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Biomedical subjects

M Laub

Publications and source records attributed to M Laub.

At least 19 recordsLinked to original sources
PubMed1992

Ca(2+)-dependent ubiquitination of calmodulin in yeast.

Recently we were able to show that calmodulin from vertebrates, plants (spinach) and the mold Neurospora crassa can be covalently conjugated to ubiquitin in a Ca(2+)-dependent manner by ubiquityl-calmodulin synthetase (uCaM-synthetase) from mammalian sources [R. Ziegenhagen and H.P. Jennissen (1990) FEBS Lett. 273, 253-256]. It was therefore of high interest to investigate whether this covalent modification of calmodulin also occurs in one of the simplest eukaryotes, the unicellular Saccharomyces cerevisiae. Yeast calmodulin was therefore purified from bakers yeast. In contrast to calmodulin from spinach and N. crassa it does not activate phosphorylase kinase. Crude yeast uCaM-synthetase conjugated ubiquitin Ca(2+)-dependently to yeast and mammalian (bovine) calmodulin. Yeast calmodulin was also a substrate for mammalian (reticulocyte) uCaM-synthetase. As estimated from autoradiograms the monoubiquitination product (first-order conjugate) of yeast calmodulin has an apparent molecular mass of ca. 23-26 kDa and the second-order conjugate an apparent molecular mass of ca. 28-32 kDa. Two to three ubiquitin molecules can be incorporated per yeast calmodulin. Experiments with methylated ubiquitin in the heterologous reticulocyte system indicate that, as with vertebrate calmodulins, only one lysine residue of yeast calmodulin reacts with ubiquitin so that the incorporation of multiple ubiquitin molecules will lead to a polyubiquitin chain. These results also indicate that the ability of coupling ubiquitin to calmodulin was acquired at a very early stage in evolution.

Animals↗
PubMed1992

Sublingual premedication with brotizolam.

This randomized, double-blind and double-dummy study was carried out in order to compare the perioperative sedation after premedication with either brotizolam 0.25-0.50 mg sublingually or diazepam 5-10 mg orally. Sixty-two patients aged 18-60 years scheduled for minor gynaecological surgery in general anaesthesia were included. Assessments were: 1. auditory continued response time (ACRT); 2. coma scale; 3. anxiety scale; and 4. final patient questionnaire. One hour after premedication the brotizolam group was more sedated, based on ACRT (P < 0.01) and the coma scale (P < 0.05). The final questionnaire showed (P < 0.05) that the brotizolam group was more satisfied with the effect of the premedication. Seven hours after the premedication the ACRT scores in both groups were similar to those before premedication and all the patients could walk about freely. In conclusion, as a premedicant in outpatients sublingual brotizolam appears to be a good alternative to diazepam.

Administration, Oral↗
PubMed1991

Ubiquitination of endogenous calmodulin in rabbit tissue extracts.

Previously we were able to show that purified calmodulins from vertebrates, plants (spinach) and the mold Neurospora crassa can be covalently conjugated to ubiquitin in a Ca(2+)-dependent manner. It was therefore pertinent to answer the question if a tissue extract contains all the components necessary for the endogenous synthesis of ubiquityl calmodulin (uCaM). Therefore [125I]ubiquitin, ATP/Mg2+ and Ca2+ were added to tissue extracts enriched by a single ion exchange step. In such extracts of red blood cells, skeletal muscle and testis a novel ubiquitin conjugate of 27-29 kDa is formed. This novel band could be identified as ubiquityl-calmodulin by the following methods: (i) identical Rf-value of novel conjugate and standard uCaM in SDS-PAGE; (ii) Ca(2+)-dependent conjugate formation; (iii) Ca(2+)-dependent adsorption to fluphenazine-Sepharose; (iv) Ca(2+)-dependent mobility change of the novel conjugate during SDS-PAGE; and (v) inhibition of conjugate band formation by phosphorylase kinase. These experiments clearly demonstrate that ubiquityl calmodulin can be endogenously generated in enriched cellular extracts and strongly indicate that this reaction is of importance in vivo.

Adenosine Triphosphate↗
PubMed1990

Lytic cocktail in children. Rectal versus intramuscular administration.

The efficacy of the lytic cocktail (1 ml contains pethidine 28 mg, promethazine 7 mg, chlorpromazine 7 mg) administered intramuscularly or rectally as premedication was studied in 51 children aged 1-12 years who had minor elective otological surgery. One group received 0.05 ml/kg intramuscularly (maximum dose 2.0 ml) and the other 0.07 ml/kg per rectum (maximum dose 2.8 ml). Most were satisfactorily sedated before operation, but after operation the rectally premedicated children were less sedated, which was in agreement with lower plasma pethidine concentrations in this group. The rectal dose should be increased if prolonged postoperative sedation is desireable.

Administration, Rectal↗
PubMed1990

Role of small calibre chest tube drainage for iatrogenic pneumothorax.

A 2 mm Teflon catheter was used as a chest tube in 28 patients with iatrogenic pneumothorax. Frequent aspirations through the catheter were performed in 16 of the patients. In the remaining 12 patients the catheter was connected to a one way flutter valve. The treatment was successful in 27 of the 28 patients--one patient required a large calibre chest tube. The mean drainage time was 48 hours. The small catheter technique is superior to the use of a large intercostal drain as it is much less traumatic and troublesome. The small calibre chest tube with a one way valve is recommended as a safe and easy technique.

Adult↗
PubMed1990

[Midazolam and ketamine for rectal premedication and induction of anesthesia in children].

Fifteen healthy children 2-10 years old and scheduled for elective surgery, received midazolam 0.35 mg/kg body weight and atropine 0.025 mg/kg as rectal premedication about 35 min before the induction of anesthesia. The induction itself was carried out in a separate and quiet room next to the operating theatre by rectal administration of ketamine 10 mg/kg and midazolam 0.2 mg/kg. With the children breathing spontaneously, anesthesia was maintained by repetitive i.v. bolus injections of ketamine. The sedative and anticholinergic effects of the premedication were satisfactory. Induction of anesthesia was smooth. Consciousness was lost after 9-15 (mean 13) min. No significant adverse effects on hemodynamics or respiration were noted. Recovery from anesthesia was uneventful. No cases of rectal irritation or unpleasant dreams were reported. Post-operative analgesia was good. In conclusion, rectal administration of midazolam and atropine for premedication, followed by ketamine and midazolam for the induction of anesthesia, proved to be a pleasant, safe, and reliable method in pediatric anesthesia.

Administration, Rectal↗
PubMed1989

[A review of pulmonary histiocytosis X].

The article contains a review and two case reports of pulmonary histiocytosis-X. This is a rare disease entity comprising about 3% of all chronic interstitial lung diseases. Diagnosis is confirmed by histological and electronmicroscopic demonstration of the typical histiocytosis-X cell. The course of the disease varies. About 25% of the patients show spontaneous remission, in 40% the changes remain stationary, while 35% progress and eventually die from respiratory insufficiency or cor pulmonale. Treatment with glucocorticoids and cytostatics should be initiated at high disease activity, with progressive X-ray changes and decreasing pulmonary function.

Adult↗
PubMed1989

Rectal induction of anaesthesia in children. A comparison between ketamine-midazolam and halothane for induction and maintenance of anaesthesia.

Thirty children were randomly allocated to one of three anaesthetic techniques. Rectal anaesthesia induction with a mixture of ketamine 10 mg.kg-1 BW and midazolam 0.2 mg.kg-1 BW and maintenance of anaesthesia with either intravenous ketamine or halothane were compared to induction and maintenance with halothane. Rectal induction was found reliable and useful. The frequency of side effects, the recovery time, and the time until the child could be discharged were similar in the groups maintained with halothane, whereas recovery was prolonged when intravenous ketamine was used for maintenance.

Anesthesia, Inhalation↗
PubMed1989

Endotoxemia and enhanced generation of oxygen radicals by neutrophils from patients undergoing cardiopulmonary bypass.

Plasma endotoxin concentrations and oxidative burst response of peripheral blood polymorphonuclear leukocytes were examined in 12 patients undergoing coronary artery bypass. The measurements were made just before the operation, 5 minutes after removal of the aortic crossclamp, and 24 hours after the operation. Endotoxin was quantitated by a combination of a sensitive Limulus amebocyte lysate assay and rocket immunoelectrophoresis measuring picogram amounts of endotoxin. Peripheral blood neutrophils were purified by a two-step dextran sedimentation and metrizoate sodium Ficoll (Lymphoprep., Nyegaard, Oslo, Norway) centrifugation. The oxidative burst response of these cells was measured for their ability to generate superoxide anion and was determined by a cytochrome c reduction assay. Preoperatively, all the plasma samples except one were free of endotoxin. The endotoxin levels reached 100 pg/ml 5 minutes after removal of the aortic crossclamp, and except in one sample they had decreased 24 hours after the operation. Studies on the generation of superoxide by neutrophils showed a decline in the response 5 minutes after removal of the aortic crossclamp and an enhancement of the response to f-Met-Leu-Phe by cells obtained from 11 of 12 patients 24 hours postoperatively. In vitro addition of bacterial lipopolysaccharide to blood from healthy individuals also enhanced the superoxide response of the neutrophils. We conclude that during cardiopulmonary bypass the circulating blood is contaminated by endotoxin and the neutrophils are primed for enhanced generation of oxygen radicals. The released oxygen radicals may be involved in the tissue damage observed in these patients.

Aged↗
PubMed1989

[A new formulation of etomidate in lipid emulsion--bioavailability and venous provocation].

In a prospective, randomized study of 16 volunteers, a new galenic formulation of the induction hypnotic etomidate in lipid emulsion was compared with the commercial form in propylene glycol (Hypnomidate). After 0.3 mg/kg etomidate plasma levels (HPLC) and hypnotic effects (visual EEG analysis) of both formulations were almost identical. Onset of action occurred after 41.6 s in the propylene glycol group (group I) and 35.6 s in the lipid emulsion group (group II). The hypnotic effect (greater than or equal to D0) lasted 7 min 20 s in group I and 6 min in group II. Plasma levels in group I decreased from 630 ng/ml after 2 min to 170 after 8 min and 37 after 130 min. With group II the plasma levels decreased from 770 ng/ml after 2 min to 150 after 8 min and 42 after 130 min (Fig. 1). In the propylene glycol experiment, 4 of 8 volunteers reported pain on injection. Within 7 days 4 persons developed phlebitis or thrombophlebitis. One showed signs of an allergic reaction (urticaria). With the new formulation of etomidate in lipid emulsion, neither venous sequelae nor allergic reactions were observed in any of the 8 volunteers (Table 2).

Adult↗
PubMed1988

Ubiquitin-calmodulin conjugating activity from cardiac muscle.

Enzyme activity capable of covalently linking ubiquitin to bovine calmodulin in an ATP-dependent manner has been detected in rabbit cardiac muscle demonstrating that this enzyme occurs not only in reticulocytes but also in other tissues and possibly all tissues and cells which contain calmodulin as intracellular Ca2+-acceptor protein. This is of special interest since a ubiquitin-dependent proteolytic activity could previously not be detected in cardiac muscle. The name ubiquityl-calmodulin synthetase [uCaM-synthetase, ubiquityl:calmodulin ligase (EC 6.3.?.?)] is therefore suggested for this enzyme. In crude cardiac muscle extracts uCaM-Synthetase displays a specific activity of 93 nUnits/mg in comparison to reticulocyte lysate with 270 nUnits/mg as measured by the fluphenazine-Sepharose affinity adsorbent test (FP-test). Analysis of the ubiquitination product (125I-uCaM) by polyacrylamide electrophoresis in the presence of SDS followed by autoradiography reveals a major double band with molecular masses of 27 and 29 kDa (mono-ubiquitination products) respectively. In addition two novel minor bands (17 and 20 kDa) of smaller molecular mass than the monoubiquitination products were detected. These are probably proteolytic breakdown products of uCaM. A model is suggested for a specific function of this synthetase in the Ca2+-dependent breakdown of calmodulin in vertebrate (eukaryotic) cells.

Adenosine Triphosphate↗
PubMed1981

[Electroencephalographically determined sedative effects (vigilosomnography) of the new Thienodiazepin-derivate clotiazepam (author's transl)].

In a double blind, randomized clinical study eighteen volunteers received either placebo or 5 mg diazepam or 5 mg clotiazepam at three different times at an interval of one week. Beside other parameters which have been measured a 60-minute polygraphic EEG recording was made thirty minutes after administration of the drugs. The vigilosomnograms revealed clear and reliable differences between placebo and the two active substances and suggest a sedative effect of both substances at the dose level used. There was only a slight difference between the two active substances. 5 mg clotiazepam produced a slightly stronger sedation than 5 mg diazepam. However, the records of autonomic side effects and subjective statements regarding the patients' condition showed that clotiazepam is associated with less side effects than diazepam.

Adult↗
PubMed1981

[The antagonistic effect of physostigmine on sedation by lormetazepam (author's transl)].

The purpose of this study was to determine the arousal effect of physostigmine after lormetazepam sedation on the human EEG. 12 male volunteers received 2 mg/kg bm lormetazepam and 30 minutes later physostigmine 2 mg preceded by atropine 1 mg. Generally an arousal effect of physostigmine could be clinically observed and more objectively demonstrated by reduced sleep stages in the vigilosomnogram (p less than 0.05). 2 volunteers did not fall asleep. 9 volunteers were awake 5-12 minutes after termination of physostigmine injection. 1 volunteer did not show any effect. Resedation and parasympathetic side effects did not occur. In earlier studies deep sleep stages after lormetazepam 1 or 2 mg/70 kg bm lasted 70 to 120 minutes. Physostigmine is recommended to counteract undesirable benzodiazepine induced sedation.

Anti-Anxiety Agents↗
PubMed1979

[The hypnotic effect of the new benzodiazepine derivative lormetazepam when given intravenously (author's transl)].

1. 7 groups of 3 healthy male volunteers each, at the age of 21--27 years received various doses of Lormetazepam (0.0635 to 4.0 mg/70 kg). -- 2. The drug was injected intravenously during 60 s. Before, during and up to 4 hours after the injections the EEG, eye-movements, ECG and respiration was recorded and blood pressures measured at given time intervals. -- 3. The vigilo-somnograms showed after the injections a change in the EEG-stages, indicating a reduction of alertness, transitions into reduced wakefulness or beginning stages of sleep. Corresponding to clinical signs one can speak with i.v. applied doses of 0.0635 to 0.5 mg/70 kg of tranquilizing, with 1 mg/70 kg of sedative and with 2--4 kg of hypnotic effects. There has been a good dosage-efficiency relation. -- 4. Side-effects or unwarranted symptoms have not been seen during the clinical observations.

Adult↗
PubMed1978

[The effect of naloxone and levallorphane following fentanyl on the blood gases, EEG and psychodiagnostic tests (author's transl)].

After administration of fentanyl, 0.15 mg naloxone or levallorphan or placebo were given several times and in increased doses and at same intervals of time to six volunteers. The experiment has been done after the rules of a double blind study. Naloxone has shown its superiority to levallorphan. The study demonstrated a faster and better action of naloxone in the way of a return to initial conditions of respiratory frequency, blood gases, and EEG. The concentration and attention faculties after naloxone have become clearly better in contrary to the results after levallorphan. At the end of an anaesthetic procedure, the greatest care should be given to the patient. First of all effective antagonism of the respiratory depression should be obtained without concomitant sedative and psychomimetic effects. The use of antagonists with agonist properties to reverse respiratory depression due to a morphinomimetic drug is not justified and so naloxone should supplant levallorphan.

Adult↗