Tubular Epithelial Structures Research Articles

ULTRASTRUCTURAL CHANGES IN THE KIDNEYS OF RATS DURING THE EARLY AND LATE STAGES OF ACUTE RESPIRATORY DISTRESS SYNDROME

Introduction. Acute respiratory distress syndrome (ARDS) is characterized by severe hypoxemia and activation of the inflammatory cascade, which leads to multi-organ failure. Kidneys are one of the organs commonly affected by ARDS. However, the extent of ultrastructural changes in the parenchyma and stroma of the kidneys at different stages of ARDS progression remains unclear. The aim of this study was to use transmission electron microscopy to study the main components of the kidneys in rats at the early and late stages of experimentally induced ARDS. Materials and methods. The study included 24 healthy, sexually mature male rats weighing 200–220 g, divided into three groups: intact animals, 24 hours post-ARDS induction, and 14 days after the start of the experiment. ARDS was modeled by intranasal administration of lipopolysaccharide (5 mg/kg body weight) under anesthesia with ketamine at a dose of 50 mg/kg. Terminal anesthesia was performed using sodium thiopental at a dose of 150 mg/kg. Results: Submicroscopic examination of the kidneys from intact rats revealed no species-specific structural abnormalities. In the early stage of ARDS (24 hours post-modeling), renal corpuscles showed signs of vascular endothelial damage, fragmentation of the glomerular basement membrane, and degeneration of organelles and nuclear components in tubular epithelial cells. By day 14 of ARDS progression, signs of damage to the filtration barrier persisted, resulting in podocyte swelling. However, partial restoration of the tubular epithelial cell structure was observed, indicating the onset of the resolution phase of ARDS, as evidenced by the gradual recovery of the kidney ultrastructure. Conclusions. During the early stage of modeled ARDS, kidney damage manifests through destructive changes in the glomerular apparatus and renal tubular epithelial cells. In the late stage, although glomerular damage remains, partial restoration of the renal tubular epithelial cell structure is still evident.

Protective Effect of Klotho on Acute Kidney Injury Caused by Contrast Agents

Contrast-induced nephropathy (CIN) is currently the third leading cause of iatrogenic renal failure. This research mainly explores the protective effect of Klotho on CIN. Klotho (10 ng/g) was administered after the establishment of a CIN mouse model, and the changes of tissue structure and renal function were observed, and the Wnt/β-catenin pathway and senescence-related factors were detected. Compared with the control group, the brush border of renal tubular epithelial cells disappeared, cytoplasmic vacuole-like changes, renal tubular dilatation, and renal function were significantly reduced in the model group. Klotho treatment can effectively alleviate changes in renal tubular epithelial structure and function. Compared with the model group, Klotho treatment can obviously inhibit the expression of P27 and P53, and promote the expression of Sirt1 and Bmi-1, and Klotho can regulate the Wnt/β-catenin pathway. Exogenous Klotho can slow down nephrocyte senescence by regulating the Wnt/β-catenin pathway, thereby protecting kidney.

Study to Evaluate Prediction of Invasion in Breast Carcinoma Diagnosed on FNAC

Background: FNAC is minimally invasive, produces a speedy result and is inexpensive than biopsy. This remains one of the most important technique from a practical point of view for diagnosis in most of breast lesion. Tubular or angular epithelial structures, malignant cells adherent to fibrous stroma, presence of intracytoplasmic lumina in malignant cells, fibroblast proliferation and fragments of elastoid stroma were predictive of invasion if associated with breast carcinoma. Objectives: To evaluate invasion criteria in fine needle aspiration cytology (FNAC) of histologically diagnosed invasive breast carcinoma. Material and methods: A prospective study of FNAC of breast lesions was carried out along with its histopathological correlation. All cases were diagnosed as invasive breast cancer in histopathological examination. All cytological breast cancer was evaluated for five features of invasive carcinoma. Results: We found that out of five predictive features Malignant Cells Adherent to stroma and Fibroblast Proliferation are most frequently seen in invasive breast carcinoma and their predictive value 78.26% for the both. Intracytoplasmic lumina in malignant cells and Fragments of elastoid stroma are the least features seen in invasive breast carcinoma and their predictive value 39.13% and 52.17%. Conclusion: In our study of prediction of invasion in breast carcinoma by FNAC, malignant cell adherent to stroma and Fibroblast proliferation are most consistent findings in invasive breast carcinoma. Intracytoplasmic lumina in malignant cells is least seen among breast carcinoma.

Combination exposure of melamine and cyanuric acid is associated with polyuria and activation of NLRP3 inflammasome in rats.

The molecular mechanisms of melamine-induced renal toxicity have not been fully understood. The purpose of the study aimed to investigate whether melamine and cyanuric acid induced NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome activation in the kidney, which may contribute to abnormal water and sodium handling in a rat model. Wistar rats received melamine (Mel; 200 mg·kg body wt-1·day-1), cyanuric acid (CA; 200 mg·kg body wt-1·day-1), or Mel plus CA (Mel + CA; 100 mg·kg body wt-1·day-1, each) for 2 wk. Mel + CA caused damaged tubular epithelial structure and organelles, dilated tubular lumen, and inflammatory responses. Crystals were observed in urine and serum specimen, also in the lumen of dilated distal renal tubules. The combined ingestion of Mel and CA in rats caused a markedly impaired urinary concentration, which was associated with reduced protein expression of aquaporin (AQP)1, 2, and 3 in inner medulla and α-Na-K-ATPase and Na-K-2Cl transporters in cortex and outer medulla. Mel + CA treatment was associated with increased protein expression of CD3 and mRNA levels of CD68 and F4/80 as well as phosphorylation of NF-κB in the kidney. Mel + CA treatment increased protein and mRNA expression of NLRP3 inflammasome components apoptosis-associated speck-like protein containing a caspase recruitment domain, caspase-1, and IL-1β in the inner medulla of rats. NF-κB inhibitor Bay 11-7082 reduced IL-1β expression induced by Mel + CA and prevented downregulation of AQP2 in inner medullary collecting duct cell suspensions. In conclusion, Mel + CA treatment caused urinary-concentrating defects and reduced expression of renal AQPs and key sodium transporters, which is likely due to the inflammatory responses and activation of NLRP3 inflammasome induced by crystals formed in the kidney.

Epithelial Cell Repopulation and Preparation of Rodent Extracellular Matrix Scaffolds for Renal Tissue Development.

This protocol details the generation of acellular, yet biofunctional, renal extracellular matrix (ECM) scaffolds that are useful as small-scale model substrates for organ-scale tissue development. Sprague Dawley rat kidneys are cannulated by inserting a catheter into the renal artery and perfused with a series of low-concentration detergents (Triton X-100 and sodium dodecyl sulfate (SDS)) over 26 hr to derive intact, whole-kidney scaffolds with intact perfusable vasculature, glomeruli, and renal tubules. Following decellularization, the renal scaffold is placed inside a custom-designed perfusion bioreactor vessel, and the catheterized renal artery is connected to a perfusion circuit consisting of: a peristaltic pump; tubing; and optional probes for pH, dissolved oxygen, and pressure. After sterilizing the scaffold with peracetic acid and ethanol, and balancing the pH (7.4), the kidney scaffold is prepared for seeding via perfusion of culture medium within a large-capacity incubator maintained at 37 °C and 5% CO2. Forty million renal cortical tubular epithelial (RCTE) cells are injected through the renal artery, and rapidly perfused through the scaffold under high flow (25 ml/min) and pressure (~230 mmHg) for 15 min before reducing the flow to a physiological rate (4 ml/min). RCTE cells primarily populate the tubular ECM niche within the renal cortex, proliferate, and form tubular epithelial structures over seven days of perfusion culture. A 44 µM resazurin solution in culture medium is perfused through the kidney for 1 hr during medium exchanges to provide a fluorometric, redox-based metabolic assessment of cell viability and proliferation during tubulogenesis. The kidney perfusion bioreactor permits non-invasive sampling of medium for biochemical assessment, and multiple inlet ports allow alternative retrograde seeding through the renal vein or ureter. These protocols can be used to recellularize kidney scaffolds with a variety of cell types, including vascular endothelial, tubular epithelial, and stromal fibroblasts, for rapid evaluation within this system.

Cadherin 99C regulates apical expansion and cell rearrangement during epithelial tube elongation

Apical and basolateral determinants specify and maintain membrane domains in epithelia. Here, we identify new roles for two apical surface proteins – Cadherin 99C (Cad99C) and Stranded at Second (SAS) – in conferring apical character in Drosophila tubular epithelia. Cad99C, the Drosophila ortholog of human Usher protocadherin PCDH15, is expressed in several embryonic tubular epithelial structures. Through loss-of-function and overexpression studies, we show that Cad99C is required to regulate cell rearrangement during salivary tube elongation. We further show that overexpression of either Cad99C or SAS causes a dramatic increase in apical membrane at the expense of other membrane domains, and that both proteins can do this independently of each other and independently of mislocalization of the apical determinant Crumbs (Crb). Overexpression of Cad99C or SAS results in similar, but distinct effects, suggesting both shared and unique roles for these proteins in conferring apical identity.

Cadherin 99C regulates apical expansion and cell rearrangement during epithelial tube elongation

Apical and basolateral determinants specify and maintain membrane domains in epithelia. Here, we identify new roles for two apical surface proteins - Cadherin 99C (Cad99C) and Stranded at Second (SAS) - in conferring apical character in Drosophila tubular epithelia. Cad99C, the Drosophila ortholog of human Usher protocadherin PCDH15, is expressed in several embryonic tubular epithelial structures. Through loss-of-function and overexpression studies, we show that Cad99C is required to regulate cell rearrangement during salivary tube elongation. We further show that overexpression of either Cad99C or SAS causes a dramatic increase in apical membrane at the expense of other membrane domains, and that both proteins can do this independently of each other and independently of mislocalization of the apical determinant Crumbs (Crb). Overexpression of Cad99C or SAS results in similar, but distinct effects, suggesting both shared and unique roles for these proteins in conferring apical identity.

Inconclusive or erroneous fine‐needle aspirates of breast with adequate and representative material: A cytologic/histologic study

Adequately cellular and representative fine-needle aspirates (FNAs) of breast have a high diagnostic accuracy. There is, however, a recognized category designated as "gray zone" where a definitive diagnosis cannot be reached. We reviewed our experience in this category to identify useful diagnostic parameters. Twenty-four such FNAs with surgical follow-up were retrieved from AUBMC files (2003-2009). Cytology slides were reviewed blindly. All cases were females, 29-73 years. There were three erroneous and 21 inconclusive diagnoses. The majority (15) was invasive adenocarcinomas: two cribriform, four tubular, one lobular, and eight not otherwise specified. The remaining cases were papillary and fibroepithelial tumors (three each), ductal carcinoma in situ, cribriform (two), and one adenomyoepithelioma (AME). Useful diagnostic features included: (1) Biphasic cell population with focal nuclear atypia and intranuclear and cytoplasmic vacuolar inclusions (AME). (2) Complex clusters of epithelial cells with cribriform architecture (cribriform carcinoma). (3) Rigid tubular epithelial structures with abrupt change in diameter, ending in pointed tips with abnormal branching (tubular carcinoma). (4) Cellular stromal fragments (fibroepithelial tumors). (5) Papillary fibrovascular cores, columnar cells, and three-dimensional papillary epithelial fragments (papillary tumors). Myoepithelial cells classically described in benign aspirates were not always a discriminatory factor. The "gray zone" in breast FNA is usually due to overlapping cytologic features of some benign and malignant lesions. Useful distinguishing cytologic features are described.

Abstract 224: Novel potential precursor structures for BRCA1-associated breast cancer

Abstract Objectives: Female individuals with BRCA1 germline mutation have an 80-90% risk to develop breast cancer during their lifetime. BRCA1 cancers are distinct from sporadic breast cancers as they more frequently show high-grade histology and are typically estrogen receptor and HER2-negative. While sporadic breast ductal carcinoma is thought to be preceded by in-situ precursors, the presence of precursors is uncertain in BRCA1 cancers. To better understand breast carcinogenesis in BRCA1 patients, we developed an approach to perform unprecedently detailed structural analysis of breast tissue. Design: A prophylactic mastectomy product of a BRCA1 patient with history of contralateral breast cancer was obtained after routine pathological evaluation then trimmed into 0.3 × 1 x1.5 cm tissue blocks (n=94). Initial sections from each block were H&E stained and microscopically evaluated. Any lobular or ductal structure with increased cellularity was recorded as hyperplastic event. Correlation of hyperplastic events on the surface of blocks and topographic information of events led to the identification of “hot” regions with larger numbers of these events. From the center of this region, the block was serially sectioned at 5μm-depth. H&E staining of every tenth section allowed a three-dimensional (3D) reconstruction of all hyperplastic events. The same procedure was applied to a normal control tissue product of a prophylactic mastectomy in a non-BRCA1 patient with personal history of contralateral breast cancer. Results: We identified five novel “isolated epithelial structures” within BRAC1 breast tissue. On a single two dimensional (2D) slide, these isolated epithelial structures resemble regular lobular and ductal structures with hyperplastic features; while after 3D reconstruction with 2D slides, they revealed in isolation from connection to regular anatomic epithelial structures and were entirely separated by mesenchymal tissue. Importantly, we report in detail an isolated tubular epithelial structure in association with an incidental millimeter-sized, BRCA1-deficient cancer focus. This structure is 2mm in length, mostly surrounded by myoepithelial cells, and remarkable for simultaneous development of lobular and ductal hyperplasia including flat epithelial hyperplasia. The transition zone into cancer is characterized by loss of myoepithelial cells and significant cytologic atypia. Conclusions: Our thorough examination of BRCA1 breast tissue allowed for the first time the identification of isolated epithelial structures. Our identification of one isolated epithelial structure in connection with the development of an infiltrating carcinoma focus strongly suggests that isolated epithelial structures are potential precursors for BRCA1 breast cancers. Analysis of these structures may lead to the discovery of new preventive and therapeutic targets. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 224. doi:10.1158/1538-7445.AM2011-224

Salvianolic acid B reverses the epithelial-to-mesenchymal transition of HK-2 cells that is induced by transforming growth factor-β

Salvianolic acid B (Sal B) is the most abundant bioactive molecule from Radix Salviae Miltiorrhizae, and has recently been used for treating renal fibrosis in traditional Chinese medicine. Here we investigated the ability reversal of Sal B to reverse the transdifferentiation of human kidney proximal tubular epithelial cells that was induced by transforming growth factor-beta 1 (TGF-β1). The effects of Sal B on HK-2 cell morphology were observed by phase contrast microscopy, while alpha smooth muscle actin and E-cadherin were studied by immunocytochemistry and real-time reverse transcription polymerase chain reaction, respectively. Exposure of HK-2 cells to TGF-β1 for 72 h induced a complete conversion of the epithelial cells to myofibroblasts. When HK-2 cells were co-incubated with Sal B and TGF-β1 for a further 72 h, the morphology of myofibroblasts returned to that of proximal tubular epithelial cells, whereas the myofibroblast phenotype was maintained after exposure of cells to TGF-β1 for 144 h. Sal B reduced alpha smooth muscle actin levels and increased E-cadherin levels compared with their epithelial-to-mesenchymal transition controls. The reversal effect of Sal B was dose-dependent. That Sal B reverses the epithelial-to-mesenchymal transition in vitro suggests that it could possibly facilitate the repair of tubular epithelial structures and the regression of renal fibrosis in injured kidneys.

Nectin proteins are expressed at early stages of nephrogenesis and play a role in renal epithelial cell morphogenesis

Development of the nephron requires conversion of the metanephric mesenchyme into tubular epithelial structures with specifically organized intercellular junctions. The nectin proteins are a family of transmembrane proteins that dimerize to form intercellular junctional complexes between epithelial cells. In this study, we demonstrate that nectin junctions appear during the earliest stages of epithelial cell morphogenesis in the murine nephron concurrently with the transition of mesenchymal cells into epithelial cells. We have defined the role of nectin during epithelial cell morphogenesis by studying nectin in a three-dimensional culture of Madin-Darby canine kidney (MDCK) cells. In a three-dimensional culture of MDCK cells grown in purified type 1 collagen, expression of a dominant negative form of nectin causes disruption of the formation of cell polarity and disruption of tight junction (TJ) formation, as measured by zonula occludens-1 (ZO-1) localization. In MDCK cells cultured in Matrigel, exogenous expression of nectin-1 causes disruption of normal epithelial cell cyst formation and decreased apoptosis. These data demonstrate that nectins play an important role in normal epithelial cell morphogenesis and may play a role in mesenchymal-to-epithelial transition during nephrogenesis by providing an antiapoptotic signal and promoting the formation of TJs and cell polarity.

Myxoid Renal Tumor With Myoepithelial Differentiation Mimicking a Salivary Gland Pleomorphic Adenoma: Description of a Case

We herein report an unusual case of a low-grade myxoid renal epithelial neoplasm, with peculiar and previously unreported morphologic and immunohistochemical features. The lesion was characterized by noninfiltrative borders, myxoid stroma and elongated tubular and cordlike epithelial structures. These were lined by 2 different epithelial cell types, flat and elongated basal cells and cuboidal to spindle shaped eosinophilic luminal cells, with low-grade nuclear features and a few small nucleoli. The lesion morphologically resembled a pleomorphic adenoma of the salivary gland. The immunohistochemical profile interestingly confirmed the myoepithelial differentiation of the basal epithelial layer, as demonstrated by the coexpression of several myoepithelial markers such as p63, caldesmon, calponin, smooth muscle actin, and S-100, together with epithelial markers such as low and high-molecular weight cytokeratins. The tumor proved benign at follow-up. A definitive classification and histogenetic interpretation of this previously unreported tumor type awaits description of further cases showing similar features which, perhaps, as it may happen, went so far unnoticed.

Bone Morphogenic Protein-7 Induces Mesenchymal to Epithelial Transition in Adult Renal Fibroblasts and Facilitates Regeneration of Injured Kidney

In the kidney, a unique plasticity exists between epithelial and mesenchymal cells. During kidney development, the metanephric mesenchyme contributes to emerging epithelium of the nephron via mesenchymal to epithelial transition (MET). In the injured adult kidney, renal epithelia contribute to the generation of fibroblasts via epithelial-mesenchymal transition, facilitating renal fibrosis. Recombinant human bone morphogenic protein (BMP)-7, a morphogen that is essential for the conversion of epithelia from condensing mesenchyme during kidney development, enhances the repair of tubular structures in the kidney. In this setting, BMP-7 inhibits epithelial-mesenchymal transition involving adult renal epithelial tubular cells and decreases secretion of type I collagen by adult renal fibroblasts. In search of a mechanism behind the ability of BMP-7 to repair damaged renal tubules, we hypothesized that systemic treatment with BMP-7 might induce MET involving adult renal fibroblasts in the injured kidney, generating functional epithelial cells. Here we report that BMP-7 induces formation of epithelial cell aggregates in adult renal fibroblasts associated with reacquisition of E-cadherin expression and decreased motility, mimicking the effect of BMP-7 on embryonic metanephric mesenchyme to generate epithelium. In addition, we provide evidence that BMP-7-mediated repair of renal injury is associated with MET involving adult renal interstitial fibroblasts in mouse models for renal fibrosis. Collectively, these findings suggest that adult renal fibroblasts might retain parts of their original embryonic imprint and plasticity, which can be re-engaged by systemic administration of BMP-7 to mediate repair of tubular injury in a fibrotic kidney.

Exogenous alpha-1-Acid Glycoprotein Protects against Renal Ischemia-Reperfusion Injury by Inhibition of Inflammation and Apoptosis

Although ischemia-reperfusion (I/R) injury represents a major problem in posttransplant organ failure, effective treatment is not available. The acute phase protein alpha-1-acid glycoprotein (AGP) has been shown to be protective against experimental I/R injury. The effects of AGP are thought to be mediated by fucose groups expressed on the AGP protein inhibiting neutrophil infiltration. However, the precise mechanism of protection remains to be established. We therefore studied the effects of exogenous human AGP (hAGP) in a mouse model of ischemic acute renal failure. Mice were subjected to renal I/R and treated with hAGP, fucose-depleted hAGP, or control treated. Also, transgenic mice over-expressing rat AGP or wild-type controls were subjected to renal I/R. Treatment was with hAGP as well as fucose-depleted hAGP protected mice against I/R-induced acute renal failure. Surprisingly, AGP-over-expressing mice were not protected against I/R injury. Both natural and fucose-depleted hAGP inhibited the activation of the complement system, as determined by renal C3 deposition and influx of neutrophils measured by immunohistochemistry and myeloperoxidase-enzyme-linked immunoadsorbent assay. Tubular epithelial cell structure (actin cytoskeleton) and cell-cell interaction (tight-junction architecture) were completely preserved in AGP-treated mice. Also, epithelial caspase activation and apoptotic DNA cleavage were prevented by AGP treatment. Both natural and fucose-depleted hAGP protect against renal I/R injury by preservation of tubular epithelial structure and inhibition of apoptosis and subsequent inflammation. Therefore, hAGP can be regarded as a potential new therapeutic intervention in the treatment of acute renal failure, as seen after transplantation of ischemically injured kidneys.

Proximal tubular epithelial hyperplasia in patients with chronic glomerular proteinuria

Proteinuria is known to affect the proximal tubular epithelial structure and function. The present study tested the hypothesis that chronic proteinuria leads to hyperplasia of proximal tubular epithelium. This hypothesis was tested by morphometric analysis of the renal biopsy specimens in two groups of patients. Group A (N = 15) was composed of patients with chronic glomerular proteinuria who, for clinical indications, underwent renal biopsy of their native kidneys on two separate occasions. The proteinuria was sustained during the first and second renal biopsies in all but two of the patients with minimal change nephrotic syndrome who experienced transient remission. Group B (N = 10) was composed of patients with little or no proteinuria who underwent renal biopsy because of unexplained hematuria and whose renal biopsy showed only thin glomerular basement membrane (GBM) disease. In Group A, the mean number of epithelial cell nuclei per proximal tubule cross-section increased significantly from the first to the second renal biopsy (11.0 +/- 2.7 vs. 13.0 +/- 2.2, P = 0.005, paired t-test). Also, those with severe proteinuria showed proximal tubules with reactive epithelium (large pale nuclei with a high nucleus to cytoplasm ratio) and marked hyperplasia (double and triple layers of epithelium). Such changes were not seen in group B renal biopsies. Compared with group A biopsies, group B biopsies showed a lower mean value for proximal tubular epithelial cell nuclei per tubular cross-section (P = 0.056) and a higher mean proximal tubular volume (P = 0.049). As a consequence, the mean number of nuclei per relative tubular volume was significantly greater in group A compared with group B (0.55 +/- 0.14 vs. 0.40 +/- 0.06, P = 0.003, by Wilcoxon rank sum). Chronic heavy proteinuria is associated with hyperplasia of proximal tubular epithelium and contraction of proximal tubular volume. These events may impair glomerular filtration and represent another mechanism of progression of renal disease.

Epithelial/mesenchymal interactions and branching morphogenesis of the lung

The establishment of branched tubular epithelial structures is critical for the viability of multicellular organisms: the tracheal system in Drosophila and the vertebrate lung being two such structures. Although there are obvious differences in the complexity of these branched organs, many of the underlying mechanisms and genes regulating their development appear to have been evolutionarily conserved.

Autosomal dominant polycystic kidney disease: A genetic perspective

Summary: Important advances in understanding the common genetic disease, autosomal dominant polycystic kidney disease (ADPKD), have been made in last 3 years through the identification and characterization of the major genes, PKDI and PKD2. the PKDI and PDK2 genes map to the chromosomal regions, 16p13.3 (within a complex reiterated area) and 4q21‐23, respectively, and encode transcripts of over 14kb (PKDI) and 5 kb (PKD2). the predicted PKD1 protein, polycystin, is 4302/3 aa with a calculated molecular mass of approximately 460 kDa. Polycystin has a large extracellular region containing motifs involved in protein‐protein and protein‐carbohydrate interactions, and is attached to the membrane with multiple transmembrane regions. PKD2 is a small integral membrane protein (110 kD) with cytoplasmic N and C termini, 6 transmembrane domains and a region of homology with polycystin. Similarity of PKD2 to voltage‐gated ion channels and an area of homology between polycystin and a receptor for egg jelly protein, which is thought to regulate ion channels, suggests a role for the ADPKD proteins in ion transport. the PKD1 and PKD2 genes are expressed in most tissues and polycystin has been localised to tubular epithelial structures in the fetal and adult kidney. A Western product of approximately 400 kDa has been detected in membrane fractions of renal tissue and strong polycystin expression has been noted in PKD1 cystic epithelia. the mutations detected at PKD1 and PKD2 suggest that these germline changes are inactivating. A specific syndrome due to a deletion of PKD1 and the adjacent TSC2 gene is associated with early onset polycystic kidney disease and tuberous sclerosis. Recent evidence of somatic mutation in cystic epithelia suggests that PKD1 is recessive at the cellular level, although this appears a odds with the continued polycystin expression noted in these cells. Further studies to determine the precise mutational mechanism and the normal role of the ADPKD proteins is required.

Immunohistochemistry of Medulloepithelioma and Neural Tube

Immunohistochemistry profiles of medulloepithelioma (from two 2 1/2-year-old girls who had cerebral medulloepitheliomas and a 35-week postconceptional female infant with congenital posterior fossa tumor) and neural tube are compared. Microscopically, the tumors contained a medulloepitheliomatous component, manifested as tubular epithelial structures lined by pseudostratified columnar epithelium delineated by well-defined basement membranes. In all cases, glial and neuronal differentiation were noted to differing extents. The medulloepitheliomatous components did not exhibit glial fibrillary acidic protein, neuron-specific enolase, or S-100 protein reactivity. Neurofilament, cytokeratin, and epithelial membrane antigen were focally present in one case. Extensive nestin immunopositivity was confined to the basal cell layer of the epithelium, leaving the luminal surface unreactive or slightly reactive. These cells also displayed a reactivity to vimentin and to microtubule-associated protein type 5 similar to that of cells of the primitive neural tube. The similarity between the immunohistochemical profile of medulloepithelioma and that of neural tube epithelium suggests a possible reexpression of that component of the genome responsible for neural tube growth and differentiation in medulloepithelioma.

Collagenous Spherulosis in Chondroid Syringomas

We report a case of collagenous spherulosis (CS) incidentally found in a chondroid syringoma of the facial skin. The lesion was studied by routine light microscopy, special stains, immunohistochemical methods, x-ray spectrophotometry, and electron microscopy. Light microscopy revealed solitary and confluent eosinophilic globules with radiating fibrillary structures within and around the lumina of the tubuloglandular components of chondroid syringoma. The fibrillary structures stained strongly for collagen and reticulin and less intensely for acidic mucopolysaccharides. Immunohistochemically, the globules were focally positive only for collagen type IV. Electron microscopy revealed radiating collagen fibers surrounded by basal lamina-like material. No inorganic crystals were identified by x-ray spectrophotometry. We conclude that (a) CS is not specific to breast but also occurs in chondroid syringomas; (b) the term collagenous spherulosis is appropriate because collagen fibers were demonstrated histochemically and ultrastructurally in the spherules; (c) CS appears to be associated with tubular epithelial structures; (d) there was no immunohistochemical evidence of myoepithelial differentiation. The etiology and significance of CS remain obscure.

Three-Dimensional Analysis of 61 Human Endolymphatic Ducts and Sacs in Ears with and without Meniere's Disease

We used light microscopy and computerized graphic reconstruction techniques to examine the endolymphatic duct and sac in 20 pairs of bones from patients with Menière's disease and 21 bones from controls. The diameters of the endolymphatic duct and the proximal portion of the vestibular aqueduct were significantly smaller in Menière's disease ears than in controls. Graphic reconstructions showed the Menière's sacs to be smaller and to have fewer tubular epithelial structures in the intraosseous portion than in the control ears. The median volume of the sac in the Menière's disease side was substantially lower than in the contralateral ear. The width of the external aperture of the vestibular aqueduct was significantly smaller in Menière's disease ears than in controls. These findings indicate that the size not only of the vestibular aqueduct but also of the sac is reduced in Menière's disease. The results may suggest that the endolymphatic sac is pathologically changed in Menière's disease and that a reduced resorptive capacity of a small endolymphatic sac could result in endolymphatic hydrops.