Sarcomatoid carcinoma of the prostate. A clinicopathologic study of 12 patients.

Sarcomatoid carcinoma of the prostate is a rare tumor that can be difficult to distinguish from a true sarcoma. The authors report 12 patients in whom the typical light microscopic appearance of prostatic adenocarcinoma was accompanied by the appearance of spindled or pleomorphic sarcomatoid areas within the same specimen or in subsequent accessions. Immunostaining or electron microscopic study demonstrated epithelial differentiation within the sarcomatoid area(s) in 6 of the 11 patients in whom special studies were performed. All nine patients for whom follow-up data were available died of disease within 3 to 48 months (median time until death, 12.0 months) after the appearance of the sarcomatoid carcinoma, and the clinical course in each instance was characterized by aggressive local recurrence. Our experience confirms that sarcomatoid carcinoma of the prostate is an aggressive variant of prostatic adenocarcinoma.     

Ribosome-lamella complexes in a case of transitional cell carcinoma involving the prostate

We report ribosome-lamella complexes (RLC) in cancer cells of transitional cell carcinoma (TCC) of the prostate in a 52-year-old Caucasian man. Histopathologically, cancer cells were proliferated in various-sized nests, mostly associated with central necrosis. Some invaded into the surrounding normal glandular space and the stroma, with occasional lymphatic invasion. Fine structural study of cancer cells revealed that cross-sectioned RLC as well as densely aggregated ribosomes were detected in their cytoplasm, situated close to, but not directly connected with, dilated rough endoplasmic reticulum. These were composed of a concentric alternative arrangement of both lamellae and ribosomes. In the central and surrounding parts of the RLC, ribosomes were observed, revealing a smooth transition to the ribosomal component of RLC in size and shape. The presence of both RLC and dense aggregation of ribosomes close to the rough endoplasmic reticulum suggests that their functions might be related to specific or aberrant protein synthesis under unknown conditions. Although RLC have been often reported in hematopoietic malignancies, their occurrence in the malignant epithelial component has been only reported in a case of pulmonary adenocarcinoma. This is the first report of RLC in TCC in the literature.     

Co-detection and discrimination of six human herpesviruses by multiplex PCR-ELAHA.

BACKGROUND: Herpesviruses are a significant cause of human morbidity. Traditional approaches to the identification of these viruses require infectious or at least antigenic virus. Multiplex PCR (mPCR) is capable of simultaneously amplifying a range of targets from a single preparation of nucleic acids and when combined with a suitable detection assay, it is capable of discriminating each of the amplicons. OBJECTIVES: Several methods have been described in the literature, however, they lack one or more significant design features required to suitably control a routinely applied nucleic acid amplification assay. We aimed to design a multiplex herpesvirus PCR that could co-amplify eight human herpesvirus targets plus an internal control (IC) molecule in a single tube. STUDY DESIGN: Primers were designed to target the DNA polymerase genes of each of the human herpesviruses. Synthetic controls were developed to act as templates for the evaluation of assay sensitivity and specificity and for development of an in-house competitive quantitative PCR. Amplicon was discriminated using a simplified enzyme linked amplicon hybridisation assay (ELAHA). RESULTS AND CONCLUSIONS: For routine diagnostic use we reduced the number of herpesviral targets from 8 to 6 in order to maintain adequate clinical sensitivity. The ELAHA proved more sensitive than agarose gel electrophoresis. Additionally, 36 cytomegalovirus positive patients were examined with an in-house quantitative PCR-ELAHA which was developed to confirm that that the mPCR's co-detection limit of 10(2) copy of synthetic template per millilitre was relevant for use in detecting virus from clinical samples. The mPCR-ELAHA was then applied to the screening of 174 patient specimens resulting in a specificity of 98% and a sensitivity of 93%. This preliminary study demonstrated that the mPCR-ELAHA was a complete approach to the detection of herpesviruses from a range of clinical samples and disease states.     

The anti-apoptotic factor Bcl-2 can functionally substitute for the B cell survival but not for the marginal zone B cell differentiation activity of BAFF

The TNF family ligand B cell-activating factor (BAFF, BLyS, TALL-1) is an essential factor for B cell development. BAFF binds to three receptors, BAFF-R, transmembrane activator and CAML interactor (TACI), and B cell maturation antigen (BCMA), but only BAFF-R is required for successful survival and maturation of splenic B cells. To test whether the effect of BAFF is due to the up-regulation of anti-apoptotic factors, TACI-Ig-transgenic mice, in which BAFF function is inhibited, were crossed with transgenic mice expressing FLICE-inhibitory protein (FLIP) or Bcl-2 in the B cell compartment. FLIP expression did not rescue B cells, while enforced Bcl-2 expression restored peripheral B cells and the ability to mount T-dependent antibody responses. However, many B cells retained immaturity markers and failed to express normal amounts of CD21. Marginal zone B cells were not restored and the T-independent IgG3, but not IgM, response was impaired in the TACI-IgxBcl-2 mice. These results suggest that BAFF is required not only to inhibit apoptosis of maturating B cells, but also to promote differentiation events, in particular those leading to the generation of marginal zone B cells.     

The Src kinase Lyn is a negative regulator of mast cell proliferation

Previous investigators have reported that deletion of the protein tyrosine kinase Lyn alters mast cell (MC) signaling responses but does not affect or reduces the cytokine-mediated proliferation of mouse bone marrow-derived MC (BMMC) precursors and of mature MC. We observed that Lyn-deficient mice have more peritoneal MC than wild-type (WT) mice. Studies to explore this unexpected result showed that Lyn(-/-) BM cells expand faster than WT cells in response to interleukin (IL)-3 and stem-cell factor over the 4-5 weeks required to produce a >95% pure population of granular, receptor with high affinity for immunoglobulin E-positive BMMC. Furthermore, differentiated Lyn(-/-) BMMC continue to proliferate more rapidly than WT BMMC and undergo less apoptosis in response to cytokine withdrawal. Additionally, Lyn(-/-) BMMC support greater IL-3-mediated phosphorylation of the prosurvival kinase, Akt, and the proliferative kinase, extracellular-regulated kinase 1/2. These results identify Lyn as a negative regulator of murine MC survival and proliferation.     

A solid-phase competition ELISA for measuring antibody to foot-and-mouth disease virus

A solid-phase competition ELISA has been developed to measure antibodies to foot-and-mouth disease (FMD) virus and has been validated using an extensive range of sera from cattle. The assay uses polyclonal antisera and inactivated purified 146S antigens of FMD virus and was compared with the liquid-phase blocking ELISA and the virus neutralisation test on a range of serum sets. When examining test sera at a 1:5 dilution with a cut-off point of 30% inhibition of reaction, the solid-phase competition ELISA was as sensitive as the liquid-phase blocking ELISA for sera from infected or vaccinated animals. The limit of detection of the solid-phase ELISA was similar to that of the liquid-phase assay and both tests had lower limit of detection (i.e. were able to detect lower amounts of antibody) than the virus neutralisation test. The specificity of the solid-phase ELISA was considerably higher than that of the liquid-phase blocking ELISA and almost equivalent to that of the virus neutralisation test. The assay thus retains the sensitivity of the liquid-phase blocking ELISA whilst being easier to use, more robust and specific, and therefore offers an improvement for FMD virus antibody detection.     

Comparison of Micro-ID and API 20E systems for identification of Enterobacteriaceae.

The Micro-ID 4-h identification system for Enterobacteriaceae was compared to the API 20E overnight method, using 230 fresh clinical isolates and 74 stock cultures. Agreement was 97.8% for the clinical isolates and 93.2% for the stock cultures. Eighty-seven percent of primary culture plates containing gram-negative rods yielded sufficient growth to perform the 4-h Micro-ID identification on the same day the organisms were isolated.