Polyadenylation of mRNA is a key step in post-transcriptional control of gene expression. Therefore, age-dependent changes in poly(A) synthesis have to play a crucial role in the course of cellular aging. In this review, the importance of the signal sequence, poly(A), in determining mRNA stability and intracellular distribution of mRNA during aging is discussed.

Aging↗

PubMedDate not supplied

Protein-protein interaction of the Ro-ribonucleoprotein particle using multiple antigenic peptides.

Protein protein interactions play a significant role in maintaining the structural and functional integrity of the cell. We used multiple antigen peptides (MAPs) to analyze such interactions within the Ro (or SSA) ribonucleoprotein complex. Our data showed that 60 kD Ro and La colocalize in the nucleus of the cell. Previous data have indicated that 60 kD Ro and La co-exist via interactions with the hYRNAs. We were interested to see whether 60 kD Ro and La interact with each other through protein protein interactions. MAPs were produced with sequences derived from the autoepitopes of 60 kD Ro. When used in agarose immunodiffusion certain MAPs formed precipitin lines specifically with Ro and La antigens. Used in affinity chromatography the Ro MAPs purified the Ro ribonucleoprotein particle from lymphocyte extract. Solid phase immunoassay and surface plasmon resonance (SPR) confirmed the observations obtained with agarose diffusion. Using SPR, kinetic analyses gave an apparent affinity constant of about 1 x 10(7) M(-1) for Ro-MAP-60 kD Ro interactions. The autoantigens Ro and La are specific targets in autoimmune diseases, particularly systemic lupus erythematosus (SLE) and Sjögren's syndrome, and are known to exist together as a complex with hYRNAs. The present data indicate that there are protein-protein interactions between Ro and La.

Amino Acid Sequence↗

PubMedDate not supplied

Evaluation of efficacy and plasma concentrations of ropivacaine in continuous axillary brachial plexus block: high dose for surgical anesthesia and low dose for postoperative analgesia.

BACKGROUND AND OBJECTIVES: Ropivacaine is a potent local anesthetic that, experimentally at low concentrations, produces an effective block of pain conducting nerve fibers. Therefore, it was hypothesized that 0.1% and 0.2% ropivacaine would provide clinically adequate postoperative analgesia in continuous axillary plexus block. METHODS: Sixty patients (ASA I-II) scheduled for elective hand or forearm surgery received 5 mg/kg of 0.75% ropivacaine for axillary block using nerve stimulator technique. One hour later, in random order, a continuous infusion of either 0.1% ropivacaine (0.125 mg/kg/h), 0.2% ropivacaine (0.25 mg/kg/h) or saline 6 to 11 mL/h was started. RESULTS: The mean total ropivacaine dose for the surgical block was 5.1 to 5.2 mg/kg with the supplementation. All patients were pain free for the first 12 to 15 hours after the block. The need for postoperative analgesics during the infusion was similar in all groups. After the initial block, the maximum plasma concentrations (mean 2.5 microg/mL) were measured at 45 or 60 minutes after injection. The highest individual plasma concentration was 4.2 microg/mL. Despite the high venous peak concentration, no toxic reactions were observed. The mean peak plasma concentration (Cmax) was 2.2+/-0.5 microg/mL for saline, 2.6+/-0.8 microg/mL for 0.1% ropivacaine, and 2.6+/-0.7 microg/mL for 0.2% ropivacaine. During the continuous infusion of 24 hours, the ropivacaine concentration declined steadily. CONCLUSIONS: Ropivacaine is safe and effective for axillary brachial plexus block. The continuous infusion of 0.1% or 0.2% ropivacaine was no more beneficial than an infusion of saline in relieving postoperative pain in patients having elective hand surgery. None of the infusions were sufficient to adequately treat the patients' pain without the addition of adjunct agents.

Adult↗

PubMedDate not supplied

Toxicity and mutagenicity of molds of the Aspergillus glaucus group. Identification of physcion and three related anthraquinones as main toxic constituents from Aspergillus chevalieri.

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Animals↗

PubMedDate not supplied

Clinical research: is the filling missing from the medical research sandwich?

Clinical research is essential for patients to benefit from the advances of medical science. Particularly needed are thorough and imaginative investigations into applied physiology, clinical observation, and patients' experience. This can help clinicians and their patients to distinguish between pathology and healthy variation, interpret diagnostic information, understand what patients want and gain from health care, and apply study results to individuals' problems. Clinical research has not grown as much as other forms of medical research, and is sometimes regarded as unscientific. Young academic clinicians are often persuaded that the only road to science leads through the laboratory. Clinical research, however, offers equal opportunities for original enquiry, rigour and excellence. The medical research sandwich will continue to provide an unbalanced diet unless research leaders and funders take the clinical setting more seriously.

Evidence-Based Medicine↗

PubMedDate not supplied

Toxicity and mutagenicity of anthraquinones from Aspergillus chevalieri.

More than 100 strains of the Aspergillus glaucus group were cultivated on synthetic media for 11 days at 28 degrees C. Organic extracts of fungal material were screened by thin-layer chromatography (TLC) for the mycotoxins aflatoxins B1,2 and G1,2, sterigmatocystin, ochratoxin A, gliotoxin, patulin, and xanthocillin X. None of these toxins were produced in detectable amounts under experimental conditions. Nevertheless, organic extracts exhibited high toxicity after intraperitoneal (i.p.) administration in mice. Aspergillus chevalieri strain ZT 8268 was selected for further investigation of its toxic metabolites. The main toxic action was attributed to the four anthraquinone derivatives, physicion, physcionanthrone B, physciondianthrone, and erythroglaucin, which were isolated and identified. No toxic effects were found after oral administration. Using the Salmonella/mammalian microsome test, mutagenic activity (frame-shift) was detected in strain TA 1537 in the presence of S-9 liver microsome preparation.

Animals↗

PubMedDate not supplied

[Neonatal lupus erythematosus].

The neonatal lupus erythematosus syndrome, first described by McCuistion and Schoch in 1954, is associated with characteristic skin lesions and congenital heart block in the new-born, and the presence of Ro-(SSA), La-(SSB), or RNP antibodies in mothers and infants. A transplacental transference of maternal autoantibodies is discussed as possible pathophysiologic mechanism in neonatal lupus. The symptoms, the onset, and recently published pathogenetic concepts are reviewed.

Antibodies, Antinuclear↗

PubMedDate not supplied

[The Ro/SS-A antigen-antibody system].

First described in 1969 by Clark et al., the Ro/SS-A antibody system has proved most important in the evaluation of lupus patients possessing prominent photosensitive cutaneous lesions. Ro antibodies are also seen in patients with primary Sjögren's syndrome, neonatal lupus erythematosus, congenital heart block and ANA-negative LE. The most recent data of biochemical characterization have led to the supposition that these antibodies may exert a direct pathogenic effect. In this review the current knowledge concerning the Ro-antigen-antibody system is summarized.

Antibodies, Antinuclear↗

PubMedDate not supplied

[Age-dependent gene induction in the quail oviduct. Role of post-transcriptional changes in the aging process].

In 1974 we introduced the quail oviduct system to molecular gerontology as a model for investigating age-dependent gene realization at the molecular level. During ageing the amounts of synthesized ovalbumin and avidin, the two major oviduct proteins, decrease to reach almost 0-values. Soon it emerged that the reasons for the reduced ovalbumin and avidin syntheses were not only on the transcriptional but in addition on the posttranscriptional level. It was found that the observed reduced capacity for protein biosynthesis was an age-correlated impairment of those enzyme systems which are involved in the processing of hnRNA to mRNA and in the transport of mRNA from nucleus to cytoplasm. After having firstly discovered and purified some key enzymes of mRNA processing ( endoribonucleases IV, V and VII; U1- snRNP -associated endoribonuclease; poly(A)-specific exoribonuclease ), and secondly studied in detail the enzymically controlled nucleocytoplasmic mRNA transport system, we observed that polyadenylation and perhaps also splicing of hnRNA (two processes in posttranscriptional modification of mRNA) are impaired during ageing. Pronounced changes occur especially at the level of polyadenylation of hnRNA; analytic and enzymic studies revealed that, in parallel with ageing, poly(A) catabolism increases although poly(A) anabolism remains unchanged. The consequences of this change are: reduced stability of mRNA, probably reduced splicing efficiency, reduced binding of mRNA to the inner nuclear membrane or lamina, and reduced nucleocytoplasmic transport of mRNA. The data suggest that changes at the posttranscriptional level are as important in ageing as changes in transcription, and they may explain the observed, age-dependent reduction of the amount of functional mRNA in the cytoplasm.

Aging↗