Pbp1p, a factor interacting with Saccharomyces cerevisiae poly(A)-binding protein, regulates polyadenylation

The poly(A) tail of an mRNA is believed to influence the initiation of translation, and the rate at which the poly(A) tail is removed is thought to determine how fast an mRNA is degraded. One key factor associated with this 3'-end structure is the poly(A)-binding protein (Pab1p) encoded by the PAB1 gene in Saccharomyces cerevisiae. In an effort to learn more about the functional role of this protein, we used a two-hybrid screen to determine the factor(s) with which it interacts. We identified five genes encoding factors that specifically interact with the carboxy terminus of Pab1p. Of a total of 44 specific clones identified, PBP1 (for Pab1p-binding protein) was isolated 38 times. Of the putative interacting genes examined, PBP1 promoted the highest level of resistance to 3-aminotriazole (>100 mM) in constructs in which HIS3 was used as a reporter. We determined that a fraction of Pbp1p cosediments with polysomes in sucrose gradients and that its distribution is very similar to that of Pab1p. Disruption of PBP1 showed that it is not essential for viability but can suppress the lethality associated with a PAB1 deletion. The suppression of pab1Delta by pbp1Delta appears to be different from that mediated by other pab1 suppressors, since disruption of PBP1 does not alter translation rates, affect accumulation of ribosomal subunits, change mRNA poly(A) tail lengths, or result in a defect in mRNA decay. Rather, Pbp1p appears to function in the nucleus to promote proper polyadenylation. In the absence of Pbp1p, 3' termini of pre-mRNAs are properly cleaved but lack full-length poly(A) tails. These effects suggest that Pbp1p may act to repress the ability of Pab1p to negatively regulate polyadenylation.     

Prediction of psychosis. A step towards indicated prevention of schizophrenia

BACKGROUND: The identification of people at high risk of becoming psychotic within the near future creates opportunities for early intervention prior to the onset of psychosis to prevent or minimise later ill-health. The present study combines current knowledge about risk factors for schizophrenia with our knowledge of psychotic prodromes in an attempt to identify a group particularly vulnerable to impending psychosis. We wanted to identify people with high likelihood of transition to psychosis within a follow-up period of 12 months, and to determine the rate of transition to psychosis in this group. METHOD: Various state and trait risk factors for psychosis were used alone and in combination to operationally define a putatively high-risk group. Operationalised criteria for onset of psychosis were established. The individuals were assessed monthly on measures of psychopathology for six months. RESULTS: Eight out of 20 people made the transition to frank psychosis within a six-month follow-up period. Follow-up of this group is still in progress, and the 12 month transition rate might prove to be higher still. CONCLUSIONS: We have demonstrated that it is possible to identify individuals with a high likelihood of onset of psychosis within a brief follow-up period. This lays the foundation for early treatment in an attempt to prevent, delay or minimise the severity of first onset of schizophrenia.     

Long-term follow-up of cranial bone graft in dorsal nasal augmentation

A follow-up of 363 cranial bone grafts for nasal reconstruction is presented. The main indications for the surgery were congenital, posttraumatic, or postrhinoplasty deformity. The results were satisfactory in the vast majority of cases. The complications associated with the grafts and with the donor site are discussed, as are the methods to treat and prevent these complications from occurring.     

Phase I study of the orally administered butyrate prodrug, tributyrin, in patients with solid tumors

Butyrates have been studied as cancer differentiation agents in vitro and as a treatment for hemoglobinopathies. Tributyrin, a triglyceride with butyrate molecules esterified at the 1, 2, and 3 positions, induces differentiation and/or growth inhibition of a number of cell lines in vitro. When given p.o. to rodents, tributyrin produces substantial plasma butyrate concentrations. We treated 13 patients with escalating doses of tributyrin from 50 to 400 mg/kg/day. Doses were administered p.o. after an overnight fast, once daily for 3 weeks, followed by a 1-week rest. Intrapatient dose escalation occurred after two courses without toxicity greater than grade 2. The time course of butyrate in plasma was assessed on days 1 and 15 and after any dose escalation. Grade 3 toxicities consisted of nausea, vomiting, and myalgia. Grades 1 and 2 toxicities included diarrhea, headache, abdominal cramping, nausea, anemia, constipation, azotemia, lightheadedness, fatigue, rash, alopecia, odor, dysphoria, and clumsiness. There was no consistent increase in hemoglobin F with tributyrin treatment. Peak plasma butyrate concentrations occurred between 0.25 and 3 h after dose, increased with dose, and ranged from 0 to 0.45 mM. Peak concentrations did not increase in three patients who had dose escalation. Butyrate pharmacokinetics were not different on days 1 and 15. Because peak plasma concentrations near those effective in vitro (0.5-1 mM) were achieved, but butyrate disappeared from plasma by 5 h after dose, we are now pursuing dose escalation with dosing three times daily, beginning at a dose of 450 mg/kg/day.     

Second-generation three-dimensional reconstruction for rotational three-dimensional angiography

RATIONALE AND OBJECTIVES: The purpose of this study was to assess the feasibility and accuracy of three-dimensional (3D) reconstruction techniques for digital subtraction angiography (DSA) in planning and evaluation of minimally invasive image-controlled therapy. MATERIALS AND METHODS: Using a standard, commercially available system, the authors acquired DSA images and corrected them for inherent distortions. They designed and implemented parallel and multiresolution versions of cone-beam reconstruction techniques to reconstruct high-resolution targeted volumes in a short period of time. Testing was performed on anatomically correct, calibrated in vitro models of a cerebral aneurysm. These models were used with a pulsatile circulation circuit to allow for blood flow simulation during DSA, computed tomographic (CT) angiography, and magnetic resonance (MR) angiography image acquisitions. RESULTS: The multiresolution DSA-based reconstruction protocol and its implementation allowed the authors to achieve reconstruction times and levels of accuracy for the volume measurement of the aneurysmal cavities that were considered compatible with actual clinical practice. Comparison with data obtained from other imaging modalities shows that, besides vascular tree depiction, the DSA-based true 3D technique provides volume estimates at least as good as those obtained from CT and MR angiography. CONCLUSION: The authors demonstrated the feasibility and potential of true 3D reconstruction for angiographic imaging with DSA. On the basis of the model testing, this work addresses both the timing and quantification required to support minimally invasive image-controlled therapy.     

The effects of hyperbaric oxygen on normal and ischemic colon anastomoses

A pregnant woman with transient gastric obstruction was fed by enteral nutrition alone for 11 wk and 6 d. Her body mass index of 23.2 kg/m2 before pregnancy declined to 21.8 kg/m2 after delivery. Although she did not gain weight during enteral nutrition, fetal growth, estimated by ultrasonography, was normal, and she delivered a 3030-g female infant at 38 wk gestation. The blood laboratory data during pregnancy and the breast milk after pregnancy were also normal. The results suggest that factors other than maternal weight gain alone should be considered in the evaluation of nutritional status for the pregnant woman.     

Multicenter trial in North America of UroLume urinary sphincter prosthesis

We investigated the effectiveness and associated complications of treatment with an endoluminal urethral sphincter prosthesis in 153 spinal cord injury men (mean age 36 years, range 16 to 74 years) with urodynamically diagnosed detrusor-external sphincter dyssynergia. These patients were prospectively treated with a urethral sphincter stent at 15 centers in North America. Followup ranged from 2 to 33 months. Voiding pressures averaged 76 +/- 28, 42 +/- 21, 44 +/- 38, 35 +/- 18 and 32 +/- 20 cm. water, respectively, before prosthesis insertion in 153 patients and at 3 months in 123, 6 months in 114, 12 months in 98 and 24 months in 22. A significant decrease in voiding pressure was noted in the 22 patients at 24 months compared with matched preoperative data (80 +/- 25 cm. water, p = 0.03). The residual urine decreased from 181 +/- 154 ml. before insertion to 82 +/- 93 ml. at 24 months (p = 0.01). Maximum cystometric capacity remained constant, with a mean of 195 +/- 158 ml. before insertion to 248 +/- 122 ml. at 24 months (p = 0.17). No significant differences were apparent after 24 months of followup in any of the urodynamic parameters between 44 patients with and 109 without previous external sphincterotomy. Hemorrhage requiring blood transfusion, obstructive hyperplastic epithelial overgrowth and soft tissue erosion did not occur. No deleterious effects were observed on renal or erectile function. Of the patients 43 (28.1%) required 2 prostheses to bridge the external sphincter completely. Stent removal was required in 10 patients. Seven explantations were required for prosthesis migration, 1 for pain and urethral edema, 1 for inability to maintain a condom catheter, and 1 for nonepithelialization and secondary bladder neck obstruction. A total of 13 patients (8.5%) required a subsequent operation for bladder neck obstruction. Therefore, the sphincter prosthesis is an attractive modality for the treatment of external sphincter dyssynergia in patients with and without previous external sphincterotomy because of its ease of deployment and minimal associated morbidity.     

Importance of protein kinase C for normal development of transmitter release properties in embryonic chick sympathetic neurons in culture

Three new dammarane-type triterpenoid saponins, bacopasaponins A, B and C, of biological interest have been isolated from the reputed Indian medicinal plant Bacopa monniera and identified as 3-O-alpha-L-arabinopyranosyl-20-O-alpha-L-arabinopyranosyl-+ ++jujubogenin, 3-O-[alpha-L-arabinofuranosyl (1--> 2)alpha-L-arabinopyranosyl]pseudojujubogenin and 3-O-[beta-D-glucopyranosyl (1 -->3)[alpha-L-arabinofuranosyl (1--> 2)]alpha-L-arabinopyranosyl]pseudojujubogenin by spectroscopic methods and some chemical transformations. The hitherto undetermined configurations at C-20 and C-22 of pseudojujubogenin were elucidated by phase-sensitive ROESY, and 1H and 13C signals of the saponins were assigned by DEPT, 1H-1H COSY, HSQC and HMBC techniques.     

Alcoholic beverage preference and risks of alcohol-related medical consequences: a preliminary report from the National Longitudinal Alcohol Epidemiologic Survey

In studying the alcohol-morbidity association, a substantial amount of attention and efforts has been focused on volume of alcohol intake. Considerably less is known about the differential health effects of beverage types. The present study used a most recent national household survey of the U.S. general population on drinking practices, alcohol use disorders, and their associated disabilities. The prevalence of a broad range of alcohol-related diseases was examined with respect to preferred beverage type, as well as consumption level. Our findings showed a reduced health risk associated with beer and wine drinking for a number of physical disorders, and a somewhat favorable cardiovascular effect of these two beverage types in relation to abstention. Among preferrers of beer, wine, and liquor, the results indicate that liquor preference is associated with elevated morbidity for several medical consequences. However, interpretation of results and the public health implications of these findings need to be taken cautiously, because sociodemographic and other behavioral characteristics were not considered in this preliminary report.     

Update on implantable cardioverter-defibrillators. New, safer devices have led to changes in indications

The safety and efficacy of ICDs have improved significantly in the past few years. Recent evidence supports the value of these devices not only for secondary prevention of sudden cardiac death, but also for primary prevention in post-myocardial infarction patients with poor left ventricular function, unsustained ventricular tachycardia, and inducible ventricular tachycardia on electrophysiologic study. Transvenous defibrillation using the defibrillator case as the high-voltage electrode and a biphasic shock is currently the procedure of choice. Implantation is simple, and the defibrillation thresholds are acceptably low. However, the possibility of interactions must be considered in patients with cardiac pacemakers.