Five tissue antigens have been identified which appear in carcinoma arising in the ovary. Antisera to a variety of human tissues were absorbed with a saline extract of normal ovary as well as plasma; five distinct antigens (A1-A4, TA) were detected in ovarian tumor extracts as well as in normal tissues. Al, A2, and A3 were widely distributed in normal tissues while A4 was found principally in buffy coat blood cells and spleen, and TA was mainly associated with normal cervix but was variably detected in liver and lung. Heating the tumor extract to 56° resulted in inactivation of Al, A2, and A3. A4 was inactivated at 80°, whereas TA was stable at 100°. Pronase treatment readily abolished A3 activity, more slowly inactivated Al, A2, and A4, and only very slowly destroyed TA. Partial separation of the antigens was obtained by Sephadex G-200 chromatography. TA from individual benign and malignant tumors as well as normal cervix appears to be the same molecule by criteria of immunodiffusion, Immunoelectrophoresis, and gel filtration. The potential use of these antigens as tracers of ovarian carcinoma is indicated.
Somatostatin inhibits colonic ion secretion in animal models and cultured intestinal cell lines via somatostatin receptor subtype 2 and subtype 1, respectively. In a recent in vitro ion transport study of the human colon, somatostatin was shown to stimulate short-circuit current, a measure of electrogenic ion transport. In this study we have used the reverse-transcription polymerase chain reaction (RT-PCR) and measurements of changes in short-circuit current (Isc) in response to receptor subtype-specific analogs of somatostatin, to define the somatostatin receptor subtype responsible for the stimulation of short-circuit current in human colon. Somatostatin receptor subtypes 1, 2, and 5, but not 3 and 4, were detected in the human colonic epithelium. Measurements of short-circuit current showed somatostatin and octreotide (1 micromol/liter) increased the prostaglandin stimulated short-circuit current by 12.3+/-1 and 11.0+/-1 microA/cm2, respectively. Similarly, analogs selective for somatostatin receptor subtypes 2 and 5 (1 micromol/liter) produced an increase of short-circuit current of 11.7+/-1 and 13.2+/-1 microA/cm2, respectively. However, at a concentration (10 nmol/liter) near the EC50, the somatostatin receptor subtype 2 analog increased short-circuit current by 9+/-1 microA/cm2, whereas the receptor subtype 5 analog had no effect. There was no difference in receptor expression or effect of the peptides related to the anatomical site of tissue collection. In conclusion, human colonic mucosa expresses multiple somatostatin receptor subtypes, of which subtype 2 mediates the stimulatory effect of somatostatin on ion transport.
Es sind fünf Gewebsantigene identifiziert worden, die in einem Ovarialkarzinom auftreten. Antisera gegen eine Reihe von menschlichen Geweben wurden zusammen mit einem Kochsalzextrakt sowohl vom normalen Ovar als auch vom Plasma absorbiert; fünf verschiedene Antigene (A1-A4, TA) wurden sowohl in Extrakten von Ovarialtu-moren als auch in normalen Geweben nachgewiesen. Al, A2 und A3 waren in normalen Geweben weit verbreitet, während A4 haupt-sächlich im Blut- und Milz-Leukozytenfilm (buffy coat) gefunden wurde. TA kam vorwiegend in der normalen Zervix vor, aber auch in unterschiedlicher Weise in der Leber und der Lunge. Die Erwärmung des Tumorextraktes auf 56° führte zur Inaktivierung von Al, A2 und A3. A4 wurde bei 80° inaktiviert, während TA bei 100° stabil war. Eine Pronasebehandlung hob die A3-Aktivität rasch auf, während die Inaktivierung von Al, A2 und A4 langsamer ablief und die Zerstörung von TA sehr langsam vonstatten ging. Eine teilweise Trennung der Antigene wurde durch eine Sephadex-G-200-Chromatographie erreicht. TA sowohl von individuellen gut- und bösartigen Tumoren als auch von normaler Zervix scheint aufgrund der Immundiffusion, Immunelektrophorese und Gelfiltration das gleiche Molekül zu sein. Auf die potentielle Verwendung dieser Antigene zur Erkennung von Ovarialkarzinomen wird hingewiesen.
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