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Ultrastructure of the echinoderm cuticle after fast-freezing/freeze substitution and conventional chemical fixations.

The cuticles of the pedicellaria primordia in the sea urchin Paracentrotus lividus and of the tube foot disk in the sea star Asterias rubens were preserved by different methods, viz., glutaraldehyde fixation followed by osmium tetroxide postfixation, glutaraldehyde-ruthenium red fixation followed by osmium tetroxide-ruthenium red postfixation, and two fast freezing / freeze substitution methods (FF/FS). The gross ultrastructure of the cuticle as well as the influence of the preservation method on this ultrastructure were identical for the two tissues studied. The cuticle ultrastructure was poorly preserved after glutaraldehyde fixation / osmium tetroxide postfixation. Its preservation was improved after ruthenium red was added in the fixative and postfixative, but the best preservation was consistently achieved using FF/FS. Both low-pressure freezing (plunge freezing) and high-pressure freezing were tested, the latter giving seemingly better results. With these methods, the cuticle appeared to be composed of a proximal lower cuticle, an intermediate upper cuticle, and a distal fuzzy coat. In particular, cryoimmobilization methods emphasized or revealed the occurrence of a well-developed fibrillar lower cuticle in the pedicellaria, the complexity of the upper cuticle which consisted of several zones, and the importance of the usually poorly preserved fuzzy coat that is actually the thickest layer of the cuticle. These observations bring new insights on the functions of the cuticle, and particularly of the fuzzy coat. According to its preservation characteristics, the fuzzy coat presumably consists mostly of proteoglycans. This composition could give it shock absorption and antifouling properties. Furthermore, its important thickness also implies that molecules detected by the short sensory cilia must diffuse through and could be selected by the fuzzy coat.

Animals↗

Ultrastructure of prostatic intraepithelial neoplasia.

BACKGROUND: Prostatic intraepithelial neoplasia (PIN) is the most likely precursor of prostatic adenocarcinoma. However, the ultrastructural features of PIN have not been defined in properly fixed tissues. METHODS: In this study, we examined a total of 84 acini from 11 cases of high-grade PIN and matched benign epithelium and adenocarcinoma from patients undergoing radical prostatectomy. Specimens from each case were immediately fixed in glutaraldehyde after surgical removal and processed routinely to ensure optimal preservation. RESULTS: High-grade PIN displayed ultrastructural features that were intermediate between those of benign epithelium and adenocarcinoma. These included the presence of cells with a variable number of cytoplasmic secretory vacuoles, luminal apocrine blebs, large nuclei with coarsely clumped chromatin, enlarged nucleoli, prominent apical microvilli, intact or discontinuous basal cell layer, and intact basement membrane. CONCLUSIONS: Our results indicate that PIN shares many ultrastructural characteristics with adenocarcinoma, supporting its role as a premalignant lesion.

Adenocarcinoma↗

Ultrastructural localization of the intercellular adhesion molecule (ICAM-1) on the cell surface of high endothelial venules in lymph nodes.

BACKGROUND: The high endothelial venules (HEV) in the lymph nodes are essential for lymphocyte recirculation. As a first step, the HEV surface interacts with lymphocytes through adhesion molecules. It is important to know where adhesion molecules are expressed on the surface ultrastructure and how these structures interact with lymphocytes. METHODS: To demonstrate the ultrastructural mechanism of interaction between the HEV surface and lymphocytes through the intercellular adhesion molecule (ICAM-1), rat mesenteric lymph nodes were perfused through the superior mesenteric artery with the primary antibody (antirat ICAM-1 antibody) and secondary antibody (antimouse IgG coupled to 15 nm gold particles), which were diluted with hypothermic University of Wisconsin (UW) solution. After the immunoreaction, we analyzed the HEV three-dimensionally and quantitatively using immunoscanning electron microscopy (ISEM) combined with transmission electron microscopy (TEM). RESULTS: HEV expressed ICAM-1 in a 5-30-fold higher concentration than other vessels. Its distribution was extensive over the luminal surface of the cell down to the junctional area. The endothelial surface of HEV undulated to form branched microfolds, along which ICAM-1 was expressed. Cytoplasmic processes of lymphocytes were seen in microfurrows between microfolds and adhered to the sides of the folds. CONCLUSIONS: These observations imply that the microfolds expressing ICAM-1 and microfurrows are specific ultrastructural features for trapping lymphocytes, thus initiating lymphocyte emigration into the lymph node parenchyma.

Animals↗

Three-dimensional ultrastructure of the surface of the tongue of the rat snake, Elaphe climacophora.

BACKGROUND: Many studies have been performed to clarify the relationship between behavioral performance of the tongue and Jacobson's organ. The purpose of the present study was to examine the ultrastructural features of the surface of the tongue of the rat snake, Elaphe climacophora, and to delineate the functional relationship between the tongue and Jacobson's organ from a morphological perspective. METHODS: The three-dimensional ultrastructure of the surface of the tongue of the rat snake Elaphe climacophora was investigated by scanning electron microscopy. RESULTS: Most of the surface of the bifurcated apex of the tongue was relatively smooth. Dome-shaped, hemispherical bulges or microfacets were compactly arranged on the epithelial cell surface over this entire region. Intercellular borders were clearly recognizable as striations. These features were almost the same as those of the dorsal surface of the transitional area between the bifurcated lingual apex and the anterior part of the lingual body. In the posterior half of the lingual body, no microfacets were seen at all. Both microridges and microvilli were compactly distributed on cell surfaces. CONCLUSIONS: No evidence was obtained from our ultrastructural analysis for an important role of the lingual apex in the vomeronasal system. By contrast, the epithelial surface of the body of the tongue appeared suitable for retaining stimulating compounds.

Animals↗

Ultrastructural characterization of preosteoclasts derived from bone marrow progenitors stimulated by osteoclast colony stimulating factor.

BACKGROUND: Osteoclast colony stimulating factor (O-CSF) is an osteoclast-specific growth factor that stimulates the clonal growth of primitive osteoclast progenitors from bone marrow cells in culture. To characterize the morphology of immature osteoclasts (preosteoclasts) arising from complex hematopoietic tissues, progenies of O-CSF-responsive progenitors were cocultured with devitalized calvariae, and their cytochemical and ultrastructural features were examined. METHODS: Murine bone marrow cells were cultured in semisolid medium for 14 days in the presence of O-CSF. Colonies derived from osteoclast progenitors were then cocultured with devitalized mouse calvariae for 5 days. Cells attached to the calvariae were stained for tartrate resistant acid phosphatase (TRAPase), and the ultrastructure of these cells was examined by transmission electron microscopy. Bone marrow cells stimulated by macrophage colony stimulating factor (M-CSF) were similarly studied as a control. RESULTS: O-CSF-induced preosteoclasts stained strongly positive for TRAPase when cocultured with calvariae. These cells showed single nuclei, and their cytoplasm contained numerous mitochondria, vacuoles, granules, and coated vesicles. The ruffled cell border consisted of short, blunt, fingerlike projections. The adjacent clear zone contained abundant microtubules, microfilaments, and long narrow channels. M-CSF-induced macrophages were TRAPase negative, with no ruffled borders or clear zones. CONCLUSIONS: All the characteristic features of active osteoclasts were observed in the cells derived from O-CSF-responsive bone marrow progenitors except that these cells were mononucleated, and their ruffled borders were not fully convoluted, indicative of their immature nature. This study documents for the first time the ultrastructural characteristics of preosteoclasts derived from cultured bone marrow progenitors in early stages of development.

Acid Phosphatase↗

Ultrastructural characterization of internal basement membrane of junctional epithelium at dentogingival border.

BACKGROUND: Although a number of electron microscopic observations of the dentogingival border have been reported, observation of the detailed ultrastructure of the internal basement membrane of the junctional epithelium at the border has not yet been done. METHODS: The internal basement membrane of a rhesus monkey (Macaca mulatta) was ultrastructurally characterized with high-resolution electron microscopy. The head and neck region of a 5-year-old animal was perfused with a fixative containing 1.25% glutaraldehyde, 0.75% formaldehyde, and 0.04% CaCl2 in 0.1 M phosphate buffer, pH 7.4. Isolated mandibular segments were further fixed with 2.5% glutaraldehyde, 2% formaldehyde, and CaCl2 (300 mg/l) in 0.1 M sodium cacodylate buffer, pH 7.4, for 24 hr at 4 degrees C. The segments were then demineralized and cut into small pieces that were postfixed with 1% osmium tetroxide and further processed for electron microscopy. RESULTS: The internal basement membrane takes the form of both a common basement membrane and, in places, a multilayered basement membrane. This basement membrane was found to have fundamental ultrastructural features common to other basement membranes. That is, the bulk of the basement membrane is composed of a network of irregular anastomosing strands referred to as "cords." Heparan sulfate proteoglycan-containing ribbonlike 4.5-5-nm-wide "double tracks" were also present in this basement membrane. However, the lamina densa of this basement membrane was unusually thick (160 nm) compared with the thickness (30-60 nm) in other basement membranes, and the cords were also much thicker (8.3 +/- 1.9 nm vs. the usual 3-5 nm). CONCLUSIONS: From these results, it is concluded that this particular basement membrane is specialized for mechanical strength. This specialization is likely to be suitable for the purpose of the tight sealing of the periodontal tissues from the oral environment.

Animals↗

Immunocytochemical and ultrastructural characterization of prolactin, growth hormone, and somatolactin cells from the Mediterranean yellowtail (Seriola dumerilii, Risso 1810).

BACKGROUND: Prolactin (PRL), growth hormone (GH), and somatolactin (SL) are structurally related pituitary hormones that belong to a peptide family. Whereas growth hormone and prolactin are present in the hypophysis of all vertebrates, somatolactin, a recently discovered hormone, has been found only in fish. It has been demonstrated immunocytochemically in a few teleost species; ultrastructurally, cells producing this hormone have been characterized only in one species of salmon. In this paper, we identify and characterize ultrastructurally the cells producing these three hormones in Mediterranean yellowtail (Seriola dumerilii). METHODS: Pituitaries from adult specimens were dissected out and processed for electron microscopy. The immunogold technique was performed in some ultrathin sections using fish primary antibodies. RESULTS: PRL cells had round, peripherally distributed, very electron-dense, homogeneous secretory granules of variable size. GH cells had dense, round secretory granules with a conspicuous scalloped membrane, which were grouped in the cell area near the neurohypophysis. SL cells had round, polymorphic, or very irregularly shaped secretory granules, the last seeming to arise from the fusion of various secretory granules. The population of secretory granules varied greatly from one cell to another. In all cases, immunogold labeling was seen exclusively in the secretory granules. Exocytosis was observed in all cell types. Some of the PRL, GH, and SL cells showed involutive features. CONCLUSIONS: PRL, GH, and SL, although structurally and functionally related, are secreted by ultrastructurally different cells in the pituitary of M. yellowtail.

Animals↗

Ultrastructural features of odontoclasts that resorb enamel in human deciduous teeth prior to shedding.

Three dental hard tissues, i.e., cementum, dentin, and enamel, are resorbed by multinucleated cells referred to as "odontoclasts." These cells have morphological and functional characteristics similar to those of bone-resorbing osteoclasts. However, concerning enamel resorption, which is a process that may occur during tooth eruption, satisfactory ultrastructural data on odontoclastic resorption are still lacking. Ultrastructural and histochemical characteristics of odontoclasts resorbing enamel of human deciduous teeth prior to shedding were examined by means of light microscopy and transmission and scanning electron microscopy. Odontoclasts that that resorbed enamel were tartrate-resistant acid phosphatase (TRAP)-positive multinucleated giant cells that were essentially the same as those that resorbed dentin and cementum. Ultrastructurally, they had numerous mitochondria, lysosomes, and free polysomes in their cytoplasm. In addition, they were characteristically rich in large cytoplasmic vacuoles containing enamel crystals in the cytoplasm opposite the ruffled border. Although they extended a well-developed, ruffled border against enamel surface, a clear zone--an area typically devoid of organelles--was rarely seen in these cells. In many cases, the cells were in very close contact with the enamel surface by the peripheral part of their cytoplasm. The enamel prisms at the resorption surface contained more loosely packed and electron-lucent enamel crystals compared with those of unresorbed, intact enamel. Furthermore, numerous thin needle- or plate-like enamel crystals that were liberated from the enamel matrix were found in the extracellular channels of the ruffled border and in various-sized cytoplasmic vacuoles in their cytoplasm. The superficial layer of the enamel matrix undergoing odontoclastic resorption stained positively with toluidine blue and for TRAP activity. The results of the present study suggest that odontoclasts resorbing enamel secrete acids as well as organic components, including hydrolytic enzymes, into the resorption zone underlying their ruffled border and that they phagocytose crystals that have been liberated from the partially demineralized enamel matrix by acids, subsequently dissolving them intracellularly.

Acid Phosphatase↗

Ultrastructure and lectin cytochemistry of the cloacal pelvic glands in the male newt Triturus marmoratus marmoratus.

The cloacal organ of Salamandridae species contains four glands: pelvic, dorsal, ventral, and Kingsbury's glands. Pelvic glands have been studied only by light microscopy with conventional methods, and consist of multiple tubular serous glands with a prismatic epithelium which contains numerous PAS positive secretory granules. The present report is an ultrastructural and lectin cytochemistry characterization of the pelvic glands of Triturus marmoratus marmoratus throughout the reproductive cycle. Our methods consisted of conventional electron microscopy, and colloidal-gold lectin cytochemistry of the following lectins: WGA, ConA, LcA, UEA-I, PNA, SBA, and HPA. In the prereproductive period, the glands showed a tall epithelium which consisted of two cell types, dark and clear cells, surrounded by elongated, myoepithelial cells. Both dark and clear cells showed the ultrastructural characteristics of secretory cells, and exhibited many secretory granules in the apical cytoplasm. Areas showing densely packed, degenerating cell organelles--which were not surrounded by membrane--were observed in the dark cells whereas the clear cells showed large heterolysosomes. In the postreproductive period the number of secretory granules decreased, the rough endoplasmic reticulum was less developed, and areas of degenerating organelles were absent. In addition, small basal cells appeared. The results of the lectin histochemistry study were similar in both reproductive periods. In the epithelial cells, the rough endoplasmic reticulum, the Golgi complex, and secretory granules exclusively labeled to ConA. In all cell types, the nuclei reacted to all lectins while the cytosol only reacted to LcA lectin. The ultrastructural and histochemical characteristics of the pelvic glands of T. marmoratus suggest that these glands could be homologous to the mammalian seminal vesicles and prostate.

Animals↗

Synaptic ultrastructure in nerve terminals of Drosophila larvae overexpressing the learning gene dunce.

We investigated synaptic ultrastructure of individual nerve ending varicosities at the Drosophila larval neuromuscular junction in transgenic larvae overexpressing the learning gene dunce (dnc) in the nervous system. It was previously shown that cAMP is reduced to one-third normal in these larvae and that they have fewer nerve terminal varicosities and smaller junction potentials, although transmitter release from individual nerve ending varicosities is not significantly altered. We tested the hypothesis that synaptic ultrastructure is modified to compensate for possible reduced efficacy of synaptic transmission resulting from lower than normal cAMP. Synaptic size and number of presynaptic dense bodies (active zone structures) per synapse are modestly enhanced in transgenic larvae overexpressing the dnc gene product and in rutabaga (rut(1)) mutant larvae, which have reduced adenylyl cyclase activity and reduced neural cAMP. The incidence of complex synapses (possessing 2 or more presynaptic dense bodies) was not consistently different in experimental larvae compared to controls. The observations suggest that chronic reduction of cAMP levels in the nervous system of Drosophila larvae, although leading to a modest compensatory change in synaptic structure, does not markedly alter several synaptic ultrastructural parameters which are thought to influence the strength of transmitter release; thus, homeostatic mechanisms do not act to maintain normal-sized junction potentials by altering synaptic structure.

Animals↗

Egg jelly layers of Xenopus laevis are unique in ultrastructure and sugar distribution.

Jelly coats surrounding the eggs of the South African clawed toad, Xenopus laevis, consist of three transparent, gelatinous layers: the innermost layer (J1), the middle layer (J2), and the outer layer (J3). The distribution of N-acetylglucosamine within these jelly coats, as probed with FITC-conjugated wheat germ agglutinin (WGA-FITC), and the matrix ultrastructure of each layer, as visualized in platinum replicas produced by the quickfreeze, deep-etch, and rotary-shadowing technique, suggests that each layer has a unique fiber and glycoprotein composition. J1 extends nearly 200 microns from the egg surface and exhibits no WGA-FITC staining. Stereo images of platinum replicas indicates that J1 consists of a tightly knit network of 5-10 nm fibers decorated with 10-20 nm particulate components. In contrast, J2 is a relatively thin layer, extending only 25-40 microns from the outer aspect of J1. When visualized by confocal microscopy, J2 displays a multilayered WGA-FITC staining pattern. The ultrastructure of J2 consists of sheets of fine fibers that run parallel to one another and that can be identified by their ability to bind WGA-colloidal gold. The fibers of each sheet run at an oblique angle to fibers in neighboring layers. J3 extends 100 microns or more from J2. The WGA-FITC staining pattern shows high intensity in its outer region and less intensity in regions closer to J2. Like J1, the J3 ultrastructure consists of a network of 5-10 nm fibers, decorated with 10-20 nm particulate components. The results of these studies add to a growing body of information that suggests the jelly coats surrounding the eggs of many animals consist of a fibrous glycoprotein superstructure that acts as a scaffold to which globular glycoproteins are bound.

Animals↗

Nucleolar ultrastructure in bovine nuclear transfer embryos.

Nuclear transfer experiments in mammals have attempted to reprogram a donor nucleus to a state equivalent to the zygotic one. Reprogramming of the donor nucleus is, among other features, indicated by a synthesis of ribosomal RNA (rRNA). The initiation of rRNA synthesis is simultaneously reflected in nuclear morphology as a transformation of the nucleolus precursor body into a functional rRNA synthesising nucleolus with a characteristic ultrastructure. We examined nucleolar ultrastructure in bovine in vitro produced (control) embryos and in nuclear transfer embryos reconstructed from a MII phase (nonactivated) or S phase (activated) cytoplasts. Control embryos were fixed at the two-, four-, early eight- and late eight-cell stages; nuclear transfer embryos were fixed at 1 and 3 hr post fusion and at the two-, four-, and eight-cell stages. Control embryos possessed a nucleolar precursor body throughout all three cell cycles. In the eight-cell stage embryo, a primary vacuole appeared as an electron lucid area originating in the centre of the nucleolar precursor body. In nuclear transfer embryos reconstructed from nonactivated cytoplasts, the nuclear envelope was fragmented or completely broken down at 1 hr after fusion and, by 3 hr after fusion, it was restored again. At this time, the reticulated fibrillo-granular nucleolus had an almost round shape. The nucleolar precursor body seen in the two-cell stage nuclear transfer embryos consisted of intermingled filamentous components and secondary vacuoles. A nucleolar precursor body typical for the two-cell stage control embryos was never observed. None of the reconstructed embryos of this group reached the eight-cell stage. Nuclear transfer embryos reconstructed from activated cytoplasts, in contrast, exhibited a complete nuclear envelope at all time intervals after fusion. In the two-cell stage nuclear transfer embryo, the originally reticulated nucleolus of the donor blastomere had changed into a typical nucleolar precursor body consisting of a homogeneous fibrillar structure. A primary vacuole appeared in the four-cell stage nuclear transfer embryos, which was one cell cycle earlier than in control embryos. Only nuclear transfer embryos reconstructed from activated cytoplasts underwent complete remodelling of the nucleolus. The reorganisation of the donor nucleolar architecture into a functionally active nucleolus was observed as early as in the four-cell stage nuclear transfer embryo. These ultrastructural observations were correlated with our autoradiographic data on the initiation of RNA synthesis in nuclear transfer embryos.

Animals↗

Ultrastructural aspects of peptidergic modulation in the peripheral nervous system of Helix pomatia.

The ultrastructural characteristics of peptidergic peripheral contacts in the snail, Helix pomatia, were investigated, with special attention to the innervation of the heart, buccal mass, and salivary gland by Mytilus inhibitory peptide-immunoreactive neurons. Following the application of correlative light- and electron-microscopic pre-embedding immunocytochemistry, the peripheral tissues reveal a rich innervation by Mytilus inhibitory peptide-immunoreactive elements. These neurons establish three types of neuromuscular contacts in the heart and buccal mass: (1) close (16-20 nm) unspecialized membrane contacts; (2) contacts with a relative wide (40-100 nm) intersynaptic cleft; and (3) labeled varicosties located freely in the extracellular space, far (0. 5-several microm) from the muscle cells. In the salivary gland, the immunoractive profiles contact both the muscular and glandular elements with close (type 1) and wider (type 2) membrane attachments. The great majority of Mytilus inhibitory peptide-immunoreactive profiles contain an ultrastructurally uniform population of large (120-150 nm) electron dense granules. The ultrastructural features of the innervation by Mytilus inhibitory peptide-immunoreactive elements are compared with those established by immunogold labelled FMRFamide-containing profiles in the heart and salivary gland. These latter display similarities in forming the different kinds of intercellular contacts, and differences in the morphological variability of the content of granules in the immunolabeled profiles. The results suggest diverse, non-synaptic modulatory roles of neuropeptides in the peripheral nervous system of Helix pomatia, including localized membrane effects and neurohormonal-like remote global controls, that may also be of significance in orchestrating the effects of neuropeptides released at the same time on different targets.

Animals↗

Hindbrain floor plate of the rat: ultrastructural changes occurring during development.

Most of the molecular and experimental studies on the floor plate (FP) have been performed on the FP region extending along the spinal cord. However, little is known about the hindbrain FP. The FP undergoes regional and temporal changes throughout development, but information with respect to the ultrastructural correlate of such changes is missing. The present investigation was focused on the ultrastructural developmental changes occurring in the FP of the rat hindbrain. The FP cells of the hindbrain secrete a material reacting with antibodies against the secretory glycoproteins of the subcommissural organ (AFRU). This antibody was used to perform an ultrastructural immunocytochemical analysis of the rat FP. From E-12 on, there is a progressive increase in the development of the rough endoplasmic reticulum (RER), so that by E-18, it has reached a high degree of hypertrophy. A unique feature of the hindbrain FP cells is the presence of tubular formations and 140-nm vesicles that appear to originate from RER cisternae. The labelling of these two structures with AFRU and Concanavalin A strongly suggests that they are pre-Golgi compartments containing secretory material. Since these structures are present in the basal process and in the apical cell pole of the FP cells, the possibility that they release their content at these sites, is discussed. It is proposed that a secretory mechanism bypassing the Golgi apparatus (constitutive secretion?) operates in the FP cells. The presence of apoptotic cells within the FP of E-20 embryos and newborns suggests that death, and not re-differentiation, is the fate of the FP cells.

Animals↗

The ultrastructure of osteosarcoma. A review of twenty cases.

The ultrastructural features of 20 cases of osteosarcoma are discussed. Characteristically, the malignant cells (osteoblasts) contained large quantities of dilated, anastomosing rough endoplasmic reticulum, ofter forming large lakes. Mitochondria were sparse. Similar features are seen in osteoblasts in normal developing bone. Marked ultrastructural similarities of cells from chondrosarcomatous, fibrosarcomatous and typical osteosarcomatous areas of these tumors strongly supports the concept that these neoplastic cells all arise from the same progenitor cell. Malignant giant cells were readily differentiated from benign osteoclasts. The most significant ultrastructural findings were the varying degrees of calcification in the intercellular areas (osteoid), ranging from an extensive dense deposition of hydroxyapatite crystals which obscured the underlying collagen fibers, to focal collectors, or puffs, of slender needle-shaped hydroxyapatite crystals deposited on or along collagen fibers. The earliest apparent evidence of calcification was the presence of small electron-dense particles on or in collagen fibers.

Adolescent↗

An ultrastructural and histochemical study of the mucous membrane adjacent to and remote from carcinoma of the colon.

The material was taken from surgical specimens of large intestine resected for carcinoma. A parallel study by electron microscopy and mucin histochemistry was made on fragments from "transitional" (TR) mucosa (adjacent to carcinoma) and "normal" (N) mucosa (remote from the tumor). These were compared with similar studies on the mucosa from control individuals. Histochemically, the "TR" mucosa shows an increase in sialomucins as compared with the "N" and control mucosae, where sulphomucins normally predominate. At the ultrastructural level, the "TR" mucosa is characterized by the following changes which may precede the histochemical variations: A) alteration in the relative proportions of the different cell types, along the crypt, with a persistence of immature and intermediate cells at higher levels of the crypt than in the control. Mature absorptive cells are fewer and bear an inverse relationship to intermediate cells. Goblet cells are increased in number and size. B) Appearance of electron-dense bodies 0.15-0.3mum in in diameter and membrane limited. C) An elaborated and enlarged Golgi zone showing increased secretory activity. It is suggested that mucin and ultrastructural changes described in the "TR" zone may indicate a failure in the normal process of cell differentiation along the crypt. Previous work7,8 further suggests that the mucin changes may be primary, reflecting a cellular response to unknown stimuli (i.e., carcinogens) rather than a local secondary effect of tumor growth. As for the ultrastructural features in the "TR" mucosa, the secondary effect cannot be excluded at the present.

Carcinoma↗

Ultrastructural characteristics of sinus histiocytic reaction in lymph nodes draining various stages of breast cancer.

An ultrastructural study of sinus histiocytosis (SH) in axillary lymph nodes was undertaken in 20 patients with primary cancer of the breast. The lymph node responses were first classified by means of light microscopy, according to previously established criteria. The ultrastructural findings established three major patterns of SH response in cancer-draining lymph nodes: developing SH, positive SH, and degenerative SH. These patterns followed closely the classification obtained by light microscopy. An important finding of electron microscopy was the presence of early activation of histiocytes (developing SH) in microscopy (negative SH). The striking ultrastructural resemblance of histiocytes in positive SH to epithelioid cells seen in delayed hypersensitivity reactions (TB) again points to the fact that the positive SH pattern represents a tumor-host reaction of the delayed hypersensitivity type. Finally, although the presence of virus has been shown to play a role in spontaneous BALB/c murine breast tumor, no virions could be found in human cancer-draining lymph nodes.

Axilla↗

Yolk sac carcinoma (endodermal sinus tumor): ultrastructure and histogenesis of gonadal and extragonadal tumors in comparison with normal human yolk sac.

Human yolk sac carcinomas have been studied only twice with the electron microscope, and have never been compared at this level with normal human yolk sac. In the present study, the ultrastructural features of three primary ovarian yolk sac carcinomas, omental metastases from one of these, and a primary retroperitoneal yolk sac carcinoma in a male are reported, as are the ultrastructural findings in human yolk sac from normal 7- and 12-week gestations. The most prominent feature of the tumors is the presence of voluminous basement membrane material (the nature of which is confirmed by indirect enzyme-labeled antibody technique in one case) in both intra-and extracellular location, corresponding to the PAS-positive hyaline globules seen in these tumors by light microscopy. The tumor cells are also demonstrated to produce this material in tussue culture. Although basement membrane has not been described previously in normal human yolk sac at 8 and 10 weeks' gestation, it was present in the 7-week specimen which we studied, suggesting that its production may be a feature of only very young sac. Other ultrastructural findings are also similar in human yolk sac carcinoma, normal human yolk sac, and rodent yolk sac and yolk sac carcinomas. Thus, these studies confirm the suggested germ cell-derived yolk sac origin of the human tumor.

Adult↗