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Biomedical subjects

R B Nagle

Publications and source records attributed to R B Nagle.

At least 109 records · Page 6Linked to original sources

Ribosome-lamellae complexes in benign plasma cells accompanying neoplastic infiltrates.

Two examples of ribosome-lamellae complexes (RLCs) occurring in benign plasma cells are presented. These were seen utilizing transmission electron microscopy in a case of mycosis fungoides in skin and a fibrosarcoma of a lower extremity. In both cases the accompanying plasmacytic infiltrate was interpreted as reactive and not malignant. Once thought to be a specific marker for hairy cell leukemia, RLCs now have been described in a wide variety of neoplastic diseases (mostly hematologic) and in a few examples of nonneoplastic conditions. RLCs have not been described previously in benign plasma cells. A review of the literature with respect to occurrence and significance of RLCs is presented.

Adult↗

The probable origin of an anemone cell tumor: metastatic transitional cell carcinoma producing HCG.

A neoplasm of unknown origin in cervical and axillary lymph nodes was diagnosed as anemone cell tumor by ultrastructural examination. Three years after the initial diagnosis of anemone cell tumor, a high-grade transitional cell carcinoma of the bladder was discovered. The results of immunoperoxidase staining of the cervical lymph node, axillary lymph node, and bladder tumors for keratin, carcinoembryonic antigen, and human chorionic gonadotropin (HCG) strongly suggest that the anemone cell tumors in this case represent metastases of bladder carcinoma cells capable of producing HCG.

Axilla↗

An ultrastructural cytochemical stain specific for neuroendocrine neoplasms.

Previous work from our laboratory has indicated that the uranaffin reaction, when run under specific conditions, will stain neurosecretory granules. In this ultrastructural cytochemical study, we analyzed the granule-staining properties of 13 normal, 10 abnormal (non-neoplastic), and 138 neoplastic tissues in an attempt to evaluate the specificity of the uranaffin reaction for diagnostic purposes when compared with routinely processed specimens. For the uranaffin reaction, previously fixed tissue stored in buffer was rinsed with 0.9% NaCl and reacted with a 4% aqueous solution of uranyl acetate (pH 3.9) for 48 hours. After three NaCl rinses, the tissue was dehydrated and processed for electron microscopy. The granules of normal or non-neoplastic neuroendocrine cells that stained positively with the uranaffin reaction included pancreatic islet cells, thyroid C cells, adrenal medullary cells, parathyroid chief cells, and the neuroendocrine cells of the intestine. All 42 neuroendocrine neoplasms studied possessed abundant uranaffin-positive granules and included carcinoids, oat cell carcinomas, islet cell neoplasms, medullary carcinomas of the thyroid, pheochromocytomas, carotid body paragangliomas, a pituitary adenoma, Merkel cell carcinomas, parathyroid adenomas, and a neuroblastoma. All 96 control neoplasms that were not classified as neuroendocrine in nature were negative for neurosecretory granules when studied with the uranaffin reaction and included 13 neoplasms derived from endocrine glands, 57 neoplasms from secretory epithelium, 10 of hematopoietic origin, and 16 miscellaneous neoplasms. It was determined that the uranaffin reaction is a useful ultrastructural cytochemical marker for neuroendocrine granules and helped distinguish these cytoplasmic organelles from ultrastructurally similar granules derived from non-neuroendocrine cells.

Adult↗

Cystic hygroma reconsidered: hamartoma or neoplasm? Primary culture of an endothelial cell line from a massive cervicomediastinal hygroma with bony lymphangiomatosis.

A young woman presented with massive enlargement of a giant cervicomediastinal cystic hygroma, which communicated in part with the thoracic duct and was associated with generalized bony lymphangiomatosis. Modern imaging and sophisticated intraoperative physiologic monitoring made one-stage resection feasible. Tissue culture of explants of the hygroma yielded a primary endothelial cell line still surviving after 18 months, which, like the cyst-lining endothelium in the original resected specimen, reacted positively for Factor VIII-associated antigen. These findings, in conjunction with the histologic picture, support the notion that cystic hygroma represents an expanding proliferating endothelial growth process and not simply a sequestered lymphatic receptacle.

Adult↗

Quantitative electron microscopy in the diagnosis of mycosis fungoides. A simple analysis of lymphocytic nuclear convolutions.

In the present study we compared the accuracy of three different ultrastructural methods used to confirm clinically proved cases of mycosis fungoides (MF) from skin biopsy specimens. Method 1 is a qualitative method and confirmed the diagnosis of MF in only 44% of the patients with MF. Method 2 involved image analysis of lymphocytic nuclei and confirmed the diagnosis of MF in only 67% of the patients with MF. The most sensitive ultrastructural method for confirming the diagnosis of MF was a simple scoring of the number of sharply angled nuclear invaginations in 100 lymphocytes (method 3). Control biopsy specimens had many more lymphocytes (19% to 55%) with no sharply angled nuclear invaginations compared with those from patients with MF (3% to 15%). The clinical diagnosis of MF was confirmed in 100% of our patients with MF using method 3.

Biopsy↗

Congenital blood cysts of the heart valves.

Congenital blood cysts of the heart valves are found most commonly on the tricuspid and mitral valves of fetuses and infants. Hearts available following 38 random autopsies of fetuses and infants 2 years of age or younger were examined. Blood cysts were found in 18 cases (47 per cent) in which ages ranged from 26 weeks of gestation to 11 months. The cysts varied in diameter, from microscopic to 3 mm. Affected valves had from one to 20 cysts. Light microscopic examination of serially sectioned paraffin-embedded tissue and plastic-embedded tissue and scanning electron microscopic examination revealed connections between the cyst lumens and ventricles via small endothelium-lined channels. The cyst structure suggested formation from ventricular endothelial infoldings in the valve leaflet base, which bulged into the atrium because of the pressure gradient present during valve closure. Blood cysts are a common finding in neonates dying of various causes and probably have no clinical significance. There is no association with asphyxia as previously described. Blood cysts may persist and enlarge to form giant cysts of the heart valves.

Aortic Valve↗

The use of antikeratin antibodies in the diagnosis of human neoplasms.

The presence of intracellular keratin was examined in 230 human neoplasms using indirect immunofluorescence on fresh frozen, acetone-fixed sections. The use of antikeratin antibodies raised in rabbits against human callus and purified by affinity chromatography proved to be a rapid, sensitive, and reliable method of demonstrating keratin. Epithelial tissues and epithelial-derived neoplasms were found to contain keratin, whereas tissues and neoplasms of mesenchymal, lymphoreticular, or neural crest origin did not contain intracellular keratin. This technic is a useful adjunct for the surgical pathologist in the diagnosis of poorly differentiated neoplasms. Its application either confirmed, modified, or in several instances, changed the original light microscopic impression. The modified or changed diagnoses were confirmed by transmission electron microscopy.

Adult↗

Quantitative electron microscopic study of membranous glomerulopathy.

Primary and secondary membranous glomerulopathy (MGN) may be indistinguishable by light microscopy and immunofluorescence. It has been noted occasionally anecdotally that the distribution of subepithelial immune complex deposits by electron microscopy may differ between these two subgroups. The authors examined 23 cases of primary and 22 cases of secondary MGN and quantitated the percentage of glomerular basement membrane occupied by immune complexes for each group. Mean percentage involvement of GBM with deposits was 49% +/- 15% for the primary group and 16% +/- 15% for the secondary group; these were statistically significantly different at the P less than 0.05 level. When far-advanced disease cases (Churg Class IV) were eliminated from the groups, the mean percentage involvement of GBM was 48% +/- 15% and 12% +/- 7% for the idiopathic and secondary groups, respectively (P less than 0.01). The quantitative differences in involvement of the GBM with immune complex deposits between primary and secondary MGN may represent fundamentally different types of antigen-antibody complexes or variable patterns in deposition of complexes derived from the circulation or formed in situ.

Adult↗

Immunohistochemical demonstration of keratins in human ovarian neoplasms. A comparison of methods.

A comparison of five immunohistochemical methods for the demonstration of keratins in human ovarian neoplasms using affinity-purified polyclonal rabbit antibody was made. The use of indirect immunofluorescence on frozen sections briefly fixed in acetone was found to be the most sensitive method and demonstrated keratin in all 14 primary and 1 metastatic ovarian epithelial neoplasms studied. Protein A-peroxidase, peroxidase--antiperoxidase (PAP), indirect peroxidase, or the avidin--biotinylated peroxidase complex (ABC) methods applied to formalin-fixed tissues were less sensitive and led to false negative results in 9 of 15, 1 of 15, 8 of 15, and 6 of 15 cases, respectively. A single case of dysgerminoma failed to reveal keratin by any method.

Female↗

An ultrastructural study of intranuclear rodlets in a malignant extracranial neuroepithelial neoplasm.

This report describes for the first time the presence of intranuclear rodlets in a malignant extracranial neuroepithelial neoplasm. This malignant neoplasm appeared poorly differentiated by light microscopy and presented initially as a diagnostic problem. Electron microscopy revealed neoplastic cells joined by macula adherens-type junctions and containing numerous interdigitating cell processes diagnostic of a neuroepithelial neoplasm. A quantitative analysis of 500 cells revealed the presence of intranuclear rodlets in 5% of the neoplastic cells. The rodlets were composed of individual filaments that measured 7-9 nm in width. An extensive review of the literature revealed the high frequency of reported rodlets in normal neurons, normal paraneurons, neoplasms of the nervous system, and paraneuromas. The significance of this interesting structure to the physiology of the cell is discussed.

Aged↗

The effect of macrophages on the metabolism of glomerular cells: preliminary studies.

Human glomerular epithelial and mesangial cells were grown in vitro and shown to have distinctive morphologic and functional characteristics. Glomerular epithelial cells or mesangial cells cultured in wells of flat-bottom microtiter plates were treated for 4 hr with dialyzed macrophage supernatants obtained from cultures of mouse peritoneal macrophages or human peripheral monocytes. DNA, RNA, and protein synthesis were evaluated by incorporation of radioactive precursors. Macrophage supernatants stimulated RNA and protein synthesis in epithelial cells but failed to stimulate DNA synthesis. The macrophage factor(s) showed a dose-response activity, was nondialyzable, was destroyed by freezing and thawing, and did not seem to be species specific. In contrast to the results obtained with glomerular epithelial cells, mesangial cell DNA synthesis was stimulated by macrophage supernatants. The observed metabolic effects of macrophage products on glomerular cells in vitro are consistent with observations of in vivo glomerular response to injury in which epithelial cells may be activated to form new basement membrane while mesangial cells may respond by proliferating. These data further support the theory of macrophage involvement in the pathology of glomerulonephritis.

Animals↗

An ultrastructural evaluation of the cell organelle specificity of the uranaffin reaction in two human endocrine neoplasms.

The organelle specificity of the uranaffin reaction was determined by subjecting two human neoplasms (a pheochromocytoma and islet cell carcinoma) to four different experimental conditions. In Uranaffin Procedure (UP) I, fixed tissue was immersed in 0.9% sodium chloride (NaCl) before reacting with 4% uranyl acetate (pH 3.9) for 24 hours. In UP II, the tissue was prepared as in UP I with the exception that the tissue was immersed in uranyl acetate for 48 hours. In UP III, fixed tissue was prepared as in UP I with the exception that tissue was immersed in 0.1M cacodylate buffer (pH 7.2) instead of 0.9% NaCl. In UP IV, fixed tissue was prepared as in UP III with the exception that the tissue was immersed in uranyl acetate for 48 hours instead of 24 hours. When UPs I and II were utilized, only three cell organelles showed electron-dense reactivity: the nucleus, ribosomes, and cytoplasmic neurosecretory-like granules. In the nucleus, the nuclear chromatin, nucleolus, interchromatinic granules and perichromatinic granules were intensely stained. The reaction product in all of the uranaffin-positive organelles had a finely granular appearance. When fixed tissue was immersed in cacodylate buffer instead of isotonic saline, a non-specific reactivity was observed. The reaction product in some areas had a distinct crystalline appearance and filled some areas of the cytosol, the cisternae of the endoplasmic reticulum, the Golgi apparatus, the perinuclear cisternae, the nucleus, nucleolus, mitochondria, neurosecretory-like granules and larger lysosome-like bodies. There was a statistically significant (p less than 0.05) increase in the number of uranaffin-positive granules/mu2 when both endocrine neoplasms were reacted with uranyl acetate for 48 hours instead of 24 hours. The increase in uranaffin-positive granules using UP II did not result in an increase in non-specificity of the staining reaction.

Adenoma, Islet Cell↗

Studies on prolonged spermatozoa survival in Chiroptera: a morphological examination of storage and clearance of intrauterine and cauda epididymal spermatozoa in the bats Myotis lucifugus and M. velifer.

The cauda epididymidis, uterine corpus, and cornua and uterotubal junction of Myotis function to retain and preserve normal spermatozoa throughout hibernation. In none of the sites do spermatozoa show features that might account for their extended viability. Spermatozoa stored in the uterus and epididymis show no special orientation toward the epithelium lining these sites, whereas an intimate relationship is established between some sperm and the epithelial cells of the uterotubal junction which might either account for extended postcoital sperm survival or forecast their removal from further participation. Transmission and scanning electron microscopic observations do not disclose any morphological changes in stored luminal spermatozoa. A low rate of phagocytosis of sperm is evident in the female tract during hibernation. However, spermatozoa are evidently not vulnerable to being removed from the storage sites until spring arousal when ovulation occurs. Both uterotubal epithelial cells and phagocytes appear to be involved in the disposal of spermatozoa in the female, whereas epididymal spermatozoa apparently are primarily voided during urination. A mechanism that delays capacitation must underlie the ability of spermatozoa to survive in the female reproductive tract of the hibernating bat.

Animals↗

Glomerular accumulation of monocytes and macrophages in experimental glomerulonephritis associated with Trypanosoma rhodesiense infection.

Experimental infection in rabbits with a human isolate of Trypanosoma rhodesiense led to the formation of circulating immune complexes and glomerulonephritis. Granular deposits of C3 and lesser amounts of IgM and IgG were seen deposited in the glomeruli in a primarily mesangial pattern. The glomeruli became hypercellular beginning on day 7. This was associated with diffuse swelling and vacuolation of endothelial cells with focal loss of fenestrae, as well as vacuolation of mesangial cells processes protruding into the capillary lumina. The hypercellularity became maximal on day 21 and was accompanied by proteinuria and increased tubular hyaline droplets. The hypercellularity was in large part due to the accumulation of monocytes as demonstrated by nonspecific cytoplasmic esterase stains. Counts of the number of monocytic cellular profiles per glomerulus showed that maximal numbers were reached on the 21st day of the infection. Ultrastructural examination confirmed the presence of monocytes within capillary lumina and macrophages within mesangial regions. Electron-dense deposits were rarely seen by transmission electron microscopy, and the heavy granular deposits of IgM and C3 observed by immunofluorescence were attributed to ingested proteins within macrophages. This study implies an active role for monocytes and macrophages in immune complex-mediated glomerulonephritis.

Animals↗

The ultrastructure of the thin limbs of Henle in Kidneys of the desert heteromyid (Perognathus penicillatus).

The thin limbs of both long- and short-looped nephrons in Perognathus kidneys were studied with transmission and scanning electron microscopy. The superficial nephrons have a short thin limb located in the vascular bundles of the outer medulla and are characterized by a simple, low-lying epithelium (0.4 +/- 0.1 mu thickness). In contrast, the first descending part of the thin limb of the majority of midcortical and juxtamedullary nephrons has a relatively thick epithelium (1.7 +/- 0.6 mu in thickness) with marked lateral and basal interdigitation and a dense surface covering of microvilli. The remaining part of the long descending thin limb is relatively simple with a low-lying epithelium (0.6 +/- 0.1 mu in thickness), decorated on its surface by sparse microplicae. The bend of the loop and the ascending limb are covered by a very simple low-lying epithelium (0.6 +/- 0.2 mu in thickness) with relatively little surface modification. The extreme urine-concentrating ability of Perognathus does not appear to be due to the development of a unique thin loop epithelium but rather to the extensive length of the inner and outer medulla.

Animals↗