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The effect of thyroid hormones (thyroxine and triiodothyronine) on catecholamine receptors in isolated rat fat cells was investigated. Binding of (3H)isoproterenol and (3H)norepinephrine were increased by thyroid hormones. (3H)isoproterenol binding was more enhanced than (3H)norepinephrine binding. Triiodothyronine had a more potent effect than thyroxine. (3H)isoproterenol was used to estimate the number or affinity of beta-adrenergic receptors in rat fat cells treated with thyroid hormones. The binding sites for (3H)isoproterenol were the same in untreated and with triiodothyronine treated fat cells. The equilibrium dissociation constants (KD) for the interaction of receptors with (3H)isoproterenol were altered in thyroid hormone treated cells. There was a significant difference between the untreated and triiodothyronine treated fat cells in the affinity of beta-adrenergic receptor binding sites for (3H)isoproterenol. Thyroid hormone could alter negative cooperative site-to-site interaction among the binding sites for (3H)isoproterenol.

Summary A new microtome is described which allows the rapid preparation of equal slices of well-defined thickness of fresh human tissue, especially adipose tissue. Presetting the microtome for a section thickness of 500 pm, we found a variation of about 5% with human adipose tissue. Slices of human adipose tissue sliced by the microtome showed a higher sensitivity to insulin and a better reproducibility of results than slices prepared freehand.

The role of thyroid hormones on lipolysis in human subcutaneous adipose tissue was investigated. Incubation of subcutaneous fat pads with thyroxine (0.1--10 000 nM) augmented the subsequent isoproterenol stimulation of lipolysis, measured by glycerol release. The basal lipolysis could not by stimulated by thyroxine. The theophylline- and dibutyryl-cyclic AMP stimulated lipolysis also could not be increased by thyroxine at these concentrations. In separate studies, the effect of thyroxine (0.01 pM--1 microM) and triiodothyronine (0.01 pM--1 microM) on cyclic AMP accumulation was examined. No effect of thyroid hormones on cyclic AMP accumulation was seen in non-isoproterenol stimulated tissue. Fat pads stimulated by isoproterenol and then treated with thyroid hormones showed marked increases in accumulation of cyclic AMP as compared to control tissue in the presence of isoproterenol alone.

Alternating fluid rinsing with a modified glyceromono-octanoate (GMOC) and bile salt-EDTA (BA-EDTA) solution via an endoscopically placed indwelling nasal biliary catheter was performed on 15 patients (13 women, 2 men) with recurrent stones in the choledochal duct after cholecystectomy. Of 12 radiotranslucent and three radioopaque concrements with a mean diameter of 1.72 X 2.05 cm (largest concrement: 3.0 X 3.5, smallest 1.0 X 2.1 cm) 13 were dissolved (87% success rate). In one patient chemolitholysis had to be stopped because of electrolyte abnormalities, before treatment had been completed. After the end of treatment all patients were free of symptoms and during a fairly long follow-up period no stone recurrences were observed.

For palliative therapy during the chronic phase of CML busulfan has proved to be the drug of choice. During the past years hydroxyurea and also interferon-alpha have gained increasing significance since they might prolong the duration of the chronic phase. In a multicenter study it is being determined, whether the use of hydroxyurea or of interferon-alpha instead of busulfan prolongs the duration of the chronic phase of Philadelphia positive CML. Additional goals are the examination of whether the types of disease evolution and the terminal phases differ between the treatment groups, and the prospective recognition of prognostic criteria for the duration of the chronic phase of CML. By December 31, 1987, 326 CML-patients had been randomized, 150 for busulfan, 150 for hydroxyurea and 26 for interferon-alpha. The average age is 50 years. 59 patients reached the end of the chronic phase, 55 died. The mean observation time of all patients is 1.34 years. At present no significant difference in survival is recognizable between the busulfan and hydroxyurea groups. Fewer adverse effects have been observed in the hydroxyurea group. Philadelphia chromosome negative patients show a higher average age and tend to have lower white blood cell and platelet counts. The number of patients having received interferon-alpha is still too small to allow evaluation. This report intends to document organization and progress of this study which to our knowledge is, at present, the largest ongoing prospective multicenter study on the therapy of CML.

A patient who had been admitted to hospital for surgical treatment of inguinal hernias was found to have a blood group phenotype of A1B in the presence of a non-auto-anti-B. No previous records of the patient's blood group were available. The serological workup including absorption and saliva inhibiton studies yielded a high probability for an acquired B-antigen which is known to be often associated with carcinoma of the colon. Subsequent coloscopy revealed the presence of a carcinoma of the sigmoid, unaccessable to palpation. To our knowledge this is the first report in the literature that the serological diagnosis of an acquired B-antigen led to the detection of a hitherto undetected carcinoma.

The specific binding of (3H) isoproterenol to isolated fat cells of human and rat was characterized. Binding of (3H) isoproterenol to isolated fat cells of rat was saturable with 420 pmol of (3H) isoproterenol bound/100 mg of lipid. Half-maximal saturation occurred at 5 microM providing an estimate of the equilibrium dissociation constant, KD, for the interaction of (3H) isoproterenol with its binding sites. Kinetic analysis of (3H) isoproterenol binding provided a value of 2.01 x 10(4) min-1. M-1 for the forward bimolecular rate constant, k1. Dissociation of (3H) isoproterenol was a first order reaction with a rate constant, k2, of 0.62 x 10(-1) min-1. The ratio k2/k1 = 3.07 microM provides an independent measurement of the KD for the interaction of (3H) isoproterenol with its binding sites which is in agreement with the values obtained by steady state analysis (3 to 5 microM). The apparent equilibrium dissociation constant, KD, for the interaction of (3H) isoproterenol with its receptor in human fat cells obtained by steady state analysis was 1 to 0.9 microM. Scatchard- and Hill-analysis suggest the possibility of different negatively cooperative interactions among the binding sites in human and rat. beta-Adrenergic agonists competed for the binding sites. The order of potency was isoproterenol greater than epinephrine greater than norepinephrine. Compounds such as DOPA, dopamine and (m-Hydroxyphenyl)2-methyl-aminoethanol which are structurally related to catecholamines had little or no affinity for (3H) isoproterenol binding sites.

Aktivitatsmessungen von Insulin in Flussigkeiten mit Hilfe biologischer Verfahren haben auch heute noch grose Bedeutung. Die immunologischen Mesverfahren fur Insulin (vgl. S. 69) haben trotz weit hoherer Sensitivitat und groserer Prazision die biologischen Insulinaktivitatsmessungen nicht vollstandig verdrangen konnen. Fur die Bearbeitung bestimmter wissenschaftlicher Fragestellungen ist die Erfassung der biologischen Insulinwirkung von Korperflussigkeiten oder anderen Medien noch weiterhin unerlaslich, wie sich erst jungst bei Entdeckung des Proinsulins wieder gezeigt hat (Steiner, 1967). Im Blut werden sowohl mit der immunologischen als auch mit der biologischen Methode Substanzen erfast, die strukturell mit dem aus Pankreata isolierten und von Sanger und Tuppy (1951) in seiner Struktur aufgeklarten Insulinmolekul nicht identisch sind. Dieser Tatsache tragt man Rechnung durch die Bezeichnung „insulinahnliche Wirkung“ oder „insulin-like-activity (ILA)“ fur den biologischen Mes wert und „immunologisch mesbares Insulin (IMI)“ fur das immunologisch ermittelte Resultat.

Prostaglandine sind hormonartige Wirkstoffe, denen als Grundstruktur eine C20-Carbonsaure gemeinsam ist und die inzwischen aus zahlreichen Geweben des Saugetierorganismus isoliert werden konnten. Die durchschnittliche Gewebskonzentration betragt 0,5 bis 1,0 µg/g Frischgewicht. Als Wirkkonzentrationen wurden Werte im Bereich von 0,1 bis 0,001 µg/ml ermittelt [1].

Fettgewebe kann sich nur unter dem Einflus von Insulin entwickeln, und folglich kann eine Adipositas nicht ohne eine vermehrte Produktion von Insulin. entstehen. Entsprechend erhohte Blutinsulinspiegel mit gesteigerter reaktiver Insulinsekretion bei Adiposen wurden in den letzten Jahren auch wiederholt nachgewiesen (Grodsky et al., 1963; Melani et al., 1967). Ebenso konnten bei adiposen potentiellen Diabetikern prinzipiell gleichartige Befunde erhoben werden (Ditscnuneit et al., 1962; Camarini-Devalos et al., 1963; Steinke et al., 1963; Soeldner U. Sloan, 1964). Bei diesen ist nur der reaktive Insulinanstieg geringer ausgepragt, was wir auf eine anhaltend starkere Stimulation des Inselzellsystems infolge leicht erhohter Blutzuckerspiegel bezogen haben (Ditschuneit, 1965).

Zur quantitativen Bestimmung von Insulin im Blut stehen uns bisher nur biologische Methoden zur Verfugung. Sie sind, wie alle biologischen Mesverfahren, mit einer erheblichen Fehlerbreite behaftet. Als Masstab fur die Insulinwirkung wurde in den letzten Jahren in zunehmendem Mase die Bildung von C14O2 aus 1-C14-Glucose durch isoliertes epididymales Rattenfettgewebe gewahlt. Uber unsere eigenen Erfahrungen mit dieser Methode und uber klinisch-experimentelle Untersuchungen haben wir vor dieser Gesellschaft und an anderer Stelle bereits berichtet (1—9) Die Fehlerbreite dieser Methode liegt zu einem erheblichen Teil in der Schwierigkeit der quantitativen Erfassung des entwickelten radioaktiven Kohlendioxyds und nicht nur in der biologischen Mesverfahren allgemein anhaftenden Streuung begrundet.

The best known physiologic significance of growth hormone (GH) is induction and maintenance of longitudinal growth. An isolated GH deficiency does not induce fatal metabolic disturbances but it severely retards skeletal development. As GH secretion persists in adulthood, it remains questionable whether the only function of GH is stimulation of growth. Several clinical and experimental observations indicate that GH may increase fat catabolism which can be recognised by a lowering of respiratory quotient and increased ketogenesis (Prader et al., 1967; Rabinowitz, Klassen and Ziegler, 1965; Tanner and Whitehouse, 1967; Gaebler, 1930; Bennett et al., 1948).

Bei den selten anzutreffenden Fallen von Insulinresistenz, die nach der allgemein gebrauchlichen Definition von Martin u. Mitarb. (1) einen Insulinbedarf von mindestens 200 E an zwei aufeinanderfolgenden Tagen aufweisen, wird immer wieder die Bildung von Insulinantikorpern mit blockierenden Eigenschaften diskutiert. In den seltensten Fallen konnten aber quantitative Beziehungen zwischen der Hohe des Antikorpertiters und dem klinischen Bild hergestellt werden, so das Zweifel aufkommen, ob der serologisch fasbare Antikorper auch die biologische Insulinwirkung zu neutralisieren vermag.