Does disparate occurrence of autoregulatory programmed frameshifting in decoding the release factor 2 gene reflect an ancient origin with loss in independent lineages?

In Escherichia coli an autoregulatory mechanism of programmed ribosomal frameshifting governs the level of polypeptide chain release factor 2. From an analysis of 20 sequences of genes encoding release factor 2, we infer that this frameshift mechanism was present in a common ancestor of a large group of bacteria and has subsequently been lost in three independent lineages.     

Analytical and clinical performance characteristics of Tandem-MP Ostase, a new immunoassay for serum bone alkaline phosphatase

The performance characteristics of the Tandem-MP Ostase assay, a new microplate immunoassay for bone-specific alkaline phosphatase (bone ALP; EC 3.1.3.1) in human sera, are described. Bone ALP is bound to streptavidin-coated microwells by a single biotinylated anti-bone ALP monoclonal antibody. Antigen is detected by the addition of p-nitrophenyl phosphate. The assay is performed at room temperature in <90 min. Imprecision was 2.3-6.1% with a detection limit of 0.6 microg/L. Method comparison of bone ALP measurements with the Tandem-MP Ostase assay and the mass-based Tandem-R Ostase assay (n = 285) indicated regression statistics of Tandem-MP Ostase = 1.03 Tandem-R Ostase + 0.22 microg/L, S(y/x) = 4.0 microg/L, r = 0.97. Serum bone ALP values in apparently healthy men and in pre- and postmenopausal women were also similar between the two Ostase assay formats. Liver ALP reactivity determined using the slope and heat inactivation methods was similar in both Ostase assays. Liver ALP reactivity ranged from 3 microg/L (heat inactivation) to 6 microg/L (slope method) per 100 U/L of liver ALP activity, whereas bone ALP reactivity was 37 microg/L per 100 U/L of bone ALP activity, indicating a liver ALP relative reactivity of 8.1-16.2%. Similar results were obtained with the Alkphase-B bone ALP immunoassay. The Tandem-MP Ostase bone ALP assay demonstrated increased concentrations of serum bone ALP in conditions where bone metabolism is increased and showed a rapid, temporal decrease in serum bone ALP in Paget disease patients on bisphosphonate therapy. In conclusion, the Tandem-MP Ostase assay for serum bone ALP is a rapid, simple, robust nonisotopic alternative to the Tandem-R Ostase immunoradiometric assay that provides an accurate and sensitive assessment of bone turnover.     

Diagnosis of prostatic carcinoma: value of random transrectal sonographically guided biopsies

OBJECTIVE: We studied the efficacy of random, transrectal sonographically guided biopsies in the diagnosis of prostatic carcinoma in a high-risk population. SUBJECTS AND METHODS: During a 2-year period, 570 transrectal sonographically guided prostatic biopsies were done because of clinical findings suggestive of prostatic carcinoma. Biopsies of hypoechoic lesions that were suggestive of carcinoma and segmental random biopsies of normal-appearing lobes of the prostate were performed. Transrectal sonographic findings were correlated with results of pathologic examination of the biopsy specimen and with surgical results, when available. RESULTS: Of the 202 patients found to have carcinoma, the carcinoma was detected with directed biopsy in 145 patients (72%). One hundred twenty (71%) of 169 carcinomas were detected with random biopsy when that procedure was performed. Random biopsies were the only method of diagnosing 57 (28%) of the 202 carcinomas, increasing the yield by 39%. CONCLUSION: Yield of carcinoma on transrectal sonographically guided biopsies increases significantly when segmental random biopsies are performed. Transrectal sonographically guided biopsies should include cores through hypoechoic lesions that are suggestive of carcinoma and bilateral segmental random biopsies.     

Structurally related but functionally distinct yeast Sm D core small nuclear ribonucleoprotein particle proteins

Spliceosome assembly during pre-mRNA splicing requires the correct positioning of the U1, U2, U4/U6, and U5 small nuclear ribonucleoprotein particles (snRNPs) on the precursor mRNA. The structure and integrity of these snRNPs are maintained in part by the association of the snRNAs with core snRNP (Sm) proteins. The Sm proteins also play a pivotal role in metazoan snRNP biogenesis. We have characterized a Saccharomyces cerevisiae gene, SMD3, that encodes the core snRNP protein Smd3. The Smd3 protein is required for pre-mRNA splicing in vivo. Depletion of this protein from yeast cells affects the levels of U snRNAs and their cap modification, indicating that Smd3 is required for snRNP biogenesis. Smd3 is structurally and functionally distinct from the previously described yeast core polypeptide Smd1. Although Smd3 and Smd1 are both associated with the spliceosomal snRNPs, overexpression of one cannot compensate for the loss of the other. Thus, these two proteins have distinct functions. A pool of Smd3 exists in the yeast cytoplasm. This is consistent with the possibility that snRNP assembly in S. cerevisiae, as in metazoans, is initiated in the cytoplasm from a pool of RNA-free core snRNP protein complexes.     

Abandoning informed consent: an idea whose time has not yet come

In a recent critique of informed consent, Robert Veatch argues that the practice is in principle unable to attain the goals for which it was developed. We argue that Veatch's focus on the theoretical impossibility of determining patients' best interests is misapplied to the practical discipline of medicine, and that he wrongly assumes that the patient-physician communication fails to provide the knowledge needed to insure the patient's best interests. We further argue that Veatch's suggested alternative, value-based patient-professional pairing, is, on his own terms, impossible to implement. Finally, we reexamine the philosophical and practical justifications for informed consent and conclude that the practice should be retained.