Macrofollicular encapsulated variant of papillary thyroid carcinoma as a potential pitfall in histologic and cytologic diagnosis. A report of three cases

BACKGROUND: Macrofollicular encapsulated papillary carcinoma (MEPC) is a variant of papillary carcinoma with a favorable clinical course. Its characteristic histologic pattern could be mistaken for that of an adenoma or hyperplastic nodule. Fine needle aspiration of this neoplasm may not show the particular nuclear features of papillary carcinoma, so the cytologic diagnosis may be benign. CASE REPORTS: Three paradigmatic cases of MEPC with different histologic patterns, diagnosed as a follicular neoplasm using fine needle aspiration biopsy (FNAB) are described. Preoperative cytology showed scattered clusters of thyrocytes with prominent nuclear pleomorphism and irregularities and focal oxyphilic changes mixed with colloid and aggregates of typical thyrocytes. The histologic picture exhibits small, neoplastic foci showing a microfollicular structure within an encapsulated neoplasm with a macrofollicular pattern. In microfollicular areas obvious nuclear pseudoinclusions were seldom observed. CONCLUSION: MEPC represents a challenging tumor subtype that infrequently shows the pathognomonic cytologic characteristics of papillary carcinoma, and therefore it is much more difficult to diagnose with a FNAB. Nuclear pleomorphism and irregularity of the nuclear membrane of thyrocytes are clues to this variant, although in some cases a clear-cut preoperative diagnosis cannot be made.     

Apple 1-aminocyclopropane-1-carboxylate synthase in complex with the inhibitor L-aminoethoxyvinylglycine. Evidence for a ketimine intermediate

The 1.6-A crystal structure of the covalent ketimine complex of apple 1-aminocyclopropane-1-carboxylate (ACC) synthase with the potent inhibitor l-aminoethoxyvinylglycine (AVG) is described. ACC synthase catalyzes the committed step in the biosynthesis of ethylene, a plant hormone that is responsible for the initiation of fruit ripening and for regulating many other developmental processes. AVG is widely used in plant physiology studies to inhibit the activity of ACC synthase. The structural assignment is supported by the fact that the complex absorbs maximally at 341 nm. These results are not in accord with the recently reported crystal structure of the tomato ACC synthase AVG complex, which claims that the inhibitor only associates noncovalently. The rate constant for the association of AVG with apple ACC synthase was determined by stopped-flow spectrophotometry (2.1 x 10(5) m(-1) s(-1)) and by the rate of loss of enzyme activity (1.1 x 10(5) m(-1) s(-1)). The dissociation rate constant determined by activity recovery is 2.4 x 10(-6) s(-1). Thus, the calculated K(d) value is 10-20 pm.     

Flavonoid glycosides from Centaurea pseudoscabiosa subsp. pseudoscabiosa from Turkey

Three flavonoid glycosides were isolated and characterized, together with a further 13 substances belonging to various classes of compounds, in particular two phenolic acids, a coumarin, a sugar and nine flavonoids from the flowered aerial parts of Centaurea pseudoscabiosa subsp. pseudoscabiosa Boiss. et Buhse (Asteraceae). Some considerations about their evolutionary meaning are provided.     

PIP(2)-PDZ domain binding controls the association of syntenin with the plasma membrane

PDZ proteins organize multiprotein signaling complexes. According to current views, PDZ domains engage in protein-protein interactions. Here we show that the PDZ domains of several proteins bind phosphatidylinositol 4,5-bisphosphate (PIP(2)). High-affinity binding of syntenin to PIP(2)-containing lipid layers requires both PDZ domains of this protein. Competition and mutagenesis experiments reveal that the protein and the PIP(2) binding sites in the PDZ domains overlap. Overlay assays indicate that the two PDZ domains of syntenin cooperate in binding to cognate peptides and PIP(2). Experiments on living cells demonstrate PIP(2)-dependent and peptide-dependent modes of plasma membrane association of the PDZ domains of syntenin. These observations suggest that local changes in phosphoinositide concentration control the association of PDZ proteins with their target receptors at the plasma membrane.     

DNA-based methods for the detection and the identification of phytoplasmas in insect vector extracts

DNA extraction and storage methods have been evaluated with laboratory-reared leafhoppers and/or field-collected leafhoppers and psyllids. Detection of four different phytopathogenic phytoplasmas, belonging to three taxonomic groups, has been achieved by several direct or nested polymerase chain reaction (PCR) methods with such DNA extracts. Reactions differed in both the 16/23S ribosomal primer pairs used and the specific assay and cycling conditions. Merits and possible hindrances of the various primer pairs, in relation to insect DNA extracts, are discussed. However, identification of the phytoplasma(s) necessarily relied on comparison of the polymorphism in length of the amplified DNA fragments obtained by restriction with appropriate endonucleases. Endonuclease digestion is crucial for determining the identity (subgroup affiliation) of phytoplasmas of the same groups that can be carried by an individual vector.     

Cultivation of Mycobacterium bovis BCG in bioreactors

The Mycobacterium bovis BCG vaccine for commercial use is classically produced as surface pellicles by culture on synthetic medium. Under these conditions, reproducibility of the cultures and quality assessment are hampered by slow growth of the bacilli, the formation of bacterial aggregates and a high proportion of dead bacilli after processing and final formulation of the vaccine. Here, we established dispersed cultures of M. bovis BCG in synthetic media in small-scale bioreactors. These cultures allow recording and adjusting of culture parameters and give rise to single bacilli with a high degree of live bacteria. In the murine model, bioreactor-grown M. bovis BCG exhibited slightly stronger replication and persistence than the vaccine produced under the classical conditions. The protective efficacy against challenge with M. tuberculosis was identical for both vaccine preparations.     

Antitumor vaccines: is it possible to prevent a tumor?

The main medical use of vaccines is to induce a state of immunity in healthy individuals to protect them from deadly or dangerous diseases. In the field of cancer immunology, however, vaccines are being used in patients as therapy, often with a very poor success rate against advanced disease. This paper reviews recent preclinical evidence in favor of the prophylactic use of immunological approaches to cancer. Successful attempts at immunological cancer prevention in HER-2/neu transgenic mice are described as an example. The specific properties of the HER-2/neu gene product as a tumor antigen, and the nature of the immune responses induced by effective preventive treatments are reviewed. Although the very high rate of mammary carcinoma prevention in mice has generated enthusiasm, it should not be forgotten that such treatments, when administered to healthy humans at risk of cancer, may carry the risk of inducing autoimmunity. These issues can be addressed in preclinical studies in appropriate animal models.