The clinical significance of class III (suspicious) urine cytology

I. Sternberg, R. Rona, S. Olsfanger, S. Lew and I. Leibovitch The clinical significance of class III (suspicious) urine cytology Background: Urine cytology, combined with cystoscopy, is the mainstay of the diagnosis and surveillance of urothelial carcinoma (UC). While classes I and II urine cytology are considered benign and classes IV and V are considered malignant the clinical significance of class III urine cytology is unclear. We evaluated the positive predictive value of class III urine cytology for concurrent and subsequent UC. Methods: The records of all class III urine cytology cases during a 3‐year period were retrospectively reviewed for the presence of concurrent and subsequent UC, determined by cystoscopy and histological confirmation. Results: Of 111 cases, 54 (48.7%) were associated with concurrent UC and 14 (12.6%) with subsequent UC after an initial evaluation negative for malignancy, with a mean time to diagnosis of 10.8 months. Of 27 cases of class III urine cytology with no prior history of UC, 13 (48.1%) had concomitant UC and none had subsequent UC. Of 84 cases of class III urine cytology with a prior history of UC, 41 (48.8%) had a concomitant diagnosis of UC and 14 (16.7%) developed UC during their follow‐up, leading to a total of 55 (65.5%) cases of UC. Conclusions: Patients with class III urine cytology and a prior history of UC should undergo a full initial evaluation of their urinary tract, and should be followed vigorously if this evaluation is negative for malignancy. Patients without a prior diagnosis of UC and class III urine cytology should also undergo a full initial evaluation, while further larger studies are needed to elucidate the need for further follow‐up in such patients.     

Cellulase production and ammonia metabolism in Trichoderma reesei on high levels of cellulose.

Trichoderma can be cultured in stirred-tank fermentors on high (8%) cellulose concentrations without increasing the salt concentration of the medium when NH4OH is used to control pH and as a nitrogen source. Approximately 90% of the ammonia consumed by the organism can be added as NH4OH. The advantage of using high concentrations of cellulose is that culture filtrates with greater cellulase activity are obtained. The advantage of a low salts medium is that unwanted solutes in the final enzyme preparation are reduced. The appearance of cellulase in the medium occurs later than net ammonia uptake so that only 20% of the final amount of cellulase has appeared when 80% of the maximum amount of ammonia has been consumed.     

An analysis of conformational changes on protein-protein association: implications for predictive docking.

Conformational changes on complex formation have been measured for 39 pairs of structures of complexed proteins and unbound equivalents, averaged over interface and non-interface regions and for individual residues. We evaluate their significance by comparison with the differences seen in 12 pairs of independently solved structures of identical proteins, and find that just over half have some substantial overall movement. Movements involve main chains as well as side chains, and large changes in the interface are closely involved with complex formation, while those of exposed non-interface residues are caused by flexibility and disorder. Interface movements in enzymes are similar in extent to those of inhibitors. All eight of the complexes (six enzyme-inhibitor and two antibody-antigen) that have structures of both components in an unbound form available show some significant interface movement. However, predictive docking is successful even when some of the largest changes occur. We note however that the situation may be different in systems other than the enzyme-inhibitors which dominate this study. Thus the general model is induced fit but, because there is only limited conformational change in many systems, recognition can be treated as lock and key to a first approximation.     

Oxidation of Isomaltose by Pseudomonas taetrolens

Pseudomonas taetrolens NRRL B14 oxidized isomaltose without hydrolysis of the 1–6 glycosidic linkage. The resulting isomaltobionic acid was identified by chromatographic studies of acid hydrolysates and reconversion to isomaltose.     

Positive and negative tissue-specific signaling by a nematode epidermal growth factor receptor.

The major determinants of receptor tissue tyrosine kinase (RTK) signaling specificity have been proposed to be Src homology 2 (SH2) binding sites, phosphotyrosine-containing oligopeptides in the cytoplasmic domain of the receptor. The Caenorhabditis elegans epidermal growth factor receptor homologue LET-23 has multiple functions during development and has eight potential SH2-binding sites in a region carboxyl terminal to its kinase domain. By analyzing transgenic nematodes for three distinct LET-23 functions, we show that six of eight potential sites function in vivo and that they are required for most, but not all, of LET-23 activity. A single site is necessary and sufficient to promote wild-type fertility. Three other sites activate the RAS pathway and are involved only in viability and vulval differentiation. A fifth site is promiscuous and can mediate all three LET-23 functions. An additional site mediates tissue-specific negative regulation. Putative SH2 binding sites are thus key effectors of both cell-specific and negative regulation in an intact organism. We suggest two distinct mechanisms for tissue-specific RTK-mediated signaling. A positive mechanism would promote RTK function through effectors present only in certain cell types. A negative mechanism would inhibit RTK function through tissue-specific negative regulators.