Human achaete-scute homologue (hASH1) mRNA level as a diagnostic marker to distinguish esthesioneuroblastoma from poorly differentiated tumors arising in the sinonasal tract

Distinction of high-grade esthesioneuroblastomas from other poorly differentiated tumors arising in the nasal cavity is an important diagnostic challenge because it determines patient management and prognosis. The human achaete-scute homologue (hASH1) gene is critical in olfactory neuronal differentiation and is expressed in immature olfactory cells; therefore, it could have potential use as a diagnostic marker The aim of the present study was to determine the value of hASH1 messenger RNA (mRNA) levels in differentiating esthesioneuroblastoma from other poorly differentiated tumors. A real-time polymerase chain reaction assay was developed, permitting the comparative determination of hASH1 mRNA levels in triplicate in a double-blind pilot study including 24 frozen cases of esthesioneuroblastoma and poorly differentiated tumors. All 4 positive cases were esthesioneuroblastomas, and all 19 poorly differentiated tumors were negative. In addition, there was an inverse association between the grade of esthesioneuroblastomas and hASH1 mRNA levels. The hASH1 mRNA level might represent a useful tool for distinguishing esthesioneuroblastoma from poorly differentiated tumors of the sinonasal region.     

Idiopathic aneurysm of the pulmonary artery trunk. Report of a case

Aneurysms of the aorta are frequent and treatment is well known, correlated with a statistical risk of rupture. Pulmonary artery aneurysms are less frequent. They may occur in connection with other conditions (infection, cardiopathy, notably pulmonary artery hypertension, endovascular trauma) or much more exceptionally regarded as idiopathic. Chest x-ray, CT-scan and digitalized pulmonary angiography and echocardiography give the diagnosis and help evaluate extension and localization. We report the case of a 72-year-old woman who developed idiopathic aneurysm of the left pulmonary artery which was discovered fortuitously. Because of the stability of the lesion and the lack of any worsening factor, we decided not to operate this high-risk patient. After 3 years, no complication has been observed and the CT-scan shows no evolution. In case of proximal idiopathic aneurysm of the pulmonary artery, the indication of surgery should be discussed.     

Cardiac complications of infectious endocarditis

Factors predisposing to cardiac complications and influencing hospital survival, were analysed in a retrospective study of 101 cases of infective endocarditis. Heart failure occurred in 52 p. 100 of our patients. A significantly greater incidence of heart failure was observed in endocarditis with no preexisting heart disease (p less than 0.01), aortic and mitral valve involvement (p less than 0.01), staphylococcus aureus infections (p less than 0.05), arrhythmias (p less than 0.001), and conduction disturbances (p less than 0.01). Significantly more patients with congestive cardiac failure died in hospital (51 p. 100) than those without congestive cardiac failure (17 p. 100) (p less than 0.001). Severe heart failure before treatment (p less than 0.05), streptococcus D endocarditis (p = 0.05), supraventricular arrhythmias (p less than 0.05), and intracardiac conduction disturbances (p less than 0.05), significantly increased the hospital mortality in patients with congestive heart failure. Electrocardiographic findings revealed arrhythmias in 34 p. 100 of cases, more commonly with mitral valve involvement (71 p. 100) and 52 p. 100 died in hospital. The development of intracardiac conduction disturbance during the course of 18 cases of endocarditis (aortic valve in 11 cases) was associated with a hospital mortality rate of 60 p. 100. The incidence of pericarditis and pulmonary embolism was 4 and 7 p. 100 respectively, and all patients died in hospital. Acute inferior myocardial infarction compatible with coronary embolism was suspected in one patient. Early cardiac valve replacement improved the hospital survival in patients with cardiac complications of infective endocarditis.     

Cardiogenic shock due to myocardial infarction: surgical revascularization with centrifugal left ventricular assistance. Report of 2 cases treated successfully

Cardiogenic shock in the acute phase of myocardial infarction still carries a high mortality. In young patients who cannot be revascularised by angioplasty, when medical therapy is failing, some workers recommend an energetic approach, even cardiac transplantation, often with the bridge of mechanical cardiac assistance. This is not possible everywhere, thus preventing possible myocardial salvage and resulting in fairly high mortality. The authors report two cases in which endoluminal revascularisation was not possible and so complete surgical revascularisation with left ventricular assistance was chosen. The two patients survived and one was successfully transplanted electively. This management may be proposed in young patients with multiple occlusions of large coronary arteries in post-infarction cardiogenic shock when medical management is failing despite intra-aortic balloon pumping.     

Switching to darunavir/ritonavir 800/100 mg once‐daily containing regimen maintains virological control in fully suppressed pre‐treated patients infected with HIV‐1

The objective of this study was to evaluate the switch to once‐daily darunavir/ritonavir 800/100 mg in treatment‐experienced patients with suppressed HIV‐1 replication on a twice‐daily ritonavir‐boosted protease‐inhibitor (bid PI/r) containing regimen, that is in a setting where genotypic resistance test cannot be performed. In this open label, non‐comparative, multicenter study, patients on a bid PI/r‐containing triple combination, with suppressed viral replication, were switched to once‐daily darunavir/r 800/100 mg containing triple combination. The primary endpoint was the proportion of patients with plasma HIV‐RNA < 50 copies/ml 24 weeks after the switch. Intensive darunavir pharmacokinetic evaluation was performed at Week 4 (W4) in 11 patients. Eighty‐five patients were enrolled. All had HIV‐RNA < 50 copies/ml at screening with a pre‐exposure to a median of 2 PI/r (1–5). By intent‐to‐treat analysis (missing = failure), 78/85 patients (92%, 95% CI [83;96]) maintained an HIV‐RNA < 50 copies/ml at W24. Seven patients experienced protocol‐defined treatment failure between baseline and W24: Two had confirmed low‐level viral rebound, one discontinued study treatment for adverse event, three withdrew their consent, and one was lost to follow‐up. By on‐treatment analysis, 78/80 patients (97%, 95% CI [91;99]) maintained an HIV‐RNA < 50 copies/ml at W24. Results were similar at Week 48. The median area under the darunavir plasma concentration–time curve measured in 11 patients was 61,380 ng hr/ml; darunavir median trough concentration 1,340 ng/ml and darunavir half‐life was 12.2 hr. Tolerability of once‐daily darunavir/r 800/100 mg was excellent. Optimally suppressed, treatment‐experienced patients can switch safely from a twice‐daily PI/r regimen to a once‐daily darunavir/r 800/100 mg containing regimen. J. Med. Virol. 85:8–15, 2012. © 2012 Wiley Periodicals, Inc.     

Molecular Evidence of Helicobacter Pylori Infection in Prostate Tumors

Objectives

To determine whether Helicobacter pylori (H. pylori) is detectable in both benign prostatic hyperplasia (BPH) and prostate cancer (PCa). Epidemiological studies have shown significant associations between infective chronic prostatitis and prostatic carcinoma. Many bacteria have been found in the prostate of patients with chronic prostatitis, BPH, and PCa.

Methods

One hundred consecutive patients with prostate diseases were enrolled in the study. Detection of H. pylori DNA in prostate tissue from patients with BPH and PCa was performed using both immunohistochemistry and PCR, and the results were confirmed by DNA sequencing. Odds ratios and the Fisher Exact test were used for the analysis of the associations between the variables.

Results

Among the patients, 78% had BPH and 19% had PCa. While immunohistochemistry showed no positive sample for H. pylori, PCR combined with sequencing detected H. pylori DNA in prostate tissue samples from 5 patients. However, statistical analysis of the data showed that BPH and PCa are not significantly associated with the presence of H. pylori DNA in prostate tissue (odds ratio = 0.94, 95% confidence interval = 0.09–23.34, one-tailed Chi-square value = 0.660, p > 0.05). The limitation of this study was the small number of PCa patients.

Conclusions

This study provides, for the first time, molecular evidence of the presence of H. pylori DNA in prostatic tissue of patients with BPH and PCa. It paves the way for further comprehensive studies to examine the association of H. pylori infection with BPH and PCa.Key Words: Helicobacter pylori infection, Prostate cancer, Benign prostate hyperplasia, PCR     

RhoB prenylation is driven by the three carboxyl-terminal amino acids of the protein: evidenced in vivo by an anti-farnesyl cysteine antibody

Protein isoprenylation is a lipid posttranslational modification required for the function of many proteins that share a carboxyl-terminal CAAX motif. The X residue determines which isoprenoid will be added to the cysteine. When X is a methionine or serine, the farnesyl-transferase transfers a farnesyl, and when X is a leucine or isoleucine, the geranygeranyl-transferase I, a geranylgeranyl group. But despite its CKVL motif, RhoB was reported to be both geranylgeranylated and farnesylated. Thus, the determinants of RhoB prenylation appear more complex than initially thought. To determine the role of RhoB CAAX motif, we designed RhoB mutants with modified CAAX sequence expressed in baculovirus-infected insect cells. We demonstrated that RhoB was prenylated as a function of the three terminal amino acids, i.e., RhoB bearing the CAIM motif of lamin B or CLLL motif of Rap1A was farnesylated or geranylgeranylated, respectively. Next, we produced a specific polyclonal antibody against farnesyl cysteine methyl ester allowing prenylation analysis avoiding the metabolic labeling restrictions. We confirmed that the unique modification of the RhoB CAAX box was sufficient to direct the RhoB distinct prenylation in mammalian cells and, inversely, that a RhoA-CKVL chimera could be alternatively prenylated. Moreover, the immunoprecipitation of endogenous RhoB from cells with the anti-farnesyl cysteine antibody suggested that wild-type RhoB is farnesylated in vivo. Taken together, our results demonstrated that the three last carboxyl amino acids are the main determinants for RhoB prenylation and described an anti-farnesyl cysteine antibody as a useful tool for understanding the cellular control of protein farnesylation.     

No benefits of ultrafractionation in two head-and-neck cancer cell lines with different inherent radiosensitivity

PURPOSE: To assess if ultrafractionation is applicable in the context of an unknown hyperradiosensitivity (HRS) status, we studied the survival and repair capacity of two tumor cell lines after irradiation with two different dose/fractionation schedules that can be used in a clinical setting. MATERIALS AND METHODS: Squamous cell carcinoma cell lines SCC-3 (radioresistant) and SCC-6 (radiosensitive) were used. Survival was studied by clonogenic assay after multiple fractions of 0.5 Gy (2 fractions/day, 6-h interval) and 2 Gy (1 fraction/day) for a total dose of 8 Gy of gamma-rays. The capacity to repair single-strand and double-strand breaks (SSB, DSB) was assessed by comet assay. The messenger RNA (mRNA) levels of DNA-dependent protein kinase (PK) components were analyzed by RNase protection and real-time polymerase chain reaction (PCR). RESULTS: In both cell lines, no apparent difference was noted between the two fractionation protocols. In particular for SCC-3, the mean surviving fraction tended to be lower after 2 Gy than after 0.5 Gy fractions. In SCC-3 and SCC-6 no significant difference was observed in the repair capacity of SSB and DSB after exposure to single doses of 0.5 Gy or 2 Gy. After exposure to the same single doses, the mRNA levels of DNA-PK catalytic subunit (PKcs), Ku 70, and Ku 80 were similar. CONCLUSIONS: Our data do not support the concept of ultrafractionation, at least when using fractions of 0.5 Gy in the cell lines studied. This suggests that methods for testing HRS status in individual tumors need to be developed before the relevance of ultrafractionation can be investigated in the clinic.