Prostate cancer: local staging with endorectal magnetic resonance imaging

BACKGROUND: Prostate cancer has received increasing attention during the past decades. Staging of tumors before treatment is imperative for planning appropriate therapy. The purpose of this study is to assess the role of endorectal magnetic resonance imaging (MRI) in local staging of prostate cancer. METHODS: Endorectal MRI was performed in 31 patients with histologically-proven prostate cancer. MRI was done three to 100 days (mean, 32.1 days) after either transrectal ultrasonography (TRUS) with biopsy or transurethral resection of the prostate (TURP). Radical prostatectomies were performed within two weeks after MRI. The diagnostic accuracy of endorectal MRI for local tumor staging, specifically for extracapsular extension (ECE) and seminal vesicle invasion (SVI), was evaluated by correlating MRI results with histopathologic findings of whole-mount specimens. RESULTS: The accuracy of endorectal MRI for the detection of tumor presence and estimation of tumor volume was 48%. Sensitivity, specificity and positive predictive value for evaluation of ECE were 88%, 69% and 80%, respectively, and for SVI, were 66%, 84% and 50%, respectively. The overall accuracy of MRI in local tumor staging (using the TMN system) was 61%. Accuracy in differentiating localized from invasive cancer was 84%. CONCLUSION: Endorectal MRI is not accurate enough to detect tumor presence or estimate tumor volume. Diagnostic accuracy for local tumor staging is unsatisfactory. However, endorectal MRI is highly accurate in differentiating localized (stage B) from invasive (stage C) cancer.     

Complete nucleotide sequence of HTLV-II isolate NRA: comparison of envelope sequence variation of HTLV-II isolates from U.S. blood donors and U.S. and Italian i.v. drug users

Seven cardiac electrophysiology stimulators from four manufacturers (Biotronik, Bloom, Digitimer and Medtronic) in common current use are reviewed. The stimulators differ in the features provided and the design adopted to achieve these features. The number of output channels ranges from one to four, the number of extra-stimuli available ranges from two to six, and these can be delivered as a variety of sequences. Some of the stimulators (Digitimer and Bloom) are modular while others (Biotronik and Medtronic 532 series) are of an integrated design comprising a single physical unit. The design of the Medtronic EP-2 has both integrated and modular characteristics. The features of the stimulators associated with input, output, control and the user interface are specifically reviewed. The features are also compared against the published recommendations of the American Heart Association. In addition, a summary of stimulator user comments from a number of electrophysiology centres is presented. All of the stimulators fulfil, or are close to fulfilling, basic electrophysiological requirements, but some provide more complex facilities such as would be required by specialist centres.     

Comparison of MODIS gross primary production estimates for forests across the U.S.A. with those generated by a simple process model, 3-PGS

Since 2000, NASA's Moderate Resolution Imaging Spectro-radiometer (MODIS) has provided 1 × 1 km estimates of 8-day gross primary production (GPP). The MODIS algorithm computes GPP as a simple function of absorbed photosynthetically active radiation and a regionally assigned light-use conversion efficiency (LUE) that is reduced if temperature or atmospheric vapor pressure deficits are suboptimal. We compared MODIS-derived GPP estimates for forested areas across the United States of America (U.S.A.) with those generated by the 3-PGS (Physiological Principles Predicting Growth using Satellite data) model, the latter of which considers spatial variation in available soil water storage capacity (ASWC) and nitrogen content. We expected seasonal and annual MODIS GPP values to be in close agreement with those derived from the 3-PGS model in regions with adequate precipitation, soil water storage, and moderately fertile soils. 3-PGS was initially run with STATSGO-derived soils information provided by the Oak Ridge National Laboratory. The analysis was expanded to include sensitivity analyses with ASWC set at 50, 100, 300, and 400 mm to identify areas within nine major ecoregions where drought might prove to be a major limitation on GPP. The majority of forests across the U.S.A. were relatively insensitive to large variations in ASW storage. In areas where ASWC was assumed < 200 mm and average annual rainfall was < 100 mm yr^− 1, GPP was predicted to be reduced by > 60%. There was generally good agreement (within 20%) between MODIS and 3-PGS estimates of forest GPP across the U.S.A. GPP predicted by the MODIS model was generally higher in ecoregions with substantial drought and with relatively low soil fertility. The latter, which influences LUE, was more than twice as important as soil drought.     

Detection of skeletal metastases in Nigerian breast cancer patients: evaluation of radioisotope bone scan and radiography

Cerebellar granule cells isolated from postnatal day 7 mice, and cultured in minimal medium containing only insulin-like growth factor-I (IGF-I), both survive and differentiate. This differentiation is marked by neurite growth and expression of genes associated with terminal differentiation, the myocyte-specific enhancer factor 2A (MEF2A) and the alpha 6 subunit of the gamma-aminobutyric acidA receptor (GABAA alpha 6). Percoll gradient purified granule cells maintained without IGF-I, in minimal medium alone or in medium containing the antioxidant N-acetylcysteine (NAC), also express MEF2A and GABAA alpha 6. Thus, cultured granule neurons can differentiate to some extent cell-autonomously and IGF-I may not be a critical factor for this process.     

TR1, a new member of the tumor necrosis factor receptor superfamily, induces fibroblast proliferation and inhibits osteoclastogenesis and bone resorption

A newly identified member of the tumor necrosis factor receptor (TNFR) superfamily shows activities associated with osteoclastogenesis inhibition and fibroblast proliferation. This new member, called TR1, was identified from a search of an expressed sequence tag database, and encodes 401 amino acids with a 21-residue signal sequence. Unlike other members of TNFR, TR1 does not contain a transmembrane domain and is secreted as a 62 kDa glycoprotein. TR1 gene maps to chromosome 8q23-24.1 and its mRNA is abundantly expressed on primary osteoblasts, osteogenic sarcoma cell lines, and primary fibroblasts. The receptors for TR1 were detected on a monocytic cell line (THP-1) and in human fibroblasts. Scatchard analyses indicated two classes of high and medium-high affinity receptors with a kD of approximately 45 and 320 pM, respectively. Recombinant TR1 induced proliferation of human foreskin fibroblasts and potentiated TNF-induced proliferation in these cells. In a coculture system of osteoblasts and bone marrow cells, recombinant TR1 completely inhibited the differentiation of osteoclast-like multinucleated cell formation in the presence of several bone-resorbing factors. TR1 also strongly inhibited bone-resorbing function on dentine slices by mature osteoclasts and decreased 45Ca release in fetal long-bone organ cultures. Anti-TR1 monoclonal antibody promoted the formation of osteoclasts in mouse marrow culture assays. These results indicate that TR1 has broad biological activities in fibroblast growth and in osteoclast differentiation and its functions.     

Calcium/calmodulin-dependent protein kinase IV is cleaved by caspase-3 and calpain in SH-SY5Y human neuroblastoma cells undergoing apoptosis

We have previously demonstrated cleavage of alpha-spectrin by caspase-3 and calpain during apoptosis in SH-SY5Y neuroblastoma cells (Nath, R., Raser, K. J., Stafford, D., Hajimohammadreza, I., Posner, A., Allen, H., Talanian, R. V., Yuen, P., Gilbertsen, R. B., and Wang, K. K. (1996) Biochem. J. 319, 683-690). We demonstrate here that calcium/calmodulin-dependent protein kinase IV (CaMK IV) is cleaved during apoptosis by caspase-3 and calpain. We challenged SH-SY5Y cells with the pro-apoptotic agent thapsigargin. Western blot analysis revealed major CaMK IV breakdown products of 40, 38, and 33 kDa. Digestion of control SH-SY5Y lysate with purified caspase-3 produced a 38-kDa CaMK IV fragment; digestion with purified calpain produced a major fragment of 40 kDa. Pretreatment with carbobenzoxy-Asp-CH2OC(O)-2,6-dichlorobenzene or Z-Val-Ala-Asp-fluoromethylketone was able to block the caspase-3-mediated production of the 38-kDa fragment both in situ and in vitro. Calpain inhibitor II similarly blocked formation of the calpain-mediated 40-kDa fragment both in situ and in vitro. Digestion of recombinant CaMK IV by other caspase family members revealed that only caspase-3 produces a fragmentation pattern consistent to that seen in situ. The major caspase-3 and calpain cleavage sites are respectively identified as PAPD176*A and CG201*A, both within the CaMK IV catalytic domain. Furthermore, calmodulin-stimulated protein kinase activity decreases within 6 h in thapsigargin-treated SH-SY5Y. The loss of activity precedes cell death.     

Arabidopsis mutants define a central role for the xanthophyll cycle in the regulation of photosynthetic energy conversion

A conserved regulatory mechanism protects plants against the potentially damaging effects of excessive light. Nearly all photosynthetic eukaryotes are able to dissipate excess absorbed light energy in a process that involves xanthophyll pigments. To dissect the role of xanthophylls in photoprotective energy dissipation in vivo, we isolated Arabidopsis xanthophyll cycle mutants by screening for altered nonphotochemical quenching of chlorophyll fluorescence. The npq1 mutants are unable to convert violaxanthin to zeaxanthin in excessive light, whereas the npq2 mutants accumulate zeaxanthin constitutively. The npq2 mutants are new alleles of aba1, the zeaxanthin epoxidase gene. The high levels of zeaxanthin in npq2 affected the kinetics of induction and relaxation but not the extent of nonphotochemical quenching. Genetic mapping, DNA sequencing, and complementation of npq1 demonstrated that this mutation affects the structural gene encoding violaxanthin deepoxidase. The npq1 mutant exhibited greatly reduced nonphotochemical quenching, demonstrating that violaxanthin deepoxidation is required for the bulk of rapidly reversible nonphotochemical quenching in Arabidopsis. Altered regulation of photosynthetic energy conversion in npq1 was associated with increased sensitivity to photoinhibition. These results, in conjunction with the analysis of npq mutants of Chlamydomonas, suggest that the role of the xanthophyll cycle in nonphotochemical quenching has been conserved, although different photosynthetic eukaryotes rely on the xanthophyll cycle to different extents for the dissipation of excess absorbed light energy.     

Diagnostic accuracy of HIV-associated central nervous system toxoplasmosis

Our objective was to examine the accuracy of diagnosis of HIV-associated central nervous system (CNS) toxoplasmosis. Individuals diagnosed with HIV-associated CNS toxoplasmosis and controls were ascertained from a population-based database. Diagnosis was confirmed by response to therapy or by histology. Symptoms, results of anti-Toxoplasma serology and use of Pneumocystis carinii pneumonia (PCP) prophylaxis were recorded. Central nervous system toxoplasmosis was confirmed in 54 (76%) of 75 patients. Reactive anti-Toxoplasma serology was associated with CNS toxoplasmosis (OR=20.4, 95% CI 3.1-175.8). Adjusting for CD4 and use of dapsone or aerosolized pentamidine, trimethoprim-sulphamethoxazole (TMP-SMX) for PCP prophylaxis was associated with lower likelihood of CNS toxoplasmosis (OR 0.3, 95% CI 0.1-0.7). Diagnosis of CNS toxoplasmosis is often incorrect. Another diagnosis is most likely in patients who are anti-Toxoplasma seronegative or who are receiving prophylactic TMP-SMX.