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K Gemzell Danielsson

Publications and source records attributed to K Gemzell Danielsson.

5 recordsLinked to original sources

Degradation of proinsulin C-peptide in kidney and placenta extracts by a specific endoprotease activity.

Degradation of proinsulin C-peptide in mouse kidney and human placenta extracts was studied using reverse-phase high-performance liquid chromatography and nano-electrospray mass spectrometry. In total, 15 proteolytic cleavage sites were identified in human and mouse C-peptides. Early sites included the peptide bonds N-terminal of Val/Leu10, Leu12, Leu21, Leu24 and Leu26 in different combinations for the two tissues and two peptides. Notably, these cleavages were N-terminal of a hydrophobic residue, and all but one N-terminal of Leu. A late degradation product of the human peptide detected in the kidney extract was the C-terminal hexapeptide, containing just one residue more than the biologically active C-terminal pentapeptide of C-peptide. We conclude that the degradation of C-peptide in kidney and placenta follows similar patterns, dominated by endopeptidase cleavages N-terminal of Leu.

Amino Acid Sequence↗

The effect of antiprogestin on integrin expression in human endometrium: an immunohistochemical study.

Integrins are cell surface receptors for the extracellular matrix and connect extracellular cell adhesion proteins to cytoskeletal components. Several investigators have recently described the expression of different integrins in the human endometrium as markers of receptivity. In the present study we investigated the effect of various doses of the antiprogestin mifepristone on the endometrial expression of integrins during the implantation phase. Endometrial biopsies from healthy fertile women were obtained in the midluteal phase. The study included one control and one, two or three treatment cycles. In treatment cycles either 2.5 (n = 9) or 5 mg (n = 5) of mifepristone was administered once weekly, 0.5 mg daily (n = 5), or 200 mg as a single dose administered on day 2 after the luteinizing hormone surge (day LH + 2; n = 8). By using polyclonal antibodies against integrin alpha(v)beta3, subunit beta3 and subunit alpha4 we found reduced immunostaining for alpha4 and beta3 subunit in glandular epithelium after treatment with mifepristone while alpha(v)beta3, expression appeared to be unaffected. No differences between treatment groups were noted. This study demonstrates that treatment with mifepristone interferes with integrin distribution during the implantation window. This may imply that the contraceptive effect of mifepristone is primarily due to impaired endometrial receptivity. However, since no effect was shown on the distribution of the vitronectin receptor, this integrin might be regulated differently by other factors such as cytokines.

Adult↗

Effect of antiprogestin, hCG and a prostaglandin analogue on human uterine contractility.

In the present study, the effect of hCG and RU 486 on non-pregnant uterine contractility and the sensitivity of the myometrium to the prostaglandin analogue misoprostol (GD Searle, Chicago, IL, USA) was evaluated. Seven healthy female volunteers participated in the study. Uterine contractility was recorded on cycle day LH+13 in two cycles. After recording the spontaneous contractility, 200 micrograms and 400 micrograms of misoprostol were administered orally at an interval of 45-60 minutes. In the second month, 5,000 IU hCG was administered on cycle day LH+8 and 10,000 hCG on cycle days LH+10 and LH+12, and 200 mg RU 486 on cycle day LH+11, 48 hours prior to the recording. In three women, a third month was included in which the same treatment, except for RU 486, was given. Treatment with hCG delayed menstrual bleeding and resulted in a significant increase in the concentration of plasma progesterone. Following hCG, the degree of uterine contractility was reduced, while after hCG and RU 486 the uterus was significantly more active. In the control cycle and following hCG alone, misoprostol had a slight stimulatory effect. When RU 486 was added, the degree of contractility following misoprostol was 4 to 9 times greater than that found if RU 486 was not given. Late luteal administration of RU 486 is not an effective method of fertility regulation. The results of the present study indicate that a combination of RU 486 and misoprostol will be more suitable for this purpose.

Administration, Oral↗

Pregnancy termination.

During pregnancy, the antiprogestin mifepristone will induce uterine contractions, increase the sensitivity of the myometrium to prostaglandin, and ripen the cervix. These effects indicate that mifepristone can be used for termination of pregnancy. The clinical experience has shown that mifepristone is sufficiently effective for this purpose only if combined with a suitable prostaglandin, e.g. gemeprost or misoprostol. The combined treatment has been used for termination of early pregnancy (up to 63 days of amenorrhea) and for termination of second trimester pregnancy. During early pregnancy, the recommended dose of mifepristone is 600 mg (although 200 mg seems sufficient), followed 36-48 h later by 0.4-0.8 mg misoprostol administered either orally or vaginally, or vaginal administration of 1.0 mg gemeprost. For termination of second trimester pregnancy, the treatment with mifepristone is most commonly combined with 1.0 mg gemeprost repeated at 3-6-h intervals. The combined treatment is as effective and safe during early pregnancy as is the alternative vacuum aspiration and is also equally acceptable if the woman is allowed to choose the method she prefers. During the second trimester, the pretreatment will significantly reduce the duration of labor, dose of prostaglandin, and the frequency of side effects.

Abortifacient Agents, Nonsteroidal↗