PubMed Health⌕ Search

Biomedical subjects

D Larsen

Publications and source records attributed to D Larsen.

26 records · Page 2Linked to original sources

Diazomethyl ketone substrate derivatives as active-site-directed inhibitors of thiol proteases. Papain.

The diazomethyl ketones of z-Phe-Phe inactivate papain by a stoichiometric reaction at the active-center thiol. Since the reagents are stable in mercaptoethanol, their reaction with papain is judged to be the result of complex formation characteristic of affinity-labeling reagents. The diazomethyl ketones react by a mechanism different from that of chloromethyl ketones, since the pH dependence of their inactivation of papain is different, the rate increasing with decreasing pH. This relationship has been observed in other cases, such as in the reaction of azaserine with glutamine amidotransferases [Buchanan, J. M. (1973), Adv. Enzmol. Relat. Areas Mol. Biol. 39, 91], and is interpreted as an indication of reaction with a thiol group in its protonated form.

Affinity Labels↗

Active-site-directed alkylation of chymotrypsin by reagents utilizing various departing groups.

Affinity-labeling reagents are useful for the inactivation of proteases in vivo but are apparently limited in application by the possibility of side reactions. In addition, increased specificity would be desirable. Substrate-derived chloromethyl ketones, one class of protease inhibitors, have been examined with the hope that replacement of the departing group halogen by other substituents might lead to improved inhibitor characteristics. Analogues of Z-Phe-Ch2X were synthesized in which X is a sulfonate or carboxylate substituent and examined as inactivators of chymotrypsin. The sulfonate esters were found to be more reactive than the previously studied halogen derivatives.

Alkylating Agents↗

Expression of alkaline phosphatase in differentiated rat labyrinthine trophoblast tissue.

In this report, we describe the generation of specific antibodies to rat alkaline phosphatase and the temporal and regional characteristics of alkaline phosphatase expression during maturation of the rat chorioallantoic placenta. An antipeptide antiserum was generated to the amino terminal 15 amino acids of rat alkaline phosphatase. The antiserum specifically recognized alkaline phosphatase. Alkaline phosphatase expression was monitored in the junctional and labyrinth zones of the chorioallantoic placenta by Western and Northern blot analyses. Alkaline phosphatase protein and mRNA were present in both the junctional and labyrinth zones on day 13 of gestation. As gestation advanced, alkaline phosphatase mRNA and protein expression decreased below the limits of detection in the junctional zone, while alkaline phosphatase expression increased in the labyrinth zone. Labyrinthine alkaline phosphatase migrated predominantly as a 95-kDa species, whereas rat kidney expressed exclusively the 75-kDa species. Enzymatic deglycosylation of the 75- and 95-kDa alkaline phosphatase species resulted in the generation of a 55-kDa species. In summary, alkaline phosphatase expression is a useful indicator of trophoblast differentiation.

Alkaline Phosphatase↗

Microcatheter embolization of non-neurologic traumatic vascular lesions.

PURPOSE: The authors report their experience over a 28-month period with embolization of 23 non-neurologic traumatic vascular lesions in 21 patients with use of a coaxial microcatheter coil delivery system. PATIENTS AND METHODS: The injuries included pseudoaneurysms (n = 17), arteriovenous fistulas (n = 3), and sites of extravasation (n = 3) and were caused by gunshot, shotgun, and stab wounds, as well as motor vehicle accidents and iatrogenic trauma. All microcatheter embolizations except one were performed with 2.2-F Tracker-18 catheters inserted coaxially through 5.0-5.5-F guiding catheters. In one case, a coaxial 3-F Teflon catheter was used. In all cases platinum microcoils (almost all non-fibril) and/or straight platinum embolization wires (with fibrils) were used. RESULTS: Twenty-one (91%) of 23 vascular lesions were successfully occluded with use of the microcatheter system. The two cases in which microcatheter embolization failed were successfully managed by using larger catheters and steel coils. Two patients with hepatic vascular lesions (one site of extravasation and a pseudoaneurysm) and one patient with a lower extremity arteriovenous fistula required two procedures each for successful treatment. Procedures were life-saving in at least two patients. Two lesions recurred during follow-up ranging from 3 days to 17 months. Both of these recurrences were successfully treated with transcatheter embolization, in one case with use of microcatheters. CONCLUSION: Microcatheter embolization with platinum coils and wires is an effective means for treating traumatic vascular lesions. A coaxial microcatheter system allows for easier, more rapid coil/wire delivery to smaller, spasm-prone arteries in such cases.

Adult↗

Specific antibody responses and generation of antigenic variants in chickens immunized against a virulent avian influenza virus.

To examine the specificity of the antibody response to the influenza hemagglutinin and the generation of antigenic variants, chickens were immunized against the highly virulent H5 virus A/Ty/Ont/7732/66 (H5N9) and then challenged with a lethal dose of the virus. The antibody responses of these chickens to the hemagglutinin (HA) were examined with an enzyme-linked immunosorbent assay (ELISA) in which their sera were titrated for the ability to block the binding of monoclonal antibodies (MAbs) to five distinct neutralizing epitopes on the viral HA. Based on the ELISA results, a majority (5/6) of the chickens produced antibodies to three of the five neutralizing epitopes on the viral HA. After challenge, two of six immunized chickens shed virus and died; antigenic comparisons of isolates from these two chickens indicated the presence of an antigenic variant; i.e., there was a change in one neutralizing epitope on the HA of virus shed by one chicken. None of the chickens had produced antibodies to this particular epitope on the viral HA. Inoculation of chickens with this variant resulted in 100% mortality, demonstrating that a change in this particular epitope did not alter the virulence of the virus. These studies indicate that chickens immunized against highly virulent influenza viruses may excrete virulent variants following challenge with live virus.

Animals↗

From hand to mouth.

Explore the source record for details and available documents.

Aerospace Medicine↗