Resistance of purified cholera toxin to enzymatic treatment with pancreatic elastase and papain

Summary Treatment of Cholera toxin with pancreatic elastase and papain in vitro shoed a high resistance of the toxin molecule to these enzymes, under non-denaturing conditions or in the presence of 2M urea. These experiments support the hypothesis of a particularly stable molecular structure of the toxin, as an explanation of its activity in the intestinal lumen where the pancreatic proteases are active.     

RNA fragments, in vivo inhibitors of Shope fibroma and vaccinia virus multiplication]

RNA-fragments rich in purine nucleotides and resulting from degradation of ribosomal RNA from E. coli M 500 Sho-R with pancreatic RNase exhibit only in vivo an inhibitory effect on Shope fibroma and vaccinia virus multiplication.     

Conduction velocity of peristaltic waves in the in vivo ureter: application of a new diameter gauge

Summary The conduction velocity of peristaltic movements of the canine ureter was measured under anaesthesia with a new type of diameter gauge using an image sensor. The peristaltic velocity was 34.1±6.2 mm/sec in 10 experiments. Noradrenaline at a low dosage of 1 g/kg i.v. reduced the resting diameter, increased the conduction velocity to 47–56 mm/sec, and approximately doubled the frequency of contraction. The application of acetylcholine also caused an increase in both frequency and conduction velocity (42–46 mm/sec). A plot of the conduction velocity against the mean period of peristaltic contraction was hyperbolic in shape.     

Hormone content of mouse pancreatic islets subjected to different in vivo and in vitro functional demands

Summary Mice treated for 4 days with tolbutamide displayed decreased serum glucose values with a concomitant decrease of their islet insulin content. Mouse islets cultured for 1 week at a low (3 mM) or a high (28 mM) glucose concentration contained less insulin than non-cultured islets and islets cultured at a medium (11 mM) glucose concentration. All groups of cultured islets contained more glucagon than non-cultured islets. The somatostatin content of high- and medium-glucose cultured islets was higher than that of freshly isolated islets.The skilled technical assistance of Astrid Nordin, Ewa Forsbeck and Eva Törnelius is gratefully acknowledged. Financial support was received from the Swedish Medical Research Council (12X-109; 12X-2297), the Nordic Insulin Fund and the Swedish Diabetes Association.     

Inhibition of cortisol metabolism in vitro by 2-methylnaphthoquinone (menadione): A possible interpretation of the potentiation of cortisol activity in vivo

Résumé Le degré de réduction du noyeau A du cortisole par les microsomes du foie du rat et par le NADPH est inhibé du 50% par le méthyle-2-naphtoquinone (ménadione). L'inhibition est partiellement allégée par l'addition de NADPH ce qui indique que la ménadione gêne la disponibilité du NADPH. En effet, il s'est trouvé que la ménadione active la diminution de NADPH par les microsomes du foie. Il est possible que l'augmentation précédemment signalée de l'activité pharmacologique du cortisole par la ménadione est apparentée à l'inhibition du métabolisme du cortisole.     

Immunological blockade of the adenohypophysis and its possible application in prophylaxis and therapy of neoplasia

Zusammenfassung Die Anwendung von anti-Adenohypophysen-Serum in der Therapie gewisser Wachstumshormon-abhängiger menschlicher Tumoren wird vorgeschlagen. Der Vorschlag einer derartigen immunologischen Intervention basiert auf der bekannten Hormonabhängigkeit oder-empfindlichkeit zahlreicher Tumoren und auf der Tatsache einer langanhaltenden Hemmung Wachstumshormon produzierender Zellen am experimentellen Tier. Viele Tumoren beim Menschen haben wahrscheinlich die Hormon-Abhängigkeit der normalen Gewebe oder Drüsen, von denen sie sich herleiten, beibehalten. Da Mangel an Wachstumshormon keine schädigenden Wirkungen auf andere vitale Funktionen hervorruft, wird die Herstellung eines anti-Menschen-Adenohypophysenserums und dessen Anwendung bei nachgewiesenermassen hormonabhängigen Tumoren oder Metastasen, wie z.B. bei gewissen Formen des Brustkrebses, vorgeschlagen. Eine Beeinflussung der Akromegalie und gewisser Formen von hypophysärer Diabetes durch dasselbe Antiserum kann ebenfalls in Betracht gezogen werden.     

New selective inhibitors of the transmembrane Ca conductivity in mammalian myocardial fibres. Studies with the voltage clamp technique

Zusammenfassung Die Ca⁺⁺-Leitfähigkeit der Myokardfaser-Membran wird durch Verapamil und sein Methoxyderivat D 600 teilweise bis zum vollständigen Verlust reduziert. Dieser Effekt erfolgt selektiv, da die Na⁺-Leitfähigkeit der Membran unbeeinflusst bleibt. Die während der Erregung der Myokardfaser fliessenden transmembranären Ca⁺⁺- und Na⁺-Ströme benutzen demzufolge voneinander unabhängige Membrankanäle.     

Monoamine oxidase inhibitors antagonize the acceleration of brain dopamine synthesis induced by neuroleptic drugs in vivo: Implications for the treatment of tardive dyskinesia

Zusammenfassung Pargylin und Pheniprazin vermindern stark die Dopa-Anreicherung (erhöhte Dopamin-Synthesegeschwindigkeit) im corpus striatum der Ratte nach Trifluoperazin und Tetrabenazin. Dopamin-spezifische MAO-Hemmer könnten deshalb therapeutischen Wert haben in der Kontrolle von tardiver Dyskinesia, die möglicherweise durch erhöhte Bildung und Umsatz von Dopamin unter dem Einfluss von anti-psychotischen Drogen hervorgerufen wird.     

Potentiative effects of sulfhydryl compounds on carrageenin-induced oedema in rats and relationship to their potencies as inhibitors of angiostin-converting enzyme in vivo

Summary Carrageenin-induced oedema in rats was potentiated by oral administration of (4R)-3-[(2S)-3-mercapto-2-methylpropanoyl]-4-thiazolidinecarboxylic acid (SA291) and related sulfhydryl compounds, and the effect was closely correlated with their potencies as inhibitors of angiotensin-converting enzyme in vivo.Acknowledgment. The authors wish to thank Prof. H. Fujimura, Department of Pharmacology, Gifu University School of Medicine, for his helpful advice.     

Potentiative effects of sulfhydryl compounds on carrageenin-induced oedema in rats and relationship to their potencies as inhibitors of angiostin-coverting enzyme in vivo.

Carrageenin-induced oedema in rats was potentiated by oral administration of (4R)-3-[(2S)-3-mercapto-2-methylpropanoyl]-4-thiazolidinecarboxylic acid (SA291) and related sulfhydryl compounds, and the effect was closely correlated with their potencies as inhibitors of angiotensin-converting enzyme in vivo.     

Prevention of graft-versus-host-disease with preserved graft-versus-leukemia-effect by ex vivo and in vivo modulation of CD4+ T-cells

This is the first report showing that an epitope-specific ex vivo modulation of an allogeneic hematopoietic stem cell graft by the anti-human CD4 antibody MAX.16H5 IgG₁ simultaneously facilitates the anti-tumor capacity of the graft (Graft-versus-leukemia effect, GvL) and the long-term suppression of the deleterious side effect Graft-versus-host-disease (GvHD). To distinguish and consolidate GvL from GvHD, the anti-human CD4 antibody MAX16.H5 IgG₁ was tested in murine GvHD and tumor models. The survival rate was significantly increased in recipients receiving a MAX.16H5 IgG₁ short-term (2 h) pre-incubated graft even when tumor cells were co-transplanted or when recipient mice were treated by MAX.16H5 IgG₁ before transplantation. After engraftment, regulatory T-cells are generated only supporting the GvL effect. It was also possible to transfer the immune tolerance from GvHD-free recipient chimeras into third party recipient mice without the need of reapplication of MAX.16H5 IgG₁ anti-human CD4 antibodies. These findings are also benefical for patients with leukemia when no matched related or unrelated donor is available and provides a safer allogeneic HSCT, which is more effective against leukemia. It also facilitates allogeneic (stem) cell transplantations for other indications (e.g., autoimmune-disorders).     

Mitochondrial activity: A possible determinant of anoxic injury in renal medulla

Summary In brain¹, heart² and kidney³, cell work in the absence of oxygen has been thought to precipitate anoxic damage by increasing the rate of depletion of cellular energy stores. In the medullary thick ascending limb of isolated perfused rat kidneys, however, reduction of ATP synthesis by a variety of mitochondrial or metabolic inhibitors caused ATP depletion comparable to that produced by oxygen deprivation but did not reproduce the lesions of anoxia. In these cells, unrestrained mitochondrial activity may be an important source of anoxic injury.