Related F-box proteins control cell death in Caenorhabditis elegans and human lymphoma

Cell death is a common metazoan cell fate, and its inactivation is central to human malignancy. In Caenorhabditis elegans, apoptotic cell death occurs via the activation of the caspase CED-3 following binding of the EGL-1/BH3-only protein to the antiapoptotic CED-9/BCL2 protein. Here we report a major alternative mechanism for caspase activation in vivo involving the F-box protein DRE-1. DRE-1 functions in parallel to EGL-1, requires CED-9 for activity, and binds to CED-9, suggesting that DRE-1 promotes apoptosis by inactivating CED-9. FBXO10, a human protein related to DRE-1, binds BCL2 and promotes its degradation, thereby initiating cell death. Moreover, some human diffuse large B-cell lymphomas have inactivating mutations in FBXO10 or express FBXO10 at low levels. Our results suggest that DRE-1/FBXO10 is a conserved regulator of apoptosis.     

Coexistence of anti-RNA polymerase III and anti-U1RNP antibodies in patients with systemic lupus erythematosus: two cases without features of scleroderma

Anti-RNA polymerase III (RNAP III) antibodies are highly specific for scleroderma (SSc) and associated with diffuse SSc and renal crisis. Coexistence of anti-RNAP III and other SSc autoantibodies is rarely documented. We report three cases with coexisting anti-RNAP III and anti-U1RNP. Autoantibodies in 3829 sera from rheumatology clinics were screened by immunoprecipitation. Anti-RNAP III-positive sera were also examined by immunofluorescence and anti-RNAP III ELISA. In total, 35 anti-RNAP III-positive sera were identified by immunoprecipitation, in which three had coexisting anti-U1RNP. All three were anti-RNAP III ELISA positive. Two had anti-RNAP I dominant (vs. RNAP III) reactivity and showed strong nucleolar staining. A case with anti-U1/U2RNP (U2RNP dominant) had systemic lupus erythematosus (SLE)-SSc overlap syndrome; however, the remaining two cases had SLE without signs of SSc. All three cases of anti-RNAP III?+?U1RNP fulfilled ACR SLE criteria but none in the group with anti-RNAP III alone (p?=?0.0002). In contrast, only one case in the former group had sclerodermatous skin changes and Raynaud's phenomenon, vs. 92% with scleroderma in the latter (p?相似文献   

Curriculum directions and strategies for the implementation of a new pedagogic proposal

This study is aimed at contributing to the transformation movement to be developed in the Nursing Courses/Schools. The contribution refers to the formation of nurses with autonomy and discernment, to ensure the construction of the model of health attention, to the production of new knowledge and to the delivery of quality services directed to the health needs of the population. This study brings some conceptual and methodological reflections that may direct the change in the nurse formation process, as well as pointing strategies to implement the new pedagogic proposal from the challenge posed by the implementation of the National Curriculum Directions for Undergraduate Nursing Courses.     

Bedside diagnostic laparoscopy for critically ill patients: a retrospective study of 62 patients

Background

Bedside diagnostic laparoscopy has an important role of diagnosing acute abdomen in critically ill patients hospitalized in the intensive care unit (ICU). Delayed diagnosis of intraabdominal pathology increases the morbidity and mortality rates for these patients, whose clinical signs often are absent due to analgesic medication and sedation.

Methods

In this retrospective study performed from January 2007 to December 2009, 62 consecutive ICU patients whose blood test results showed them to be hemodynamically unstable underwent bedside diagnostic laparoscopy. The inclusion criteria specified clinically suspected acute cholecystitis, unknown sepsis, acidosis with a high level of lactate, elevated lab tests (white blood cell count, bilirubin, lactic dehydrogenase, creatine phosphokinase, gamma glutamyl transferase [??GT]), and acute anemia with suspected intraabdominal bleeding. The major contraindications to bedside diagnostic laparoscopy were coagulopathy, endocranic hypertension, and heart failure. Patients with a clear indication for an open surgical procedure were excluded from the study.

Results

Of the 62 patients who underwent bedside diagnostic laparoscopy, 43 (69.3?%) had positive findings and 29 (46.7?%) had acute acalculous cholecystitis. The mean operation time was 38 min, and no procedure-related deaths occurred. The procedure was performed for postsurgery patients, especially after cardiac operations, and for trauma or septic patients. Respiratory and hemodynamic parameters were monitored before, during, and after the procedure.

Conclusions

As a minimally invasive procedure, bedside diagnostic laparoscopy can be performed in the ICU for hemodynamically unstable patients. It is safe procedure with high diagnostic accuracy for acute intraabdominal conditions that avoids negative laparotomies for unstable patients. The bedside diagnostic laparoscopy procedure is not performed widely, and prospective studies are needed to better evaluate outcome and advantages for critically ill patients.     

PFAPA syndrome and Behçet’s disease: a comparison of two medical entities based on the clinical interviews performed by three different specialists

Clinical Rheumatology - The pediatric syndrome characterized by periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) and adult Behçet’s disease share some...     

Differential Reactivity to IMPDH2 by Anti-rods/rings Autoantibodies and Unresponsiveness to Pegylated Interferon-alpha/Ribavirin Therapy in US and Italian HCV Patients

Purpose

Autoantibodies to cytoplasmic structures called rods and rings (RR) are primarily specific to patients with hepatitis C virus (HCV) infection treated with pegylated interferon-alpha/ribavirin (IFN/R). Our aim is to examine anti-RR antibodies specificity and correlation with the response to IFN/R therapy in two independent cohorts (US and Italy) of HCV patients.

Methods

Sera from the US cohort (n?=?47) and the Italian cohort (n?=?46) pre-selected for anti-RR antibodies were analyzed by immunofluorescence and radioimmunoprecipitation. The prevalence and titers of anti-RR were analyzed for correlation with the response to IFN/R therapy.

Results

In the US cohort, anti-RR antibodies were more frequently non-responders to IFN/R (71 % vs 29 % responders). Titers in responder patients (n?=?11) were ≤1:3200, whereas titers in non-responder patients (n?=?27) reached 1:819,200 (p?=?0.0016). In the Italian cohort, anti-RR titers ranged from 1:200 to >1:819,200 and only relapsers had the highest anti-RR titers. Radioimmunoprecipitation demonstrated that anti-RR autoantibodies were mainly anti-inosine monophosphate dehydrogenase 2 (IMPDH2) - 96 % in the Italian cohort vs. 53 % in the US cohort.

Conclusions

In the two cohorts analyzed, the anti-IMPDH2 response as a component of the anti-RR response is much more prominent in the Italian cohort. The reason for the difference between the US and Italian cohorts is unclear but it possibly illustrates the heterogeneity in response and the overall negative correlation between the production of these autoantibodies and response to IFN/R therapy. Patients with high titer anti-RR antibodies are either relapsers (Italian) or non-responders/relapsers (US).     

Gemcitabine and cisplatin versus mitomycin, ifosfamide, and cisplatin in advanced non-small-cell lung cancer: A randomized phase III study of the Italian Lung Cancer Project.

PURPOSE: To compare gemcitabine and cisplatin (GC) with mitomycin, ifosfamide, and cisplatin (MIC) chemotherapy in patients with stage IIIB (limited to T4 for pleural effusion and N3 for supraclavicular lymph nodes) or stage IV non-small-cell lung cancer (NSCLC). The end points were the evaluation of quality of life (QoL), response rates, survival, and toxicity. PATIENTS AND METHODS: Three hundred seven patients were randomized to receive either gemcitabine 1,000 mg/m(2) on days 1, 8, and 15 plus cisplatin 100 mg/m(2) on day 2, every 28 days, or mitomycin 6 mg/m(2), ifosfamide 3,000 mg/m(2), and mesna on day 1 plus cisplatin 100 mg/m(2) on day 2, every 28 days. The whole-blood cell count was repeated on day 1 in both arms and weekly in the GC arm before each gemcitabine administration. RESULTS: No major differences in changes in QoL were observed between the two treatment arms. The objective response rate was 38% in the GC arm compared with 26% in the MIC arm (P =.029). The median survival time was 8.6 months in the GC arm and 9.6 months in the MIC arm (P =.877, log-rank test). Grade 3 and 4 thrombocytopenia was significantly worse in the GC arm (64% v 28%, P <.001), whereas grade 3 and 4 alopecia was reported more commonly in the MIC arm (39% v 12%, P <. 001). CONCLUSION: We report an increased response rate without changes in QoL and a similar overall survival, time to progression, and time to treatment failure for the GC when compared with the MIC regimen in the treatment of advanced NSCLC.     

Weekly gemcitabine in advanced bladder cancer: A preliminary report from a phase I study

BACKGROUND: Gemcitabine (2'2-difluorodeoxycytidine; GEM) is a novel deoxycytidineanalogue with promising antitumor activity, currently underphase II investigation at doses >800 mg/m²/week. PATIENTS AND METHODS: The present report summarizes the results obtained in a cohortof 15 patients with metastatic bladder cancer included in alarger phase I study, receiving GEM at therapeutically activedoses (     

Secondary Ekbom syndrome to organic disorder: report of three cases

The Ekbom syndrome, also known as delusion of parasitosis or acarophobia is an obsessive phobic state in which the patient thinks, imagines or believes that his or her skin is infested by parasites. In the hallucinatory state, he/she removes parts of the skin, identifying them as parasites. It can be primary or secondary to other organic or psychiatric diseases. Generally speaking these patients take a long time to seek for medical support and the dermatologist is almost always the first physician to see them. Here we describe three patients with delusional parasitosis associated with organic disorders.