Suppression of tumor growth and cell proliferation by p13II, a mitochondrial protein of human T cell leukemia virus type 1

Human T cell leukemia virus type 1 encodes an "accessory" protein named p13(II) that is targeted to mitochondria and triggers a rapid flux of K(+) and Ca(2+) across the inner membrane. In this study, we investigated the effects of p13(II) on tumorigenicity in vivo and on cell growth in vitro. Results showed that p13(II) significantly reduced the incidence and growth rate of tumors arising from c-myc and Ha-ras-cotransfected rat embryo fibroblasts. Consistent with these findings, HeLa-derived cell lines stably expressing p13(II) exhibited markedly reduced tumorigenicity, as well as reduced proliferation at high density in vitro. Mixed culture assays revealed that the phenotype of the p13(II) cell lines was dominant over that of control lines and was mediated by a heat-labile soluble factor. The p13(II) cell lines exhibited an enhanced response to Ca(2+)-mediated stimuli, as measured by increased sensitivity to C2-ceramide-induced apoptosis and by cAMP-responsive element-binding protein (CREB) phosphorylation in response to histamine. p13(II)-expressing Jurkat T cells also exhibited reduced proliferation, suggesting that the protein might exert similar effects in T cells, the primary target of HTLV-1 infection. These findings provide clues into the function of p13(II) as a negative regulator of cell growth and underscore a link between mitochondria, Ca(2+) signaling, and tumorigenicity.     

Indications, results of therapy and factors which influence survival in patients treated with intra-aortic balloon counterpulsation

BACKGROUND AND AIM: During nearly 40 years of intraaortic balloon counterpulsation (IABP) application in advanced medical therapy more and more indications for this treatment have been proposed. Despite increasing experience with IABP, the clinical effects of IABP use are still unclear. The aim of this study was to determine results of IABP use and factors which influence survival in cardiogenic shock (CS) caused by different clinical disorders when treated with IABP. METHODS: 73 patients (mean age 58.3+/-12.6 years, 54 males) undergoing IABP were included in the study. Data were collected retrospectively. After analysis of the whole population a subgroup of patients admitted due to acute myocardial infarction (AMI) was evaluated. The in-hospital and overall mortality rates were assessed. RESULTS: In-hospital death occurred in 31 (42.5%) patients. Over half of these patients (n=17; 54.8%) died during first 7 days from admission. The main reason for IABP introduction was CS due to acute coronary syndrome (ACS) at admission in 62 (84.9%) patients. The in-hospital mortality in patients with AMI complicated by CS was 40.7%. The features which significantly influenced survival in patients with AMI were age--patients who died were older (64+/-8.9 vs. 58.6+/-9,1; p=0.0285), and ST segment changes--there was lower mortality rate in a subgroup with ST elevation AMI (18 vs. 6 patients, p=0.003). We also observed slightly higher incidence of anterior wall AMI in survivors than in non-survivors (p=0.06). CONCLUSION: Our study presents several disorders which may be treated with IABP. Acute MI still remains the most frequent indication for IABP insertion. In the present study, AMI survivors and non-survivors, differed mainly in age, ST segment changes and infarction site. Non ST segment elevation AMI was associated with worse prognosis.     

Drug resistance trends among previously treated tuberculosis patients in a national registry in Peru, 1994-2001.

SETTING: National mycobacteriology reference laboratory in Peru conducting routine testing of susceptibility to isoniazid, rifampin, ethambutol, pyrazinamide, and streptomycin, in Mycobacterium tuberculosis isolates from previously treated patients. OBJECTIVE: To determine the percentage of isolates resistant to each of five anti-tuberculosis agents and to ascertain in these data the presence of trends of clinical relevance. DESIGN: Retrospective study of a national registry of M. tuberculosis isolates from patients referred for drug susceptibility testing between 1994 and 2001. RESULTS: Among 14,736 isolates tested, 10,837 (73.5%, 95%CI 72.8-74.3) demonstrated anti-tuberculosis resistance, and 8455 (57.4%, 95%CI 56.6-58.2) demonstrated resistance to at least both isoniazid and rifampin, by convention defined as multidrug-resistant tuberculosis (MDR-TB). A significant increasing trend could be discerned for resistance to each of the drugs tested and in isolates classified as MDR-TB (P < 0.001 for trend). Additional clinically relevant trends were found in polyresistance and multidrug resistance percentages. CONCLUSIONS: Data from a national reference laboratory can be used to inform the design of retreatment regimens.     

Replication of avocado sunblotch viroid: evidence for a symmetric pathway with two rolling circles and hammerhead ribozyme processing.

The structure of a series of RNAs extracted from avocado infected by the 247-nt avocado sunblotch viroid (ASBVd) was investigated. The identification of multistranded complexes containing circular ASBVd RNAs of (+) and (-) polarity suggests that replication of ASBVd proceeds through a symmetric pathway with two rolling circles where these two circular RNAs are the templates. This is in contrast to the replication of potato spindle tuber viroid and probably of most of its related viroids, which proceeds via an asymmetric pathway where circular (+)-strand and linear multimeric (-)-strand RNAs are the two templates. Linear (+) and (-) ASBVd RNAs of subgenomic length (137 nt and about 148 nt, respectively) and one linear (+)-strand ASBVd RNA of supragenomic length (383-384 nt) were also found in viroid-infected tissue. The two linear (+)-strand RNAs have the same 5'- and 3'-terminal sequences, with the supragenomic species being a fusion product of the monomeric and subgenomic (+)-strand ASBVd RNAs. The 3' termini of these two (+)-strand molecules, which at least in the subgenomic RNA has an extra nontemplate cytidylate residue, could represent sites of either premature termination of the (+)-strands or specific initiation of the (-)-strands. The 5' termini of sub- and supragenomic (+)-strand and the 5' terminus of the subgenomic (-)-strand ASBVd RNA are identical to those produced in the in vitro self-cleavage reactions of (+) and (-) dimeric ASBVd RNAs, respectively. These observations strongly suggest that the hammerhead structures which mediate the in vitro self-cleavage reactions are also operative in vivo.     

Suggestive linkage on chromosome 1 for a quantitative alcohol-related phenotype

BACKGROUND: Alcohol dependence is a clinically and etiologically heterogeneous disorder. Accordingly, a variety of subtypes of alcohol-dependent individuals have been proposed, and multiple operational definitions of alcohol use, abuse, and dependence have been used in linkage analyses directed toward detecting genes involved in alcohol use and problems. Here, we develop quantitative phenotypes that characterize drinking patterns among both alcoholic and nonalcoholic subjects, and use these phenotypes in subsequent linkage analyses. METHODS: More than 9000 individuals from alcoholic and control families were administered a semistructured interview and personality questionnaire as part of the initial stage of the Collaborative Study on the Genetics of Alcoholism (COGA). A principal component analysis was conducted on items that captured many of the dimensions of drinking and related behaviors, including aspects of alcohol use, antisocial behavior and affective disturbance when drinking, and personality. Factor scores were computed for all individuals. Nonparametric linkage analyses were conducted on these factor scores, in the initial COGA sample consisting of 987 individuals from 105 extended families, and in a replication sample consisting of 1295 individuals from 157 extended families. RESULTS: Three factors were identified, accounting for 68% of the total variance. The most promising regions of linkage appeared for factor 2, on which higher scores indicate a later age of onset of regular drinking and higher harm avoidance. Chromosome 1 yielded consistent evidence of linkage in both samples, with a maximum lod score of 3.3 when the samples were combined for analysis. Consistent suggestion of linkage also was found to chromosome 15. CONCLUSIONS: Developing novel phenotypes that more accurately model the effect of influential genes may help efforts to detect genes involved in complex disorders. Applying principal component analysis in the COGA sample provided support for some regions of linkage previously reported in COGA, and identified other new, promising regions of linkage.     

Effect of a physical training program using the Pilates method on flexibility in elderly subjects

The adaptations of the human body resulting from the aging process especially loss of flexibility can increase the risk of falls and the risk of developing other health conditions. Exercise training, in particular the Pilates exercise method, has become an important form of physical activity that minimizes the deleterious effects of aging on flexibility. Few studies have evaluated the effect of this training method on body flexibility among elderly. We aimed to evaluate the effects of physical training using the Pilates method on body flexibility of elderly individuals. Eighteen elderly women and two elderly men (aged 70 ± 4 years) followed a 10-week Pilates training program. Individuals were recruited from the local community via open invitations. At study entry, none of them had limited mobility (walking requiring the use of walkers or canes). Furthermore, those with neurologic, muscular, or psychiatric disorders as well as those using an assistive device for ambulation were excluded secondary to limited participation. Flexibility assessment tests (flexion, extension, right and left tilt, and right and left rotation of the cervical and thoracolumbar spine; flexion, extension, abduction, and lateral and medial right and left rotation of the glenohumeral joint; flexion, extension, abduction, adduction, and lateral and medial rotation of the right and left hip; and flexion of the right and left knee) were performed by a blinded evaluator using a flexometer before and after the training period. All assessments were carried out at the same time of day. There was an observed increase in flexion (22.86 %; p < 0.001), extension (10.49 %; p < 0.036), and rotation to the left side (20.45 %; p < 0.019) of the cervical spine; flexion (16.45 %; p < 0.001), extension (23.74 %; p = 0.006), lateral bending right (39.52 %; p < 0.001) and left (38.02 %; p < 0.001), and right rotation (24.85 %; p < 0.001) and left (24.24 %; p < 0.001) of the thoracolumbar spine; flexion (right—8.80 %, p = 0.034; left—7.03 %, p = 0.050), abduction (right—20.69 %, p < 0.001; left—16.26 %, p = 0.005), and external rotation (right—116.07 % and left—143 %; p < 0.001 for both directions) of the glenohumeral joint; flexion (right—15.83 %, p = 0.050; left—9.55 %, p = 0.047) of the hips; and bending (right—14.20 %, p = 0.006; left—15.20 %, p = 0.017) the knees. The joint with the greatest magnitude of improvement was the thoracolumbar spine. Thus, this type of training may minimize the deleterious effects of aging and may improve the functionality of elderly individuals, which would reduce the likelihood of accidents (especially falls).