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Biomedical subjects

M Konig

Publications and source records attributed to M Konig.

7 recordsLinked to original sources
PubMed2001

Absence of delta -9-tetrahydrocannabinol dysphoric effects in dynorphin-deficient mice.

The involvement of dynorphin on Delta-9-tetrahydrocannabinol (THC) and morphine responses has been investigated by using mice with a targeted inactivation of the prodynorphin (Pdyn) gene. Dynorphin-deficient mice show specific changes in the behavioral effects of THC, including a reduction of spinal THC analgesia and the absence of THC-induced conditioned place aversion. In contrast, acute and chronic opioid effects were normal. The lack of negative motivational effects of THC in the absence of dynorphin demonstrates that this endogenous opioid peptide mediates the dysphoric effects of marijuana.

Analgesia↗
PubMed2000

Th2-dependent airway eosinophilia is regulated by preproenkephalin.

We have used preproenkephalin (PPNK)-deficient mice to study the role of PPNK in the development of airway inflammation. Airway eosinophilia was established by either sensitization followed by airway challenge with OVA or by infection with Nippostrongylus brasiliensis. Both models induce a strong Th2 immune response, characterized by an IL-5-dependent airway eosinophilia. We observed that although the accumulation of lymphocytes in the airways of PPNK-deficient mice was similar to that induced in control mice, IL-5 production and eosinophil infiltration were reduced. We conclude from this work that PPNK has a role in enhancing Th2 cell function and that this molecule may be an important target in asthma immunotherapy.

Animals↗
PubMed1999

Preproenkephalin is a Th2 cytokine but is not required for Th2 differentiation in vitro.

Preproenkephalin (PPNK) mRNA expression has been detected in many cells of the immune system, including monocytes and lymphocytes. In the present paper, the expression of PPNK mRNA in purified CD4+ Th1 and Th2 lymphocyte subpopulations is investigated and correlated with the presence of the opioid neuropeptides leu- and met-enkephalin. We found that PPNK mRNA and met-enkephalin were present at higher levels in the Th2 cultures compared with the Th1 cultures. Lymphocytes from PPNK-deficient mice were then used to look at the role of PPNK in Th2 lymphocyte differentiation. Lymphocytes from these mice could be driven into a Th2 phenotype, suggesting that cultures containing IL-4 do not require PPNK for Th2 differentiation.

Animals↗
PubMed1998

Redesigning nucleic acids.

A research program has applied the tools of synthetic organic chemistry to systematically modify the structure of DNA and RNA oligonucleotides to learn more about the chemical principles underlying their ability to store and transmit genetic information. Oligonucleotides (as opposed to nucleosides) have long been overlooked by synthetic organic chemists as targets for structural modification. Synthetic chemistry has now yielded oligonucleotides with 12 replicatable letters, modified backbones, and new insight into why Nature chose the oligonucleotide structures that she did.

Catalysis↗
PubMed1996

Budding of rabies virus particles in the absence of the spike glycoprotein.

Budding of enveloped viruses from cellular membranes is believed to de pend on the presence of transmembrane spike proteins interacting with cytoplasmic virus components. To address the mechanism of rhabdovirus budding, we generated rabies virus mutants deficient for the glycoprotein G or the G cytoplasmic tail. We found that spikeless rhabdovirus particles were released from cells infected with the G-deficient mutant, demonstrating that a viral surface protein is not required to drive the budding process. However, particle production is enhanced approximately 6-fold and 30-fold in the presence of tailless G or G, respectively. This reveals that G also possesses an intrinsic and independent exocytosis activity. We propose a model according to which efficient budding of rhabdoviruses is achieved by a concerted action of both core and spike proteins.

Amino Acid Sequence↗
PubMed1992

Cloning and characterization of a vasopressin V2 receptor and possible link to nephrogenic diabetes insipidus.

The antidiuretic effect of arginine vasopressin (AVP) is mediated by renal-type (V2) receptors linked to adenylyl cyclase. We report here the cloning of the rat kidney V2 AVP receptor complementary DNA that encodes a 370-amino-acid protein with a transmembrane topography characteristic of G protein-coupled receptors, and with similarity to the V1a (hepatic) AVP receptor in its seven membrane-spanning domains. Expression of the cloned cDNA in mammalian cells showed specific ligand binding and activity characteristic of the native V2 AVP receptor. The receptor messenger RNA is detected only in the kidney. The human V2 receptor gene has been localized to the long arm of the X chromosome close to the locus for nephrogenic diabetes insipidus, an X-linked recessive disorder characterized by renal resistance to the antidiuretic action of AVP.

Adenylyl Cyclases↗