Mast cell infiltration associated with tubulointerstitial fibrosis in chronic Aristolochic Acid Nephropathy

2005 ◽  
Vol 24 (2) ◽  
pp. 41-47 ◽  
Author(s):  
Yichao Wu ◽  
Zhihong Liu ◽  
Weixin Hu ◽  
Leishi Li
Keyword(s):  
Mast Cell ◽  
Aristolochic Acid ◽  
Interstitial Fibrosis ◽  
Smooth Muscle Actin ◽  
Periodic Acid ◽  
Basement Membranes ◽  
Cell Infiltration ◽  
Alpha Smooth Muscle Actin ◽  
Periodic Acid Schiff ◽  
Aristolochic Acid Nephropathy

Aristolochic Acid Nephropathy (AAN) is regarded as a kind of toxic nephropathy caused by the formation of DNA- aristolochic acid adducts in renal parenchymal cells. However, the underlying mechanisms driving the progression of renal interstitial fibrosis in AAN still remains unclear. This study aims to elucidate the role of some immunological factors, especially mast cells (MCs), in the pathogenesis of AAN. Sixteen patients with AAN were enrolled in this study, including five acute and 11 chronic AAN. Monoclonal antibodies against human tryptase, alpha smooth muscle actin (α-SMA), and CD68 were applied on serial sections, which were further counterstained with Periodic Acid-Schiff. It was found that massive tryptase-positive MCs were observed in the fibrotic areas in chronic AAN, especially around thickened tubular basement membranes where myofibroblasts accumulated too. In contrast, MCs infiltrated to a less extent in acute AAN, and were barely found in normal control kidneys. In chronic AAN, the number of MCs in the tubulointerstitium was positively correlated with the degree of renal fibrosis ( r=0.64, P<0.05), but not with serum creatinine levels. Meanwhile, the recruitment of MCs into the renal interstitium is accompanied with local proliferation of myofibroblasts. Macrophages were not abundant, neither in acute nor in chronic AAN. Our findings show for the first time that mast cell infiltration seems to be associated with the progression of fibrosis in the renal tubulointerstitium in chronic AAN.

scholarly journals A Case of Canine Apocrine Sweat Gland Adenoma, Clear Cell Variant

2005 ◽  
Vol 42 (2) ◽  
pp. 215-218 ◽  
Author(s):  
K. Nibe ◽  
K. Uchida ◽  
T. Itoh ◽  
S. Tateyama
Keyword(s):  
Sweat Gland ◽  
Clear Cell ◽  
Smooth Muscle Actin ◽  
Periodic Acid ◽  
Alpha Smooth Muscle Actin ◽  
Periodic Acid Schiff ◽  
Clear Cells ◽  
Apocrine Sweat Gland ◽  
Cell Variant ◽  
Clear Cell Variant

A cutaneous mass at the base of the retroauricular region of a 4-year-old, female Golden Retriever was examined pathologically. Histologically, the mass formed multiple nodules consisting of a proliferation of large clear cells with abundant cytoplasm. Mitotic figures among the neoplastic cells were very sparse. The large clear cells were intensely positive for cytokeratins (AE1/AE4, cytokeratin 8 and 18) and moderately positive for lysozyme and contained periodic acid-Schiff-positive granules in the cytoplasm. In addition, small flat cells lined the islands of neoplastic large clear cells, and these were strongly positive for alpha-smooth muscle actin and vimentin, and some were positive for cytokeratin (AE1/AE4), suggesting they were myoepithelial cells. No local recurrence or metastasis has been recognized during the 18 months since surgical excision. On the basis of these findings, the present tumor was diagnosed as apocrine sweat gland adenoma, clear cell variant. There have been few previous reports of canine apocrine adenomas showing a clear cell morphology.

scholarly journals Spontaneous Lung Lesions in Aging Laboratory Rabbits (Oryctolagus cuniculus)

2016 ◽  
Vol 54 (1) ◽  
pp. 178-187 ◽  
Author(s):  
T. K. Cooper ◽  
J. W. Griffith ◽  
Z. C. Chroneos ◽  
J. M. Izer ◽  
L. B. Willing ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Actin ◽  
Periodic Acid ◽  
Genetic Defect ◽  
Clinical Signs ◽  
Heterotopic Bone ◽  
Alpha Smooth Muscle Actin ◽  
Periodic Acid Schiff ◽  
Lung Lesions ◽  
Age Related

Spontaneous age-related lesions of laboratory rabbits are not well documented in the contemporary scientific literature. A retrospective study of diagnostic necropsies of 36 rabbits >2 years of age found a number of common lung lesions. Fibromuscular intimal hyperplasia affected medium and to a lesser extent large pulmonary arteries and was present to a variable extent in all 36 rabbits >2 years of age. The lesions were characterized by fragmentation and/or reduplication of the internal elastic lamina (IEL), proliferation of smoothelin+/alpha-smooth muscle actin (α-SMA)+/vimentin− smooth muscle cells and fewer smoothelin−/α-SMA+/vimentin+ myofibroblasts, and intimal deposition of collagen without thrombosis, embolism, or evidence of pulmonary hypertension. Pulmonary emphysema, present in 30/36 rabbits, was characterized by the loss of alveolar septa; most affected rabbits did not have clinical signs of respiratory disease. In 8/13 rabbits of the inbred EIII/JC audiogenic strain, we identified a unique syndrome of granulomatous pneumonia containing hyaline brown to gray, globular to ring-like acellular material that was Alcian blue and periodic acid-Schiff positive. The material was immunoreactive for surfactant protein-A and had the ultrastructural appearance of multilamellar vesicles, suggesting a genetic defect in surfactant metabolism. Additionally, we found small benign primary lung tumors (fibropapillomas, 5 rabbits) not previously described. Other findings included heterotopic bone (5 rabbits), subacute to chronic suppurative bronchopneumonia, pyogranulomatous pneumonia with plant material, and pulmonary artifacts from barbiturate euthanasia solution.

Tubular overexpression of Gremlin in transgenic mice aggravates renal damage in diabetic nephropathy

2015 ◽  
Vol 309 (6) ◽  
pp. F559-F568 ◽  
Author(s):  
Vanessa Marchant ◽  
Alejandra Droguett ◽  
Graciela Valderrama ◽  
M. Eugenia Burgos ◽  
Daniel Carpio ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Renal Damage ◽  
Transforming Growth Factor ◽  
Mesangial Cells ◽  
Interstitial Fibrosis ◽  
Smooth Muscle Actin ◽  
Periodic Acid ◽  
Kidney Tissue ◽  
Renal Tubules ◽  
Periodic Acid Schiff

Diabetic nephropathy (DN) is currently a leading cause of end-stage renal failure worldwide. Gremlin was identified as a gene differentially expressed in mesangial cells exposed to high glucose and in experimental diabetic kidneys. We have described that Gremlin is highly expressed in biopsies from patients with diabetic nephropathy, predominantly in areas of tubulointerstitial fibrosis. In streptozotocin (STZ)-induced experimental diabetes, Gremlin deletion using Grem1 heterozygous knockout mice or by gene silencing, ameliorates renal damage. To study the in vivo role of Gremlin in renal damage, we developed a diabetic model induced by STZ in transgenic (TG) mice expressing human Gremlin in proximal tubular epithelial cells. The albuminuria/creatinuria ratio, determined at week 20 after treatment, was significantly increased in diabetic mice but with no significant differences between transgenic (TG/STZ) and wild-type mice (WT/STZ). To assess the level of renal damage, kidney tissue was analyzed by light microscopy (periodic acid-Schiff and Masson staining), electron microscopy, and quantitative PCR. TG/STZ mice had significantly greater thickening of the glomerular basement membrane, increased mesangial matrix, and podocytopenia vs. WT/STZ. At the tubulointerstitial level, TG/STZ showed increased cell infiltration and mild interstitial fibrosis. In addition, we observed a decreased expression of podocin and overexpression of monocyte chemoattractant protein-1 and fibrotic-related markers, including transforming growth factor-β1, Col1a1, and α-smooth muscle actin. Together, these results show that TG mice overexpressing Gremlin in renal tubules develop greater glomerular and tubulointerstitial injury in response to diabetic-mediated damage and support the involvement of Gremlin in diabetic nephropathy.

Dexrazoxane Alleviated Doxorubicin-Induced Nephropathy in Rats

Pharmacology ◽  
2022 ◽  
pp. 1-10
Author(s):  
Huihui Hu ◽  
Caipeng Xie ◽  
Zeping Weng ◽  
Pei Yu ◽  
Yuqiang Wang ◽  
...  
Keyword(s):  
Renal Function ◽  
Transforming Growth Factor ◽  
Interstitial Fibrosis ◽  
Smooth Muscle Actin ◽  
Periodic Acid ◽  
Kidney Tissue ◽  
Tunel Staining ◽  
Protective Effects ◽  
Renal Interstitial Fibrosis ◽  
Alpha Smooth Muscle Actin

<b><i>Introduction:</i></b> Doxorubicin (DOX), an anthracycline antitumor agent, has been widely used against various solid tumors and hematological malignancies. However, the clinical application of DOX is restricted by its multiple organ toxicity including nephrotoxicity. This study investigated the protective effects and mechanisms of dexrazoxane (DZR) against DOX-induced nephropathy in rats. <b><i>Methods:</i></b> Male Sprague Dawley rats received 2.5 mg/kg DOX once a week for 5 consecutive weeks. 24-h urinary protein and renal function injury biomarkers were determined to evaluate the renal function. Histopathological changes and glomerulosclerosis were examined by hematoxylin and eosin and periodic acid-Schiff staining. The change of renal ultrastructure in the DOX-induced rats was observed by the electron microscopy. The renal apoptosis was detected by TUNEL staining and measured the protein expression of Caspase-3, Bcl-2, and Bax. Renal interstitial fibrosis was determined by Masson staining and immunohistochemistry examination. The levels of vimentin, alpha-smooth muscle actin (α-SMA), and transforming growth factor β (TGF-β) in kidney tissue were detected by Western blot. <b><i>Results:</i></b> DZR pretreatment markedly raised the survival rate and improved the renal dysfunction in DOX-treated rats. DZR ameliorated DOX-induced histopathological lesion of glomerular and tubular and apoptosis. DZR restored the oxidant/antioxidant balance via regulating the levels of MDA, SOD, and TAC. DZR reduced DOX-induced collagen IV deposition and renal interstitial fibrosis and downregulated the fibrosis-related protein expressions of vimentin, α-SMA, and TGF-β1. <b><i>Conclusion:</i></b> Our results suggest DZR exerted its protective effects against DOX-induced nephropathy through inhibition of lipid peroxidation, apoptosis, and fibrosis.

scholarly journals Huangqi-Danshen Decoction Ameliorates Adenine-Induced Chronic Kidney Disease by Modulating Mitochondrial Dynamics

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Xinhui Liu ◽  
Shiying Huang ◽  
Fochang Wang ◽  
Lin Zheng ◽  
Jiandong Lu ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Interstitial Fibrosis ◽  
Mitochondrial Dynamics ◽  
Smooth Muscle Actin ◽  
Periodic Acid ◽  
Public Health Problem ◽  
High Morbidity ◽  
Tubular Atrophy ◽  
Periodic Acid Schiff

Chronic kidney disease (CKD) is a leading public health problem with high morbidity and mortality. However, the therapies remain limited. Traditional Chinese medicine (TCM) has been used for treating kidney disease for thousands of years and is an effective alternative treatment for CKD patients in China and other Asian countries. In the present study, we aimed to investigate the effect and mechanism of Huangqi-Danshen decoction (HDD), a TCM herbal decoction, on treating CKD. CKD rat model was induced by adding 0.75% adenine to the diet for 4 weeks. HDD extract was administrated orally to CKD rats at the dose of 4.7 g/kg/d for consecutive 4 weeks in adenine-induced CKD rats. Kidney function was evaluated by the levels of serum creatinine (Scr) and blood urea nitrogen (BUN). The pathological changes of kidney tissues were observed by periodic acid-Schiff (PAS) and Masson’s trichrome staining. The proteins expression of renal fibrosis and mitochondrial dynamics were determined and quantified by Western blot analysis. CKD rats showed obvious decline in renal function as evidenced by increased levels of Scr and BUN, which were blunted by HDD treatment. HDD could also improve tubular atrophy and interstitial fibrosis of CKD rats. Moreover, HDD downregulated fibronectin, type IV collagen, and α-smooth muscle actin expression in CKD rats. Furthermore, mitochondrial dynamics was disturbed in CKD rats, which manifested as increased mitochondrial fission and decreased mitochondrial fusion. HDD treatment restored mitochondrial dynamics in CKD rats by repressing dynamin-related protein 1 and Mid 49/51 expression, promoting mitofusin 2 expression, and suppressing optic atrophy 1 proteolysis. In conclusion, HDD could significantly retard CKD progression through modulating mitochondrial dynamics.

scholarly journals Histological and Immunohistochemical Characterization of Vascular Alterations in Meninges of Cats Infected with Gurltia paralysans

Pathogens ◽  
2022 ◽  
Vol 11 (1) ◽  
pp. 88
Author(s):  
Svenja Hartung ◽  
Angelika Weyrich ◽  
Manuel Moroni ◽  
Marcelo Gómez ◽  
Christiane Herden
Keyword(s):  
Spinal Cord ◽  
South America ◽  
Smooth Muscle Actin ◽  
Periodic Acid ◽  
Clinical Signs ◽  
Vascular Lesions ◽  
Alpha Smooth Muscle Actin ◽  
Periodic Acid Schiff ◽  
Tissue Samples

Gurltia paralysans, a metastrongyloid nematode, parasitizes in meningeal vessels in the thoracolumbar spinal cord of cats in South America and causes progressive paraparesis. Recently, the first report outside of South America described gurltiosis in a cat in Spain. As this parasitic disease has so far been largely neglected, especially outside of South America, the aim of the present case study was to add knowledge to the histologic and immunohistochemical characterization of central nervous lesions. To this purpose, formalin-fixed and paraffin-embedded (FFPE) tissue samples from the spinal cord and brain of five cats affected by clinical signs caused by Gurltia paralysans and of three control cats without CNS lesions were histopathologically examined using hematoxylin and eosin stain (HE), Elastica van Gieson stain, as well as periodic acid–Schiff (PAS) reaction. Moreover, immuno- histochemistry for alpha smooth muscle actin and Factor VIII-related antigen were performed to characterize vascular lesions. Lesions were consistent with previous descriptions and were mainly located in the spinal cord and consisted of chronic suppurative or lymphoplasmahistiocytic meningi tis as well as suppurative vasculitis, congestion and varicosis of meningeal veins. In view of the recent detection of this parasite in Europe and the increasing inner-European transport of rescued domestic cats, veterinarians in Europe should be aware of the clinical and pathomorphological presentation of this disease.

Conjunctival myxoid stromal tumour: a distinctive clinicopathological and immunohistochemical study

2018 ◽  
Vol 103 (9) ◽  
pp. 1259-1265 ◽  
Author(s):  
Xiao-Yi Qin ◽  
Zhe-Hao Jin ◽  
You-Pei Wang ◽  
Zong-Duan Zhang
Keyword(s):  
Smooth Muscle Actin ◽  
Periodic Acid ◽  
Clinical Findings ◽  
Stromal Tumour ◽  
Bulbar Conjunctiva ◽  
Low Grade ◽  
Ki 67 ◽  
Periodic Acid Schiff ◽  
Multiple Spindle ◽  
Immunohistochemical Stains

Background/aimsTo describe the clinicopathological and immunohistochemical characteristics of 10 patients representing a new entity of benign conjunctival myxoid stromal tumours.MethodsRetrospective review of clinical findings, histopathological and immunohistochemical studies identified 10 cases of low-grade conjunctival myxoid stromal tumours. Specimens were routinely processed and stained with H&E. Immunohistochemical stains for CD34, CD68, vimentin, S100, smooth muscle actin (SMA), myosin, desmin, actin, Bcl-2 and Ki-67 were performed. Specific stains for Alcian-blue periodic acid-Schiff (AB-PAS) and aldehyde fuchsin stains were also performed.ResultsTen patients with an average age of 45.6±11.1 years had a tender white or faint yellow to red mass on the bulbar conjunctiva. All the lesions were completely removed, and none of the patients relapsed. Histologically, all neoplasms consisted of spindle-shaped cells that showed signs of pseudonuclear inclusions, multinuclear cells and had no atypia. The stroma consisted of a large amount of mucus and was infiltrated with delicate to ropey collagens, a few mast cells and new vessels. Immunohistochemical stains were positive for CD34, vimentin and Bcl-2; partial positive for CD68; very low for Ki-67; and negative for S100, SMA, myosin, desmin and actin. AB-PAS suggested that the stroma was mucinous.ConclusionsThese rare benign mesenchymal conjunctival tumours are mostly unilateral and occur in the bulbar conjunctiva. Complete resection is the radical treatment. These lesions are characterised by multiple spindle cells, a large amount of mucus, and sharing similar basic histopathological features with conjunctival myxoma and conjunctival stromal tumour. We suggest naming these lesions ‘conjunctival myxoid stromal tumours’.

scholarly journals Canine Cutaneous Clear Cell Adnexal Carcinoma: Histopathology, Immunohistochemistry, and Biologic Behavior of 26 Cases

2005 ◽  
Vol 17 (5) ◽  
pp. 403-411 ◽  
Author(s):  
F. Y. Schulman ◽  
T. P. Lipscomb ◽  
T. J. Atkin
Keyword(s):  
Clear Cell ◽  
Regional Lymph Node ◽  
Smooth Muscle Actin ◽  
Periodic Acid ◽  
Dermal Papilla ◽  
Low Grade ◽  
Periodic Acid Schiff ◽  
Regional Lymph Nodes ◽  
S 100 ◽  
Clear Cytoplasm

Thirty tumors including 27 distinctive cutaneous neoplasms and 3 metastatic tumors from 26 dogs were collected from diagnostic submissions to 3 laboratories. Characteristic histopathologic features included location in the subcutis or dermis (or both); lobular, nodular, and nest-like architecture; and a component of epithelioid cells with clear cytoplasm. Additional features present in most cases included follicular dermal papilla-like structures, low mitotic index, nuclear pleomorphism, necrosis, and mineralization. Cytoplasmic periodic acid Schiff—positivity, which was abolished by pretreatment with diastase, indicated the presence of glycogen in all cases. The oil red O stain did not demonstrate cytoplasmic lipid. Melanin granules, accentuated by the Fontana-Masson method, were observed infrequently. A sparsely cellular mucinous stroma and stromal cartilaginous differentiation were uncommon. By immunohistochemistry, neoplastic cells stained positively for cytokeratin (29 of 29), vimentin (28 of 28), S-100 protein (24 of 29), and melan A (8 of 12); results were negative for smooth muscle actin and calponin in all cases. Clinical follow-up information was obtained on all 26 dogs. One tumor recurred, 1 metastasized to a regional lymph node, and 1 metastasized to regional lymph nodes twice. In another case, possible pulmonary metastasis was noted radiographically. The findings are consistent with a poorly differentiated, low-grade, adnexal carcinoma of the skin. Similar canine cutaneous neoplasms have been reported as “clear-cell hidradenocarcinoma” and “follicular stem cell carcinoma.” The authors propose the designation “cutaneous clear cell adnexal carcinoma.”

scholarly journals The adverse effect of long term intake of Monosodium Glutamate on kidney performance

2021 ◽  
Vol 880 (1) ◽  
pp. 012056
Author(s):  
Amer M. Hussin ◽  
Ali A. Tala’a ◽  
Safa Abdul Naser Fadhil ◽  
Hamzah Abdulrahman Salman
Keyword(s):  
Mesangial Cells ◽  
Periodic Acid ◽  
Monosodium Glutamate ◽  
Environmental Pollutant ◽  
Basement Membranes ◽  
Male Rats ◽  
Periodic Acid Schiff ◽  
Histological Techniques ◽  
Treatment Groups

Abstract Monosodium glutamate (MSG) is a food additive that is considered as a water and environmental pollutant and affects the tissues of the living being. This study was aimed to find the effect of long-term administration of MSG on the mass of mesangial cells of the kidneys. Forty adult male rats were divided into four groups (10 each). Control groups 1&2 were supplied orally with distilled water for 30 and 60 days, respectively. Treatment groups 1&2 were supplied orally with 15 mg/kg Bwt of MSG for 30 & 60 days, respectively. Control and treatment groups were sacrificed, specimens of kidneys were obtained, fixed with 10% neutral buffered formalin, processed by Routine histological techniques, stained by Hematoxylin and eosin, and PAS (Periodic Acid-Schiff) stains then examined under the light microscope. The result found enlargement in a mesangial mass represented by hypertrophy and hyperplasia of mesangial cells leading to mesangial proliferative glomerulonephritis. Accordingly, the study showed an increase in creatinine values, indicating a disturbance in renal function. This will lead to a decrease in the sizes of the glomeruli of renal corpuscles and a relative increase of Bowman’s space. With the time of the experiment, the glomerular capillaries and gates of basement membranes will be closed, resulting in renal filtration disorders. It was concluded that the long-term intake of MSG leads to indirect narrowing of the glomerular capillary lumen, causing kidney failure.

scholarly journals The presence of mast cell precursors in rat peripheral blood

Blood ◽  
1981 ◽  
Vol 58 (3) ◽  
pp. 544-551 ◽  
Author(s):  
D Zucker-Franklin ◽  
G Grusky ◽  
N Hirayama ◽  
E Schnipper
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Alcian Blue ◽  
Peripheral Blood ◽  
Periodic Acid ◽  
Phenotypic Expression ◽  
Soft Agar ◽  
Sulfated Polysaccharides ◽  
Periodic Acid Schiff ◽  
Agar Culture

Abstract Soft agar culture of mononuclear cell fractions prepared from rat peripheral blood yielded numerous colonies consisting of mast cells. The mast cell nature of the cells was established by ultrastructural and histochemical analyses as well as by the demonstration the the colonies contained histamine and that the cells possessed receptors for the Fc component of IgE. Stringent criteria for the distinction of mast cells from monocytes/macrophages that could have metachromatic inclusions were applied. The alcian-blue-safranin technique delineated the maturation of mast cell granules by showing the loss of alcian-blue and increase in safranin-positive organelles presumed to reflect the increase in N-sulfated polysaccharides representing heparin. The mast cells exhibited low or absent reactions for peroxidase, alpha-naphthyl butyrate, periodic acid Schiff, and Sudan black reacting lipid, whereas macrophages stained in parallel were positive for these substances. Since it is known that extracellular conditions may cause variations in phenotypic expression, the observations have led to the hypothesis that mast cells and macrophages may have a common precursor.

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