Stromal mesenchyme cell genes of the human prostate and bladder

Background

Stromal mesenchyme cells play an important role in epithelial differentiation and likely in cancer as well. Induction of epithelial differentiation is organ-specific, and the genes responsible could be identified through a comparative genomic analysis of the stromal cells from two different organs. These genes might be aberrantly expressed in cancer since cancer could be viewed as due to a defect in stromal signaling. We propose to identify the prostate stromal genes by analysis of differentially expressed genes between prostate and bladder stromal cells, and to examine their expression in prostate cancer.

Methods

Immunohistochemistry using antibodies to cluster designation (CD) cell surface antigens was first used to characterize the stromas of the prostate and bladder. Stromal cells were prepared from either prostate or bladder tissue for cell culture. RNA was isolated from the cultured cells and analyzed by DNA microarrays. Expression of candidate genes in normal prostate and prostate cancer was examined by RT-PCR.

Results

The bladder stroma was phenotypically different from that of the prostate. Most notable was the presence of a layer of CD13⁺ cells adjacent to the urothelium. This structural feature was also seen in the mouse bladder. The prostate stroma was uniformly CD13^-. A number of differentially expressed genes between prostate and bladder stromal cells were identified. One prostate gene, proenkephalin (PENK), was of interest because it encodes a hormone. Secreted proteins such as hormones and bioactive peptides are known to mediate cell-cell signaling. Prostate stromal expression of PENK was verified by an antibody raised against a PENK peptide, by RT-PCR analysis of laser-capture microdissected stromal cells, and by database analysis. Gene expression analysis showed that PENK expression was down-regulated in prostate cancer.

Conclusion

Our findings show that the histologically similar stromas of the prostate and bladder are phenotypically different, and express organ-specific genes. The importance of these genes in epithelial development is suggested by their abnormal expression in cancer. Among the candidates is the hormone PENK and the down-regulation of PENK expression in cancer suggests a possible association with cancer development.     

Immunological and echocardiographic evaluation of decellularized versus cryopreserved allografts during the Ross operation.

OBJECTIVE: Compare the immunological and echocardiographic data of decellularized versus cryopreserved allografts used for RVOT reconstruction during Ross operation. METHODS: From 16/01/03 thru 07/10/03, 20 Ross operations were performed using decellularized (n=11) or cryopreserved (n=9) allografts. Echocardiography was done at discharge, 1, 3, 6 and 12 months and annually thereafter. Samples for determination of antibodies against HLA class I and II were obtained preoperatively and at days 5, 10, 30, 90 and 180 postoperatively. These samples were tested by the ELISA method in LAT-M dishes (unspecific) for identification of circulating antibodies and the results expressed as mean sample values (Is=DO/cutoff). If positive, LAT-E (specific) was performed and PRA levels determined. RESULTS: There was no mortality. Cryopreserved allografts showed marked Is values elevations for class I and II antibodies which started at the first month and remained elevated up to 6 months. In contrast, of the patients receiving decellularized allografts, seven remained negative, two patients had only marginal elevation of class I antibodies and two patients showed abnormal elevations of PRA levels. This response happened earlier than in the cryopreserved group, starting on the 5th postoperative day and has returned to baseline levels in one case. Echocardiography showed mild, but significant, elevation of gradients in cryopreserved valves but none in the decellularized. CONCLUSIONS: Decellularized allografts had normal function up to 18 months and showed important reduction of the immunogenic response when compared to cryopreserved valves.     

Risk factors for secondary dilatation of the aorta after acute type A aortic dissection.

OBJECTIVES: Prompt diagnosis of subsequent dilatation of the dissected aorta is crucial to reduce late mortality in these patients. This study focuses on risk factors for dilatation of the aorta after type A aortic dissection (AADA) affecting a normal-sized or slightly dilated aorta. METHODS: Overall 531 CT scans were analysed. Patients were included in the study if at least 3 CT scans were available after operative repair. 64 patients (59.8%) out of 107 patients full-field the inclusion criteria. Volumetric analyses of the aorta were performed. Patients were divided in 3 groups: group A included 26 patients (40.6%) without progression of the aortic diameter, group 2, 27 patients (42.2%) with slight progression and group 3, 11 patients (17.2%) with important progression, requiring surgery in 9 patients (81.8%). Risk-factors for progression of the aortic size were analysed and compared between the groups. RESULTS: Patients from group 3 were younger 57.7+/-13.4 vs. 61.9+/-11.6 in group 1 (P<0.05) and were more frequent female (45.4 vs. 23.1%; P<0.05). Dissection of the supraaortic branches (100 vs. 80.8%; P<0.05), the presence of preoperative cerebral, visceral or peripheral malperfusion (54.6 vs. 26.9%; P<0.05) and contrast enhancement in the false lumen during the follow-up (72.7 vs. 57.7%; P=0.07) were additional risk factors for late aortic dilatation in these patients. CONCLUSIONS: Acute type A aortic dissection in younger patients, involving the supraaortic branches and/or combined with malperfusion syndrome favour secondary dilatation. A close follow-up is mandatory to prevent acute complications of the diseased downstream aorta following repair of a AADA.     

Does the extent of lymph node dissection influence outcome in patients with stage I non-small-cell lung cancer?

OBJECTIVE: To assess the therapeutic effect of the extent of lymph node dissection performed in patients with a stage pI non-small-cell lung cancer (NSCLC). METHODS: We analysed data on 465 patients with stage I NSCLC who were treated with surgical resection and some form of lymph node sampling. The median number of lymph node sampled was 10 and the median number of ipsilateral mediastinal lymph node stations sampled was two. We chose to define a procedure that harvested 10 or more lymph nodes and sampled two or more ipsilateral mediastinal stations as a lymphadenectomy, by contrast with sampling when one or both criteria were not satisfied. The effect of the surgical techniques: lymph node sampling (LS; n=207) vs. lymphadenectomy (LA; n=258) on 30-day mortality and overall survival were investigated. RESULTS: A total of 6244 lymph nodes was examined, including 4306 mediastinal lymph nodes. The mean (+/-SD) numbers of removed lymph nodes were 7+/-6.1 per patient following LS vs.18.6+/-9.3 following LA (P=0.001). An average mean of 1+/-0.90 mediastinal lymph node station per patient was sampled following LS vs. 2.7+/-0.8 following LA (P<10(-6)). Overall 30-day mortality rates were 2.4 and 3.1%, respectively. LA was disclosed as a favourable prognosticator at multivariate analysis (Hazard Risk: 1.43; 95% Confidence Interval: 1.00-2.04; P=0.048), together with younger patient age, absence of blood vessels invasion, and smaller tumour size. CONCLUSIONS: Importance of lymph node dissection affects patients outcome, while it does not enhance the operative mortality. A minimum of 10 lymph nodes assessed, and two mediastinal stations sampled are suggested as possible pragmatic markers of the quality of lymphadenectomy.     

FVIIa corrects the coagulopathy of fulminant hepatic failure but may be associated with thrombosis: A report of four cases

PURPOSE: During liver transplantation, excessive blood losses are correlated with increased morbidity and mortality. Blood losses are particularly high in the case of urgent liver transplantation for fulminant hepatic failure (FHF). Recombinant activated factor VII (rFVIIa) has shown promise in treating the coagulopathy of liver disease. We review our experience with the use of rFVIIa in treating the coagulopathy of FHF during urgent liver transplantation. CLINICAL FEATURES: We report four patients with FHF who met King's College criteria for liver transplantation and in whom rFVIIa was used after conventional means for treating the associated coagulopathy had failed. In all patients, the coagulation defect was corrected by rFVIIa. However, thrombotic complications occurred in two patients (myocardial ischemia and portal vein thrombosis) and the implication of rFVIIa cannot be excluded. CONCLUSION: We conclude that rFVIIa is effective in the correction of the coagulopathy associated with FHF. However, thrombotic events are of concern and therefore, further studies are warranted to define the safety of rFVIIa in that setting.     

Quadritherapy vs standard tritherapy immunosuppressant regimen after heart transplantation: A propensity score–matched cohort analysis

After heart transplant, adding everolimus (EVL) to standard immunosuppressive regimen mostly relies on converting calcineurin inhibitors (CNIs) into EVL. The aim of this study was to describe the effects of combining low‐dose EVL and CNIs in maintenance immunosuppression regimen (quadritherapy) and compare it with standard tritherapy associating standard‐dose CNIs, mycophenolate mofetil, and corticosteroids. In the 3‐year registry cohort of heart transplanted patients, those who received quadritherapy were compared with those who received tritherapy. EVL was added after 3 months posttransplant. Three analyses were performed to control for confounders: propensity score matching, multivariable survival, and inverse probability score weighting analyses. Among 213 patients who were included (75 with quadritherapy), propensity score matching selected 64 unique pairs of patients with similar characteristics. In the matched cohort (n = 128), quadritherapy was associated with fewer deaths (3 [4.7%] vs 17 [21.9%], P = .007) and biopsy‐proven acute rejections (15 [23.4%] vs 31 [48.4%], P = .002). These results were confirmed in the overall cohort (n = 213), after multivariable and inverse probability score weighting analyses. Renal function and donor‐specific HLA‐antibodies remained similar in both groups. Low‐dose combination quadritherapy was associated with fewer deaths and rejections, compared with standard immunosuppression tritherapy.     

Malaria-specific transgenic CD4(+) T cells protect immunodeficient mice from lethal infection and demonstrate requirement for a protective threshold of antibody production for parasite clearance

T cells are important in the immune response to malaria, both for their cytokines and their help for antibody production. To look at the relative importance of these roles, a T-cell receptor (TCR) transgenic mouse has been generated carrying a TCR specific for an epitope of the merozoite surface protein 1 (MSP-1) of the malaria parasite, Plasmodium chabaudi. In adoptive transfer experiments, malaria-specific CD4(+) T cells expand and produce interferon gamma (IFN-gamma) early in infection, but the population contracts quickly despite prolonged persistence of the parasite. MSP-1-specific CD4(+) cells can protect immunodeficient mice from lethal infection; however, the parasite is only completely cleared in the presence of B cells showing that T helper cells are critical. Levels of malaria-specific antibody and the speed of their production clearly correlate with the time of resolution of infection, indicating that a critical threshold of antibody production is required for parasite clearance. Furthermore, T cells specific for a shed portion of MSP-1 are able to provide help for antibody to the protective region, which remains bound to the infected erythrocyte, suggesting that MSP-1 has all of the components necessary for a good vaccine.     

Follicular lymphoma international prognostic index

The prognosis of follicular lymphomas (FL) is heterogeneous and numerous treatments may be proposed. A validated prognostic index (PI) would help in evaluating and choosing these treatments. Characteristics at diagnosis were collected from 4167 patients with FL diagnosed between 1985 and 1992. Univariate and multivariate analyses were used to propose a PI. This index was then tested on 919 patients. Five adverse prognostic factors were selected: age (> 60 years vs 60 years), Ann Arbor stage (III-IV vs I-II), hemoglobin level (< 120 g/L vs 120 g/L), number of nodal areas (> 4 vs 4), and serum LDH level (above normal vs normal or below). Three risk groups were defined: low risk (0-1 adverse factor, 36% of patients), intermediate risk (2 factors, 37% of patients, hazard ratio [HR] of 2.3), and poor risk ( 3 adverse factors, 27% of patients, HR = 4.3). This Follicular Lymphoma International Prognostic Index (FLIPI) appeared more discriminant than the International Prognostic Index proposed for aggressive non-Hodgkin lymphomas. Results were very similar in the confirmation group. The FLIPI may be used for improving treatment choices, comparing clinical trials, and designing studies to evaluate new treatments.      

Attacking Key Performance Indicators in Soccer: Current Practice and Perceptions from the Elite to Youth Academy Level

Key Performance Indicators (KPIs) are used to evaluate the offensive success of a soccer team (e.g. penalty box entries) or player (e.g. pass completion rate). However, knowledge transfer from research to applied practice is understudied. The current study queried practitioners (n = 145, mean ± SD age: 36 ± 9 years) from 42 countries across different roles and levels of competition (National Team Federation to Youth Academy levels) on various forms of data collection, including an explicit assessment of twelve attacking KPIs. 64.3% of practitioners use data tools and applications weekly (predominately) to gather KPIs during matches. 83% of practitioners use event data compared to only 52% of practitioners using positional data, with a preference for shooting related KPIs. Differences in the use and value of metrics derived from positional tracking data (including Ball Possession Metrics) were evident between job role and level of competition. These findings demonstrate that practitioners implement KPIs and gather tactical information in a variety of ways with a preference for simpler metrics related to shots. The low perceived value of newer KPIs afforded by positional data could be explained by low buy-in, a lack of education across practitioners, or insufficient translation of findings by experts towards practice.Key points

• Soccer practitioners collect data and evaluate performance in a variety of ways depending on the level of competition and their role within a club or federation.
• Practitioners reported a preference for shooting related metrics gathered by event data compared to KPIs offered by optical positional tracking technology.
• Despite increased interest and the capability to measure contextual aspects of passing performance with tracking technology, most practitioners still rely on more easily computed metrics (e.g. Pass Completion Percentage) and ball possession KPIs (e.g. Total Duration of Possession).
• This study highlights a gap in knowledge transfer between research and practice, encouraging increased education and collaborative efforts between data/sport scientists and practitioners to progress the field of analytics towards practical use in soccer.

Key words: Football, soccer, match analysis, performance analysis, applied data-science