scholarly journals A Transplantable Syngeneic Allograft Mouse Model for Nongestational Choriocarcinoma of the Ovary

2019 ◽  
Vol 56 (3) ◽  
pp. 399-403 ◽  
Author(s):  
Ludmila Szabova ◽  
Baktiar Karim ◽  
Melanie Gordon ◽  
Lucy Lu ◽  
Nathan Pate ◽  
...  
Keyword(s):  
Mouse Model ◽  
Periodic Acid ◽  
Treatment Strategies ◽  
Genetically Engineered ◽  
Ovarian Tumors ◽  
Periodic Acid Schiff ◽  
Genetic Mouse Model ◽  
Rare Malignancy ◽  
Schiff Reaction

Nongestational choriocarcinoma is a rare malignancy in humans with poor prognosis. Naturally occurring choriocarcinoma is also rare in laboratory mice, and no genetic mouse model accurately recapitulates the features of this cancer. Here we report development of a genetically engineered mouse (GEM) model with alterations in Brca2, Trp53, and RB that develops ovarian tumors. Most of the ovarian tumors displayed histological characteristics of nongestational choriocarcinoma of the ovary (NGCO) (47%) with abundant syncytiotrophoblasts and cytotrophoblasts, positive immunolabeling for human chorionic gonadotropin, and positive periodic acid–Schiff reaction. The rest of the ovarian tumors were serous epithelial ovarian carcinoma (SEOC) (26%) or mixed tumors consisting of NGCO and SEOC (26%). We further established syngeneic orthotopic mouse models for NGCO by in vivo passaging of GEM tumors. These metastatic models provide a platform for evaluating new treatment strategies in preclinical studies aimed at improving outcomes in choriocarcinoma patients.

scholarly journals Ectopic atrial arrhythmias arising from canine thoracic veins during in vivo stellate ganglia stimulation

2008 ◽  
Vol 295 (2) ◽  
pp. H691-H698 ◽  
Author(s):  
Alex Y. Tan ◽  
Shengmei Zhou ◽  
Byung Chun Jung ◽  
Masahiro Ogawa ◽  
Lan S. Chen ◽  
...  
Keyword(s):  
Pulmonary Vein ◽  
Sinus Node ◽  
Periodic Acid ◽  
Sympathetic Innervation ◽  
Sympathetic Nerves ◽  
Atrial Arrhythmias ◽  
Periodic Acid Schiff ◽  
Stellate Ganglia ◽  
Ectopic Beats

The purpose of the present study was to determine whether thoracic veins may act as ectopic pacemakers and whether nodelike cells and rich sympathetic innervation are present at the ectopic sites. We used a 1,792-electrode mapping system with 1-mm resolution to map ectopic atrial arrhythmias in eight normal dogs during in vivo right and left stellate ganglia (SG) stimulation before and after sinus node crushing. SG stimulation triggered significant elevations of transcardiac norepinephrine levels, sinus tachycardia in all dogs, and atrial tachycardia in two of eight dogs. Sinus node crushing resulted in a slow junctional rhythm (51 ± 6 beats/min). Subsequent SG stimulation induced 20 episodes of ectopic beats in seven dogs and seven episodes of pulmonary vein tachycardia in three dogs (cycle length 273 ± 35 ms, duration 16 ± 4 s). The ectopic beats arose from the pulmonary vein ( n = 11), right atrium ( n = 5), left atrium ( n = 2), and the vein of Marshall ( n = 2). There was no difference in arrhythmogenic effects of left vs. right SG stimulation (13/29 vs. 16/29 episodes, P = nonsignificant). There was a greater density of periodic acid Schiff-positive cells ( P < 0.05) and sympathetic nerves ( P < 0.05) at the ectopic sites compared with other nonectopic atrial sites. We conclude that, in the absence of a sinus node, thoracic veins may function as subsidiary pacemakers under heightened sympathetic tone, becoming the dominant sites of initiation of focal atrial arrhythmias that arise from sites with abundant sympathetic nerves and periodic acid Schiff-positive cells.

scholarly journals The potential renal toxicity of silver nanoparticles after repeated oral exposure and its underlying mechanisms

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Hamed Nosrati ◽  
Manijeh Hamzepoor ◽  
Maryam Sohrabi ◽  
Massoud Saidijam ◽  
Mohammad Javad Assari ◽  
...  
Keyword(s):  
Silver Nanoparticles ◽  
Molecular Mechanisms ◽  
Renal Toxicity ◽  
Periodic Acid ◽  
Critical Role ◽  
Oral Exposure ◽  
Control Group ◽  
Rt Pcr ◽  
Periodic Acid Schiff

Abstract Background Silver nanoparticles (AgNPs) can accumulate in various organs after oral exposure. The main objective of the current study is to evaluate the renal toxicity induced by AgNPs after repeated oral exposure and to determine the relevant molecular mechanisms. Methods In this study, 40 male Wistar rats were treated with solutions containing 30, 125, 300, and 700 mg/kg of AgNPs. After 28 days of exposure, histopathological changes were assessed using hematoxylin-eosin (H&E), Masson’s trichrome, and periodic acid-Schiff (PAS) staining. Apoptosis was quantified by TUNEL and immunohistochemistry of caspase-3, and the level of expression of the mRNAs of growth factors was determined using RT-PCR. Results Histopathologic examination revealed degenerative changes in the glomeruli, loss of tubular architecture, loss of brush border, and interrupted tubular basal laminae. These changes were more noticeable in groups treated with 30 and 125 mg/kg. The collagen intensity increased in the group treated with 30 mg/kg in both the cortex and the medulla. Apoptosis was much more evident in middle-dose groups (i.e., 125 and 300 mg/kg). The results of RT-PCR indicated that Bcl-2 and Bax mRNAs upregulated in the treated groups (p < 0.05). Moreover, the data related to EGF, TNF-α, and TGF-β1 revealed that AgNPs induced significant changes in gene expression in the groups treated with 30 and 700 mg/kg compared to the control group. Conclusion Our observations showed that AgNPs played a critical role in in vivo renal toxicity.

scholarly journals Effect of activity on performance and morphology in ischaemic rat slow muscles

1990 ◽  
Vol 152 (1) ◽  
pp. 265-279
Author(s):  
A. Corsi ◽  
A. L. Granata ◽  
O. Hudlicka
Keyword(s):  
Blood Supply ◽  
Periodic Acid ◽  
Capillary Density ◽  
Muscle Performance ◽  
Similar Proportion ◽  
Periodic Acid Schiff ◽  
Rat Soleus Muscle ◽  
Improved Performance ◽  
Isometric Twitch ◽  
Schiff Reaction

Muscle performance and structure was studied in rat soleus muscle with limited blood supply in combination with chronic muscle stimulation. Blood supply to the lower leg was restricted by ligation of the common iliac artery, electrodes were implanted in the vicinity of the sciatic nerve and ankle flexors were denervated. Three days later, soleus and gastrocnemius muscles were stimulated at 4 Hz four times a day for a period of 20 min with 2 h intervals between stimulations; this procedure was continued for 4 days. Muscle performance, histochemistry and ultrastructure were studied on the eighth day after operation in these muscles and in ischaemic unstimulated muscles with denervated ankle flexors. Both were compared with control animals. Muscles with limited blood supply developed less isometric twitch tension than control muscles (peak twitch tension in ischaemic muscle was 60.3 +/− 4.8 g g-1 muscle, mean +/− S.E.M., compared to 79.7 +/− 6.9 g g-1 in control muscle; tensions after 5 min contraction were 54.5 +/− 5.5 g g-1 in ischaemic muscle compared to 70.6 +/− 6 g g-1 in controls). Stimulated muscles with limited blood supply had higher peak (85 +/− 16.6 g g-1) and final (87 +/− 12 g g-1) tensions, and also fatigued less than muscles with limited blood supply but no stimulation. Histochemical estimation of capillary density (by staining for alkaline phosphatase) and slow (SO) and fast (FOG) fibres (by myosin ATPase staining) revealed similar capillary to fibre ratios (2.5) and a similar proportion of FOG fibres (around 18%) in all muscles. The proportion of glycogen-depleted fibres (estimated from the periodic acid Schiff reaction, PAS) in muscles removed from animals 10 min after a 5 min period of isometric twitches was significantly lower in ischaemic muscles (45.1 +/− 1.9%) than in control (80.5 +/− 1.5%) or chronically stimulated ischaemic muscles (67.3 +/− 4.0%). Electron microscopy showed disorganised myofibrils with Z-line streaming in 7.48 +/− 3.04% of fibres in muscles with limited blood supply. Swollen and degenerated mitochondria, dilated sarcoplasmic reticulum and areas of disrupted sarcolemma were also observed. Stimulated ligated muscles showed a significantly lower proportion of fibres with disorganised filaments (0.65 +/− 0.32%) and other signs of damage were much less frequent. The reduced damage and improved performance of chronically stimulated slow muscle may be the result of improved microcirculation, preventing accumulation of lactate.

scholarly journals Activation and activity of glycosylated KLKs 3, 4 and 11

2018 ◽  
Vol 399 (9) ◽  
pp. 1009-1022 ◽  
Author(s):  
Shihui Guo ◽  
Peter Briza ◽  
Viktor Magdolen ◽  
Hans Brandstetter ◽  
Peter Goettig
Keyword(s):  
Physiological Function ◽  
Periodic Acid ◽  
Hek293 Cells ◽  
Secretory Expression ◽  
Detailed Characterization ◽  
Periodic Acid Schiff ◽  
Clinical Biomarkers ◽  
Schiff Reaction

Abstract Human kallikrein-related peptidases 3, 4, 11, and KLK2, the activator of KLK3/PSA, belong to the prostatic group of the KLKs, whose major physiological function is semen liquefaction during the fertilization process. Notably, these KLKs are upregulated in prostate cancer and are used as clinical biomarkers or have been proposed as therapeutic targets. However, this potential awaits a detailed characterization of these proteases. In order to study glycosylated prostatic KLKs resembling the natural proteases, we used Leishmania (LEXSY) and HEK293 cells for secretory expression. Both systems allowed the subsequent purification of soluble pro-KLK zymogens with correct propeptides and of the mature forms. Periodic acid-Schiff reaction, enzymatic deglycosylation assays, and mass spectrometry confirmed the glycosylation of these KLKs. Activation of glycosylated pro-KLKs 4 and 11 turned out to be most efficient by glycosylated KLK2 and KLK4, respectively. By comparing the glycosylated prostatic KLKs with their non-glycosylated counterparts from Escherichia coli, it was observed that the N-glycans stabilize the KLK proteases and change their activation profiles and their enzymatic activity to some extent. The functional role of glycosylation in prostate-specific KLKs could pave the way to a deeper understanding of their biology and to medical applications.

scholarly journals IMMU-10. ESTABLISHING EFFECTIVE MODELS FOR IMMUNOTHERAPY IN GBM

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi121-vi121
Author(s):  
Daniel Zamler ◽  
Er-Yen Yen ◽  
Takashi Shingu ◽  
Jiangong Ren ◽  
Cynthia Kassab ◽  
...  
Keyword(s):  
Mouse Model ◽  
Cell Function ◽  
Genetically Engineered ◽  
Death Sentence ◽  
Immune Microenvironment ◽  
Knockout Mouse Model ◽  
Arginase 1 ◽  
Genetically Engineered Mouse Model ◽  
Human Gbm

Abstract The introduction of immunotherapies has been paradigm shifting for cancers that were previously a death sentence. However, preclinical/clinical studies on glioblastoma (GBM) have generated mixed outcomes in patients, likely due to its great heterogeneity of immune microenvironment, particularly the myeloid cell populations. Primary patient studies have been limited by a difficulty in performing longitudinal studies, uncontrolled environmental conditions, and genetic variability. There is also, unfortunately, a paucity of mouse models that effectively re-capitulate the immune microenvironment of the human disease. To address these difficulties, we have established the Qk/p53/Pten (QPP) triple knockout mouse model established in our lab. The QPP model uses a cre-lox system to induce Qk deletion on a Pten−/−; p53−/− background which helps NSCs maintain their stemness outside the SVZ in Nes-CreERT2;QkiL/L PtenL/L p53L/L mice, which develops glioblastoma with survival of ~105 days. We have preliminarily assessed the QPP tumors as a faithful model to study the immune response to GBM and found them to recapitulate human GBM with respect to differential response to checkpoint blockade therapy and myeloid and T-cells histopathologically, particularly regarding upregulation of Arginase-1 (Arg1). Arg1 is the canonical marker for tumor-associated macrophages (TAMs), which is a major population of myeloid cells that greatly infiltrate in human GBM, sometimes making up more than ~30% of all GBM cells. Given TAMs’ prevalence in the tumor microenvironment and their upregulation of Arg1 in both human GBM and our QPP model, we are testing whether manipulation of Arg1 will impact TAM function and influence GBM growth. We are also evaluating arginine metabolism in TAMs effect on T cell function in GBM. Lastly, we have developed a genetically engineered mouse model to study the role of Arg1 knockout in a GBM context in-vivo. Our studies suggest that Arg1 plays an important role in GBM immune interaction.

scholarly journals Nme1 and Nme2 genes exert metastasis-suppressor activities in a genetically engineered mouse model of UV-induced melanoma

2020 ◽  
Vol 124 (1) ◽  
pp. 161-165
Author(s):  
Nidhi Pamidimukkala ◽  
Gemma S. Puts ◽  
M. Kathryn Leonard ◽  
Devin Snyder ◽  
Sandrine Dabernat ◽  
...  
Keyword(s):  
Mouse Model ◽  
Suppressor Gene ◽  
Genetically Engineered ◽  
In Vivo Model ◽  
Metastasis Suppressor ◽  
Specific Context ◽  
Genetically Engineered Mouse Model ◽  
Metastatic Activity ◽  
First Time

AbstractNME1 is a metastasis-suppressor gene (MSG), capable of suppressing metastatic activity in cell lines of melanoma, breast carcinoma and other cancer origins without affecting their growth in culture or as primary tumours. Herein, we selectively ablated the tandemly arranged Nme1 and Nme2 genes to assess their individual impacts on metastatic activity in a mouse model (HGF:p16−/−) of ultraviolet radiation (UVR)-induced melanoma. Metastatic activity was strongly enhanced in both genders of Nme1- and Nme2-null mice, with stronger activity in females across all genotypes. The study ascribes MSG activity to Nme2 for the first time in an in vivo model of spontaneous cancer, as well as a novel metastasis-suppressor function to Nme1 in the specific context of UVR-induced melanoma.

scholarly journals THE HISTOCHEMICAL INTERPRETATION OF THE COMPLEX RESULTS OF METHYLATION UPON GASTROINTESTINAL TRACT MUCINS, WITH SPECIAL REFERENCE TO THE PERIODIC ACID-SCHIFF REACTIVITY

1974 ◽  
Vol 22 (10) ◽  
pp. 986-991 ◽  
Author(s):  
P. E. REID ◽  
C. F. A. CULLING ◽  
W. L. DUNN
Keyword(s):  
Sialic Acid ◽  
Gastrointestinal Tract ◽  
Special Reference ◽  
Periodic Acid ◽  
Separate Study ◽  
Sulfate Ester ◽  
Periodic Acid Schiff ◽  
Smith Degradation ◽  
Vicinal Diol ◽  
Schiff Reaction

The histochemical use of methylation has complex results; particularly in respect of the periodic acid-Schiff reaction, these are analyzed and discussed. Methods are described which allow the separate study of the following effects: (a) the removal of the KOH/periodic acid-Schiff effect; (b) removal of sialic acid from a potential vicinal diol; and (c) the removal of O-sulfate ester from a potential vicinal diol. The use of the Smith degradation technique, in addition to the above, also allows inferences to be drawn in respect of the structure of the mucins (glycoproteins) being investigated.

scholarly journals Necroptosis Contributes to Urban Particulate Matter-Induced Airway Epithelial Injury

2018 ◽  
Vol 46 (2) ◽  
pp. 699-712 ◽  
Author(s):  
Feng Xu ◽  
Man Luo ◽  
Lulu He ◽  
Yuan Cao ◽  
Wen Li ◽  
...  
Keyword(s):  
Particulate Matter ◽  
Pulmonary Inflammation ◽  
Periodic Acid ◽  
Enzyme Linked Immunosorbent Assay ◽  
Periodic Acid Schiff ◽  
Mucus Production ◽  
Gm Csf ◽  
Mucin Expression

Background/Aims: Necroptosis, a form of programmed necrosis, is involved in the pathologic process of several kinds of pulmonary diseases. However, the role of necroptosis in particulate matter (PM)–induced pulmonary injury remains unclear. The objective of this study is to investigate the involvement of necroptosis in the pathogenesis of PM-induced toxic effects in pulmonary inflammation and mucus hyperproduction, both in vitro and in vivo. Methods: PM was administered into human bronchial epithelial (HBE) cells or mouse airways, and the inflammatory response and mucus production were assessed. The mRNA expressions of IL6, IL8 and MUC5AC in HBE cells and Cxcl1, Cxcl2, and Gm-csf in the lung tissues were detected by quantitative real-time RT-PCR. The secreted protein levels of IL6 and IL8 in culture supernatants and Cxcl1, Cxcl2, and Gm-csf in bronchoalveolar lavage fluid (BALF) were detected by enzyme-linked immunosorbent assay (ELISA). We used Western blot to measure the protein expressions of necroptosis-related proteins (RIPK1, RIPK3, and Phospho-MLKL), NF-κB (P65 and PP65), AP-1 (P-c-Jun and P-c-Fos) and MUC5AC. Cell necrosis and mitochondrial ROS were detected using flow cytometry. In addition, pathological changes and scoring of lung tissue samples were monitored using hemoxylin and eosin (H&E), periodic acid-schiff (PAS) and immunohistochemistry staining. Results: Our study showed that PM exposure induced RIP and MLKL-dependent necroptosis in HBE cells and in mouse lungs. Managing the necroptosis inhibitor Necrostatin-1 (Nec-1) and GSK’872, specific molecule inhibitors of necroptosis, markedly reduced PM-induced inflammatory cytokines, e.g., IL6 and IL8, and MUC5AC in HBE cells. Similarly, administering Nec-1 significantly reduced airway inflammation and mucus hyperproduction in PM-exposed mice. Mechanistically, we found PM–induced necroptosis was mediated by mitochondrial reactive oxygen species-dependent early growth response gene 1, which ultimately promoted inflammation and mucin expression through nuclear factor κB and activator protein-1 pathways, respectively. Conclusions: Our results demonstrate that necroptosis is involved in the pathogenesis of PM–induced pulmonary inflammation and mucus hyperproduction, and suggests that it may be a novel target for treatment of airway disorders or disease exacerbations with airborne particulate pollution.

scholarly journals Acute lymphoblastic leukemia with unusual cytoplasmic granulation: a morphologic, cytochemical, and ultrastructural study

Blood ◽  
1986 ◽  
Vol 68 (2) ◽  
pp. 406-411 ◽  
Author(s):  
J Fradera ◽  
E Velez-Garcia ◽  
JG White
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Periodic Acid ◽  
Periodic Acid Schiff ◽  
Acute Leukemias ◽  
Ultrastructural Studies ◽  
Sudan Black B ◽  
Blast Cells ◽  
Chediak Higashi Syndrome ◽  
Schiff Reaction

Abstract The classification of the acute leukemias depends mainly on the morphologic and cytochemical evaluation of the blast forms. One of the main accepted morphologic criteria in the differentiation between acute lymphoblastic leukemia (ALL) and acute myeloblastic leukemia (AML) is the absence of granules in the blast cells of ALL. We evaluated a patient with ALL in whom granules were present in the cytoplasm of 35% of the blast cells, as seen in AML. Cytochemical evaluation was performed, including periodic acid-Schiff reaction, Sudan black B, alpha-naphthyl acetate, alpha-naphthyl butyrate, naphthol AS-D chloroacetate, and acid phosphatase stains. The results of these studies confirmed the morphologic impression and diagnosis of ALL. Ultrastructural evaluation revealed that the granules consisted of many tiny vesicles closely packed together in a proteinaceous matrix, resembling to some extent the inclusions described in lymphocytes in the Chediak-Higashi syndrome, but clearly different. The morphologic, cytochemical, and ultrastructural studies of this unique case are presented in detail. To our knowledge, this is the first time that such granules have been described in blast cells of ALL.

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