hubei 430072 (China)

2014-01-14

RNA folding kinetics is directly tied to RNA biological functions. We introduce here a new approach for predicting the folding kinetics of RNA secondary structure with pseudoknots. This approach is based on our previous established helix-based method for predicting the folding kinetics of RNA secondary structure. In this approach, the transition rates for an elementary step: (1) formation, (2) disruption of a helix stem, and (3) helix formation with concomitant partial melting of an incompatible helix, are calculated with the free energy landscape. The folding kinetics of the Hepatitis delta virus (HDV) ribozyme and the mutated sequences are studied with this method. The folding pathways are identified by recursive searching the states with high net flux-in(out) population starting from the native state. The theory results are in good agreement with that of the experiments. The results indicate that the bi-phasic folding kinetics for the wt HDV sequence is ascribed to the kinetic partitioning mechanism: Part of the population will quickly fold to the native state along the fast pathway, while another part of the population will fold along the slow pathway, in which the population is trapped in a non-native state. Single mutation not only changes the folding rate but also the folding pathway.

Desempenho animal em pasto de aveia e azevém com distintas biomassas de lâminas foliares Animal performance in oat and Italian ryegrass pastures under leaf lamina biomass levels

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Duilio Guerra Bandinelli

2005-12-01

Full Text Available O objetivo deste trabalho foi avaliar o efeito de biomassas de lâminas foliares no desempenho animal. Utilizou-se mistura de aveia (Avena strigosa Schreb e azevém (Lolium multiflorum Lam., para determinar quantidades adequadas de sua biomassa no manejo da pastagem. Foram realizados dois experimentos, na estação fria de 2002 e 2003. Na avaliação de 2002, os valores de biomassa de lâminas foliares foram de 360 kg ha-1 (baixa e 630 kg ha-1 (alta. Em 2003, foram obtidas biomassas de 352, 422 e 507 kg ha-1, classificadas como baixa, média e alta, respectivamente. O método de pastejo foi contínuo, com taxa de lotação variada; os animais utilizados foram terneiros da raça Charolês e cruzados com Nelore, com idade inicial de nove meses. As variáveis de produção animal avaliadas, nos dois anos, foram: ganho médio diário, carga animal e ganho de peso vivo por área. As distintas biomassas de lâminas foliares mantidas não são fatores limitantes ao desempenho animal.The objective of this work was to evaluate the effect of different leaf lamina biomass over animal performance. A mixture of oat (Avena strigosa Schreb and Italian ryegrass (Lolium multiflorum Lam. was used to determine adequate levels of leaf lamina biomass for pasture management. Two trials were made, in 2002 and 2003 cool seasons. In 2002 evaluation, leaf lamina biomass values were of 360 kg ha-1 (low and 630 kg ha-1 (high. In 2003, values obtained for leaf lamina biomasses were of 352, 422 and 507 kg ha-1, being classified as low, medium and high, respectively. Grazing method was continuous, with variable stocking rate; testing animals were calves of Charolais breed and its crosses with Nelore breed, with initial age of nine months. Evaluated variables in animal production, in both years, were: average daily gain, stocking rate and live weight gain per area. Leaf lamina biomasses evaluated are not limiting factors to animal performance.

Self-folding origami at any energy scale

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Pinson, Matthew B.; Stern, Menachem; Carruthers Ferrero, Alexandra; Witten, Thomas A.; Chen, Elizabeth; Murugan, Arvind

2017-05-01

Programmable stiff sheets with a single low-energy folding motion have been sought in fields ranging from the ancient art of origami to modern meta-materials research. Despite such attention, only two extreme classes of crease patterns are usually studied; special Miura-Ori-based zero-energy patterns, in which crease folding requires no sheet bending, and random patterns with high-energy folding, in which the sheet bends as much as creases fold. We present a physical approach that allows systematic exploration of the entire space of crease patterns as a function of the folding energy. Consequently, we uncover statistical results in origami, finding the entropy of crease patterns of given folding energy. Notably, we identify three classes of Mountain-Valley choices that have widely varying `typical' folding energies. Our work opens up a wealth of experimentally relevant self-folding origami designs not reliant on Miura-Ori, the Kawasaki condition or any special symmetry in space.

Anatomy and Histology of an Epicanthal Fold.

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Park, Jae Woo; Hwang, Kun

2016-06-01

The aim of this study is to elucidate the precise anatomical and histological detail of the epicanthal fold.Thirty-two hemifaces of 16 Korean adult cadavers were used in this study (30 hemifaces with an epicanthal fold, 2 without an epicanthal fold). In 2 patients who had an epicanthoplasty, the epicanthal folds were sampled.In a dissection, the periorbital skin and subcutaneous tissues were removed and the epicanthal fold was observed in relation to each part of the orbicularis oculi muscle. Specimens including the epicanthal fold were embeddedin in paraffin, sectioned at 10 um, and stained with Hematoxylin-Eosin. The horizontal section in the level of the paplebral fissure was made and the prepared slides were observed under a light microscope.In the specimens without an epicanthal fold, no connection between the upper preseptal muscle and the lower preseptal muscle was found. In the specimens with an epicanthal fold, a connection of the upper preseptal muscle to the lower preseptal muscle was observed. It was present in all 15 hemifaces (100%). There was no connection between the pretarsal muscles. In a horizontal section, the epicanthal fold was composed of 3 compartments: an outer skin lining, a core structure, and an innerskin lining. The core structure was mainly composed of muscular fibers and fibrotic tissue and they were intermingled.Surgeons should be aware of the anatomical details of an epicanthal fold. In removing or reconstructing an epicanthal fold, the fibromuscular core band should also be removed or reconstructed.

The review on tessellation origami inspired folded structure

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Chu, Chai Chen; Keong, Choong Kok

2017-10-01

Existence of folds enhances the load carrying capacity of a folded structure which makes it suitable to be used for application where large open space is required such as large span roof structures and façade. Folded structure is closely related to origami especially the tessellation origami. Tessellation origami provides a folded configuration with facetted surface as a result from repeated folding pattern. Besides that, tessellation origami has flexible folding mechanism that produced a variety of 3-dimensional folded configurations. Despite the direct relationship between fold in origami and folded structure, the idea of origami inspired folded structure is not properly reviewed in the relevant engineering field. Hence, this paper aims to present the current studies from related discipline which has direct relation with application of tessellation origami in folded structure. First, tessellation origami is properly introduced and defined. Then, the review covers the topic on the origami tessellation design suitable for folded structure, its modeling and simulation method, and existing studies and applications of origami as folded structure is presented. The paper also includes the discussion on the current issues related to each topic.

Vocal Fold Vibratory Changes Following Surgical Intervention.

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Chen, Wenli; Woo, Peak; Murry, Thomas

2016-03-01

High-speed videoendoscopy (HSV) captures direct cycle-to-cycle visualization of vocal fold movement in real time. This ultrafast recording rate is capable of visualizing the vibratory motion of the vocal folds in severely disordered phonation and provides a direct method for examining vibratory changes after vocal fold surgery. The purpose of this study was to examine the vibratory motion before and after surgical intervention. HSV was captured from two subjects with identifiable midvocal fold benign lesions and six subjects with highly aperiodic vocal fold vibration before and after phonosurgery. Digital kymography (DKG) was used to extract high-speed kymographic vocal fold images sampled at the midmembranous, anterior 1/3, and posterior 1/3 region. Spectral analysis was subsequently applied to the DKG to quantify the cycle-to-cycle movements of the left and the right vocal fold, expressed as a spectrum. Before intervention, the vibratory spectrum consisted of decreased and flat-like spectral peaks with robust power asymmetry. After intervention, increases in spectral power and decreases in power symmetry were noted. Spectral power increases were most remarkable in the midmembranous region of the vocal fold. Surgical modification resulted in improved lateral excursion of the vocal folds, vibratory function, and perceptual measures of Voice Handicap Index-10. These changes in vibratory behavior trended toward normal vocal fold vibration. Copyright © 2016 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

Folding of non-Euclidean curved shells

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Bende, Nakul; Evans, Arthur; Innes-Gold, Sarah; Marin, Luis; Cohen, Itai; Santangelo, Christian; Hayward, Ryan

2015-03-01

Origami-based folding of 2D sheets has been of recent interest for a variety of applications ranging from deployable structures to self-folding robots. Though folding of planar sheets follows well-established principles, folding of curved shells involves an added level of complexity due to the inherent influence of curvature on mechanics. In this study, we use principles from differential geometry and thin shell mechanics to establish fundamental rules that govern folding of prototypical creased shells. In particular, we show how the normal curvature of a crease line controls whether the deformation is smooth or discontinuous, and investigate the influence of shell thickness and boundary conditions. We show that snap-folding of shells provides a route to rapid actuation on time-scales dictated by the speed of sound. The simple geometric design principles developed can be applied at any length-scale, offering potential for bio-inspired soft actuators for tunable optics, microfluidics, and robotics. This work was funded by the National Science Foundation through EFRI ODISSEI-1240441 with additional support to S.I.-G. through the UMass MRSEC DMR-0820506 REU program.

Improving Protein Fold Recognition by Deep Learning Networks

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Jo, Taeho; Hou, Jie; Eickholt, Jesse; Cheng, Jianlin

2015-12-01

For accurate recognition of protein folds, a deep learning network method (DN-Fold) was developed to predict if a given query-template protein pair belongs to the same structural fold. The input used stemmed from the protein sequence and structural features extracted from the protein pair. We evaluated the performance of DN-Fold along with 18 different methods on Lindahl’s benchmark dataset and on a large benchmark set extracted from SCOP 1.75 consisting of about one million protein pairs, at three different levels of fold recognition (i.e., protein family, superfamily, and fold) depending on the evolutionary distance between protein sequences. The correct recognition rate of ensembled DN-Fold for Top 1 predictions is 84.5%, 61.5%, and 33.6% and for Top 5 is 91.2%, 76.5%, and 60.7% at family, superfamily, and fold levels, respectively. We also evaluated the performance of single DN-Fold (DN-FoldS), which showed the comparable results at the level of family and superfamily, compared to ensemble DN-Fold. Finally, we extended the binary classification problem of fold recognition to real-value regression task, which also show a promising performance. DN-Fold is freely available through a web server at http://iris.rnet.missouri.edu/dnfold.

Improving Protein Fold Recognition by Deep Learning Networks.

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Jo, Taeho; Hou, Jie; Eickholt, Jesse; Cheng, Jianlin

2015-12-04

For accurate recognition of protein folds, a deep learning network method (DN-Fold) was developed to predict if a given query-template protein pair belongs to the same structural fold. The input used stemmed from the protein sequence and structural features extracted from the protein pair. We evaluated the performance of DN-Fold along with 18 different methods on Lindahl's benchmark dataset and on a large benchmark set extracted from SCOP 1.75 consisting of about one million protein pairs, at three different levels of fold recognition (i.e., protein family, superfamily, and fold) depending on the evolutionary distance between protein sequences. The correct recognition rate of ensembled DN-Fold for Top 1 predictions is 84.5%, 61.5%, and 33.6% and for Top 5 is 91.2%, 76.5%, and 60.7% at family, superfamily, and fold levels, respectively. We also evaluated the performance of single DN-Fold (DN-FoldS), which showed the comparable results at the level of family and superfamily, compared to ensemble DN-Fold. Finally, we extended the binary classification problem of fold recognition to real-value regression task, which also show a promising performance. DN-Fold is freely available through a web server at http://iris.rnet.missouri.edu/dnfold.

Measuring in-vivo and in-situ ex-vivo the 3D deformation of the lamina cribrosa microstructure under elevated intraocular pressure

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Wei, Junchao; Yang, Bin; Voorhees, Andrew P.; Tran, Huong; Brazile, Bryn; Wang, Bo; Schuman, Joel; Smith, Matthew A.; Wollstein, Gadi; Sigal, Ian A.

2018-02-01

Elevated intraocular pressure (IOP) deforms the lamina cribrosa (LC), a structure within the optic nerve head (ONH) in the back of the eye. Evidence suggests that these deformations trigger events that eventually cause irreversible blindness, and have therefore been studied in-vivo using optical coherence tomography (OCT), and ex-vivo using OCT and a diversity of techniques. To the best of our knowledge, there have been no in-situ ex-vivo studies of LC mechanics. Our goal was two-fold: to introduce a technique for measuring 3D LC deformations from OCT, and to determine whether deformations of the LC induced by elevated IOP differ between in-vivo and in-situ ex-vivo conditions. A healthy adult rhesus macaque monkey was anesthetized and IOP was controlled by inserting a 27- gauge needle into the anterior chamber of the eye. Spectral domain OCT was used to obtain volumetric scans of the ONH at normal and elevated IOPs. To improve the visibility of the LC microstructure the scans were first processed using a novel denoising technique. Zero-normalized cross-correlation was used to find paired corresponding locations between images. For each location pair, the components of the 3D strain tensor were determined using non-rigid image registration. A mild IOP elevation from 10 to 15mmHg caused LC effective strains as large as 3%, and about 50% larger in-vivo than in-situ ex-vivo. The deformations were highly heterogeneous, with substantial 3D components, suggesting that accurate measurement of LC microstructure deformation requires high-resolution volumes. This technique will help improve understanding of LC biomechanics and how IOP contributes to glaucoma.

Dose-dependent effects of Lactobacillus rhamnosus on serum interleukin-17 production and intestinal T-cell responses in pigs challenged with Escherichia coli.

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Zhu, Yao-Hong; Li, Xiao-Qiong; Zhang, Wei; Zhou, Dong; Liu, Hao-Yu; Wang, Jiu-Feng

2014-03-01

The mechanism underlying the dose effect of probiotics on ameliorating diarrhea has not been fully elucidated. Here, low (1 × 10(9) CFU/ml) or high (1 × 10(11) CFU/ml) doses of Lactobacillus rhamnosus ATCC 7469 were administered orally to piglets for 1 week before F4 (K88)-positive enterotoxigenic Escherichia coli (F4(+) ETEC) challenge. Administration of a low, but not a high, dose of L. rhamnosus decreased the percentage of CD3(+) CD4(+) CD8(-) T cells in the peripheral blood. Notably, transiently increased serum concentrations of interleukin-17A (IL-17A) were observed after F4(+) ETEC challenge in pigs pretreated with a high dose of L. rhamnosus. Administration of L. rhamnosus increased the percentage of the small intestinal lamina propria CD3(+) CD4(+) CD8(-) cells and Peyer's patch CD3(+) CD4(-) CD8(-) and CD3(-) CD4(-) CD8(+) cells. The percentage of ileal intraepithelial CD3(+) CD4(-) CD8(+) cells increased only in the high-dose piglets. Administration of L. rhamnosus downregulated expression of ileal IL-17A after F4(+) ETEC challenge but had no effect on expression of gamma interferon (IFN-γ), IL-12, IL-4, and FOXP3 mRNA in the small intestine. Expression of jejunal IL-2, ileal transforming growth factor β1 (TGF-β1), and ileal IL-10 was upregulated in the low-dose piglets after F4(+) ETEC challenge. Our findings suggest that amelioration of infectious diarrhea in piglets by L. rhamnosus is associated with the generation of lamina propria CD3(+) CD4(+) CD8(-) T cells, the expansion of Peyer's patch CD3(+) CD4(-) CD8(-) and CD3(-) CD4(-) CD8(+) cells, and the attenuation of F4(+) ETEC-induced increase in CD3(+) CD4(+) CD8(+) T cells in the small intestine. However, consumption of high doses of L. rhamnosus may increase levels of serum IL-17A after F4(+) ETEC challenge, thus eliciting a strong proinflammatory response.

Infection with CagA-positive Helicobacter pylori strain containing three EPIYA C phosphorylation sites is associated with more severe gastric lesions in experimentally infected Mongolian gerbils (Meriones unguiculatus).

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Ferreira Júnior, M; Batista, S A; Vidigal, P V T; Cordeiro, A A C; Oliveira, F M S; Prata, L O; Diniz, A E T; Barral, C M; Barbuto, R C; Gomes, A D; Araújo, I D; Queiroz, D M M; Caliari, M V

2015-04-27

Infection with Helicobacter pylori strains containing high number of EPIYA-C phosphorylation sites in the CagA is associated with significant gastritis and increased risk of developing pre-malignant gastric lesions and gastric carcinoma. However, these findings have not been reproduced in animal models yet. Therefore, we investigated the effect on the gastric mucosa of Mongolian gerbil (Meriones unguiculatus) infected with CagA-positive H. pylori strains exhibiting one or three EPIYA-C phosphorilation sites. Mongolian gerbils were inoculated with H. pylori clonal isolates containing one or three EPIYA-C phosphorylation sites. Control group was composed by uninfected animals challenged with Brucella broth alone. Gastric fragments were evaluated by the modified Sydney System and digital morphometry. Clonal relatedness between the isolates was considered by the identical RAPD-PCR profiles and sequencing of five housekeeping genes, vacA i/d region and of oipA. The other virulence markers were present in both isolates (vacA s1i1d1m1, iceA2, and intact dupA). CagA of both isolates was translocated and phosphorylated in AGS cells. After 45 days of infection, there was a significant increase in the number of inflammatory cells and in the area of the lamina propria in the infected animals, notably in those infected by the CagA-positive strain with three EPIYA-C phosphorylation sites. After six months of infection, a high number of EPIYA-C phosphorylation sites was associated with progressive increase in the intensity of gastritis and in the area of the lamina propria. Atrophy, intestinal metaplasia, and dysplasia were also observed more frequently in animals infected with the CagA-positive isolate with three EPIYA-C sites.  We conclude that infection with H. pylori strain carrying a high number of CagA EPIYA-C phosphorylation sites is associated with more severe gastric lesions in an animal model of H. pylori infection.

Sensitive quantification of the HIV-1 reservoir in gut-associated lymphoid tissue.

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Sara Morón-López

Full Text Available The implementation of successful strategies to achieve an HIV cure has become a priority in HIV research. However, the current location and size of HIV reservoirs is still unknown since there are limited tools to evaluate HIV latency in viral sanctuaries such as gut-associated lymphoid tissue (GALT. As reported in the so called "Boston Patients", despite undetectable levels of proviral HIV-1 DNA in blood and GALT, viral rebound happens in just few months after ART interruption. This fact might imply that current methods are not sensitive enough to detect residual reservoirs. Showing that, it is imperative to improve the detection and quantification of HIV-1 reservoir in tissue samples. Herein, we propose a novel non-enzymatic protocol for purification of Lamina Propria Leukocytes (LPL from gut biopsies combined to viral HIV DNA (vDNA quantification by droplet digital PCR (ddPCR to improve the sensitivity and accuracy of viral reservoir measurements (LPL-vDNA assay.Endoscopic ileum biopsies were sampled from 12 HIV-1-infected cART-suppressed subjects. We performed a DTT/EDTA-based treatment for epithelial layer removal followed by non-enzymatic disruption of the tissue to obtain lamina propria cell suspension (LP. CD45+ cells were subsequently purified by flow sorting and vDNA was determined by ddPCR.vDNA quantification levels were significantly higher in purified LPLs (CD45+ than in bulk LPs (p<0.01. The levels of vDNA were higher in ileum samples than in concurrent PBMC from the same individuals (p = 0.002. As a result of the increased sensitivity of this purification method, the Poisson 95% confidence intervals of the vDNA quantification data from LPLs were narrower than that from bulk LPs. Of note, vDNA was unambiguously quantified above the detection limit in 100% of LPL samples, while only in 58% of bulk LPs.We propose an innovative combined protocol for a more sensitive detection of the HIV reservoir in gut-associated viral sanctuaries

Infection with CagA-positive Helicobacter pylori strain containing three EPIYA C phosphorylation sites is associated with more severe gastric lesions in experimentally infected Mongolian gerbils (Meriones unguiculatus

Directory of Open Access Journals (Sweden)

M. Ferreira Júnior

2015-04-01

Full Text Available Infection with Helicobacter pylori strains containing high number of EPIYA-C phosphorylation sites in the CagA is associated with significant gastritis and increased risk of developing pre-malignant gastric lesions and gastric carcinoma. However, these findings have not been reproduced in animal models yet. Therefore, we investigated the effect on the gastric mucosa of Mongolian gerbil (Meriones unguiculatus infected with CagA-positive H. pylori strains exhibiting one or three EPIYA-C phosphorilation sites. Mongolian gerbils were inoculated with H. pylori clonal isolates containing one or three EPIYA-C phosphorylation sites. Control group was composed by uninfected animals challenged with Brucella broth alone. Gastric fragments were evaluated by the modified Sydney System and digital morphometry. Clonal relatedness between the isolates was considered by the identical RAPD-PCR profiles and sequencing of five housekeeping genes, vacA i/d region and of oipA. The other virulence markers were present in both isolates (vacA s1i1d1m1, iceA2, and intact dupA. CagA of both isolates was translocated and phosphorylated in AGS cells. After 45 days of infection, there was a significant increase in the number of inflammatory cells and in the area of the lamina propria in the infected animals, notably in those infected by the CagA-positive strain with three EPIYA-C phosphorylation sites. After six months of infection, a high number of EPIYA-C phosphorylation sites was associated with progressive increase in the intensity of gastritis and in the area of the lamina propria. Atrophy, intestinal metaplasia, and dysplasia were also observed more frequently in animals infected with the CagA-positive isolate with three EPIYA-C sites.  We conclude that infection with H. pylori strain carrying a high number of CagA EPIYA-C phosphorylation sites is associated with more severe gastric lesions in an animal model of H. pylori infection.

Expression and distribution patterns of Mas-related gene receptor subtypes A-H in the mouse intestine: inflammation-induced changes.

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Avula, Leela Rani; Buckinx, Roeland; Favoreel, Herman; Cox, Eric; Adriaensen, Dirk; Van Nassauw, Luc; Timmermans, Jean-Pierre

2013-05-01

Mas-related gene (Mrg) receptors constitute a subfamily of G protein-coupled receptors that are implicated in nociception, and are as such considered potential targets for pain therapies. Furthermore, some Mrgs have been suggested to play roles in the regulation of inflammatory responses to non-immunological activation of mast cells and in mast cell-neuron communication. Except for MrgD, E and F, whose changed expression has been revealed during inflammation in the mouse intestine in our earlier studies, information concerning the remaining cloned mouse Mrg subtypes in the gastrointestinal tract during (patho) physiological conditions is lacking. Therefore, the present study aimed at identifying the presence and putative function of these remaining cloned Mrg subtypes (n = 19) in the (inflamed) mouse intestine. Using reverse transcriptase-PCR, quantitative-PCR and multiple immunofluorescence staining with commercial and newly custom-developed antibodies, we compared the ileum and the related dorsal root ganglia (DRG) of non-inflamed mice with those of two models of intestinal inflammation, i.e., intestinal schistosomiasis and 2,4,6-trinitrobenzene sulfonic acid-induced ileitis. In the non-inflamed ileum and DRG, the majority of the Mrg subtypes examined were sparsely expressed, showing a neuron-specific expression pattern. However, significant changes in the expression patterns of multiple Mrg subtypes were observed in the inflamed ileum; for instance, MrgA4, MrgB2and MrgB8 were expressed in a clearly increased number of enteric sensory neurons and in nerve fibers in the lamina propria, while de novo expression of MrgB10 was observed in enteric sensory neurons and in newly recruited mucosal mast cells (MMCs). The MrgB10 expressing MMCs were found to be in close contact with nerve fibers in the lamina propria. This is the first report on the expression of all cloned Mrg receptor subtypes in the (inflamed) mouse intestine. The observed changes in the expression and

Synovial folds in equine articular process joints

DEFF Research Database (Denmark)

Thomsen, Line Nymann; Berg, Lise Charlotte; Markussen, Bo

2013-01-01

Cervical synovial folds have been suggested as a potential cause of neck pain in humans. Little is known about the extent and characteristics of cervical synovial folds in horses.......Cervical synovial folds have been suggested as a potential cause of neck pain in humans. Little is known about the extent and characteristics of cervical synovial folds in horses....

In Vivo Changes in Lamina Cribrosa Microarchitecture and Optic Nerve Head Structure in Early Experimental Glaucoma.

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Kevin M Ivers

Full Text Available The lamina cribrosa likely plays an important role in retinal ganglion cell axon injury in glaucoma. We sought to (1 better understand optic nerve head (ONH structure and anterior lamina cribrosa surface (ALCS microarchitecture between fellow eyes of living, normal non-human primates and (2 characterize the time-course of in vivo structural changes in the ONH, ALCS microarchitecture, and retinal nerve fiber layer thickness (RNFLT in non-human primate eyes with early experimental glaucoma (EG. Spectral domain optical coherence tomography (SDOCT images of the ONH were acquired cross-sectionally in six bilaterally normal rhesus monkeys, and before and approximately every two weeks after inducing unilateral EG in seven rhesus monkeys. ONH parameters and RNFLT were quantified from segmented SDOCT images. Mean ALCS pore area, elongation and nearest neighbor distance (NND were quantified globally, in sectors and regionally from adaptive optics scanning laser ophthalmoscope images. In bilaterally normal monkeys, ONH parameters were similar between fellow eyes with few inter-eye differences in ALCS pore parameters. In EG monkeys, an increase in mean ALCS Depth (ALCSD was the first structural change measured in 6 of 7 EG eyes. A decrease in mean minimum rim width (MRW simultaneously accompanied this early change in 4 of 6 EG eyes and was the first structural change in the 7th EG eye. Mean ALCS pore parameters were among the first or second changes measured in 4 EG eyes. Mean ALCS pore area and NND increased in superotemporal and temporal sectors and in central and peripheral regions at the first time-point of change in ALCS pore geometry. RNFLT and/or mean ALCS radius of curvature were typically the last parameters to initially change. Survival analyses found mean ALCSD was the only parameter to significantly show an initial change prior to the first measured loss in RNFLT across EG eyes.

Potential of a polygonal prism and lamina; Takakuchu men no potential

Energy Technology Data Exchange (ETDEWEB)

Koyama, S

1996-05-01

With the use of rectangular coordinates O-XYZ, the potential of a calculation point P is expressed in the form of a triple repeated integral of a density {sigma} at point Q in the mass. The potential at the density {sigma} assumed to be 1 is named the potential of a polygonal prism. Further, a double repeated integral with an integral concerning Z removed from the triple integral is named the potential of polygonal lamina. This potential can be expressed in a quadratic form (linear form) with 2nd order partial derivative (1st order partial derivative) as a coefficient. On the contrary, in order to extract the 1st/2nd order partial derivatives from this potential by partial differential, it requires partial differentiation with these partial derivatives considered to be a constant. The reason that they can be realized is attributable to the zero result of the linear form which has as the coefficient a 3rd order partial derivative concerning the variable of integration in a primitive function. If this relation is used, the integral calculation and description may be simplified. An explanation was given with examples enumerated so that these conditions might be understood.

Dynamics of Folds in the Plane

Science.gov (United States)

Krylov, Nikolai A.; Rogers, Edwin L.

2011-01-01

Take a strip of paper and fold a crease intersecting the long edges, creating two angles. Choose one edge and consider the angle with the crease. Fold the opposite edge along the crease, creating a new crease that bisects the angle. Fold again, this time using the newly created crease and the initial edge, creating a new angle along the chosen…

Teaching computers to fold proteins

DEFF Research Database (Denmark)

Winther, Ole; Krogh, Anders Stærmose

2004-01-01

A new general algorithm for optimization of potential functions for protein folding is introduced. It is based upon gradient optimization of the thermodynamic stability of native folds of a training set of proteins with known structure. The iterative update rule contains two thermodynamic averages...

Origami-Inspired Folding of Thick, Rigid Panels

Science.gov (United States)

Trease, Brian P.; Thomson, Mark W.; Sigel, Deborah A.; Walkemeyer, Phillip E.; Zirbel, Shannon; Howell, Larry; Lang, Robert

2014-01-01

To achieve power of 250 kW or greater, a large compression ratio of stowed-to-deployed area is needed. Origami folding patterns were used to inspire the folding of a solar array to achieve synchronous deployment; however, origami models are generally created for near-zero-thickness material. Panel thickness is one of the main challenges of origami-inspired design. Three origami-inspired folding techniques (flasher, square twist, and map fold) were created with rigid panels and hinges. Hinge components are added to the model to enable folding of thick, rigid materials. Origami models are created assuming zero (or near zero) thickness. When a material with finite thickness is used, the panels are required to bend around an increasingly thick fold as they move away from the center of the model. The two approaches for dealing with material thickness are to use membrane hinges to connect the panels, or to add panel hinges, or hinges of the same thickness, at an appropriate width to enable folding.

Database Survey of Anti-Inflammatory Plants in South America: A Review

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Leônia Maria Batista

2011-04-01

Full Text Available Inflammation is a complex event linked to tissue damage whether by bacteria, physical trauma, chemical, heat or any other phenomenon. This physiological response is coordinated largely by a variety of chemical mediators that are released from the epithelium, the immunocytes and nerves of the lamina propria. However, if the factor that triggers the inflammation persists, the inflammation can become relentless, leading to an intensification of the lesion. The present work is a literature survey of plant extracts from the South American continent that have been reported to show anti-inflammatory activity. This review refers to 63 bacterial families of which the following stood out: Asteraceae, Fabaceae, Euphorbiaceae, Apocynaceae and Celastraceae, with their countries, parts used, types of extract used, model bioassays, organisms tested and their activity.

Database Survey of Anti-Inflammatory Plants in South America: A Review

Science.gov (United States)

de Morais Lima, Gedson Rodrigues; de Albuquerque Montenegro, Camila; de Almeida, Cynthia Layse Ferreira; de Athayde-Filho, Petrônio Filgueiras; Barbosa-Filho, José Maria; Batista, Leônia Maria

2011-01-01

Inflammation is a complex event linked to tissue damage whether by bacteria, physical trauma, chemical, heat or any other phenomenon. This physiological response is coordinated largely by a variety of chemical mediators that are released from the epithelium, the immunocytes and nerves of the lamina propria. However, if the factor that triggers the inflammation persists, the inflammation can become relentless, leading to an intensification of the lesion. The present work is a literature survey of plant extracts from the South American continent that have been reported to show anti-inflammatory activity. This review refers to 63 bacterial families of which the following stood out: Asteraceae, Fabaceae, Euphorbiaceae, Apocynaceae and Celastraceae, with their countries, parts used, types of extract used, model bioassays, organisms tested and their activity. PMID:21731467

Primary intestinal lymphangiectasia successfully treated by segmental resections of small bowel.

Science.gov (United States)

Kim, Na Rae; Lee, Suk-Koo; Suh, Yeon-Lim

2009-10-01

Primary intestinal lymphangiectasia is a rare cause of protein-losing enteropathy and usually presents with intermittent diarrhea or malnutrition. Diagnosis depends largely on its pathologic condition demonstrating greatly dilated lymphatics mainly in the lamina propria of the mucosa. We report a case of primary intestinal lymphangiectasia, of the diffuse type, presenting with abdominal pain and voluminous diarrhea in a previously healthy 8-year-old boy. He had periumbilical pain for 3 months before presentation. He was managed by segmental bowel resections and end-to-end anastomoses. The histopathologic condition of the resected small intestine showed lymphatic dilation limited mainly to the subserosa and mesentery but was not prominent in the mucosa. Abdominal pain and diarrhea subsided postoperatively. The present case is the fourth report describing a response to operative resection.

Clinical Toxoplasma gondii, Hammondia heydorni, and Sarcocystis spp. infections in dogs.

Science.gov (United States)

Dubey, J P; Ross, A D; Fritz, D

2003-12-01

Concurrent infections with coccidians Toxoplasma gondii, Sarcocystis spp., and a Hammondia heydorni-like parasite were identified in tissues of three littermate pups on a Kelpie dog breeding farm in Australia. In total, 20 pups in four litters had died following vaccination with an attenuated distemper virus vaccine. Toxoplasma gondii tachyzoites were identified immunohistochemically in tissues of two dogs. Sarcocystis sp. sporocysts were seen in the intestinal lamina propria of two dogs. Asexual and sexual stages of H. heydorni-like parasite were found in enterocytes of the small intestine of two dogs. Ultrastructural development of schizonts and gamonts of this parasite is described. None of the protozoa in these dogs reacted with antibodies to Neospora caninum. Feeding of uncooked tissue of sheep was considered to be the likely source of infection for these coccidians in dogs.

Collagenous gastritis in the pediatric age

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Antonio Rosell-Camps

2015-05-01

Full Text Available Collagenous gastritis (CG is an uncommon condition known in the pediatric age. It is characterized by the presence of subepithelial collagen bands (> 10 μm associated with lymphoplasmacytic infiltration of the stomach's lamina propria. Symptoms manifested by patients with CG may be common with many other disorders. It typically manifests with epigastralgia, vomiting, and iron deficiency during pre-adolescence. This condition's pathophysiology remains unclear. In contrast to adults, where association with collagenous colitis and other autoimmune conditions is more common, pediatric involvement is usually confined to the stomach. Drugs of choice include proton pump inhibitors and corticoids. A case is reported of a 12-year-old girl with abdominal pain and ferritin deficiency who was diagnosed with CG based on gastric biopsy and experienced a favorable outcome.

Experimental infection by Yersinia ruckeri O1 biotype 2 induces brain lesions and neurological signs in rainbow trout (Oncorhynchus mykiss)

DEFF Research Database (Denmark)

Strøm, H. K.; Ohtani, M.; Nowak, B.

2018-01-01

was then monitored for 22 days post-infection (dpi). Organs were sampled at 3 dpi and also from moribund fish showing signs of severe systemic infection such as bleeding, exophthalmia or erratic swimming behaviour. Y. ruckeri was observed in the meninges and diencephalon of the brain, and lamina propria of olfactory...... organ at 3 dpi. At 12 dpi, Y. ruckeri had spread throughout the brain including cranial connective tissues and ventricles and the infection was associated with haemorrhages and an infiltration with leucocytes. Y. ruckeri infection and associated with leucocyte infiltration were observed at 13 dpi....... In conclusion, Y. ruckeri strain 07111224 causes encephalitis in the acute phase of infection, which could explain why Y. ruckeri-affected fish show exophthalmia and erratic swimming known as signs of ERM....

Erythropoietin resistance in end-stage renal disease patient with gastric antral vascular ectasia

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Desiree Ji Re Lee

2015-09-01

Full Text Available AbstractWe observed a case of recombinant human erythropoietin resistance caused by Gastric Antral Vascular Ectasia in a 40-year-old female with ESRD on hemodialysis. Some associated factors such as autoimmune disease, hemolysis, heart and liver disease were discarded on physical examination and complementary tests. The diagnosis is based on the clinical history and endoscopic appearance of watermelon stomach. The histologic findings are fibromuscular proliferation and capillary ectasia with microvascular thrombosis of the lamina propria. However, these histologic findings are not necessary to confirm the diagnosis. Gastric Antral Vascular Ectasia is a serious condition and should be considered in ESRD patients on hemodialysis with anemia and resistance to recombinant human erythropoietin because GAVE is potentially curable with specific endoscopic treatment method or through surgical procedure.

Vocal fold hemorrhage: factors predicting recurrence.

Science.gov (United States)

Lennon, Christen J; Murry, Thomas; Sulica, Lucian

2014-01-01

Vocal fold hemorrhage is an acute phonotraumatic injury treated with voice rest; recurrence is a generally accepted indication for surgical intervention. This study aims to identify factors predictive of recurrence based on outcomes of a large clinical series. Retrospective cohort. Retrospective review of cases of vocal fold hemorrhage presenting to a university laryngology service. Demographic information was compiled. Videostroboscopic exams were evaluated for hemorrhage extent, presence of varix, mucosal lesion, and/or vocal fold paresis. Vocal fold hemorrhage recurrence was the main outcome measure. Follow-up telephone survey was used to complement clinical data. Forty-seven instances of vocal fold hemorrhage were evaluated (25M:22F; 32 professional voice users). Twelve of the 47 (26%) patients experienced recurrence. Only the presence of varix demonstrated significant association with recurrence (P = 0.0089) on multivariate logistic regression. Vocal fold hemorrhage recurred in approximately 26% of patients. Varix was a predictor of recurrence, with 48% of those with varix experiencing recurrence. Monitoring, behavioral management and/or surgical intervention may be indicated to treat patients with such characteristics. © 2013 The American Laryngological, Rhinological and Otological Society, Inc.

Geometric U-folds in four dimensions

Science.gov (United States)

Lazaroiu, C. I.; Shahbazi, C. S.

2018-01-01

We describe a general construction of geometric U-folds compatible with a non-trivial extension of the global formulation of four-dimensional extended supergravity on a differentiable spin manifold. The topology of geometric U-folds depends on certain flat fiber bundles which encode how supergravity fields are globally glued together. We show that smooth non-trivial U-folds of this type can exist only in theories where both the scalar and space-time manifolds have non-trivial fundamental group and in addition the scalar map of the solution is homotopically non-trivial. Consistency with string theory requires smooth geometric U-folds to be glued using subgroups of the effective discrete U-duality group, implying that the fundamental group of the scalar manifold of such solutions must be a subgroup of the latter. We construct simple examples of geometric U-folds in a generalization of the axion-dilaton model of \

Guiding the folding pathway of DNA origami.

Science.gov (United States)

Dunn, Katherine E; Dannenberg, Frits; Ouldridge, Thomas E; Kwiatkowska, Marta; Turberfield, Andrew J; Bath, Jonathan

2015-09-03

DNA origami is a robust assembly technique that folds a single-stranded DNA template into a target structure by annealing it with hundreds of short 'staple' strands. Its guiding design principle is that the target structure is the single most stable configuration. The folding transition is cooperative and, as in the case of proteins, is governed by information encoded in the polymer sequence. A typical origami folds primarily into the desired shape, but misfolded structures can kinetically trap the system and reduce the yield. Although adjusting assembly conditions or following empirical design rules can improve yield, well-folded origami often need to be separated from misfolded structures. The problem could in principle be avoided if assembly pathway and kinetics were fully understood and then rationally optimized. To this end, here we present a DNA origami system with the unusual property of being able to form a small set of distinguishable and well-folded shapes that represent discrete and approximately degenerate energy minima in a vast folding landscape, thus allowing us to probe the assembly process. The obtained high yield of well-folded origami structures confirms the existence of efficient folding pathways, while the shape distribution provides information about individual trajectories through the folding landscape. We find that, similarly to protein folding, the assembly of DNA origami is highly cooperative; that reversible bond formation is important in recovering from transient misfoldings; and that the early formation of long-range connections can very effectively enforce particular folds. We use these insights to inform the design of the system so as to steer assembly towards desired structures. Expanding the rational design process to include the assembly pathway should thus enable more reproducible synthesis, particularly when targeting more complex structures. We anticipate that this expansion will be essential if DNA origami is to continue its

Self-folding graphene-polymer bilayers

Energy Technology Data Exchange (ETDEWEB)

Deng, Tao [Institute of Microelectronics, Tsinghua University, Beijing 100084 (China); Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, Maryland 21218 (United States); Yoon, ChangKyu [Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, Maryland 21218 (United States); Jin, Qianru [Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, Maryland 21218 (United States); Li, Mingen [Department of Physics, Johns Hopkins University, Baltimore, Maryland 21218 (United States); Liu, Zewen [Institute of Microelectronics, Tsinghua University, Beijing 100084 (China); Gracias, David H., E-mail: dgracias@jhu.edu [Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, Maryland 21218 (United States); Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, Maryland 21218 (United States)

2015-05-18

In order to incorporate the extraordinary intrinsic thermal, electrical, mechanical, and optical properties of graphene with three dimensional (3D) flexible substrates, we introduce a solvent-driven self-folding approach using graphene-polymer bilayers. A polymer (SU-8) film was spin coated atop chemically vapor deposited graphene films on wafer substrates and graphene-polymer bilayers were patterned with or without metal electrodes using photolithography, thin film deposition, and etching. After patterning, the bilayers were released from the substrates and they self-folded to form fully integrated, curved, and folded structures. In contrast to planar graphene sensors on rigid substrates, we assembled curved and folded sensors that are flexible and they feature smaller form factors due to their 3D geometry and large surface areas due to their multiple rolled architectures. We believe that this approach could be used to assemble a range of high performance 3D electronic and optical devices of relevance to sensing, diagnostics, wearables, and energy harvesting.

Comparison of 640-Slice Multidetector Computed Tomography Versus 32-Slice MDCT for Imaging of the Osteo-odonto-keratoprosthesis Lamina.

Science.gov (United States)

Norris, Joseph M; Kishikova, Lyudmila; Avadhanam, Venkata S; Koumellis, Panos; Francis, Ian S; Liu, Christopher S C

2015-08-01

To investigate the efficacy of 640-slice multidetector computed tomography (MDCT) for detecting osteo-odonto laminar resorption in the osteo-odonto-keratoprosthesis (OOKP) compared with the current standard 32-slice MDCT. Explanted OOKP laminae and bone-dentine fragments were scanned using 640-slice MDCT (Aquilion ONE; Toshiba) and 32-slice MDCT (LightSpeed Pro32; GE Healthcare). Pertinent comparisons including image quality, radiation dose, and scanning parameters were made. Benefits of 640-slice MDCT over 32-slice MDCT were shown. Key comparisons of 640-slice MDCT versus 32-slice MDCT included the following: percentage difference and correlation coefficient between radiological and anatomical measurements, 1.35% versus 3.67% and 0.9961 versus 0.9882, respectively; dose-length product, 63.50 versus 70.26; rotation time, 0.175 seconds versus 1.000 seconds; and detector coverage width, 16 cm versus 2 cm. Resorption of the osteo-odonto lamina after OOKP surgery can result in potentially sight-threatening complications, hence it warrants regular monitoring and timely intervention. MDCT remains the gold standard for radiological assessment of laminar resorption, which facilitates detection of subtle laminar changes earlier than the onset of clinical signs, thus indicating when preemptive measures can be taken. The 640-slice MDCT exhibits several advantages over traditional 32-slice MDCT. However, such benefits may not offset cost implications, except in rare cases, such as in young patients who might undergo years of radiation exposure.

How old is your fold?

NARCIS (Netherlands)

Winstanley, Henry F.; Abeln, Sanne; Deane, Charlotte M.

Motivation: At present there exists no age estimate for the different protein structures found in nature. It has become clear from occurrence studies that different folds arose at different points in evolutionary time. An estimation of the age of different folds would be a starting point for many

Stromatolite laminae (Lagoa Vermelha, Brasil) as archives for reservoir age changes

Science.gov (United States)

Bruggmann, Sylvie; Vasconcelos, Crisogono; Hajdas, Irka

2016-04-01

As laminated biogenic or abiogenic sedimentary structures [1], stromatolites record environmental changes along growth profiles, revealing possible changes in reservoir ages due to input of older carbon. A modern stromatolite sample was collected in Lagoa Vermelha (100 km east of Rio de Janeiro, Brasil) an area known for upwelling of South Atlantic Central Water (SACW). 34 samples from a transect cutting the lamination were collected with a hand-driller for standard geochemistry and 14C AMS analyses. Shells collected in 2015 were analysed for estimation of the present-day reservoir age. 14C ages of laminae and the reservoir age were used to apply the age-depth model to the stromatolite transect with the OxCal depositional model (Marine13 calibration curve; [2]). Small-scale changes in the composition of laminae report environmental changes, e.g. upwelling. The well-laminated middle part (laminated boundstone; ca. 4cm) of the stromatolite transect was found to have grown in a short time period of less than 100 years (1163-1210 14C y BP), with four excursions towards older 14C ages (ca. 1200 14C y BP). To detect possible changes of marine 14C, calendar years assuming a stable modern reservoir age were used to simulate atmospheric 14C ages with the southern hemisphere IntCal13 atmospheric calibration curve [3]. The offset between the measured and simulated 14C ages indicates a variability of the reservoir age between -99 and 268 14C y with highest reservoir correction found for the layers with indication of environmental changes (e.g. upwelling). Thus, this simulation confirms the occurrence of older carbon and points out the sensitivity of stromatolites for changing reservoir ages. [1] M.A. Semikhatov, C.D. Gebelein, P. Cloud, S.M. Awramik, W.C. Benmore (1979). Stromatolite morphogenesis - progress and problems. Canadian Journal of Earth Sciences, 19:992-1015. [2] P.J. Reimer, E. Bard, A. Bayliss, J. W. Beck, P. G. Blackwell, C. Bronk Ramsey, C. E. Buck, H. Cheng, R

Muscular anatomy of the human ventricular folds.

Science.gov (United States)

Moon, Jerald; Alipour, Fariborz

2013-09-01

Our purpose in this study was to better understand the muscular anatomy of the ventricular folds in order to help improve biomechanical modeling of phonation and to better understand the role of these muscles during phonatory and nonphonatory tasks. Four human larynges were decalcified, sectioned coronally from posterior to anterior by a CryoJane tape transfer system, and stained with Masson's trichrome. The total and relative areas of muscles observed in each section were calculated and used for characterizing the muscle distribution within the ventricular folds. The ventricular folds contained anteriorly coursing thyroarytenoid and ventricularis muscle fibers that were in the lower half of the ventricular fold posteriorly, and some ventricularis muscle was evident in the upper and lateral portions of the fold more anteriorly. Very little muscle tissue was observed in the medial half of the fold, and the anterior half of the ventricular fold was largely devoid of any muscle tissue. All 4 larynges contained muscle bundles that coursed superiorly and medially through the upper half of the fold, toward the lateral margin of the epiglottis. Although variability of expression was evident, a well-defined thyroarytenoid muscle was readily apparent lateral to the arytenoid cartilage in all specimens.

Exact folded-band chaotic oscillator.

Science.gov (United States)

Corron, Ned J; Blakely, Jonathan N

2012-06-01

An exactly solvable chaotic oscillator with folded-band dynamics is shown. The oscillator is a hybrid dynamical system containing a linear ordinary differential equation and a nonlinear switching condition. Bounded oscillations are provably chaotic, and successive waveform maxima yield a one-dimensional piecewise-linear return map with segments of both positive and negative slopes. Continuous-time dynamics exhibit a folded-band topology similar to Rössler's oscillator. An exact solution is written as a linear convolution of a fixed basis pulse and a discrete binary sequence, from which an equivalent symbolic dynamics is obtained. The folded-band topology is shown to be dependent on the symbol grammar.

Vocal fold paresis - a debilitating and underdiagnosed condition.

Science.gov (United States)

Harris, G; O'Meara, C; Pemberton, C; Rough, J; Darveniza, P; Tisch, S; Cole, I

2017-07-01

To review the clinical signs of vocal fold paresis on laryngeal videostroboscopy, to quantify its impact on patients' quality of life and to confirm the benefit of laryngeal electromyography in its diagnosis. Twenty-nine vocal fold paresis patients were referred for laryngeal electromyography. Voice Handicap Index 10 results were compared to 43 patients diagnosed with vocal fold paralysis. Laryngeal videostroboscopy analysis was conducted to determine side of paresis. Blinded laryngeal electromyography confirmed vocal fold paresis in 92.6 per cent of cases, with vocal fold lag being the most common diagnostic sign. The laryngology team accurately predicted side of paresis in 76 per cent of cases. Total Voice Handicap Index 10 responses were not significantly different between vocal fold paralysis and vocal fold paresis groups (26.08 ± 0.21 and 22.93 ± 0.17, respectively). Vocal fold paresis has a significant impact on quality of life. This study shows that laryngeal electromyography is an important diagnostic tool. Patients with persisting dysphonia and apparently normal vocal fold movement, who fail to respond to appropriate speech therapy, should be investigated for a diagnosis of vocal fold paresis.

Adaptive Origami for Efficiently Folded Structures

Science.gov (United States)

2016-02-01

heating. Although a large fold angle at a high temperature is desirable in order to extrapolate the origami geometry toward closure, more emphasis is...AFRL-RQ-WP-TR-2016-0020 ADAPTIVE ORIGAMI FOR EFFICIENTLY FOLDED STRUCTURES James J. Joo and Greg Reich Design and Analysis Branch... ORIGAMI FOR EFFICIENTLY FOLDED STRUCTURES 5a. CONTRACT NUMBER In-house 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 61102F 6. AUTHOR(S) James J

Vocal fold paralysis secondary to phonotrauma.

Science.gov (United States)

Klein, Travis A L; Gaziano, Joy E; Ridley, Marion B

2014-01-01

A unique case of acute onset vocal fold paralysis secondary to phonotrauma is presented. The cause was forceful vocalization by a drill instructor on a firearm range. Imaging studies revealed extensive intralaryngeal and retropharyngeal hemorrhage. Laryngoscopy showed a complete left vocal fold paralysis. Relative voice rest was recommended, and the patient regained normal vocal fold mobility and function after approximately 12 weeks. Copyright © 2014 The Voice Foundation. All rights reserved.

100-fold but not 50-fold dystrophin overexpression aggravates electrocardiographic defects in the mdx model of Duchenne muscular dystrophy

Directory of Open Access Journals (Sweden)

Yongping Yue

2016-01-01

Full Text Available Dystrophin gene replacement holds the promise of treating Duchenne muscular dystrophy. Supraphysiological expression is a concern for all gene therapy studies. In the case of Duchenne muscular dystrophy, Chamberlain and colleagues found that 50-fold overexpression did not cause deleterious side effect in skeletal muscle. To determine whether excessive dystrophin expression in the heart is safe, we studied two lines of transgenic mdx mice that selectively expressed a therapeutic minidystrophin gene in the heart at 50-fold and 100-fold of the normal levels. In the line with 50-fold overexpression, minidystrophin showed sarcolemmal localization and electrocardiogram abnormalities were corrected. However, in the line with 100-fold overexpression, we not only detected sarcolemmal minidystrophin expression but also observed accumulation of minidystrophin vesicles in the sarcoplasm. Excessive minidystrophin expression did not correct tachycardia, a characteristic feature of Duchenne muscular dystrophy. Importantly, several electrocardiogram parameters (QT interval, QRS duration and the cardiomyopathy index became worse than that of mdx mice. Our data suggests that the mouse heart can tolerate 50-fold minidystrophin overexpression, but 100-fold overexpression leads to cardiac toxicity.

In Vivo Confocal Microscopy and Anterior Segment Optic Coherence Tomography Findings in Ocular Ochronosis

Directory of Open Access Journals (Sweden)

Elif Demirkilinc Biler

2015-01-01

Full Text Available Purpose. To report clinical and in vivo confocal microscopy (IVCM findings of two patients with ocular ochronosis secondary due to alkaptonuria. Materials and Methods. Complete ophthalmologic examinations, including IVCM (HRT II/Rostock Cornea Module, Heidelberg, Germany, anterior segment optical coherence tomography (AS-OCT (Topcon 3D spectral-domain OCT 2000, Topcon Medical Systems, Paramus, NJ, USA, corneal topography (Pentacam, OCULUS Optikgeräte GmbH, Wetzlar, Germany, and anterior segment photography, were performed. Results. Biomicroscopic examination showed bilateral darkly pigmented lesions of the nasal and temporal conjunctiva and episclera in both patients. In vivo confocal microscopy of the lesions revealed prominent degenerative changes, including vacuoles and fragmentation of collagen fibers in the affected conjunctival lamina propria and episclera. Hyperreflective pigment granules in different shapes were demonstrated in the substantia propria beneath the basement membrane. AS-OCT of Case 1 demonstrated hyporeflective areas. Fundus examination was within normal limits in both patients, except tilted optic discs with peripapillary atrophy in one of the patients. Corneal topography, thickness, and macular OCT were normal bilaterally in both cases. Conclusion. The degenerative and anatomic changes due to ochronotic pigment deposition in alkaptonuria can be demonstrated in detail with IVCM and AS-OCT. Confocal microscopic analysis in ocular ochronosis may serve as a useful adjunct in diagnosis and monitoring of the disease progression.

Sarcoidosis Presenting as Bilateral Vocal Fold Immobility.

Science.gov (United States)

Hintze, Justin M; Gnagi, Sharon H; Lott, David G

2018-05-01

Bilateral true vocal fold paralysis is rarely attributable to inflammatory diseases. Sarcoidosis is a rare but important etiology of bilateral true vocal fold paralysis by compressive lymphadenopathy, granulomatous infiltration, and neural involvement. We describe the first reported case of sarcoidosis presenting as bilateral vocal fold immobility caused by direct fixation by granulomatous infiltration severe enough to necessitate tracheostomy insertion. In addition, we discuss the presentation, the pathophysiology, and the treatment of this disease with a review of the literature of previously reported cases of sarcoidosis-related vocal fold immobility. Sarcoidosis should therefore be an important consideration for the otolaryngologist's differential diagnosis of true vocal fold immobility. Copyright © 2018 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

Extreme Mechanics: Self-Folding Origami

Science.gov (United States)

Santangelo, Christian D.

2017-03-01

Origami has emerged as a tool for designing three-dimensional structures from flat films. Because they can be fabricated by lithographic or roll-to-roll processing techniques, they have great potential for the manufacture of complicated geometries and devices. This article discusses the mechanics of origami and kirigami with a view toward understanding how to design self-folding origami structures. Whether an origami structure can be made to fold autonomously depends strongly on the geometry and kinematics of the origami fold pattern. This article collects some of the results on origami rigidity into a single framework, and discusses how these aspects affect the foldability of origami. Despite recent progress, most problems in origami and origami design remain completely open.

Multi-crease Self-folding by Global Heating.

Science.gov (United States)

Miyashita, Shuhei; Onal, Cagdas D; Rus, Daniela

2015-01-01

This study demonstrates a new approach to autonomous folding for the body of a 3D robot from a 2D sheet, using heat. We approach this challenge by folding a 0.27-mm sheetlike material into a structure. We utilize the thermal deformation of a contractive sheet sandwiched by rigid structural layers. During this baking process, the heat applied on the entire sheet induces contraction of the contracting layer and thus forms an instructed bend in the sheet. To attain the targeted folding angles, the V-fold spans method is used. The targeted angle θout can be kinematically encoded into crease geometry. The realization of this angle in the folded structure can be approximately controlled by a contraction angle θin. The process is non-reversible, is reliable, and is relatively fast. Our method can be applied simultaneously to all the folds in multi-crease origami structures. We demonstrate the use of this method to create a lightweight mobile robot.

[Clinical analysis of vocal fold firbrous mass].

Science.gov (United States)

Chen, Hao; Sun, Jing Wu; Wan, Guang Lun; Hu, Yan Ming

2018-03-01

To explore the character of laryngoscopy finding, voice, and therapy of vocal fold fibrous mass. Clinical data, morphology, voice character, surgery and pathology of 15 cases with vocal fold fibrous mass were analyzed. The morbidity of vocal fold fibrous mass might be related to overuse of voice and laryngopharyngeal reflex. Laryngoscopy revealed shuttle line appearance, smoothness and decreased mucosal wave of vocal fold. These patients were invalid for voice training and might be improved by surgery, but recovery is slow. The morbidity of vocal fold fibrous mass might be related to overuse of voice and laryngopharyngeal reflex. Conservative treatment is ineffective for this disease, and surgery might improve. Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.

Factors that affect coseismic folds in an overburden layer

Science.gov (United States)

Zeng, Shaogang; Cai, Yongen

2018-03-01

Coseismic folds induced by blind thrust faults have been observed in many earthquake zones, and they have received widespread attention from geologists and geophysicists. Numerous studies have been conducted regarding fold kinematics; however, few have studied fold dynamics quantitatively. In this paper, we establish a conceptual model with a thrust fault zone and tectonic stress load to study the factors that affect coseismic folds and their formation mechanisms using the finite element method. The numerical results show that the fault dip angle is a key factor that controls folding. The greater the dip angle is, the steeper the fold slope. The second most important factor is the overburden thickness. The thicker the overburden is, the more gradual the fold. In this case, folds are difficult to identify in field surveys. Therefore, if a fold can be easily identified with the naked eye, the overburden is likely shallow. The least important factors are the mechanical parameters of the overburden. The larger the Young's modulus of the overburden is, the smaller the displacement of the fold and the fold slope. Strong horizontal compression and vertical extension in the overburden near the fault zone are the main mechanisms that form coseismic folds.

RNAslider: a faster engine for consecutive windows folding and its application to the analysis of genomic folding asymmetry.

Science.gov (United States)

Horesh, Yair; Wexler, Ydo; Lebenthal, Ilana; Ziv-Ukelson, Michal; Unger, Ron

2009-03-04

Scanning large genomes with a sliding window in search of locally stable RNA structures is a well motivated problem in bioinformatics. Given a predefined window size L and an RNA sequence S of size N (L free energy (MFE) for the folding of each of the L-sized substrings of S. The consecutive windows folding problem can be naively solved in O(NL3) by applying any of the classical cubic-time RNA folding algorithms to each of the N-L windows of size L. Recently an O(NL2) solution for this problem has been described. Here, we describe and implement an O(NLpsi(L)) engine for the consecutive windows folding problem, where psi(L) is shown to converge to O(1) under the assumption of a standard probabilistic polymer folding model, yielding an O(L) speedup which is experimentally confirmed. Using this tool, we note an intriguing directionality (5'-3' vs. 3'-5') folding bias, i.e. that the minimal free energy (MFE) of folding is higher in the native direction of the DNA than in the reverse direction of various genomic regions in several organisms including regions of the genomes that do not encode proteins or ncRNA. This bias largely emerges from the genomic dinucleotide bias which affects the MFE, however we see some variations in the folding bias in the different genomic regions when normalized to the dinucleotide bias. We also present results from calculating the MFE landscape of a mouse chromosome 1, characterizing the MFE of the long ncRNA molecules that reside in this chromosome. The efficient consecutive windows folding engine described in this paper allows for genome wide scans for ncRNA molecules as well as large-scale statistics. This is implemented here as a software tool, called RNAslider, and applied to the scanning of long chromosomes, leading to the observation of features that are visible only on a large scale.

Physics of protein folding

Science.gov (United States)

Finkelstein, A. V.; Galzitskaya, O. V.

2004-04-01

Protein physics is grounded on three fundamental experimental facts: protein, this long heteropolymer, has a well defined compact three-dimensional structure; this structure can spontaneously arise from the unfolded protein chain in appropriate environment; and this structure is separated from the unfolded state of the chain by the “all-or-none” phase transition, which ensures robustness of protein structure and therefore of its action. The aim of this review is to consider modern understanding of physical principles of self-organization of protein structures and to overview such important features of this process, as finding out the unique protein structure among zillions alternatives, nucleation of the folding process and metastable folding intermediates. Towards this end we will consider the main experimental facts and simple, mostly phenomenological theoretical models. We will concentrate on relatively small (single-domain) water-soluble globular proteins (whose structure and especially folding are much better studied and understood than those of large or membrane and fibrous proteins) and consider kinetic and structural aspects of transition of initially unfolded protein chains into their final solid (“native”) 3D structures.

Natural triple beta-stranded fibrous folds.

Science.gov (United States)

Mitraki, Anna; Papanikolopoulou, Katerina; Van Raaij, Mark J

2006-01-01

A distinctive family of beta-structured folds has recently been described for fibrous proteins from viruses. Virus fibers are usually involved in specific host-cell recognition. They are asymmetric homotrimeric proteins consisting of an N-terminal virus-binding tail, a central shaft or stalk domain, and a C-terminal globular receptor-binding domain. Often they are entirely or nearly entirely composed of beta-structure. Apart from their biological relevance and possible gene therapy applications, their shape, stability, and rigidity suggest they may be useful as blueprints for biomechanical design. Folding and unfolding studies suggest their globular C-terminal domain may fold first, followed by a "zipping-up" of the shaft domains. The C-terminal domains appear to be important for registration because peptides corresponding to shaft domains alone aggregate into nonnative fibers and/or amyloid structures. C-terminal domains can be exchanged between different fibers and the resulting chimeric proteins are useful as a way to solve structures of unknown parts of the shaft domains. The following natural triple beta-stranded fibrous folds have been discovered by X-ray crystallography: the triple beta-spiral, triple beta-helix, and T4 short tail fiber fold. All have a central longitudinal hydrophobic core and extensive intermonomer polar and nonpolar interactions. Now that a reasonable body of structural and folding knowledge has been assembled about these fibrous proteins, the next challenge and opportunity is to start using this information in medical and industrial applications such as gene therapy and nanotechnology.

In vivo measurement of vocal fold surface resistance.

Science.gov (United States)

Mizuta, Masanobu; Kurita, Takashi; Dillon, Neal P; Kimball, Emily E; Garrett, C Gaelyn; Sivasankar, M Preeti; Webster, Robert J; Rousseau, Bernard

2017-10-01

A custom-designed probe was developed to measure vocal fold surface resistance in vivo. The purpose of this study was to demonstrate proof of concept of using vocal fold surface resistance as a proxy of functional tissue integrity after acute phonotrauma using an animal model. Prospective animal study. New Zealand White breeder rabbits received 120 minutes of airflow without vocal fold approximation (control) or 120 minutes of raised intensity phonation (experimental). The probe was inserted via laryngoscope and placed on the left vocal fold under endoscopic visualization. Vocal fold surface resistance of the middle one-third of the vocal fold was measured after 0 (baseline), 60, and 120 minutes of phonation. After the phonation procedure, the larynx was harvested and prepared for transmission electron microscopy. In the control group, vocal fold surface resistance values remained stable across time points. In the experimental group, surface resistance (X% ± Y% relative to baseline) was significantly decreased after 120 minutes of raised intensity phonation. This was associated with structural changes using transmission electron microscopy, which revealed damage to the vocal fold epithelium after phonotrauma, including disruption of the epithelium and basement membrane, dilated paracellular spaces, and alterations to epithelial microprojections. In contrast, control vocal fold specimens showed well-preserved stratified squamous epithelia. These data demonstrate the feasibility of measuring vocal fold surface resistance in vivo as a means of evaluating functional vocal fold epithelial barrier integrity. Device prototypes are in development for additional testing, validation, and for clinical applications in laryngology. NA Laryngoscope, 127:E364-E370, 2017. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

MARATHON DESPITE UNILATERAL VOCAL FOLD PARALYSIS

Directory of Open Access Journals (Sweden)

Matthias Echternach

2008-06-01

Full Text Available The principal symptoms of unilateral vocal fold paralysis are hoarseness and difficulty in swallowing. Dyspnea is comparatively rare (Laccourreye et al., 2003. The extent to which unilateral vocal fold paralysis may lead to respiratory problems at all - in contrast to bilateral vocal fold paralysis- has not yet well been determined. On the one hand, inspiration is impaired with unilateral vocal fold paralysis; on the other hand, neither the position of the vocal fold paralysis nor the degree of breathiness correlates with respiratory parameters (Cantarella et al., 2003; 2005. The question of what respiratory stress a patient with a vocal fold paresis can endure has not yet been dealt with.A 43 year-old female patient was suffering from recurrent unspecific respiratory complaints for four months after physical activity. During training for a marathon, she experienced no difficulty in breathing. These unspecific respiratory complaints occurred only after athletic activity and persisted for hours. The patient observed neither an increased coughing nor a stridor. Her voice remained unaltered during the attacks, nor were there any signs of a symptomatic gastroesophageal reflux or infectious disease. A cardio-pulmonary and a radiological examination by means of an X-ray of the thorax also revealed no pathological phenomena. As antiallergic and antiobstructive therapy remained unsuccessful, a laryngological examination was performed in order to exclude a vocal cord dysfunction.Surprisingly enough, the laryngostroboscopy showed, as an initial description, a vocal fold paralysis of the left vocal fold in median position (Figure 1. The anamnestic background for the cause was unclear. The only clue was a thoracotomy on the left side due to a pleuritis in childhood. A subsequent laryngoscopic examination had never been performed. Good mucosa waves and amplitudes were shown bilateral with complete glottal closure. Neither in the acoustic analysis, nor in the

Fold and Fit: Space Conserving Shape Editing

KAUST Repository

Ibrahim, Mohamed

2017-09-01

We present a framework that folds man-made objects in a structure-aware manner for space-conserving storage and transportation. Given a segmented 3D mesh of a man-made object, our framework jointly optimizes for joint locations, the folding order, and folding angles for each part of the model, enabling it to transform into a spatially efficient configuration while keeping its original functionality as intact as possible. That is, if a model is supposed to withstand several forces in its initial state to serve its functionality, our framework places the joints between the parts of the model such that the model can withstand forces with magnitudes that are comparable to the magnitudes applied on the unedited model. Furthermore, if the folded shape is not compact, our framework proposes further segmentation of the model to improve its compactness in its folded state.

Self-folding miniature elastic electric devices

International Nuclear Information System (INIS)

Miyashita, Shuhei; Meeker, Laura; Rus, Daniela; Tolley, Michael T; Wood, Robert J

2014-01-01

Printing functional materials represents a considerable impact on the access to manufacturing technology. In this paper we present a methodology and validation of print-and-self-fold miniature electric devices. Polyvinyl chloride laminated sheets based on metalized polyester film show reliable self-folding processes under a heat application, and it configures 3D electric devices. We exemplify this technique by fabricating fundamental electric devices, namely a resistor, capacitor, and inductor. Namely, we show the development of a self-folded stretchable resistor, variable resistor, capacitive strain sensor, and an actuation mechanism consisting of a folded contractible solenoid coil. Because of their pre-defined kinematic design, these devices feature elasticity, making them suitable as sensors and actuators in flexible circuits. Finally, an RLC circuit obtained from the integration of developed devices is demonstrated, in which the coil based actuator is controlled by reading a capacitive strain sensor. (paper)

Distinction between porcine circovirus type 2 enteritis and porcine proliferative enteropathy caused by Lawsonia intracellularis

DEFF Research Database (Denmark)

Jensen, Tim Kåre; Vigre, Håkan; Svensmark, B.

2006-01-01

The presence of porcine circovirus type 2 (PCV2) was studied immunohistochemically in formalin-fixed, paraffin wax-embedded samples of intestinal tissue from 80 pigs with a clinical history suggestive of Lawsonia intracellularis-associated diarrhoea. Histopathologically, enteritis of varying...... in the submucosa, lamina propria and crypt epithelium, as well as in the lymphoid tissue of the ileum and colon. Multinucleated giant cells, however, were seen in both infections. PCV2 was about three times more likely to be detected in L. intracellularis-negative than in L. intracellularis-positive samples (P ... intensity was diagnosed in 64 of the pigs. Of these 64 animals, 34 (18%) were infected with both PCV2 and L. intracellularis. Of the remaining 30 cases of enteritis, 23 (77%) were attributed to PCV2 infection alone. The PCV2-associated enteritis cases showed necrotizing ileitis and colitis...

Microvascular lesions of the true vocal fold.

Science.gov (United States)

Postma, G N; Courey, M S; Ossoff, R H

1998-06-01

Microvascular lesions, also called varices or capillary ectasias, in contrast to vocal fold polyps with telangiectatic vessels, are relatively small lesions arising from the microcirculation of the vocal fold. Varices are most commonly seen in female professional vocalists and may be secondary to repetitive trauma, hormonal variations, or repeated inflammation. Microvascular lesions may either be asymptomatic or cause frank dysphonia by interrupting the normal vibratory pattern, mass, or closure of the vocal folds. They may also lead to vocal fold hemorrhage, scarring, or polyp formation. Laryngovideostroboscopy is the key in determining the functional significance of vocal fold varices. Management of patients with a varix includes medical therapy, speech therapy, and occasionally surgical vaporization. Indications for surgery are recurrent hemorrhage, enlargement of the varix, development of a mass in conjunction with the varix or hemorrhage, and unacceptable dysphonia after maximal medical and speech therapy due to a functionally significant varix.

Approaching climate-adaptive facades with foldings

DEFF Research Database (Denmark)

Sack-Nielsen, Torsten

2014-01-01

envelopes based on folding principles such as origami. Three major aspects cover the project’s interest in this topic: Shape, kinetics and the application of new multi-functional materials form the interdisciplinary framework of this research. Shape// Initially small paper sketch models demonstrate folding...

Design and simulation of origami structures with smooth folds.

Science.gov (United States)

Peraza Hernandez, E A; Hartl, D J; Lagoudas, D C

2017-04-01

Origami has enabled new approaches to the fabrication and functionality of multiple structures. Current methods for origami design are restricted to the idealization of folds as creases of zeroth-order geometric continuity. Such an idealization is not proper for origami structures of non-negligible fold thickness or maximum curvature at the folds restricted by material limitations. For such structures, folds are not properly represented as creases but rather as bent regions of higher-order geometric continuity. Such fold regions of arbitrary order of continuity are termed as smooth folds . This paper presents a method for solving the following origami design problem: given a goal shape represented as a polygonal mesh (termed as the goal mesh ), find the geometry of a single planar sheet, its pattern of smooth folds, and the history of folding motion allowing the sheet to approximate the goal mesh. The parametrization of the planar sheet and the constraints that allow for a valid pattern of smooth folds are presented. The method is tested against various goal meshes having diverse geometries. The results show that every determined sheet approximates its corresponding goal mesh in a known folded configuration having fold angles obtained from the geometry of the goal mesh.

Melody discrimination and protein fold classification

Directory of Open Access Journals (Sweden)

Robert P. Bywater

2016-10-01

Full Text Available One of the greatest challenges in theoretical biophysics and bioinformatics is the identification of protein folds from sequence data. This can be regarded as a pattern recognition problem. In this paper we report the use of a melody generation software where the inputs are derived from calculations of evolutionary information, secondary structure, flexibility, hydropathy and solvent accessibility from multiple sequence alignment data. The melodies so generated are derived from the sequence, and by inference, of the fold, in ways that give each fold a sound representation that may facilitate analysis, recognition, or comparison with other sequences.

Folded Plate Structures as Building Envelopes

DEFF Research Database (Denmark)

Falk, Andreas; Buelow, Peter von; Kirkegaard, Poul Henning

2012-01-01

This paper treats applications of cross-laminated timber (CLT) in structural systems for folded façade solutions. Previous work on CLT-based systems for folded roofs has shown a widening range of structural possibilities to develop timber-based shells. Geometric and material properties play...... CLT-based systems, which are studied and analysed by using a combination of digital tools for structural and environmental design and analysis. The results show gainful, rational properties of folded systems and beneficial effects from an integration of architectural and environmental performance...... criteria in the design of CLT-based façades....

Mechanical Models of Fault-Related Folding

Energy Technology Data Exchange (ETDEWEB)

Johnson, A. M.

2003-01-09

The subject of the proposed research is fault-related folding and ground deformation. The results are relevant to oil-producing structures throughout the world, to understanding of damage that has been observed along and near earthquake ruptures, and to earthquake-producing structures in California and other tectonically-active areas. The objectives of the proposed research were to provide both a unified, mechanical infrastructure for studies of fault-related foldings and to present the results in computer programs that have graphical users interfaces (GUIs) so that structural geologists and geophysicists can model a wide variety of fault-related folds (FaRFs).

Bifurcation of self-folded polygonal bilayers

Science.gov (United States)

Abdullah, Arif M.; Braun, Paul V.; Hsia, K. Jimmy

2017-09-01

Motivated by the self-assembly of natural systems, researchers have investigated the stimulus-responsive curving of thin-shell structures, which is also known as self-folding. Self-folding strategies not only offer possibilities to realize complicated shapes but also promise actuation at small length scales. Biaxial mismatch strain driven self-folding bilayers demonstrate bifurcation of equilibrium shapes (from quasi-axisymmetric doubly curved to approximately singly curved) during their stimulus-responsive morphing behavior. Being a structurally instable, bifurcation could be used to tune the self-folding behavior, and hence, a detailed understanding of this phenomenon is appealing from both fundamental and practical perspectives. In this work, we investigated the bifurcation behavior of self-folding bilayer polygons. For the mechanistic understanding, we developed finite element models of planar bilayers (consisting of a stimulus-responsive and a passive layer of material) that transform into 3D curved configurations. Our experiments with cross-linked Polydimethylsiloxane samples that change shapes in organic solvents confirmed our model predictions. Finally, we explored a design scheme to generate gripper-like architectures by avoiding the bifurcation of stimulus-responsive bilayers. Our research contributes to the broad field of self-assembly as the findings could motivate functional devices across multiple disciplines such as robotics, artificial muscles, therapeutic cargos, and reconfigurable biomedical devices.

Coarsely resolved topography along protein folding pathways

Science.gov (United States)

Fernández, Ariel; Kostov, Konstantin S.; Berry, R. Stephen

2000-03-01

The kinetic data from the coarse representation of polypeptide torsional dynamics described in the preceding paper [Fernandez and Berry, J. Chem. Phys. 112, 5212 (2000), preceding paper] is inverted by using detailed balance to obtain a topographic description of the potential-energy surface (PES) along the dominant folding pathway of the bovine pancreatic trypsin inhibitor (BPTI). The topography is represented as a sequence of minima and effective saddle points. The dominant folding pathway displays an overall monotonic decrease in energy with a large number of staircaselike steps, a clear signature of a good structure-seeker. The diversity and availability of alternative folding pathways is analyzed in terms of the Shannon entropy σ(t) associated with the time-dependent probability distribution over the kinetic ensemble of contact patterns. Several stages in the folding process are evident. Initially misfolded states form and dismantle revealing no definite pattern in the topography and exhibiting high Shannon entropy. Passage down a sequence of staircase steps then leads to the formation of a nativelike intermediate, for which σ(t) is much lower and fairly constant. Finally, the structure of the intermediate is refined to produce the native state of BPTI. We also examine how different levels of tolerance to mismatches of side chain contacts influence the folding kinetics, the topography of the dominant folding pathway, and the Shannon entropy. This analysis yields upper and lower bounds of the frustration tolerance required for the expeditious and robust folding of BPTI.

Idiopathic unilateral vocal-fold paralysis in the adult.

Science.gov (United States)

Rubin, F; Villeneuve, A; Alciato, L; Slaïm, L; Bonfils, P; Laccourreye, O

2018-02-02

To analyze the characteristics of adult idiopathic unilateral vocal-fold paralysis. Retrospective study of diagnostic problems, clinical data and recovery in an inception cohort of 100 adult patients with idiopathic unilateral vocal-fold paralysis (Group A) and comparison with a cohort of 211 patients with isolated non-idiopathic non-traumatic unilateral vocal-fold paralysis (Group B). Diagnostic problems were noted in 24% of cases in Group A: eight patients with concomitant common upper aerodigestive tract infection, five patients with a concomitant condition liable to induce immunodepression and 11 patients in whom a malignant tumor occurred along the path of the ipsilateral vagus and inferior laryngeal nerves or in the ipsilateral paralyzed larynx. There was no recovery of vocal-fold motion beyond 51 months after onset of paralysis. The 5-year actuarial estimate for recovery differed significantly (Pvocal-fold paralysis. In non-traumatic vocal-fold paralysis in adult patients, without recovery of vocal-fold motion, a minimum three years' regular follow-up is recommended. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

A comparison of RNA folding measures

DEFF Research Database (Denmark)

Freyhult, E.; Gardner, P. P.; Moulton, V.

2005-01-01

the behaviour of these measures over a large range of Rfam ncRNA families. Such measures can be useful in, for example, identifying novel ncRNAs, and indicating the presence of alternate RNA foldings. Results Our analysis shows that ncRNAs, but not mRNAs, in general have lower minimal free energy (MFE) than....... Conclusion Due to the correlations between the different measures we find that it is sufficient to use only two of them in RNA folding studies, one to test if the sequence in question has lower energy than a random sequence with the same dinucleotide frequency (the Z-score) and the other to see......Background In the last few decades there has been a great deal of discussion concerning whether or not noncoding RNA sequences (ncRNAs) fold in a more well-defined manner than random sequences. In this paper, we investigate several existing measures for how well an RNA sequence folds, and compare...

Endoscopic monitoring the estrous phase of Arabian mares with assaying its biopsy

Directory of Open Access Journals (Sweden)

Mohamed Fathi

2017-01-01

Full Text Available Objective: To evaluate the changes occur in the vagina, cervix and endometrium during the pre- ovulatory period in Arabian mares by using endoscope as a diagnostic tool as well as the availability of taking an endoscopic biopsy during this stage.Methods: Ten cyclic and healthy arabian mares were subjected to ultrasound scanning of their ovaries to estimate the diameter of the preovulatory follicles, collection of blood samples for estimating the hormonal levels (Estradiol-17 β and progestrone for confirming the estrous phase, endoscopic monitoring their vagina, cervix and endometrium, the availability of taking biopsical samples and histological examination of the obtained samples.Results: The obtained data revealed that, the mean diameter of the preovulatory follicles was (3.95±0.34 cm, the plasma estradiol and progestrone levels were (85.98±5.26 pg/mL and (0.73±0.23 ng/mL, respectively, endoscopic monitoring the vagina, cervix and endometrium revealed hyperemic vaginal mucous membrane, soft and opened cervical ostium with abundant estrous mucous and folding, hyperemic and edematous appearance of the endometrium, respectively and the histological features of the biopsical endometrial samples revealed that, The lamina propria-sub mucosa was packed with simple or branched tubular glands lined with simple columnar epithelium showing oval or rounded dark nuclei with different degrees of secretory activities of the glands.Conclusions: The endoscope proved to be a reliable tool for confirming the estrous phase in mares and monitoring the gross features of the vagina, the cervix and the endometrium, in addition to the availability of taking biopsical smears.

The Ventricular-Fold Dynamics in Human Phonation

OpenAIRE

Bailly , Lucie; Henrich Bernardoni , Nathalie; Müller , Frank; Rohlfs , Anna-Katharina; Hess , Markus

2014-01-01

International audience; Purpose: In this study, the authors aimed (a) to provide a classification of the ventricular-fold dynamics during voicing, (b) to study the aerodynamic impact of these motions on vocal-fold vibrations, and (c) to assess whether ventricularfold oscillations could be sustained by aerodynamic coupling with the vocal folds. Method: A 72-sample database of vocal gestures accompanying different acoustical events comprised highspeed cinematographic, audio, and electroglottogr...

Single-Chain Folding of Synthetic Polymers: A Critical Update.

Science.gov (United States)

Altintas, Ozcan; Barner-Kowollik, Christopher

2015-11-23

The current contribution serves as a critical update to a previous feature article from us (Macromol. Rapid Commun. 2012, 33, 958-971), and highlights the latest advances in the preparation of single chain polymeric nanoparticles and initial-yet promising-attempts towards mimicking the structure of natural biomacromolecules via single-chain folding of well-defined linear polymers via so-called single chain selective point folding and repeat unit folding. The contribution covers selected examples from the literature published up to ca. September 2015. Our aim is not to provide an exhaustive review but rather highlight a selection of new and exciting examples for single-chain folding based on advanced macromolecular precision chemistry. Initially, the discussion focuses on the synthesis and characterization of single-chain folded structures via selective point folding. The second part of the feature article addresses the folding of well-defined single-chain polymers by means of repeat unit folding. The current state of the art in the field of single-chain folding indicates that repeat unit folding-driven nanoparticle preparation is well-advanced, while initial encouraging steps towards building selective point folding systems have been taken. In addition, a summary of the-in our view-open key questions is provided that may guide future biomimetic design efforts. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Effect of Vocal Fold Medialization on Dysphagia in Patients with Unilateral Vocal Fold Immobility.

Science.gov (United States)

Cates, Daniel J; Venkatesan, Naren N; Strong, Brandon; Kuhn, Maggie A; Belafsky, Peter C

2016-09-01

The effect of vocal fold medialization (VFM) on vocal improvement in persons with unilateral vocal fold immobility (UVFI) is well established. The effect of VFM on the symptom of dysphagia is uncertain. The purpose of this study is to evaluate dysphagia symptoms in patients with UVFI pre- and post-VFM. Case series with chart review. Academic tertiary care medical center. The charts of 44 persons with UVFI who underwent VFM between June 1, 2013, and December 31, 2014, were abstracted from a prospectively maintained database at the University of California, Davis, Voice and Swallowing Center. Patient demographics, indications, and type of surgical procedure were recorded. Self-reported swallowing impairment was assessed with the validated 10-item Eating Assessment Tool (EAT-10) before and after surgery. A paired samples t test was used to compare pre- and postmedialization EAT-10 scores. Forty-four patients met criteria and underwent either vocal fold injection (73%) or thyroplasty (27%). Etiologies of vocal fold paralysis were iatrogenic (55%), idiopathic (29%), benign or malignant neoplastic (9%), traumatic (5%), or related to the late effects of radiation (2%). EAT-10 (mean ± SD) scores improved from 12.2 ± 11.1 to 7.7 ± 7.2 after medialization (P dysphagia and report significant improvement in swallowing symptoms following VFM. The symptomatic improvement appears to be durable over time. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2016.

Nomenclature proposal to describe vocal fold motion impairment

NARCIS (Netherlands)

Rosen, Clark A.; Mau, Ted; Remacle, Marc; Hess, Markus; Eckel, Hans E.; Young, VyVy N.; Hantzakos, Anastasios; Yung, Katherine C.; Dikkers, Frederik G.

2016-01-01

The terms used to describe vocal fold motion impairment are confusing and not standardized. This results in a failure to communicate accurately and to major limitations of interpreting research studies involving vocal fold impairment. We propose standard nomenclature for reporting vocal fold

Nomenclature proposal to describe vocal fold motion impairment

NARCIS (Netherlands)

Rosen, Clark A.; Mau, Ted; Remacle, Marc; Hess, Markus; Eckel, Hans E.; Young, VyVy N.; Hantzakos, Anastasios; Yung, Katherine C.; Dikkers, Frederik G.

The terms used to describe vocal fold motion impairment are confusing and not standardized. This results in a failure to communicate accurately and to major limitations of interpreting research studies involving vocal fold impairment. We propose standard nomenclature for reporting vocal fold

Curved Folded Plate Timber Structures

OpenAIRE

Buri, Hans Ulrich; Stotz, Ivo; Weinand, Yves

2011-01-01

This work investigates the development of a Curved Origami Prototype made with timber panels. In the last fifteen years the timber industry has developed new, large size, timber panels. Composition and dimensions of these panels and the possibility of milling them with Computer Numerical Controlled machines shows great potential for folded plate structures. To generate the form of these structures we were inspired by Origami, the Japanese art of paper folding. Common paper tessellations are c...

Dysphonia and vocal fold telangiectasia in hereditary hemorrhagic telangiectasia.

Science.gov (United States)

Chang, Joseph; Yung, Katherine C

2014-11-01

This case report is the first documentation of dysphonia and vocal fold telangiectasia as a complication of hereditary hemorrhagic telangiectasia (HHT). Case report of a 40-year-old man with HHT presenting with 2 years of worsening hoarseness. Hoarseness corresponded with a period of anticoagulation. Endoscopy revealed vocal fold scarring, vocal fold telangiectasias, and plica ventricular is suggestive of previous submucosal vocal fold hemorrhage and subsequent counterproductive compensation with ventricular phonation. Hereditary hemorrhagic telangiectasia may present as dysphonia with vocal fold telangiectasias and place patients at risk of vocal fold hemorrhage. © The Author(s) 2014.

Accurately controlled sequential self-folding structures by polystyrene film

Science.gov (United States)

Deng, Dongping; Yang, Yang; Chen, Yong; Lan, Xing; Tice, Jesse

2017-08-01

Four-dimensional (4D) printing overcomes the traditional fabrication limitations by designing heterogeneous materials to enable the printed structures evolve over time (the fourth dimension) under external stimuli. Here, we present a simple 4D printing of self-folding structures that can be sequentially and accurately folded. When heated above their glass transition temperature pre-strained polystyrene films shrink along the XY plane. In our process silver ink traces printed on the film are used to provide heat stimuli by conducting current to trigger the self-folding behavior. The parameters affecting the folding process are studied and discussed. Sequential folding and accurately controlled folding angles are achieved by using printed ink traces and angle lock design. Theoretical analyses are done to guide the design of the folding processes. Programmable structures such as a lock and a three-dimensional antenna are achieved to test the feasibility and potential applications of this method. These self-folding structures change their shapes after fabrication under controlled stimuli (electric current) and have potential applications in the fields of electronics, consumer devices, and robotics. Our design and fabrication method provides an easy way by using silver ink printed on polystyrene films to 4D print self-folding structures for electrically induced sequential folding with angular control.

Unraveling metamaterial properties in zigzag-base folded sheets.

Science.gov (United States)

Eidini, Maryam; Paulino, Glaucio H

2015-09-01

Creating complex spatial objects from a flat sheet of material using origami folding techniques has attracted attention in science and engineering. In the present work, we use the geometric properties of partially folded zigzag strips to better describe the kinematics of known zigzag/herringbone-base folded sheet metamaterials such as Miura-ori. Inspired by the kinematics of a one-degree of freedom zigzag strip, we introduce a class of cellular folded mechanical metamaterials comprising different scales of zigzag strips. This class of patterns combines origami folding techniques with kirigami. Using analytical and numerical models, we study the key mechanical properties of the folded materials. We show that our class of patterns, by expanding on the design space of Miura-ori, is appropriate for a wide range of applications from mechanical metamaterials to deployable structures at small and large scales. We further show that, depending on the geometry, these materials exhibit either negative or positive in-plane Poisson's ratios. By introducing a class of zigzag-base materials in the current study, we unify the concept of in-plane Poisson's ratio for similar materials in the literature and extend it to the class of zigzag-base folded sheet materials.

RNAslider: a faster engine for consecutive windows folding and its application to the analysis of genomic folding asymmetry

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Ziv-Ukelson Michal

2009-03-01

Full Text Available Abstract Background Scanning large genomes with a sliding window in search of locally stable RNA structures is a well motivated problem in bioinformatics. Given a predefined window size L and an RNA sequence S of size N (L 3 by applying any of the classical cubic-time RNA folding algorithms to each of the N-L windows of size L. Recently an O(NL2 solution for this problem has been described. Results Here, we describe and implement an O(NLψ(L engine for the consecutive windows folding problem, where ψ(L is shown to converge to O(1 under the assumption of a standard probabilistic polymer folding model, yielding an O(L speedup which is experimentally confirmed. Using this tool, we note an intriguing directionality (5'-3' vs. 3'-5' folding bias, i.e. that the minimal free energy (MFE of folding is higher in the native direction of the DNA than in the reverse direction of various genomic regions in several organisms including regions of the genomes that do not encode proteins or ncRNA. This bias largely emerges from the genomic dinucleotide bias which affects the MFE, however we see some variations in the folding bias in the different genomic regions when normalized to the dinucleotide bias. We also present results from calculating the MFE landscape of a mouse chromosome 1, characterizing the MFE of the long ncRNA molecules that reside in this chromosome. Conclusion The efficient consecutive windows folding engine described in this paper allows for genome wide scans for ncRNA molecules as well as large-scale statistics. This is implemented here as a software tool, called RNAslider, and applied to the scanning of long chromosomes, leading to the observation of features that are visible only on a large scale.

Transient intermediates are populated in the folding pathways of single-domain two-state folding protein L

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Maity, Hiranmay; Reddy, Govardhan

2018-04-01

Small single-domain globular proteins, which are believed to be dominantly two-state folders, played an important role in elucidating various aspects of the protein folding mechanism. However, recent single molecule fluorescence resonance energy transfer experiments [H. Y. Aviram et al. J. Chem. Phys. 148, 123303 (2018)] on a single-domain two-state folding protein L showed evidence for the population of an intermediate state and it was suggested that in this state, a β-hairpin present near the C-terminal of the native protein state is unfolded. We performed molecular dynamics simulations using a coarse-grained self-organized-polymer model with side chains to study the folding pathways of protein L. In agreement with the experiments, an intermediate is populated in the simulation folding pathways where the C-terminal β-hairpin detaches from the rest of the protein structure. The lifetime of this intermediate structure increased with the decrease in temperature. In low temperature conditions, we also observed a second intermediate state, which is globular with a significant fraction of the native-like tertiary contacts satisfying the features of a dry molten globule.

Protein Folding Free Energy Landscape along the Committor - the Optimal Folding Coordinate.

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Krivov, Sergei V

2018-06-06

Recent advances in simulation and experiment have led to dramatic increases in the quantity and complexity of produced data, which makes the development of automated analysis tools very important. A powerful approach to analyze dynamics contained in such data sets is to describe/approximate it by diffusion on a free energy landscape - free energy as a function of reaction coordinates (RC). For the description to be quantitatively accurate, RCs should be chosen in an optimal way. Recent theoretical results show that such an optimal RC exists; however, determining it for practical systems is a very difficult unsolved problem. Here we describe a solution to this problem. We describe an adaptive nonparametric approach to accurately determine the optimal RC (the committor) for an equilibrium trajectory of a realistic system. In contrast to alternative approaches, which require a functional form with many parameters to approximate an RC and thus extensive expertise with the system, the suggested approach is nonparametric and can approximate any RC with high accuracy without system specific information. To avoid overfitting for a realistically sampled system, the approach performs RC optimization in an adaptive manner by focusing optimization on less optimized spatiotemporal regions of the RC. The power of the approach is illustrated on a long equilibrium atomistic folding simulation of HP35 protein. We have determined the optimal folding RC - the committor, which was confirmed by passing a stringent committor validation test. It allowed us to determine a first quantitatively accurate protein folding free energy landscape. We have confirmed the recent theoretical results that diffusion on such a free energy profile can be used to compute exactly the equilibrium flux, the mean first passage times, and the mean transition path times between any two points on the profile. We have shown that the mean squared displacement along the optimal RC grows linear with time as for

Quantitative electromyographic characteristics of idiopathic unilateral vocal fold paralysis.

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Chang, Wei-Han; Fang, Tuan-Jen; Li, Hsueh-Yu; Jaw, Fu-Shan; Wong, Alice M K; Pei, Yu-Cheng

2016-11-01

Unilateral vocal fold paralysis with no preceding causes is diagnosed as idiopathic unilateral vocal fold paralysis. However, comprehensive guidelines for evaluating the defining characteristics of idiopathic unilateral vocal fold paralysis are still lacking. In the present study, we hypothesized that idiopathic unilateral vocal fold paralysis may have different clinical and neurologic characteristics from unilateral vocal fold paralysis caused by surgical trauma. Retrospective, case series study. Patients with unilateral vocal fold paralysis were evaluated using quantitative laryngeal electromyography, videolaryngostroboscopy, voice acoustic analysis, the Voice Outcome Survey, and the Short Form-36 Health Survey quality-of-life questionnaire. Patients with idiopathic and iatrogenic vocal fold paralysis were compared. A total of 124 patients were recruited. Of those, 17 with no definite identified causes after evaluation and follow-up were assigned to the idiopathic group. The remaining 107 patients with surgery-induced vocal fold paralysis were assigned to the iatrogenic group. Patients in the idiopathic group had higher recruitment of the thyroarytenoid-lateral cricoarytenoid muscle complex and better quality of life compared with the iatrogenic group. Idiopathic unilateral vocal fold paralysis has a distinct clinical presentation, with relatively minor denervation changes in the involved laryngeal muscles, and less impact on quality of life compared with iatrogenic vocal fold paralysis. 4. Laryngoscope, 126:E362-E368, 2016. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

Solvent Effects on Protein Folding/Unfolding

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García, A. E.; Hillson, N.; Onuchic, J. N.

Pressure effects on the hydrophobic potential of mean force led Hummer et al. to postulate a model for pressure denaturation of proteins in which denaturation occurs by means of water penetration into the protein interior, rather than by exposing the protein hydrophobic core to the solvent --- commonly used to describe temperature denaturation. We study the effects of pressure in protein folding/unfolding kinetics in an off-lattice minimalist model of a protein in which pressure effects have been incorporated by means of the pair-wise potential of mean force of hydrophobic groups in water. We show that pressure slows down the kinetics of folding by decreasing the reconfigurational diffusion coefficient and moves the location of the folding transition state.

Current Understanding and Future Directions for Vocal Fold Mechanobiology

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Li, Nicole Y.K.; Heris, Hossein K.; Mongeau, Luc

2013-01-01

The vocal folds, which are located in the larynx, are the main organ of voice production for human communication. The vocal folds are under continuous biomechanical stress similar to other mechanically active organs, such as the heart, lungs, tendons and muscles. During speech and singing, the vocal folds oscillate at frequencies ranging from 20 Hz to 3 kHz with amplitudes of a few millimeters. The biomechanical stress associated with accumulated phonation is believed to alter vocal fold cell activity and tissue structure in many ways. Excessive phonatory stress can damage tissue structure and induce a cell-mediated inflammatory response, resulting in a pathological vocal fold lesion. On the other hand, phonatory stress is one major factor in the maturation of the vocal folds into a specialized tri-layer structure. One specific form of vocal fold oscillation, which involves low impact and large amplitude excursion, is prescribed therapeutically for patients with mild vocal fold injuries. Although biomechanical forces affect vocal fold physiology and pathology, there is little understanding of how mechanical forces regulate these processes at the cellular and molecular level. Research into vocal fold mechanobiology has burgeoned over the past several years. Vocal fold bioreactors are being developed in several laboratories to provide a biomimic environment that allows the systematic manipulation of physical and biological factors on the cells of interest in vitro. Computer models have been used to simulate the integrated response of cells and proteins as a function of phonation stress. The purpose of this paper is to review current research on the mechanobiology of the vocal folds as it relates to growth, pathogenesis and treatment as well as to propose specific research directions that will advance our understanding of this subject. PMID:24812638

A partially folded intermediate species of the β-sheet protein apo-pseudoazurin ism trapped during proline-limited folding

NARCIS (Netherlands)

Reader, J.S.; van Nuland, N.A.J.; Thompson, G.S.; Ferguson, S.J.; Dobson, C.M.; Radford, S.E.

2001-01-01

The folding of apo-pseudoazurin, a 123-residue, predominantly -sheet protein with a complex Greek key topology, has been investigated using several biophysical techniques. Kinetic analysis of refolding using farand near-ultraviolet circular dichroism (UV CD) shows that the protein folds slowly to

A case of bilateral vocal fold mucosal bridges, bilateral trans-vocal fold type III sulci vocales, and an intracordal polyp.

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Tan, Melin; Pitman, Michael J

2011-07-01

We present a patient with a novel finding of bilateral mucosal bridges, bilateral type III trans-vocal fold sulci vocales, and a vocal fold polyp. Although sulci and mucosal bridges occur in the vocal folds, it is rare to find multiples of these lesions in a single patient, and it is even more uncommon when they occur in conjunction with a vocal fold polyp. To our knowledge, this is the first description of a vocal fold polyp in combination with multiple vocal fold bridges and multiple type III sulci vocales in a single patient. To describe and visually present the diagnosis and treatment of a patient with an intracordal polyp, bilateral mucosal bridges, as well as bilateral type III trans-vocal fold sulci vocales. Presentation of a set of high definition intraoperative photos displaying the extent of the vocal fold lesions and the resection of the intracordal polyp. This patient presented with only 6 months of significant dysphonia. It was felt that the recent change in voice was because of the polyp and not the bridges or sulci vocales. Considering the patient's presentation and the possible morbidity of resection of mucosal bridges and sulci, only the polyp was excised. Postoperatively, the patient's voice returned to his acceptable mild baseline dysphonia, and the benefit has persisted 6 months postoperatively. The combination of bilateral mucosal bridges, bilateral type III sulcus vocalis, and an intracordal polyp in one patient is rare if not novel. Treatment of the polyp alone returned the patient's voice to his lifelong baseline of mild dysphonia. Copyright © 2011 The Voice Foundation. Published by Mosby, Inc. All rights reserved.

A Rat Excised Larynx Model of Vocal Fold Scar

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Welham, Nathan V.; Montequin, Douglas W.; Tateya, Ichiro; Tateya, Tomoko; Choi, Seong Hee; Bless, Diane M.

2009-01-01

Purpose: To develop and evaluate a rat excised larynx model for the measurement of acoustic, aerodynamic, and vocal fold vibratory changes resulting from vocal fold scar. Method: Twenty-four 4-month-old male Sprague-Dawley rats were assigned to 1 of 4 experimental groups: chronic vocal fold scar, chronic vocal fold scar treated with 100-ng basic…

Method of generating ploynucleotides encoding enhanced folding variants

Energy Technology Data Exchange (ETDEWEB)

Bradbury, Andrew M.; Kiss, Csaba; Waldo, Geoffrey S.

2017-05-02

The invention provides directed evolution methods for improving the folding, solubility and stability (including thermostability) characteristics of polypeptides. In one aspect, the invention provides a method for generating folding and stability-enhanced variants of proteins, including but not limited to fluorescent proteins, chromophoric proteins and enzymes. In another aspect, the invention provides methods for generating thermostable variants of a target protein or polypeptide via an internal destabilization baiting strategy. Internally destabilization a protein of interest is achieved by inserting a heterologous, folding-destabilizing sequence (folding interference domain) within DNA encoding the protein of interest, evolving the protein sequences adjacent to the heterologous insertion to overcome the destabilization (using any number of mutagenesis methods), thereby creating a library of variants. The variants in the library are expressed, and those with enhanced folding characteristics selected.

The distribution of deformation in parallel fault-related folds with migrating axial surfaces: comparison between fault-propagation and fault-bend folding

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Salvini, Francesco; Storti, Fabrizio

2001-01-01

In fault-related folds that form by axial surface migration, rocks undergo deformation as they pass through axial surfaces. The distribution and intensity of deformation in these structures has been impacted by the history of axial surface migration. Upon fold initiation, unique dip panels develop, each with a characteristic deformation intensity, depending on their history. During fold growth, rocks that pass through axial surfaces are transported between dip panels and accumulate additional deformation. By tracking the pattern of axial surface migration in model folds, we predict the distribution of relative deformation intensity in simple-step, parallel fault-bend and fault-propagation anticlines. In both cases the deformation is partitioned into unique domains we call deformation panels. For a given rheology of the folded multilayer, deformation intensity will be homogeneously distributed in each deformation panel. Fold limbs are always deformed. The flat crests of fault-propagation anticlines are always undeformed. Two asymmetric deformation panels develop in fault-propagation folds above ramp angles exceeding 29°. For lower ramp angles, an additional, more intensely-deformed panel develops at the transition between the crest and the forelimb. Deformation in the flat crests of fault-bend anticlines occurs when fault displacement exceeds the length of the footwall ramp, but is never found immediately hinterland of the crest to forelimb transition. In environments dominated by brittle deformation, our models may serve as a first-order approximation of the distribution of fractures in fault-related folds.

An overlapping region between the two terminal folding units of the outer surface protein A (OspA) controls its folding behavior.

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Makabe, Koki; Nakamura, Takashi; Dhar, Debanjan; Ikura, Teikichi; Koide, Shohei; Kuwajima, Kunihiro

2018-04-27

Although many naturally occurring proteins consist of multiple domains, most studies on protein folding to date deal with single-domain proteins or isolated domains of multi-domain proteins. Studies of multi-domain protein folding are required for further advancing our understanding of protein folding mechanisms. Borrelia outer surface protein A (OspA) is a β-rich two-domain protein, in which two globular domains are connected by a rigid and stable single-layer β-sheet. Thus, OspA is particularly suited as a model system for studying the interplays of domains in protein folding. Here, we studied the equilibria and kinetics of the urea-induced folding-unfolding reactions of OspA probed with tryptophan fluorescence and ultraviolet circular dichroism. Global analysis of the experimental data revealed compelling lines of evidence for accumulation of an on-pathway intermediate during kinetic refolding and for the identity between the kinetic intermediate and a previously described equilibrium unfolding intermediate. The results suggest that the intermediate has the fully native structure in the N-terminal domain and the single layer β-sheet, with the C-terminal domain still unfolded. The observation of the productive on-pathway folding intermediate clearly indicates substantial interactions between the two domains mediated by the single-layer β-sheet. We propose that a rigid and stable intervening region between two domains creates an overlap between two folding units and can energetically couple their folding reactions. Copyright © 2018. Published by Elsevier Ltd.

Clinical Assessment of Lamina Cribrosa Curvature in Eyes with Primary Open-Angle Glaucoma.

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Yong Woo Kim

Full Text Available Quantitative evaluation of lamina cribrosa (LC posterior bowing in primary open-angle glaucoma (POAG eyes using swept-source optical coherence tomography.Patients with POAG (n = 123 eyes and healthy individuals of a similar age (n = 92 eyes were prospectively recruited. Anterior laminar insertion depth (ALID was defined as the vertical distance between the anterior laminar insertion and a reference plane connecting the Bruch's membrane openings (BMO. The mean LC depth (mLCD was approximated by dividing the area enclosed by the anterior LC, the BMO reference plane, and the two vertical lines for ALID measurement by the length between those two vertical lines. The LC curvature index was defined as the difference between the mLCD and the ALID. The factors influencing the LC curvature index were evaluated.The ALID and mLCD were significantly larger in POAG eyes than in healthy controls (P -6 dB and moderate-to-advanced glaucoma (MD < -6 dB, P = 0.95.LC posterior bowing was increased in POAG eyes, and was significantly associated with structural optic nerve head (ONH changes but not with functional glaucoma severity. Quantitative evaluation of LC curvature can facilitate assessment of glaucomatous ONH change.

Effects of AVX-470, an Oral, Locally Acting Anti-Tumour Necrosis Factor Antibody, on Tissue Biomarkers in Patients with Active Ulcerative Colitis.

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Hartman, Deborah S; Tracey, Daniel E; Lemos, Brenda R; Erlich, Emma C; Burton, Randall E; Keane, David M; Patel, Rutvij; Kim, Skaison; Bhol, Kailash C; Harris, M Scott; Fox, Barbara S

2016-06-01

AVX-470 is an orally administered, bovine-derived, anti-tumour necrosis factor (TNF) antibody with local activity in the gastrointestinal tract. In the first-in-human clinical trial of AVX-470 in active ulcerative colitis, we evaluated inflammatory biomarkers in colon tissue as measures of disease activity and early response to treatment. Thirty-six patients received active drug (AVX-470 at 0.2, 1.6 or 3.5g/day) or placebo over 4 weeks. Colon biopsy samples were collected from 5 regions of colon at baseline and week 4. Tissue inflammatory biomarkers were evaluated by immunohistochemistry and quantitative reverse transcription-polymerase chain reaction (qRT-PCR), epithelial cell apoptosis by terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) and bovine immunoglobulin by immunohistochemistry and mass spectrometry. Endoscopic activity (Ulcerative Colitis Endoscopic Index of Severity [UCEIS]) at colonoscopy was assessed in each colonic region by a central reader. Bovine immunoglobulin was observed in mucosal tissue before and after dosing in lamina propria and submucosal layers of biopsy tissue. Baseline levels of TNF, myeloperoxidase (MPO), CD68 and interleukin (IL)-1β and, to a lesser extent, IL-6 mRNA were 2- to 3-fold higher in distal vs proximal colon tissue, corresponding to the 2- to 3-fold differences in baseline severities of endoscopic scores. Reductions of >10-fold in TNF and, to lesser extents, in MPO and epithelial cell apoptosis were observed in proximal and distal colon biopsies after 4 weeks of AVX-470 3.5g/day treatment. Reductions in TNF scores were correlated with changes in MPO and CD3 immunohistochemistry scores. These results are consistent with anti-TNF activity of orally administered AVX-470 in colon mucosal tissue in ulcerative colitis patients and demonstrate the utility of tissue biomarkers in assessing disease and treatment response in early clinical studies. This trial was registered with Clinicaltrials.gov as study NCT

Incidence of vocal fold immobility in patients with dysphagia.

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Leder, Steven B; Ross, Douglas A

2005-01-01

This study prospectively investigated the incidence of vocal fold immobility, unilateral and bilateral, and its influence on aspiration status in a referred population of 1452 patients for a dysphagia evaluation from a large, urban, tertiary-care, teaching hospital. Main outcome measures included overall incidence of vocal fold immobility and aspiration status, with specific emphasis on age, etiology, and side of vocal fold immobility, i.e., right, left, or bilateral. Overall incidence of vocal fold immobility was 5.6% (81 of 1452 patients), including 47 males (mean age 55.7 yr) and 34 females (mean age 59.7 yr). In the subgroup of patients with vocal fold immobility, 31% (25 of 81) exhibited unilateral right, 60% (49 of 81) unilateral left, and 9% (7 of 81) bilateral impairment. Overall incidence of aspiration was found to be 29% (426 of 1452) of all patients referred for a swallow evaluation. Aspiration was observed in 44% (36 of 81) of patients presenting with vocal fold immobility, i.e., 44% (11 of 25) unilateral right, 43% (21 of 49) unilateral left, and 57% (4 of 7) bilateral vocal fold immobility. Left vocal fold immobility occurred most frequently due to surgical trauma. A liquid bolus was aspirated more often than a puree bolus. Side of vocal fold immobility and age were not factors that increased incidence of aspiration. In conclusion, vocal fold immobility, with an incidence of 5.6%, is not an uncommon finding in patients referred for a dysphagia evaluation in the acute-care setting, and vocal fold immobility, when present, was associated with a 15% increased incidence of aspiration when compared with a population already being evaluated for dysphagia.

Basilar membrane and reticular lamina motion in a multi-scale finite element model of the mouse cochlea

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Soons, Joris; Dirckx, Joris; Steele, Charles; Puria, Sunil

2015-12-01

A multi-scale finite element (FE) model of the mouse cochlea, based on its anatomy and material properties is presented. The important feature in the model is a lattice of 400 Y-shaped structures in the longitudinal direction, each formed by Deiters cells, phalangeal processes and outer hair cells (OHC). OHC somatic motility is modeled by an expansion force proportional to the shear on the stereocilia, which in turn is proportional to the pressure difference between the scala vestibule and scala tympani. Basilar membrane (BM) and reticular lamina (RL) velocity compare qualitatively very well with recent in vivo measurements in guinea pig [2]. Compared to the BM, the RL is shown to have higher amplification and a shift to higher frequencies. This comes naturally from the realistic Y-shaped cell organization without tectorial membrane tuning.

Basigin/EMMPRIN/CD147 mediates neuron-glia interactions in the optic lamina of Drosophila.

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Curtin, Kathryn D; Wyman, Robert J; Meinertzhagen, Ian A

2007-11-15

Basigin, an IgG family glycoprotein found on the surface of human metastatic tumors, stimulates fibroblasts to secrete matrix metalloproteases (MMPs) that remodel the extracellular matrix, and is thus also known as Extracellular Matrix MetalloPRotease Inducer (EMMPRIN). Using Drosophila we previously identified novel roles for basigin. Specifically, photoreceptors of flies with basigin eyes show misplaced nuclei, rough ER and mitochondria, and swollen axon terminals, suggesting cytoskeletal disruptions. Here we demonstrate that basigin is required for normal neuron-glia interactions in the Drosophila visual system. Flies with basigin mutant photoreceptors have misplaced epithelial glial cells within the first optic neuropile, or lamina. In addition, epithelial glia insert finger-like projections--capitate projections (CPs)--sites of vesicle endocytosis and possibly neurotransmitter recycling. When basigin is missing from photoreceptors terminals, CP formation between glia and photoreceptor terminals is disrupted. Visual system function is also altered in flies with basigin mutant eyes. While photoreceptors depolarize normally to light, synaptic transmission is greatly diminished, consistent with a defect in neurotransmitter release. Basigin expression in photoreceptor neurons is required for normal structure and placement of glia cells.

Theoretical study of the folded waveguide

International Nuclear Information System (INIS)

Chen, G.L.; Owens, T.L.; Whealton, J.H.

1988-01-01

We have applied a three-dimensional (3-D) algorithm for solving Maxwell's equations to the analysis of foleded waveguides used for fusion plasma heating at the ion cyclotron resonance frequency. A rigorous analysis of the magnetic field structure in the folded waveguide is presented. The results are compared to experimenntal measurements. Optimum conditions for the folded waveguide are discussed. 6 refs., 10 figs

Stratigraphy and Folding in the Cenozoic Cover of a Fold-Thrust Belt in the Nallıhan Region (Ankara, Central Turkey)

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Karaaǧaç, Serdal; Koral, Hayrettin

2017-04-01

This study investigates stratigraphy and structural features in the Cenozoic sedimentary sequence of the fold-thrust belt of the Nallıhan-Ankara region, located to the north of the İzmir-Ankara-Erzincan Suture Zone. Permian-Triassic age marble intercalated with schist-phyllites, the upper Jurassic-lower Cretaceous age limestone and the upper Cretaceous age sandstone-shale alternation compose the basement in the study area. These rocks are unconformably overlain by the Cenozoic age terrestrial sedimentary and volcanic units. The Cenozoic stratigraphy begins with the Paleocene-Eocene age coal-bearing, at times, volcanic intercalated conglomerate-sandstone-mudstone alternation of alluvial-fluvial origins (Aksaklar Formation) and the tuff intercalated with lacustrine limestone, bituminous limestone (Kabalar Formation). These units are conformably overlain by the Eocene age basalt-andesite and pyroclastic rocks (Meyildere volcanics). The Paleocene-Eocene aged units are unconformably overlain by the conglomerate-sandstone-mudstone-marl of a lower-middle Miocene lacustrine environment (Hançili Formation). The terrestrial conglomerate-sandstone alternation (Örencik Formation) is the youngest unit in the Cenozoic stratigraphy, and is assumed to be of Pliocene age based its stratigraphic position on older units. Field study shows existence of both folds and faults in the sedimentary cover. Stereographic projections of bedding measured in the field shows N25W/45NW and N60W/4SE-oriented fold axes in the Paleocene-Eocene age units. There are also N76W/12SE and N88E/8NE-oriented folds. The difference in fold-axis orientations suggests that some folds may have been rotated in blocks bound by faults during the post-Paleocene/Eocene period. Whereas, the lower-middle Miocene units manifest N88W/13SE-oriented fold axes. It is thus proposed that the observed difference in the azimuth of fold axes represent two different folding phases, one with NE-SW and the other with N

Kinetics and Thermodynamics of Membrane Protein Folding

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Ernesto A. Roman

2014-03-01

Full Text Available Understanding protein folding has been one of the great challenges in biochemistry and molecular biophysics. Over the past 50 years, many thermodynamic and kinetic studies have been performed addressing the stability of globular proteins. In comparison, advances in the membrane protein folding field lag far behind. Although membrane proteins constitute about a third of the proteins encoded in known genomes, stability studies on membrane proteins have been impaired due to experimental limitations. Furthermore, no systematic experimental strategies are available for folding these biomolecules in vitro. Common denaturing agents such as chaotropes usually do not work on helical membrane proteins, and ionic detergents have been successful denaturants only in few cases. Refolding a membrane protein seems to be a craftsman work, which is relatively straightforward for transmembrane β-barrel proteins but challenging for α-helical membrane proteins. Additional complexities emerge in multidomain membrane proteins, data interpretation being one of the most critical. In this review, we will describe some recent efforts in understanding the folding mechanism of membrane proteins that have been reversibly refolded allowing both thermodynamic and kinetic analysis. This information will be discussed in the context of current paradigms in the protein folding field.

Thermodynamics of protein folding: a random matrix formulation.

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Shukla, Pragya

2010-10-20

The process of protein folding from an unfolded state to a biologically active, folded conformation is governed by many parameters, e.g. the sequence of amino acids, intermolecular interactions, the solvent, temperature and chaperon molecules. Our study, based on random matrix modeling of the interactions, shows, however, that the evolution of the statistical measures, e.g. Gibbs free energy, heat capacity, and entropy, is single parametric. The information can explain the selection of specific folding pathways from an infinite number of possible ways as well as other folding characteristics observed in computer simulation studies. © 2010 IOP Publishing Ltd

Reinke Edema: Watch For Vocal Fold Cysts.

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Tüzüner, Arzu; Demirci, Sule; Yavanoglu, Ahmet; Kurkcuoglu, Melih; Arslan, Necmi

2015-06-01

Reinke edema is one of the common cause of dysphonia middle-aged population, and severe thickening of vocal folds require surgical treatment. Smoking plays a major role on etiology. Vocal fold cysts are also benign lesions and vocal trauma blamed for acquired cysts. We would like to present 3 cases with vocal fold cyst related with Reinke edema. First case had a subepidermal epidermoid cyst with Reinke edema, which could be easily observed before surgery during laryngostroboscopy. Second case had a mucous retention cyst into the edematous Reinke tissue, which was detected during surgical intervention, and third case had a epidermoid cyst that occurred 2 months after before microlaryngeal operation regarding Reinke edema reduction. These 3 cases revealed that surgical management of Reinke edema needs a careful dissection and close follow-up after surgery for presence of vocal fold cysts.

Transiently disordered tails accelerate folding of globular proteins.

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Mallik, Saurav; Ray, Tanaya; Kundu, Sudip

2017-07-01

Numerous biological proteins exhibit intrinsic disorder at their termini, which are associated with multifarious functional roles. Here, we show the surprising result that an increased percentage of terminal short transiently disordered regions with enhanced flexibility (TstDREF) is associated with accelerated folding rates of globular proteins. Evolutionary conservation of predicted disorder at TstDREFs and drastic alteration of folding rates upon point-mutations suggest critical regulatory role(s) of TstDREFs in shaping the folding kinetics. TstDREFs are associated with long-range intramolecular interactions and the percentage of native secondary structural elements physically contacted by TstDREFs exhibit another surprising positive correlation with folding kinetics. These results allow us to infer probable molecular mechanisms behind the TstDREF-mediated regulation of folding kinetics that challenge protein biochemists to assess by direct experimental testing. © 2017 Federation of European Biochemical Societies.

Histopathological confirmation of similar intramucosal distribution of fluorescein in both intravenous administration and local mucosal application for probe-based confocal laser endomicroscopy of the normal stomach.

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Nonaka, Kouichi; Ohata, Ken; Ban, Shinichi; Ichihara, Shin; Takasugi, Rumi; Minato, Yohei; Tashima, Tomoaki; Matsuyama, Yasushi; Takita, Maiko; Matsuhashi, Nobuyuki; Neumann, Helmut

2015-12-16

Probe-based confocal laser endomicroscopy (pCLE) is capable of acquiring in vivo magnified cross-section images of the gastric mucosa. Intravenous injection of fluorescein sodium is used for confocal imaging. However, it is still under debate if local administration of the dye to the mucosa is also effective for confocal imaging as it is not yet clear if topical application also reveals the intramucosal distribution of fluorescein. The objective of this study was to evaluate the intramucosal distribution of fluorescein sodium after topical application and to compare the distribution to the conventional intravenous injection used for confocal imaging. pCLE of the stomach uninfected with Helicobacter pylori was performed in a healthy male employing intravenous administration and local mucosal application of fluorescein. The mucosa of the lower gastric body was biopsied 1 min and 5 min after intravenous administration or local mucosal application of fluorescein, and the distribution of fluorescein in the biopsy samples was examined histologically. Green fluorescence was already observed in the cytoplasm of fundic glandular cells in the biopsied deep mucosa 1 min after local mucosal application of fluorescein. It was also observed in the foveolar lumen and inter-foveolar lamina propria, although it was noted at only a few sites. In the tissue biopsied 5 min after the local mucosal application of fluorescein, green fluorescence was more frequently noted in the cytoplasm of fundic glandular cells than in that 1 min after the local mucosal application of fluorescein, although obvious green fluorescence was not identified in the foveolar lumen or inter-foveolar lamina propria. The distribution of intravenously administered fluorescein in the cytoplasm of fundic glandular cells was also clearly observed similarly to that after local mucosal application of fluorescein. Green fluorescence in more cells was observed in many cells 5 min after intravenous administration compared

Lack of mucosal immune reconstitution during prolonged treatment of acute and early HIV-1 infection.

Directory of Open Access Journals (Sweden)

Saurabh Mehandru

2006-12-01

Full Text Available During acute and early HIV-1 infection (AEI, up to 60% of CD4(+ T cells in the lamina propria of the lower gastrointestinal (GI tract are lost as early as 2-4 wk after infection. Reconstitution in the peripheral blood during therapy with highly active antiretroviral therapy (HAART is well established. However, the extent of immune reconstitution in the GI tract is unknown.Fifty-four AEI patients and 18 uninfected control participants underwent colonic biopsy. Forty of the 54 AEI patients were followed after initiation of antiretroviral therapy (18 were studied longitudinally with sequential biopsies over a 3-y period after beginning HAART, and 22 were studied cross sectionally after 1-7 y of uninterrupted therapy. Lymphocyte subsets, markers of immune activation and memory in the peripheral blood and GI tract were determined by flow cytometry and immunohistochemistry. In situ hybridization was performed in order to identify persistent HIV-1 RNA expression. Of the patients studied, 70% maintained, on average, a 50%-60% depletion of lamina propria lymphocytes despite 1-7 y of HAART. Lymphocytes expressing CCR5 and both CCR5 and CXCR4 were persistently and preferentially depleted. Levels of immune activation in the memory cell population, CD45RO+ HLA-DR+, returned to levels seen in the uninfected control participants in the peripheral blood, but were elevated in the GI tract of patients with persistent CD4+ T cell depletion despite therapy. Rare HIV-1 RNA-expressing cells were detected by in situ hybridization.Apparently suppressive treatment with HAART during acute and early infection does not lead to complete immune reconstitution in the GI mucosa in the majority of patients studied, despite immune reconstitution in the peripheral blood. Though the mechanism remains obscure, the data suggest that there is either viral or immune-mediated accelerated T cell destruction or, possibly, alterations in T cell homing to the GI tract. Although clinically

Dose-Dependent Effects of Lactobacillus rhamnosus on Serum Interleukin-17 Production and Intestinal T-Cell Responses in Pigs Challenged with Escherichia coli

Science.gov (United States)

Zhu, Yao-Hong; Li, Xiao-Qiong; Zhang, Wei; Zhou, Dong; Liu, Hao-Yu

2014-01-01

The mechanism underlying the dose effect of probiotics on ameliorating diarrhea has not been fully elucidated. Here, low (1 × 109 CFU/ml) or high (1 × 1011 CFU/ml) doses of Lactobacillus rhamnosus ATCC 7469 were administered orally to piglets for 1 week before F4 (K88)-positive enterotoxigenic Escherichia coli (F4+ ETEC) challenge. Administration of a low, but not a high, dose of L. rhamnosus decreased the percentage of CD3+ CD4+ CD8− T cells in the peripheral blood. Notably, transiently increased serum concentrations of interleukin-17A (IL-17A) were observed after F4+ ETEC challenge in pigs pretreated with a high dose of L. rhamnosus. Administration of L. rhamnosus increased the percentage of the small intestinal lamina propria CD3+ CD4+ CD8− cells and Peyer's patch CD3+ CD4− CD8− and CD3− CD4− CD8+ cells. The percentage of ileal intraepithelial CD3+ CD4− CD8+ cells increased only in the high-dose piglets. Administration of L. rhamnosus downregulated expression of ileal IL-17A after F4+ ETEC challenge but had no effect on expression of gamma interferon (IFN-γ), IL-12, IL-4, and FOXP3 mRNA in the small intestine. Expression of jejunal IL-2, ileal transforming growth factor β1 (TGF-β1), and ileal IL-10 was upregulated in the low-dose piglets after F4+ ETEC challenge. Our findings suggest that amelioration of infectious diarrhea in piglets by L. rhamnosus is associated with the generation of lamina propria CD3+ CD4+ CD8− T cells, the expansion of Peyer's patch CD3+ CD4− CD8− and CD3− CD4− CD8+ cells, and the attenuation of F4+ ETEC-induced increase in CD3+ CD4+ CD8+ T cells in the small intestine. However, consumption of high doses of L. rhamnosus may increase levels of serum IL-17A after F4+ ETEC challenge, thus eliciting a strong proinflammatory response. PMID:24389928

Association of Lung Inflammatory Cells with Small Airways Function and Exhaled Breath Markers in Smokers - Is There a Specific Role for Mast Cells?

Directory of Open Access Journals (Sweden)

Yvonne Nussbaumer-Ochsner

Full Text Available Smoking is associated with a mixed inflammatory infiltrate in the airways. We evaluated whether airway inflammation in smokers is related to lung function parameters and inflammatory markers in exhaled breath.Thirty-seven smokers undergoing lung resection for primary lung cancer were assessed pre-operatively by lung function testing including single-breath-nitrogen washout test (sb-N2-test, measurement of fractional exhaled nitric oxide (FeNO and pH/8-isoprostane in exhaled breath condensate (EBC. Lung tissue sections containing cancer-free large (LA and small airways (SA were stained for inflammatory cells. Mucosal (MCT respectively connective tissue mast cells (MCTC and interleukin-17A (IL-17A expression by mast cells was analysed using a double-staining protocol.The median number of neutrophils, macrophages and mast cells infiltrating the lamina propria and adventitia of SA was higher than in LA. Both MCTC and MCT were higher in the lamina propria of SA compared to LA (MCTC: 49 vs. 27.4 cells/mm2; MCT: 162.5 vs. 35.4 cells/mm2; P<0.005 for both instances. IL-17A expression was predominantly detected in MCTC of LA. Significant correlations were found for the slope of phase III % pred. of the sb-N2-test (rs= -0.39, for the FEV1% pred. (rs= 0.37 and for FEV1/FVC ratio (rs=0.38 with MCT in SA (P<0.05 for all instances. 8-isoprostane concentration correlated with the mast cells in the SA (rs=0.44, there was no correlation for pH or FeNO with cellular distribution in SA.Neutrophils, macrophages and mast cells are more prominent in the SA indicating that these cells are involved in the development of small airway dysfunction in smokers. Among these cell types, the best correlation was found for mast cells with lung function parameters and inflammatory markers in exhaled breath. Furthermore, the observed predominant expression of IL-17A in mast cells warrants further investigation to elucidate their role in smoking-induced lung injury, despite the

Fluorescence of Alexa fluor dye tracks protein folding.

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Simon Lindhoud

Full Text Available Fluorescence spectroscopy is an important tool for the characterization of protein folding. Often, a protein is labeled with appropriate fluorescent donor and acceptor probes and folding-induced changes in Förster Resonance Energy Transfer (FRET are monitored. However, conformational changes of the protein potentially affect fluorescence properties of both probes, thereby profoundly complicating interpretation of FRET data. In this study, we assess the effects protein folding has on fluorescence properties of Alexa Fluor 488 (A488, which is commonly used as FRET donor. Here, A488 is covalently attached to Cys69 of apoflavodoxin from Azotobacter vinelandii. Although coupling of A488 slightly destabilizes apoflavodoxin, the three-state folding of this protein, which involves a molten globule intermediate, is unaffected. Upon folding of apoflavodoxin, fluorescence emission intensity of A488 changes significantly. To illuminate the molecular sources of this alteration, we applied steady state and time-resolved fluorescence techniques. The results obtained show that tryptophans cause folding-induced changes in quenching of Alexa dye. Compared to unfolded protein, static quenching of A488 is increased in the molten globule. Upon populating the native state both static and dynamic quenching of A488 decrease considerably. We show that fluorescence quenching of Alexa Fluor dyes is a sensitive reporter of conformational changes during protein folding.

Fold and Fit: Space Conserving Shape Editing

KAUST Repository

Ibrahim, Mohamed; Yan, Dong-Ming

2017-01-01

We present a framework that folds man-made objects in a structure-aware manner for space-conserving storage and transportation. Given a segmented 3D mesh of a man-made object, our framework jointly optimizes for joint locations, the folding order

Inverse folding of RNA pseudoknot structures

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Li Linda YM

2010-06-01

Full Text Available Abstract Background RNA exhibits a variety of structural configurations. Here we consider a structure to be tantamount to the noncrossing Watson-Crick and G-U-base pairings (secondary structure and additional cross-serial base pairs. These interactions are called pseudoknots and are observed across the whole spectrum of RNA functionalities. In the context of studying natural RNA structures, searching for new ribozymes and designing artificial RNA, it is of interest to find RNA sequences folding into a specific structure and to analyze their induced neutral networks. Since the established inverse folding algorithms, RNAinverse, RNA-SSD as well as INFO-RNA are limited to RNA secondary structures, we present in this paper the inverse folding algorithm Inv which can deal with 3-noncrossing, canonical pseudoknot structures. Results In this paper we present the inverse folding algorithm Inv. We give a detailed analysis of Inv, including pseudocodes. We show that Inv allows to design in particular 3-noncrossing nonplanar RNA pseudoknot 3-noncrossing RNA structures-a class which is difficult to construct via dynamic programming routines. Inv is freely available at http://www.combinatorics.cn/cbpc/inv.html. Conclusions The algorithm Inv extends inverse folding capabilities to RNA pseudoknot structures. In comparison with RNAinverse it uses new ideas, for instance by considering sets of competing structures. As a result, Inv is not only able to find novel sequences even for RNA secondary structures, it does so in the context of competing structures that potentially exhibit cross-serial interactions.

Ab initio folding of mixed-fold FSD-EY protein using formula-based polarizable hydrogen bond (PHB) charge model

Science.gov (United States)

Zhang, Dawei; Lazim, Raudah; Mun Yip, Yew

2017-09-01

We conducted an all-atom ab initio folding of FSD-EY, a protein with a ββα configuration using non-polarizable (AMBER) and polarizable force fields (PHB designed by Gao et al.) in implicit solvent. The effect of reducing the polarization effect integrated into the force field by the PHB model, termed the PHB0.7 was also examined in the folding of FSD-EY. This model incorporates into the force field 70% of the original polarization effect to minimize the likelihood of over-stabilizing the backbone hydrogen bonds. Precise folding of the β-sheet of FSD-EY was further achieved by relaxing the REMD structure obtained in explicit water.

Efeitos da inalação passiva da fumaça de cigarro sobre as pregas vocais de ratos Effects of passive smoke inhalation on the vocal cords of rats

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Josilene Luciene Duarte

2006-04-01

other areas of the larynx and inflammatory reaction of the lamina propria were also not observed. CONCLUSION: It was concluded that the passive inhalation of cigarette smoke yields important morphological changes in the vocal fold epithelium, which may progress to neoplasia.

Morphometric Study of Vocal Folds in Indian Cadavers

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Rawal J.D.

2015-06-01

Full Text Available Introduction: -The larynx is an air passage and a sphincteric device used in respiration and phonation. The larynx, from inside outwards has a framework of mucosa surrounded by fibro-elastic membrane which in turn is surrounded by cartilages and then a layer of muscles. Vocal folds are intrinsic ligament of larynx covered by mucosal folds. Larynx generates sound through rhythmic opening and closing of the vocal folds. The perceived pitch of human voice mainly depends upon fundamental frequency of sound generated by larynx. Aim: - The aim of present study is to measure various dimensions of vocal folds in Indian cadavers. Material & Methods: - 50 larynx were obtained from embalmed cadavers, of which 10 larynx were of females. Vocal cords were dissected from the larynx and morphometric analysis was done. Results and Conclusions: - The average total length of the vocal folds was found to be 16.11 mm. ± 2.62 mm. in male and 14.10 mm. ± 1.54 mm. in female cadavers. The average width of the vocal folds was found to be 4.38 mm. ± 0.74 mm. in male and 3.60 mm. ± 0.64 mm. in female cadavers. The average total length of the membranous part of the vocal folds was found to be 11.90 mm. ± 1.86 mm. in male and 10.45 mm. ± 1.81 mm. in female cadavers. The average ratio of the length of the membranous and the cartilaginous parts of the vocal folds was calculated to be 3.10 ± 0.96in male and 2.85 ± 0.73in female cadavers.

Merging monads and folds for functional programming

NARCIS (Netherlands)

Meijer, E.; Jeuring, J.T.

1995-01-01

These notes discuss the simultaneous use of generalised fold operators and monads to structure functional programs. Generalised fold operators structure programs after the decomposition of the value they consume. Monads structure programs after the computation of the value they produce. Our programs

Impact of hydrodynamic interactions on protein folding rates depends on temperature

Science.gov (United States)

Zegarra, Fabio C.; Homouz, Dirar; Eliaz, Yossi; Gasic, Andrei G.; Cheung, Margaret S.

2018-03-01

We investigated the impact of hydrodynamic interactions (HI) on protein folding using a coarse-grained model. The extent of the impact of hydrodynamic interactions, whether it accelerates, retards, or has no effect on protein folding, has been controversial. Together with a theoretical framework of the energy landscape theory (ELT) for protein folding that describes the dynamics of the collective motion with a single reaction coordinate across a folding barrier, we compared the kinetic effects of HI on the folding rates of two protein models that use a chain of single beads with distinctive topologies: a 64-residue α /β chymotrypsin inhibitor 2 (CI2) protein, and a 57-residue β -barrel α -spectrin Src-homology 3 domain (SH3) protein. When comparing the protein folding kinetics simulated with Brownian dynamics in the presence of HI to that in the absence of HI, we find that the effect of HI on protein folding appears to have a "crossover" behavior about the folding temperature. This means that at a temperature greater than the folding temperature, the enhanced friction from the hydrodynamic solvents between the beads in an unfolded configuration results in lowered folding rate; conversely, at a temperature lower than the folding temperature, HI accelerates folding by the backflow of solvent toward the folded configuration of a protein. Additionally, the extent of acceleration depends on the topology of a protein: for a protein like CI2, where its folding nucleus is rather diffuse in a transition state, HI channels the formation of contacts by favoring a major folding pathway in a complex free energy landscape, thus accelerating folding. For a protein like SH3, where its folding nucleus is already specific and less diffuse, HI matters less at a temperature lower than the folding temperature. Our findings provide further theoretical insight to protein folding kinetic experiments and simulations.

Frustration in Condensed Matter and Protein Folding

Science.gov (United States)

Li, Z.; Tanner, S.; Conroy, B.; Owens, F.; Tran, M. M.; Boekema, C.

2014-03-01

By means of computer modeling, we are studying frustration in condensed matter and protein folding, including the influence of temperature and Thomson-figure formation. Frustration is due to competing interactions in a disordered state. The key issue is how the particles interact to reach the lowest frustration. The relaxation for frustration is mostly a power function (randomly assigned pattern) or an exponential function (regular patterns like Thomson figures). For the atomic Thomson model, frustration is predicted to decrease with the formation of Thomson figures at zero kelvin. We attempt to apply our frustration modeling to protein folding and dynamics. We investigate the homogeneous protein frustration that would cause the speed of the protein folding to increase. Increase of protein frustration (where frustration and hydrophobicity interplay with protein folding) may lead to a protein mutation. Research is supported by WiSE@SJSU and AFC San Jose.

1,25(OH)2 vitamin D3 binding sites in male sex organs of the Siberian hamster (Phodopus sungorus). An autoradiographic study

International Nuclear Information System (INIS)

Schleicher, G.; Bartke, A.; Bidmon, H.J.; Stumpf, W.E.

1993-01-01

Using autoradiography, binding sites for 1,25(OH)2 vitamin D3 are found in certain genital organs of male Siberian hamsters (Phodopus sungorus), in particular in basal epithelial cells and fibroblasts of the lamina propria of prostate glands. Scattered labeled cells are also present in the epithelium of coagulation and urethral glands. In contrast to the findings in mice, under the conditions of the experiment, 1,25(OH)2 vitamin D3 binding sites are not recognizable in other accessory sex glands and gonads. The frequency of basal epithelial cells with [3H]1,25(OH)2 vitamin D3 nuclear binding is higher in regressed dorsal prostate glands of animals living in short photoperiods. The data suggest that 1,25(OH)2 vitamin D3 may promote proliferation and differentiation in basal epithelial cells, modulated by the seasonal and functional status of the animal

Estrogen receptors in the human male prostatic urethra and prostate in prostatic cancer and benign prostatic hyperplasia

DEFF Research Database (Denmark)

Bødker, A; Bruun, J; Balslev, E

1999-01-01

Estrogen receptors (ERs) in the prostate and prostatic urethra were examined in 33 men with benign prostatic hyperplasia (BPH) and in 11 with prostate cancer (PC). The Abbot monoclonal ER-ICA assay was used for immunohistochemical investigation. In the BPH group, ERs were revealed in the prostatic...... stroma in eight cases and in the glandular epithelium in one. In four cases ERs were seen in the prostatic stroma and in the glandular epithelium. In the prostatic urethra, ERs were found in 19 cases located in the urothelium, lamina propria and/or periurethral glands. In the PC group, ERs were...... demonstrated in the prostatic stroma and/or prostatic urethra in 6 out of 11 cases. In both BPH and PC patients, immunoreactivity was weak and confined to few cells, indicating low ER content in the prostate as well as in the prostatic urethra. Dextran-coated charcoal (DCC) analysis was used for detection...

Excreted/secreted Trichuris suis products reduce barrier function and suppress inflammatory cytokine production of intestinal epithelial cells

DEFF Research Database (Denmark)

Hiemstra, I. H.; Klaver, E. J.; Vrijland, K.

2014-01-01

The administration of helminths is considered a promising strategy for the treatment of autoimmune diseases due to their immunomodulatory properties. Currently, the application of the helminth Trichuris suis as a treatment for Crohn's disease is being studied in large multi-center clinical trials....... The intestinal epithelium forms an efficient barrier between the intestinal lumen containing the microbial flora and helminths, and dendritic cells (DCs) present in the lamina propria that determine the TH response. Here, we investigated how excreted/secreted (E/S) products of T. suis affect the barrier function...... of intestinal epithelial cells (IECs) in order to reach the DCs and modulate the immune response. We show that T. suis E/S products reduce the barrier function and the expression of the tight junction proteins EMP-1 and claudin-4 in IEC CMT93/69 monolayers in a glycan-dependent manner. This resulted...

Esophagitis and enteritis caused by herpesvirus in pigeons.

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Egobol, L.

2002-01-01

Full Text Available The pigeon squabs, aged 5-26 day-old, showed clinical signs of dullness, anorexia, indigestion, reten-tion of feed in crop, progressive emaciation then died. The morbidity rate and mortality rate were 7.14% (50/700. The adult pigeons did not show any signs of disease. From pathological finding, pharyngitis, esophagitis were found with diphtheritic membrane covering necrotic ulcers on the mucosa of pharynx, esophagus and crop. From histopathological findings, esophagitis with epithelial hyperplasia and sloughed, lamina propria mucosa edema with lymphoid cells infiltration were found in duodenum and jejunum. The intranuclear inclusion body, Cowdry type A, was found in epithelial mucosa of esophagus, enterocyte of jejunum and lymphoid cells in spleen. FA test to duck virus enteritis and inoculation to ducklings showed negative results. Electron microscopic study revealed electron dense core sized 146-167 nm., which was identified as herpesvirus.

Immunomodulatory effects of Hericium erinaceus derived polysaccharides are mediated by intestinal immunology.

Science.gov (United States)

Sheng, Xiaotong; Yan, Jingmin; Meng, Yue; Kang, Yuying; Han, Zhen; Tai, Guihua; Zhou, Yifa; Cheng, Hairong

2017-03-22

This study was aimed at investigating the immunomodulating activity of Hericium erinaceus polysaccharide (HEP) in mice, by assessing splenic lymphocyte proliferation (cell-mediated immunity), serum hemolysin levels (humoral immunity), phagocytic capacity of peritoneal cavity phagocytes (macrophage phagocytosis), and NK cell activity. ELISA of immunoglobulin A (SIgA) in the lamina propria, and western blotting of small intestinal proteins were also performed to gain insight into the mechanism by which HEP affects the intestinal immune system. Here, we report that HEP improves immune function by functionally enhancing cell-mediated and humoral immunity, macrophage phagocytosis, and NK cell activity. In addition, HEP was found to upregulate the secretion of SIgA and activate the MAPK and AKT cellular signaling pathways in the intestine. In conclusion, all these results allow us to postulate that the immunomodulatory effects of HEP are most likely attributed to the effective regulation of intestinal mucosal immune activity.

Light and Energy Based Therapeutics for Genitourinary Syndrome of Menopause: Consensus and Controversies

Science.gov (United States)

Tadir, Yona; Gaspar, Adrian; Lev-Sagie, Ahinoam; Alexiades, Macrene; Alinsod, Red; Bader, Alex; Calligaro, Alberto; Elias, Jorge A.; Gambaciani, Marco; Gaviria, Jorge E.; Iglesia, Cheryl B.; Selih-Martinec, Ksenija; Mwesigwa, Patricia L.; Ogrinc, Urska B.; Salvatore, Stefano; Scollo, Paolo; Zerbinati, Nicola; Nelson, John Stuart

2018-01-01

Gynecologist and plastic surgeons pioneered the application of lasers in medicine and surgery almost 5 decades ago, initially used to treat cervical and vaginal pathologies. Ever since, energy-based devices have been deployed to treat pelvic pathologies and improve fertility. Recent technological developments triggered an unprecedented wave of publications, assessing the efficacy of fractional laser, and radiofrequency on the vaginal wall in reversing natural aging processes. Studies have shown that a certain degree of thermal energy deposited on the vaginal wall stimulates proliferation of the glycogen-enriched epithelium, neovascularization, and collagen formation in the lamina propria, and improves natural lubrication and control of urination. This review aimed to review such data and to guide future research. A unique assembly of experts from around the globe, compiled and edited this manuscript based on a thorough literature review and personal experience. Lasers Surg. Med. 49:137–159, 2017. PMID:28220946

The impact of intraglottal vortices on vocal fold dynamics

Science.gov (United States)

Erath, Byron; Pirnia, Alireza; Peterson, Sean

2016-11-01

During voiced speech a critical pressure is produced in the lungs that separates the vocal folds and creates a passage (the glottis) for airflow. As air passes through the vocal folds the resulting aerodynamic loading, coupled with the tissue properties of the vocal folds, produces self-sustained oscillations. Throughout each cycle a complex flow field develops, characterized by a plethora of viscous flow phenomena. Air passing through the glottis creates a jet, with periodically-shed vortices developing due to flow separation and the Kelvin-Helmholtz instability in the shear layer. These vortices have been hypothesized to be a crucial mechanism for producing vocal fold vibrations. In this study the effect of vortices on the vocal fold dynamics is investigated experimentally by passing a vortex ring over a flexible beam with the same non-dimensional mechanical properties as the vocal folds. Synchronized particle image velocimetry data are acquired in tandem with the beam dynamics. The resulting impact of the vortex ring loading on vocal fold dynamics is discussed in detail. This work was supported by the National Science Foundation Grant CBET #1511761.

Folding models for elastic and inelastic scattering

International Nuclear Information System (INIS)

Satchler, G.R.

1982-01-01

The most widely used models are the optical model potential (OMP) for elastic scattering, and its generalization to non-spherical shapes, the deformed optical model potential (DOMP) for inelastic scattering. These models are simple and phenomenological; their parameters are adjusted so as to reproduce empirical data. Nonetheless, there are certain, not always well-defined, constraints to be imposed. The potential shapes and their parameter values must be reasonable and should vary in a smooth and systematic way with the masses of the colliding nuclei and their energy. One way of satisfying these constraints, without going back to a much more fundamental theory, is through the use of folding models. The basic justification for using potentials of the Woods-Saxon shape for nucleon-nucleus scattering, for example, is our knowledge that a nuclear density distribution is more-or-less constant in the nuclear interior with a diffuse surface. When this is folded with a short-range nucleon-nucleon interaction, the result is a similar shape with a more diffuse surface. Folding procedures allow us to incorporate many aspects of nuclear structure (although the nuclear size is one of the most important), as well as theoretical ideas about the effective interaction of two nucleons within nuclear matter. It also provides us with a means of linking information obtained from nuclear (hadronic) interactions with that from other sources, as well as correlating that from the use of different hadronic probes. Folding model potentials, single-folded potentials, and the double-folding model including applications to heavy-ion scattering are discussed

Folds and Etudes

Science.gov (United States)

Bean, Robert

2007-01-01

In this article, the author talks about "Folds" and "Etudes" which are images derived from anonymous typing exercises that he found in a used copy of "Touch Typing Made Simple". "Etudes" refers to the musical tradition of studies for a solo instrument, which is a typewriter. Typing exercises are repetitive attempts to type words and phrases…

Pathophysiology of the nodular and micronodular small bowel fold

International Nuclear Information System (INIS)

Olmstead, W.W.; Ros, P.R.; Moser, R.P.; Shekitka, K.M.; Lichtenstein, J.E.; Buck, J.L.

1987-01-01

The normal small bowel fold is easily seen on conventional studies of the small intestine, but visualization of the small bowel villus is just at the resolution of current roentgenographic technique. When the villi are enlarged, they can be seen radiographically as an irregularity or micronodularity of the small bowel fold. The anatomy of the fold and the pathophysiology of diseases producing fold nodularity (tumor, inflammatory disease, NLH, mastocytosis) and micronodularity (lymphangiectasia, Waldenstrom macroglobulinemia, Whipple disease) are presented, with an emphasis on radiologic-pathologic correlation. The radiologist should suggest certain diseases or conditions based on the roentgenographic characteristics of the closely analyzed small bowel fold

A bidirectional shape memory alloy folding actuator

International Nuclear Information System (INIS)

Paik, Jamie K; Wood, Robert J

2012-01-01

This paper presents a low-profile bidirectional folding actuator based on annealed shape memory alloy sheets applicable for meso- and microscale systems. Despite the advantages of shape memory alloys—high strain, silent operation, and mechanical simplicity—their application is often limited to unidirectional operation. We present a bidirectional folding actuator that produces two opposing 180° motions. A laser-patterned nickel alloy (Inconel 600) heater localizes actuation to the folding sections. The actuator has a thin ( < 1 mm) profile, making it appropriate for use in robotic origami. Various design parameters and fabrication variants are described and experimentally explored in the actuator prototype. (paper)

Miniaturization of Multiple-Layer Folded Patch Antennas

DEFF Research Database (Denmark)

Zhang, Jiaying; Breinbjerg, Olav

2009-01-01

A new folded patch antenna with multiple layers was developed in this paper, by folding the patch in a proper way, and a highly miniaturized antenna can be realized. The multiple layer patch with 4-layer and 6-layer are designed and evaluated at 2.4 GHz, 915 MHz, and 415 MHz respectively. Then a 4...... layer patch is fabricated and measured to validate the design method. The theoretical analysis, design and simulations, fabrications, as well as the measurements are presented in this paper. All the results show that the folded patch antenna is a good candidate in making a highly miniaturized compact...

The histological components of the phoniatrical body-cover model in minipigs of different ages.

Directory of Open Access Journals (Sweden)

Anja Lang

Full Text Available Pigs are models in human phoniatry. However, features of maturation and ageing have not been considered with regard to the so-called body-cover model in this species. Therefore, the glottis of "young" (2-3 months; n = 6 and "old" (4-7 years; n = 6 minipigs was investigated. Their cranial (CraF and caudal (CauF vocal folds were histomorphometrically and stratigraphically analysed with emphasis on their amounts of collagen structures and elastic fibres. A dense subepithelial layer (SEL was a distinct feature of CraF and CauF of both age groups; it was spread upon the underlying loose, flexible "cover" like a fibro-elastic membrane. The "cover" was characterised by the so-called superficial layer (SL, which was distinctly loose in the "young" minipigs, but had a much denser texture in the "old" minipigs. Here, the SL was dominated by elastic fibres in the CraF, but was of mixed qualities (collagenous and elastic in the CauF. The structural requirements for the SL's function as a loose "cover" were thus met only in the "young" animals. A clearly demarcated intermediate layer (IL--characterised by high amounts of elastic fibres (as in humans--was only found in the CraF of the "young" animals. In the "old" animals, it had lost its demarcation. In the depth of the CraF of the "old" animals, many thick collagen fibre bundles were detected in a location equivalent to that of the vocal muscle in the CauF. The development of their large diameters was interpreted as part of the maturation process, thereby supporting the hypothesis of their functional importance as a component of the "body." In the CauF, the amounts of collagen structures increased throughout the entire lamina propria, resulting in a loss of demarcated stratigraphical subdivisions in the "old" minipigs. This situation resembled that described in the vocal fold of geriatric humans.

Deformation and kinematics of the central Kirthar Fold Belt, Pakistan

Science.gov (United States)

Hinsch, Ralph; Hagedorn, Peter; Asmar, Chloé; Nasim, Muhammad; Aamir Rasheed, Muhammad; Kiely, James M.

2017-04-01

The Kirthar Fold Belt is part of the lateral mountain belts in Pakistan linking the Himalaya orogeny with the Makran accretionary wedge. This region is deforming very oblique/nearly parallel to the regional plate motion vector. The study area is situated between the prominent Chaman strike-slip fault in the West and the un-deformed foreland (Kirthar Foredeep/Middle Indus Basin) in the East. The Kirthar Fold Belt is subdivided into several crustal blocks/units based on structural orientation and deformation style (e.g. Kallat, Khuzdar, frontal Kirthar). This study uses newly acquired and depth-migrated 2D seismic lines, surface geology observations and Google Earth assessments to construct three balanced cross sections for the frontal part of the fold belt. Further work was done in order to insure the coherency of the built cross-sections by taking a closer look at the regional context inferred from published data, simple analogue modelling, and constructed regional sketch sections. The Khuzdar area and the frontal Kirthar Fold Belt are dominated by folding. Large thrusts with major stratigraphic repetitions are not observed. Furthermore, strike-slip faults in the Khuzdar area are scarce and not observed in the frontal Kirthar Fold Belt. The regional structural elevation rises from the foreland across the Kirthar Fold Belt towards the hinterland (Khuzdar area). These observations indicate that basement-involved deformation is present at depth. The domination of folding indicates a weak decollement below the folds (soft-linked deformation). The fold pattern in the Khuzdar area is complex, whereas the large folds of the central Kirthar Fold Belt trend SSW-NNE to N-S and are best described as large detachment folds that have been slightly uplifted by basement involved transpressive deformation underneath. Towards the foreland, the deformation is apparently more hard-linked and involves fault-propagation folding and a small triangle zone in Cretaceous sediments

Radiometric Dating of Folds: A new approach to determine the timing of deformation at shallow-crustal conditions, with examples from the Mexican Fold-Thrust Belt

Science.gov (United States)

Fitz Diaz, E.; van der Pluijm, B. A.

2012-12-01

We are developing a robust method to obtain absolute ages of folds that were formed at shallow crustal conditions. The method takes advantage of illite neocrystallization in folded, clay-bearing layers and the ability to obtain accurate retention and total gas ages from small size fractions using encapsulated Ar analysis, analogous to prior work on fault gouge dating. We illustrate our approach in folded Cretaceous shale-bentonitic layers that are interbedded with carbonates of the Zimapán and the Tampico-Misantla cretaceous basins in central-eastern Mexico. Basinal carbonates were buried by syntectonic turbidites and inverted during the formation of the Mexican Fold-Thrust in the Late Cretaceous. Results were obtained from four chevron folds that are representative of different stages of deformation, burial/temperature conditions and location within this thin-skinned orogenic wedge: two from the Zimapán Basin (Folds 1 and 2) in the west and two from the Tampico-Misantla Basin (Folds 3 and 4) in the east. Mineralogic compositions and variations in illite-polytypes, crystallite-size (CS) and Ar/Ar ages were obtained from size fractions in limbs and hinges of folded layers. Ar retention ages produce a folding age of ~81 Ma for Fold 1 and ~69 Ma for Fold 2, which are fully consistent with stratigraphic limits from syn-orogenic turbidities and observed overprinting events in the Mexican Fold-Thrust Belt. The total gas age of Fold 3, on the easternmost margin of the Tampico-Misantla Basin is similar to that of Fold 2, indicating that the second event is regional in scale. In addition to presenting a new, reliable method to constrain the timing of local deformation, we interpret folding and associated clay neo-mineralization in terms of the regional burial history, and localization and propagation of deformation within a heterogeneous orogenic wedge involving progressive deformation of two basins separated by a platform block.

Estimated Trans-Lamina Cribrosa Pressure Differences in Low-Teen and High-Teen Intraocular Pressure Normal Tension Glaucoma: The Korean National Health and Nutrition Examination Survey

OpenAIRE

Lee, Si Hyung; Kwak, Seung Woo; Kang, Eun Min; Kim, Gyu Ah; Lee, Sang Yeop; Bae, Hyoung Won; Seong, Gong Je; Kim, Chan Yun

2016-01-01

Background To investigate the association between estimated trans-lamina cribrosa pressure difference (TLCPD) and prevalence of normal tension glaucoma (NTG) with low-teen and high-teen intraocular pressure (IOP) using a population-based study design. Methods A total of 12,743 adults (? 40 years of age) who participated in the Korean National Health and Nutrition Examination Survey (KNHANES) from 2009 to 2012 were included. Using a previously developed formula, cerebrospinal fluid pressure (C...

Iterative Controller Tuning for Process with Fold Bifurcations

DEFF Research Database (Denmark)

Huusom, Jakob Kjøbsted; Poulsen, Niels Kjølstad; Jørgensen, Sten Bay

2007-01-01

Processes involving fold bifurcation are notoriously difficult to control in the vicinity of the fold where most often optimal productivity is achieved . In cases with limited process insight a model based control synthesis is not possible. This paper uses a data driven approach with an improved...... version of iterative feedback tuning to optimizing a closed loop performance criterion, as a systematic tool for tuning process with fold bifurcations....

Vocal Fold Injection: Review of Indications, Techniques, and Materials for Augmentation

OpenAIRE

Mallur, Pavan S.; Rosen, Clark A.

2010-01-01

Vocal fold injection is a procedure that has over a 100 year history but was rarely done as short as 20 years ago. A renaissance has occurred with respect to vocal fold injection due to new technologies (visualization and materials) and new injection approaches. Awake, un-sedated vocal fold injection offers many distinct advantages for the treatment of glottal insufficiency (vocal fold paralysis, vocal fold paresis, vocal fold atrophy and vocal fold scar). A review of materials available and ...

Experimental investigation into the mechanism of folding

NARCIS (Netherlands)

Kuenen, Ph.H.; Sitter, de L.U.

1938-01-01

The investigation of geological structures due to folding led de Sitter to form an opinion on the mechanical problems involved (Bibl. 7). His principal contention is that in simple cases the relative movements of particles with respect to eachother during deformation leading to a fold, have been

SDEM modelling of fault-propagation folding

DEFF Research Database (Denmark)

Clausen, O.R.; Egholm, D.L.; Poulsen, Jane Bang

2009-01-01

and variations in Mohr-Coulomb parameters including internal friction. Using SDEM modelling, we have mapped the propagation of the tip-line of the fault, as well as the evolution of the fold geometry across sedimentary layers of contrasting rheological parameters, as a function of the increased offset......Understanding the dynamics and kinematics of fault-propagation-folding is important for evaluating the associated hydrocarbon play, for accomplishing reliable section balancing (structural reconstruction), and for assessing seismic hazards. Accordingly, the deformation style of fault-propagation...... a precise indication of when faults develop and hence also the sequential evolution of secondary faults. Here we focus on the generation of a fault -propagated fold with a reverse sense of motion at the master fault, and varying only the dip of the master fault and the mechanical behaviour of the deformed...

Endoscopic Anatomy of the Tensor Fold and Anterior Attic.

Science.gov (United States)

Li, Bin; Doan, Phi; Gruhl, Robert R; Rubini, Alessia; Marchioni, Daniele; Fina, Manuela

2018-02-01

Objectives The objectives of the study were to (1) study the anatomical variations of the tensor fold and its anatomic relation with transverse crest, supratubal recess, and anterior epitympanic space and (2) explore the most appropriate endoscopic surgical approach to each type of the tensor fold variants. Study Design Cadaver dissection study. Setting Temporal bone dissection laboratory. Subjects and Methods Twenty-eight human temporal bones (26 preserved and 2 fresh) were dissected through an endoscopic transcanal approach between September 2016 and June 2017. The anatomical variations of the tensor fold, transverse crest, supratubal recess, and anterior epitympanic space were studied before and after removing ossicles. Results Three different tensor fold orientations were observed: vertical (type A, 11/28, 39.3%) with attachment to the transverse crest, oblique (type B, 13/28, 46.4%) with attachment to the anterior tegmen tympani, and horizontal (type C, 4/28, 14.3%) with attachment to the tensor tympani canal. The tensor fold was a complete membrane in 20 of 28 (71.4%) specimens, preventing direct ventilation between the supratubal recess and anterior epitympanic space. We identified 3 surgical endoscopic approaches, which allowed visualization of the tensor fold without removing the ossicles. Conclusions The orientation of the tensor fold is the determining structure that dictates the conformation and limits of the epitympanic space. We propose a classification of the tensor fold based on 3 anatomical variants. We also describe 3 different minimally invasive endoscopic approaches to identify the orientation of the tensor fold while maintaining ossicular chain continuity.

A nomenclature paradigm for benign midmembranous vocal fold lesions.

Science.gov (United States)

Rosen, Clark A; Gartner-Schmidt, Jackie; Hathaway, Bridget; Simpson, C Blake; Postma, Gregory N; Courey, Mark; Sataloff, Robert T

2012-06-01

There is a significant lack of uniform agreement regarding nomenclature for benign vocal fold lesions (BVFLs). This confusion results in difficulty for clinicians communicating with their patients and with each other. In addition, BVFL research and comparison of treatment methods are hampered by the lack of a detailed and uniform BVFL nomenclature. Clinical consensus conferences were held to develop an initial BVFL nomenclature paradigm. Perceptual video analysis was performed to validate the stroboscopy component of the paradigm. The culmination of the consensus conferences and the video-perceptual analysis was used to evaluate the BVFL nomenclature paradigm using a retrospective review of patients with BVFL. An initial BVFL nomenclature paradigm was proposed utilizing detailed definitions relating to vocal fold lesion morphology, stroboscopy, response to voice therapy and intraoperative findings. Video-perceptual analysis of stroboscopy demonstrated that the proposed binary stroboscopy system used in the BVFL nomenclature paradigm was valid and widely applicable. Retrospective review of 45 patients with BVFL followed to the conclusion of treatment demonstrated that slight modifications of the initial BVFL nomenclature paradigm were required. With the modified BVFL nomenclature paradigm, 96% of the patients fit into the predicted pattern and definitions of the BVFL nomenclature system. This study has validated a multidimensional BVFL nomenclature paradigm. This vocal fold nomenclature paradigm includes nine distinct vocal fold lesions: vocal fold nodules, vocal fold polyp, pseudocyst, vocal fold cyst (subepithelial or ligament), nonspecific vocal fold lesion, vocal fold fibrous mass (subepithelial or ligament), and reactive lesion. Copyright © 2011 The American Laryngological, Rhinological, and Otological Society, Inc.

Benign Lesions of The Vocal Fold

Directory of Open Access Journals (Sweden)

Ozgur Surmelioglu

2013-02-01

Full Text Available Benign lesions of vocal folds are common disorders. Fifty percent of patients who have sound complaints are found to have these lesions after endoscopic and stroboscopic examinations. Benign vocal fold diseases are primarily caused by vibratory trauma. However they may also occur as a result of viral infections and congenital causes. These lesions are often presented with the complaints of dysphonia. [Archives Medical Review Journal 2013; 22(1.000: 86-95

Laryngeal ultrasound and pediatric vocal fold nodules.

Science.gov (United States)

Ongkasuwan, Julina; Devore, Danielle; Hollas, Sarah; Jones, Jeremy; Tran, Brandon

2017-03-01

The term vocal fold nodules refers to bilateral thickening of the membranous folds with minimal impairment of the vibratory properties of the mucosa. Nodules are thought to be related to repetitive mechanical stress, associated with voice use patterns. Diagnosis is typically made in the office via either rigid or flexible laryngeal stroboscopy. Depending on the individual child, obtaining an optimal view of the larynx can be difficult if not impossible. Recent advances in high-frequency ultrasonography allows for transcervical examination of laryngeal structures. The goal of this project was to determine if laryngeal ultrasound (LUS) can be used to identify vocal fold nodules in dysphonic children. Prospective case-control study in which the patient acted as his or her own control. Forty-six pediatric patients were recruited for participation in this study; the mean age was 4.8 years. Twenty-three did not have any vocal fold lesions and 23 had a diagnosis of vocal fold nodules on laryngeal stroboscopy. Recorded LUSs were reviewed by two pediatric radiologists who were blinded to the nodule status. There was substantial inter-rater agreement (κ = 0.70, 95% confidence interval [CI]: 0.50-0.89) between the two radiologists regarding the presence of nodules. There was also substantial agreement (κ = 0.87, 95% CI: 0.72-1) between LUS and laryngeal stroboscopy. Sensitivity of LUS was 100% (95% CI: 85%-100%) and specificity was 87% (95% CI: 66%-97%). LUS can be used to identify vocal fold nodules in children with substantial agreement with laryngeal stroboscopy. 3b Laryngoscope, 127:676-678, 2017. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

Diagnostic and therapeutic pitfalls in benign vocal fold diseases

Science.gov (United States)

Bohlender, Jörg

2013-01-01

More than half of patients presenting with hoarseness show benign vocal fold changes. The clinician should be familiar with the anatomy, physiology and functional aspects of voice disorders and also the modern diagnostic and therapeutic possibilities in order to ensure an optimal and patient specific management. This review article focuses on the diagnostic and therapeutic limitations and difficulties of treatment of benign vocal fold tumors, the management and prevention of scarred vocal folds and the issue of unilateral vocal fold paresis. PMID:24403969

Monadic Maps and Folds for Arbitrary Datatypes

NARCIS (Netherlands)

Fokkinga, M.M.

Each datatype constructor comes equiped not only with a so-called map and fold (catamorphism), as is widely known, but, under some condition, also with a kind of map and fold that are related to an arbitrary given monad. This result follows from the preservation of initiality under lifting

Analysis of high-fold gamma data

International Nuclear Information System (INIS)

Radford, D. C.; Cromaz, M.; Beyer, C. J.

1999-01-01

Historically, γ-γ and γ-γ-γ coincidence spectra were utilized to build nuclear level schemes. With the development of large detector arrays, it has became possible to analyze higher fold coincidence data sets. This paper briefly reports on software to analyze 4-fold coincidence data sets that allows creation of 4-fold histograms (hypercubes) of at least 1024 channels per side (corresponding to a 43 gigachannel data space) that will fit onto a few gigabytes of disk space, and extraction of triple-gated spectra in a few seconds. Future detector arrays may have even much higher efficiencies, and detect as many as 15 or 20 γ rays simultaneously; such data will require very different algorithms for storage and analysis. Difficulties inherent in the analysis of such data are discussed, and two possible new solutions are presented, namely adaptive list-mode systems and 'list-list-mode' storage

Folds in multilayered rocks of Proterozoic age, Rajasthan, India

Indian Academy of Sciences (India)

R. Narasimhan (Krishtel eMaging) 1461 1996 Oct 15 13:05:22

Johnson and Johnson 2002 etc) shows that the fold shape modification may be brought about by buckling and flattening operating simultaneously throughout the development of fold. In the present paper a series of F1 folds devel- oped in slates with interlayered alternations with quartzite of Proterozoic age and unaffected ...

Self-folding polymeric containers for encapsulation and delivery of drugs.

Science.gov (United States)

Fernandes, Rohan; Gracias, David H

2012-11-01

Self-folding broadly refers to self-assembly processes wherein thin films or interconnected planar templates curve, roll-up or fold into three dimensional (3D) structures such as cylindrical tubes, spirals, corrugated sheets or polyhedra. The process has been demonstrated with metallic, semiconducting and polymeric films and has been used to curve tubes with diameters as small as 2nm and fold polyhedra as small as 100nm, with a surface patterning resolution of 15nm. Self-folding methods are important for drug delivery applications since they provide a means to realize 3D, biocompatible, all-polymeric containers with well-tailored composition, size, shape, wall thickness, porosity, surface patterns and chemistry. Self-folding is also a highly parallel process, and it is possible to encapsulate or self-load therapeutic cargo during assembly. A variety of therapeutic cargos such as small molecules, peptides, proteins, bacteria, fungi and mammalian cells have been encapsulated in self-folded polymeric containers. In this review, we focus on self-folding of all-polymeric containers. We discuss the mechanistic aspects of self-folding of polymeric containers driven by differential stresses or surface tension forces, the applications of self-folding polymers in drug delivery and we outline future challenges. Copyright © 2012 Elsevier B.V. All rights reserved.

Competition between folding and glycosylation in the endoplasmic reticulum

DEFF Research Database (Denmark)

Holst, B; Bruun, A W; Kielland-Brandt, Morten

1996-01-01

Using carboxypeptidase Y in Saccharomyces cerevisiae as a model system, the in vivo relationship between protein folding and N-glycosylation was studied. Seven new sites for N-glycosylation were introduced at positions buried in the folded protein structure. The level of glycosylation of such new...... acceptor sites. In some cases, all the newly synthesized mutant protein was modified at the novel site while in others no modification took place. In the most interesting category of mutants, the level of glycosylation was dependent on the conditions for folding. This shows that folding and glycosylation...

Vocal Fold Collision Modeling

DEFF Research Database (Denmark)

Granados, Alba; Brunskog, Jonas; Misztal, M. K.

2015-01-01

When vocal folds vibrate at normal speaking frequencies, collisions occurs. The numerics and formulations behind a position-based continuum model of contact is an active field of research in the contact mechanics community. In this paper, a frictionless three-dimensional finite element model...

The four-fold way

International Nuclear Information System (INIS)

Terazawa, H.

1986-01-01

The four-fold way is proposed in a minimal composite model of quarks and leptons. Various new pictures and consequences are presented and discussed. They include 1) generation, 2) quark-lepton mass spectrum, 3) quark mixing, 4) supersymmetry, 5) effective gauge theory. (author)

Vocal fold elasticity of the Rocky Mountain elk (Cervus elaphus nelsoni) – producing high fundamental frequency vocalization with a very long vocal fold

OpenAIRE

Riede, Tobias; Titze, Ingo R.

2008-01-01

The vocal folds of male Rocky Mountain elk (Cervus elaphus nelsoni) are about 3 cm long. If fundamental frequency were to be predicted by a simple vibrating string formula, as is often done for the human larynx, such long vocal folds would bear enormous stress to produce the species-specific mating call with an average fundamental frequency of 1 kHz. Predictions would be closer to 50 Hz. Vocal fold histology revealed the presence of a large vocal ligament between the vocal fold epithelium and...

Ligand-promoted protein folding by biased kinetic partitioning.

Science.gov (United States)

Hingorani, Karan S; Metcalf, Matthew C; Deming, Derrick T; Garman, Scott C; Powers, Evan T; Gierasch, Lila M

2017-04-01

Protein folding in cells occurs in the presence of high concentrations of endogenous binding partners, and exogenous binding partners have been exploited as pharmacological chaperones. A combined mathematical modeling and experimental approach shows that a ligand improves the folding of a destabilized protein by biasing the kinetic partitioning between folding and alternative fates (aggregation or degradation). Computationally predicted inhibition of test protein aggregation and degradation as a function of ligand concentration are validated by experiments in two disparate cellular systems.

Vocal fold composition and early glottic carcinoma infiltration

Directory of Open Access Journals (Sweden)

Fang Qin

2012-08-01

Full Text Available Abstract Background Current imaging techniques provide only limited information pertaining to the extent of infiltration of laryngeal carcinomas into vocal fold tissue layers. Therefore, it is needed to seek the contribute to the body of knowledge surrounding examination and characterization in laryngeal carcinoma infiltration. Methods Excised larynges were collected from 30 male laryngectomy patients with an average age of 43.5 years (ranging 36 to 55 years and history of smoking (≥10 years exhibiting T1, T2, or subglottal (normal vocal fold carcinomas. Vocal folds were preserved via freezing or immersion in paraffin. The depth of the mucosa, submucosa, and muscular layers in both normal vocal folds and tumor tissues of afflicted vocal folds was measured. Results The average depths of the mucosa, submucosa, and muscular layers in normal vocal folds were 0.15 ± 0.06 mm, 2.30 ± 0.59 mm, and 2.87 ± 0.88 mm, respectively. Infiltration measurements of T1 tumors showed a depth of 1.62 ± 0.51 mm and 1.32 ± 0.49 mm in frozen sections and paraffin-embedded samples, respectively. Similarly, T2 tumors showed a depth of 2.87 ± 0.68 mm and 2.58 ± 0.67 mm in frozen sections and paraffin-embedded samples, respectively. T1 and T2 tumors occupied 24.8 ± 10 and 48.5 ± 15 percent of the normal vocal fold depth, respectively. Conclusion This data provides a baseline for estimating infiltration of laryngeal carcinomas in vocal fold tissue layers, of particular interest to surgeons. This information may be used to assess typical depths of infiltration, thus allowing for more appropriate selection of surgical procedures based on individual patient assessment.

Improvement of a Vocal Fold Imaging System

Energy Technology Data Exchange (ETDEWEB)

Krauter, K. G. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

2017-02-01

Medical professionals can better serve their patients through continual update of their imaging tools. A wide range of pathologies and disease may afflict human vocal cords or, as they’re also known, vocal folds. These diseases can affect human speech hampering the ability of the patient to communicate. Vocal folds must be opened for breathing and the closed to produce speech. Currently methodologies to image markers of potential pathologies are difficult to use and often fail to detect early signs of disease. These current methodologies rely on a strobe light and slower frame rate camera in an attempt to obtain images as the vocal folds travel over the full extent of their motion.

In vitro folding of inclusion body proteins.

Science.gov (United States)

Rudolph, R; Lilie, H

1996-01-01

Insoluble, inactive inclusion bodies are frequently formed upon recombinant protein production in transformed microorganisms. These inclusion bodies, which contain the recombinant protein in an highly enriched form, can be isolated by solid/liquid separation. After solubilization, native proteins can be generated from the inactive material by using in vitro folding techniques. New folding procedures have been developed for efficient in vitro reconstitution of complex hydrophobic, multidomain, oligomeric, or highly disulfide-bonded proteins. These protocols take into account process parameters such as protein concentration, catalysis of disulfide bond formation, temperature, pH, and ionic strength, as well as specific solvent ingredients that reduce unproductive side reactions. Modification of the protein sequence has been exploited to improve in vitro folding.

Arytenoid and posterior vocal fold surgery for bilateral vocal fold immobility.

Science.gov (United States)

Young, VyVy N; Rosen, Clark A

2011-12-01

Many procedures exist to address the airway restriction often seen with bilateral vocal fold immobility. We review the most recent studies involving arytenoid and/or posterior vocal fold surgery to provide an update on the issues related to these procedures. Specific focus is placed on selection of the surgical approach and operative side, use of adjunctive therapies, and outcome measures including decannulation rate, revision and complication rate, and postoperative results. Ten studies were identified between 2004 and 2011. Modifications to the orginal transverse cordotomy and medial arytenoidectomy techniques continue to be investigated to seek improvement in dyspnea symptoms with minimal decline in voice and/or swallowing function. Decannulation rates for these approaches are high. Postoperative dysphagia appears to be less commonly observed but requires continued study. The use of mitomycin-C in these procedures has been poorly studied to date. Both transverse cordotomy and medial arytenoidectomy procedures result in high success rates. However, many questions related to these procedures remain unanswered, particularly with respect to preoperative and postoperative evaluations of voice quality, swallowing function, and pulmonary status. There is need for rigorous prospective clinical studies to address these many issues further.

Self-Folding Textiles through Manipulation of Knit Stitch Architecture

Directory of Open Access Journals (Sweden)

Chelsea E. Knittel

2015-12-01

Full Text Available This research presents a preliminary study on finding predictable methods of controlling the self-folding behaviors of weft knit textiles for use in the development of smart textiles and garment devices, such as those with shape memory, auxetic behavior or transformation abilities. In this work, Shima Seiki SDS-One Apex computer-aided knitting technology, Shima Seiki industrial knitting machines, and the study of paper origami tessellation patterns were used as tools to understand and predict the self-folding abilities of weft knit textiles. A wide range of self-folding weft knit structures was produced, and relationships between the angles and ratios of the knit and purl stitch types were determined. Mechanical testing was used as a means to characterize differences produced by stitch patterns, and to further understand the relationships between angles and folding abilities. By defining a formulaic method for predicting the nature of the folds that occur due to stitch architecture patterns, we can better design self-folding fabrics for smart textile applications.

FoldEco: A Model for Proteostasis in E. coli

Directory of Open Access Journals (Sweden)

Evan T. Powers

2012-03-01

Full Text Available To gain insight into the interplay of processes and species that maintain a correctly folded, functional proteome, we have developed a computational model called FoldEco. FoldEco models the cellular proteostasis network of the E. coli cytoplasm, including protein synthesis, degradation, aggregation, chaperone systems, and the folding characteristics of protein clients. We focused on E. coli because much of the needed input information—including mechanisms, rate parameters, and equilibrium coefficients—is available, largely from in vitro experiments; however, FoldEco will shed light on proteostasis in other organisms. FoldEco can generate hypotheses to guide the design of new experiments. Hypothesis generation leads to system-wide questions and shows how to convert these questions to experimentally measurable quantities, such as changes in protein concentrations with chaperone or protease levels, which can then be used to improve our current understanding of proteostasis and refine the model. A web version of FoldEco is available at http://foldeco.scripps.edu.

Evolution of a protein folding nucleus.

Science.gov (United States)

Xia, Xue; Longo, Liam M; Sutherland, Mason A; Blaber, Michael

2016-07-01

The folding nucleus (FN) is a cryptic element within protein primary structure that enables an efficient folding pathway and is the postulated heritable element in the evolution of protein architecture; however, almost nothing is known regarding how the FN structurally changes as complex protein architecture evolves from simpler peptide motifs. We report characterization of the FN of a designed purely symmetric β-trefoil protein by ϕ-value analysis. We compare the structure and folding properties of key foldable intermediates along the evolutionary trajectory of the β-trefoil. The results show structural acquisition of the FN during gene fusion events, incorporating novel turn structure created by gene fusion. Furthermore, the FN is adjusted by circular permutation in response to destabilizing functional mutation. FN plasticity by way of circular permutation is made possible by the intrinsic C3 cyclic symmetry of the β-trefoil architecture, identifying a possible selective advantage that helps explain the prevalence of cyclic structural symmetry in the proteome. © 2015 The Protein Society.

Hierarchical Diagnosis of Vocal Fold Disorders

Science.gov (United States)

Nikkhah-Bahrami, Mansour; Ahmadi-Noubari, Hossein; Seyed Aghazadeh, Babak; Khadivi Heris, Hossein

This paper explores the use of hierarchical structure for diagnosis of vocal fold disorders. The hierarchical structure is initially used to train different second-level classifiers. At the first level normal and pathological signals have been distinguished. Next, pathological signals have been classified into neurogenic and organic vocal fold disorders. At the final level, vocal fold nodules have been distinguished from polyps in organic disorders category. For feature selection at each level of hierarchy, the reconstructed signal at each wavelet packet decomposition sub-band in 5 levels of decomposition with mother wavelet of (db10) is used to extract the nonlinear features of self-similarity and approximate entropy. Also, wavelet packet coefficients are used to measure energy and Shannon entropy features at different spectral sub-bands. Davies-Bouldin criterion has been employed to find the most discriminant features. Finally, support vector machines have been adopted as classifiers at each level of hierarchy resulting in the diagnosis accuracy of 92%.

Vascular lesions of the vocal fold.

Science.gov (United States)

Gökcan, Kürşat Mustafa; Dursun, Gürsel

2009-04-01

The aim of the study was to present symptoms, laryngological findings, clinical course, management modalities, and consequences of vascular lesions of vocal fold. This study examined 162 patients, the majority professional voice users, with vascular lesions regarding their presenting symptoms, laryngological findings, clinical courses and treatment results. The most common complaint was sudden hoarseness with hemorrhagic polyp. Microlaryngoscopic surgery was performed in 108 cases and the main indication of surgery was the presence of vocal fold mass or development of vocal polyp during clinical course. Cold microsurgery was utilized for removal of vocal fold masses and feeding vessels cauterized using low power, pulsed CO(2) laser. Acoustic analysis of patients revealed a significant improvement of jitter, shimmer and harmonics/noise ratio values after treatment. Depending on our clinical findings, we propose treatment algorithm where voice rest and behavioral therapy is the integral part and indications of surgery are individualized for each patient.

The effect of surface electrical stimulation on vocal fold position.

Science.gov (United States)

Humbert, Ianessa A; Poletto, Christopher J; Saxon, Keith G; Kearney, Pamela R; Ludlow, Christy L

2008-01-01

Closure of the true and false vocal folds is a normal part of airway protection during swallowing. Individuals with reduced or delayed true vocal fold closure can be at risk for aspiration and may benefit from intervention to ameliorate the problem. Surface electrical stimulation is currently used during therapy for dysphagia, despite limited knowledge of its physiological effects. Prospective single effects study. The immediate physiological effect of surface stimulation on true vocal fold angle was examined at rest in 27 healthy adults using 10 different electrode placements on the submental and neck regions. Fiberoptic nasolaryngoscopic recordings during passive inspiration were used to measure change in true vocal fold angle with stimulation. Vocal fold angles changed only to a small extent during two electrode placements (P vocal fold abduction was 2.4 degrees; while horizontal placements of electrodes in the submental region produced a mean adduction of 2.8 degrees (P = .03). Surface electrical stimulation to the submental and neck regions does not produce immediate true vocal fold adduction adequate for airway protection during swallowing, and one position may produce a slight increase in true vocal fold opening.

Experimental investigation of protein folding and misfolding.

Science.gov (United States)

Dobson, Christopher M

2004-09-01

Newly synthesised proteins need to fold, often to intricate and close-packed structures, in order to function. The underlying mechanism by which this complex process takes place both in vitro and in vivo is now becoming understood, at least in general terms, as a result of the application of a wide range of biophysical and computational methods used in combination with the techniques of biochemistry and protein engineering. It is increasingly apparent, however, that folding is not only crucial for generating biological activity, but that it is also coupled to a wide range of processes within the cell, ranging from the trafficking of proteins to specific organelles to the regulation of cell growth and differentiation. Not surprisingly, therefore, the failure of proteins to fold appropriately, or to remain correctly folded, is associated with a large number of cellular malfunctions that give rise to disease. Misfolding, and its consequences such as aggregation, can be investigated by extending the types of techniques used to study the normal folding process. Application of these techniques is enabling the development of a unified description of the interconversion and regulation of the different conformational states available to proteins in living systems. Such a description proves a generic basis for understanding the fundamental links between protein misfolding and its associated clinical disorders, such as Alzheimer's disease and Type II diabetes, and for exploring novel therapeutic strategies directed at their prevention and treatment on a rational basis.

Vocal fold contact patterns based on normal modes of vibration.

Science.gov (United States)

Smith, Simeon L; Titze, Ingo R

2018-05-17

The fluid-structure interaction and energy transfer from respiratory airflow to self-sustained vocal fold oscillation continues to be a topic of interest in vocal fold research. Vocal fold vibration is driven by pressures on the vocal fold surface, which are determined by the shape of the glottis and the contact between vocal folds. Characterization of three-dimensional glottal shapes and contact patterns can lead to increased understanding of normal and abnormal physiology of the voice, as well as to development of improved vocal fold models, but a large inventory of shapes has not been directly studied previously. This study aimed to take an initial step toward characterizing vocal fold contact patterns systematically. Vocal fold motion and contact was modeled based on normal mode vibration, as it has been shown that vocal fold vibration can be almost entirely described by only the few lowest order vibrational modes. Symmetric and asymmetric combinations of the four lowest normal modes of vibration were superimposed on left and right vocal fold medial surfaces, for each of three prephonatory glottal configurations, according to a surface wave approach. Contact patterns were generated from the interaction of modal shapes at 16 normalized phases during the vibratory cycle. Eight major contact patterns were identified and characterized by the shape of the flow channel, with the following descriptors assigned: convergent, divergent, convergent-divergent, uniform, split, merged, island, and multichannel. Each of the contact patterns and its variation are described, and future work and applications are discussed. Copyright © 2018 Elsevier Ltd. All rights reserved.

Force generation by titin folding.

Science.gov (United States)

Mártonfalvi, Zsolt; Bianco, Pasquale; Naftz, Katalin; Ferenczy, György G; Kellermayer, Miklós

2017-07-01

Titin is a giant protein that provides elasticity to muscle. As the sarcomere is stretched, titin extends hierarchically according to the mechanics of its segments. Whether titin's globular domains unfold during this process and how such unfolded domains might contribute to muscle contractility are strongly debated. To explore the force-dependent folding mechanisms, here we manipulated skeletal-muscle titin molecules with high-resolution optical tweezers. In force-clamp mode, after quenching the force (force trace contained rapid fluctuations and a gradual increase of average force, indicating that titin can develop force via dynamic transitions between its structural states en route to the native conformation. In 4 M urea, which destabilizes H-bonds hence the consolidated native domain structure, the net force increase disappeared but the fluctuations persisted. Thus, whereas net force generation is caused by the ensemble folding of the elastically-coupled domains, force fluctuations arise due to a dynamic equilibrium between unfolded and molten-globule states. Monte-Carlo simulations incorporating a compact molten-globule intermediate in the folding landscape recovered all features of our nanomechanics results. The ensemble molten-globule dynamics delivers significant added contractility that may assist sarcomere mechanics, and it may reduce the dissipative energy loss associated with titin unfolding/refolding during muscle contraction/relaxation cycles. © 2017 The Protein Society.

Solitons and protein folding: An In Silico experiment

Energy Technology Data Exchange (ETDEWEB)

Ilieva, N., E-mail: nevena.ilieva@parallel.bas.bg [Institute of Information and Communication Technologies, Bulgarian Aacademy of Sciences, Sofia (Bulgaria); Dai, J., E-mail: daijing491@gmail.com [School of Physics, Beijing Institute of Technology, Beijing (China); Sieradzan, A., E-mail: adams86@wp.pl [Faculty of Chemistry, University of Gdańsk, Gdańsk (Poland); Niemi, A., E-mail: Antti.Niemi@physics.uu.se [Department of Physics and Astronomy, Uppsala University, Uppsala (Sweden); LMPT–CNRS, Université de Tours, Tours (France)

2015-10-28

Protein folding [1] is the process of formation of a functional 3D structure from a random coil — the shape in which amino-acid chains leave the ribosome. Anfinsen’s dogma states that the native 3D shape of a protein is completely determined by protein’s amino acid sequence. Despite the progress in understanding the process rate and the success in folding prediction for some small proteins, with presently available physics-based methods it is not yet possible to reliably deduce the shape of a biologically active protein from its amino acid sequence. The protein-folding problem endures as one of the most important unresolved problems in science; it addresses the origin of life itself. Furthermore, a wrong fold is a common cause for a protein to lose its function or even endanger the living organism. Soliton solutions of a generalized discrete non-linear Schrödinger equation (GDNLSE) obtained from the energy function in terms of bond and torsion angles κ and τ provide a constructive theoretical framework for describing protein folds and folding patterns [2]. Here we study the dynamics of this process by means of molecular-dynamics simulations. The soliton manifestation is the pattern helix–loop–helix in the secondary structure of the protein, which explains the importance of understanding loop formation in helical proteins. We performed in silico experiments for unfolding one subunit of the core structure of gp41 from the HIV envelope glycoprotein (PDB ID: 1AIK [3]) by molecular-dynamics simulations with the MD package GROMACS. We analyzed 80 ns trajectories, obtained with one united-atom and two different all-atom force fields, to justify the side-chain orientation quantification scheme adopted in the studies and to eliminate force-field based artifacts. Our results are compatible with the soliton model of protein folding and provide first insight into soliton-formation dynamics.

Solitons and protein folding: An In Silico experiment

International Nuclear Information System (INIS)

Ilieva, N.; Dai, J.; Sieradzan, A.; Niemi, A.

2015-01-01

Protein folding [1] is the process of formation of a functional 3D structure from a random coil — the shape in which amino-acid chains leave the ribosome. Anfinsen’s dogma states that the native 3D shape of a protein is completely determined by protein’s amino acid sequence. Despite the progress in understanding the process rate and the success in folding prediction for some small proteins, with presently available physics-based methods it is not yet possible to reliably deduce the shape of a biologically active protein from its amino acid sequence. The protein-folding problem endures as one of the most important unresolved problems in science; it addresses the origin of life itself. Furthermore, a wrong fold is a common cause for a protein to lose its function or even endanger the living organism. Soliton solutions of a generalized discrete non-linear Schrödinger equation (GDNLSE) obtained from the energy function in terms of bond and torsion angles κ and τ provide a constructive theoretical framework for describing protein folds and folding patterns [2]. Here we study the dynamics of this process by means of molecular-dynamics simulations. The soliton manifestation is the pattern helix–loop–helix in the secondary structure of the protein, which explains the importance of understanding loop formation in helical proteins. We performed in silico experiments for unfolding one subunit of the core structure of gp41 from the HIV envelope glycoprotein (PDB ID: 1AIK [3]) by molecular-dynamics simulations with the MD package GROMACS. We analyzed 80 ns trajectories, obtained with one united-atom and two different all-atom force fields, to justify the side-chain orientation quantification scheme adopted in the studies and to eliminate force-field based artifacts. Our results are compatible with the soliton model of protein folding and provide first insight into soliton-formation dynamics

Visualization of protein folding funnels in lattice models.

Directory of Open Access Journals (Sweden)

Antonio B Oliveira

Full Text Available Protein folding occurs in a very high dimensional phase space with an exponentially large number of states, and according to the energy landscape theory it exhibits a topology resembling a funnel. In this statistical approach, the folding mechanism is unveiled by describing the local minima in an effective one-dimensional representation. Other approaches based on potential energy landscapes address the hierarchical structure of local energy minima through disconnectivity graphs. In this paper, we introduce a metric to describe the distance between any two conformations, which also allows us to go beyond the one-dimensional representation and visualize the folding funnel in 2D and 3D. In this way it is possible to assess the folding process in detail, e.g., by identifying the connectivity between conformations and establishing the paths to reach the native state, in addition to regions where trapping may occur. Unlike the disconnectivity maps method, which is based on the kinetic connections between states, our methodology is based on structural similarities inferred from the new metric. The method was developed in a 27-mer protein lattice model, folded into a 3×3×3 cube. Five sequences were studied and distinct funnels were generated in an analysis restricted to conformations from the transition-state to the native configuration. Consistent with the expected results from the energy landscape theory, folding routes can be visualized to probe different regions of the phase space, as well as determine the difficulty in folding of the distinct sequences. Changes in the landscape due to mutations were visualized, with the comparison between wild and mutated local minima in a single map, which serves to identify different trapping regions. The extension of this approach to more realistic models and its use in combination with other approaches are discussed.

The nature of folded states of globular proteins.

Science.gov (United States)

Honeycutt, J D; Thirumalai, D

1992-06-01

We suggest, using dynamical simulations of a simple heteropolymer modelling the alpha-carbon sequence in a protein, that generically the folded states of globular proteins correspond to statistically well-defined metastable states. This hypothesis, called the metastability hypothesis, states that there are several free energy minima separated by barriers of various heights such that the folded conformations of a polypeptide chain in each of the minima have similar structural characteristics but have different energies from one another. The calculated structural characteristics, such as bond angle and dihedral angle distribution functions, are assumed to arise from only those configurations belonging to a given minimum. The validity of this hypothesis is illustrated by simulations of a continuum model of a heteropolymer whose low temperature state is a well-defined beta-barrel structure. The simulations were done using a molecular dynamics algorithm (referred to as the "noisy" molecular dynamics method) containing both friction and noise terms. It is shown that for this model there are several distinct metastable minima in which the structural features are similar. Several new methods of analyzing fluctuations in structures belonging to two distinct minima are introduced. The most notable one is a dynamic measure of compactness that can in principle provide the time required for maximal compactness to be achieved. The analysis shows that for a given metastable state in which the protein has a well-defined folded structure the transition to a state of higher compactness occurs very slowly, lending credence to the notion that the system encounters a late barrier in the process of folding to the most compact structure. The examination of the fluctuations in the structures near the unfolding----folding transition temperature indicates that the transition state for the unfolding to folding process occurs closer to the folded state.

Modeling Vocal Fold Intravascular Flow using Synthetic Replicas

Science.gov (United States)

Terry, Aaron D.; Ricks, Matthew T.; Thomson, Scott L.

2017-11-01

Vocal fold vibration that is induced by air flowing from the lungs is believed to decrease blood flow through the vocal folds. This is important due to the critical role of blood flow in maintaining tissue health. However, the precise mechanical relationships between vocal fold vibration and blood perfusion remain understudied. A platform for studying liquid perfusion in a synthetic, life-size, self-oscillating vocal fold replica has recently been developed. The replicas are fabricated using molded silicone with material properties comparable to those of human vocal fold tissues and that include embedded microchannels through which liquid is perfused. The replicas are mounted on an air flow supply tube to initiate flow-induced vibration. A liquid reservoir is attached to the microchannel to cause liquid to perfuse through replica in the anterior-posterior direction. As replica vibration is initiated and amplitude increases, perfusion flow rate decreases. In this presentation, the replica design will be presented, along with data quantifying the relationships between parameters such as replica vibration amplitude, stiffness, microchannel diameter, and perfusion flow rate. This work was supported by Grant NIDCD R01DC005788 from the National Institutes of Health.