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Biomedical subjects

G Keller

Publications and source records attributed to G Keller.

At least 145 records · Page 8Linked to original sources
PubMed1985

Cis-acting sequences that affect the expression of the human fetal gamma-globin genes.

We have identified the sequences in the human gamma-globin gene promoter that are required for efficient and accurate transcription by using deletion mutants and in vitro site-directed mutagenesis. More than 131 bp (which include the 'CACA' sequence) upstream from the Cap site, are required for efficient transcription of the gamma-promoter. Furthermore, the 27 bp tandemly duplicated segment including the conserved 'CCAAT' box (represented only once in the beta promoter and required for its function) is not essential for the gamma-promoter, since scanning-linker mutants lacking part or all of the proximal 'CAT' box exhibited a 1.5 to 4.0 fold increase in the promoter function compared to the wild type. These data and the recently described point mutations in the regions of the A gamma and G gamma promoters associated with hereditary persistence of fetal hemoglobin, support the notion that the DNA sequences of the gamma-promoter region should be involved in the developmental regulation of globin genes. Molecular analysis of naturally occuring deletion-mutations in the beta-globin gene cluster leading to increased production of HbF in adult life, showed that irrespective of the nature of the deletions, they exhibit identical clinical and cellular phenotypes on interaction with the beta S gene. Erythroid progenitor cells from these individuals respond in vitro, to the same extent to the modulating effects of exogenous factors such as the 'switching activity' of fetal sheep serum with respect to their pattern of hemoglobin synthesis.

Base Sequence↗
PubMed1985

Cytohormonal and cancer screening procedure for endometrial carcinoma.

The results of cancer-screening (by Papanicolaou) and of cytohormonal examinations were evaluated in 208 patients with endometrial adenocarcinoma. The occurrence rate of atypical cells in vaginal smears was 44.2%. It was higher in the more advanced cases and after the menopause, and an inverse relationship was found with the degree of maturation of the vaginal epithelium. -It was concluded that the combination of hormonal and cancer-screening cytodiagnostic procedures, using vaginal smears alone, can hardly facilitate the early diagnosis of endometrial carcinomas. Higher efficiency could only be expected from direct endometrial smears and by frequent screening of the population at highest risk.

Adenocarcinoma↗
PubMed1984

Lipoprotein synthesis and secretion by cultured rat hepatocytes. Parallel inhibition of secretion of VLDL, HDL and albumin by monensin.

The biosynthesis and secretion of very-low-density lipoproteins (VLDL) and high-density lipoproteins (HDL) by cultured normal rat hepatocytes was investigated with particular emphasis on its modification by monensin. This acidic ionophore coordinately inhibited the rates of secretion of the several VLDL apolipoproteins and the VLDL lipids, suggesting an effect late in the process of biosynthesis and secretion, probably at the stage of exiting from the Golgi apparatus. The secretion of immunoreactive albumin into the medium was comparably inhibited, implying that the pathway and mechanisms involved in albumin secretion may be closely similar to those for VLDL synthesis and secretion. Secretion of phospholipids and of apolipoproteins E and A-I in the HDL fraction increased progressively with time over 18 h in control incubations but was strongly inhibited by monensin. During extended incubation with monensin at high concentrations (10 microM), there was a net release to the medium of a number of hepatocyte proteins, including some that comigrated with apolipoprotein A-I and apolipoprotein C, making it appear that monensin increased the secretion of these apolipoproteins. However, using labeled amino acids, it was shown by autoradiography and by immunoprecipitation that secretion of newly-synthesized, radioactive apolipoprotein A-I and apolipoprotein C was actually inhibited by monensin. These results are compatible with the conclusion that HDL synthesis and secretion may occur by mechanisms closely related to those for synthesis and secretion of albumin and VLDL.

Amino Acids↗
PubMed1984

Clonal generation of multipotent and unipotent hemopoietic blast cell colonies in vitro.

Colonies with a unique compact morphology and displaying high replating potential develop in methycellulose cultures when bone marrow cells from hydroxyurea- or 5-fluorouracil-treated mice are cultured in the presence of syngeneic thymocytes. These compact colonies are clonal, originating from a single unit, the compact-colony-forming unit (CFU). Based on replating analysis, at least three groups of compact colonies exist: (1) those that do not replate, (2) those that replate and give only GM colonies, and (3) those that give rise to granulocyte-macrophage (GM), erythroid (E), and mixed-erythroid (MIX/E) colonies. Colonies in the last group have a mean size of 2,060 cells and generate an average of 244 colonies in secondary cultures. Velocity sedimentation studies showed the compact-CFU to be similar in size to the MIX/E-CFU, sedimenting at rates between 3.5 and 7 mm/hour. In addition to giving rise to large numbers of in vitro CFU, compact-CFU are also able to generate day 8 spleen colony-forming units (CFU-S).

Animals↗
PubMed1984

Radon-222 concentrations and decay-product equilibrium in dwellings and in the open air.

Results are presented of measurements of the activity concentrations of 222Rn and its short-lived decay products and the 212Pb/212Bi concentrations in more than 200 dwellings in West Germany and in the open air. For more than 130 measurements of the equilibrium factor F in dwellings the median value was found to be 0.3. Measurements of F in the open air under various conditions resulted in a mean value of about 0.4. The results of the investigations showed that indoors F depends only slightly on ventilation, indoor 222Rn concentration and other parameters. The equilibrium factor F in the open air, however, was found to depend on meteorological conditions. Empirical correlations from the data obtained for the daughter/222Rn concentration ratios were derived to provide relations for the prediction of the individual daughter product concentrations at a measured 222Rn level. It was established that the daughter/222Rn concentration ratios for indoor air do not change within the range of 222Rn concentrations investigated (1-370 Bq X m-3). These relations, however, are not valid for the daughter/222Rn concentration ratios in outdoor air. The correlations derived further suggest that the individual daughter product concentrations may be assessed with sufficient accuracy by only measuring the 222Rn concentrations. Thus the daughter ratios obtained in this way should enable good estimates of the lung dose for members of the public due to inhalation of the short-lived 222Rn daughters and the dose contribution of the individual 222Rn-daughter products.

Air Pollutants↗
PubMed1984

Regulation and coupling of argECBH mRNA and enzyme synthesis in cell extracts of Escherichia coli.

Cell extracts from Escherichia coli were used to study both transcription and coupled translation of the argECBH gene cluster. Argininosuccinase (the argH enzyme) and N-acetylornithinase (the argE enzyme) were synthesized for 90 to 120 min, and hybridizable argECBH mRNA was synthesized for 60 min after the addition of a lambda or phi 80 dargECBH DNA template. L-Arginine (2.5 mM) repressed synthesis by argR+ extracts of argECBH mRNA 2-, to 3-fold, argE enzyme 5- to 8-fold, and argH enzyme 20- to 60-fold. Repression was specific for L-arginine, and argR extracts were insensitive to added L-arginine. The argECBH mRNA made under conditions of restricted protein synthesis had reduced ability to function in the formation of the argE and argH enzymes and was found to be predominantly 6 to 8S in sucrose density gradients. When protein synthesis was allowed, the mRNA formed was functional, and large amounts of 14 to 23S argECBH mRNA appeared on sucrose gradients. An S-100 supernatant freed of ribosomes was capable of producing hybridizable arg mRNA, but significant functional message was only produced when ribosomes were present. When purified RNA polymerase was used, the formation of short 6 to 8S argECBH mRNA was dependent upon added rho protein. The data suggest that rho-dependent sites in the argECBH operon allow early termination of mRNA synthesis when transcription is not coupled to active enzyme synthesis.

Amidohydrolases↗
PubMed1984

[The effects of REM sleep deprivation on the motor behavior of rats].

The effects of rapid-eye-movement (REM) sleep deprivation for 72 h on motor behaviour of rats have been studied. It has been shown both an increased spontaneous locomotor activity and an enhanced rotational behaviour after unilateral intrastriatal injection of dopamine 24 h and 48 h after the end of REM sleep deprivation. The enhancement of motor activity after REM sleep deprivation points to changes in the dopaminergic transmission system. But it is not yet clear, if the main cause of these effects is the development of a super-sensitivity of postsynaptic dopaminergic receptors. In the same way interactions between the dopaminergic system and other inhibitory transmission systems may play an important role, explaining effects of REM sleep deprivation.

Animals↗
PubMed1983

Construction and characterization of plasmid vectors for cloning in Staphylococcus aureus and Staphylococcus carnosus.

Several plasmid vectors for cloning in Staphylococcus aureus and S. carnosus have been constructed and characterized. The chimeric plasmids are composed of parts of the following parental plasmids: The chloramphenicol-resistance plasmid, pC194, the tetracycline-resistance plasmid, pMK148, and the erythromycin-resistance plasmid, pE12. All the chimeric plasmids confer two selectable antibiotic-resistance markers on host cells. Insertional inactivation of the various antibiotic-resistance markers occurred at the BclI site of pE12, and the Sau96- or AvaII-site of pMK148; only a slight inactivation of the chloramphenicol-resistance marker occurred at the HaeIII-site of pC194. The chimeric plasmids pCT20 and pCE10 are both stable in S. aureus and S. carnosus. In addition, the hybrid plasmids of pCT20 and pCE10, containing lambda-DNA fragments in various restriction sites between 0.4 and 1.2 kb, are stably maintained. The inserted lambda-DNA fragments appear unchanged.

Chloramphenicol↗
PubMed1982

Activity concentrations of 222Rn, 220Rn, and their decay products in german dwellings, dose calculations and estimate of risk.

Measurements of the concentrations of 222Rn, its short-lived decay products and of 212Pb - 212Bi were performed in 150 dwellings and in the open air in the Federal Republic of Germany. The concentrations of 222Rn was measured by electrostatic deposition of 218Po. The concentration of the short-lived decay products were measured by air sampling and alpha-spectroscopy. It was found that inside dwellings the average potential alpha-energy concentration of the short-lived daughters is about three times higher than in the open air. The total potential alpha-energy concentration indoors amounts to 2.6 . 10(-3) Working Level (W.L.). Direct measurements of the equilibrium factor inside dwellings gave a mean value of 0.3. A strong dependence of the potential alpha energy concentration on the ventilation rate in dwellings has been observed. These ventilation effects exceed the effects caused by differences in the activity concentrations due to different building materials. The dose calculation results in an average dose to the whole lung due to the inhalation of short-lived radon daughters of about 0.05-0.2 m/Gy/a. An estimate of risk - based on the risk factors for uranium miners - shows an average lifetime risk of about 6 . 10(-4) for the incidence of lung cancer caused by inhalation of radon and thoron daughters in dwellings in the Federal Republic of Germany.

Germany, West↗
PubMed1982

[Peritoneography for identification of non palpable herniation].

Peritoneography with trijodic contrast medium is a simple but very effective method to identify non palpable herniations causing inguinal pain of unknown origin. It is also very useful for early detection of recurrent herniations after surgery as well as for diagnosis of non palpable umbilical herniations in adipose patients, and for demonstration of herniastions of the abdominal wall after trauma. Technique of investigation and radiological symptoms are described following experience with 154 outpatients. In 25% of these patients during clinical investigation no herniation was found.

Abdominal Injuries↗
PubMed1980

Hemopoietic colonies on the chorioallantoic membrane of the chick embryo: induction by embryonic, adherent, non-hemopoietic spleen cells.

Granulocytic and erythrocytic colonies developed on the chick embryo chorioallantoic membrane (CAM) following the inoculation of chick embryo spleen cells. Dose response and kinetic experiments showed that the colonies were derived from cell aggregates present in the inoculum. Dissociation and reaggregation studies of the CAM colony-inducing cells (CAM-CIC) indicated that these cells must be present as aggregates in order to form colonies. Results from the morphology and cell marker experiments suggested that the colony-inducing aggregates (CAM-CIA) attract and support the differentiation of primitive host hemopoietic cells. The physical characteristics of the CAM-CIC, which are different from those of the hemopoietic progenitor cells, indicated that they represent a stromal cell population of the chick embryo spleen. Further evidence supporting this notion was provided by the radiation studies which showed that the colony-inducing ability of the CAM-CIC is radioresistant. The above characteristics of the CAM-CIC strongly suggest that they represent the stromal cells of the chick embryo spleen which influence hemopoiesis.

Allantois↗
PubMed1980

[Aldose-reductase inhibitors and cataract formation (author's transl)].

Flavonoids are known as potent inhibitors of aldose reductase, an enzyme that may initiate cataract formation in diabetes. We have tested the inhibitory activity of new flavone derivatives on a homogenate of lens epithelium. Compounds which inhibited the enzyme activity by more than 50 percent at 10(-60) M were then tested on rat lenses perfused in a 0.027 M glucose solution. Our preliminary studies indicate that these new flavone derivatives can prevent or delay the formation of cataract in an in-vitro model.

Aldehyde Reductase↗
PubMed1979

Oxygen consumption during maintenance hemodialysis.

The influence of hemodialysis on oxygen consumption was studied in 15 patients on maintenance dialysis. Red cell 2,3-DPG, P50, an inverse measure of oxygen affinity of hemoglobin, arterial and central venous blood gases and cardiac index were measured. 2,3-DPG remained unchanged, whereas in vivo P50 fell significantly during dialysis due to a rise of pH (Bohr effect). Arterial PO2 was lower after than before dialysis, but arterial and central venous oxygen saturations did not change significantly. Cardiac index increased from 3.66 to 4.0k liter/min/m2. Oxygen consumption rose from 120.5 to 131.7 ml/min/m2 (p less than 0.05), the rise being accounted for by an increase in cardiac index and by a slight post-dialysis hemoconcentration. However, even correcting for these parameters did not reveal a decrease in oxygen consumption. It is concluded that, contrary to previous assumptions, the hemodialysis-induced rise in pH with its consequent increase of oxygen hemoglobin affinity did not impair oxygen delivery in this group of patients on maintenance dialysis.

Adult↗