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Biomedical subjects

G Vogt

Publications and source records attributed to G Vogt.

At least 19 recordsLinked to original sources
PubMed1992

Cloning and expression of a novel mouse somatostatin receptor (SSTR2B).

A mouse somatostatin (SS) receptor cDNA was cloned from neuroblastoma x glioma (NG108-15) cells. The sequence is almost identical to that of the mouse SSTR2 receptor [(1992) Proc. Natl. Acad. Sci. USA 89, 251)] but lacks about 300 nucleotides between transmembrane domain VII and the C-terminus. This spliced variant of SSTR2 (designated SSTR2B) encodes a protein which is 23 residues shorter than that predicted from the SSTR2 sequence, and differs in 15 amino acids at the C-terminus. mRNA corresponding to SSTR2B occurs in mouse tissues in higher abundance than that of SSTR2. SSTR2B binds SS peptides with high affinity when expressed in mammalian cells.

Amino Acid Sequence↗
PubMed1992

Stereoisomers of calcium antagonists which differ markedly in their potencies as calcium blockers are equally effective in modulating drug transport by P-glycoprotein.

The (-)-isomer of verapamil is 10-fold more potent as a calcium antagonist than the (+)-isomer. However, both enantiomers are equally effective in increasing cellular accumulation of anticancer drugs [Gruber et al., Int J Cancer 41: 224-226, 1988]. In addition to verapamil, there exists a wide variety of stereoisomers with phenylalkylamines and dihydropyridine structures which markedly differ in their potency as calcium antagonists. We have tested these drugs for their ability to increase intracellular accumulation of [3H]vinblastine ([3H]VBL) in a doxorubicin-resistant cell line (F4-6RADR) derived from the Friend mouse leukemia cell line (F4-6P) and in COS-7 monkey kidney cells. Both cell types express substantial amounts of multidrug resistance gene 1 mRNA and P-glycoprotein as revealed by RNA and immuno blot analysis. The enantiomers with phenylalkylamine structures [(+/-)-verapamil; (+/-)-devapamil; (+/-)-emopamil)] and with dihydropyridine structures [(+/-)-isradipine; (+/-)-nimodipine; (+/-)-felodipine; (+/-)-nitrendipine; (+/-)-niguldipine] increased [3H]VBL accumulation in both cell lines at micromolar concentrations. Although the stereoisomers of these drugs differ markedly in their potency as calcium channel blockers they were about equally effective in increasing VBL levels in the cells. There was no substantial difference in the potencies of the phenylalkylamine drugs in affecting cellular [3H]VBL transport. Major potency differences, however, were observed in the dihydropyridine drug series with the niguldipine isomers as the most effective drugs. Moreover, the niguldipine enantiomers were equally as effective in reversing VBL resistance in F4-6RADR cells as were the verapamil enantiomers. Since (-)-niguldipine (B859-35) displays a 45-fold lower affinity for calcium channel binding sites than (+)-niguldipine, but is equally potent in inhibiting drug transport by P-glycoprotein and in reversing drug resistance, it may be, in addition to (+)-verapamil, another useful candidate drug for the treatment of multidrug resistance in cancer patients.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1992

Specific and non-specific immunity and protection of macaques against SIV infection.

The simian immunodeficiency virus is a retrovirus closely related to the human immunodeficiency viruses; it induces an AIDS-like disease in macaques, and provides therefore an obvious animal model for anti-lentiviral drug and vaccine strategy assessments. In our experiment, we immunized rhesus macaques with a purified and formalin-inactivated whole SIVmac251 antigen preparation. Most of these monkeys were still protected for more than 4 months following a heterologous SIVsm intravenous challenge. Both virus stocks, for vaccine preparation and challenge, were provided by culture supernatants of infected T cells of human origin. Four of the protected macaques were then reimmunized with the same antigen preparation and rechallenged intravenously with a homologous rhesus cell grown SIVmac251. Unexpectedly, all animals developed clinical and biological evidence of infection by day 15 after the second challenge.

Animals↗
PubMed1992

Identification of a neutralizing domain in the external envelope glycoprotein of simian immunodeficiency virus.

Two murine monoclonal antibodies (MAbs), designated MATG2014 and MATG2033, were generated. They are reactive with the external envelope glycoprotein gp130 of the simian immunodeficiency virus of macaque monkey (SIVmac251), and display a cell-free virus neutralizing activity in vitro. In addition, MATG2014 cross-reacts with HIV-2Rod gp140. Epitope mapping of these MAbs was performed by screening and SIVmac peptide library expressed in yeast and confirmed using synthetic peptides. MATG2014 and MATG2033 recognize two overlapping epitopes localized in an 18 residue domain between amino acid 171 and 188 of the SIVmac251 gp130. Sera from experimentally SIV-infected macaques are immunoreactive with this neutralizing domain. Sequence comparison with related SIV and HIV-2 viral strains indicates a low variability of this region, consistent with the cross-reactivity of MATG2014 with HIV-2Rod gp140. This domain should then be considered in designing experimental vaccines.

Amino Acid Sequence↗
PubMed1992

Searching for distantly related protein sequences in large databases by parallel processing on a transputer machine.

AliMac is an implementation of a sensitive sequence alignment algorithm on a parallel computer. The method achieves reliable alignments for very distantly related sequences from a combined use of amino acid exchange weights and physicochemical characteristics. The algorithm is computing intensive and its usage on conventional computers is limited to a relatively small number of sequences. The parallel implementation uses a Macintosh IIcx host computer and 21 transputers and achieves 22 times the speed of a VAX 8650 at a fraction of the cost. This paper describes the AliMac hardware and software and discusses problems and peculiarities of parallel implementations, especially with transputers. Finally, several popular sequence alignment algorithms are compared in their ability to detect distantly related sequences in searching large databases.

Algorithms↗
PubMed1991

In vivo decondensation of chromatin and nucleolar fibrillar component by Leucaena leucocephala ingredient.

Feeding of the shrimp, Penaeus monodon, with diets containing leaf meal of the leguminous shrub, Leucaena leucocephala, resulted in complete chromatin decondensation of hepatopancreas cells. The fibrillar component of the nucleolus was decondensed in parallel, whereas the granular component remained intact. This unique combination of nuclear signs was accompanied by only moderate alterations of other cell organelles. Our findings therefore demonstrate an encouraging possibility to manipulate the chromatin organization in living cells. Furthermore, ultrastructural features obtained thus far only in isolated and chromatin-depleted nuclei could be verified. These are, for instance, filament bundles which attach the nucleolus to the nuclear periphery, or a filamentous skeleton of the nuclear pores. In addition, the attachment of chromatin to the inner membrane of the nuclear envelope was observed. Decondensation was probably caused by the major Leucaena ingredient mimosine and is obviously related to its copper chelating properties.

Animals↗
PubMed1991

Antibody-dependent enhancement and neutralization pattern of sera from SIV-infected or HIV-2-vaccinated rhesus monkeys.

Neutralizing and enhancing activities in sera were detected by using an in vitro infection assay of HUT78 cells. Ten animals were vaccinated with HIV-2ROD recombinant vaccinia viruses and respective purified proteins. Only sera from monkeys vaccinated with env elicited neutralizing antibodies. No antibody-dependent enhancement (ADE) properties were detected in all the tested sera. Six other macaques were infected with SIV-mac251. All of them had detectable ADE properties in their sera. No major neutralizing activity was detected.

AIDS Vaccines↗
PubMed1989

Biosynthesis of Astacus protease, a digestive enzyme from crayfish.

For the first time, the site of biosynthesis of a well characterized invertebrate digestive enzyme is localized. The enzyme chosen, Astacus protease, is a zinc-metalloenzyme occuring in high concentration in the gastric fluid of the freshwater crayfish Astacus astacus. Enzyme production was stimulated in adult crayfish either by feeding or by removal of the gastric fluid. Immunohistochemistry, cytology and investigation with radioactive tracers demonstrate that in the hours following stimulation, new enzyme was produced in the F-cells of the midgut gland and subsequently discharged into the midgut gland lumen. The enzyme was then accumulated and stored extracellularly in the cardiac stomach in active form. The mechanism of enzyme production observed in Astacus differs considerably from vertebrates suggesting an alternative model for synthesis and storage of digestive enzymes.

Animals↗
PubMed1978

Esophageal dysfunction and its pathogenesis in progressive systemic sclerosis.

In 25 patients with progressive systemic sclerosis esophageal involvement was studied prospectively by analysing subjective symptoms and radiological and manometric criteria. In all patients abnormal motility could be demonstrated by X-ray and/or manometry: radiologically in 18 (72%), manometrically in 22 (88%) cases. Dysphagia was present only in 11 patients (44%). Six patients (24%) had no subjective symptoms in spite of severe objective esophageal abnormalities. Therefore, the absence of esophageal symptoms does not exclude advanced affliction of the esophagus. To determine the pathogenesis of esophageal dysfunction the effects of 3.5 microgram/kg carbachol and of 0.6 microgram/kg pentagastrin i.m. on the lower esophageal sphincter pressure (LESP), on the amplitude and on the duration of peristaltic esophageal contractions were studied at random in 12 of the patients and 12 normal controls. The results suggest a primary myogenic genesis of the motor abnormalities by atrophy and sclerosis of esophageal smooth muscle.

Adult↗