The cellular tandemization of the herpes simplex virus (HSV) thymidine kinase (tk) gene was studied in tk- mouse fibroblasts after gene transfer by microinjection into the nucleus or by calcium phosphate-mediated transfection. Three different DNA substrates, designed to yield simple integration patterns, were used: a gel-purified 3.6-kb Bam HI fragment containing the HSV tk gene; the same fragment self-ligated; and the 3.6-kb fragment ligated to a Bam HI-cleaved subset of genomic mouse DNA. The genomic DNA of six independently isolated transformed cell lines was analyzed by Southern blotting and the structure of the tk-specific DNA was studied. The data suggest that modifications (mutations, deletions, recombination events, and recircularization, etc.) of the input DNA fragment occur early after its introduction into the cell. Subsequently these structures are multiplied in a directional manner, generating larger arrays of DNA with distinct and regularly repeated areas. These concatemers can eventually be integrated into the host genome.

Animals↗

PubMed1985

Target size of 5'-nucleotidase in smooth muscle.

Target size of the 5'-nucleotidase in six different smooth muscles was determined by radiation inactivation. The enzyme in the soluble fraction of rat myometrium and vas deferens gave a target size of approximately 80,000 daltons. The plasma membrane bound 5'-nucleotidase however, gave target size of 80,000 to 110,000 daltons in rat gastric fundus and vas deferens and dog stomach and ileum, 135,000 daltons in rat mesenteric artery and 210,000 daltons in rat myometrium.

5'-Nucleotidase↗

PubMed1985

[Activity of urease in microcapsules].

The activity of urease in microcapsules formed by a symplex membrane from cellulose sulphate and polydimethyldiallyl ammonium chloride is studied and compared with that of free urease in solution. Both free and encapsulated urease exhibits a similar pH optimum. The interaction of urease with cellulose sulphate causes a decrease of the activity down to 35 to 38%. In spite of its lower absolute activity the encapsulated urease shows a higher long time stability than the free urease. The presented immobilization method for urease could be of importance for an active detoxification in uremia.

Capsules↗

PubMed1984

Tumor blood flow and O2 availability during hemodilution.

Experiments were performed to study the influence of localized and systemic hemodilution on tumor blood flow and on O2 availability in the tumor tissue. The results obtained clearly show that both localized and systemic hemodilution can distinctly improve nutritive blood flow through solid tumors. This can be utilized to enhance pharmacokinetics of antitumor drugs. Due to the improved metabolic status, the pharmacodynamics of some antitumor drugs should also be enhanced. To achieve a maximum improvement of the oxygen supply to the tumor, hematocrit values should not be decreased below 0.20 in localized hemodilution, and 0.30 in systemic hemodilution.

Animals↗

PubMed1984

Contraception with an LHRH agonist: effect on gonadotrophin and steroid secretion patterns.

Chronic treatment with the LHRH agonist D-Ser(TBU)6-LHRH (1-9)-EA (buserelin) has been suggested as a contraceptive method since it has been shown to inhibit ovulation. To elucidate the mechanism of this paradoxical action, we investigated the pattern of gonadotrophin and steroid secretion after the daily intranasal application of 300 micrograms of the agonist. Ten volunteers with ovulatory cycles received the analogue from Day 1 to Day 22 and 5 mg norethisterone acetate from Day 16 to Day 22. Blood samples were taken on Day 1, 15, and 21 every 15 min for 6 h after the application of the agonist. LH secretion was increased nine-fold on the first treatment day as compared to Day 2 of the preceding control cycle. Thereafter, it decreased slowly but was still elevated five-fold on Day 21 of treatment. FSH release increased three-fold on Day 1 but decreased thereafter to values similar to those of the controls. During treatment with the analogue, the LH/FSH ratio changed from 1.3 (controls) to 3.8 on Day 1 and to 5.5 on Day 15 and 21 of treatment. Although the ovary retained follicular activity, ovulation was inhibited in every treatment cycle. This seemed to be due to an impairment of follicular steroid synthesis as indicated by a significant increase of 17 alpha-hydroxyprogesterone and testosterone levels for several hours after the application of the analogue. It appears that at least during the first treatment cycle of daily administration of buserelin the abolishment of pulsatile gonadotrophin release, and the abnormally increased ratio of LH/FSH secretion may possibly impair follicular maturation and thus contribute to the inhibition of ovulation.

17-alpha-Hydroxyprogesterone↗

PubMed1984

[The natural history of diabetes with respect to disorders of insulin function].

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Adolescent↗

PubMed1984

[The use of neuroleptanesthesia in adenotonsillectomy in children].

Two groups of 100 children each who underwent adenoidectomy and/or tonsillectomy were anaesthetised by halothane 1% or by a neuroleptic technique (NLA) using fentanyl 0.0025 mg/kg and droperidol 0.125 mg/kg as a fixed combination (Thalamonal). Both techniques were supplemented with nitrous oxide/oxygen 4/2 l. All children were premedicated with atropine 0.015 mg/kg, fentanyl 0.0025 mg/kg and droperidol 0.125 mg/kg i.m. Quality of premedication and postoperative behaviour and analgesia were assessed by standardised criteria. 93% of the patients arrived at the theatre sleeping or detached, 75% showed almost no reactions to venipuncture. Heart rate during surgery in both groups increased by 13%, mean arterial blood pressure in the NLA group increased by 9% and in the halothane group dropped by 5%. Postoperatively blood pressure in NLA patients returned to normal, while in the halothane group there was a transient rise by 10%. Protective reflexes and consciousness were restored in the NLA group earlier. After halothane, stridor occurred in eight cases upon extubation. Postoperative analgesia scores in NLA patients were double those in the halothane group. Moderate metabolic acidosis and slight hypercapnia were postoperatively present in both groups twice. Modified neuroleptanaesthesia proved equal to halothane anaesthesia for ENT surgery. No respiratory depression was seen. Advantages like uncomplicated quick recovery and protracted postoperative analgesia are opposed by disadvantages like inferior vegetative blockade and inferior pharmacokinetics. Close postoperative supervision in a recovery room is a prerequisite to using this NLA technique.

Adenoidectomy↗

PubMed1983

Study of H2O2-supported N-demethylations catalyzed by cytochrome P-450 and horseradish peroxidase.

H2O2-supported oxidative demethylation reactions catalyzed by cytochrome P-450 and horseradish peroxidase have been compared. In contrast to peroxidase catalyzed reactions no free substrate radicals could be detected by EPR stopped flow measurements in demethylation reactions catalyzed by highly purified cytochrome P-450 although the rate of product formation for both enzyme systems was identical. These findings cause doubts in a general peroxide dependent demethylation mechanism valid for all hemoproteins and in the hypothesis that free substrate radicals are principally formed during cytochrome P-450 catalysis.

Aminopyrine↗

PubMed1979

[Epidemiology of hepatitis A: serological study among a French population (author's transl)].

To investigate the prevalence and distribution of antibodies to hepatitis A antigen (anti HAV Ab) we tested 848 French people living mainly but not exclusively in Franche-Comté (East of France). In Franche-Comté, 76 per cent of all the subjects studied were found to be anti-Hav ab positive, as determined by specific radio-immuno-assay. The rate of antibody detection was correlated with age; the prevalence was low (38 per cent) in childhood and adolescence, gradually increasing throught adulthood, and reaching its peak level (greater than 95 per cent) in people aged 40 and above. Anti-HAV Ab was detected more frequently in farmers (89 per cent), factory workers (87 per cent) and office employees (80 per cent) than in hospital personnel (53 per cent). Socioeconomic differences were found to be important in young people but tended to disappear at about 40 years of age. No difference was found in the prevalence of anti-HAV Ab between national servicemen from Franche-Comté and those from other regions. In 3 per cent of cases anti-HBs Ab was associated with the presence of anti HAV Ab. The subject possessing anti HBS Ab had the same prevalence of anti-HAV Ab (75 per cent) as those without (76 per cent).

Adolescent↗