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Biomedical subjects

I Hoffmann

Publications and source records attributed to I Hoffmann.

At least 73 records · Page 4Linked to original sources
PubMed1993

The genetics of skeletal development.

A genetic analysis of biologic processes has provided substantial advances in developmental biology. Whereas the genetic analysis of Drosophila is a potent system, recently developed tools have enabled a genetic analysis of the development of vertebrates. For these studies, numerous mouse mutants are available and many more will be introduced in the near future. Mutations involving the skeleton are easy to detect. This article reports the phenotype and molecular analysis of two mutant mouse strains with skeletal abnormalities, undulated (un) and Danforth's short tail (Sd). The role of the corresponding genes in skeletal development of these two mutants and the basis for their genetic interaction are discussed.

Alleles↗
PubMed1992

Histone H4 mRNA levels are down-regulated by 3' RNA processing during terminal differentiation of myoblasts.

The capacity for 3' processing of the histone H4 pre-mRNA is lost following differentiation of rat L6 myoblasts to myotubes. Nuclear extracts prepared from proliferating myoblasts, but not differentiated myotubes, actively process histone H4 pre-mRNA in vitro. The activity of two factors required for 3' processing, the heat-labile factor and U7 snRNP, also changes during the differentiation period, concurrent with the loss of 3' processing activity. During myotube formation, the activity of the heat-labile factor decreases significantly while the 5' sequences of the U7 snRNA become progressively resistant to micrococcal nuclease digestion. Thus, the dramatic down-shift in histone H4 mRNA levels which occurs during myoblast differentiation is controlled at both the transcriptional and posttranscriptional level.

Animals↗
PubMed1991

Lung cancer and the changing cigarette.

Epidemiological studies have shown that the long-term smoker of low-yield cigarettes has a 20-50% lower risk of lung cancer than the smoker of high-yield cigarettes. This risk reduction is attributed to changes in the make-up of cigarettes and especially to the introduction of filter tips. Other changes relate to the use of tobaccos that produce lower smoke yields, including reconstituted and expanded tobaccos, as well as utilization of porous cigarette paper and perforated filter tips. New developments in the make-up of commercial cigarettes must be monitored in order to prevent unfavourable introductions. Although a smoke-free society should be the major public health goal, recent consumer statistics do not support this goal. Thus, a strong social case is made for further developments in the low-yield cigarette.

Humans↗
PubMed1990

Cell cycle-dependent regulation of histone precursor mRNA processing by modulation of U7 snRNA accessibility.

Histone gene expression is regulated both during and after transcription, with the turnover of histone messenger RNA and the regulation of its 3' processing being the principal factors that determine the size of the histone mRNA pool during the cell cycle. The mature ends of the replication-dependent histone mRNAs are generated during 3' processing by endonucleolytic cleavage of a large primary transcript. This reaction depends on a highly conserved stem-loop structure also included in the mature RNA, and a purine-rich sequence lying downstream within the spacer transcript. Three factors involved in this reaction which act in trans have been identified: the U7 small nuclear ribonucleoprotein particle (snRNP), the heat-labile factor, and the hairpin-binding factor. Here we show how U7 snRNP participates in the regulation of 3' processing: the 5' sequences of the U7 snRNA that hybridize with the downstream spacer motif during 3' processing are occluded in the G0 stage of the cell cycle but are exposed and free to interact with histone pre-mRNA during S phase, when histone mRNA synthesis is at its peak.

Animals↗
PubMed1988

Crystallization and preliminary investigation of single crystals of deoxyuridine triphosphate nucleotidohydrolase from Escherichia coli.

Deoxyuridine triphosphate nucleotidohydrolase (dUTPase), an enzyme in the nucleotide metabolism that is a pyrophosphatase hydrolyzing dUTP, has been crystallized. The crystals belong to the trigonal space group R3 and diffract beyond 2 A. The native dUTPase crystals and a mercury derivative are stable in the X-ray beam and are suitable for a high resolution X-ray structure analysis.

Amino Acid Sequence↗
PubMed1988

The potential of preoperative autologous blood donation to reduce intraoperative homologous blood transfusions in a municipal hospital.

The possibility of introducing autologous blood donation as a standard procedure in elective surgery is investigated, taking as an example a typical tertiary care municipal hospital. Homologous blood transfusions were necessary in 808 of a total of 10,128 cases. In 109 out of 311 cases, which amounts to 35% of all cases with elective surgery and homologous blood transfusion, autologous blood transfusion would retrospectively have been possible, saving a total of 327 blood units.

Blood Transfusion, Autologous↗
PubMed1987

Overproduction and large-scale preparation of deoxyuridine triphosphate nucleotidohydrolase from Escherichia coli.

A recombinant plasmid, pHW1, directing the overproduction of the enzyme deoxyuridine 5'-triphosphate nucleotidohydrolase (dUTPase, EC 3.6.1.23) from Escherichia coli has been constructed. A 1900-base DNA fragment carrying the structural gene for the enzyme (dut) has been recloned into a runaway replication vector that also carries the strong leftward promoter (pL) of bacteriophage lambda. Upon temperature shift, an E. coli strain carrying the new plasmid gives an increase in dUTPase activity of about 600-fold in rich medium compared to wild-type bacteria. The 64-kDa protein corresponding to the mature form of the enzyme reaches 20% of the total protein content of the bacterial cell. Using this strain, a simplified procedure has been developed for the purification of dUTPase. The purification steps consist of extraction of the cytoplasmic proteins, ammonium sulfate precipitation, anion-exchange chromatography and gel filtration on FPLC. The new overproducing plasmid and the simplified purification procedure developed will make it possible to purify dUTPase in sufficient amounts for detailed characterization studies.

DNA, Recombinant↗
PubMed1987

Significance of exposure to sidestream tobacco smoke.

The presence of toxins and carcinogens in ambient air polluted with tobacco smoke is largely due to the sidestream smoke emissions from the smouldering tobacco products. Levels of these toxins and carcinogens in sidestream smoke often exceed their concentrations in mainstream smoke. Dosimetry of tobacco-specific markers of exposure in physiologic fluids suggests that in regard to nicotine--which is the major tobacco alkaloid--exposure of humans to environmental tobacco smoke causes but a few percent of the nicotine levels reached as a result of active inhalation of cigarette mainstream smoke. Yet, this measurement of exposure is not universally applicable to all of the tobacco smoke pollutants in this complex matrix. Existing knowledge of the chemical composition of sidestream smoke and evidence of biological activity of sidestream smoke components suggests that this environmental pollutant has carcinogenic potential. Significance of exposure to environmental tobacco smoke must be evaluated on the basis of the severity of the pollution, the duration of exposure and personal variations in uptake.

Air Pollutants↗
PubMed1982

Pharmacology of nomifensine.

Nomifensine, a representative of a new class of chemical substances, is a compound of low toxicity and of wide therapeutical range. Nomifensine is absorbed very well, has a rapid onset of action, has no sedative effect and does not prolong alcohol-induced anaesthesia. In studies on thymoleptic activity, nomifensine showed a good and persistent activity, particularly after oral treatment. It had a better quantitative effect than the tricyclic reference compounds from which it differs by the lack of distinct anticholinergic activity. The efficacy of nomifensine does not decrease during long-term treatment. The mechanism of action of nomifensine, whose thymoleptic activity resembles that of a tricyclic antidepressant, may be explained by the influence on the catecholamine metabolism, but contrary to tricyclic compounds, nomifensine also influences the dopamine uptake. The increase in motility induced by nomifensine is based on a different mechanism as that induced by phenylalkylamines. Particularly noteworthy are the lack of a systemic effect, the remarkably slight influence on the cardiovascular system, and the slight cardio-toxicity in comparison with reference compounds. Nomifensine showed an interesting activity component in the protective influence on stress-induced ulcers. The results of kinetic studies of nomifensine in animals explain the rapid onset of action and indicate an easy use in therapy.

Animals↗
PubMed1980

Serum concentrations of vitamin E in healthy infants fed commercial milks.

Serum vitamin E concentrations were determined in 60 term and 26 premature infants during the first 2 months of life. All infants received commercial milk formula containing vitamin E. In addition, premature infants older than 10 days were given vitamin E orally as a multivitamin preparation. Thus, daily intake of vitamin E was nearly 1.2 mg/kg body weight in term infants and 2--3 mg/kg body weight in premature infants. In term infants serum levels of vitamin E rose from 2.6 mg/l (cord blood) to 7.0 mg/l (3rd--13th day) and 9.1 mg/l (16th--25th day) and remained at 10 mg/l (in the second month of life). Hemoglobin concentration and red cell number decreased continuously due to physiological anemia of infancy. In premature infants mean values of vitamin E were the same as in term infants. Vitamin E deficiency with hemolytic anemia could be demonstrated in a 2 months old infant suffering from cystic fibrosis.

Anemia, Hemolytic↗
PubMed1980

Modulation by endogenous dopamine of the release of acetylcholine in the caudate nucleus of the rabbit.

Slices of the caudate nucleus of rabbits were preincubated with 3H-choline and then superfused. Stimulation by electrical pulses at 3 Hz or by 25 mmol/l potassium elicited an increase in tritium outflow which was calcium-dependent and, in the case of electrical stimulation, tetrodotoxin-sensitive. The dopamine receptor agonist apomorphine (0.01-1 mumol/l) decreased, whereas the antagonist haloperidol increased the electrically evoked overflow of tritium. Nomifensine and cocaine, used at concentrations known to inhibit the re-uptake of dopamine, also reduced the evoked overflow of tritium, and this reduction was antagonized by haloperidol. Combined pretreatment with reserpine and alpha-methyltyrosine methylester (alpha-MT), which lowered dopamine levels by 99.5%, increased the electrically evoked overflow, as did bretylium which is shown here to block action potential-induced release of dopamine. The facilitation by haloperidol and bretylium as well as the inhibition by nomifensine and cocaine were diminished or abolished after pretreatment with reserpine plus alpha-MT. Apomorphine decreased, and haloperidol increased, the potassium-evoked overflow of tritium; the effects were not changed by tetrodotoxin. The results indicate that the striatal dopamine receptors which, when activated, depress the release of acetylcholine, are akin to the D-2 type. Endogenous dopamine also acts on the receptors as shown by several manipulations with known effects on dopaminergic transmission. A large fraction of these dopamine receptors may be located on the cholinergic axon terminals.

Acetylcholine↗
PubMed1979

Pharmacology of anti-anxiety drugs with special reference to clobazam.

1 In several studies clobazam exhibited a potency which ranges between that of chlordiazepoxide and diazepam. Its anxiolytic and anti-aggression effects are produced by doses usually ranging below those that cause disorders in motor activity. 2 This separation was demonstrable to an even greater degree with the desmethyl metabolite. The activity of the metabolite, however, was weaker than that of the original substance. 3 The advantage of clobazam compared with the 1.4 benzodiazepines lies mainly in the fact that motor activity is influenced only after very high doses, these doses being markedly above those required to induce tranquillizing and anti-agression activities. 4 Clobazam has no marked effect on the cardiovascular system, respiration of excretion.

Aggression↗