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Biomedical subjects

M Kirchner

Publications and source records attributed to M Kirchner.

At least 37 records · Page 2Linked to original sources

[Complete trisomy 22].

In a 2 6/12-years-old girl a complete trisomy 22 was verified with the G-banding (CTG-technique). She presented with Pierre-Robin-Sequence, cardiac and renal malformations, craniofacial dysmorphia and psychomotoric retardation as it often occurs in trisomy 22. Additionally, we observed tonic-clonic seizures, remarkable dumbles on both elbows and a clavicular anomaly.

Abnormalities, Multiple↗

Phospholipase A2 inhibition by alkylbenzoylacrylic acids.

3-(4-Alkylbenzoyl)acrylic acids (ABAAs) were synthesized by acylation of alkylbenzenes with maleic anhydride and then screened in vitro for inhibition of phospholipase A2 (PLA2) from snake venom and from porcine pancreas. The inhibitory potency of ABAAs increased with the length of the alkyl residues resulting in IC50 values of between 10(-7) and 10(-4) mol/L. The most potent inhibitors of the snake venom PLA2 were the 4-(n)-hexadecyl and octadecyl (OBAA) derivatives. Kinetic experiments referred to a time-dependent inhibitory reaction. Irreversibility was examined by dilution and dialysis. A molar ratio of inactivation of OBAA of nearly 20 was estimated. Double reciprocal replots of the apparent inactivation constants to the concentration of OBAA gave a (pseudo) first order rate constant of inactivation of 2.3 min-1. For the dissociation constant of the enzyme-inhibitor intermediate, a value of 6 x 10(-6) mol/L was obtained. On the other hand, the PLA2 from porcine pancreas seemed hardly to be inhibited by ABAAs. The present data are discussed in relation to the proposed model for PLA2 inactivation by manoalide. In human PMNs leukotriene B4 and 5-HETE production was essentially reduced. In human platelets the thrombin-induced TxA2 production was reduced. Since these effects disappeared after addition of arachidonic acid, these findings refer to a PLA2 inhibition. The immunologically induced bronchospasm in guinea pigs was significantly and dose-dependently inhibited by OBAA. This indicates that ABAAs might be useful in treating allergic diseases, such as asthma, eczema, allergic shock and others.

Acrylates↗

Determination of picomole amounts of lipoxins C4, D4 and E4 by high-performance liquid chromatography with electrochemical detection.

A method for the sensitive determination of the sulphopeptide lipoxins (LXs) C4, D4 and E4 by high-performance liquid chromatography with subsequent electrochemical detection is described. The best results were obtained when the analysis was carried out with the solvent system methanol-water-trifluoroacetic acid (66:34:0.008, v/v/v). The acquired half-wave potentials were different for all investigated compounds: +1.18 V for LXC4 +1.3 V for LXD4 and +1.25 V for LXE4. The detection limits of LXC4, LXD4 and LXE4, based on a signal-to-noise ratio of 3:1, were found to be 200-700 fmol. Although sulphopeptide lipoxins possess a high molar absorptivity, electrochemical detection still is three times more sensitive than ultraviolet detection.

Arachidonic Acids↗

Delayed spontaneous pubertal growth spurt in girls with the Ullrich-Turner syndrome.

By means of an appropriate mathematical model (Sager's 2-components-concept) a delayed spontaneous pubertal growth spurt can be demonstrated in girls with 45,X Ullrich-Turner syndrome (UTS) (n1 = 45) as well as in those with 45,X/46,XX mosaicism (n2 = 14) never treated with any growth stimulating drug. On the average, this growth spurt begins later and its extent is smaller (mean growth rate = 3.10 and 2.79 cm, respectively, in the 15th year of chronological age) than in normal girls. The delay in acute growth spurt corresponds very well to the delay of skeletal maturation in the UTS (on the average 2 to 3 years of chronological age).

Adolescent↗

Who pays for new technology?

New medical technology presents an interesting dilemma. While it can offer improvements in patient care, it is often quite expensive. Thus, many health care payers may not be as willing to cover care involving new technologies.

Commerce↗

Molecular cloning of proteinase-encoding genes from cancer cells by zymogen assay and direct sequencing.

A method that permits the in vitro cloning and identification of proteolytic enzyme genes from cDNA expression libraries is described. The method can detect positive proteinase genes within 30 min following the transfer of plaques to nitrocellulose membrane filters. The method is based on the functional expression of fusion lac Z-proteinase protein in lambda gt11 infected Y1090 bacteria and does not require prior knowledge of either the sequence of the cDNA insert or a monoclonal antibody to its encoded antigen. This strategy when coupled with polymerase chain reaction of the cDNA insert using lac Z primer sequences that are flanking the EcoR1 cloning site in gt11 phage permits direct sequencing of the amplified DNA. With this method we have isolated 10 genes expressing protease activity in the human small-cell carcinoma of the lung. The same procedure could be applied to isolate unknown proteinases from cDNA libraries of virtually any eukaryotic cell.

Base Sequence↗

Activation of cancer cell proteases and cytotoxicity by EGF and PDGF growth factors.

The biological effects of EGF and PDGF growth factors on A172 and hEGFr-3T3 cell lines were studied using RBC induced cytolysis and polyacrylamide-gelatin gel electrophoresis assays. The authors report that growth factor-induced cytotoxicity in these cells is mediated by proteolytic enzymes. Treatment of A172 cells with either EGF or PDGF resulted in marked increase of their cytotoxicity (Release Index = 150%). Similarly, RBC induced release index by hEGFr-3T3 cells was elevated to 420% in the presence of 3.4 pM of EGF. However, in A172 cells, PDGF did not have a significant effect on DNA and protein synthesis indicating that stimulation of proteolytic activity is independent of the growth factor signaling pathway. Growth factor induced cytotoxicity was significantly reduced by protease inhibitors in both cell lines. Using EDTA and leupeptin several proteolytic species were identified and localized to cellular membranes as evidenced by polyacrylamide-gelatin electrophoresis assay. These data suggest that growth factors regulate the activation or secretion of proteolytic enzymes in cancer cells and may mediate the invasive and metastatic behavior of these cells.

Amiloride↗