Ectopic ACTH syndrome

Ectopic ACTH syndrome represents a cancer-induced amplification of a property [proopiomelanocortin (POMC) peptides production] normally present in the cells from which the cancer originated but with aberrant posttranslational processing of POMC resulting in a greatly elevated secretion of ACTH precursors. The classic ectopic ACTH-producing tumors described in the 1960s were highly malignant but more recently slowly growing tumors such as carcinoids are reported with increasing frequency. Clinical features of patients with ectopic ACTH were analyzed, including biochemical abnormalities, plasma ACTH, cortisol and urinary steroids. Dynamic tests such as high-dose dexamethasone suppression, metyrapone and ovine-CRH (oCRH) stimulation were explored, as well as inferior petrosal sinus ACTH sampling before and after oCRH. Among the tumor markers examined, elevation of ACTH precursors was uniformly present followed by increased output of calcitonin, gut hormones, oncofetal and placental hormones in decreasing order. Since more than 90% of ectopic ACTH tumors are neuroendocrine in nature exhibiting APUD characteristics, their 2 markers, neuron-specific enolase and chromogranins are very useful. The imaging procedures for localization of the tumor ranged from chest X-rays to computed tomography and magnetic resonance of the chest and abdomen. Abdominal ultrasonography was also useful. Finally somatostatin receptor scintigraphy permitted demonstration of unrecognized tumors and/or metastases, even when the tumors were occult. The ACTH content, immunostaining for APUD markers and altered POMC processing were evaluated in ectopic tumors and/or metastases. Occult ectopic ACTH syndrome of more than 4–6 months of symptoms without the emergence of an obvious source was reviewed. Since the tumors are often clinically and biochemically undistinguishable from pituitary-dependent Cushing's disease, inferior petrosal sinus sampling for ACTH after oCRH stimulation established the diagnosis in over 90% of the cases. 60% of the occult tumors were thoracic carcinoids (3/4 bronchial carcinoids), followed by small cell lung cancer and pancreatic neuroendocrine tumors. In 12% the primary etiology was not detected. The rare syndrome of ectopic CRH syndrome (6 published cases) leading to excessive stimulation of the pituitary which became hyperplastic and secreted excessive amounts of ACTH is discussed. Finally, the 12 published cases and 1 unreported patient with ectopic CRH-ACTH tumors were reviewed, the majority being metastatic small cell lung carcinomas, bronchial and thymic carcinoids.     

Postjunctional Origin of the indirect-like sympathomimetic effect of metanephrine and normetanephrine on blood pressure

The effects of metanephrine and normetanephrine have been compared with those from equiactive doses of the origin compounds, adrenaline and noradrenaline, on the pressor responses in rat, in order to determine whether their effects are owed, at least partially, to a releasing presynaptic action of the catecholamines in normal animals as well as those pretreated with reserpine, guanethidine and 6-OH-dopamine. Their effects have likewise been studied in isolated perfused renal arteries both in normal and reserpinized rats. None of the adrenolytic agent used were able either to reduce the duration of the hypertensive response or to accelerate tachyphylaxis. Identical results were obtained in renal artery preparations. It is thus concluded that the catecholamines stored in presynaptic endings are not involved in the observed phenomena and it is suggested that they might depend on the high doses required to produce effects equiactive to those of the origin substances.     

Changes in blood level of catecholamines during arterial blood pressure rise induced with sciatic nerve stimulation

In experiments on rabbits and dogs it was demonstrated that electrical stimulation of the centripetal fibres of the cut sciatic nerve causing a rise of the arterial blood pressure produced a significant increase in the plasma levels of adrenaline and noradrenaline. This effect was not observed in animals with sympathetic system blockade caused by administration of reserpine. These observations indicate that pressure increase after sciatic nerve stimulation is due to stimulation of the adrenergic system.     

Immobilization of the cellulolytic fungus Trichoderma reesei on the polymeric sorbent - Sorfix

Summary The immobilization of T. reesei mycelium on activated polymeric sorbent was investigated with respect to the intended flow-trough cellulase production. The retention of extracellular production of cellulolytic enzymes was monitored in a packed-column recycle reactor. Some factors affecting cellulase elution pattern are described.     

A kinetic study of the interaction of vanadate with the Ca2+ + Mg2+-dependent ATPase from sarcoplasmic reticulum.

Ca2+ + Mg2+-dependent ATPase from sarcoplasmic reticulum was inhibited by preincubation with vanadate. When the inhibited enzyme was preincubated in the presence of vanadate and assayed in its absence, a slow reactivation process was observed. This slow, hysteretic, process was exploited to study the influence of Ca2+ and ATP on the dissociation of vanadate. Ca2+ alone slowly displaced vanadate from the inhibited enzyme, and a rate constant of 0.1 min-1, at 25 degrees C, was calculated for this re-activation process. However, ATP re-activated with an apparent constant that hyperbolically depended on ATP concentration, and from it a rate constant for vanadate dissociation induced by ATP of 0.5 min-1 was calculated. It is deduced from the kinetic studies that ATP binds to the enzyme-vanadate complex, forming a ternary complex, with a dissociation constant of 4 microM, and that this binding accelerates vanadate dissociation. Binding experiments with [14C]ATP showed that ATP binds to the enzyme-vanadate complex with a dissociation constant of 12 microM, i.e. the affinities calculated with the isotope technique and the kinetic procedure are of the same order of magnitude.     

Batch culture of Candida utilis in a medium deprived of a phosphorous source

Summary Candida utilis var. major NRRL-Y-1084 was grown in a defined medium without a phosphorous (P) source. During the exponential phase, cells divided according to a specific growth rate of 0.32 h^-1, which is lower than the usual rate for a balanced medium (0.4–0.6 h^-1). The relative P content of the biomass decreased from 2.70% to 0.75% over a period of 6 h, including 2 h of cell division arrest. At the end of this period there was another interruption of cell division. After that, multiplication restarted at a considerably lower rate and it deviated slightly from the exponential pattern. The stationary phase began when biomass P content reached 0.4%–0.5%, slowly decreasing afterwards to 0.25–0.20%. Biomass synthesis was less affected than cell division by the relative decrease of endogenous P, the two processes differing partially in their kinetics. Cell lysis started shortly before the stationary phase and affected about 20% of the population by the end of the assay. RNA and P content of the resulting biomass were 2.4% and 0.25% respecitvely, P being mainly incorporated to RNA.The relationship of biomass production to glucose uptake was very low, probably because the marked P deficiency called for an increase in energy consumption for growth and specially for maintenance. Compared with yeasts grown in a balanced medium, 40% increase in glycogen was observed, whereas no mean changes in the content of cell wall carbohydrates (glucan and mannan) and that of true protein were found.Member of the Scientific Researcher's Career of the Consejo Nacional de Investigaciones Cientificas y Técnicas (CONICET). Agrentina     

Changes in cytoplasmic and lysosomal enzyme activities in cultured rat heart cells: The relationship to cell differentiation and cell population in culture

Summary Postnatal rat heart cells in culture enriched with respect to muscle cells were obtained by either high density seeding or by the replating technique. [³H]Thymidine incorporation to DNA and the enzymatic pattern of cytoplasmic and lysosomal enzymes have been studied as a function of the culture’s age, of seeding density, and replating. It was shown that (a) replating maintains predominance of myocyte population for at least 2 wk in culture; (b) heavy seeding density allows homogeneous myocyte population for the 1st wk in culture; and (c) the enzyme profile of the culture may serve as an indicator for the type of cell population in culture and its state of differentiation. This study was done as partial fulfilment of the M.Sc. thesis in Biochemistry (SY). Supported by grants from The Chief Scientist, Ministry of Health, State of Israel; The Ministry of Education and Sciences, State of Niedersachssen (FRG); and The Foundation for Heart Research from Mr. and Mrs. D. Vidal-Madjar, Paris, France.     

Einige neue oder bemerkenswerte Flechten mit gyalectoiden Apothecien von Nord-Indien und Nepal

This paper presents the results of taxonomic investigation of 8 species of lichens with gyalectoid apothecia collected in North-India and Nepal. Four species are recognized as new:Dimerella isidiata (sp. nova),D. nepalensis (sp. nova),Gyalideopsis lithophila (sp. nova) andRamonia nepalensis (sp. nova). Four species are reported for the first time from Nepal:Coenogonium moniliforme, Gyalectidium caucasicum, Gyalidea lecideopsis andG. scutellaris.