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Biomedical subjects

J Ellenberger

Publications and source records attributed to J Ellenberger.

14 recordsLinked to original sources
PubMed2000

Utilisation of bubble resonance phenomena to improve gas-liquid contact.

In several branches of science and technology a gaseous phase is dispersed into a liquid in the form of bubbles, a gaseous component then dissolves into the liquid and subsequently undergoes chemical reaction. The overall process performance can be improved substantially when the area of gas-liquid contact is increased. By subjecting the liquid phase to low frequency vibrations, the bubbles are shown to suffer significant breakage, induced by resonance. When the vibration is properly tuned, the interfacial area is found to increase by a factor of 1.8-2.4, depending on the properties of the liquid. Resonance-induced bubble breakage phenomena have a great potential for improving the rates of chemical processes involving fast reactions, with minimal energy input.

Journal Article↗
PubMed1993

Recruiting memory B cells with changed antigenic specificity.

During T cell-dependent antibody responses, the V region genes of responding B lymphocytes are physiologically mutated at a high rate. An intense selection process expands subclones of B cells producing mutant antibodies that bind Ag optimally. This implies that most mutant B cells and their antibody products are unselected and not often observed by conventional hybridoma or serum sampling procedures. Herein we show that the pool of mutant B cells includes unselected members that have acquired new antigenic specificities. Mice were immunized with a haptenated carrier protein to recruit and somatically diversity hapten-specific B cells producing antibodies with a defined V region bearing a major idiotype. During the primary immune response, the mice were given booster injections with a second related hapten conjugated to the same carrier. Hybridomas were isolated that produced idiotypic antibodies binding the second hapten but not the first. V gene sequencing analyses conclusively demonstrated that one of these was derived from a precursor B cell that expressed the defined unmutated V region with specificity for the first hapten. Sequence of the V genes expressed by the remaining six hybridomas supported this interpretation. In essence, single B cell clones were mutationally diversified to include members that had lost an original antigenic specificity while acquiring a new one, and the mutants were recruited into the memory compartment by antigenic selection. These results support the view that selection processes in vivo normally reveals only a small fraction of a mutationally diversified B cell clone. They also suggest a potential route by which antibodies of differing antigenic specificities can be generated from a single B cell clone of predefined origin and antigenic specificity.

Amino Acid Sequence↗
PubMed1986

Safety assessment of brotizolam.

Brotizolam (2-bromo-4-(2-chlorophenyl)-9-methyl-6H-thieno [3,2-f]-1,2,4-triazolo[4,3-a]-1,4-diazepine, We 941, Lendormin), a new hypnotic, was submitted to a comprehensive range of safety assessment tests. Acute (single dose) toxicity was very low, while in subacute and chronic studies in rodents, signs of toxicity were first seen at doses of 400 mg/kg or more. Histopathological changes were only seen in the 1 1/2-year study. Ataxia, salivation, and diarrhea were observed in a 4-week intravenous study in dogs, and ataxia, increased feed intake, muscular spasms, increased liver weight, and lipid depletion of the adrenal cortex in two oral studies in monkeys. Reproductive studies in the rat and the rabbit revealed no disturbances in fertility, nor were any embryotoxic or teratogenic effects detected in doses of up to 30 mg/kg. Only at 400 mg/kg was litter mortality increased. Local tolerance tests in rabbits indicated good compatibility of brotizolam when administered intramuscularly, intra-arterially, or intravenously. No signs of any genotoxic action could be detected. A carcinogenicity study in mice showed no evidence of any oncogenic effect, while in rats, although the incidence of certain tumors appeared somewhat higher in the high-dose group, this could be explained by the range of biological variation within the strain, a possible modulating effect on the immune system due to the stress of a very high dose, and a functional effect on the thyroid. These studies thus demonstrate that brotizolam has a remarkably wide therapeutic range.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Methodologies for the determination of various genetic effects in permeable strains of E. coli K-12 differing in DNA repair capacity. Quantification of DNA adduct formation, experiments with organ homogenates and hepatocytes, and animal-mediated assays.

Derivatives of E. coli K-12 strain 343/113 differing in DNA repair capacity, in permeability to large molecules, and in some metabolizing activities (nitroreductase, glutathione), were constructed for the quantitative determination of the induction of various genetic effects, such as forward and back mutations, lysogenic induction of prophage lambda, and repairable DNA damage. These E. coli strains can be used in assay procedures which allow variation and control over several experimental conditions, such as oxygen tension, time, pH, temperature of incubation and growth phase of the indicator cells. Methods are described for the simultaneous determination of genetic effects and of DNA-adduct formation during mutagen treatment, i.e. by using radio-labeled compounds or by means of an enzyme-linked immunosorbent assay (ELISA). Mammalian biotransformation of xenobiotics can be investigated by including various fractions of mammalian organs in the system. Examples of the relative effectiveness of the activating potential of S9, S100 and isolated hepatocytes for dialkylnitrosamines and other carcinogens are presented. Host-mediated assays, finally, are described which, in addition to gene mutations, can also be used for the determination of repairable DNA damage in bacteria present in different organs, including the liver, spleen, lungs, kidneys, pancreas, and the blood stream of chemically treated mice. It is concluded that quantitative tests in vitro for assessment of induced mutagenic spectrum and genotoxic potency, combined with the host-mediated assay as a monitor, in vivo, of genotoxic factors present in various organs of animals, may become useful in the assessment of genotoxic (and possibly tumor-initiating) properties of chemicals for which long-term in-vivo mutagenicity and/or carcinogenicity data are not yet available.

Alkylation↗
PubMed1975

Mutagenic activity of cyclophosphamide, ifosfamide, and trofosfamide in different genes of escherichia coli and salmonella typhimurium after biotransformation through extracts of rodent liver.

Experiments are performed to compare the mutagenic properties of the three phosphamide esters of nitrogen mustard, cyclophosphamide (CP), ifosfamide (IF), and trofosfamide (TF), in different bacterial systems. The systems include forward mutations leading to resistance against 5-methyltryptophan (MTR) and from galR-s18 to gal-+ in Escherichia coli 343/113, back mutations from arg56 to arg-+ in Escherichia coli 343/113 and back mutations from hisG46 to his-+ in Salmonella typhimurium TA1535. CP, IF, and TF are not mutagenic per se. After biotransformation through isolated rodent liver homogenates (S-9 fraction) all three compounds exhibit mutagenic activity in the order CP smaller than IF smaller than TF. Specific activating potential of mouse liver extracts is higher than that of rat liver. Except for back mutations in S. typhimurium TA1535, all mutation systems tested show a similar pattern of induction after treatment with CP, IF, and TF. However, because gal-+ mutations are not induced by CP under conditions where arg-+ and MTR are induced, it is suggested that more than one mutational system be used in routine mutagenicity testing.

Animals↗