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1.
Hum Pathol ; 128: 110-123, 2022 10.
Article in English | MEDLINE | ID: mdl-35926808

ABSTRACT

Juxtaglomerular cell tumors and glomus tumors both arise from perivascular mesenchymal cells. Juxtaglomerular cells are specialized renin-secreting myoendocrine cells in the afferent arterioles adjacent to glomeruli, and juxtaglomerular tumors derived from these cells are therefore unique to the kidney. In contrast, glomus tumors have been described at numerous anatomic sites and may show significant morphologic and immunophenotypic overlap with juxtaglomerular tumors when occurring in the kidney. Although ultrastructural studies and immunohistochemistry for renin may distinguish these entities, these diagnostic modalities are often unavailable in routine clinical practice. Herein, we studied the clinicopathologic features of a large series of juxtaglomerular tumors (n = 15) and glomus tumors of the kidney (n = 9) to identify features helpful in their separation, including immunohistochemistry for smooth muscle actin (SMA), CD34, collagen IV, CD117, GATA3, synaptophysin, and renin. Markers such as SMA (juxtaglomerular tumors: 12/13, 92%; glomus tumors: 9/9, 100%), CD34 (juxtaglomerular tumors: 14/14, 100%; glomus tumors: 7/9, 78%), and collagen IV (juxtaglomerular tumors: 5/6, 83%; glomus tumors: 3/3, 100%) were not helpful in separating these entities. In contrast to prior reports, all juxtaglomerular tumors were CD117 negative (0/12, 0%), as were glomus tumors (0/5, 0%). Our results show that juxtaglomerular tumors have a younger age at presentation (median age: 27 years), female predilection, and frequently exhibit diffuse positivity for renin (10/10, 100%) and GATA3 (7/9, 78%), in contrast to glomus tumors (median age: 51 years; renin: 0/6, 0%; GATA3: 0/6, 0%). These findings may be helpful in distinguishing these tumors when they exhibit significant morphologic overlap.


Subject(s)
Adenoma , Glomus Tumor , Kidney Neoplasms , Actins/analysis , Adenoma/pathology , Adult , Antigens, CD34/analysis , Collagen Type IV/analysis , Female , GATA3 Transcription Factor/analysis , Glomus Tumor/chemistry , Glomus Tumor/diagnosis , Humans , Juxtaglomerular Apparatus/metabolism , Juxtaglomerular Apparatus/pathology , Juxtaglomerular Apparatus/ultrastructure , Kidney/pathology , Kidney Neoplasms/chemistry , Middle Aged , Renin/analysis , Renin/metabolism , Synaptophysin/analysis
2.
Am J Physiol Renal Physiol ; 320(3): F492-F504, 2021 03 01.
Article in English | MEDLINE | ID: mdl-33491562

ABSTRACT

Although macula densa (MD) cells are chief regulatory cells in the nephron with unique microanatomical features, they have been difficult to study in full detail due to their inaccessibility and limitations in earlier microscopy techniques. The present study used a new mouse model with a comprehensive imaging approach to visualize so far unexplored microanatomical features of MD cells, their regulation, and functional relevance. MD-GFP mice with conditional and partial induction of green fluorescent protein (GFP) expression, which specifically and intensely illuminated only single MD cells, were used with fluorescence microscopy of fixed tissue and live MD cells in vitro and in vivo with complementary electron microscopy of the rat, rabbit, and human kidney. An elaborate network of major and minor cell processes, here named maculapodia, were found at the cell base, projecting toward other MD cells and the glomerular vascular pole. The extent of maculapodia showed upregulation by low dietary salt intake and the female sex. Time-lapse imaging of maculapodia revealed highly dynamic features including rapid outgrowth and an extensive vesicular transport system. Electron microscopy of rat, rabbit, and human kidneys and three-dimensional volume reconstruction in optically cleared whole-mount MD-GFP mouse kidneys further confirmed the presence and projections of maculapodia into the extraglomerular mesangium and afferent and efferent arterioles. The newly identified dynamic and secretory features of MD cells suggest the presence of novel functional and molecular pathways of cell-to-cell communication in the juxtaglomerular apparatus between MD cells and between MD and other target cells.NEW & NOTEWORTHY This study illuminated a physiologically regulated dense network of basal cell major and minor processes (maculapodia) in macula densa (MD) cells. The newly identified dynamic and secretory features of these microanatomical structures suggest the presence of novel functional and molecular pathways of cell-to-cell communication in the juxtaglomerular apparatus between MD and other target cells. Detailed characterization of the function and molecular details of MD cell intercellular communications and their role in physiology and disease warrant further studies.


Subject(s)
Glomerular Mesangium/ultrastructure , Juxtaglomerular Apparatus/ultrastructure , Kidney Glomerulus/ultrastructure , Kidney Tubules/ultrastructure , Animals , Cell Communication/physiology , Epithelial Cells/cytology , Epithelial Cells/ultrastructure , Glomerular Mesangium/cytology , Kidney Glomerulus/cytology , Kidney Tubules/cytology , Mice , Rabbits , Rats
3.
Anat Rec (Hoboken) ; 303(11): 2904-2916, 2020 11.
Article in English | MEDLINE | ID: mdl-32470206

ABSTRACT

The aim was to analyze the morphology of normal human macula densa (MD), evaluate the cells that may be responsible for its turnover, and collect quantitative data. Of four samples of normal human renal tissue, two were embedded in resin to measure the longitudinal extension and examine the ultrastructure of the MD, the other two were embedded in paraffin to study apoptosis and cell proliferation. The MD is composed of a monolayer tissue about 40 µm long, which includes 35-40 cells arranged in overlapping rows. Ultrastructurally, MD cells show two polarized portions: an apical end, with sensory features, and a basolateral aspect, with paracrine function. MD cells are connected apically by tight junctions, with/without adherens junctions, which form a barrier between the distal tubule lumen and the interstitium. Cells in degeneration, often associated with macrophages, and undifferentiated cells were found in the MD and adjacent distal tubule. A filamentous mat previously described in proximal tubule scattered tubular cells (STCs) was detected in the basal cytoplasm in undifferentiated cells. The tissue was consistently negative for the proliferation marker Ki67 and for the apoptotic markers caspase-3 and caspase-9. This work confirms our earlier morphological findings and provides new data: (a) MD cells display both apical adherens and tight junctions, the latter forming a tubulo-mesangial barrier; (b) the MD is a monolayer made up of about 40 cells arranged in rows; (c) the simultaneous presence of degenerating (8-13%) and undifferentiated (4-13%) cells reminiscent of STCs suggests a non-negligible cell turnover.


Subject(s)
Juxtaglomerular Apparatus/anatomy & histology , Aged , Caspase 3/metabolism , Caspase 9/metabolism , Female , Humans , Immunohistochemistry , Juxtaglomerular Apparatus/metabolism , Juxtaglomerular Apparatus/ultrastructure , Male , Microscopy, Electron, Transmission , Middle Aged , Nitric Oxide Synthase Type I/metabolism
4.
Morfologiia ; 147(1): 53-8, 2015.
Article in Russian | MEDLINE | ID: mdl-25958729

ABSTRACT

To observe the formation of blood flow in the juxtaglomerular pathway in comparative-anatomical and age-related aspects, 484 kidneys from the representatives of the five classes of vertebrates, 50 kidneys of human fetuses and 193 kidneys of normal individuals of different ages were studied. Macro-microscopic, histological and morphometric methods were used. In all the mammalian animal species, the significant development of vascular glomeruli and peritubular capillaries was observed. In human kidneys, the relative content of cortical and medullary arterial vessels was maximal in juvenile age. With age, this parameter was found to decrease both in renal cortex and medulla. The differentiation of renal tissue into the cortex and the medulla, that began in birds and was finally formed in mammals, explains the appearance of cortical and juxtamedullary blood flow pathways. During the antenatal period of human development, renal juxtaglomerular pathway of blood flow prevails over the cortical one. The diminished significance of juxtamedullary pathway of blood flow in elderly and senile age determines the decreased adaptive capacities of intraorgan renal arterial bed in the norm.


Subject(s)
Aging/pathology , Juxtaglomerular Apparatus/blood supply , Kidney/blood supply , Aged , Animals , Arteries/growth & development , Arteries/ultrastructure , Capillaries/pathology , Capillaries/ultrastructure , Female , Hemodynamics , Humans , Juxtaglomerular Apparatus/growth & development , Juxtaglomerular Apparatus/ultrastructure , Kidney/pathology , Kidney/ultrastructure
7.
Pathol Res Pract ; 207(2): 79-85, 2011 Feb 15.
Article in English | MEDLINE | ID: mdl-21159450

ABSTRACT

Lipofuscin-like granules, first described by Biava and West in 1965, are a subcellular, quasi-physiologic finding mainly seen in the smooth muscle cells of renal arterioles, but also in juxtaglomerular cells and the lacis cells of human kidneys. They increase in number in subjects affected by arterial hypertension and diabetes. They do not correlate with a specific primary renal disease. Lipofuscin-like granules are not related to renin granules. The world literature on this subject is almost non-existent, and the awareness of this finding or its clinical significance among either pathologists or nephrologists is very poor. We incidentally observed these lipofuscin-like granules in 8 cases during the routine electron microscope examination of 440 renal biopsies, and report herein on their ultrastructural features. Six of these 8 patients were affected by arterial hypertension, one of whom was also concomitantly affected by diabetes mellitus. These lipofuscin-like granules appear as dense bodies with a lipid component, a coarsely granular matrix, and a crystalloid component which may appear in a band or dot pattern, according to the plane of sectioning. The pathologist has to be aware of these lipofuscin-like granules in order not to confuse them with the semicircularly organized (fingerprint) linear immune deposits associated with some specific glomerulopathies.


Subject(s)
Cytoplasmic Granules/chemistry , Cytoplasmic Granules/ultrastructure , Juxtaglomerular Apparatus/chemistry , Juxtaglomerular Apparatus/ultrastructure , Kidney Diseases/diagnosis , Lipofuscin/analysis , Adult , Aged , Arterioles/chemistry , Arterioles/ultrastructure , Biopsy , Diabetes Mellitus , Female , Humans , Hypertension/complications , Incidental Findings , Juxtaglomerular Apparatus/blood supply , Kidney Diseases/complications , Kidney Diseases/metabolism , Kidney Diseases/pathology , Male , Microscopy, Electron , Middle Aged , Myocytes, Smooth Muscle/chemistry , Myocytes, Smooth Muscle/ultrastructure , Retrospective Studies , Young Adult
8.
Int. j. morphol ; 28(3): 723-728, Sept. 2010. ilus
Article in English | LILACS | ID: lil-577177

ABSTRACT

Although the structure and the functions of juxtaglomerular cells (JG) have been well defined, there is still a controversy about the secretory mechanisms of renin from these cells. It has been assumed that exocytosis is the main secretory mechanism in these cells in many studies, while others suggest that secretion occurs in a quite different way in these cells. There are several studies suggesting that diacrine secretion, which is very difficult to visualize, might be the other mechanism for secretion of renin. This study is an attempt to find the answers of these questions by identifying the fine structural features of the secretory granules in juxtaglomerular cells. Cyclosporin A (CyA) has been used in the current experimental study since it has already been reported that this drug increases the number of JG cells and stimulates secretion of Renin. Twelve female Sprague-Dawley rats had daily intraperitoneal injections of CyA for ten weeks. Tissue specimens from the kidneys of these animals were examined by electron microscopy. Fine structural characteristics of the secretory granules of juxtaglomerular cells have been examined. Considerable amount of granules, which goes to the exocytotic process, have been observed. Additionally, several cells, which their granules had been secreting their contents in a different way, were found. This was interpreted as the secretion type of diacrine secretion. In conclusion, this in vivo study presents morphologic evidences demonstrating that both exocytosis and diacrine secretion might occur in JG cells. We also had a chance to observe secretory granule probably exhibiting "diacrine secretion", which is very difficult to visualize, at electron microscope level for the first time. This report also provides morphologic proof which shows that these two distinct secretory mechanisms might occur simultaneously in the same juxtaglomerular cell.


Aunque la estructura y las funciones de las células yuxtaglomerulares (JG) han sido bien definidas, todavía existe controversia acerca de los mecanismos de secreción de renina en estas células. Se ha supuesto, en muchos estudios, que la exocitosis es el principal mecanismo de secreción de estas células, mientras que otros autores sugieren que la secreción se produce de una manera muy diferente en estas células. Hay varios estudios que plantean que la secreción diacrina, que es muy difícil de visualizar, podría ser otro mecanismo para la secreción de renina. Este estudio tiene como objetivo encontrar las respuestas a estas interrogantes mediante la identificación de las características estructurales de la secreción de gránulos en las células yuxtaglomerulares. Ciclosporina A (CyA) se ha utilizado en el estudio experimental actual, debido a que se ha informado que este medicamento aumenta el número de células JG y estimula la secreción de renina. Doce ratas hembras Sprague-Dawley fueron diariamente inyectadas por vía intraperitoneal, con CyA durante diez semanas. Las muestras de tejido renal de estos animales fueron examinadas a través de microscopía electrónica. Detalladas características estructurales han sido examinadas en los gránulos secretores de las células yuxtaglomerulares. Se ha observado una cantidad considerable de gránulos, que va con el proceso de exocitosis. Además, se encontaron células que habían secretado el contenido de sus gránulos de manera diferente. Esto fue interpretado como secreción de tipo diacrina. En conclusión, este estudio in vivo presenta evidencias morfológicas que demuestran que tanto la exocitosis y la secreción diacrina podría ocurrir en células JG. También tuvimos la oportunidad de observar probables gránulos secretores, que mostrarían "la secreción diacrina", que es muy difícil de visualizar, a nivel de microscopía electrónica. Este informe también proporciona la prueba morfológica que demuestra que estos dos mecanismos...


Subject(s)
Animals , Female , Rats , Juxtaglomerular Apparatus/physiology , Juxtaglomerular Apparatus/ultrastructure , Cytoplasmic Granules/physiology , Cytoplasmic Granules/ultrastructure , Renin , Juxtaglomerular Apparatus/cytology , Juxtaglomerular Apparatus , Cyclosporine/pharmacology , Exocytosis , Cytoplasmic Granules , Microscopy, Electron , Rats, Sprague-Dawley
10.
Anal Quant Cytol Histol ; 29(4): 208-16, 2007 Aug.
Article in English | MEDLINE | ID: mdl-17879628

ABSTRACT

OBJECTIVE: To examine the effects of the renin-angiotensin system (RAS) on renal arterioles to determine the association between the distribution of angiotensin II AT1 receptors and the morphologic and physiologic heterogeneity of renal arterioles. STUDY DESIGN: To estimate the number of angiotensin II AT1 receptors along the length of the arterioles and per arteriole, we combined immunoelectron microscopy with stereology. RESULTS: The number of AT1 receptor molecules was significantly lower in the renin-positive smooth muscle cells (SMCs) than in the renin-negative SMCs of the afferent and efferent arterioles. There were no significant differences along and between the afferent and efferent arterioles in relative number of AT1 receptors of endothelial cells or SMCs. CONCLUSION: Our results suggest that the heterogeneous activity of angiotensin II in SMCs and the different permeabilities of the endothelium along the afferent arterioles are probably not controlled directly by angiotensin II AT1 receptors. However, the activity of the RAS is possibly involved in the significantly reduced number of receptors in renin-granulated cells. An understanding of how the number of AT1 receptors on the SMC surface is controlled may furnish a new path for pharmacologically changing RAS activity on SMCs.


Subject(s)
Juxtaglomerular Apparatus/metabolism , Kidney Glomerulus/blood supply , Receptor, Angiotensin, Type 1/metabolism , Renin-Angiotensin System/physiology , Afferent Pathways/metabolism , Animals , Arterioles/metabolism , Arterioles/ultrastructure , Efferent Pathways/metabolism , Fluorescent Antibody Technique, Indirect , Gold Colloid , Juxtaglomerular Apparatus/ultrastructure , Kidney Glomerulus/ultrastructure , Male , Microscopy, Immunoelectron , Rats , Rats, Wistar , Receptor, Angiotensin, Type 1/ultrastructure , Staining and Labeling
11.
J Neurophysiol ; 96(5): 2354-63, 2006 Nov.
Article in English | MEDLINE | ID: mdl-16855116

ABSTRACT

Understanding the intrinsic membrane properties of juxtaglomerular (JG) cells is a necessary step toward understanding the neural basis of olfactory signal processing within the glomeruli. We used patch-clamp recordings and two-photon Ca(2+) imaging in rat olfactory bulb slices to analyze a long-lasting plateau potential generated in JG cells and characterize its functional input-output roles in the glomerular network. The plateau potentials were initially generated by dendritic calcium channels. Bath application of Ni(2+) (250 microM to 1 mM) totally blocked the plateau potential. A local puff of Ni(2+) on JG cell dendrites, but not on the soma, blocked the plateau potentials, indicating the critical contribution of dendritic Ca(2+) channels. Imaging studies with two-photon microscopy showed that a dendritic Ca(2+) increase was always correlated with a dendritic but not a somatic plateau potential. The dendritic Ca(2+) conductance contributed to boosting the initial excitatory postsynaptic potentials (EPSPs) to produce the plateau potential that shunted and reduced the amplitudes of the following EPSPs. This enables the JG cells to act as low-pass filters to convert high-frequency inputs to low-frequency outputs. The low frequency (2.6 +/- 0.8 Hz) of rhythmic plateau potentials appeared to be determined by the intrinsic membrane properties of the JG cell. These properties of the plateau potential may enable JG cells to serve as pacemaker neurons in the synchronization and oscillation of the glomerular network.


Subject(s)
Calcium Signaling/physiology , Dendrites/physiology , Juxtaglomerular Apparatus/physiology , Olfactory Bulb/physiology , Animals , Cadmium/pharmacology , Calcium Channels/drug effects , Calcium Channels/physiology , Calcium Signaling/drug effects , Dendrites/ultrastructure , Diagnostic Imaging , Electric Stimulation , Electrophysiology , Excitatory Postsynaptic Potentials/drug effects , Excitatory Postsynaptic Potentials/physiology , Female , In Vitro Techniques , Juxtaglomerular Apparatus/drug effects , Juxtaglomerular Apparatus/ultrastructure , Male , Membrane Potentials/drug effects , Membrane Potentials/physiology , Nickel/pharmacology , Olfactory Bulb/drug effects , Olfactory Bulb/ultrastructure , Patch-Clamp Techniques , Rats , Rats, Sprague-Dawley , Sodium Channels/drug effects , Sodium Channels/physiology
12.
Arch Pathol Lab Med ; 130(5): 707-11, 2006 May.
Article in English | MEDLINE | ID: mdl-16683889

ABSTRACT

CONTEXT: Juxtaglomerular cell tumor is a rare renal neoplasm. Renin immunohistochemistry and electron microscopic documentation of rhomboid crystals are the primary methods of diagnosing this benign tumor. OBJECTIVES: In this retrospective study, we evaluated the morphologic, immunohistochemical, and ultrastructural features of 5 cases of juxtaglomerular cell tumor to determine the effectiveness of CD34 and CD117 immunohistochemistry for the diagnosis of this tumor. DESIGN: We reviewed 5 cases with clinical, histologic, immunohistochemical, and ultrastructural aspects. RESULTS: Three women and 2 men with a mean age of 37.8 years (range, 16-60 years) were included in this study. All patients presented with severe hypertension. All tumors were well circumscribed and ranged from 1.5 cm to 8.5 cm (mean, 4.4 cm). On light microscopic examination, we found solid sheets and nests of tumor cells with oval-to-round nuclei and eosinophilic cytoplasm. Low-power microscopic examination disclosed a hemangiopericytic vascular pattern. Immunohistochemistry results were as follows: vimentin (positive), renin (weakly positive), smooth muscle actin (focal immunoreactivity), and cytokeratin (negative). All 5 tumors were immunoreactive for CD34 and CD117. Electron microscopy revealed rhomboid crystals in the cytoplasm. Postoperatively, 4 patients were normotensive and 1 patient experienced persistent mild hypertension. CONCLUSIONS: Our findings indicate that immunohistochemistry for CD34 and CD117 are effective at diagnosing juxtaglomerular cell tumor. Juxtaglomerular cell tumor should be considered in the diagnosis of any renal tumors with epithelioid cells and negative initial cytokeratin immunohistochemistry.


Subject(s)
Adenocarcinoma/pathology , Antigens, CD34/analysis , Juxtaglomerular Apparatus/pathology , Kidney Neoplasms/pathology , Proto-Oncogene Proteins c-kit/analysis , Adenocarcinoma/chemistry , Adenocarcinoma/surgery , Adolescent , Adult , Biomarkers, Tumor/analysis , Female , Humans , Hypertension/diagnosis , Juxtaglomerular Apparatus/ultrastructure , Kidney Neoplasms/chemistry , Kidney Neoplasms/surgery , Male , Middle Aged , Tomography, X-Ray Computed , Treatment Outcome
13.
Zhonghua Zhong Liu Za Zhi ; 27(5): 302-5, 2005 May.
Article in Chinese | MEDLINE | ID: mdl-15996328

ABSTRACT

OBJECTIVE: To investigate the clinical characteristics, morphologic and immunohistochemical features, diagnosis, differential diagnosis, histogenesis and prognosis of renal juxtaglomerular cell tumor (JGCT). METHODS: Light microscopic observation; immunohistochemical assay of CK8, E-cadherin/CK7, CD10, Vim, Actin, CD34, S100, HMB45, CD31, Chr, Syn and CD117, EM; and follow-up were done on all 4 surgically treated JGCT patients. RESULTS: All 4 JGCT were observed in young adult with clinically uncontrolled severe hypertension. Grossly, the tumor was encapsulated and small in size. Microscopically, the tumor cells grew in sheets predominantly, but papillary and onion-like pattern could also be seen. The stroma contained prominent vasculature that consisted of numerous thin-wall vessels clustering around thick-walled vessels. Tumor cells were rather small, polygonal, with slightly eosinophilic cytoplasm and ill-defined cell border. Nuclei were uniform in size but nuclear atypia and mitosis could be seen. Numerous mast cells were scattered among the tumor cells, and tubules were identified in 3 of 4 cases with positive expression of distal tubule marker of E-cadherin/CK7. Tumor cells positively expressed Vim, Actin, calponin, and CD34. All cases presented ultrastructural features of distinct rhomboid-shaped crystal. There was no recurrence or metastasis but hypertension persisted in three during follow-up (mean 37 months) for all 4 JGCT patients. CONCLUSION: JGCT, originating from the juxtaglomerular cell, has a distinct benign entity, and it is typically found in young adults with severe hypertension. It has a unique morphology and ultrastructure features and positive immunoreactivity to Vim, Actin, calponin and CD34.


Subject(s)
Antigens, CD34/analysis , Calcium-Binding Proteins/analysis , Juxtaglomerular Apparatus/pathology , Kidney Neoplasms/pathology , Microfilament Proteins/analysis , Actins/analysis , Adolescent , Adult , Female , Humans , Hypertension/etiology , Immunohistochemistry , Juxtaglomerular Apparatus/chemistry , Juxtaglomerular Apparatus/ultrastructure , Kidney Neoplasms/chemistry , Kidney Neoplasms/ultrastructure , Male , Calponins
14.
Am J Surg Pathol ; 28(8): 1098-102, 2004 Aug.
Article in English | MEDLINE | ID: mdl-15252319

ABSTRACT

Juxtaglomerular cell tumor is a rare renal neoplasm arising from the juxtaglomerular apparatus. Approximately 70 cases have been reported in the English literature since it was first described by Robertson et al in 1967. This tumor has been considered benign and resection has so far been curative. In this paper, we report the first metastatic juxtaglomerular cell tumor. The 15-cm tumor occurred in the right kidney of a 46-year-old man. It invaded the renal vein, and was treated by radical nephrectomy in 1995. The diagnosis at that time was renal cell carcinoma. The patient was well for 6 years and then developed bilateral lung masses, which were resected. Microscopically, the tumors from the kidney and the lungs were similar, consisting of solid sheets of uniformly round-to-polygonal cells intermixed with abundant delicate vasculature. Both renal and pulmonary tumors were positive for vimentin, renin, and only focally to CD34. Electron microscopic studies performed on the paraffin-embedded renal tumor and formalin-fixed lung tumor revealed the typical rhomboid crystals of proto-renin. In consideration of the characteristic morphologic features, immunohistochemistry, and the presence of rhomboid crystals of proto-renin, the diagnosis was modified to malignant juxtaglomerular cell tumor.


Subject(s)
Carcinoma, Renal Cell/secondary , Juxtaglomerular Apparatus/ultrastructure , Kidney Neoplasms/pathology , Lung Neoplasms/secondary , Biomarkers, Tumor/analysis , Carcinoma, Renal Cell/chemistry , Carcinoma, Renal Cell/surgery , Crystallization , Humans , Immunoenzyme Techniques , Kidney Neoplasms/chemistry , Kidney Neoplasms/surgery , Lung Neoplasms/chemistry , Lung Neoplasms/surgery , Male , Middle Aged , Renin/analysis , Renin/ultrastructure , Vimentin/analysis
15.
Zhonghua Bing Li Xue Za Zhi ; 32(6): 511-5, 2003 Dec.
Article in Chinese | MEDLINE | ID: mdl-14761594

ABSTRACT

OBJECTIVE: To study the morphologic characteristics and immunophenotype of juxtaglomerular cell tumor of the kidney (JGCT), with discussion on its diagnostic clues and possible histogenesis. METHODS: The clinical, pathologic and immunohistochemical features of 5 cases of JGCT were evaluated. In addition, 5 cases of hemangiopericytoma and 5 cases of cutaneous glomus tumor were selected for comparative immunohistochemical analysis. RESULTS: The JGCT cases came from 4 females and 1 male (mean age at diagnosis = 32 years). All of them manifested symptoms of systemic hypertension. Four of the patients received partial nephrectomy and the remaining patient was treated by radial nephrectomy. All of them were followed up for a period of 4 to 66 months (average = 27 months). There was no evidence of local recurrence or distant metastases. On gross examination, these JGCTs were well-circumscribed and situated in the renal cortex and measured 4.4 cm in greatest dimension on average. Histologically, the tumor was characterized by the following three features: (1) solid sheets of relatively uniform polygonal to round cells with lightly eosinophilic cytoplasm, sometimes containing PAS-positive intracytoplasmic granules; (2) absence of or very scanty mitotic figures; (3) interstitium rich in thin-walled capillaries, associated with focal hyaline change and hemangiopericytoma-like architectural pattern. Under electron microscopy, characteristic rhomboid-shaped renin granules were found in the cytoplasm. All JGCTs were immunoreactive for renin, CD34, actin, and calponin. In contrast, all glomus tumors were negative for renin and all hemangiopericytomas were negative for actin. CONCLUSIONS: JGCT is a rare benign renal neoplasm typically found in young adults and manifests as systemic hypertension. The tumor cells may be originated from modified vascular smooth muscle cells. The identification of renin granules by electron microscopy and demonstration of the characteristic immunophenotype is the key to correct pathologic diagnosis.


Subject(s)
Juxtaglomerular Apparatus/pathology , Kidney Neoplasms/pathology , Adult , Antigens, CD34/analysis , Calcium-Binding Proteins/analysis , Female , Humans , Immunohistochemistry , Juxtaglomerular Apparatus/chemistry , Juxtaglomerular Apparatus/ultrastructure , Keratins/analysis , Male , Microfilament Proteins , Microscopy, Electron , Middle Aged , Calponins
16.
Virchows Arch ; 438(6): 618-23, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11469695

ABSTRACT

BACKGROUND: Our goal was to investigate the effect of antihypertensive drugs on the juxtaglomerular apparatus (JGA) in young type-1 diabetic patients with microalbuminuria. METHODS: Twelve patients were allocated to treatment with either an angiotensin-converting enzyme inhibitor (group 1, six subjects) or a beta-receptor blocker (group 2, six subjects). A comparable group of nine patients without antihypertensive treatment provided reference values (group 3, nine subjects). Renal biopsies were taken at baseline and after a median of 40 months (groups 1 and 2) and 30 months (group 3). Using light microscopy with 1microm serial sections of the plastic-embedded biopsies, volumes of the JGA and glomerulus and areas of the macula densa and lumina of the afferent and efferent arterioles were obtained. RESULTS: A significant decrease of the volume of the JGA (P=0.026) and of the volume of the JGA relative to that of its corresponding glomerulus (P=0.0005) was noted in the reference group only. Negative correlations existed between the increase in the luminal area of the afferent arteriole and mean diastolic blood pressure in the study period in group 1 (P=0.024) and group 2 (P=0.032). CONCLUSIONS: Our results showed that a decrease in the size of the JGA is offset by antihypertensives. The negative correlation between the change in the luminal area of the afferent arteriole and mean diastolic blood pressure in groups 1 and 2 suggest that renal protection in antihypertensive treatment may be through a better constriction of the afferent arteriole protecting the glomerulus from systemic blood pressure.


Subject(s)
Albuminuria/drug therapy , Antihypertensive Agents/therapeutic use , Diabetes Mellitus, Type 1/drug therapy , Diabetic Nephropathies/prevention & control , Juxtaglomerular Apparatus/drug effects , Adolescent , Adrenergic beta-Antagonists/administration & dosage , Adrenergic beta-Antagonists/therapeutic use , Adult , Albuminuria/pathology , Albuminuria/physiopathology , Angiotensin-Converting Enzyme Inhibitors/administration & dosage , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Antihypertensive Agents/administration & dosage , Diabetes Mellitus, Type 1/pathology , Diabetes Mellitus, Type 1/physiopathology , Diabetic Nephropathies/physiopathology , Enalapril/administration & dosage , Enalapril/therapeutic use , Female , Humans , Juxtaglomerular Apparatus/ultrastructure , Male , Metoprolol/administration & dosage , Metoprolol/therapeutic use
17.
Am J Cardiol ; 86(11): 1198-204, 2000 Dec 01.
Article in English | MEDLINE | ID: mdl-11090791

ABSTRACT

We present evidence of 2 distinct glomerular abnormalities in cyanotic congenital heart disease--vascular and nonvascular--each believed to reflect a distinct pathogenesis. Glomeruli from both kidneys were studied with light microscopy in 13 necropsied cyanotic patients and in 8 controls. The vascular study characterized hilar arteriolar dilatation, capillary diameter, glomerular diameter, and capillary engorgement with red blood cells. The nonvascular study characterized juxtaglomerular cellularity, mesangeal cellularity, mesangeal matrix, focal interstitial fibrosis, and megakaryocytic nuclei per cm2 of renal cortex. There was a significant increase in each of the above vascular and nonvascular items of interest relative to controls. Electron microscopy identified whole megakaryocytes with their cytoplasm in glomeruli. The vascular abnormality is believed to result from intraglomerular release of nitric oxide. The nonvascular abnormality is believed to result from platelet-derived growth factor and transforming growth factor-beta.


Subject(s)
Cyanosis/pathology , Heart Defects, Congenital/pathology , Kidney Diseases/pathology , Kidney Glomerulus/ultrastructure , Adult , Biopsy , Cell Division , Cyanosis/complications , Female , Glomerular Mesangium/ultrastructure , Heart Defects, Congenital/complications , Humans , Juxtaglomerular Apparatus/ultrastructure , Kidney Diseases/etiology , Male , Middle Aged , Renal Artery/ultrastructure , Renal Veins/ultrastructure , Severity of Illness Index
18.
J Biol Chem ; 275(51): 40378-84, 2000 Dec 22.
Article in English | MEDLINE | ID: mdl-10995772

ABSTRACT

Mice lacking a functional Ren-1(d) gene exhibit a complete lack of renal juxtaglomerular cell granulation and atypical macula densa morphology. Transgenic mice carrying a 145-kilobase BAC clone encompassing the Ren-1(d) and Ren-2 loci were generated, characterized, and backcrossed with Ren-1(d-/-) mice. Homozygous Ren-1(d)-null mice expressing the BAC clone exhibited complete restoration of normal renal structure. Homologous recombination in Escherichia coli was used to generate a modified version of the BAC clone, in which an IRESbeta-geo cassette was inserted specifically into the Ren-1(d) gene. When introduced into the germline, the modified clone provided a marker for juxtaglomerular cell differentiation and beta-geo was expressed appropriately in juxtaglomerular cells throughout development. Parallel backcross experiments onto the Ren-1(d)-null background demonstrated that the juxtaglomerular cells expressed the modified Ren-1(d) locus in the absence of regranulation. These data demonstrate that the nongranulated cells constitute bona fide juxtaglomerular cells despite their altered morphology, that overexpression of renin-2 cannot compensate for the loss of renin-1(d), and that primary structural differences between the two isoforms are responsible for the differences in granulation. The use of BAC modification as part of functional complementation studies illustrates the potential for in vivo molecular dissection of key physiological mechanisms.


Subject(s)
Chromosomes, Artificial, Bacterial , Juxtaglomerular Apparatus/metabolism , Recombination, Genetic , Renin/genetics , Animals , Base Sequence , DNA Primers , Immunohistochemistry , Juxtaglomerular Apparatus/cytology , Juxtaglomerular Apparatus/ultrastructure , Mice , Mice, Transgenic , Microscopy, Electron
19.
Gen Comp Endocrinol ; 116(2): 192-203, 1999 Nov.
Article in English | MEDLINE | ID: mdl-10562449

ABSTRACT

The gene for adrenomedullin (AM), a multifunctional peptide hormone, is expressed in mammalian renal tissue and has been shown to stimulate renin release. The exact cell source of this peptide and its gene-related partner, proadrenomedullin N-terminal 20 peptide (PAMP), in kidney is still uncertain. In the present study we have identified PAMP-immunoreactive cells in the kidney of different mammalian species, including man, by light microscopy. In addition, these cells have been further studied in mouse kidney by both light and electron microscopic techniques. At the light microscopic level, PAMP immunolabeling is preferentially located in the subendothelial cells of the enlarged glomerular afferent arterioles, that is, in the juxtaglomerular cells. However, these cells do not show immunolabeling for AM. At the electron microscopic level, the immunostaining appears inside the renin-containing secretory granules of the juxtaglomerular cells. These results confirm the direct link between renin and the AM peptide family and provide a morphological basis for studying the potential modulatory function of AM and PAMP in the control of renin activity. In contrast, neither AM nor PAMP immunoreactivities were detected in the kidney of nonmammalian vertebrates, other than in blood vessels of particular species, providing a new phylogenetic difference in the juxtaglomerular apparatus between mammalian and nonmammalian vertebrates.


Subject(s)
Juxtaglomerular Apparatus/chemistry , Peptide Fragments/analysis , Protein Precursors/analysis , Proteins/analysis , Adrenomedullin , Animals , Cattle , Chickens , Cytoplasmic Granules/chemistry , Dogs , Guinea Pigs , Humans , Iguanas , Juxtaglomerular Apparatus/ultrastructure , Kidney/chemistry , Lizards , Mice , Microscopy, Electron , Necturus , Rats , Xenopus laevis , Zebrafish
20.
Anat Histol Embryol ; 28(1): 45-8, 1999 Mar.
Article in English | MEDLINE | ID: mdl-10208035

ABSTRACT

The intrarenal distribution of renin in the cat kidney was evaluated in a semi-quantitative immunocytochemical study using a cross-reacting antiserum directed against purified renin. In addition, the morphology of the juxtaglomerular apparatus was studied electron-microscopically. The majority of renin in the cat kidney was located in the distal portion of the afferent arteriole. The values for the juxtaglomerular index and the renin-positive portion of the afferent arteriole were 30.6 +/- 3.2% and 49.9 +/- 8.3 microns, respectively. In addition, scattered renin-positive cells were found far from the vascular pole and even in the interlobular artery. Also, some vasa efferentia contained renin-positive cells. In 70% of the cats studied, renin-positive cells were located in the glomerular mesangium. The majority of the renin-positive mesangial cells were located in the vicinity of the glomerular stalk, but in some cases the centrilobular mesangium also contained renin-positive cells.


Subject(s)
Arterioles/enzymology , Juxtaglomerular Apparatus/enzymology , Juxtaglomerular Apparatus/ultrastructure , Renal Circulation , Renin/analysis , Animals , Arterioles/cytology , Cats , Female , Glomerular Mesangium/blood supply , Male
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