A novel,noncanonical mechanism of cytoplasmic polyadenylation operates in Drosophila embryogenesis

Cytoplasmic polyadenylation is a widespread mechanism to regulate mRNA translation that requires two sequences in the 3′ untranslated region (UTR) of vertebrate substrates: the polyadenylation hexanucleotide, and the cytoplasmic polyadenylation element (CPE). Using a cell-free Drosophila system, we show that these signals are not relevant for Toll polyadenylation but, instead, a “polyadenylation region” (PR) is necessary. Competition experiments indicate that PR-mediated polyadenylation is required for viability and is mechanistically distinct from the CPE/hexanucleotide-mediated process. These data indicate that Toll mRNA is polyadenylated by a noncanonical mechanism, and suggest that a novel machinery functions for cytoplasmic polyadenylation during Drosophila embryogenesis.     

Unsuspected infection is infrequent in asymptomatic outpatients with refractory ascites undergoing therapeutic paracentesis

OBJECTIVE: Large-volume paracentesis is a safe and effective means of treating patients with refractory ascites. However, there is limited information regarding the need for ascitic fluid studies in asymptomatic outpatients presenting for therapeutic paracentesis. The aim of this prospective study was to define the incidence and natural history of peritoneal fluid infection in asymptomatic outpatients undergoing therapeutic paracentesis. METHODS: Over a 13-month period, 118 therapeutic paracenteses were performed in 29 outpatients with decompensated cirrhosis (Child-Pugh class B = 38%, C = 62%). After a brief medical history and physical examination, ascitic fluid cell count with differential and culture were obtained from all participating subjects. Seven (24%) of the subjects were receiving norfloxacin prophylaxis, accounting for antibiotic coverage during 40% of the procedures performed. The clinical course and outcome of study subjects during a mean follow-up of 137 days was reviewed. RESULTS: All 118 (100%) of the ascitic fluid samples demonstrated absolute neutrophil counts of <250/mm3 (mean = 6.5 +/- 22.5 pmn/mm3). Asymptomatic bacterascites was identified from three of the 118 (2.5%) fluid samples, but all of these subjects spontaneously recovered without treatment or sequelae. During follow-up, six episodes of symptomatic or hospital-associated peritoneal fluid infection were identified in study participants, emphasizing the importance of fluid studies in other clinical settings. CONCLUSIONS: Although further studies are needed, the routine culture of ascitic fluid in asymptomatic outpatients with refractory ascites requiring therapeutic paracentesis may not be necessary when there is a low index of suspicion for occult infection. In circumstances of clinical uncertainty, however, obtaining ascitic fluid cell counts with differential is recommended to insure patient safety.     

Introduction to Conformal Radiation Therapy-A Historical Overview

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Vitamin D, parathyroid hormone levels and bone mineral density in community-dwelling older women: The Rancho Bernardo Study

Vitamin D (25(OH)D) increases the efficiency of intestinal calcium absorption. Low levels of serum calcium stimulate the secretion of parathyroid hormone (PTH), which maintains serum calcium levels at the expense of increased bone turnover, bone loss and increased risk of fractures. We studied the association between 25(OH)D and PTH levels, and their associations with bone mineral density (BMD), bone loss, and prevalence of hip fractures in 615 community-dwelling postmenopausal aged 50–97 years. Mean level of 25(OH)D and PTH were 102.0 nmol/l±35.0 nmol/l and 49.4 ng/l±23.2 nmol/l, respectively; 49% of women were current hormone therapy users. The overall prevalence of vitamin D insufficiency (25(OH)D<50 nmol/l) was 2%, and prevalence of high PTH levels (>65 ng/l) was 17.4%. In multiple linear regression analyses hip BMD was negatively and independently associated with PTH levels ( p =0.04), and positively and independently associated with 25(OH)D levels ( p =0.03). There were only 23 women (3.7%) who experienced a hip fracture. In age-adjusted analyses there were no significant differences of 25(OH)D and PTH levels by hip fracture status. Across the entire range of values, the overall correlation between 25(OH)D and PTH was moderate ( r =–0.20). However, after the threshold vitamin D level of 120 nmol/l, all PTH values were below 65 ng/l. Further studies are necessary to identify the optimal vitamin D levels necessary to prevent secondary hyperparathyroidism.     

Acute stages of batrachotoxin-induced neuropathy: a morphologic study of a sodium-channel toxin

Summary The acute effects of batrachotoxin, a steroidal neurotoxin which opens the membrane sodium channel, were observed morphologically at various time points up to 3 h after injection into rat peroneal nerve. Three changes were found. First, there was massive swelling of the axon at the node of Ranvier accompanied by retraction of paranodal myelin. Second, a similar swelling of unmyelinated axons was seen. Third, extracellular fluid accumulated along the internode in the adaxonal space, the intraperiod line of myelin and, rarely, the external mesaxon, with concomitant shrinkage of the axon. The first two changes might be explained on the basis of massive shift of sodium through the batrachotoxin-modified sodium channel into the axon and subsequent osmotic shift of fluid. The reason for the third change is not clear but probably also has a ionic basis.