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Follicular dendritic cell sarcoma of the breast.

Extranodal follicular dendritic cell sarcoma (FDCS) is an extremely uncommon tumor with only a single case arising in the breast having been reported. We describe the clinico-pathological features of an additional FDCS of the lower outer quadrant of the right breast in a 40-year-old woman. The tumor showed three patterns of growth, i.e., diffuse, myxoid and fascicular. The neoplastic cells were large, polygonal, with a slightly eosinophilic cytoplasm and oval or convoluted nuclei. They were intermingled with small lymphocytes, plasma cells and a few bizarre multinucleated giant cells. In the fascicular areas, the cells were spindled, while in the myxoid areas they showed a dendritic-like appearance, with long cytoplasmic processes. Mitoses were numerous and often atypical. The neoplastic cells were intensely immunoreactive for CD21, S-100 protein and epithelial membrane antigen, and focally for CD35, CD68 and cytokeratins. Polymerase chain reaction analysis did not reveal any Epstein Barr virus genome in the neoplastic tissue. Electron microscopy highlighted numerous interdigitating cytoplasmic processes with intercellular junctions of the serrated, immature desmosomal or undifferentiated types. The post-surgical course of the patient was uneventful and she is currently free of disease 19 months after surgery.

Adult↗

Spindle cell myoepithelial tumours of the parotid gland with extensive lipomatous metaplasia. A report of four cases with immunohistochemical and ultrastructural findings.

We report four cases of parotid gland tumours composed predominantly of spindle-shaped myoepithelial cells and mature adipocytes. The central portion of one tumour showed extensive adipose differentiation, whereas in the peripheral parts there were small foci of ductal epithelium arranged in cords and tubules within an abundant myxoid stroma. The other cases were adipose spindle cell myoepitheliomas without an obvious glandular component. Under high-power examination, a transition between modified spindle-shaped myoepithelial cells and adipocytes was observed, and this was confirmed with immunohistochemistry. Ultrastructurally, the modified myoepithelial cells showed intracytoplasmic tonofilaments, bundles of actin microfilaments and lipid droplets. A possible pathogenesis is proposed of true metaplastic transformation of myoepithelial cells to adipocytes. This lesion is important to identify correctly, as inadequate surgery can lead to recurrence.

Adenoma, Pleomorphic↗

Do Blastocystis hominis colony forms undergo programmed cell death?

Ultrastructural observations were made on colony forms of the protozoan parasite, Blastocystis hominis. Cross-sections of entire colonies were observed by TEM. Cells within a colony were heterogeneous in morphology, consisting of vacuolar, amoeboid, multivacuolar and unusual forms. Dying cells appeared to be in the process of fragmenting into numerous membranebound vesicles, giving rise to empty spaces within the colony. Interestingly, older colonies appeared to show cell fragmentation which resulted in larger, membranebound structures. Numerous cytoplasmic inclusions were present in the central vacuole of some cells, with many containing mitochondria. Amoeboid forms were observed to harbour small membrane-bound vesicles in endosome-like compartments. Other unusual features included margination of chromatin material and distinct blebbing of nuclei. These ultrastructural features suggest that B. hominis colony forms perhaps undergo a form of programmed cell death.

Animals↗

Undifferentiated embryonal sarcoma with unusual features arising within mesenchymal hamartoma of the liver: report of a case and review of the literature.

Undifferentiated embryonal sarcoma (UES) is a rare and highly malignant hepatic neoplasm, affecting almost exclusively the pediatric population. It has replaced malignant mesenchymoma, under which diagnostic term the first three cases were described. A link between embryonal sarcoma and mesenchymal hamartoma of the liver (MHL) has long been proposed, because of clinicopathologic overlaps of these entities; however, until recently, this association remained tenuous. Cases of UES arising in a background of mesenchymal hamartoma of the liver have previously been reported in two teenage girls. Discovery of a similar genetic abnormality in MHL and UES has clinched the supposed link between them. There have also been two reports of UES with prominent cystification, one associated with peripheral eosinophilia, and thereby masquerading as hydatid cyst of the liver. We report a case of UES arising in a young boy with MHL, with unusual histologic features, including large mesothelial-lined cysts and ectopic adrenal cortical tissue under Glisson's capsule.

Antineoplastic Combined Chemotherapy Protocols↗

Flavonol ring B-specific O-glucosyltransferases: purification, production of polyclonal antibodies, and immunolocalization.

UDP-glucose: flavonol 2'- and 5'-O-glucosyltransferases (E.C.2.4.1.-) from leaves of Chrysosplenium americanum were copurified to apparent homogeneity by successive chromatography on Sephacryl S-200, UDP-glucuronic acid-agarose, Mono P, Superose 12, and Mono Q columns. Both enzymes have similar properties except for their substrate specificity and stability (J. Chromatogr. 388, 235, 1987). The purified protein was used as the source of antigen to produce polyclonal antibodies in rabbits. In situ localization of the O-glucosyltransferases was studied by applying a postembedding immunogold labeling technique on ultrathin sections of Lowicryl K4M- and LR White-embedded tissues. Postfixation with osmium tetroxide followed by embedding in LR White resulted in good preservation of membrane ultrastructure, although protein antigenicity was greatly reduced. Leaf sections embedded in Lowicryl K4M had an extracted appearance; however, they retained a high degree of protein antigenicity revealing the deposition of gold particles in the periplasmic region of cells. Considering the compromise chosen in this study to retain antigenicity over preservation of membrane ultrastructure, the results suggest that the "easily solubilized" O-glucosyltransferases of C. americanum may actually be associated with vesicle-like structures and cytoplasmic membranes.

Antibody Formation↗

Ionic coupling and mitotic synchrony of siblings in a Drosophila cell line.

Following mitosis in many cell lines, siblings remain adjoined in dyads until further cell division. We report here a series of experiments designed to ascertain the nature of this apposition in the embryonic Kc cell line of Drosophila melanogaster. We have found that (1) cell division in siblings is highly synchronized when compared to that in nonsiblings: (2) siblings in dyads are dye coupled with respect to Lucifer Yellow, but intercellular diffusion of larger molecules (FITC-dextran at 6 and 24 kDa) is retarded: (3) siblings are electrically coupled by an ungated low-resistance intercellular connection which is resistant to treatment with octanol and CO2, both known to close gap junction channels: and (4) members of a dyad are joined by a cytoplasmic bridge. Structures resembling septate junctions are also found between siblings and between cells in aggregates. The evidence accumulated here suggests that cytokinesis in Kc dyads is incomplete, resulting in an intercellular pathway that may provide for the passage of a molecular or electrical signal that regulates subsequent mitosis.

Animals↗

Immunohistochemical characterization, distribution, and ultrastructure of lymphocytes bearing T-cell receptor gamma/delta in inflammatory bowel disease.

Phenotypic characterization and distribution of gamma/delta T lymphocytes in the intestinal mucosa were investigated in ulcerative colitis and Crohn's disease by immunohistochemistry. The ratio of delta(+) cells to CD3(+) cells in the intraepithelial space of colon was decreased in Crohn's disease (13%) and strikingly decreased in ulcerative colitis (8%) compared with the control (36%). Delta(+) cells in the lamina propria were also decreased, particularly in the distal ileum of Crohn's disease (4%), compared with the control (15%). On the contrary, the cells gathered at the severe inflammatory sites with other inflammatory cells, including beta(+) cells, and were densely distributed in the T-cell zone around lymphoid follicles. Phenotypic characterization showed that delta(+) lamina proprial lymphocytes of colon were mainly CD4(-)CD8(-) in the control (80%) and Crohn's disease (59%). However, in ulcerative colitis, CD4(-)CD8(-) delta(+) lymphocytes were rarely found (3%). This reflects the difference of immunologic background between the two diseases. Immunoelectron microscopically, these cells in inflammatory bowel disease were rich with vesicular structures in cytoplasms, whereas those in the control group contained electron-opaque granules. The decrease and the morphological change may be closely related to the weakness of mucosal defense.

Adult↗

Binding of [125I]concanavalin A by interspecific amoeba hybrids.

Two types of interspecific amoeba hybrids, viz. PnIc (Amoeba proteus nucleus in A. indica cytoplasm) and InPc (A. indica nucleus in A. proteus cytoplasm), were tested for their [125I]Concanavalin A (Con A) binding activity at different periods of time. The cell surface binding of the labelled Con A was reduced to approx. 40 and 75% in the PnIc and InPc cells, respectively, 96 h after the cells were made hybrids. A significant increase in the binding of radioactive Con A was observed after the homologous nucleus was back transferred into InPc cells, but not in PnIc cells. No significant difference in the binding of the radioactive Con A was found between the progeny of the hybrid amoebae and the control amoebae. The Con A binding activity of the interspecific amoebae has been discussed in relation to the changes in the cytoplasmic membrane structures which presumably play a role in the formation of cell surface in the amoebae.

Amoeba↗

Novel activin receptors: distinct genes and alternative mRNA splicing generate a repertoire of serine/threonine kinase receptors.

We have cloned ActR-IIB, which encodes four new activin receptor isoforms belonging to the protein serine/threonine kinase receptor family. Two of the ActR-IIB isoforms have higher affinity for activin A than the previously cloned activin receptor and differ from each other by the inclusion of an alternatively spliced segment in the cytoplasmic juxtamembrane region. A second alternative splicing event generates two additional receptor isoforms that lack a proline cluster in the external juxtamembrane region and have lower affinity for activin A. All isoforms bind inhibin A with low affinity. Thus, the repertoire of activin receptors includes species that differ in ligand binding affinity, cytoplasmic domain structure, or both. This receptor heterogeneity might underlie the sharply different responses that activin can elicit in a dose- or cell-specific manner.

3T3 Cells↗

In vitro aggregation of syncytia and cells of a Hexactinellida sponge.

Membrane recognition has been analyzed by studying the reaggregation of syncytia and cells dissociated from the tissues of the sponge Rhabdocalyptus dawsoni. Four obvious features are recognized. 1) There is true morphogenesis, led by the syncytia, which gives rise to compact, often very large (O.5 cm) aggregation bodies. Each body is a giant macrophagic syncytium surrounding groups of discrete undifferentiated cells. 2) Special coupling structures, the cytoplasmic perforate septa, establish communication between all body compartments, both syncytial and cellular. The whole aggregate can, therefore, be compared to one vast multinucleated cell. 3) During in vitro aggregation, membrane recognition processes permit different syncytia and cells to fuse, and internal compartmentalization is then achieved by the cytoplasmic septa. 4) Fragments of the flagellated choanosome, which is characteristic of sponges, are internalized by the syncytia. Following the collapse of the aggregate they degenerate. The survival of the body appears to depend on skeleton formation.

Animals↗

Nonerythroid spectrin (fodrin) is a prominent component of the cochlear hair cells.

We studied the distribution of nonerythroid spectrin, fodrin, in surface preparations and cryosections of the cochlear hair cells as well as isolated hair cells of the guinea pig by using a monoclonal antibody (Mab) reacting with Mr 240 kD alpha-fodrin polypeptide. The Mab gave a strong reaction with the cuticular plate of both the inner and outer hair cells (IHCs and OHCs). Stereocilia were nonreactive and only a weak cell surface reaction was seen in the supporting cells. In the outer hair cells the upper turns of the cochlea, fodrin was observed in a cytoplasmic spiralling structure extending from the cuticular plate towards the cell nucleus. Some labelling was also seen along the cell surface membrane and in the synaptic region. The results suggest that fodrin may be an important constituent in the active processes of hair cells such as cell motility and/or signal transduction.

Animals↗

Effects of surface-active agents on drug susceptibility levels and ultrastructure of Mycobacterium avium complex organisms isolated from AIDS patients.

The multiple-drug-resistance property of Mycobacterium avium complex (MAC) is mainly attributed to a cell envelope permeability barrier. MAC treated with subinhibitory levels of dimethyl sulfoxide (DMSO) and ethylenediaminetetraacetic acid (disodium salt) (EDTA) did not have altered minimum inhibitory concentration (MIC) levels or show ultrastructural changes; the effect of sodium dodecyl sulfate (SDS) was variable. With SDS, the visualization of the nucleoid and ribosomes decreased, and amorphous electron-dense material accumulated near the structurally altered cytoplasmic membrane and cell wall. Use of 0.005% Tween-80 resulted in a 2-4-fold reduction in MIC in the case of rifampicin, ansamycin (LM 427), cephapirin, and ciprofloxacin. Tween-80 treated cells were swollen, and deposits of low electron-density accumulated in the cytoplasm; distortions in the outer-cell integuments were observed. These findings are consistent with the idea that Tween-80 increases cell-envelope permeability, thereby enhancing drug penetrability and reducing MIC levels. Because of the action of Tween-80, its use in drug-susceptibility media or diluent fluids should be avoided.

Acquired Immunodeficiency Syndrome↗

Mechanism of multidrug resistance in human tumour cell lines and complete reversion of cellular resistance.

The biochemical basis of the multidrug-resistant (MDR) phenotype has been investigated in drug-resistant sublines derived from LoVo and SW984 human colon carcinoma cell lines by doxorubicin selection. Besides drug extrusion through the plasma membrane, two further observations, both ascribable to the drug transport property of the gp170 glycoprotein, were made. First drug deposition into cytoplasmic membranous structures which allows cells to tolerate a high intracellular drug concentration since it prevents drugs from reaching their cellular target site(s). Secondly drug removal from the complexes formed by interaction of drug with target cellular macromolecules, a phenomenon which extends its an effect that continues after treatment and appears to be the most important resistance mechanism in MDR cells. Treatments based on the gp170 inhibitory property of verapamil were developed that allowed abrogation of resistance in MDR cell lines, a strategy that may be applicable to therapy treatments.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Histochemical localization of complex carbohydrates in the nasolabial glands of the Japanese deer (Cervus nippon yakushimae).

The localization of complex glycoconjugates in the nasolabial glands of the Japanese deer (C. nippon yakushimae) was studied using various histochemical methods, including lectin histochemistry, viewed using both light and electron microscopy. The secretory epithelium and luminal secretion of the deer nasolabial glands exhibited neutral and acidic glycoconjugates with different saccharide residues (alpha-D-mannose, alpha-N-acetyl-D-galactosamine, beta-D-galactose, beta-N-acetyl-D-glucosamine and sialic acid). Additionally, O-acetylated sialic acids were detectable in the glandular acini. The results obtained are discussed with regard to the specific functions of the glandular secretion, which may particularly improve water retention on the skin surface and protect against physical damage as well as microbial contamination. Furthermore, our results support the view of a salivary nature of this gland type.

Animals↗

Basal cell adenoma-an unusual presentation.

Basal cell adenoma is an uncommon epithelial neoplasm of the salivary gland most commonly arising in the parotid glands. We report a case of basal cell adenoma of the minor salivary gland presenting as a slowly progressing, large parapharyngeal mass. Histopathology revealed a well-encapsulated mass with characteristic histomorphology. Immunohistochemistry showed selective positivity for pancytokeratin, S-100, and smooth muscle actin in the tumor which highlighted the participation of myoepithelial cells in histogenesis. In addition, positivity was noted for carcinoembryonic antigen and vimentin. Ultrastructural analysis showed characteristic features including reduplicated basal laminae around the tumor cells, presence of intermediary filaments, and rough endoplasmic reticulum in the cytoplasm. There are no reports of basal cell adenoma presenting as a parapharyngeal mass lesion in the available English literature. This case highlights the rarity of this tumor with regard to its site of origin, possibly from a minor salivary gland.

Actins↗

Heat shock protein 70 is translocated to lipid droplets in rat adipocytes upon heat stimulation.

In mammalian cells, lipid storage droplets contain a triacylglycerol and cholesterol ester core surrounded by a phospholipid monolayer into which a number of proteins are imbedded. These proteins are thought to be involved in modulating the formation and metabolic functions of the lipid droplet. In this study, we show that heat stress upregulates several heat shock proteins (Hsps), including Hsp27, Hsp60, Hsp70, Hsp90, and Grp78, in primary and differentiated adipocytes. Immunostaining and immunoblotting data indicate that among the Hsps examined, only Hsp70 is induced to redirect to the lipid droplet surface in heat-stressed adipocytes. The thermal induction of Hsp70 translocation to lipid droplet does not typically happen in a temperature- or time-dependent manner and occurs abruptly at 30-40 min and rapidly achieves a steady state within 60 min after 40 degrees C stress of adipocytes. Though Hsp70 is co-localized with perilipin on the lipid droplets in stressed adipocytes, immunoprecipitation experiments suggest that Hsp70 does not directly interact with perilipin. Alkaline treatments indicate that Hsp70 associates with the droplet surface through non-hydrophobic interactions. We speculate that Hsp70 might noncovalently associate with monolayer microdomains of the lipid droplet in a manner similar to its interaction with lipid bilayer moieties composed of specific fatty acids. As an acute and specific cellular response to the heat stimulation, accumulation of Hsp70 on adipocytes lipid droplets might be involved in stabilizing the droplet monolayer, transferring nascent proteins to the lipid droplets, or chaperoning denatured proteins on the droplet for subsequent refolding.

Adipocytes↗

Reduction of SNAP25 in acid secretion defect of Foxl1-/- gastric parietal cells.

Foxl1 is a winged helix transcription factor expressed in the mesenchyme of the gastrointestinal tract. In the absence of Foxl1, parietal cells fail to secrete gastric acid in response to various secretagogue stimuli including cAMP. A marked decrease in H+,K(+)-ATPase expression was observed even though a substantial number of parietal cells still existed in Foxl1-deficient mice. Ultrastructural analysis suggested that the gastric acid secretion defect in Foxl1-deficient mice is mainly due to impairment in the fusion of cytoplasmic tubulovesicular structures to the apical canalicular plasma membrane. Among the molecules involved in the membrane fusion event, only SNAP25 showed a significant decrease in mRNA expression, which likely caused the impairment in acid secretion from parietal cells in Foxl1-deficient mice, with the reduction in H+,K(+)-ATPase expression contributing to additional effect.

Animals↗