High-grade mucoepidermoid carcinoma of the breast. Fine needle aspiration cytology and clinicopathologic study of a case

A primary high-grade mucoepidermoid carcinoma of the breast was evaluated preoperatively by fine needle aspiration (FNA) cytology in a 72-year-old woman. The smears showed a mixed pattern consisting of clusters of poorly differentiated squamous cells, keratinized squamous cells and vacuolated mucin-secreting cells. The subsequent mastectomy specimen showed a tumor with the features of a high-grade mucoepidermoid carcinoma. Electron microscopy confirmed the diagnosis, reflecting the epidermoid and glandular differentiation of the tumor. The course was rapidly fatal, and the patient died a few months after presentation. A review of the literature indicated that mucoepidermoid carcinoma of the breast is a very rare neoplasm; the FNA cytologic features described in this report may constitute a basis to preoperatively recognize this tumor.     

Abscisic acid and mefluidide in the regulation of cold hardiness development in Solanum tuberosum L. potato

Plants of Solanum tuberosum L. potato do not cold acclimate when exposed to low temperature such as 5°C, day/night. When ABA (45 M) was added to the culture medium, stem-cultured plantlets of S. tuberosum, cv. Red Pontiac, either grown at 20°C/15°C, day/night, or at 5°C, increased in cold hardiness from –2°C (killing temperature) to –4.5°C. The increase in cold hardiness could be inhibited in both temperature regimes if cycloheximide (70 M) was added to the culture medium at the inception of ABA treatment. Cycloheximide did not inhibit cold hardiness development, however, when it was added to the culture medium 3 days after ABA treatment.When pot-grown plants were foliar sprayed with mefluidide (50 M), ABA content increased from 10 nmol to 30 nmol g^–1 dry weight and plants increased in cold hardiness from –2°C to about –3.5°C. The increases in free ABA and cold hardiness occurred only in plants grown at 20°C/15°C; neither ABA nor cold hardiness increased in plants grown at 5°C.The results suggest that an increase in ABA and a subsequent de novo synthesis of proteins are required for the development of cold hardiness in S. tuberosum regardless of temperature regime, and that the inability to synthesize ABA at low temperature, rather than protein synthesis, appears to be the reason why S. tuberosum does not cold acclimate.     

The control of Ca2+ homeostasis: role of intracellular rapidly exchanging Ca2+ stores.

The role of rapidly exchanging intracellular Ca²⁺ stores in the control of Ca²⁺ homeostasis is reviewed. The following issues are discussed: the reasons why such stores exist in eukaryotic cells; the differences between the terminal cisternae of the skeletal muscle sarcoplasmic reticulum, which have direct, physical connection with the T tubules of the plasmalemma, and the Ca²⁺ stores located in the depth of the cytoplasm, which are stimulated by second messengers; the cytological nature (subcompartments of the ER) of the rapidly exchanging Ca²⁺ stores and their functional significance. The conclusions introduce recent developments in which intracellular Ca²⁺ stores have been investigated also by molecular biology techniques.     

High-resolution solution structure of two members of a conformationally homogeneous combinatorial peptide library based on the classical zinc-finger motif

Summary We describe the high-resolution structure by NMR of two peptides that belong to a combinatorial library based on the zinc-finger motif. The library represents, to the best of our knowledge, the first example of a conformationally homogeneous peptide library and was obtained by introducing random residues in five positions of the -helical portion of a 26-residue consensus peptide (CP1) belonging to the Cys²-Hys² zinc-finger family. The result was shown to be a highly homogeneous -helical library (Bianchi et al., 1995). The structures of the parent compound (CP1) and of a representative member (CP1m) that was selected by screening the library with a monoclonal antibody are compared in detail as an example of the very high stability of the zinc-finger scaffold upon sequence variability. The two peptides exhibit an extremely high degree of structural similarity. The use of this type of conformationally constrained combinatorial library might represent a step forward in the design of peptidomimetics, as it considerably accelerates the process of the identification of the spatial relationship among the pharmacophoric groups.Abbreviations t-Bu tert-butyloxycarbonyl - Fmoc 9-fluorenylmethoxycarbonyl     

Preferred conformation of peptides rich in Ac8c,a medium-ring alicyclic Cα,α-disubstituted glycine

A complete series of terminally blocked, monodispersed homo-oligopeptides (to the pentamer level) from the sterically demanding, medium-ring alicyclic C^α,α-disubstituted glycine 1-aminocyclooctane-1-carb oxylic acid (Ac₈c), and two Ala/Ac₈c tripeptides, were synthesized by solution methods and fully characterized. The preferred conformation of all the oligopeptides was determined in deuterochloroform solution by IR absorption and ¹H-NMR. The molecular structures of the amino acid derivative Z-Ac₈c-OH, the dipeptide pBrBz- (Ac₈c)₂-OH and the tripeptide pBrBz-(Ac₈c)₃-OtBu were assessed in the crystal state by X-ray diffraction. Conformational energy computations were performed on the monopeptide Ac-Ac₈c-NHMe. Taken together, the results obtained strongly support the view that the Ac₈c residue is an effective β-turn and helix former. A comparison is also made with the conformational preferences of α-aminoisobutyric acid, the prototype of C^{α, α}-disubstituted glycines, and of the other members of the family of 1-aminocycloalkane-1-carboxylic acids (Ac_nc, with n=3, 5–7) investigated so far. The implications for the use of the Ac₈c residue in peptide conformational design are considered.     

The beta subunit of E. coli glycyl-tRNA synthetase plays a major role in tRNA recognition.

The contributions made by the alpha and beta subunits of E. coli glycyl-tRNA synthetase to the recognition of tRNA have been investigated via binding and immunological methods. Using the nitrocellulose filter assay, we have shown that isolated beta subunit, but not the alpha subunit, binds [14C]glycyl-tRNA with an affinity comparable to that of the native enzyme. Further, the data indicate that the beta subunit possesses one binding site for glycyl-tRNA while the native or reconstituted enzyme (alpha 2 beta 2) has two sites. Rabbit antibodies directed at the beta subunit or the holoenzyme inhibit efficiently the ability of the enzyme to aminoacylate tRNA while alpha-subunit antibodies have a smaller effect. Since none of the antisera have an appreciable effect on the ATP-PPi exchange activity of the enzyme under these conditions, the beta-subunit (and holoenzyme) antisera evidently interfere with productive tRNA binding. Taken together, the data indicate that the larger, beta subunit of glycyl-tRNA synthetase plays a major role in tRNA recognition.     

Primary multilobated T-cell lymphoma of the breast diagnosed by fine needle aspiration cytology and immunocytochemistry

The fine needle aspiration (FNA) cytologic, immunocytochemical and ultrastructural findings of a primary multilobated T-cell lymphoma arising in the breast of a 61-year-old woman are described. Large pleomorphic multilobated malignant cells were primarily identified as lymphomatous in origin and phenotypically as T-cells by a selected panel of monoclonal antibodies applied to the original smears obtained by FNA biopsy. This appears to be the second report of a multilobated lymphoma arising in the breast and the first with a T-cell phenotype in this anatomic site.     

Attenuation of pulmonary and systemic vasoconstriction with pentoxifylline and aminophylline

The effects of acute administration of therapeutic doses (1-10 mg/kg) of pentoxifylline and aminophylline on the resistance of the systemic and pulmonary circuits in anaesthetized dogs and pigs were tested. During room air breathing, neither of the two substances caused a significant change in systemic vascular resistance (SVR) or pulmonary vascular resistance (PVR). During hypoxia (10% O2 and nitrogen), however, both substances caused a significant reduction in PVR (p less than 0.05) without affecting SVR. The largest dose of pentoxifylline decreased PVR from 7.8 +/- 2.8 to 4.4 +/- 1.5 in dogs and from 9.9 +/- 1.4 to 5.8 +/- 0.6 mmHg.L-1.min in pigs. Aminophylline was equally effective and selective in lowering PVR but not SVR during hypoxia. When SVR was elevated in dogs by continuous infusion of angiotensin, pentoxifylline lowered SVR from 139 +/- 27 to 83 +/- 20 mmHg.L-1.min (p less than 0.05). The simultaneous small elevation in PVR during angiotensin infusion was also attenuated to base-line value by pentoxifylline injection. These results suggest that xanthines, in therapeutic doses, can have a profound vasodilator effect on either the systemic or on the pulmonary circuit, only wherever the vessels are constricted. The vasodilatory effect of pentoxifylline is viewed as a second beneficial effect besides the benefit derived from its action on erythrocyte deformability.     

A novel cross-shear metric for application in computer simulation of ultra-high molecular weight polyethylene wear

Wear testing of polyethylene in total joint replacements is common and required for any new device. Computational wear modelling has obvious utility in this context as it can be conducted with much greater economy than physical testing. Archard's law has become the accepted standard for wear simulation in total joints but it does not account for cross-shear, which is known to increase wear significantly relative to unidirectional sliding. The purpose of this study was to develop a robust cross-shear model applicable to any interface geometry under any kinematic conditions. The proposed metric, x ^*, is distinguished from existing cross-shear models by the fact that it measures cross-path motion incrementally throughout a motion cycle and quantifies cross-shear based on incremental changes in sliding direction. Validation showed strong support for the predictive capability of x ^* when applied to pin-on-disc test data.