Expression of bcl-2 in Enteric Neurons in Normal Human Bowel and Hirschsprung Disease

1999 ◽  
Vol 123 (12) ◽  
pp. 1264-1268 ◽  
Author(s):  
Tomas Wester ◽  
Yngve Olsson ◽  
Leif Olsen
Keyword(s):  
Ganglion Cells ◽  
Neuron Specific Enolase ◽  
Hirschsprung Disease ◽  
Immunohistochemical Analysis ◽  
Nerve Fibers ◽  
Enteric Neurons ◽  
Normal Colon ◽  
Normal Human ◽  
Immunohistochemical Methods

Abstract Objective.—The bcl-2 protein has the functional role of blocking apoptosis, ie, programmed cell death. This protein is widely expressed in the developing central and peripheral nervous systems. The purpose of this study was to map bcl-2 expression in the human enteric nervous system, as this has not previously been done. Methods.—Rectal specimens were obtained at autopsy of 13 fetuses at 13 to 31 weeks of gestation. Normal colon was also obtained from 5 children and 2 adults, and, in addition, ganglionic and aganglionic bowel resected in 11 patients with Hirschsprung disease was examined. Specimens were fixed in formalin, embedded in paraffin, and analyzed with immunohistochemical methods, using antibodies raised against bcl-2 and neuron-specific enolase (NSE). Results.—The bcl-2 protein was expressed in myenteric and submucous ganglion cells in fetuses, children, and adults. Nerve fibers of the enteric plexuses that were bcl-2 immunoreactive were few compared with the number of NSE-immunoreactive nerve fibers. In aganglionic bowel no bcl-2–or NSE-immunoreactive ganglion cells were revealed. Results of NSE immunohistochemistry showed clearly stained hypertrophic nerve bundles, known to be of extrinsic origin, which were only weakly bcl-2 immunoreactive. Conclusion.—Expression of bcl-2 in enteric ganglion cells of the myenteric and submucous plexuses is displayed in the fetus and during childhood and is also retained in adult bowel. Immunohistochemical analysis of bcl-2 provides a good marker for identification of ganglion cells in Hirschsprung disease and may also be valuable for the diagnosis of disorders characterized by hypoganglionosis or hyperganglionosis.

Total Colonic Aganglionosis: Case Report, Practical Diagnostic Approach and Pitfalls

2010 ◽  
Vol 134 (10) ◽  
pp. 1467-1473 ◽  
Author(s):  
Raja Rabah
Keyword(s):  
Transition Zone ◽  
Ganglion Cells ◽  
Hirschsprung Disease ◽  
Rectal Biopsy ◽  
Nerve Fibers ◽  
Submucosal Plexus ◽  
Total Colonic Aganglionosis ◽  
Biopsy Specimens ◽  
Suction Rectal Biopsy ◽  
Acetylcholinesterase Staining

Abstract Hirschsprung disease remains a challenging diagnosis for many pathologists. The disease is characterized by a lack of ganglion cells in the myenteric and submucosal plexus, associated with increased numbers of acetylcholinesterase-positive nerve fibers. Hypertrophic nerve fibers are present in most but not all patients. Total colonic aganglionosis (TCA) is an uncommon form of Hirschsprung disease with clinical, histologic, and genetic differences and is even more difficult to diagnose and manage. This case illustrates some of the difficulties frequently faced by the pathologists dealing with total colonic aganglionosis. Suction rectal biopsy specimens often lack significant nerve hypertrophy and positive acetylcholinesterase staining, which aid in the diagnosis. Pathologists have to depend mainly on the lack of ganglion cells in adequate submucosa to establish the diagnosis. Transition zone is often long in total colonic aganglionosis and interpretation of frozen sections can be difficult. The presence of several uniformly distributed clusters of mature ganglion cells and lack of nerve hypertrophy are required to avoid connections at the transition zone.

Hypoglycemic detection at the portal vein is mediated by capsaicin-sensitive primary sensory neurons

2007 ◽  
Vol 293 (1) ◽  
pp. E96-E101 ◽  
Author(s):  
Satoshi Fujita ◽  
MaryAnn Bohland ◽  
Graciela Sanchez-Watts ◽  
Alan G. Watts ◽  
Casey M. Donovan
Keyword(s):  
Portal Vein ◽  
Sensory Neurons ◽  
Jugular Vein ◽  
Immunohistochemical Analysis ◽  
Nerve Fibers ◽  
Similar Response ◽  
Primary Sensory Neurons ◽  
Calcitonin Gene ◽  
Epinephrine Concentration

To elucidate the type of spinal afferent involved in hypoglycemic detection at the portal vein, we considered the potential role of capsaicin-sensitive primary sensory neurons. Specifically, we examined the effect of capsaicin-induced ablation of portal vein afferents on the sympathoadrenal response to hypoglycemia. Under anesthesia, the portal vein was isolated in rats and either capsaicin (CAP) or the vehicle (CON) solution applied topically. During the same surgery, the carotid artery (sampling) and jugular vein (infusion) were cannulated. One week later, all animals underwent a hyperinsulinemic hypoglycemic clamp, with glucose (variable) and insulin (25 mU·kg−1·min−1) infused via the jugular vein. Systemic hypoglycemia (2.76 ± 0.05 mM) was induced by minute 75 and sustained until minute 105. By design, no significant differences were observed in arterial glucose or insulin concentrations between groups. When hypoglycemia was induced in CON, the plasma epinephrine concentration increased from 0.67 ± 0.05 nM at basal to 36.15 ± 2.32 nM by minute 105. Compared with CON, CAP animals demonstrated an 80% suppression in epinephrine levels by minute 105, 7.11 ± 0.55 nM ( P < 0.001). A similar response to hypoglycemia was observed for norepinephrine, with CAP values suppressed by 48% compared with CON. Immunohistochemical analysis of the portal vein revealed an 85% decrease in the number of calcitonin gene-related peptide-reactive nerve fibers following capsaicin-induced ablation. That the suppression in the sympathoadrenal response was comparable to our previous findings for total denervation of the portal vein indicates that hypoglycemic detection at the portal vein is mediated by capsaicin-sensitive primary sensory neurons.

scholarly journals lncRNA-RMST functioned as a SOX2 transcription co-regulator to regulate miR-1251 in the progression of Hirschsprung’s disease

2020 ◽  
Author(s):  
Lingling Zhou ◽  
Zhengke Zhi ◽  
Pingfa Chen ◽  
Zhonghong Wei ◽  
Chunxia Du ◽  
...  
Keyword(s):  
Hirschsprung's Disease ◽  
Hirschsprung’S Disease ◽  
Hirschsprung Disease ◽  
Underlying Mechanism ◽  
Bioinformatic Analysis ◽  
Enteric Neurons ◽  
Intron Region ◽  
Non Coding Rnas ◽  
And Migration

ABSTRACTHirschsprung’s disease (HSCR) is a congenital disorder characterized by the absence of enteric neural crest cells (ENCCs). Non-coding RNAs including long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) have been authenticated as important regulators of biological functions. We conducted a microarray analysis and found lncRNA Rhabdomyosarcoma 2-associated transcript (RMST) was down-regulated in the stenotic segment of HSCR patients. MiR-1251 is transcribed from the intron region of RMST and was also low-expressed. When the expression of RMST or miR-1251 was reduced, the cell proliferation and migration were attenuated. However, RMST didn’t affect the expression of miR-1251 directly found in this study. Through bioinformatic analysis, transcription factor SOX2 was predicted to bind to the promoter region of miR-1251 which was confirmed by CHIP assay. Herein, we demonstrated that RMST exerted as a co-regulator of SOX2 to regulate the expression of miR-1251. Furtherly, AHNAK was proved to be the target gene of miR-1251 in this study. Taken together, we revealed the role of RMST/SOX2/miR-1251/AHNAK pathway in the occurrence of Hirschsprung’s disease and provided a potential therapeutic target for this disease.SUMMARY STATEMENTHirschsprung disease (HSCR) is characterized by a deficit in enteric neurons, however, the underlying mechanism remains unclear. This study revealed the role of lnc-RMST during the occurrence of HSCR.

Histochemical Diagnosis of Hirschsprung Disease

PEDIATRICS ◽  
1982 ◽  
Vol 69 (6) ◽  
pp. 755-761
Author(s):  
Carolyn Coker Huntley ◽  
Louis deS. Shaffner ◽  
Venkata R. Challa ◽  
Anne D. Lyerly
Keyword(s):  
Lamina Propria ◽  
False Positive ◽  
Ganglion Cells ◽  
False Negative ◽  
Hirschsprung Disease ◽  
Nerve Fibers ◽  
Infants And Children ◽  
Muscularis Mucosa ◽  
False Positive Reactions ◽  
In Infants And Children

A histochemical staining technique for detection of acetylcholinesterase (AChE) in rectal suction biopsies was compared with the presence or absence of ganglion cells in full-thickness or suction biopsies for the diagnosis of Hirschsprung disease (HD) in infants and children. Biopsies from 55 of 58 children were adequate for both the AChE assay and routine pathologic examination for ganglion cells. Two patterns of AChE staining were noted. With pattern A, prominent nerve fibers staining for AChE were seen throughout the muscularis mucosa and the lamina propria. With pattern B, similar fibers were seen only in the muscularis mucosa and the areas of lamina propria that were immediately adjacent. No "false-negative" AChE staining reactions were found in patients with HD. No "false-positive" reactions showing pattern A were found. This pattern was diagnostic for HD. Three false-positive reactions were found showing pattern B in patients with conditions other than HD. Among 22 patients with HD, 19 were males and three were females. Pattern A occurred in all age groups and in both sexes. Pattern B in patients with HD was seen exclusively in male infants 1 month of age or less. Experience suggests that the AChE staining of rectal suction biopsies is an excellent screening test for HD in infants and children. If pattern B is encountered, however, the specimen should be examined by routine pathologic techniques for the presence of submucosal ganglion cells.

scholarly journals Axonal Protection by Nicotinamide Riboside via SIRT1-Autophagy Pathway in TNF-Induced Optic Nerve Degeneration

2020 ◽  
Vol 57 (12) ◽  
pp. 4952-4960
Author(s):  
Yasushi Kitaoka ◽  
Kana Sase ◽  
Chihiro Tsukahara ◽  
Naoki Fujita ◽  
Ibuki Arizono ◽  
...  
Keyword(s):  
Optic Nerve ◽  
Ganglion Cells ◽  
Immunohistochemical Analysis ◽  
Nerve Fibers ◽  
Nerve Degeneration ◽  
Autophagic Flux ◽  
Nicotinamide Riboside ◽  
Axon Loss ◽  
Autophagy Pathway ◽  
Optic Nerve Degeneration

Abstract Nicotinamide adenine dinucleotide (NAD+) synthesis pathway has been involved in many biological functions. Nicotinamide riboside (NR) is widely used as an NAD+ precursor and known to increase NAD+ level in several tissues. The present study aimed to examine the effect of NR on tumor necrosis factor (TNF)-induced optic nerve degeneration and to investigate whether it alters SIRT1 expression and autophagic status in optic nerve. We also examined the localization of nicotinamide riboside kinase 1 (NRK1), which is a downstream enzyme for NR biosynthesis pathway in retina and optic nerve. Intravitreal injection of TNF or TNF plus NR was performed on rats. The p62 and LC3-II protein levels were examined to evaluate autophagic flux in optic nerve. Immunohistochemical analysis was performed to localize NRK1 expression. Morphometric analysis showed substantial axonal protection by NR against TNF-induced axon loss. TNF-induced increment of p62 protein level was significantly inhibited by NR administration. NR administration alone significantly increased the LC3-II levels and reduced p62 levels compared with the basal levels, and upregulated SIRT1 levels in optic nerve. Immunohistochemical analysis showed that NRK1 exists in retinal ganglion cells (RGCs) and nerve fibers in retina and optic nerve. NR administration apparently upregulated NRK1 levels in the TNF-treated eyes as well as the control eyes. Pre-injection of an SIRT1 inhibitor resulted in a significant increase of p62 levels in the NR plus TNF treatment group, implicating that SIRT1 regulates autophagy status. In conclusion, NRK1 exists in RGCs and optic nerve axons. NR exerted protection against axon loss induced by TNF with possible involvement of upregulated NRK1 and SIRT1-autophagy pathway.

Hirschsprung Disease and Use of Calretinin in Inadequate Rectal Suction Biopsies

2013 ◽  
Vol 137 (8) ◽  
pp. 1099-1102 ◽  
Author(s):  
David Hernandez Gonzalo ◽  
Thomas Plesec
Keyword(s):  
Gold Standard ◽  
Clinical Course ◽  
Ganglion Cells ◽  
Hirschsprung Disease ◽  
Disease Status ◽  
Nerve Fibers ◽  
Clinical Suspicion ◽  
Muscularis Mucosae ◽  
Hematoxylin Eosin

Context.—Up to 17% of all rectal suction biopsies performed in the evaluation of Hirschsprung disease are considered inadequate. In most instances, inadequate biopsies contain too little submucosa or are taken within the anal transition zone. Objectives.—To examine the utility of calretinin stain in the workup of inadequate biopsies for patients with clinical suspicion of Hirschsprung disease. Design.—A retrospective analysis was conducted of all rectal suction biopsies performed in the evaluation of Hirschsprung disease during the previous 12 years that were considered “inadequate.” Seventeen cases were identified, and Hirschsprung disease status was determined by clinical or surgical follow-up. Immunohistochemistry for calretinin was performed for all cases containing columnar mucosa, which were evaluated without knowledge of clinical course. Results.—All 12 patients without Hirschsprung disease had calretinin-positive nerve fibers in the lamina propria or muscularis mucosae, and all 5 patients with Hirschsprung disease had no calretinin staining of nerves. Conclusions.—In this retrospective series, calretinin immunohistochemistry correctly predicted outcome in all instances. Although the gold standard for the diagnosis of Hirschsprung disease in rectal suction biopsies remains the evaluation of ganglion cells in a hematoxylin-eosin staining with sufficient submucosa, calretinin immunohistochemistry is quite helpful in triaging further workup based on clinical suspicion.

Characterization of the Transition Zone in Short Segment Hirschsprung Disease Using Calretinin Immunostaining

2021 ◽  
pp. 109352662110539
Author(s):  
Franziska Righini-Grunder ◽  
Dorothée Bouron-Dal Soglio ◽  
Lara Hart ◽  
Ann Aspirot ◽  
Christophe Faure ◽  
...  
Keyword(s):  
Transition Zone ◽  
Ganglion Cells ◽  
Short Form ◽  
Hirschsprung Disease ◽  
Nerve Fibers ◽  
Normal Density ◽  
Short Segment ◽  
Pull Through ◽  
Distal Border ◽  
Proximal Border

Introduction: The detailed expression pattern of calretinin immunohistochemistry in the transition zone (TZ) of Hirschsprung disease (HSCR) has not yet been reported. This study aims to examine the value of calretinin immunohistochemistry for more accurately determining the distal and proximal border of the TZ in short segment HSCR. Methods: Specimens of pull-through surgery from 51 patients with short form of HSCR were analyzed on two longitudinal strips using hematoxylin and eosin (H&E) staining and calretinin immunohistochemistry. Results: In all but two patients, the first appearance of calretinin expression was seen on mucosal nerve fibers before the appearance of any ganglion cells, indicating the distal border of the TZ. The maximum distance between the distal border of the TZ and the proximal border of the TZ, defined by ganglion cells in a normal density on H&E stained sections, a strong calretinin expression on mucosal nerve fibers and in >80% of submucosal and myenteric ganglion cells, with no nerve hypertrophy and absence of ganglionitis was 60 mm. Conclusion: The distal border of the TZ is characterized by calretinin positive intramucosal neurites in nearly all of short form of HSCR and not by calretinin expression on ganglion cells.

Localization of ahe alpha 6 and beta 4 integrin subunits in normal human non-lymphoid tissues

1992 ◽  
Vol 103 (4) ◽  
pp. 1243-1247 ◽  
Author(s):  
P.G. Natali ◽  
M.R. Nicotra ◽  
A. Bigotti ◽  
C. De Martino
Keyword(s):  
Epithelial Cells ◽  
Peripheral Nerves ◽  
Immunohistochemical Analysis ◽  
Wide Distribution ◽  
Basement Membranes ◽  
Laminin Receptor ◽  
Lymphoid Tissues ◽  
Small Vessels ◽  
Normal Human

The alpha 6/beta 4 integrin, of undefined receptor activity, has been shown to be expressed in a variety of murine epithelial cells. To gain information on the role of this heterodimer in tissue architecture as well as in malignant transformation we have performed an extensive immunohistochemical analysis of normal human tissues using monoclonal antibodies to alpha 6 and beta 4 subunits. Because alpha 6 is known to associate also with the beta 1 subunit to form a non-promiscuous receptor for laminin, the expression of beta 1 chain was also evaluated. The results of this study have shown that the alpha 6 chain has a wide distribution in tissues, including small vessels and peripheral nerves. alpha 6 colocalizes with beta 4 and beta 1 in most epithelial cells at the basolateral or basal aspect abutting the basement membrane. In a minority of tissues lacking beta 4, the alpha 6 chain is coexpressed with beta 1. These findings demonstrate that the expression of alpha 6/beta 1 laminin receptor and alpha 6/beta 4 heterodimer is phylogenetically conserved, suggesting that they are likely to play an important role in cellular scaffolding through binding to laminin and to still uncharacterized ligand/s present in basement membranes.

The Role of the Organ of Corti in Auditory Nerve Stimulation

1973 ◽  
Vol 82 (4) ◽  
pp. 464-472 ◽  
Author(s):  
Merle Lawrence ◽  
Lars-Göran Johnsson
Keyword(s):  
Auditory Nerve ◽  
Dynamic Range ◽  
Ganglion Cells ◽  
Organ Of Corti ◽  
Nerve Fibers ◽  
Nerve Degeneration ◽  
Direct Stimulation ◽  
Afferent Nerve Fibers ◽  
Stimulation Of

An analysis of the contribution to hearing made by the presence of a normal organ of Corti as compared to direct electric stimulation of the nerve leads to the following conclusions: The portion of the basal turn of the cochlea which can be stimulated contains activity regions primarily limited to frequencies above 5000 Hz. Electrical stimulation of sensory afferent nerve fibers gives rise to sensations of very limited dynamic range compared to normal adequate stimulation through the organ of Corti. Following destruction of the organ of Corti, the speed of nerve degeneration in man is not known, but appears to be slow. Some ganglion cells almost always persist but it is doubtful that these are excitable. The severe nerve degeneration known to be present in most cases of human deafness raises critical questions about the feasibility and logic of a direct stimulation of the auditory nerve in these patients. The unavoidable damage to the capillaries and endosteum of the walls of the scala tympani by insertion of a wire is certain to produce further degeneration and new bone formation.

STEROID RECEPTOR PHENOTYPE, EXPRESSION OF HER-2/NEU, PD-1, PD-L1 AND LYMPHOCYTIC-MACROPHAGAL INFILTRATION OF ENDOMETRIAL CARCINOMAS: COMPARISON OF MODERN MOLECULAR BIOLOGICAL TYPES OF THE DISEASE (THE ROLE OF BODY MASS INDEX)

2020 ◽  
Vol 66 (1) ◽  
pp. 71-78
Author(s):  
Lev Bershteyn ◽  
Aleksandr Ivantsov ◽  
Aglaya Ievleva ◽  
A. Venina ◽  
I. Berlev
Keyword(s):  
Body Mass Index ◽  
Body Mass ◽  
Tumor Tissue ◽  
Immunohistochemical Analysis ◽  
The Body ◽  
Molecular Profile ◽  
Total N ◽  
Number Of Patients ◽  
Her 2

The aim of this study was to evaluate steroid receptors’ status of tumor tissue in different molecular biological types of endometrial cancer (EC), subdivided according to the current classification, and their colonization by lymphocytic and macrophage cells, taking into account body mass index of the patients. Materials and methods: Material from treatment-naive patients with EC (total n = 229) was included; the number of sick persons varied depending on the method used. The average age of patients was close to 60 years, and about 90% of them were postmenopausal. It was possible to divide the results of the work into two main subgroups: a) depending on the molecular biological type of the tumor (determined on the basis of genetic and immunohistochemical analysis), and b) depending on the value of the body mass index (BMI). The latter approach was used in patients with EC type demonstrating a defective mismatch repair of the incorrectly paired nucleotides (MMR-D) and with a type without characteristic molecular profile signs (WCMP), but was not applied (due to the smaller number of patients) in EC types with a POLE gene mutation or with expression of the oncoprotein p53. According to the data obtained, when comparing various types of EC, the lowest values of Allred ER and PR scores were revealed for POLE-mutant and p53 types, while the “triple-negative” variant of the tumor (ER-, PR-, HER2/neu-) was most common in POLE-mutant (45.5% of cases) and WCMP (19.4%) types of EC. The p53+ type of EC is characterized by inclination to the higher expression of the macrophage marker CD68 and lymphocytic Foxp3, as well as mRNA of PD-1 and SALL4. In addition to the said above, for WCMP type of EC is peculiar, on the contrary, a decrease in the expression of lymphocytic markers CD8 (protein) and PD-L1 (mRNA). When assessing the role of BMI, its value of >30.0 (characteristic for obesity) was combined with an inclination to the increase of HER-2/neu expression in the case of MMR-D EC type and to the decrease of HER-2 /neu, FOXp3 and ER expression in WCMP type. Conclusions: The accumulated information (mainly describing here hormonal sensitivity of the tumor tissue and its lymphocytic-macrophage infiltration) additionally confirms our earlier expressed opinion that the differences between women with EC are determined by both the affiliation of the neoplasm to one or another molecular biological type (subdivided according to the contemporary classification), as well as by body mass value and (very likely) the associated hormonal and metabolic attributes.

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