Methods for generating point mutations at predetermined sites of RNA or DNA genomes have been developed. With Qbeta RNA as a template, minus strands were synthesized in vitro in a stepwise, substrate-controlled reaction. The nucleotide analogue N4-hydorxyCMP was introduced in the desired position, the minus strands were completed with the four standard triphosphates and used as templates to synthesize plus strands; about 30% of the progeny plus strands showed a base transition at the position corresponding to the nucleotide analogue. Two mutant RNAs with extracistronic nucleotide substitutions have been generated; one of these was viable, albeit with a reduced propagation rate, while the other was non-infectious. Furthermore, mutants with changes at the initiation codon of the coat cistron were prepared. An analysis of ribosome binding to such mutant RNAs revealed the importance of the A-U-G region for the formation of the initiation complex. With a similar approach applied to the beta-globin complementary DNA (CDNA) plasmid PbetaG, point mutations have been introduced at the positions corresponding to amino acids 121 to 123.

Base Sequence↗

PubMedDate not supplied

Assessment of enterohepatic circulation of radioactivity following a single dose of [14C]nimodipine in the rat.

4 male Sprague-Dawley rats with bile-duct fistulae were joined in a cascade. The first animal was given 5 mg/kg of [14C]-labelled nimodipine administered intraduodenally as a bolus. The bile of animals 1 and 2 was dynamically infused intraduodenally respectively into animals 2 and 3 and the bile of animal 3 was collected in fractions and infused i.d. into animal 4. The excretion and the course of the plasma concentration were studied radiometrically. The described investigation technique allows a detailed determination of the quantity and the kinetics of reabsorption and excretion during each observed pass of radioactivity in the enterohepatic circulation. On the basis of the balance between radioactivity administered and recovered and of the course of the plasma concentration it has been shown, on the example of nimodipine, that the experiment successfully simulates the situation in the intact animal. The [14C]Nimodipine radioactivity is subject to pronounced enterohepatic circulation: on average 43% of the amount excreted with the bile is reabsorbed with each recirculation and 57% is excreted with the faeces, 81% and 19% of the quantity reabsorbed being excreted respectively with the bile and urine. Because of the repeated reabsorption, the effective dose is increased by 54% and the drop in plasma concentration is slowed down in the middle time interval between 3 and 15 h after administration. The kinetic processes (absorption, excretion) become slower with each recirculation. An increasing fraction of the absorbed radioactivity undergoes direct hepatic excretion, by-passing the systemic circulation.

Animals↗

PubMedDate not supplied

PTA and stenting of benign venous stenoses in the pelvis: long-term results.

PURPOSE: To provide follow-up data on endovascular intervention for venous stenoses in the pelvis. METHODS: Between 1985 and 1995, 35 patients presented with 42 stenoses of the pelvic veins after operative thrombectomy and creation of an arteriovenous fistula, combined with intraoperative venous angioscopy. All patients underwent angioplasty and, if unsuccessful, percutaneous insertion of an endovascular stent (n = 7). RESULTS: Angioplasty with and without endovascular stenting was technically successful in 34 of 35 patients (97%). Average length of the stenoses was 20.6 mm (range 10-90 mm), average diameter before dilation 4.1 mm (range 2-6 mm), and average diameter after dilation 10.1 mm (range 5-18 mm). Intraoperative angioscopy showed pathologic findings (intimal laceration or residual thrombotic material) in 14 patients. After an average follow-up period of 4.13 years, 24 (69%) patients had patent veins. The difference in the primary patency rate between patients with angioscopically abnormal veins (6 of 14 patients, corresponding to a patency rate of 43%) and patients with angioscopically normal veins after thrombectomy (18 of 21 patients, corresponding to a patency rate of 86%) was statistically significant (p<0.01, log rank test). CONCLUSIONS: Percutaneous transluminal angioplasty and/or stenting are good treatment modalities for pelvic vein stenosis following surgical thrombectomy. Angioscopically abnormal veins have a poorer long-term patency, regardless of the type of intervention.

Adult↗

PubMedDate not supplied

[Work disability work in the first year of chronic polyarthritis. A comparison with members of the legal health health insurance].

Even though sick-leave (SL) is a direct consequence of the reduction of work capacity due to the disease, this has not gained much attention in early rheumatoid arthritis (RA). Therefore, the occurrence and duration of SL (defined as the history of SL as certified by a physician) was determined in a cross-sectional multicenter study of early RA (< or = 12 months duration) and compared to the members of the compulsory health insurance. One hundred and thirty four gainfully employed consecutive outpatients fulfilled > or = 4 of 7 ACR 1987 criteria of RA: 85 females (63% of 134 patients), age 50 years (median), disease duration 7 months (median). SL due to RA occurred in 102 of 134 patients (76%). The duration of SL because of RA was 11 days per month (about one-third of the disease duration) in males and 8 days per months (one-quarter of the time since the onset of RA) in females. SL due to RA was five times longer than expected from controls. In addition to SL because of RA, SL due to other causes occurred with a similar duration as in controls. Already in the first year of RA the large proportion of patients with SL due to RA and the long SL duration indicate the extent of substantial handicap concerning gainful employment.

Absenteeism↗